Circulation StudioCardiovascular simulation

Circulation Studio / Reference library

Works cited

References for the teaching collection, waveform interpretation, and the Studio’s educational models.

Teaching sources

Adapted from V2 Hemodynamics MOR JD updated, CCM / Cardiology Half-day Series.

  1. Lilly. Pathophysiology of Heart Disease, 5th ed., 2011.
  2. Davidson et al. Cardiac Catheterization, in Braunwald’s Heart Disease, 9th ed., 2012.
  3. Murphy, Lloyd et al. Mayo Clinic Cardiology: Concise Textbook, 4th ed., 2013.
  4. Naidu et al. SCAI shock classification update, JACC, 2022.

Reference library

  1. Olshansky B, Chung MK, Pogwizd SM, Goldschlager N. Arrhythmia Essentials. 2nd ed. Elsevier; 2017. Ch. 1–2, 4–5, 7.
  2. Stouffer GA, editor. Cardiovascular Hemodynamics for the Clinician. Blackwell Publishing; 2008. pp. 26, 55, 71.
  3. Block B. Color Atlas of Ultrasound Anatomy. Thieme; 2004. pp. 88–89.
  4. Ragosta M. Textbook of Clinical Hemodynamics. 2nd ed. Elsevier; 2018. pp. 36, 39, 59–60.
  5. Steimle AE, Stevenson LW, Chelimsky-Fallick C, et al. Sustained hemodynamic efficacy of therapy tailored to reduce filling pressures in survivors with advanced heart failure. Circulation. 1997;96(4):1165–1172. doi:10.1161/01.CIR.96.4.1165 ↗

Waveform & physiology sources

Sources inform the synthetic teaching traces. Model responses are illustrative and not clinically validated.

  1. Valve sounds and splitting. Physiologic S2; RBBB and S1; abnormal S2. Opening-snap hemodynamics; valve opening and ejection clicks; prolapse and loading. Illustrative timing, not severity measurements.
  2. 12-lead ECG patterns. AHA/ACCF/HRS: conduction and ST–T interpretation. HRS ventricular arrhythmia consensus and ACC morphology reference. Synthetic examples; morphology does not prove origin.
  3. Waveform Quiz. Question patterns draw on the pressure, rhythm and valve references below; resistance calculations use mean pressure gradients and forward flow. Merck Manual: cardiac catheterization and normal pressure ranges. Randomized vitals are bounded teaching variations, not patient cases.
  4. ASD, PAPVR, PDA, VSD and Eisenmenger physiology. Gurvitz M, et al. 2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease. Circulation. 2026;153:e115–e251. Sections 4.1, 4.4.6.
  5. ASD respiratory filling and S2 splitting. O’Toole JD, Reddy PS, Curtiss EI, Shaver JA. The mechanism of splitting of the second heart sound in atrial septal defect. Circulation. 1977;56:1047–1053. Original catheter study.
  6. Shunt flow measurements. 2022 ESC/ERS pulmonary hypertension guideline, section 5.1.12.1: saturation sampling and direct Fick in shunts; thermodilution is unsuitable with shunting.
  7. Squat, stand from squat and handgrip. American Heart Association, Hypertrophic Cardiomyopathy: Diagnosis and Clinical Implications of Structural Phenotypes, clinical teaching transcript; ESC, mitral disease and dynamic auscultation.
  8. Passive leg raise. Monnet X, Teboul JL. Passive leg raising: five rules, not a drop of fluid! Crit Care. 2015;19:18. Methodology.
  9. RA, RV, PA, wedge and LV pressure contours. Stouffer, 2008; Ragosta, 2018; AHA, Cardiac Hemodynamics; ATS, PA waveform teaching.
  10. ECG timing, conduction and pacing. Olshansky et al., Arrhythmia Essentials. AHA/ACCF/HRS ECG standardization, part III; 2019 ESC SVT guidelines.
  11. Valsalva phase responses. Goldstein DS, Cheshire WP Jr. Beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver. Clin Auton Res. 2017;27:361–367. Physiology review. Echocardiographic evaluation in healthy subjects and patients with and without heart failure.
  12. Wiggers diagrams and pressure–volume loops. Klabunde RE. CV Physiology: ventricular pressure–volume relationships, effects of preload, afterload and inotropy, and cardiac cycle and heart sounds.
  13. Post-PVC response in HOCM. Brockenbrough EC, Braunwald E, Morrow AG. A hemodynamic technic for the detection of hypertrophic subaortic stenosis. Circulation. 1961;23:189–194. Original report.
  14. Combined valve physiology. Bansal et al., serial LV outflow obstruction (2021); Salustri & Almaghrabi, mitral hemodynamics (2018).
  15. Carabello pullback sign. Carabello BA, Barry WH, Grossman W. Changes in arterial pressure during left heart pullback in patients with aortic stenosis: a sign of severe aortic stenosis. Am J Cardiol. 1979;44:424–427. Study.
  16. Constriction versus restriction. Talreja DR, Nishimura RA, Oh JK, Holmes DR. Constrictive pericarditis in the modern era: novel criteria for diagnosis in the cardiac catheterization laboratory. J Am Coll Cardiol. 2008;51:315–319. Study.
  17. IABP pressure contours and timing. Getinge. Cardiosave IABP Operation/Transport Quick Reference Guide, software B. Manufacturer guide.
  18. V-A ECMO, arterial pulsatility and LV loading. Lorusso R, et al. ELSO interim guidelines for venoarterial extracorporeal membrane oxygenation in adult cardiac patients. ASAIO J. 2021;67:827–844. Guideline. Mourad M, et al. Pulse pressure and end-tidal carbon dioxide for monitoring low native cardiac output during veno-arterial ECLS. Crit Care. 2020;24:569. Prospective study.
  19. Impella flow and unloading. Abiomed. Impella Ventricular Support Systems: Instructions for Use & Clinical Reference Manual. FDA-hosted labeling.
  20. Supported chamber pressures and pressure–volume loops. Donker DW, Brodie D, Henriques JPS, Broomé M. Left ventricular unloading during veno-arterial ECMO: a simulation study. ASAIO J. 2019;65:11–20. Simulation study.
  21. Arterial reservoir model during continuous support. Westerhof N, Lankhaar JW, Westerhof BE. The arterial Windkessel. Med Biol Eng Comput. 2009;47:131–141. Model review.
  22. Plethysmography and respiratory timing. Allen J. Photoplethysmography and its application in clinical physiological measurement. Physiol Meas. 2007;28:R1–R39. Review. University of Iowa, Ventilator 101: respiratory rate and I:E timing.
  23. Case pulse oximetry. FDA. Pulse Oximeters.
  24. Disease pressure and resistance targets. 2022 ESC/ERS pulmonary hypertension guidelines and 2020 ACC/AHA valvular heart disease guideline.
Measurement assumptions

BSA 2.0 m². Estimated MAP = (SBP + 2 × DBP) / 3. SVR uses displayed CVP and output; recorded PA means may differ from arithmetic estimates.

ScvO₂ ≠ SvO₂. Thermodilution is independent of assumed Fick oxygen consumption. PAWP and PCWP both mean wedge pressure.

Complete list of sources

Identifiable references from the Lab, teaching pages, cases, quiz, and earlier revisions. Original teaching assumptions are not validated patient data.

Books & original teaching material9
  1. V2 Hemodynamics MOR JD updated Joshua Durbin. CCM / Cardiology Half-day Series. Supplied teaching slides and case material.
  2. Pathophysiology of Heart Disease Lilly LS. 5th ed. 2011.
  3. Cardiac Catheterization Davidson et al. In: Braunwald’s Heart Disease. 9th ed. 2012. Reference retained from the supplied slides.
  4. Mayo Clinic Cardiology: Concise Textbook Murphy JG, Lloyd MA, editors. 4th ed. 2013.
  5. Cardiovascular Hemodynamics for the Clinician Stouffer GA, editor. Blackwell; 2008. Supplied PDF; pp. 22–24 and 67–71 inform the stationary catheter and atrial teaching traces.
  6. Textbook of Clinical Hemodynamics Ragosta M. 2nd ed. Elsevier; 2018. Supplied PDF.
  7. Color Atlas of Ultrasound Anatomy Block B. Thieme; 2004. Supplied PDF.
  8. Arrhythmia Essentials Olshansky B, Chung MK, Pogwizd SM, Goldschlager N. 2nd ed. Elsevier; 2017. Supplied PDF.
  9. Hemodynamic Rounds: Interpretation of Cardiac Pathophysiology from Pressure Waveform Analysis Kern MJ, Lim MJ, Goldstein JA, editors. 4th ed. Wiley; 2018.
Electrophysiology mapping & research methods8
  1. Revisiting the anatomy of the left ventricle in the light of knowledge of its development Crucean A, Spicer DE, Tretter JT, et al. J Anat. 2024;245:201–216. doi:10.1111/joa.14048.Qualitative LV outlet and basal vestibule anatomy informs original schematic EP examples; synthetic dimensions and surface equations are not patient measurements.
  2. Septation and separation within the outflow tract of the developing heart Webb S, Qayyum SR, Anderson RH, Lamers WH, Richardson MK. J Anat. 2003;202:327–342. doi:10.1046/j.1469-7580.2003.00168.x.Qualitative distinction between the aortic vestibule and muscular subpulmonary infundibulum; no source figure or patient geometry is copied.
  3. Relationship Between Sinus Rhythm Late Activation Zones and Critical Sites for Scar-Related Ventricular Tachycardia: A Systematic Analysis of Isochronal Late Activation Mapping Irie T, Yu R, Bradfield JS, et al. Circ Arrhythm Electrophysiol. 2015;8:390–399.Latest local electrogram offset, eight equal activation bins and >2 isochrones within a 1 cm radius. Prototype graph distances and ranking weights are original, unvalidated implementations.
  4. Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm: A New Functional Substrate Mapping Strategy Aziz Z, Shatz D, Raiman M, et al. Circulation. 2019;140:1383–1397.The primary abstract specifies >3 isochrones within a 1 cm radius; this preset remains distinct from the Irie threshold.
  5. Optimized isochronal late activation methods in the visualization and isthmus identification of ventricular tachycardia Zeldin L, Majumder JA, Yang H, et al. Heart Rhythm. 2025;22:1238–1248. doi:10.1016/j.hrthm.2024.08.038.Consulted for separate EP prediction targets. Paired presenting-rhythm and VT mapping informs research on isthmus-region discrimination; its eight-map feature analysis does not validate this application's original 60/25/15 ranking, identify a unique VT exit or constitute patient-level validation of this prototype.
  6. The V(2) transition ratio: a new electrocardiographic criterion for distinguishing left from right ventricular outflow tract tachycardia origin Betensky BP, Park RE, Marchlinski FE, et al. J Am Coll Cardiol. 2011;57:2255–2262.Restricted idiopathic outflow-tract ECG comparison; not a scar-VT isthmus or anatomical-coordinate predictor.
  7. A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex Brugada P, Brugada J, Mont L, Smeets J, Andries EW. Circulation. 1991;83:1649–1659.Background for wide-complex tachycardia interpretation. The EP prototype does not implement the complete Brugada algorithm.
  8. A real-time QRS detection algorithm Pan J, Tompkins WJ. IEEE Trans Biomed Eng. 1985;32:230–236.Beat-detection background only. The prototype uses an original amplitude-envelope detector, not the published validated processing chain.
Hemodynamics, measurement & waveforms68
  1. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography and for Heart Failure With Preserved Ejection Fraction Diagnosis: An Update From the American Society of Echocardiography Nagueh SF, Sanborn DY, Oh JK, et al. J Am Soc Echocardiogr. 2025;38(7):537–569. doi:10.1016/j.echo.2025.03.011. Newly consulted 31 October 2026 for impaired relaxation, LV chamber stiffness, preserved EF and the distinction between mean LA/PAWP and LV end-diastolic pressure. Clinical context and integrated assessment remain necessary; the Severe LVH preset's pressures, volumes and response coefficients are original educational assumptions. Rechecked 1 November 2026 for the Severe LVH Mystery dossier: preserved EF can coexist with raised filling pressure; LVH alone does not establish HCM or HFpEF. The assessment decision leaves the teaching phenotype unchanged.
  2. The Fourth Heart Sound Williams ES. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods. 3rd ed. Boston: Butterworths; 1990. Chapter 25. Newly consulted 31 October 2026 for low-pitched presystolic S4, reduced ventricular compliance and the requirement for effective atrial contraction; does not validate the original synthesized sound or imply universal S4 in LVH.
  3. Feasibility of continuous oxygen delivery and cardiac output measurement by application of the Fick principle Feustel PJ, et al. Am J Respir Crit Care Med. 1994;149:751–758. Oxygen content and Fick flow relationships.
  4. Thermodilution Assessment of Cardiac Index in Patients With Tricuspid Regurgitation Sternberg ME, et al. J Invasive Cardiol. 2023;35:E122–E125. TR does not imply a universal thermodilution bias.
  5. Underestimation of cardiac output by thermodilution in patients with tricuspid regurgitation Cigarroa RG, et al. Am J Med. 1989;86:417–420. Historical under-reading example; not a fixed correction factor.
  6. Right heart catheterization in clinical practice: a review of basic physiology and important issues relevant to interpretation Del Rio-Pertuz G, Nugent K, Argueta-Sosa E. Am J Cardiovasc Dis. 2023;13:122–137.
  7. Pulmonary artery catheterisation Gilbert-Kawai N, Chen R, Patel S. BJA Educ. 2024;24:447–457. Rechecked 2026-10-30 for the PH pressure-lab catheter schematic: SVC–RA–RV–PA progression and distal pulmonary artery occlusion with a static column reflecting left atrial pressure. The original illustration is simplified and does not validate catheter placement or wedge quality.
  8. Cardiac Hemodynamics Yeghiazarians Y. American Heart Association, 2014. Pressure waveform teaching.
  9. Pulmonary artery hemodynamics tracing American Thoracic Society. 2021 teaching resource.Previously cited PDF; the original link may now redirect.
  10. Cardiac Catheterization Merck Manual Professional Edition.
  11. Normal Pressures in the Heart and Great Vessels Merck Manual Professional Edition. Supplemental ventricular reference ranges; LVEDP 5–12 mmHg.
  12. Methods in pharmacology: measurement of cardiac output Geerts BF, Aarts LP, Jansen JR. Br J Clin Pharmacol. 2011;71:316–330.
  13. Thermodilution and Fick cardiac outputs differ: impact on pulmonary hypertension evaluation Fares WH, et al. Can Respir J. 2012;19:261–266.
  14. Time to Calm the Fick Down? A Systematic Review and Meta-Analysis of Thermodilution Compared to Direct Fick in Tricuspid Regurgitation Abualsaud R, et al. CJC Open. 2024;6:1138–1144.
  15. Calculating FICK Cardiac Output and Input StatPearls. NCBI Bookshelf.
  16. Measuring cardiac output in critically ill patients: disagreement between thermodilution-, calculated-, expired gas-, and oxygen consumption-based methods Sherman MS, Kosinski R, Paz HL, Campbell D. Cardiology. 1997;88:19–25.
  17. Features Associated With Discordance Between Pulmonary Arterial Wedge Pressure and Left Ventricular End Diastolic Pressure in Clinical Practice: Implications for Pulmonary Hypertension Classification Hemnes AR, et al. Chest. 2018;154:1099–1107.
  18. Accuracy of left atrial and pulmonary artery wedge pressure in pure mitral regurgitation in predicting left ventricular end-diastolic pressure Haskell RJ, French WJ. Am J Cardiol. 1988;61:136–141. Primary abstract rechecked 1 November 2026 for the teacher workflow: a large systolic V wave and mean wedge pressure are distinct from LV end-diastolic pressure.
  19. Sustained hemodynamic efficacy of therapy tailored to reduce filling pressures in survivors with advanced heart failure Steimle AE, Stevenson LW, Chelimsky-Fallick C, et al. Circulation. 1997;96:1165–1172. Supplied EPUB.
  20. Constrictive pericarditis in the modern era: novel criteria for diagnosis in the cardiac catheterization laboratory Talreja DR, Nishimura RA, Oh JK, Holmes DR. JACC. 2008;51:315–319.
  21. A hemodynamic technic for the detection of hypertrophic subaortic stenosis Brockenbrough EC, Braunwald E, Morrow AG. Circulation. 1961;23:189–194. Rechecked 1 November 2026 for the teacher workflow's constructed post-extrasystolic comparison of fixed and dynamic outflow obstruction; synthetic pulse factors are not fitted patient measurements.
  22. Changes in arterial pressure during left heart pullback in patients with aortic stenosis: a sign of severe aortic stenosis Carabello BA, Barry WH, Grossman W. Am J Cardiol. 1979;44:424–427. Catheter-obstruction pullback sign.
  23. The mechanism of splitting of the second heart sound in atrial septal defect O’Toole JD, Reddy PS, Curtiss EI, Shaver JA. Circulation. 1977;56:1047–1053.
  24. The arterial Windkessel Westerhof N, Lankhaar JW, Westerhof BE. Med Biol Eng Comput. 2009;47:131–141.
  25. How to measure blood pressure using an arterial catheter: a systematic 5-step approach Saugel B, et al. Critical Care. 2020;24:172.
  26. Intra-arterial blood pressure measurement: sources of error and solutions Devasahayam S, et al. Med Biol Eng Comput. 2022;60:1123–1138.
  27. Direct blood pressure measurement—dynamic response requirements Gardner RM. Anesthesiology. 1981;54:227–236.
  28. First heart sound and ejection sounds: echocardiographic and phonocardiographic correlation with valvular events Waider W, Craige E. Am J Cardiol. 1975;35:346–356.
  29. Cineradiographic studies of the early systolic click in aortic valve stenosis Epstein EJ et al. Circulation. 1965;31:842–853.
  30. Ejection clicks Jacobs WR. Clinical Methods. 3rd ed. 1990. Chapter 28.
  31. Noninvasive/invasive correlates of exaggerated ventricular interdependence in cardiac tamponade Shaver JA, Reddy PS, Curtiss EI, Ziady GM, Reddy SC. J Cardiol. 2001;37 Suppl 1:71–76.
  32. Mechanism of electrical alternans in patients with pericardial effusion Rinkenberger RL, Polumbo RA, Bolton MR, Dunn M. Cathet Cardiovasc Diagn. 1978;4:63–70.
  33. Proportional relations between systolic, diastolic and mean pulmonary artery pressure are explained by vascular properties Kind T, Faes TJC, Vonk-Noordegraaf A, Westerhof N. Cardiovasc Eng Technol. 2011;2:15–23.
  34. Golden ratio and the proportionality between pulmonary pressure components in pulmonary arterial hypertension Chemla D, et al. Chest. 2019;155:991–998.
  35. Measuring Valve Gradients and Areas Dean LS, Kern MJ. J Soc Cardiovasc Angiogr Interv. 2022;1:100433.
  36. Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness Townsend RR, Wilkinson IB, Schiffrin EL, et al. AHA scientific statement. Hypertension. 2015;66:698–722.
  37. Haemodynamic factors influencing opening snap interval in mitral stenosis Ebringer R, Pitt A, Anderson ST. Br Heart J. 1970;32:350–354.
  38. The second sound–mitral opening snap interval during exercise in the evaluation of mitral stenosis Delman AJ, Gordon GM, Stein E, Escher DJ. Circulation. 1966;33:399–403.
  39. Postural changes in left ventricular and mitral valvular dynamics in the systolic click–late systolic murmur syndrome Fontana ME, Wooley CF, Leighton R, Lewis RP. Circulation. 1975;51:165–173.
  40. Swan-Ganz True Size Thermodilution Catheters Edwards Lifesciences. Instructions for use, DOC-0552125A. Figure 2: catheter pressure progression.
  41. Mitral valve disease: correlation between the most important echocardiographic parameters and haemodynamics Salustri A, Almaghrabi A. ESC e-Journal of Cardiology Practice. 2018;16.
  42. Tricuspid Stenosis Armstrong GP; reviewed by Howlett JG. Merck Manual Professional Edition. Updated June 2025.
  43. Haemodynamic Interplay Between Concomitant Left Ventricular Outflow Tract Obstruction and Aortic Stenosis Bansal P, Lodhi H, Mathews A, et al. Interventional Cardiology Review. 2021;16:e11.
  44. Aortic Stenosis With Dynamic Left Ventricular Outflow Obstruction: Diagnostic and Management Challenges—A Case Series Qian F, McGregor P-C, Latifi AN, Aragam J. CASE. 2025;9:9–18.
  45. Managing Left Ventricular Outflow Tract Obstruction in Combined Aortic Stenosis and Hypertrophic Cardiomyopathy Shi M, Saleh D, Leya MV, Puthumana JJ, Flaherty JD, Choudhury L. JACC: Case Reports. 2024;29:102653.
  46. Cardiac tamponade in association with an atrial septal defect: echocardiographic Doppler and hemodynamic observations Joffe II, Douglas PS. J Am Soc Echocardiogr. 1996;9(6):909–914.
  47. The First Heart Sound Felner JM. Clinical Methods. 3rd ed. 1990; chapter 22.
  48. The Second Heart Sound Felner JM. Clinical Methods. 3rd ed. 1990; chapter 23.
  49. Mechanism of normal splitting of the second heart sound Curtiss EI, Matthews RG, Shaver JA. Circulation. 1975;51:157–164.
  50. Complete right bundle-branch block: echophonocardiographic study of first heart sound and right ventricular contraction times Brooks N, Leech G, Leatham A. Br Heart J. 1979;41:637–646.
  51. Physiology and cardiovascular effect of severe tension pneumothorax in a porcine model Nelson D, et al. J Surg Res. 2013;184:450–457. Animal physiology; illustrative obstructive-flow model and quiz.
  52. Thoracic trauma WSES-AAST guidelines Coccolini F, et al. World J Emerg Surg. 2025;20:78. Pleural injuries: pneumothorax and hemothorax.
  53. Impact of Concomitant Mitral Regurgitation on the Hemodynamic Indicators of Aortic Stenosis Šeman M, Stephens AF, Walton A, et al. J Am Heart Assoc. 2023;12:e025648.MR reduces forward flow and measured aortic gradients.
  54. Mitral valve disease: effects of exercise and drugs on echocardiographic parameters Brandt RR, Nishimura RA. ESC e-Journal of Cardiology Practice. 2018;16.Flow dependence and mixed mitral disease.
  55. Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation Bolen JL, Alderman EL. Circulation. 1976;53:879–883.Variable forward-flow and regurgitant responses to nitroprusside.
  56. Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction Loh E, Stamler JS, Hare JM, Loscalzo J, Colucci WS. Circulation. 1994;90:2780–2785.Reduced PVR can accompany increased wedge pressure without improved output.
  57. Influence of inhaled nitric oxide on systemic flow and ventricular filling pressure in patients receiving mechanical circulatory assistance Hare JM, et al. Circulation. 1997;95:2250–2253.Pulmonary redistribution when systemic flow cannot increase.
  58. All About Heart Rate American Heart Association. Reviewed May 13, 2024. Resting heart-rate reference for the About preview.
  59. Left atrial size, pressure, and V wave height in patients with isolated, severe, pure mitral regurgitation Pizzarello RA, et al. Cathet Cardiovasc Diagn. 1984;10:445–454. Large wedge V waves and LA compliance; V-wave height alone does not diagnose MR.
  60. The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction Korabathina R, et al. Catheter Cardiovasc Interv. 2012;80:593–600. PAPi definition; original inferior-MI cohort, not a PE-specific threshold.
  61. Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice Baumgartner H, Hung J, Bermejo J, et al. J Am Soc Echocardiogr. 2009;22:1–23. Figure 7: AF filling duration and mitral gradients; used for waveform timing, not current severity thresholds.
  62. Recommendations on the Echocardiographic Assessment of Aortic Valve Stenosis: A Focused Update Baumgartner H, Hung J, Bermejo J, et al. EACVI/ASE. J Am Soc Echocardiogr. 2017;30:372–392.Flow-dependent gradients and integrated grading; synthetic geometry categories are not clinical thresholds.
  63. Aortic valve hemodynamics in atrial fibrillation: Should the highest Doppler signal be used to estimate severity of aortic stenosis? Alsidawi S, Khan S, Pislaru SV, Nkomo VT. Echocardiography. 2018;35:869–871. Beat-dependent flow and aortic gradients.
  64. Effect of dobutamine on left ventricular relaxation and filling phase in patients with ischemic heart disease and preserved systolic function Zeppellini R, et al. Cardiovasc Drugs Ther. 1993;7:325–331. Contractility and pressure-rise response; model coefficients remain illustrative.
  65. Capillary pulse waveform in aortic stenosis Mahy IR, Shore AC, Smith LD, Tooke JE. Int J Microcirc Clin Exp. 1994;14:257–261. Peripheral expression of the obstructed arterial contour.
  66. The contemporary pulmonary artery catheter. Part 1: placement and waveform analysis Bootsma IT, Boerma EC, de Lange F, Scheeren TWL. J Clin Monit Comput. 2022;36:5–15. Catheter whip and dynamic-response artifacts; synthetic amplitudes are illustrative.
  67. The Electrocardiographic and Hemodynamic Findings in Pulmonary Stenosis with Intact Ventricular Septum Bassingthwaighte JB, Parkin TW, DuShane JW, Wood EH, Burchell HB. Circulation. 1963;28:893–905. RV pressure loading and flow-dependent pulmonary-valve gradients; historical grading thresholds are not used.
  68. Catheterization in Adults With Congenital Heart Disease: A Primer for the Noncongenital Proceduralist Miranda WR, Aboulhosn JA, Hagler DJ. JACC Cardiovasc Interv. 2022;15:907–921. Sequential catheter and peak-to-peak gradient interpretation.
Guidelines & clinical assessment41
  1. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Humbert M, Kovacs G, Hoeper MM, et al. Eur Heart J. 2022;43:3618–3731. PH definitions, diagnostic workup and Tables 16/18 risk assessment. Supplied guideline and primary publication consulted. Rechecked 2026-10-30 for the interactive RHC and therapy lab: haemodynamic definitions, PVR from mean PA/wedge pressures and cardiac output, and phenotype-specific interpretation limits. Rechecked 2026-10-31 for Current Landscape classification and editorial applicability: selected vasoreactive PAH, severe PH-ILD PDE5-inhibitor uncertainty, CTEPH scope and absence of a universal group 5 PAH-drug approach. Prominence is not an outcome-count ranking or prescribing rule.2022 essential messagesDefinitions and diagnostic pathways inform the PH workup aid and labels in the synthetic simulator-derived pressure atlas; model waveforms and schematic geometry are illustrative, not clinical recordings or validated patient measurements. Tables 16/18 inform baseline criteria and the four-strata score. The guideline table does not define a single arithmetic aggregate for comprehensive baseline assessment. Rechecked 3 November 2026 in the primary ERS guideline text for Help/Wiki framework selection: comprehensive assessment at diagnosis, four-strata follow-up assessment and the need for clinical context. Published thresholds do not clinically validate this implementation. Rechecked 7 November 2026 for annual SSc screening, DETECT guideline population, unexplained dyspnoea and CTD phenotyping. Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Guideline synthesis combines trial, registry and expert evidence. Screening likelihood, ILD stage and established PAH mortality risk are different clinical questions.
  2. 2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease Gurvitz M, et al. Circulation. 2026;153:e115–e251.
  3. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease Otto CM, Nishimura RA, Bonow RO, et al. American College of Cardiology / American Heart Association. Circulation. 2021;143:e72–e227. Rechecked 1 November 2026, sections 4.1 and 7.1, for acute AR/MR teacher workflows: acute low-forward-flow and congestion physiology, temporary support versus valve correction, and the contraindication to IABP in acute severe AR.Valvular and mixed-lesion physiology informs the model reference; numerical interaction coefficients and severity endpoints are synthetic.
  4. Acute valvular emergencies Bernard S, Deferm S, Bertrand PB. Eur Heart J Acute Cardiovasc Care. 2022;11:653–665. Newly consulted 1 November 2026 for the authored acute-MR and acute-AR teacher workflows, including acute-versus-chronic pulse-pressure and chamber-response distinctions.Staged deterioration, support and correction states are original synthetic teaching snapshots, not a predicted patient course, procedure result or treatment protocol.
  5. 2024 AHA/ACC multisociety Guideline for the Management of Hypertrophic Cardiomyopathy Ommen SR, Ho CY, Asif IM, et al. American Heart Association / American College of Cardiology. Circulation. 2024;149:e1239–e1311. Rechecked 1 November 2026 for the AS-versus-HOCM teacher workflow: dynamic LVOT obstruction depends on preload, afterload and contractility; standing and Valsalva strain are provocative assessment maneuvers.
  6. 2025 Concise Clinical Guidance: An ACC Expert Consensus Statement on the Evaluation and Management of Cardiogenic Shock Sinha SS, Morrow DA, Kapur NK, et al. JACC. 2025;85:1618–1641. Shock recognition and congestion profiles.Shock context for the model reference; the software’s color and deterioration rules are illustrative, not a guideline severity score.
  7. SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of Validation Studies Naidu SS, et al. JACC. 2022;79:933–946.2022 bedside checklist (ACC-endorsed classification)2022 consensus full text (JSCAI co-publication)A–E stage descriptions inform the original halfday shock diagram.
  8. Mixed Cardiogenic–Vasodilatory Shock: Current Insights and Future Directions Jentzer JC, et al. JACC: Advances. 2025;4:101432.
  9. Right ventricular failure ESC e-Journal of Cardiology Practice. Vol. 14.
  10. Cardiac tamponade: a clinical challenge ESC e-Journal of Cardiology Practice. 2017;15(17). Rechecked 1 November 2026 for the tamponade teacher workflow: impaired filling despite elevated intracardiac pressure, respiratory ventricular interdependence and inspiratory arterial systolic-pressure decline.
  11. Pericardiocentesis in cardiac tamponade: indications and practical aspects De Carlini CC, Maggiolini S. ESC e-Journal of Cardiology Practice. 2017;15(19). Rechecked 1 November 2026 for the tamponade teacher workflow: temporary volume support is conditional and does not relieve pericardial constraint; preload reduction can worsen compromise, while drainage permits recovery of filling and forward flow.
  12. 2019 ESC Guidelines on Acute Pulmonary Embolism Konstantinides SV et al. ESC/ERS. European Heart Journal. 2020;41:543–603.
  13. Shock Procter LD; peer review by Spain DA. MSD / Merck Manual Professional Edition. Updated July 2026.
  14. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021 Society of Critical Care Medicine / European Society of Intensive Care Medicine.
  15. KDIGO Clinical Practice Guideline for Acute Kidney Injury Kidney International Supplements. 2012;2.
  16. Emergency treatment of anaphylaxis Resuscitation Council UK. 2021 guideline and supporting resources.2021 guideline (PDF)Vasodilation, capillary leak and urgent treatment inform the teaching example; the selected high-output value is illustrative, not a guideline target.
  17. The Sepsis Manual UK Sepsis Trust. 7th ed. 2024.
  18. Contemporary Management of Cardiogenic Shock American Heart Association. Circulation. 2017.
  19. 2025 ESC/EACTS valvular heart disease guideline ESC/EACTS. European Heart Journal. 2025.2025 essential messagesMixed-valve flow and loading interactions; synthetic coupling coefficients remain illustrative.
  20. MitraClip safety and effectiveness FDA. PMA P100009. 2013.
  21. TriClip G4 safety and effectiveness FDA. PMA P230007. 2024.
  22. Invasive hemodynamics after MitraClip Bednar et al. BioMed Research International. 2016.
  23. Medical Therapy of Acute Myocardial Infarction by Application of Hemodynamic Subsets Forrester JS, Diamond G, Chatterjee K, Swan HJC. N Engl J Med. 1976;295:1356–1362.
  24. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure Heidenreich PA, et al. Circulation. 2022;145:e895–e1032.Official guideline slide set
  25. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition Rossaint R, et al. Critical Care. 2023;27:80.
  26. Diagnosis and management of pulmonary hypertension due to left heart disease or pulmonary disease European Society of Cardiology. CardioPractice, 2026. Postcapillary pressure elevation versus pulmonary vascular disease.
  27. ISHLT/HFSA Guideline on Acute Mechanical Circulatory Support International Society for Heart and Lung Transplantation / Heart Failure Society of America. 2023.
  28. Pericardial effusions: perspective of the acute cardiac care physician Jain CC, Reddy YNV. European Heart Journal: Acute Cardiovascular Care. 2023;12(7):467–474. Rechecked 1 November 2026 for the tamponade teacher workflow's preserved x/blunted y atrial contour and the distinction between measured filling pressure and transmural filling.Preserved x and blunted y descents in RA and PAWP during tamponade. Respiratory timing and amplitude remain illustrative.
  29. 2025 ESC Guidelines for the management of myocarditis and pericarditis European Society of Cardiology task force. Eur Heart J. 2025;46(40):3952–4041. doi:10.1093/eurheartj/ehaf192. Newly consulted 31 October 2026 for reversible inflammatory constriction as a subset of pericardial disease, distinct from chronic constriction. Rechecked 1 November 2026 for the tamponade teacher workflow: variable clinical presentation and respiratory ventricular interdependence. Manual synthetic endpoints do not implement a clinical treatment algorithm or predict recovery. Rechecked 1 November 2026 for the acute-pericarditis Mystery dossier: clinical evaluation, risk assessment and clinician-directed anti-inflammatory care. The assessment decision does not simulate resolution.
  30. Diagnosis of acute pericarditis Xanthopoulos A, Skoularigis J. ESC e-Journal of Cardiology Practice. 2017;15(15). 6 September 2017. Newly consulted 31 October 2026 for representative diffuse ST/PR changes and variable one-, two- or three-component friction rub; neither finding is obligatory or a standalone diagnostic classifier.
  31. Pericarditis Hoit BD; reviewed by Howlett JG. Merck Manual Professional Edition. Full review April 2026. Newly consulted 31 October 2026 for inflammatory pericardial syndromes, variable friction rub and potentially reversible constriction. The simulator does not infer etiology, prognosis or treatment response.
  32. Cardiac Tumors Baldassarre LA, Akintoye E; reviewed by Howlett JG. Merck Manual Professional Edition. Full review June 2026. Newly consulted 31 October 2026 for mobile atrial myxoma, variable positional inflow obstruction and a tumor plop in a minority of cases. The model's pressures, beat variation and synthetic audio are original teaching assumptions, not a tumor diagnosis or clinical prediction. Rechecked 1 November 2026 for the myxoma Mystery dossier: imaging-confirmed mobile obstruction and specialist/cardiac-surgical assessment. Tumor resection and embolic outcomes are not simulated.
  33. Transient constrictive pericarditis: causes and natural history Haley JH, Tajik AJ, Danielson GK, Schaff HV, Mulvagh SL, Oh JK. J Am Coll Cardiol. 2004;43(2):271–275. doi:10.1016/j.jacc.2003.08.032. Primary natural-history study newly consulted 31 October 2026 for a reversible constrictive phenotype in selected patients; no cohort-derived recovery clock or probability is implemented.
  34. Clinical Practice Algorithm for the Follow-Up of Pulmonary Stenosis Pre- and Post-Intervention American College of Cardiology. 2023. Doppler peak-gradient grades are distinct from sequential catheter gradients.
  35. Clinical Practice Algorithm For the Follow-Up of Unrepaired and Repaired Tetralogy of Fallot Moore J et al. American College of Cardiology. Updated 12 April 2026. Consulted for obstruction-dependent unrepaired physiology and heterogeneous repaired residual lesions.
  36. Tetralogy of Fallot Beerman LB; reviewed by Agus MSD. Merck Manual Professional Edition. Full review April 2023. Newly consulted 31 October 2026 for unrepaired RV outflow obstruction with a large VSD, obstruction-dependent right-to-left cyanosis, near-systemic RV pressure, RVH/right-axis ECG and the RVOT murmur rather than a high-gradient VSD murmur. Numerical endpoints and acoustic coefficients remain original teaching choices.
  37. Tetralogy of Fallot in adults. A report on 147 patients Abraham KA et al. Am J Med. 1979;66:811-816. doi:10.1016/0002-9343(79)91121-5. Original catheterization cohort; supports ventricular/aortic systolic pressure relationships, not generated numerical profiles.
  38. Determinants and Prognostic Implications of Left-Heart Filling Pressures in Tetralogy of Fallot Egbe AC et al. Can J Cardiol. 2020;36:1491-1498. doi:10.1016/j.cjca.2019.10.040. Original invasive cohort; supports variability of filling pressures rather than a universal TOF profile.
  39. Tetralogy of Fallot: Emergency Management of Hypercyanotic Tet Spells Meyer G, Jansen L, Shaw K, Franklin O. Irish Association for Emergency Medicine and Children’s Health Ireland. Version 1.0, August 2024. Consulted 31 October 2026 for qualitative dynamic-RVOT and SVR mechanisms only; pediatric emergency guidance does not validate adult generated pressure responses or doses.
  40. Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association Rychik J et al. Circulation. 2019;140:e234-e284. doi:10.1161/CIR.0000000000000696. Consulted 31 October 2026 for Fontan pathway physiology, absence of a subpulmonary pump, venous hypertension and reduced output. These qualitative principles do not validate generated numerical traces.
  41. 2025 ACC/AHA/HRS/ISACHD/SCAI Guideline for the Management of Adults With Congenital Heart Disease ACC/AHA multisociety guideline. Published in 2026; doi:10.1016/j.jacc.2025.09.006. Fontan recommendations consulted for phenotype-specific assessment and limits of pulmonary vasoactive therapy; no generated dose-response magnitude is derived from this guideline.
Rhythm & resuscitation12
  1. AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram: Part III, Intraventricular Conduction Disturbances Surawicz B, et al. Circulation. 2009.
  2. AHA/ACCF/HRS ECG Interpretation: Part IV, ST Segment, T and U Waves, and QT Interval Rautaharju PM, Surawicz B, Gettes LS. J Am Coll Cardiol. 2009;53:982–991.
  3. 2019 HRS/EHRA/APHRS/LAHRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias Cronin EM, et al. 2019. ECG morphology and fascicular ventricular tachycardia. Section 5.2 additionally consulted 3 November 2026: in scar-related reentry, surface ECG reflects the exit rather than the diastolic corridor; it does not validate AI localization or an ablation target.Reconsulted for distinct critical-isthmus and exit/breakthrough research targets. A diastolic electrogram, successful lesion or nearby substrate region does not by itself assign a proven circuit role; interpretation requires VT-specific mapping evidence and review. Separate target assessments and references must not be pooled into a single localization claim.
  4. Premature Ventricular Contractions in Athletes: Insight into Evaluation and Management Darden D, Prutkin JM. American College of Cardiology. 2022.
  5. AHA/ACCF/HRS ECG Interpretation: Part V, Cardiac Chamber Hypertrophy Hancock EW, et al. Circulation. 2009;119:e251–e261. Atrial P-wave morphology.
  6. 2018 ACC/AHA/HRS Guideline: Bradycardia and Cardiac Conduction Delay Kusumoto FM, et al. Circulation. 2019;140:e382–e482. PR interval and AV conduction; first-degree block threshold. The 180 ms sinus example is a synthetic display choice.
  7. 2019 ESC Guidelines for the management of patients with supraventricular tachycardia Brugada J, et al. Eur Heart J. 2020;41:655–720.
  8. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation American College of Cardiology / American Heart Association.
  9. Adult Advanced Life Support American Heart Association. Guidelines for CPR and Emergency Cardiovascular Care. 2025.
  10. Adult Cardiac Arrest Algorithm American Heart Association. 2025.
  11. Tachycardia recognition and diagnosis from changes in right atrial pressure waveform—a feasibility study Kaye GC, Astridge P, Perrins J. Pacing Clin Electrophysiol. 1991;14:1384–1392.
  12. The effect of atropine in vasovagal syncope induced by head-up tilt testing Santini M, Ammirati F, Colivicchi F, Gentilucci G, Guido V. Eur Heart J. 1999;20:1745–1751.
Maneuvers & the cardiac cycle27
  1. Hypertrophic Cardiomyopathy: Diagnosis and Clinical Implications of Structural Phenotypes American Heart Association. Educational podcast transcript.
  2. Physical examination in aortic valve disease: do we still need it in the modern era? Siliste RN, Siliste C. ESC e-Journal of Cardiology Practice. 26 February 2020. Existing reference rechecked 31 October 2026 for qualitative ejection/regurgitant sound character, mobile-valve clicks and acute/chronic AR differences; does not validate synthesized audio.Chronic aortic-regurgitation pulse contour; classic peripheral signs may be absent in acute regurgitation.
  3. Mitral valve disease: clinical features focusing on auscultatory findings, including auscultation of mitral valve prolapse ESC e-Journal of Cardiology Practice. Vol. 16. 1 August 2018. Existing reference rechecked 31 October 2026 for MS rumble/snap, MR/MVP timing and qualitative sound character, including potentially short or quiet acute MR. No recorded audio or acoustic coefficients are used.
  4. Cardiac Auscultation Gupta JI, Shea MJ. Merck Manual Professional Edition. Full review April 2025; updated September 2026. Existing reference rechecked 2026-10-30 for heart-sound timing, pitch and murmur contours in the original synthesized PCG demonstration; not a source of recorded audio or fitted acoustic coefficients.
  5. Passive leg raising: five rules, not a drop of fluid! Monnet X, Teboul JL. Crit Care. 2015;19:18.
  6. Beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver Goldstein DS, Cheshire WP Jr. Clin Auton Res. 2017;27:361–367.
  7. A human cardiopulmonary system model applied to the analysis of the Valsalva maneuver Lu K, Clark JW Jr, Ghorbel FH, Ware DL, Bidani A. Am J Physiol Heart Circ Physiol. 2001;281:H2661–H2679.Thoracic pressure, venous return and reflex interactions inform consistency checks. Circulation Studio uses its own simplified phase rules, not this paper’s fitted model.
  8. Echocardiographic evaluation of the Valsalva maneuver in healthy subjects and patients with and without heart failure Parisi AF, et al. Circulation. 1976;54:921–927.
  9. Valsalva maneuver Shindler D. Rutgers Robert Wood Johnson Medical School. Echocardiography teaching resource.
  10. Factors Regulating Arterial Blood Pressure Klabunde RE. Cardiovascular Physiology Concepts (CV Physiology).
  11. Cardiac Afterload Klabunde RE. Cardiovascular Physiology Concepts (CV Physiology).
  12. Ventricular Pressure–Volume Relationship Klabunde RE. Cardiovascular Physiology Concepts. Revised November 2023. Valve timing and ventricular filling.
  13. Interdependent Effects of Preload, Afterload and Inotropy on Ventricular Pressure–Volume Loops Klabunde RE. Cardiovascular Physiology Concepts (CV Physiology).
  14. Cardiac Cycle Klabunde RE. Cardiovascular Physiology Concepts. Revised November 2023. Wiggers timing and atrial-pressure interpretation.
  15. Ventricular Pressure–Volume Loop Changes in Valve Disease Klabunde RE. Cardiovascular Physiology Concepts. Revised January 2023.
  16. Valvular Stenosis Klabunde RE. Cardiovascular Physiology Concepts. Revised 2023. Systolic outflow and diastolic inflow pressure gradients.
  17. Aortic Stenosis Merck Manual Professional Edition. Systemic pressure and ventricular function.
  18. Mitral Regurgitation Armstrong GP; reviewed by Howlett JG. Merck Manual Professional. Updated July 2026. Systolic LV-to-LA regurgitation and atrial v waves.
  19. Tricuspid Regurgitation Armstrong GP. Merck Manual Professional. Updated October 2025.
  20. Pulmonary Regurgitation Armstrong GP. Merck Manual Professional Edition. Full review June 2025; updated October 2025. RV volume loading. Rechecked 31 October 2026 for the qualitative distinction between PH-related high-pitched PR and shorter, lower-pitched PR without PH. This context does not establish an etiology-specific validated acoustic model.
  21. Pulmonary Stenosis Merck Manual Professional. RV pressure loading.
  22. Aortic Regurgitation: Pressure–Volume Loop Klabunde RE. Cardiovascular Physiology Concepts. Revised January 2023.
  23. Mitral Regurgitation: Pressure–Volume Loop Klabunde RE. Cardiovascular Physiology Concepts. Revised February 2024.
  24. Spectral analysis of heart sounds: relationships between physical characteristics and S1/S2 frequency spectra Arnott PJ, Pfeiffer GW, Tavel ME. J Biomed Eng. 1984;6(2):121–128. Primary recording study newly consulted 2026-10-31 for relative S1/S2 spectral shape. Does not calibrate the original synthetic timbre coefficients.
  25. Analysis-synthesis of the phonocardiogram based on the matching pursuit method Zhang X, Durand LG, Senhadji L, Lee HC, Coatrieux JL. IEEE Trans Biomed Eng. 1998;45(8):962–971. Primary synthesis study newly consulted 2026-10-31 for multicomponent Gaussian-windowed transient representation; no patient recording or fitted reconstruction is supplied here.
  26. Continuous spectral analysis of heart murmurs for evaluating stenotic cardiac lesions Donnerstein RL. Am J Cardiol. 1989. Primary recorded stenotic/shunt-murmur spectral study newly consulted 2026-10-31 for time-varying murmur texture. Selected-population observations are not a universal murmur spectrum or severity formula.
  27. Assessment of severity of aortic stenosis through time-frequency analysis of murmur Kim D, Tavel ME. Chest. 2003;124(5):1638–1644. Primary recording study newly consulted 2026-10-31 for higher-frequency murmur content; the educational audio does not implement its severity regression or infer a clinical grade.
Mechanical circulatory support12
  1. Intra-Aortic Balloon Pumps Stanford Cardiovascular Anesthesia.
  2. Cardiosave IABP Operation/Transport Quick Reference Guide Getinge. Software B.
  3. Beat-to-beat effects of intraaortic balloon pump timing on left ventricular performance in patients with low ejection fraction Schreuder JJ, et al. Ann Thorac Surg. 2005;79:872–880.
  4. ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients Lorusso R, et al. ASAIO J. 2021;67:827–844. doi:10.1097/MAT.0000000000001510.Circuit flow, vascular load and LV unloading.
  5. Impella Ventricular Support Systems: Summary of Safety and Effectiveness Data US Food and Drug Administration / Abiomed. PMA P140003/S004. 2016.
  6. Pulse pressure and end-tidal carbon dioxide for monitoring low native cardiac output during veno-arterial ECLS Mourad M, et al. Crit Care. 2020;24:569.
  7. Left ventricular unloading during veno-arterial ECMO: a simulation study Donker DW, Brodie D, Henriques JPS, Broomé M. ASAIO J. 2019;65:11–20.
  8. Intra-Aortic Balloon Pump Exacerbates Left Ventricular Outflow Tract Obstruction in a Patient With Takotsubo and Hypertrophic Cardiomyopathy Griffin M, et al. CASE. 2023;7:502–507.
  9. Bard Sheathless Intra-Aortic Balloon Catheters: 510(k) Summary US Food and Drug Administration / Bard. K981660. Device labeling and contraindications.
  10. Pathophysiology of Heart Failure Klabunde RE. Cardiovascular Physiology Concepts. Revised November 2023.
  11. Overview, Indications, and Step-by-Step Techniques for Hemodynamic Support Devices Kandasamy VV, John AG, Singh V. ACC Coronary Interventions Handbook, Chapter 11. Accessed September 10, 2026.
  12. Comparative hemodynamic effects of Impella CP and TandemHeart Weil BR et al. JACC Cardiovasc Interv. 2016;9:2292–2303. Porcine infarction study; ventricular unloading and PV responses.
Lungs, oxygenation & imaging23
  1. Photoplethysmography and its application in clinical physiological measurement Allen J. Physiol Meas. 2007;28:R1–R39.
  2. Ventilator 101: settings, waveforms and auto-PEEP University of Iowa. Ventilator 101.Volume controlPressure supportAuto-PEEP
  3. Respiratory Rate and Pattern Braun SR. In: Clinical Methods. 3rd ed. Butterworths; 1990. Chapter 43.
  4. Pulse Oximeters US Food and Drug Administration.
  5. Pulmonary Edema Merck Manual Professional Edition.
  6. Unilateral Pulmonary Edema in Patients With Acute Mitral Regurgitation Caused by Chordal Rupture Nishimura Y, et al. Circ Rep. 2022;4:571–578.
  7. Differentiating Acute Pulmonary Edema and Asthma With the Lung Curtain Swing vs Time Graph: A Novel Application of Anatomical M-Mode Evaluation of Lung Swing Gunasegaren M, Lee CH. Chest. 2026;169:e61–e66.Previously linked respiratory imaging report; not validation of simulated respiratory-rate targets.
  8. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults Mitchell C, Rahko PS, Blauwet LA, et al. American Society of Echocardiography. J Am Soc Echocardiogr. 2019;32:1–64.Rechecked 6 November 2026 for Echo section coverage and resolution: required landmarks are sampled from the actual finite plane; synthetic geometry, acoustic material values and raster quality remain implementation assumptions.
  9. Guidelines for the Evaluation of Prosthetic Valve Function With Cardiovascular Imaging Zoghbi WA, et al. American Society of Echocardiography. 2024.
  10. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults and Special Considerations in Pulmonary Hypertension Mukherjee M, Rudski LG, Addetia K, et al. J Am Soc Echocardiogr. 2025;38:141–186. American Society of Echocardiography. Supplied guideline and primary publication consulted.Right-heart structure/function, RV inlet/apex/outflow anatomy, PH assessment and Doppler limits. Rechecked 1 November 2026; procedural mesh fitting remains schematic.
  11. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation Zoghbi WA, Adams D, Bonow RO, et al. ASE / SCMR. JASE. 2017;30:303–371.Integrated grading, color-jet limitations, chamber response, PR decay and Barlow morphology; rechecked 6 November 2026 for Echo PISA, vena contracta and regurgitant-volume methods. Original synthetic flow images are not validated quantification references.
  12. Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from ASE and EACVI Lang RM, Badano LP, Mor-Avi V, et al. J Am Soc Echocardiogr. 2015;28:1–39.e14.Chamber volumes/dimensions, EF, RV FAC, regional motion and LV wall geometry. Rechecked 1 November 2026: dimensions do not uniquely reconstruct a chamber; schematic mesh fitting and interpolation are unvalidated.
  13. Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart Cerqueira MD, Weissman NJ, Dilsizian V, et al. American Heart Association. Circulation. 2002;105:539–542.17-segment names and polar orientation; custom colors do not indicate a validated repair score.
  14. Guidelines for the Evaluation of Valvular Regurgitation After Percutaneous Valve Repair or Replacement Zoghbi WA, Asch FM, Bruce C, et al. J Am Soc Echocardiogr. 2019;32:431–475.Residual leak and obstruction require integrated assessment; geometry alone does not establish repair success.
  15. How Far Is the Sternal Angle from the Mid-right Atrium? Seth R, Magner P, Matzinger F, van Walraven C. J Gen Intern Med. 2002;17:852–856.
  16. Cardiovascular devices The Radiology Assistant. Chest radiographic device anatomy.
  17. AARC Clinical Practice Guideline: Patient-Ventilator Assessment American Association for Respiratory Care. Respir Care. 2024;69:1042–1054.Tidal volume, plateau pressure, PEEP and auto-PEEP assessment.
  18. Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome Fan E, Del Sorbo L, Goligher EC, et al. ATS/ESICM/SCCM. Am J Respir Crit Care Med. 2017;195:1253–1263.Lung-protective volume and plateau-pressure guidance.
  19. Oxygen Transport Pittman RN. Regulation of Tissue Oxygenation. Morgan & Claypool; 2011. Chapter 4.Oxygen content and the Hill dissociation relationship.
  20. Teaching an intuitive derivation of the clinical alveolar equations: mass balance as a fundamental physiological principle Wang MC, Corbridge TC, McCrimmon DR, Walter JM. Adv Physiol Educ. 2020;44:145–152.Alveolar ventilation, dead space and gas mass balance.
  21. Deadspace and the single breath test for carbon dioxide during anaesthesia and artificial ventilation Fletcher R, Jonson B. Br J Anaesth. 1984;56:109–119.Tidal volume, frequency and dead-space effects.
  22. Dynamic handgrip exercise for the evaluation of mitral valve regurgitation Alachkar MN, et al. Int J Cardiovasc Imaging. 2021;37:891–902.Variable MR response to loading.
  23. A Thrilling Precordial Honk Amoroso NS, Som S, Carabello BA. American College of Cardiology. 2016.Dynamic MR and prolapse respond differently to changes in loading.
Medication prescribing information33
  1. Isoproterenol hydrochloride injection DailyMed. US National Library of Medicine. Prescribing information.
  2. Ephedrine sulfate injection DailyMed. US National Library of Medicine. Prescribing information.
  3. Amiodarone hydrochloride injection DailyMed. US National Library of Medicine. Prescribing information.
  4. Procainamide hydrochloride injection DailyMed. US National Library of Medicine. Prescribing information.
  5. Lidocaine hydrochloride and dextrose injection DailyMed. US National Library of Medicine. Prescribing information.
  6. Vasopressin injection DailyMed. US National Library of Medicine. Prescribing information.Additional pharmacology label
  7. Phenylephrine hydrochloride injection DailyMed. US National Library of Medicine. Prescribing information.Additional pharmacology label
  8. Milrinone lactate injection DailyMed. US National Library of Medicine. Prescribing information.Additional pharmacology label
  9. Metoprolol tartrate injection DailyMed. US National Library of Medicine. Prescribing information.Earlier cited label
  10. Digoxin injection DailyMed. US National Library of Medicine. Prescribing information.Earlier cited label
  11. Furosemide injection Hospira. DailyMed prescribing information. Revised October 2024; label updated May 2026.Additional pharmacology label
  12. Nitroglycerin injection DailyMed. US National Library of Medicine. Prescribing information.Sublingual pharmacology label
  13. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis Khot UN, et al. N Engl J Med. 2003;348:1756–1763. Selected, invasively monitored LV failure; hypotension and pressor/inotrope dependence excluded.
  14. Complications Associated With Nitrate Use in Patients Presenting With Acute Pulmonary Edema and Concomitant Moderate or Severe Aortic Stenosis Claveau D, et al. Ann Emerg Med. 2015;66:355–362.e1. Retrospective evidence; vasodilator tolerance depends on context.
  15. Sodium nitroprusside injection DailyMed. US National Library of Medicine. Prescribing information.Additional pharmacology label
  16. Epoprostenol injection DailyMed. US National Library of Medicine. Prescribing information. Rechecked 2026-10-30 for pulmonary hypertension mechanism-of-action teaching.Additional pharmacology label
  17. INOmax (nitric oxide gas) DailyMed. US National Library of Medicine. Prescribing information.Additional pharmacology labelLV dysfunction: pulmonary edema and increased wedge-pressure warning.
  18. Amyl nitrite inhalant DailyMed. US National Library of Medicine. Prescribing information.
  19. Epinephrine injection DailyMed. US National Library of Medicine. Prescribing information.
  20. Dopamine hydrochloride injection DailyMed. US National Library of Medicine. Prescribing information.
  21. Dobutamine injection Hikma Pharmaceuticals USA Inc. DailyMed prescribing information; updated July 2, 2024.Contractile support, variable BP response, reduced SVR and hypotension.
  22. Norepinephrine injection DailyMed. US National Library of Medicine. Prescribing information.Vascular resistance and pressor action.
  23. OPSYNVI (macitentan and tadalafil) US prescribing information; current label accessed October 2026 Janssen Pharmaceuticals; DailyMed. 2026. Consulted for Ask the exPHert therapy options, monitoring and eligibility; local prescribing information governs use.
  24. LETAIRIS (ambrisentan) US prescribing information; current label accessed October 2026 Gilead Sciences; DailyMed. 2026. Consulted for Ask the exPHert therapy options, monitoring and eligibility; local prescribing information governs use.
  25. UPTRAVI (selexipag) US prescribing information; current label accessed October 2026 Actelion / Janssen; DailyMed. 2026. Consulted for Ask the exPHert therapy options, monitoring and eligibility; local prescribing information governs use.
  26. ADEMPAS (riociguat) US prescribing information; current label accessed October 2026 Bayer; DailyMed. 2026. Consulted for Ask the exPHert therapy options, monitoring and eligibility. Current label rechecked 2026-10-31 for Current Landscape prominence: PAH and inoperable CTEPH or persistent/recurrent PH after surgery remain separate indications; local prescribing information governs use. August 2026 FDA label rechecked 31 October 2026 for the contraindication to concomitant PDE5 inhibitors and riociguat; active-riociguat result wording must not suggest adding sildenafil/tadalafil.
  27. REMODULIN (treprostinil injection) US prescribing information; current label accessed October 2026 United Therapeutics; DailyMed. Label updated 2026-07-02; rechecked 2026-10-30 for Ask the exPHert and distinct continuous-SC treprostinil simulator route, established-treatment time context, infusion continuity and safety. The original synthetic SC response range is not a trial mean, dose-equivalence conversion or head-to-head route-potency estimate; local prescribing information governs use.
  28. TYVASO (treprostinil inhalation solution) US prescribing information; current label accessed October 2026 United Therapeutics; DailyMed. 2026. Consulted for Ask the exPHert therapy options, monitoring and eligibility. Current label rechecked 2026-10-31 for Current Landscape prominence: inhaled treatment of PH-ILD is not an indication for PH-COPD, all group 3 PH or other treprostinil routes; local prescribing information governs use.
  29. Trepulmix: European public assessment report and therapeutic indication European Medicines Agency. Authorized 2020; current indication consulted 2026-10-31 for Current Landscape editorial applicability. Continuous SC treprostinil is restricted to adults with WHO FC III–IV inoperable or persistent/recurrent CTEPH after surgery; regional authorization is not generalized to other routes or settings.
  30. ORENITRAM (oral treprostinil extended release) US prescribing information; current label accessed October 2026 United Therapeutics; DailyMed. Label updated 2024-11-20; rechecked 2026-10-30 for mechanism-of-action teaching and distinct extended-release oral treprostinil simulator route, established titration, interactions and interruption/transition safety. Synthetic response intensity is not a tablet dose or an equivalent replacement for an indicated infusion; local prescribing information governs use.
  31. Amlodipine besylate US prescribing information: mechanism of action; current label accessed October 2026 US National Library of Medicine / DailyMed. Current label consulted 2026-10-30 for pulmonary hypertension mechanism-of-action teaching and safety distinctions.
  32. REVATIO (sildenafil) prescribing information Pfizer. US prescribing information via DailyMed, consulted 31 October 2026 for PAH context and nitrate/riociguat contraindications. Supports qualitative pharmacology, not synthetic numerical pressure or dose-response predictions.
  33. Propranolol prescribing information DailyMed. US prescribing information, consulted 31 October 2026 for beta blockade, bradycardia and contraindications. The separate congenital guideline supplies the dynamic infundibular-obstruction context.
PEEP, pressure transmission & heart–lung interactions15
  1. Positive Pressure Ventilation in the Cardiac Intensive Care Unit Alviar CL, Miller PE, McAreavey D, et al. JACC. 2018;72:1532–1553.Heart–lung relationships, reduced venous return, RV loading risk and possible unloading benefit in congested hypokinetic LV failure inform phenotype-specific PEEP checks. No blanket BP penalty is imposed. Fixed transmission, recruitment and response coefficients are original teaching assumptions, not validated patient-response curves.
  2. Effect of positive end-expiratory pressure on right ventricular function in humans Pinsky MR, Desmet JM, Vincent JL. Am Rev Respir Dis. 1992;146:681–687.
  3. Cardiac performance in response to PEEP in patients with cardiac dysfunction Grace MP, Greenbaum DM. Crit Care Med. 1982;10:358–360.
  4. Hemodynamic alterations with positive end-expiratory pressure: the contribution of the pulmonary vasculature Hobelmann CF Jr, Smith DE, Virgilio RW, et al. J Trauma. 1975;15:951–959.
  5. Clinical review: Positive end-expiratory pressure and cardiac output Luecke T, Pelosi P. Crit Care. 2005;9:607–621.
  6. Guide to the SI: pressure conversion factors NIST SP 811, Appendix B.9. Conventional cmH₂O and mmHg.
  7. Interaction between respiration and right versus left ventricular volumes at rest and during exercise: a real-time cardiac magnetic resonance study Claessen G, Claus P, Delcroix M, et al. Am J Physiol Heart Circ Physiol. 2014;306:H816–H824.
  8. Prevention of complications in the cardiac intensive care unit Fordyce CB et al. AHA scientific statement. Circulation. 2020;142:e379–e406. Ventilation, RV loading and LV unloading.
  9. Cardiovascular effects of positive-pressure ventilation in normal subjects Cassidy SS et al. J Appl Physiol. 1979;47:453–461. Measured biventricular and output responses to PEEP.
  10. Respiratory-Cardiovascular Interactions During Mechanical Ventilation: Physiology and Clinical Implications Kreit J. Compr Physiol. 2022;12:3425–3448.
  11. Heart-lung interactions during mechanical ventilation: the basics Mahmood SS, Pinsky MR. Ann Transl Med. 2018;6:349.
  12. Extent to which pulmonary vascular responses to PCO₂ and PO₂ play a functional role within the healthy human lung Dorrington KL, Balanos GM, Talbot NP, Robbins PA. J Appl Physiol. 2010;108:1084–1096.
  13. Acute Effects of Positive Airway Pressure on Functional Mitral Regurgitation in Patients with Systolic Heart Failure Kato T, et al. Front Physiol. 2017;8:921.Functional MR may decrease; forward-flow response varies.
  14. Effect of PEEP, blood volume, and inspiratory hold maneuvers on venous return Berger D, et al. Am J Physiol Heart Circ Physiol. 2016;311:H794–H806.
  15. Venturi valves and minimum flow rates Intersurgical Ltd. Venturi valves product information and Venturi-7-poster-int, June 2024; accessed 30 October 2026.June 2024 minimum flow-rate posterDocuments nominal fixed-performance concentrations of 24, 28, 31, 35, 40, 50 and 60% at specified device flows. The generic educational mask assumes adequate flow; preset choice is not calibrated patient FiO2 and does not imply positive pressure. Manufacturer-specific colours and flow prescriptions are not generalized in the interface.
Biventricular diagrams & valve pressure gradients5
  1. SCAI/HFSA expert consensus document on the use of invasive hemodynamics for the diagnosis and management of cardiovascular disease Sorajja P, Borlaug BA, Dimas VV, et al. Catheter Cardiovasc Interv. 2017;89:E233–E247. Simultaneous central-pressure comparison; phase-delay, damping and peripheral-amplification limitations.
  2. Methods for measuring right ventricular function and hemodynamic coupling with the pulmonary vasculature Bellofiore A, Chesler NC. Ann Biomed Eng. 2013;41:1384–1398.
  3. Valvular insufficiency (regurgitation) Klabunde RE. Cardiovascular Physiology Concepts. Revised January 23, 2024. Systolic LV–LA pressure differences, regurgitant flow and atrial v waves.
  4. Physiology, pulse pressure Homan TD, Bordes SJ, Cichowski E. StatPearls. Updated July 10, 2023.
  5. Invasive right ventricular pressure–volume analysis Brener MI et al. Circ Heart Fail. 2022;15:e009101. Principles and practical recommendations.
Non-sustained ventricular tachycardia4
  1. 2022 ESC Guidelines for ventricular arrhythmias and prevention of sudden cardiac death Zeppenfeld K, et al. Eur Heart J. 2022;43:3997–4126.
  2. Incomplete filling and incoordinate contraction as mechanisms of hypotension during ventricular tachycardia in man Lima JAC, et al. Circulation. 1983;68:928–938.
  3. Amiodarone hydrochloride injection: prescribing information DailyMed. Ventricular arrhythmia suppression, hypotension and conduction precautions.
  4. Lidocaine hydrochloride injection: prescribing information DailyMed. Acute ventricular arrhythmias and conduction precautions.
Sedation and cardiorespiratory interactions8
  1. Propofol injectable emulsion: prescribing information DailyMed. Maintenance infusion, cardiovascular depression and ventilation.
  2. Ketamine hydrochloride injection: prescribing information DailyMed. Sympathetic responses, catecholamine depletion and respiratory precautions.
  3. Midazolam hydrochloride injection: prescribing information DailyMed. Sedation, opioid interactions and adult infusion dosing.
  4. Dexmedetomidine injection: prescribing information DailyMed. Maintenance infusion, bradycardia and hypotension; loading is not simulated.
  5. Fentanyl citrate injection: prescribing information DailyMed. Respiratory depression, opioid-sedative interactions and cardiovascular effects.
  6. Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans Kiely DG, Cargill RI, Lipworth BJ. Chest. 1996;109:1215–1221.
  7. Ketamine in the treatment of bronchospasm during mechanical ventilation Hemmingsen C, Nielsen PK, Odorico J. Am J Emerg Med. 1994;12:417–420.
  8. Negative results for ketamine use in severe acute bronchospasm: a randomised controlled trial Nedel WL, et al. Anaesthesiol Intensive Ther. 2020.
Acute PE & reperfusion6
  1. 2026 acute pulmonary embolism guideline Creager MA et al. AHA/ACC multisociety guideline. JACC. 2026.High-risk PE, RV failure, cautious fluid loading and urgent reperfusion assessment inform the PE teaching case; response magnitudes are synthetic.
  2. Utility of electrocardiographic findings in acute pulmonary embolism European Heart Journal Open. 2023;3:oead121. ECG/RV-strain associations.
  3. ECG differentiation of acute pulmonary embolism and acute coronary syndromes Annals of Noninvasive Electrocardiology. 2010. S1S2S3, S1Q3T3 and T-wave patterns are not diagnostic in isolation.
  4. Acute pulmonary embolism presenting with symptomatic bradycardia Alreshq R, Hsu G, Torosoff M. Am J Case Rep. 2019;20:748–752. Uncommon presentation; case report.
  5. 2023 ESC acute coronary syndromes guideline Byrne RA et al. European Heart Journal. 2023;44:3720–3826.
  6. Activase (alteplase) prescribing information Genentech. Revised September 2022. MI/PE indications, dosing, risks and contraindications.
Septic shock and inotropic support1
  1. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 SCCM / ESICM. 2026.Inotropes for persistent hypoperfusion with cardiac dysfunction; not routine hyperdynamic vasoplegia.
Structural Heart modeling30
  1. EAE/ASE Recommendations for Image Acquisition and Display Using Three-Dimensional Echocardiography Lang RM, Badano LP, Tsang W, et al. J Am Soc Echocardiogr. 2012;25:3–46. Primary society guideline rechecked October 30, 2026.Clear R-wave acquisition and ECG-gating limitations in 3D echo; the synthetic sinus strip, phase-zero R gate and prescribed-pressure timing are original display conventions, not patient ECG or validated electromechanical delay.
  2. MitraClip G4 device dimensions Abbott. MitraClip G4 product brochure. 2021. MAT-2103793 v1.0, p. 3.NT/NTW/XT/XTW dimensions only; schematic constraints are original and unvalidated.
  3. TriClip G4 System Instructions for Use Abbott. EL2140056, March 28, 2024. Table 2, p. 4. FDA-hosted manufacturer labeling.G4 arm dimensions; not validation of simulated capture or repair outcomes.
  4. Clip Selection Strategy with 4th Generation MitraClip Maisano F, Denti P, Mahoney P, et al. Abbott / PCR London Valves presentation. 2022. MAT-2213595 v1.0.Clinical anatomical considerations do not make the prototype a device-selection tool.
  5. Mitral Valve: TSRA Primer Kakavand M, Chen L. American Association for Thoracic Surgery. Accessed October 2026.Carpentier motion classes; synthetic preset dimensions and constraints are original.
  6. Repair-oriented classification of aortic insufficiency: impact on surgical techniques and clinical outcomes Boodhwani M, de Kerchove L, Glineur D, et al. J Thorac Cardiovasc Surg. 2009;137:286–294.Aortic functional classes; observed repair outcomes do not validate this prototype.
  7. Recommended Standards for the Performance of Transesophageal Echocardiographic Screening for Structural Heart Intervention Hahn RT, Saric M, Faletra FF, et al. American Society of Echocardiography. J Am Soc Echocardiogr. 2022;35:1–76.Ventricular remodeling and leaflet tethering; reduced coupling coefficients remain illustrative.
  8. 2020 Focused Update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation Bonow RO, O’Gara PT, Adams DH, et al. J Am Coll Cardiol. 2020;75:2236–2270.Secondary MR mechanisms; not validation of simulated repair outcomes.
  9. Fibrous Skeleton of the Heart: Anatomic Overview and Evaluation of Pathologic Conditions with CT and MR Imaging Saremi F, Sánchez-Quintana D, Mori S, et al. RadioGraphics. 2017;37:1330–1351.Fibrous continuity and muscular pulmonary support; procedural mesh dimensions are original.
  10. Cardiac anatomy revisited Anderson RH, Razavi R, Taylor AM. J Anat. 2004;205:159–177.Chamber, appendage and outflow relationships; original schematic surfaces are not patient reconstructions.
  11. A Computational Framework for Atrioventricular Valve Modeling Using Open-Source Software Wu W, Ching S, Maas SA, et al. J Biomech Eng. 2022;144(10):101012. Methodological reference; does not validate this prototype.
  12. Neochord Placement vs Triangular Resection in Mitral Valve Repair: A Finite Element Model Morgan AE, Pantoja JL, Grossi EA, et al. J Surg Res. 2016;206(1):98–105.
  13. 3D Slicer extension installation and management 3D Slicer contributors. Official Extensions user guide, consulted October 2026 for installing, enabling and restarting native extension modules. Module presence does not validate a companion workflow.
  14. QLAB cardiovascular ultrasound quantification software Philips. Official product description, consulted October 2026 for guided mitral-valve review and 3D multiplanar distance/area measurement workflows. This is workflow context, not validation of Circulation Studio measurements or equivalence to QLAB.
  15. EPIQ CVx diagnostic ultrasound system specifications Philips. Official system specifications, 2021 asset. Sections on Cardiac 3D Quantification and Mitral Valve Navigator, pp. 32–33, consulted October 2026 for plane rotation, tilt, spatial reference and measurement/reporting workflow. Proprietary implementation and clinical performance are not reproduced.
  16. SlicerHeart: an open-source cardiac modeling platform Lasso A, Herz C, Nam H, et al. Front Cardiovasc Med. 2022;9:886549. Official export and interoperability documentation consulted October 2026.
  17. Image3dAPI: ultrasound volume interface, Python examples, geometry documentation and license GE Healthcare / MedicalUltrasound. Official IImage3d interface, TestPython examples/utilities, transducer-geometry wiki and API license; consulted 3 November 2026 for the local GE converter. These sources specify data access and provenance, not validation of Circulation Studio or a supplied E95/E90 dataset.
  18. GE cardiovascular ultrasound Image3dAPI loader installation instructions GE Healthcare. Image3dLoaderGe README, 2019, distributed in the SlicerHeart GE_CVUS_Loader-3.9.0 source tree; consulted 3 November 2026 for the cardiac ProgID, 64-bit runtime and registration/manifest requirements. Vendor binaries and SDK are not redistributed by Circulation Studio.
  19. Computational simulation model of transcatheter edge-to-edge mitral valve repair: a proof-of-concept study Messika-Zeitoun D, Mousavi J, Pourmoazen M, et al. Eur Heart J Cardiovasc Imaging. 2024;25(10):1415–1422.
  20. Tricuspid valve edge-to-edge repair simulations are highly sensitive to annular boundary conditions Haese CE, Dubey V, Mathur M, et al. J Mech Behav Biomed Mater. 2025;163:106879.
  21. The effect of mitral annuloplasty shape in ischemic mitral regurgitation: a finite element simulation Wong VM, Wenk JF, Zhang Z, et al. Ann Thorac Surg. 2012;93(3):776–782.
  22. Contribution of computational model for assessment of heart tissue local stress caused by suture in LVAD implantation Chalon A, Favre J, Piotrowski B, et al. J Mech Behav Biomed Mater. 2018;82:291–298. Myocardial contact model; not validation of leaflet mechanics.
  23. A Computational Study of Patch Implantation and Mitral Valve Mechanics Singh D. University of Kentucky doctoral dissertation. 2019.
  24. DICOM image pixels, colour, compression, geometry, segmentation and surface definitions DICOM Standards Committee. Current standard, consulted October 2026.
  25. dicom-parser: browser-compatible DICOM Part 10 parsing Hafey C and Cornerstone contributors. MIT license; version 1.8.21.
  26. The assessment of mitral valve disease: a guideline from the British Society of Echocardiography Robinson S, Ring L, Augustine DX, et al. Echo Res Pract. 2021;8:G87–G136. Rechecked 6 November 2026 for Echo anatomy: asymmetric anterior/posterior leaflets, saddle annulus, papillary/chordal support and continuity. Original synthetic geometry and motion coefficients are not clinical measurements.
  27. ConnectedThresholdImageFilter: seeded intensity region growth SimpleITK contributors. Official documentation, consulted October 2026. Algorithm reference; not a validated valve classifier.
  28. vtkTetra: linear tetrahedron and contour extraction VTK contributors. Official documentation, consulted October 2026. Method reference for the original binary-surface implementation.
  29. Evolution from mitral annular dysfunction to severe mitral regurgitation in Barlow’s disease Hiemstra YL, Tomsic A, Gripari P, et al. Interact Cardiovasc Thorac Surg. 2021;32(4):506–514.Observed Barlow morphology; does not validate synthetic geometry or repair mechanics.
  30. EchoSlicer: 3D echo byte layout and scan conversion Vukadinovic M, Ieki H, Sahashi Y, Ouyang D, He B. Automated Interpretable 2D Video Extraction from 3D Echocardiography. arXiv:2511.15946, 2025; official implementation consulted October 2026. Experimental import reference, not validation of this simulator.
Pulmonary hypertension: risk, diagnosis and treatment239
  1. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension Hoeper MM, Pausch C, Olsson KM, et al. Eur Respir J. 2022;60:2102311. Primary derivation publication consulted.Three core variables, four risk grades and mean score. Original derivation used complete core measurements; cohort outcomes are not individual probabilities. Rechecked 2026-10-30 for visual-learning presentation: model eligibility and published variables remain in the original explanation; numerical scoring is unchanged.
  2. External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry Boucly A, Weatherald J, Savale L, et al. Eur Respir J. 2022;59:2102419. Primary validation publication consulted.Confirms nearest-integer rounding of the average four-strata grade, rather than always rounding upward. Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Observational validation with missing follow-up data. It does not validate screening for PAH, estimate ILD prognosis or prove that treatment triggered by the score improves survival.
  3. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies Benza RL, Gomberg-Maitland M, Elliott CG, et al. Chest. 2019;156:323–337. Primary REVEAL 2.0 publication consulted.Full model uses 13 weighted variables plus correction factor 6; category cutoffs differ from REVEAL Lite 2.
  4. Development and Validation of an Abridged Version of the REVEAL 2.0 Risk Score Calculator, REVEAL Lite 2, for Use in Patients With Pulmonary Arterial Hypertension Benza RL, Kanwar MK, Raina A, et al. Chest. 2021;159:337–346. Published online 2020. Primary full-text publication consulted.Table 1 supplies exact full and Lite points. Lite requires at least three of six variables including two of functional class, walk distance and BNP/NT-proBNP for the studied missing-data performance. Published missing-variable convention is zero points, explicitly disclosed by the calculator.
  5. Risk stratification and treatment goals in pulmonary arterial hypertension Dardi F, Boucly A, Benza R, et al. Eur Respir J. 2024;64:2401323. 7th World Symposium on Pulmonary Hypertension. Supplied paper and primary publication consulted.Risk-tool purposes, minimum evaluable elements, nearest-integer four-strata grading and the need to integrate right-heart imaging, haemodynamics, trajectory and comorbidities.
  6. Definition, classification and diagnosis of pulmonary hypertension Kovacs G, Bartolome S, Denton CP, et al. Eur Respir J. 2024;64:2401324. 7th World Symposium on Pulmonary Hypertension. Supplied paper and primary publication consulted.Definitions and clinical classification inform the transparent rule-based PH workup differential, not a validated patient classifier. Rechecked 2026-10-30 against the primary ERS publication for the PH visual topic maps: haemodynamic phenotype, clinical groups and diagnostic context. The diagrams organize existing cited text; no model or treatment rule is changed.
  7. European Respiratory Society clinical practice guidelines update for the treatment of pulmonary arterial hypertension (accepted Early View version) Kovacs G, Zeder K, Humbert M, et al. 2026. Guideline. Supplied source, cross-checked for the PH module.Accepted Early View ERS focused treatment update, supplied as “ESC 2026.pdf”; addresses sotatercept and follow-up RHC rather than replacing every section of the 2022 ESC/ERS guideline.
  8. Treatment algorithm for pulmonary arterial hypertension Chin KM, Gaine SP, Gerges C, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module. Rechecked 2026-10-30 for mechanism viewer, delivery-route distinctions and conditional treatment discussions. Primary full text rechecked 2026-10-31 for established PAH pathways, selected CCB responders and supportive oxygen in Current Landscape. Rechecked 31 October 2026 for explicit ERA/PDE5-inhibitor examples, parenteral prostacyclin names and conditional Ask the exPHert medication-class labels; not a patient-specific prescription.
  9. Pathophysiology of the right ventricle and its pulmonary vascular interaction Hemnes AR, Celermajer DS, D’Alto M, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module.
  10. Pulmonary hypertension associated with left heart disease Maron BA, Bortman G, De Marco T, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module. Primary publication rechecked 2026-10-31 for Current Landscape: optimize underlying heart failure; SGLT2 therapy is not a general PH-specific indication and PAH drugs are not broadly established in group 2.
  11. Pulmonary hypertension associated with lung diseases Shlobin OA, Adir Y, Barbera JA, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module. Primary full text rechecked 2026-10-31 for Current Landscape: phenotype-specific PH-ILD evidence and treatment uncertainty remain distinct from adverse PH-COPD findings.
  12. Chronic thromboembolic pulmonary disease Kim NH, D’Armini AM, Delcroix M, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module. Primary full text rechecked 2026-10-31 for Current Landscape: lifelong anticoagulation, VKA and antiphospholipid context, DOAC uncertainty, PEA/BPA evaluation, riociguat and selected SC treprostinil.
  13. Genetics and precision genomics approaches to pulmonary hypertension Austin ED, Aldred MA, Alotaibi M, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module.
  14. Pathology and pathobiology of pulmonary hypertension: current insights and future directions Guignabert C, Aman J, Bonnet S, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module.
  15. Emerging multimodality imaging techniques for the pulmonary circulation Rajagopal S, Bogaard HJ, Elbaz MSM, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module.
  16. Management of pulmonary hypertension in special conditions Preston IR, Howard LS, Langleben D, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module.
  17. Transplantation, bridging, and support technologies in pulmonary hypertension Savale L, Benazzo A, Corris P, et al.; 7th WSPH 2024. Consensus. Supplied source, cross-checked for the PH module.
  18. Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PULSAR) Humbert M, McLaughlin V, Gibbs JSR, et al. 2021. Trial. Supplied source, cross-checked for the PH module. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  19. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension (STELLAR) Hoeper MM, Badesch DB, Ghofrani HA, et al. 2023. Trial. Supplied source, cross-checked for the PH module. Rechecked 2026-10-30 to inform the direction and time context of bounded synthetic pulmonary-therapy teaching effects and the interactive RHC lab's later sustained sotatercept snapshot; coefficients are original, not fitted clinical dose responses or validated patient forecasts. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit. Rechecked 2026-11-01 for established ERA/PDE5 and later sotatercept treatment context. Off/On selects an original representative model endpoint, not a dose or fitted trial effect.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. The overall estimate is not a separately established SSc treatment effect and does not apply to PH-LHD or substantial PH-ILD. Hemoglobin, platelets and bleeding surveillance are relevant, particularly with SSc vascular/GI disease.
  20. Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death (ZENITH) Humbert M, McLaughlin VV, Badesch DB, et al. 2025. Trial. Supplied source, cross-checked for the PH module.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Early stopping and a composite endpoint require careful interpretation. The overall result is not independent SSc-specific efficacy or isolated mortality proof, and it does not establish treatment for non-PAH CTD-PH phenotypes.
  21. Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis (HYPERION) McLaughlin VV, Hoeper MM, Badesch DB, et al. 2025. Trial. Newly consulted source for the PH module.
  22. A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA Preston IR, Badesch D, Ghofrani HA, et al. 2025. Trial. Supplied source, cross-checked for the PH module.
  23. SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension Waxman AB, Systrom DM, Manimaran S, et al. 2024. Trial. Supplied source, cross-checked for the PH module.
  24. Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial Souza R, Badesch DB, Ghofrani HA, et al. 2023. Original research. Supplied source, cross-checked for the PH module.Study registration
  25. WINREVAIR (sotatercept-csrk) full US prescribing information, revised September 2026 Merck Sharp & Dohme; DailyMed / US FDA 2026. Label. Newly consulted source for the PH module. Current label rechecked 2026-10-31 for adult group 1 PAH applicability in Current Landscape; does not establish an indication in other PH groups.
  26. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease (INCREASE) Waxman A, Restrepo-Jaramillo R, Thenappan T, et al. 2021. Trial. Newly consulted source for the PH module. Rechecked 2026-10-31 for Current Landscape: confirmed PH-ILD and inhaled-treatment results remain distinct from adjacent IPF cohorts and other routes. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventionsReviewed 7 November 2026 for the focused CTD/SSc literature reading guide. The +31.12 m estimate is for the whole trial, not a CTD-specific effect. Short follow-up and subgroup size limit SSc-specific and survival conclusions; do not generalise to other vasodilators or all lung disease.
  27. Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results Nathan SD, Argula RG, Trivieri MG, et al. 2024. Trial. Newly consulted source for the PH module. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  28. A Comparison of Continuous Intravenous Epoprostenol (Prostacyclin) with Conventional Therapy for Primary Pulmonary Hypertension Barst RJ, Rubin LJ, Long WA, et al. 1996. Trial. Newly consulted source for the PH module. Rechecked 2026-10-30 to inform the direction and time context of bounded synthetic pulmonary-therapy teaching effects; coefficients are original, not fitted clinical dose responses.
  29. Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension (SERAPHIN) Pulido T, Adzerikho I, Channick RN, et al. 2013. Trial. Newly consulted source for the PH module.
  30. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension (AMBITION) Galiè N, Barberà JA, Frost AE, et al. 2015. Trial. Newly consulted source for the PH module. Primary abstract rechecked 2026-10-31 for Current Landscape combination-versus-monotherapy attribution.
  31. Selexipag for the Treatment of Pulmonary Arterial Hypertension (GRIPHON) Sitbon O, Channick R, Chin KM, et al. 2015. Trial. Newly consulted source for the PH module.
  32. Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension (CHEST-1) Ghofrani HA, D’Armini AM, Grimminger F, et al. 2013. Trial. Newly consulted source for the PH module. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  33. Balloon pulmonary angioplasty versus riociguat for inoperable chronic thromboembolic pulmonary hypertension (RACE) Jaïs X, Brenot P, Bouvaist H, et al. 2022. Trial. Newly consulted source for the PH module. Primary abstract rechecked 2026-10-31 for Current Landscape: the active comparison favored BPA over riociguat for PVR with more BPA-related serious adverse events; the positive comparison is not attributed independently to riociguat. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  34. Pulmonary Arterial Hypertension Hassoun PM 2021. Review. Supplied source, cross-checked for the PH module.
  35. Diagnosis of pulmonary hypertension Frost A, Badesch D, Gibbs JSR, et al.; 6th WSPH 2019. Consensus. Supplied source, cross-checked for the PH module.
  36. An Evaluation of Long-term Survival From Time of Diagnosis in Pulmonary Arterial Hypertension From the REVEAL Registry Benza RL, Miller DP, Barst RJ, et al. 2012. Original research. Supplied source, cross-checked for the PH module.
  37. Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography Augustine DX, Coates-Bradshaw LD, Willis J, et al. 2018. Guideline. Supplied source, cross-checked for the PH module.
  38. Echocardiography in Pulmonary Arterial Hypertension: Comprehensive Evaluation and Technical Considerations Topyła-Putowska W, Tomaszewski M, Wysokiński A, Tomaszewski A 2021. Review. Supplied source, cross-checked for the PH module.
  39. Echocardiographic assessment of pulmonary hypertension: standard operating procedure Howard LS, Grapsa J, Dawson D, et al. 2012. Review. Supplied source, cross-checked for the PH module.
  40. Validity of echocardiographic tricuspid regurgitation gradient to screen for new definition of pulmonary hypertension Gall H, Yogeswaran A, Fuge J, et al. 2021. Original research. Supplied source, cross-checked for the PH module.
  41. Accuracy of Doppler-Echocardiographic Mean Pulmonary Artery Pressure for Diagnosis of Pulmonary Hypertension Er F, Ederer S, Nia AM, et al. 2010. Original research. Supplied source, cross-checked for the PH module.
  42. Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomized placebo-controlled phase 2 trial Frantz RP, McLaughlin VV, Sahay S, et al. 2024. Trial. Newly consulted source for the PH module.
  43. PROSERA phase 3 seralutinib topline results (sponsor report, 23 February 2026) Gossamer Bio 2026. Sponsor report. Newly consulted source for the PH module.Sponsor-reported topline results, not a peer-reviewed full trial report; described separately from published trial evidence.
  44. Sotatercept in Pulmonary Arterial Hypertension: Central, Hematologic, and Peripheral Mechanisms of Benefit Reddy YNV, Frantz RP, Miranda WR, et al. 2026. Original research. Newly consulted source for the PH module.
  45. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease: a randomized, controlled trial Badesch DB, Tapson VF, McGoon MD, et al. 2000. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Open-label, short trial using historical definitions and conventional background care. It did not establish a separate SSc survival benefit. Infusion and central-line complications matter.
  46. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension Simonneau G, Barst RJ, Galiè N, et al. Am J Respir Crit Care Med. 2002;165:800–804. Primary randomized 12-week study in 470 participants, rechecked 2026-10-30 for the SC treprostinil direction and later-treatment context as well as landmark evidence. It does not calibrate the synthetic response strengths, compare oral versus infused route potency or establish the effect size of the four-drug teaching preset.
  47. Inhaled Iloprost for Severe Pulmonary Hypertension (AIR) Olschewski H, Simonneau G, Galiè N, et al. 2002. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  48. Bosentan Therapy for Pulmonary Arterial Hypertension (BREATHE-1) Rubin LJ, Badesch DB, Barst RJ, et al. 2002. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  49. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial (ALPHABET) Galiè N, Humbert M, Vachiéry JL, et al. 2002. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  50. Beraprost therapy for pulmonary arterial hypertension Barst RJ, McGoon M, McLaughlin V, et al. 2003. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  51. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2 Humbert M, Barst RJ, Robbins IM, et al. 2004. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  52. Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension (SUPER-1) Galiè N, Ghofrani HA, Torbicki A, et al. 2005. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  53. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study (BREATHE-5) Galiè N, Beghetti M, Gatzoulis MA, et al. 2006. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  54. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension (STEP) McLaughlin VV, Oudiz RJ, Frost A, et al. 2006. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  55. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension (COMBI) Hoeper MM, Leuchte H, Halank M, et al. 2006. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  56. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ARIES studies 1 and 2 Galiè N, Olschewski H, Oudiz RJ, et al. 2008. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  57. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study) Galiè N, Rubin LJ, Hoeper MM, et al. 2008. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  58. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension (PACES-1) Simonneau G, Rubin LJ, Galiè N, et al. 2008. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  59. Tadalafil therapy for pulmonary arterial hypertension (PHIRST) Galiè N, Brundage BH, Ghofrani HA, et al. 2009. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  60. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial (TRIUMPH-I) McLaughlin VV, Benza RL, Rubin LJ, et al. 2010. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  61. Oral treprostinil for pulmonary arterial hypertension on background ERA and/or PDE5 inhibitor therapy: FREEDOM-C Tapson VF, Torres F, Kermeen F, et al. 2012. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  62. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: FREEDOM-M Jing ZC, Parikh K, Pulido T, et al. 2013. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  63. Oral treprostinil for pulmonary arterial hypertension on background therapy: FREEDOM-C2 Tapson VF, Jing ZC, Xu KF, et al. 2013. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  64. Riociguat for the Treatment of Pulmonary Arterial Hypertension (PATENT-1) Ghofrani HA, Galiè N, Grimminger F, et al. 2013. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  65. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study Hoeper MM, Barst RJ, Bourge RC, et al. 2013. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  66. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension (COMPASS-2) McLaughlin VV, Channick RN, Ghofrani HA, et al. 2015. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  67. Macitentan for the treatment of portopulmonary hypertension (PORTICO) Sitbon O, Bosch J, Cottreel E, et al. 2019. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  68. Evaluation of Macitentan in Patients With Eisenmenger Syndrome (MAESTRO) Gatzoulis MA, Landzberg M, Beghetti M, et al. 2019. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  69. Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension: FREEDOM-EV White RJ, Jerjes-Sanchez C, Bohns Meyer GM, et al. 2020. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  70. Three- Versus Two-Drug Therapy for Patients With Newly Diagnosed Pulmonary Arterial Hypertension (TRITON) Chin KM, Sitbon O, Doelberg M, et al. 2021. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  71. Switching to riociguat versus maintenance therapy with PDE5 inhibitors in pulmonary arterial hypertension (REPLACE) Hoeper MM, Al-Hiti H, Benza RL, et al. 2021. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Primary abstract rechecked 2026-10-31 for Current Landscape: switching to riociguat was compared with continued PDE5 inhibition; the successful switching comparison is not attributed as an independent positive sildenafil or tadalafil result. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  72. Assessing Daily Life Physical Activity by Actigraphy in Pulmonary Arterial Hypertension: TRACE Howard LS, Rosenkranz S, Frantz RP, et al. 2023. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  73. Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension (A DUE) Grünig E, Jansa P, Fan F, et al. 2024. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Rechecked 2026-10-30 to inform the direction and time context of bounded synthetic pulmonary-therapy teaching effects and the interactive RHC lab's established ERA/PDE5 comparison; coefficients are original, not fitted clinical dose responses or validated patient forecasts. Rechecked 2026-11-01 for established ERA/PDE5 and later sotatercept treatment context. Off/On selects an original representative model endpoint, not a dose or fitted trial effect.
  74. Randomized, Multicenter Study to Assess the Effects of Different Doses of Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension Hoeper MM, Ewert R, Jansa P, et al. 2024. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  75. Phase 2b trial of inhaled imatinib for treatment of pulmonary arterial hypertension (IMPAHCT) Hill NS, Gillies H, Chakinala MM, et al. 2026. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  76. Topline results from the phase 3 PROSERA study evaluating seralutinib in pulmonary arterial hypertension, 23 February 2026 Gossamer Bio 2026. Sponsor report; publication status and any missed prespecified endpoint are retained in the evidence summary.
  77. Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES) McLaughlin VV, Solum D, Lachant D, et al. 2026. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  78. FDA filing acceptance of the ralinepag new drug application, 24 August 2026 United Therapeutics 2026. Sponsor report; publication status and any missed prespecified endpoint are retained in the evidence summary.
  79. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension Lewis GD, Shah R, Shahzad K, et al. 2007. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  80. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study Guazzi M, Vicenzi M, Arena R, Guazzi MD 2011. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  81. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: the RELAX randomized clinical trial Redfield MM, Chen HH, Borlaug BA, et al. 2013. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  82. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension Hoendermis ES, Liu LCY, Hummel YM, et al. 2015. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  83. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension (SIOVAC) Bermejo J, Yotti R, García-Orta R, et al. 2018. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  84. Effects of sildenafil on symptoms and exercise capacity for HFrEF and pulmonary hypertension: the SilHF study Cooper TJ, Cleland JGF, Guazzi M, et al. 2022. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  85. Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With HFpEF: PASSION Hoeper MM, Oerke B, Wissmüller M, et al. 2024. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  86. Sotatercept for CpcPH associated with heart failure: results from the phase 2 randomized placebo-controlled CADENCE study Gomberg-Maitland M, Tedford RJ, Langleben D, et al. 2026. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  87. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: LEPHT Bonderman D, Ghio S, Felix SB, et al. 2013. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  88. Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial Dachs TM, Duca F, Rettl R, et al. 2022. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  89. Macitentan in pulmonary hypertension due to left ventricular dysfunction (MELODY-1) Vachiéry JL, Delcroix M, Al-Hiti H, et al. 2018. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  90. Macitentan for HFpEF/HFmrEF and pulmonary vascular disease: results of the SERENADE randomized clinical trial Shah SJ, Bonderman D, Borlaug BA, et al. 2025. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventionsRegistered study protocol and interventions
  91. Long-term effect of bosentan on morbidity and mortality in severe chronic heart failure: primary results of ENABLE Packer M, McMurray JJV, Krum H, et al. 2017. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review consulted primary methods, 31 October 2026.Primary report: administration methods
  92. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: FIRST Califf RM, Adams KF, McKenna WJ, et al. 1997. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  93. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension: RISE-IIP Nathan SD, Behr J, Collard HR, et al. 2019. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  94. Treatment of idiopathic pulmonary fibrosis with ambrisentan: ARTEMIS-IPF Raghu G, Behr J, Brown KK, et al. 2013. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  95. Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia: BPHIT Corte TJ, Keir GJ, Dimopoulos K, et al. 2014. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  96. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis: STEP-IPF IPF Clinical Research Network; Zisman DA, Schwarz M, et al. 2010. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  97. Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis: INSTAGE Kolb M, Raghu G, Wells AU, et al. 2018. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  98. Sildenafil added to pirfenidone in advanced IPF and risk of pulmonary hypertension: a randomized phase 2b trial Behr J, Nathan SD, Wuyts WA, et al. 2021. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  99. A randomized controlled trial of bosentan in severe COPD Stolz D, Rasch H, Linka A, et al. 2008. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  100. Sildenafil in severe pulmonary hypertension associated with COPD: a randomized controlled multicenter trial Vitulo P, Stanziola A, Confalonieri M, et al. 2017. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review consulted primary methods, 31 October 2026.Primary report: administration methods
  101. Tadalafil in patients with COPD: a randomized double-blind placebo-controlled trial Goudie AR, Lipworth BJ, Hopkinson PJ, Wei L, Struthers AD 2014. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventionsStudy-specific administration evidence
  102. Tadalafil for veterans with COPD-pulmonary hypertension: a multicenter placebo-controlled randomized trial Maron BA, Choudhary G, Goldstein RL, et al. 2022. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  103. Bosentan for treatment of inoperable CTEPH: BENEFiT randomized placebo-controlled trial Jaïs X, D’Armini AM, Jansa P, et al. 2008. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  104. Predictors of long-term outcomes with riociguat for CTEPH: CHEST-2 open-label extension Simonneau G, D’Armini AM, Ghofrani HA, et al. 2016. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  105. Macitentan for inoperable CTEPH: MERIT-1, corrected republication superseding the 2017 report Ghofrani HA, Simonneau G, D’Armini AM, et al. 2024. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  106. Long-term safety and efficacy of macitentan in inoperable CTEPH: MERIT and its open-label extension Kim NH, D’Armini AM, Howard LS, et al. 2025. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  107. Subcutaneous treprostinil for severe non-operable CTEPH: CTREPH Sadushi-Kolici R, Jansa P, Kopec G, et al. 2019. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  108. Balloon pulmonary angioplasty versus riociguat in inoperable CTEPH: MR BPA Kawakami T, Matsubara H, Shinke T, et al. 2022. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Primary abstract rechecked 2026-10-31 for the active BPA–riociguat mPAP comparison; the comparison result is kept separate from individual-drug findings.
  109. Selexipag for the treatment of CTEPH: Japanese randomized placebo-controlled study Ogo T, Shimokawahara H, Kinoshita H, et al. 2022. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished.
  110. Efficacy and safety of selexipag in inoperable or persistent/recurrent CTEPH: SELECT Kim NH, Channick R, Delcroix M, et al. 2024. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  111. Results of MACiTEPH: macitentan for inoperable or persistent/recurrent CTEPH Jenkins DP, Cerovic S, Csonka D, et al. 2026. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review consulted primary methods, 31 October 2026.Registered study protocol and interventions
  112. Hospitalization for pain in sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity: Walk-PHaSST Machado RF, Barst RJ, Yovetich NA, et al. 2011. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  113. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo-controlled randomized trial Baughman RP, Culver DA, Cordova FC, et al. 2014. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  114. Riociguat for sarcoidosis-associated pulmonary hypertension: a one-year double-blind placebo-controlled trial Baughman RP, Shlobin OA, Gupta R, et al. 2022. Primary publication newly consulted for the landmark trial evidence library; population, endpoint, effect and limitations are distinguished. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  115. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model Hoeper MM, Kramer T, Pan Z, et al. 2017. Original six-variable COMPERA analysis, 2015 thresholds, available-variable averaging and minimum data requirements.
  116. Risk assessment in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension Humbert M, Farber HW, Ghofrani HA, et al. 2019. Primary PATENT/CHEST analysis explicitly describes nearest-integer rounding of the Swedish/COMPERA mean grades.Primary report / linked source
  117. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2) Rubin LJ, Galiè N, Grimminger F, et al. 2015. Primary open-label extension; selected participants, safety endpoint and uncontrolled durability findings reviewed for the PH evidence library.
  118. A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Oral Anticoagulation in Systemic Sclerosis-Related Pulmonary Arterial Hypertension—Results From the SPHInX Study Nikpour M, Calderone A, Proudman SM, et al. 2026. Primary randomized trial report; severe under-recruitment, neutral primary result and anemia findings reviewed for the PH evidence library.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Only 25 participants and a wide confidence interval: absence of demonstrated benefit is not proof of equivalence. Preserve the paper’s stated hazard-ratio direction.
  119. 2026 ESC Guidelines for the management of heart failure Køber L, Adamo M, et al.; European Society of Cardiology. 2026. Consulted for Ask the exPHert therapy options, monitoring and eligibility. Publisher-indexed recommendation rechecked 2026-10-31 for dapagliflozin and empagliflozin as underlying heart-failure therapy in Current Landscape, not a PH-specific indication; local prescribing information governs use.
  120. Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension Simonneau G, Torbicki A, Hoeper MM, et al. Eur Respir J. 2012;40:874–880. Small randomized 17-week proof-of-concept trial; consulted for the direction and time context of the synthetic selexipag PVR response, not fitted patient dose-response coefficients.
  121. Pulmonary capillary wedge pressure augments right ventricular pulsatile loading Tedford RJ, Hassoun PM, Mathai SC, et al. Circulation. 2012;125:289–297. Primary haemodynamic study consulted for the inverse pulmonary resistance/compliance relationship and its dependence on wedge pressure; the simulator pulse scaling is an original teaching approximation, not fitted clinical coefficients.
  122. The resistance-compliance product of the pulmonary circulation varies in health and pulmonary vascular disease Hadinnapola C, Li Q, Su L, Pepke-Zaba J, Toshner M. Physiol Rep. 2015;3:e12363. Primary retrospective catheterization analysis consulted for variation in pulmonary RC time across haemodynamic states; cautions against a universal fixed resistance-compliance product or patient-specific prediction from the synthetic pulse rule.
  123. Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension Khan A, White RJ, Meyer G, et al. Respir Med. 2022;193:106744. Primary optional 61-participant FREEDOM-EV RHC substudy, newly consulted 2026-10-30 for 24-week PVR, output and compliance direction and time context. No significant mean-PA-pressure change was found. These observations do not fit the synthetic model, establish route equivalence or validate an exact triple-therapy plus sotatercept effect size.Study registrationPrimary report / linked sourcePrimary report / linked sourcePrimary report / linked source
  124. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial Rubin LJ, et al. 1990. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  125. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension Rich S, Kaufmann E, Levy PS 1992. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  126. Calcium-Channel Blockers in Primary Pulmonary Hypertension: correspondence Rich S, Kaufmann E, Levy PS, et al. 1992. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  127. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension Sitbon O, Humbert M, Jaïs X, et al. 2005. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  128. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study Channick RN, Simonneau G, Sitbon O, et al. 2001. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  129. Sitaxsentan therapy for pulmonary arterial hypertension Barst RJ, Langleben D, Frost A, et al. 2004. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  130. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan Barst RJ, Langleben D, Badesch DB, et al. 2006. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  131. Thelin (sitaxentan): worldwide withdrawal for serious liver injury European Medicines Agency 2010. Label. Newly consulted for the PH trial evidence review, 30 October 2026.
  132. Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study Jing ZC, Yu ZX, Shen JY, et al. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  133. A randomized, placebo-controlled, double-blind, dose-ranging study of oral sildenafil citrate in treatment-naive children with PAH Barst RJ, Ivy DD, Gaitan G, et al. 2012. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  134. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension Barst RJ, Beghetti M, Pulido T, et al. 2014. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  135. Efficacy and safety of tadalafil in a pediatric population with pulmonary arterial hypertension: phase 3 randomized study Ivy D, Bonnet D, Berger RMF, et al. 2021. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  136. A randomized study of two ambrisentan doses in pediatric pulmonary arterial hypertension Ivy D, Beghetti M, Juaneda-Simian E, et al. 2020. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  137. Macitentan in Pediatric Pulmonary Arterial Hypertension (TOMORROW): A Randomized Clinical Trial Berger RMF, et al. 2026. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  138. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension Barst RJ, Ivy D, Dingemanse J, et al. 2003. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  139. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children: the FUTURE-1 study Beghetti M, et al. 2009. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  140. Efficacy and safety of ralinepag in PAH patients on mono or dual background therapy: phase 2 trial Torres F, Farber H, Ristic A, et al. 2019. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  141. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy Ghofrani HA, Morrell NW, Hoeper MM, et al. 2010. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  142. RESPITE: switching to riociguat in PAH patients with inadequate response to PDE5 inhibitors Hoeper MM, et al. 2017. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration route and sequence rechecked in the primary full text, 31 October 2026.
  143. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in PAH Galiè N, Müller K, Scalise AV, Grünig E 2015. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  144. Initial combination therapy of macitentan and tadalafil in pulmonary arterial hypertension Sitbon O, et al. 2020. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  145. The REPAIR Study: Effects of Macitentan on RV Structure and Function in PAH Vonk Noordegraaf A, Channick R, Cottreel E, et al. 2022. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  146. Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for PAH: a placebo-controlled trial Hiremath J, Thanikachalam S, Parikh K, et al. 2010. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  147. Intravenous treprostinil in pulmonary arterial hypertension: a controlled trial in India (conference abstract) TRUST investigators 2007. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  148. BREEZE: safety and tolerability of treprostinil inhalation powder as Tyvaso DPI in PAH Spikes LA, Bajwa AA, Burger CD, et al. 2022. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  149. INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in PAH Hill NS, Feldman JP, Sahay S, et al. 2022. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  150. Safety and tolerability of transition from inhaled treprostinil to oral selexipag: TRANSIT-1 Frost A, Janmohamed M, Fritz JS, et al. 2019. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  151. Transition from parenteral to oral treprostinil in pulmonary arterial hypertension Chakinala MM, Feldman JP, Rischard F, et al. 2017. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  152. EPITOME-2: transition to a new formulation of intravenous epoprostenol in PAH Sitbon O, Delcroix M, Bergot E, et al. 2014. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  153. Long-term treatment with sildenafil citrate in PAH: the SUPER-2 study Rubin LJ, Badesch DB, Fleming TR, et al. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  154. Tadalafil for PAH: a double-blind 52-week uncontrolled extension study Oudiz RJ, Brundage BH, Galiè N, et al. 2012. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  155. Long-term safety and efficacy of imatinib in pulmonary arterial hypertension Frost AE, Barst RJ, Hoeper MM, et al. 2015. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  156. Randomized study of adding tadalafil to existing ambrisentan in pulmonary arterial hypertension Zhuang Y, Jiang B, Gao H, Zhao W 2014. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  157. Sildenafil dosed concomitantly with bosentan for adult PAH in a randomized controlled trial Vizza CD, Jansa P, Teal S, et al. 2017. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  158. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension Oudiz RJ, Galiè N, Olschewski H, et al. 2009. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  159. Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension Montani D, Savale L, Natali D, et al. 2010. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  160. Acute hemodynamic effects of riociguat in patients with pulmonary hypertension associated with diastolic heart failure (DILATE-1): a randomized, double-blind, placebo-controlled, single-dose study. Bonderman D, Pretsch I, Steringer-Mascherbauer R, et al. 2014. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  161. Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT). Lüscher TF, Enseleit F, Pacher R, et al. 2002. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  162. Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial. Anand I, McMurray J, Cohn JN, et al. 2004. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  163. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. Packer M, McMurray J, Massie BM, et al. 2005. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  164. Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure. Sütsch G, Kiowski W, Yan XW, et al. 1998. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  165. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure. Lewis GD, Lachmann J, Camuso J, et al. 2007. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  166. Long-term use of sildenafil in the therapeutic management of heart failure. Guazzi M, Samaja M, Arena R, Vicenzi M, Guazzi MD. 2007. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review consulted primary methods, 31 October 2026.Primary report: administration methods
  167. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Guazzi M, Vicenzi M, Arena R, Guazzi MD. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventionsStudy-specific administration evidence
  168. Effects of 5′-phosphodiesterase four-week long inhibition with sildenafil in patients with chronic heart failure: a double-blind, placebo-controlled clinical trial. Behling A, Rohde LE, Colombo FC, et al. 2008. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  169. Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial. Burkhoff D, Borlaug BA, Shah SJ, et al. 2021. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  170. Comparison of acute hemodynamic effects of inhaled nitric oxide and inhaled epoprostenol in patients with pulmonary hypertension. Preston IR, Sagliani KD, Roberts KE, et al. 2013. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  171. Pulmonary hypertension associated with heart failure with preserved ejection fraction: acute hemodynamic effects of inhaled iloprost. Grossman NL, Fiack CA, Weinberg JM, Rybin DV, Farber HW. 2015. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  172. β3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial. García-Álvarez A, Blanco I, García-Lunar I, et al. 2023. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  173. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. King TE Jr, Behr J, Brown KK, et al. 2008. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  174. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. King TE Jr, Brown KK, Raghu G, et al. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  175. Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial. Raghu G, Million-Rousseau R, Morganti A, Perchenet L, Behr J; MUSIC Study Group. 2013. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  176. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Blanco I, Gimeno E, Munoz PA, et al. 2010. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  177. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial. Blanco I, Santos S, Gea J, et al. 2013. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  178. Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial. Lederer DJ, Bartels MN, Schluger NW, et al. 2012. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  179. Sildenafil improves six-minute walk distance in chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Rao RS, Singh S, Sharma BB, Agarwal VV, Singh V. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.Study-specific administration evidence
  180. Acute effects of aerosolized iloprost in COPD related pulmonary hypertension - a randomized controlled crossover trial. Boeck L, Tamm M, Grendelmeier P, Stolz D. 2012. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  181. Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial. Hoeper MM, Halank M, Wilkens H, et al. 2013. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  182. Acute effects of riociguat in borderline or manifest pulmonary hypertension associated with chronic obstructive pulmonary disease. Ghofrani HA, Staehler G, Grünig E, et al. 2015. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review consulted primary methods, 31 October 2026.Primary report: administration methods
  183. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Ghofrani HA, Wiedemann R, Rose F, et al. 2002. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  184. Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. Nathan SD, Smith P, Deng C, et al.; TETON-1 Trial Investigators. 2026. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  185. Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. Nathan SD, Smith P, Deng C, et al.; TETON-2 Trial Investigators. 2026. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  186. Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-Blind, Placebo-controlled Trial. Nathan SD, Rajicic N, Dudenhofer R, et al. 2024. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  187. Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study. Waxman A, Restrepo-Jaramillo R, Thenappan T, et al. 2023. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  188. Tenax Therapeutics Announces Topline Results from Phase 3 LEVEL Clinical Trial of TNX-103 in Patients with PH-HFpEF. Tenax Therapeutics, Inc. 2026. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  189. Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension Suntharalingam J, Treacy CM, Doughty NJ, et al. 2008. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.Study-specific administration evidence
  190. Ambrisentan for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) Escribano-Subias P, Bendjenana H, Curtis PS, Lang I, Vonk Noordegraaf A. 2019. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  191. Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension Reesink HJ, Surie S, Kloek JJ, et al. 2010. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.Study-specific administration evidence
  192. Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension Reichenberger F, Voswinckel R, Enke B, et al. 2007. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.Study-specific administration evidenceStudy-specific administration evidence
  193. Intravenous epoprostenol in inoperable chronic thromboembolic pulmonary hypertension Cabrol S, Souza R, Jaïs X, et al. 2007. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  194. Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study Tanabe N, Fukuda K, Matsubara H, et al. 2020. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  195. Ambrisentan for sarcoidosis associated pulmonary hypertension Judson MA, Highland KB, Kwon S, et al. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.Study-specific administration evidence
  196. Tadalafil therapy for sarcoidosis-associated pulmonary hypertension Ford HJ, Baughman RP, Aris R, Engel P, Donohue JF. 2016. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  197. Inhaled iloprost for sarcoidosis associated pulmonary hypertension Baughman RP, Judson MA, Lower EE, et al. 2009. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  198. Pulmonary hypertension in end-stage pulmonary sarcoidosis: therapeutic effect of sildenafil? Milman N, Burton CM, Iversen M, et al. 2008. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  199. Prostacyclin and oral vasodilator therapy in sarcoidosis-associated pulmonary hypertension: a retrospective case series Bonham CA, Oldham JM, Gomberg-Maitland M, Vij R. 2015. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.Study-specific administration evidence
  200. Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies Barst RJ, Mubarak KK, Machado RF, et al. 2010. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review consulted primary methods, 31 October 2026.
  201. Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease Minniti CP, Machado RF, Coles WA, Sachdev V, Gladwin MT, Kato GJ. 2009. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  202. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension Sitbon O, Gressin V, Speich R, et al. 2004. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  203. Long-term effects of bosentan in patients with HIV-associated pulmonary arterial hypertension Degano B, Yaïci A, Le Pavec J, et al. 2009. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  204. Ambrisentan in portopulmonary hypertension: A multicenter, open-label trial Preston IR, Burger CD, Bartolome S, et al. 2020. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  205. Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial Iversen K, Jensen AS, Jensen TV, Vejlstrup NG, Søndergaard L. 2010. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  206. Oral sildenafil treatment for Eisenmenger syndrome: a prospective, open-label, multicentre study Zhang ZN, Jiang X, Zhang R, et al. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  207. Ambrisentan for pulmonary arterial hypertension due to congenital heart disease Zuckerman WA, Leaderer D, Rowan CA, Mituniewicz JD, Rosenzweig EB. 2011. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  208. Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis-associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial. Zamanian RT, Badesch D, Chung L, et al. 2021. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Small exploratory trial and secondary/model-dependent findings. It does not establish routine rituximab treatment for SSc-PAH.
  209. Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial. Sitbon O, Skride A, Feldman J, et al. 2024. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  210. Selonsertib in adults with pulmonary arterial hypertension (ARROW): a randomised, double-blind, placebo-controlled, phase 2 trial. Rosenkranz S, Feldman J, McLaughlin VV, et al. 2021. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  211. Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension. Spiekerkoetter E, Sung YK, Sudheendra D, et al. 2017. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  212. Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension. Toshner M, Church C, Harbaum L, et al. 2022. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  213. Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial. Kawut SM, Archer-Chicko CL, DeMichele A, et al. 2017. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  214. Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial. Kawut SM, Feng R, Ellenberg SS, et al. 2024. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  215. Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials. Howard LSGE, He J, Watson GMJ, et al. 2021. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  216. Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial. Farha S, Saygin D, Park MM, et al. 2017. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  217. Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study. van Campen JS, de Boer K, van de Veerdonk MC, et al. 2016. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  218. Simvastatin as a treatment for pulmonary hypertension trial. Wilkins MR, Ali O, Bradlow W, et al. 2010. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  219. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Kawut SM, Bagiella E, Lederer DJ, et al. 2011. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  220. Atorvastatin in pulmonary arterial hypertension (APATH) study. Zeng WJ, Xiong CM, Zhao L, et al. 2012. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  221. Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension. Langleben D, Christman BW, Barst RJ, et al. 2002. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  222. MK-5475, an inhaled soluble guanylate cyclase stimulator, for treatment of pulmonary arterial hypertension: the INSIGNIA-PAH study. Humbert M, Hassoun PM, Chin KM, et al. 2024. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  223. A Phase 2 Study of the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Patients With Pulmonary Hypertension Associated With Interstitial Lung Disease. Church C, Molina-Molina M, Arias-Guillén M, et al. 2026. Trial. Newly consulted for the PH trial evidence review, 30 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  224. LIBERTY: Ubenimex in WHO group 1 PAH — posted results Eiger BioPharmaceuticals; ClinicalTrials.gov 2023. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  225. LIBERTY did not meet its primary endpoint — sponsor report Eiger BioPharmaceuticals 2018. Sponsor report. Newly consulted for the PH trial evidence review, 30 October 2026.
  226. Positive phase 2b TPIP results in PAH — sponsor topline report Insmed 2025. Sponsor report. Newly consulted for the PH trial evidence review, 30 October 2026.
  227. Phase I safety study of ranolazine in pulmonary arterial hypertension. Gomberg-Maitland M; Schilz R; Mediratta A et al. 2015. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  228. Ranolazine Improves Right Ventricular Function in Patients With Precapillary Pulmonary Hypertension: Results From a Double-Blind, Randomized, Placebo-Controlled Trial. Han Y; Forfia P; Vaidya A et al. 2021. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  229. Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study. Han QJ; Forfia P; Vaidya A et al. 2023. Original research. Newly consulted for the PH trial evidence review, 30 October 2026.
  230. Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension. Brittain EL; Niswender K; Agrawal V et al. 2020. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  231. Short-Term Hemodynamic Effects of Apelin in Patients With Pulmonary Arterial Hypertension. Brash L; Barnes GD; Brewis MJ et al. 2018. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  232. IL-1 Blockade Reduces Inflammation in Pulmonary Arterial Hypertension and Right Ventricular Failure: A Single-Arm, Open-Label, Phase IB/II Pilot Study. Trankle CR; Canada JM; Kadariya D et al. 2019. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  233. Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients. Michelakis ED; Gurtu V; Webster L et al. 2017. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  234. Effects of Trimetazidine on Right Ventricular Function and Ventricular Remodeling in Patients with Pulmonary Artery Hypertension: A Randomised Controlled Trial. Verdejo HE; Rojas A; López-Crisosto C et al. 2023. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  235. Long-term oxygen therapy in precapillary pulmonary hypertension – SOPHA study. Benjamin N; Echampati I; Harutyunova S et al. 2024. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  236. LARIAT: A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension — posted results. Reata Pharmaceuticals / Biogen; ClinicalTrials.gov 2021. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  237. CATALYST: Bardoxolone Methyl in Connective Tissue Disease-associated PAH — posted results. Reata Pharmaceuticals / Biogen; ClinicalTrials.gov 2023. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  238. INOvation-1 / PULSE-PAH-004: Pulsed Inhaled Nitric Oxide Versus Placebo in Symptomatic PAH — posted results. Bellerophon Pulse Technologies; ClinicalTrials.gov 2023. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
  239. Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension — posted results. Vanderbilt University Medical Center; ClinicalTrials.gov 2024. Trial. Newly consulted for the PH trial evidence review, 30 October 2026.
Browser audio implementation2
  1. AudioContext MDN Web Docs contributors / Mozilla. Updated May 16, 2026; accessed October 30, 2026. Technical reference newly consulted for local Web Audio lifecycle, suspension and device-latency limits; not a clinical acoustic model.
  2. AudioBufferSourceNode MDN Web Docs contributors / Mozilla. Updated September 28, 2026; accessed October 30, 2026. Technical reference newly consulted for scheduled playback of in-memory audio buffers and cancellation with stop(); the PCG synthesis and rendering constants are original teaching choices.
Cardiac image interoperability and rendering3
  1. Definition of NRRD File Format Teem contributors. Official NRRD format specification, consulted October 2026 for axis ordering, scalar encodings, geometry and declared units. Technical interoperability reference; not anatomical validation.
  2. 3D Slicer volume sequence format and data interchange 3D Slicer contributors. Official sequence developer and user documentation, consulted October 2026 for I/J/K/list axes, explicit sequence index metadata and local export workflows.
  3. WebGL 2.0 Specification Khronos Group. Technical specification, editor draft June 30, 2026, consulted for local bounded 3D texture rendering; not a validated medical-image renderer.
AI implementation and data controls5
  1. Migrate to the Responses API OpenAI. Official API documentation, consulted 31 October 2026 for response items, stateless history and store:false. Technical implementation reference, not clinical validation.
  2. Data controls in the OpenAI platform OpenAI. Official API documentation, consulted 31 October and 3 November 2026 for response-object storage, image inputs and provider retention boundaries. store:false does not itself establish zero provider retention.
  3. GPT-6.1 Sol model reference OpenAI. Official model documentation, consulted 31 October 2026 for the configurable model identifier, Responses API support and reasoning options. Model access and billing remain account-dependent.
  4. Structured model outputs OpenAI. Official Responses API documentation, consulted 31 October and 3 November 2026 for strict schema output, bounded ECG image-review fields and refusal handling. Schema compliance does not establish clinical or physiological validity.
  5. Images and vision OpenAI. Official Responses API documentation, consulted 3 November 2026 for image inputs and visual-interpretation limitations in optional ECG image review. Technical implementation reference, not ECG clinical validation.
Heart-sound synthesis and stethoscope response8
  1. Time-frequency analysis of heart murmurs. Part I: Parametric modelling and numerical simulations Debiais F, Durand LG, Pibarot P, Guardo R. Med Biol Eng Comput. 1997;35(5):474–479. doi:10.1007/BF02525526. Primary patient-recording and simulation study newly consulted 31 October 2026 for time-varying stochastic stenotic/regurgitant murmur models and the separate modeling of musical murmurs. Selected bioprosthetic-valve observations do not establish universal native-valve spectra, diagnostic pressure-response coefficients or the realism of this application's original synthesis.
  2. Windowed Sinc Interpolation Smith JO III. Physical Audio Signal Processing. Online author textbook, newly consulted 31 October 2026 for finite windowed-sinc reconstruction and interpolated fractional-phase tables. General digital-audio engineering method; does not validate the application's filter settings, perceived realism or clinical audio.
  3. Genesis of pericardial knock in constrictive pericarditis Tyberg TI, Goodyer AV, Langou RA. Am J Cardiol. 1980;46(4):570–575. Primary recorded study newly consulted and rechecked 31 October 2026: an early high-frequency knock coincided with sudden premature arrest of ventricular filling, rather than valve opening alone. Recorded 90–120 ms A2-to-knock timing in this small series is not a universal delay or a calibration of the synthetic sound.
  4. Myxoma of the left atrium. Hemodynamic and phonocardiographic consequences of sudden tumor movement Pitt A, Pitt B, Schaefer J, Criley JM. Circulation. 1967;36(3):408–416. doi:10.1161/01.CIR.36.3.408. Primary two-patient catheterization/cineangiography report newly consulted 31 October 2026 through indexed publisher text: early diastolic tumor movement, rapid atrial pressure descent despite inflow obstruction, and a plop associated with checking tumor motion. These observations do not establish universal timing, sound frequency or a fitted obstruction coefficient.
  5. Time-frequency analysis of the first heart sound. Part 1: Simulation and analysis Chen D, Durand LG, Lee HC. Med Biol Eng Comput. 1997;35(4):306–310. DOI:10.1007/BF02534081. Primary synthetic S1 study newly consulted 31 October 2026 for damped and frequency-modulated transient components. Does not validate this implementation or establish universal patient coefficients.
  6. Nonlinear transient chirp signal modeling of the aortic and pulmonary components of the second heart sound Xu J, Durand LG, Pibarot P. IEEE Trans Biomed Eng. 2000;47(10):1328–1335. DOI:10.1109/10.871405. Primary synthesis study newly consulted 31 October 2026. Short decreasing-frequency A2/P2 components were studied in four pigs with pulmonary hypertension; it does not calibrate human diagnostic audio here.
  7. Design and evaluation of a parametric model for cardiac sounds Ibarra-Hernández RF, Alonso-Arévalo MA, Cruz-Gutiérrez A, Licona-Chávez AL, Villarreal-Reyes S. Comput Biol Med. 2017;89:170–180. DOI:10.1016/j.compbiomed.2017.08.007. Primary deterministic-plus-stochastic synthesis study newly consulted 31 October 2026; a conceptual acoustic reference, not the coefficients or patient recordings used by this application.
  8. Technical Characterization of Digital Stethoscopes: Toward Scalable Artificial Intelligence-Based Auscultation Arjoune Y, Nguyen TN, Doroshow RW, Shekhar R. J Med Eng Technol. 2023;47(3):165–178. DOI:10.1080/03091902.2023.2174198. Primary device-response study newly consulted 31 October 2026 for the limits of assuming one stethoscope transfer function. No specific instrument or listening position is reproduced.
Pulmonary hypertension: journal-watch additions41
  1. Efficacy and Safety of Udenafil for the Treatment of Pulmonary Arterial Hypertension: a Placebo-controlled, Double-blind, Phase IIb Clinical Trial Chang HJ, Song S, et al.. 2019. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  2. Double-Blind, Placebo-Controlled Clinical Trial With a Rho-Kinase Inhibitor in Pulmonary Arterial Hypertension: A Pilot Efficacy Trial Fukumoto Y, Yamada N, Matsubara H, et al.. 2013. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  3. An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension Simon MA, Hanrott K, Budd DC, et al.. 2022. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration route and sequence rechecked in the primary full text, 31 October 2026.
  4. Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study) Pan Z, Marra AM, Benjamin N, et al.. 2019. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Small, single-center trial using historical inclusion and PAH definitions. Secondary findings and very few progression events do not establish routine PAH drugs for every borderline pressure or exercise-PH finding.
  5. Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension Hassoun PM, Zamanian RT, Damico R, et al.. 2015. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  6. Bosentan-based, treat-to-target therapy in patients with pulmonary arterial hypertension: results from the COMPASS-3 study Benza RL, Raina A, Gupta H, et al.. 2018. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  7. Riociguat in children with pulmonary arterial hypertension: The PATENT-CHILD study García Aguilar H, Gorenflo M, Ivy DD, et al.. 2022. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  8. Parenteral treprostinil induction for rapid attainment of therapeutic doses of oral treprostinil Miller CE, Franco V, Smith JS, et al.. 2023. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  9. Implementing the EXPEDITE parenteral induction protocol: Rapid parenteral treprostinil titration and transition to oral treprostinil Kingrey JF, Miller CE, Franco V, et al.. 2023. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  10. Phase 3, Open-Label Multicenter Study of Sotatercept in Japanese Participants With Pulmonary Arterial Hypertension Matsubara H, Tanabe N, Ogo T, et al.. 2026. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  11. Insmed announces 12-month data from the ongoing open-label extension study of TPIP in PAH Insmed Incorporated. 2026. Sponsor report. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  12. Sotatercept in Pediatric Pulmonary Hypertension: Experience from the Pediatric Pulmonary Hypertension Network Critser PJ, Krishnan US, Avitabile CM, et al.. 2026. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.Original full report: administration review
  13. Pilot Study of Endothelin Receptor Blockade in Heart Failure with Diastolic Dysfunction and Pulmonary Hypertension (BADDHY-Trial) Koller B, Steringer-Mascherbauer R, Ebner CH, et al.. 2017. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  14. BADDHY: Safety and Efficacy of Bosentan in Patients With Diastolic Heart Failure and Secondary Pulmonary Hypertension (NCT00820352) ClinicalTrials.gov; Wilhelm Grander. 2009. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  15. Phosphodiesterase 5 inhibitor sildenafil in patients with HFpEF and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study Belyavskiy E, Ovchinnikov A, Potekhina A, Ageev F, Edelmann F. 2020. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.Study-specific administration evidence
  16. Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The CAMEO-DAPA Trial Borlaug BA, Reddy YNV, Braun A, et al.. 2023. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  17. Dapagliflozin and Right Ventricular–Pulmonary Vascular Interaction in HFpEF: A Secondary Analysis of a Randomized Clinical Trial Reddy YNV, Carter RE, Sorimachi H, et al.. 2024. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  18. Empagliflozin Effects on Pulmonary Artery Pressure in Patients With Heart Failure: Results From the EMBRACE-HF Trial Nassif ME, Qintar M, Windsor SL, et al.. 2021. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  19. Complete phase 1b Part A TX45 results in PH-HFpEF: full 19-patient cohort (sponsor report, 17 May 2025) Tectonic Therapeutic. 2025. Sponsor report. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  20. Phase 1b Part B TX45 topline results in PH-HFrEF (sponsor report, 29 October 2025) Tectonic Therapeutic. 2025. Sponsor report. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  21. TX000045-002 single-dose open-label study in postcapillary PH and heart failure (EU CT 2023-508969-32-00) Tectonic Therapeutic; European Medicines Agency CTIS. 2024. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  22. Re-PHIRE (NCT05737940): AZD3427 in HF and group 2 PH, posted results, 27 October 2026 AstraZeneca; ClinicalTrials.gov. 2026. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.
  23. Re-PHIRE summary of results: AZD3427 in HF and PH-LHD (jRCT2041230006; results posted 2 October 2026) AstraZeneca; Japan Registry of Clinical Trials. 2026. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  24. Effect of bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease Valerio G, Bracciale P, D’Agostino AG. 2009. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.Study-specific administration evidence
  25. Controlled prospective randomised trial on pulmonary haemodynamics of ambulatory long-term nitric oxide and oxygen in severe COPD Vonbank K, Ziesche R, Higenbottam TW, et al.. 2003. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  26. Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension Wang L, Jin YZ, Zhao QH, et al.. 2017. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  27. A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis Nathan SD, Flaherty KR, Glassberg MK, et al.. 2020. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  28. A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen King CS, Flaherty KR, Glassberg MK, et al.. 2022. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  29. PHocus phase 2 mosliciguat results in PH-ILD (sponsor report, 8 September 2026) Roivant Sciences; Pulmovant. 2026. Sponsor report. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  30. PHocus: A Study of Mosliciguat in PH-ILD (NCT06635850) Pulmovant; ClinicalTrials.gov. 2024. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  31. A Multicenter, Single-Blind, Randomized, Warfarin-Controlled Trial of Edoxaban in Patients With Chronic Thromboembolic Pulmonary Hypertension: KABUKI Trial Hosokawa K, Watanabe H, Taniguchi Y, et al.. 2024. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  32. Evaluating the efficacy and safety of rivaroxaban as a warfarin alternative in CTEPH patients undergoing pulmonary endarterectomy: a randomized clinical trial Barati S, Amini H, Hossein Ahmadi Z, et al.. 2023. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.Study-specific administration evidence
  33. Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study Hosokawa K, Abe K, Funakoshi K, et al.. 2023. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  34. A multicenter study of anticoagulation in operable chronic thromboembolic pulmonary hypertension Bunclark K, Newnham M, Chiu YD, et al.. 2020. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  35. Long-term real-world effectiveness and safety of edoxaban in chronic thromboembolic pulmonary hypertension: a nationwide registry study Hosokawa K, Masaki K, Hirose M, et al.. 2026. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.Study-specific administration evidence
  36. Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension Morris CR, Kim HY, Wood J, et al.. 2013. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  37. Comparing the Efficacy of Tadalafil Versus Placebo on Pulmonary Artery Systolic Pressure and Right Ventricular Function in Patients with Beta-Thalassaemia Intermedia Jalalian R, Moghadamnia AA, Tamaddoni A, et al.. 2017. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  38. Evaluation of the effect of sildenafil in hemodialysis patients with pulmonary hypertension Elbraky AA, Behairy MA, Khorshid HM, et al.. 2019. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  39. Sildenafil in Hemodialysis Patients With Pulmonary Hypertension (NCT03763045): registered design and outcomes Ain Shams University / ClinicalTrials.gov. 2019. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
  40. Inhaled Prostacyclin Improves Clinical and Hemodynamic Parameters in Sarcoidosis Patients With Pulmonary Hypertension and Interstitial Lung Disease (SAPPHIRE Trial): ATS conference abstract Gomez Rojas OR, Patel DC, Eagan C, et al.. 2026. Original research. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  41. SAPPHIRE: Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension (NCT03814317) University of Florida / ClinicalTrials.gov. 2026. Trial. Newly consulted for the PH journal-watch gap review, 31 October 2026. Read the linked report and its source-status limitations.
Pulmonary hypertension: comprehensive coverage additions18
  1. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study Wilkins MR, Paul GA, Strange JW, et al. 2005. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  2. Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension Sandoval J, Torbicki A, Souza R, et al.; STRIDE-4 investigators. 2012. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  3. Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan Benza RL, Mehta S, Keogh A, Lawrence EC, Oudiz RJ, Barst RJ. 2007. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  4. SOPRANO: Macitentan in patients with pulmonary hypertension following left ventricular assist device implantation Frantz RP, Desai SS, Ewald G, et al. 2024. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026. Administration-route review used primary methods and registered intervention descriptions, 31 October 2026; details not established in accessible sources remain unspecified.Registered study protocol and interventions
  5. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study Sastry BKS, Narasimhan C, Reddy NK, Raju BS. 2004. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026. Indexed publisher Methods and Results verified eligibility and disposition; the abstract/full-text denominator discrepancy remains explicit.
  6. Clinical efficacy of phosphodiesterase-5 inhibitor tadalafil in Eisenmenger syndrome—a randomized, placebo-controlled, double-blind crossover study Mukhopadhyay S, Nathani S, Yusuf J, Shrimal D, Tyagi S. 2011. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  7. NCT01200732: Clinical efficacy of tadalafil in Eisenmenger syndrome Govind Ballabh Pant Hospital / ClinicalTrials.gov. 2010. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  8. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study Khan SS, Cuttica MJ, Beussink-Nelson L, et al. 2015. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026. PMC full text verified the paired catheterization denominator.
  9. Spironolactone in pulmonary arterial hypertension: results of a cross-over study Safdar Z, Frost A, Basant A, Deswal A, Smith EO, Entman M. 2020. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  10. Hemodynamic effects of fluoxetine in pulmonary arterial hypertension: an open label pilot study Sodimu A, Bartolome S, Igenoza OP, Chin KM. 2020. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026. PMC full text verified the two registered protocols and outcome denominators.
  11. Therapy with intermittent pulse cyclophosphamide for pulmonary hypertension associated with systemic lupus erythematosus Gonzalez-Lopez L, Cardona-Muñoz EG, Celis A, et al. 2004. Trial. Newly consulted for the unranked PH literature coverage review, 31 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.
  12. Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension Sanchez O, Sitbon O, Jaïs X, Simonneau G, Humbert M. 2006. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026. Administration route rechecked against primary methods or the registered protocol, 31 October 2026; unresolved details remain explicit.Original publisher PDF: access restricted during route review
  13. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases Jaïs X, Launay D, Yaici A, et al. 2008. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026.Original publisher PDF: access restricted during route reviewReviewed 7 November 2026 for the focused CTD/SSc literature reading guide. No randomized comparator, small selected cohort and confounding by severity. These results do not generalize to SSc-PAH or justify delaying vasodilator treatment in severe PAH.
  14. Immunosuppressive Therapy for Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases: Insights from Japanese Registry Tamura Y, Tamura Y, Takemura R, et al.; Japan Pulmonary Hypertension Registry Network. 2025. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026.Accessible treatment table: methods access remains restrictedPublisher article: full methods subscription restrictedOriginal PDF: full-text route verification pending
  15. Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension Preston IR, Klinger JR, Landzberg MJ, Houtchens J, Nelson D, Hill NS. 2001. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  16. Sarcoidosis-associated pulmonary hypertension: outcome with long-term epoprostenol treatment Fisher KA, Serlin DM, Wilson KC, Walter RE, Berman JS, Farber HW. 2006. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  17. Treatment of sarcoidosis-associated pulmonary hypertension: a two-center experience Barnett CF, Bonura EJ, Nathan SD, et al. 2009. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026.
  18. Management and long-term outcomes of sarcoidosis-associated pulmonary hypertension Boucly A, Cottin V, Nunes H, et al. 2017. Original research. Newly consulted for the unranked PH literature coverage review, 31 October 2026.Study-specific administration evidenceOriginal supplemental tables: route audit
PH literature search coverage and database methods3
  1. NCBI Entrez Programming Utilities: ESearch and ESummary National Library of Medicine. E-utilities reference. Consulted 31 October 2026 for complete PH identifier retrieval and metadata supplementation.
  2. Europe PMC RESTful Web Service Europe PMC / EMBL-EBI. Search and cursor pagination documentation. Consulted 31 October 2026; bibliographic discovery metadata is not a verified clinical appraisal.
  3. ClinicalTrials.gov API version 2 National Library of Medicine. Study API documentation. Consulted 31 October 2026 for complete PH registration searches across all statuses and study types.
Pulmonary hypertension: trial extensions and related analyses73
  1. SERAPHIN extension: macitentan safety and survival Souza R, Delcroix M, Galiè N, et al. 2022. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  2. GRIPHON extension: long-term selexipag safety and survival Galiè N, Gaine S, Channick R, et al. 2022. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  3. GRIPHON final observation: selexipag survival, safety and dosing McLaughlin VV, Howard L, Elwing J, et al. 2026. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  4. PULSAR open-label extension Humbert M, McLaughlin V, Gibbs JSR, et al. 2023. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  5. TORREY extension: inhaled seralutinib Sitbon O, Sahay S, Escribano Subías P, et al. 2025. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  6. PACES-2: long-term sildenafil added to IV epoprostenol Simonneau G, Rubin LJ, Galiè N, et al. 2014. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  7. TRIUMPH extension: long-term inhaled treprostinil Benza RL, Seeger W, McLaughlin VV, et al. 2011. Trial. Reviewed 31 October 2026 for the PH trial-family library.
  8. FUTURE-2: pediatric bosentan extension Berger RMF, Haworth SG, Bonnet D, et al. 2016. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked sourcePrimary report / linked source
  9. FUTURE-2 corrigendum Berger RMF, Haworth SG, Bonnet D, et al. 2016. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  10. FREEDOM-EV and extension: oral treprostinil survival follow-up Grünig E, Rahaghi F, Elwing J, et al. 2024. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  11. BREATHE-5 extension: bosentan in Eisenmenger syndrome Gatzoulis MA, Beghetti M, Galiè N, et al. 2008. Trial. Reviewed 31 October 2026 for the PH trial-family library.
  12. EARLY: long-term bosentan follow-up Simonneau G, Galiè N, Jansa P, et al. 2014. Trial. Reviewed 31 October 2026 for the PH trial-family library.
  13. Ralinepag phase II open-label extension Barberà J, Jansa P, Klings E, et al. 2024. Trial. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  14. FREEDOM-EXT: oral treprostinil dosing, tolerability and pharmacokinetics White RJ, Parikh K, Allen R, et al. 2020. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked sourcePrimary report / linked source
  15. Survival with first-line bosentan in primary pulmonary hypertension McLaughlin VV, Sitbon O, Badesch DB, et al. 2005. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked sourcePrimary report / linked source
  16. Correction: first-line bosentan survival report McLaughlin VV, Sitbon O, Badesch DB, et al. 2005. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  17. FUTURE-3: pediatric bosentan dosing-frequency pharmacokinetics Berger RMF, Gehin M, Beghetti M, et al. 2017. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  18. FUTURE-3: echocardiography and clinical outcomes through 72 weeks Beghetti M, Berger RMF, Bonnet D, et al. 2021. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  19. STELLAR / SOTERIA survival analysis (ATS abstract) Thakur T, Chevure J, Watzker A, Lautsch D. 2025. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  20. Pooled sotatercept long-term safety (ATS abstract) Preston IR, Gomberg-Maitland M, Hoeper MM, et al. 2025. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  21. SOTERIA updated long-term follow-up (ERS abstract) Preston IR, Badesch D, Ghofrani HA, et al. 2025. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  22. FUTURE-3 exceptional-use safety: EMA assessment European Medicines Agency. 2021. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  23. FUTURE-3 extension and exceptional-use results Actelion; ClinicalTrials.gov. 2025. Trial. Reviewed 31 October 2026 for the PH trial-family library.
  24. SERAPHIN haemodynamic substudy: the effect of macitentan on haemodynamic parameters and NT-proBNP and their association with disease progression Galiè N, Jansa P, Pulido T, et al. 2017. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  25. Effect of macitentan on hospitalizations: results from the SERAPHIN trial Channick RN, Delcroix M, Ghofrani HA, et al. 2015. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  26. Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial Mehta S, Sastry BKS, Souza R, et al. 2017. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  27. Initial combination therapy with ambrisentan and tadalafil in CTD-associated PAH: subgroup analysis from the AMBITION trial Coghlan JG, Galiè N, Barberà JA, et al. 2017. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationReviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Subgroup evidence from the parent trial, not an independent confirmatory SSc trial. Clinical failure combined several outcomes; the result is not isolated mortality proof and should not be extrapolated to PH-LHD or substantial ILD.
  28. Initial combination therapy of ambrisentan and tadalafil in CTD-PAH in the modified intention-to-treat population of the AMBITION study: post hoc analysis Kuwana M, Blair C, Takahashi T, Langley J, Coghlan JG. 2020. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  29. Targeting the Prostacyclin Pathway with Selexipag in Patients Receiving Double Combination Therapy: Insights from GRIPHON Coghlan JG, Channick R, Chin K, et al. 2018. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  30. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension Gaine S, Chin K, Coghlan G, et al. 2017. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationReviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Subgroup evidence; events were mainly progression and hospitalization. A positive composite does not establish mortality benefit. Oral selexipag does not replace IV/SC prostacyclin when parenteral therapy is indicated for high-risk PAH.
  31. Selexipag treatment for PAH associated with congenital heart disease after defect correction: insights from GRIPHON Beghetti M, Channick RN, Chin KM, et al. 2019. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  32. The impact of comorbidities on selexipag treatment effect in patients with PAH: insights from GRIPHON Rosenkranz S, Channick R, Chin KM, et al. 2022. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  33. Relationship Between Time From Diagnosis and Morbidity/Mortality in PAH: Results From the Phase III GRIPHON Study Gaine S, Sitbon O, Channick RN, et al. 2021. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  34. Early selexipag initiation and long-term outcomes: insights from randomised controlled trials in pulmonary arterial hypertension Coghlan JG, Gaine S, Channick R, et al. 2023. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  35. Atrial septal defects versus ventricular septal defects in BREATHE-5: a subgroup analysis Berger RMF, Beghetti M, Galiè N, et al. 2010. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  36. Sildenafil for pulmonary arterial hypertension associated with connective tissue disease Badesch DB, Hill NS, Burgess G, et al.; SUPER Study Group. 2007. Original research. Reviewed 31 October 2026 for the PH trial-family library.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Small post hoc subgroup, short follow-up and several dose groups. This was not a dedicated SSc trial and does not demonstrate CTD-specific survival benefit.
  37. Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension Barst RJ, Oudiz RJ, Beardsworth A, et al. 2011. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  38. Effects of dose and age on adverse events associated with tadalafil in the treatment of pulmonary arterial hypertension Berman-Rosenzweig E, Arneson C, Klinger JR. 2014. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  39. Ambrisentan response in CTD-associated PAH: a subgroup analysis of the ARIES-E clinical trial Fischer A, Denton CP, Matucci-Cerinic M, et al. 2016. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  40. Riociguat for PAH associated with connective tissue disease: results from PATENT-1 and PATENT-2 Humbert M, Coghlan JG, Ghofrani HA, et al. 2017. Original research. Reviewed 31 October 2026 for the PH trial-family library.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Small subgroup, post hoc CTD-subtype classification and selected open-label extension population. PATENT-2 is not independent randomized efficacy or survival proof. Riociguat must not be combined with PDE5 inhibitors; PAH findings do not establish treatment for PH-ILD.
  41. Riociguat for pulmonary arterial hypertension associated with congenital heart disease Rosenkranz S, Ghofrani HA, Beghetti M, et al. 2015. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  42. Riociguat treatment for portopulmonary hypertension: a subgroup analysis from the PATENT-1/-2 studies Cartin-Ceba R, Halank M, Ghofrani HA, et al. 2018. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  43. Initial combination therapy with ambrisentan and tadalafil and mortality in PAH: a secondary analysis of the randomised, controlled AMBITION study Hoeper MM, McLaughlin VV, Barberà JA, et al. 2016. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  44. Bosentan treatment for PAH related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions Denton CP, Humbert M, Rubin L, Black CM. 2006. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  45. Treprostinil, a prostacyclin analogue, in PAH associated with connective tissue disease Oudiz RJ, Schilz RJ, Barst RJ, et al. 2004. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  46. Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in PAH: Insights From the Phase III GRIPHON Study Chin KM, Rubin LJ, Channick R, et al. 2019. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  47. Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study Sitbon O, Chin KM, Channick RN, et al. 2020. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  48. Changes in REVEAL Lite 2 risk status are associated with long-term outcomes in patients with PAH: A post-hoc analysis of the GRIPHON study Benza RL, Chin KM, Gaine S, et al. 2024. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  49. Contemporary risk scores predict clinical worsening in pulmonary arterial hypertension — An analysis of FREEDOM-EV Benza RL, Gomberg-Maitland M, Farber HW, et al. 2022. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  50. Efficacy and Safety of Oral Treprostinil in Patients with PAH on Background Monotherapy or Dual Therapy Lachant D, Raina A, Krishnan M, et al. 2026. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  51. Correction: Initial combination therapy of ambrisentan and tadalafil in CTD-PAH in the modified intention-to-treat AMBITION population BMJ / Annals of the Rheumatic Diseases. 2020. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked sourcePrimary report / linked source
  52. Correction to Figures in: Macitentan Improves Health-Related Quality of Life for Patients With PAH: Results From SERAPHIN CHEST. 2018. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  53. Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study Nathan SD, Waxman A, Rajagopal S, et al. 2021. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  54. Efficacy of Inhaled Treprostinil on Multiple Disease Progression Events in Patients with Pulmonary Hypertension due to Parenchymal Lung Disease in the INCREASE Trial Nathan SD, Tapson VF, Elwing J, et al. 2022. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  55. Inhaled Treprostinil Dosage in Pulmonary Hypertension Associated With Interstitial Lung Disease and Its Effects on Clinical Outcomes Nathan SD, Deng C, King CS, et al. 2023. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  56. Inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease with less severe haemodynamics: a post hoc analysis of the INCREASE study Weatherald J, Nathan SD, El-Kersh K, et al. 2024. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked sourcePrimary report / linked source
  57. Correction: Inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease with less severe haemodynamics: a post hoc analysis of the INCREASE study BMJ Open Respiratory Research 2024. Original research. Reviewed 31 October 2026 for the PH trial-family library.
  58. Survival analysis from the INCREASE study in PH-ILD: evaluating the impact of treatment crossover on overall mortality Nathan SD, Johri S, Joly JM, et al. 2024. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  59. A Novel Approach to Clinical Change Endpoints: A Win Ratio Analysis of the INCREASE Trial Nathan SD, Medarov B, Ho L, et al. 2023. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  60. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2) Simonneau G, D’Armini AM, Ghofrani HA, et al. 2015. Trial. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  61. Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension Kim NH, D’Armini AM, Grimminger F, et al. 2017. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  62. Effect of Balloon Pulmonary Angioplasty and Riociguat on Right Ventricular Afterload and Function in CTEPH: Insights From the RACE Trial Gerges C, Jevnikar M, Brenot P, et al. 2025. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  63. REVEAL risk score in patients with chronic thromboembolic pulmonary hypertension receiving riociguat Benza RL, Farber HW, Frost A, et al. 2018. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
  64. The risk profile change in patients with severe chronic thromboembolic pulmonary hypertension treated with subcutaneous treprostinil Jansa P, Kopeć G, Torbicki A, et al. 2023. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  65. Long-Term Treatment With Subcutaneous Treprostinil in Patients With Severe Inoperable Chronic Thromboembolic Pulmonary Hypertension in the Multimodal Therapy Era (Data From CTREPH Study Open Label Extension) Jansa P, Sadushi-Kolici R, Skoro-Sajer N, et al. 2025. Trial. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  66. Effects of sildenafil on ventricular and vascular function in heart failure with preserved ejection fraction Borlaug BA, Lewis GD, McNulty SE, et al. 2015. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  67. Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the RELAX Trial Hussain I, Mohammed SF, Forfia PR, et al. 2016. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  68. Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival Bermejo J, González-Mansilla A, Mombiela T, et al. 2021. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  69. Effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension Liu LCY, Hummel YM, van der Meer P, et al. 2017. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  70. The Transition From Chronic Intravenous To Oral Levosimendan Is Safe And Effective In Patients With Pulmonary Hypertension With Heart Failure And Preserved Ejection Fraction Thenappan T, Borlaug B, Burkhoff D, et al. 2023. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  71. Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction Han MK, Bach DS, Hagan PG, et al. 2013. Original research. Reviewed 31 October 2026 for the PH trial-family library.Primary report / linked source
  72. Nintedanib and Sildenafil in Patients with Idiopathic Pulmonary Fibrosis and Right Heart Dysfunction. A Prespecified Subgroup Analysis of a Double-Blind Randomized Clinical Trial (INSTAGE) Behr J, Kolb M, Song JW, et al. 2019. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registrationPrimary report / linked source
  73. Impact of lung morphology on clinical outcomes with riociguat in patients with pulmonary hypertension and idiopathic interstitial pneumonia: A post hoc subgroup analysis of the RISE-IIP study Nathan SD, Cottin V, Behr J, et al. 2021. Original research. Reviewed 31 October 2026 for the PH trial-family library.Study registration
PH trial administration: primary protocols and formulation review31
  1. NCT01588405: Remodulin to Oral Treprostinil Transition United Therapeutics / ClinicalTrials.gov. First posted 2012. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  2. NCT03497689: EXPEDITE: Remodulin Induction Followed by Orenitram Optimization to Treat PAH United Therapeutics / ClinicalTrials.gov. First posted 2018. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  3. NCT04456998: GB002 in Adult Subjects With PAH (TORREY) GB002 / Gossamer Bio / ClinicalTrials.gov. First posted 2020. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  4. NCT05934526: Efficacy and Safety of Seralutinib in Adult Subjects With PAH (PROSERA) GB002 / Gossamer Bio / ClinicalTrials.gov. First posted 2023. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  5. NCT05036135: AV-101 Dry Powder Inhaled Imatinib in Patients With PAH (IMPAHCT) Aerovate Therapeutics / ClinicalTrials.gov. First posted 2021. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  6. NCT04732221: Efficacy and Safety of Frespaciguat (MK-5475) in PAH (INSIGNIA-PAH) Merck Sharp & Dohme / ClinicalTrials.gov. First posted 2021. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  7. NCT05147805: Efficacy, Safety and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in PAH Insmed / ClinicalTrials.gov. First posted 2021. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  8. NCT02007629: Riociguat in Patients With Insufficient Treatment Response to PDE5 Inhibitors (RESPITE) Bayer / ClinicalTrials.gov. First posted 2013. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  9. NCT01179334: Pharmacodynamic Effect of Sildenafil and Riociguat Combination (PATENT PLUS) Bayer / ClinicalTrials.gov. First posted 2010. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  10. NCT02558231: Initial Triple Versus Initial Dual Oral Combination Therapy in Newly Diagnosed PAH (TRITON) Actelion / ClinicalTrials.gov. First posted 2015. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  11. NCT01431716: Epoprostenol for Injection (EFI/ACT-385781A) in PAH (EPITOME-2) Actelion / ClinicalTrials.gov. First posted 2011. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  12. NCT02932410: Macitentan and Disease Progression in Children With PAH (TOMORROW) Actelion / ClinicalTrials.gov. First posted 2016. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  13. NCT01086540: Rituximab for Treatment of Systemic Sclerosis-associated PAH National Institute of Allergy and Infectious Diseases / ClinicalTrials.gov. First posted 2010. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  14. NCT01447628: IV Iron Replacement for Iron Deficiency in Idiopathic PAH Imperial College London / ClinicalTrials.gov. First posted 2011. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  15. NCT03057028: Pilot Study of Anakinra in PAH Virginia Commonwealth University / ClinicalTrials.gov. First posted 2017. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  16. NCT03177603: GSK2586881 Dose-escalation Study in Subjects With PAH GlaxoSmithKline / ClinicalTrials.gov. First posted 2017. Registered intervention and arm descriptions consulted 31 October 2026 for trial-specific administration route, formulation and switching sequence; protocol information does not establish efficacy.
  17. Clinical Pharmacology Review: Bosentan dispersible tablets, NDA 209279 US Food and Drug Administration. 2017. Newly consulted 31 October 2026 for the oral tablet formulations in BREATHE-3 and FUTURE-1; does not substitute for the primary trial result.
  18. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies Tselios K, Gladman DD, Urowitz MB. Open Access Rheumatology. 2017;9:1–9. doi:10.2147/OARRR.S123549. Study-specific regimen extraction in Table 2 consulted 31 October 2026 for oral prednisone and IV cyclophosphamide in Sanchez 2006 and Jaïs 2008; a review table, distinguished from directly retrieved original methods.Study-specific treatment table: structured full text
  19. Winrevair (sotatercept-csrk): original US prescribing information US Food and Drug Administration. 2024. Label cited by the PPHNet cohort and newly checked 31 October 2026, sections 2.1 and 2.4, for the subcutaneous route of its explicitly identified commercial kit. This formulation evidence is distinguished from a route sentence in the cohort methods.
  20. Cardiovascular endothelins: Essential regulators of cardiovascular homeostasis Brunner F, Brás-Silva C, Cerdeira AS, Leite-Moreira AF. Pharmacology & Therapeutics. 2006;111:508–531. Table 1, p522, consulted 31 October 2026 for the explicitly oral REACH-1 regimen. Study-specific secondary corroboration; the original trial full text was access-restricted.
  21. A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure Ameri P, Mercurio V, Pollesello P, et al. Scientific statement of the ESC Heart Failure Association and Working Group on Pulmonary Circulation and Right Ventricular Function. European Journal of Heart Failure. 2024;26:707–729. doi:10.1002/ejhf.3236. Table 1 consulted 31 October 2026 for study-specific oral sildenafil routes in Guazzi 2011 and Belyavskiy 2020; secondary corroboration is distinguished from original trial methods.
  22. Pulmonary Hypertension Secondary to COPD Shujaat A, Bajwa AA, Cury JD. Pulmonary Medicine. 2012;2012:203952. doi:10.1155/2012/203952. Section 12.5 consulted 31 October 2026 for study-specific corroboration of the oral Valerio bosentan regimen; a secondary source, alongside review of the original full paper.
  23. Sarcoidosis-Associated Pulmonary Hypertension and Lung Transplantation for Sarcoidosis Shino MY, Lynch JP III, Fishbein MC, et al. Seminars in Respiratory and Critical Care Medicine. 2014;35:362–371. doi:10.1055/s-0034-1376863. PH-targeted treatment section consulted 31 October 2026 for the explicitly oral Milman sildenafil regimen; study-specific secondary evidence is identified because the original full report remained inaccessible.
  24. Drug Therapy for Chronic Thromboembolic Pulmonary Hypertension: A Review of the Comparative Clinical Effectiveness Canadian Agency for Drugs and Technologies in Health. 2015. Appendix 2, Characteristics of Included Studies, Suntharalingam 2008 row, consulted 31 October 2026 for the chronic oral sildenafil regimen. Secondary extraction is distinguished from acute IV vasoreactivity testing and from directly accessed original trial methods.
  25. Pharmacy Update, March–April 2002: Table 3. Selected Bosentan Clinical Trials Cleveland Clinic, Center for Continuing Education. 2002. Packer REACH-1 row consulted 31 October 2026 for explicit PO administration. Institutional secondary clinical-trial table, corroborating the later peer-reviewed treatment table; no individual author is identified on the table.
  26. Tracleer (bosentan): US prescribing information, 2013 US Food and Drug Administration. 2013. Sections 3 and 11 checked 31 October 2026 for the 62.5/125-mg oral tablet formulation explicitly identified by the sarcoidosis trial registry; does not independently establish trial efficacy.
  27. Flolan (epoprostenol sodium): US prescribing information, 2018 US Food and Drug Administration. 2018. Checked 31 October 2026 to establish the IV route of the parenteral epoprostenol formulation in the fully reviewed Bonham cohort; participant-level treprostinil IV/SC attribution remains unreported.
  28. Tracleer (bosentan): US prescribing information, 2009 US Food and Drug Administration. 2009. Checked 31 October 2026 for the approved oral formulation identified in the Minniti sickle-cell cohort and its ASSET protocol context; formulation corroboration is distinguished from a literal route sentence in the cohort methods.
  29. Letairis (ambrisentan): US prescribing information, 2013 US Food and Drug Administration. 2013. Checked 31 October 2026 for the oral tablet formulation used in the named approved-regimen sickle-cell cohort; route corroboration does not establish an indication for that cohort.
  30. Warfarin Orion tablets: Summary of Product Characteristics Swedish Medical Products Agency. Sections 1–4.2 consulted 31 October 2026 for oral administration of the exact Orion warfarin product named in the Barati post-PEA study. A study-specific formulation check, not a prescribing recommendation.
  31. Daiichi Sankyo launches MINNEBRO tablets in Japan: original product outline Daiichi Sankyo. 13 May 2019. Product outline consulted 31 October 2026 for the oral tablet formulation identified in the esaxerenone study regimens; formulation corroboration only, not evidence of HFpEF or PH efficacy.
Pulmonary hypertension: routine-care cohorts and additional follow-up13
  1. Safety of macitentan for the treatment of pulmonary hypertension: Real-world experience from the OPsumit Users Registry (OPUS) and OPsumit Historical Users cohort (OrPHeUS) McLaughlin VV, Channick R, Kim NH, et al. 2022. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.
  2. Disease characteristics, treatments, and outcomes of patients with pulmonary arterial hypertension treated with selexipag in real-world settings from the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry) McLaughlin V, Farber HW, Highland KB, et al. 2024. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.
  3. Comparative Analysis of Survival in Pulmonary Arterial Hypertension for Patients Treated with Selexipag in Clinical Practice (EXPOSURE Study) Söderberg S, Escribano-Subias P, Archey C, et al. 2025. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report. Administration-route review consulted primary reports and available protocol text, 31 October 2026.Primary report: administration methods
  4. Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry Hoeper MM, Gomez Sanchez MA, Humbert M, et al. 2021. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report. Administration-route review consulted primary reports and available protocol text, 31 October 2026; Full-paper review establishes the named oral tablet formulation from its cited product information.EXPERT registered protocol: Bayer, first posted 2014Original full report: administration review
  5. Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry Ghofrani HA, Gomez Sanchez MA, Humbert M, et al. 2021. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report. Administration-route review consulted primary reports and available protocol text, 31 October 2026; Full-paper review establishes the named oral tablet formulation from its cited product information.EXPERT registered protocol: Bayer, first posted 2014Primary report: route and formulation methodsOriginal full report: administration reviewStudy-specific administration evidence
  6. Real-World Experience with Selexipag in Patients with Pulmonary Arterial Hypertension: Treatment Patterns and Outcomes across Baseline Risk Strata (SPHERE and EXPOSURE Studies) Escribano Subias P, Chakinala MM, Chin KM, et al. 2026. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.
  7. Real-World Comparison of Patients With PH-ILD Initiating Inhaled Treprostinil Versus Patients Who Remain Untreated Cassady SJ, Ramani GV, Wu B, Morland K, Burger CD. 2025. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.Primary report: route and formulation methodsPrimary report: route and formulation methods
  8. Real-World Outcomes of Inhaled Treprostinil in Pulmonary Hypertension Related to Interstitial Lung Disease: A Multicenter, Retrospective Analysis Kyle AR, Jose A, Catherman K, et al. 2026. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.Primary report: route and formulation methodsPrimary report: route and formulation methods
  9. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial Ghofrani HA, Grimminger F, Grünig E, et al. 2016. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.
  10. Long-term safety and tolerability of ambrisentan treatment for pediatric patients with pulmonary arterial hypertension: An open-label extension study Ivy D, Beghetti M, Juaneda-Simian E, et al. 2024. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report. Administration-route review consulted primary reports and available protocol text, 31 October 2026.Primary report: administration methods
  11. Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension Shah AM, Campbell P, Querejeta Roca G, et al. 2015. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.
  12. ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary hypertension Badesch DB, Feldman J, Keogh A, et al. 2012. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.
  13. Effect of ambrisentan in patients with systemic sclerosis and mild pulmonary arterial hypertension: long-term follow-up data from EDITA study Xanthouli P, Uesbeck P, Lorenz HM, et al. 2024. Primary publication newly consulted 31 October 2026 for the linked PH evidence appraisal; study design, population overlap, denominators and limitations are explicit in its detailed report.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Self-selected treatment, baseline gas-transfer differences, small single-center cohort and incomplete RHC. Comparisons are vulnerable to selection and confounding.
HFpEF: finerenone and spironolactone evidence35
  1. Finerenone and Outpatient Worsening Heart Failure With Mildly Reduced or Preserved Ejection Fraction Cunningham JW, Chatur S, Claggett BL, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  2. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction Solomon SD, McMurray JJV, Vaduganathan M, et al. 2024. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Study registration
  3. Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure With Mildly Reduced or Preserved Ejection Fraction Docherty KF, Henderson AD, Jhund PS, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  4. Effects of the Nonsteroidal MRA Finerenone With and Without Concomitant SGLT2 Inhibitor Use in Heart Failure Vaduganathan M, Claggett BL, Kulac IJ, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  5. Finerenone in Patients With a Recent Worsening Heart Failure Event: The FINEARTS-HF Trial Desai AS, Vaduganathan M, Claggett BL, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  6. Finerenone, Serum Potassium, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction Vardeny O, Vaduganathan M, Claggett BL, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  7. Finerenone and Kidney Outcomes in Patients With Heart Failure: The FINEARTS-HF Trial Mc Causland FR, Vaduganathan M, Claggett BL, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  8. Finerenone and Atrial Fibrillation in Heart Failure: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial Matsumoto S, Henderson AD, Jhund PS, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  9. Finerenone in Heart Failure With Improved Ejection Fraction: The FINEARTS-HF Randomized Clinical Trial Pabon MA, Vardeny O, Vaduganathan M, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  10. Finerenone and Blood Pressure in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The FINEARTS-HF Randomized Clinical Trial Ostrominski JW, Claggett BL, Kulac IJ, et al. 2026. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  11. Finerenone and quality of life in heart failure: component-level analyses and clinical relevance of the Kansas City cardiomyopathy questionnaire Hamatani Y, Peikert A, Claggett BL, et al. 2026. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  12. Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial Butt JH, Jhund PS, Henderson AD, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Study registrationPrimary report / linked sourcePrimary methods: administration route
  13. Finerenone Across the Spectrum of Kidney Risk in Heart Failure: The FINEARTS-HF Trial Ostrominski JW, Mc Causland FR, Claggett BL, et al. 2026. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  14. Interplay of serum potassium and kidney function with finerenone in heart failure with mildly reduced or preserved ejection fraction: Findings from FINEARTS-HF Ferreira JP, Vaduganathan M, Claggett BL, et al. 2025. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  15. Spironolactone for Heart Failure with Preserved Ejection Fraction Pitt B, Pfeffer MA, Assmann SF, et al. 2014. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Study registrationPrimary methods: administration route
  16. Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With HFpEF: The Aldo-DHF Randomized Controlled Trial Edelmann F, Wachter R, Schmidt AG, et al. 2013. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Primary methods: administration route
  17. Regional Variation in Patients and Outcomes in the TOPCAT Trial Pfeffer MA, Claggett B, Assmann SF, et al. 2015. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  18. Spironolactone Metabolites in TOPCAT — New Insights into Regional Variation de Denus S, O’Meara E, Desai AS, et al. 2017. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  19. Prognostic Importance of Changes in Cardiac Structure and Function in HFpEF and the Impact of Spironolactone Shah AM, Claggett B, Sweitzer NK, et al. 2015. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  20. Influence of Ejection Fraction on Outcomes and Efficacy of Spironolactone in Patients With HFpEF Solomon SD, Claggett B, Lewis EF, et al. 2016. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  21. Effect of Aldosterone Antagonism on Exercise Tolerance in Heart Failure With Preserved Ejection Fraction Kosmala W, Rojek A, Przewlocka-Kosmala M, et al. 2016. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Primary methods: administration route
  22. Effects of Spironolactone Treatment in Elderly Women With Heart Failure and Preserved Left Ventricular Ejection Fraction Kurrelmeyer KM, Ashton Y, Xu J, et al. 2014. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Study registrationOriginal publisher report
  23. Effect of Spironolactone on Exercise Tolerance and Arterial Function in Older Adults With HFpEF Upadhya B, Hundley WG, Brubaker PH, et al. 2017. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Study registrationOriginal study report
  24. Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease Beldhuis IE, Myhre PL, Claggett B, et al. 2019. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.Study registration
  25. SPIRIT-HF-DZHK8: ACC.26 Results — No Significant Benefit, Interpretation Limited by Under-Recruitment German Centre for Cardiovascular Research (DZHK); investigator Frank Edelmann. 2026. Sponsor report. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Original study intervention and route
  26. Spironolactone Effect on Cardiac Structure and Function of Patients With HFpEF: A Pooled Analysis of Three Randomized Trials Ferreira JP, Cleland JG, Girerd N, et al. 2023. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required. Administration route reviewed against the original report, study formulation or registered protocol, 31 October 2026.Original study intervention and route
  27. Novel Treatment for Diastolic Heart Failure in Women Baylor College of Medicine; ClinicalTrials.gov NCT00206232. 2005. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.
  28. Spironolactone in the Treatment of HFmrEF/HFpEF: Design and Baseline Characteristics of SPIRIT-HF-DZHK08 Zurkan D, Pieske B, Petutschnigg J, et al. 2026. Original research. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.
  29. SPIRonolactone In the Treatment for Heart Failure (SPIRIT-HF-DZHK8): Official Study Record German Centre for Cardiovascular Research (DZHK). 2026. Sponsor report. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.
  30. The Effect of Spironolactone on Cardiovascular Function and Markers of Fibrosis in People at Increased Risk of Developing Heart Failure: The HOMAGE Randomized Clinical Trial Cleland JGF, Ferreira JP, Mariottoni B, et al. 2021. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.
  31. Aldo-DHF: Synopsis of the Clinical Trial Report, Final 3.0, 16 August 2013 Edelmann F, Gelbrich G, Pieske B; University of Göttingen. 2013. Sponsor report. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.
  32. SPIRIT-HF: ACC.26 Conference Organizer Report of the Investigator’s Late-Breaking Results American College of Cardiology; investigator Frank Edelmann. 2026. Trial. Reviewed 31 October 2026 for underlying-HF evidence in Group 2; PH was not uniformly required.
  33. KERENDIA (finerenone): US prescribing information Bayer HealthCare Pharmaceuticals; DailyMed. Revised September 2026. Underlying heart failure with LVEF ≥40%, potassium and renal monitoring; not a PH-specific indication.
  34. 2023 ACC Expert Consensus Decision Pathway on Management of HFpEF Kittleson MM, Panjrath GS, Amancherla K, et al. J Am Coll Cardiol. 2023;81:1835–1878. Selected MRA use and monitoring in the underlying HF population.ACC key points
  35. Management of HFpEF: 2026 ACC Expert Consensus Decision Pathway Kittleson MM, Panjrath GS, Bates K, et al. J Am Coll Cardiol. 2026;88:1817–1846. Bibliographic/context check and trial identification; primary trial reports supply numerical appraisals.
Evidence interpretation and benefit–risk methods2
  1. Chapter 15: Interpreting results and drawing conclusions Schünemann HJ, Vist GE, Higgins JPT, Santesso N, Deeks JJ, Glasziou P, Akl EA, Guyatt GH. In: Cochrane Handbook for Systematic Reviews of Interventions, version 6.5. Cochrane; 2024. Chapter updated August 2023. Newly consulted 31 October 2026 for interpretation of outcomes, applicability, uncertainty and benefit–harm trade-offs. This methods guidance does not validate the application's original ordinal categories or substitute for a systematic review.
  2. Benefit-Risk Assessment for New Drug and Biological Products: Guidance for Industry US Food and Drug Administration, CDER and CBER. Final guidance, October 2023. Newly consulted 31 October 2026 for structured qualitative assessment of therapeutic context, benefits, risks and uncertainties. Its regulatory framework does not endorse this educational figure, its editorial categories or any specific treatment ranking.
HFpEF: other mineralocorticoid receptor antagonists and modulators9
  1. Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM-PEF) Deswal A, Richardson P, Bozkurt B, Mann DL. 2011. Trial. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Study registration (NCT00108251)Structured registry record
  2. Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone Mak GJ, Ledwidge MT, Watson CJ, et al. 2009. Trial. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Study registration (NCT00505336)Structured registry record
  3. Effect of AZD9977 and spironolactone on serum potassium in heart failure with preserved or mildly reduced ejection fraction, and renal impairment: A randomized trial Squire IB, Gabrielsen A, Greasley PJ, et al. 2022. Trial. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Study registration (NCT03682497)
  4. Balcinrenone plus dapagliflozin in patients with heart failure and chronic kidney disease: Results from the phase 2b MIRACLE trial Lam CSP, Køber L, Kuwahara K, et al. 2024. Trial. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Study registration (NCT04595370)Structured registry record
  5. Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis Jhund PS, Talebi A, Henderson AD, et al. 2024. Original research. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026.
  6. Implication of Mineralocorticoid Receptor Antagonist Esaxerenone in Patients With Heart Failure With Preserved Ejection Fraction Imamura T, Oshima A, Narang N, Kinugawa K. 2021. Original research. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Original full text: study formulation and route review
  7. The Role of Esaxerenone in the Continuum of Heart Failure With Preserved Ejection Fraction: Insights From a Prospective Observational Study Naruke T, Hashimura-Kakogawa M, Suzuki Y, et al. 2025. Original research. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Original full text: study formulation and route review
  8. A Prospective Crossover Clinical Trial of Esaxerenone and Eplerenone in Patients with Chronic Heart Failure Complicated by Hypertension Sezai A, Abe M, Maruyama T, et al. 2025. Trial. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Comparative clinical trial of Eplerenone and Esaxerenone for hypertension with chronic heart failureOriginal full text: study formulation and route review
  9. Cardiorenal Effects of Switching from Eplerenone to Esaxerenone in Patients with Chronic Heart Failure and Hypertension: A Prospective Clinical Study Sezai A, Abe M, Maruyama T, et al. 2026. Original research. Underlying-HF evidence; PH was not required. Reviewed 31 October 2026. Administration route and study formulation reviewed 31 October 2026; background and switch roles remain explicit.Comparative clinical trial of Eplerenone and Esaxerenone for hypertension with chronic heart failure treating EplerenoneOriginal full text: study formulation and route review
Pulmonary hypertension: 2 November 2026 journal watch32
  1. Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study Rao D, Haldeman S, Carroll J, Rao R. 2026. Primary report reviewed 2 November 2026.
  2. First Report of Real World Utilization of an Activin Signaling Inhibitor in Patients With Severe Pulmonary Arterial Hypertension in the Middle East PH RISE-ME Study Al Jabi M, Sabbour H, Mohamed L, et al. 2026. Primary report reviewed 2 November 2026.
  3. Sodium-Glucose Cotransporter-2 Inhibitors in World Health Organization Group 1 Pulmonary Arterial Hypertension: A REVEAL Lite 2-Matched Cohort With Time-Varying Exposure Analysis Hafez A, Youssef A, Nour M, et al. 2026. Primary report reviewed 2 November 2026.
  4. Novel cardiovascular magnetic resonance imaging biomarkers to track response to treatment including Sotatercept in a patient with idiopathic pulmonary arterial hypertension: a case report Castiglione A, Kjellström B, Rådegran G, Ostenfeld E. 2026. Primary report reviewed 2 November 2026.
  5. Case Report: Upfront sotatercept-based triple therapy in high-risk systemic sclerosis-associated pulmonary arterial hypertension Tamura Y, Isobe S, Fujii H, Shirai Y, Kuwana M. 2026. Primary report reviewed 2 November 2026.
  6. Salvage Use of Sotatercept for Potts Shunt in Refractory Pulmonary Hypertension Xu Z, Zhang M, Chen Y, et al. 2026. Primary report reviewed 2 November 2026.
  7. Use of sotatercept in an adolescent patient with idiopathic pulmonary arterial hypertension Kurosaki K, Akazawa Y, Yuki T, Takei K, Takigiku K. 2026. Primary report reviewed 2 November 2026.
  8. Pulmonary vasoreactive reserve in patients with idiopathic pulmonary arterial hypertension: characteristics and clinical significance Goncharova N, Lapshin K, Berezina A, et al. 2026. Primary report reviewed 2 November 2026.
  9. A156 Sotatercept in High-Risk PAH Patients Under Triple Combination Therapy, in a Greek PAH centre · PVRI 2026 Dublin Frantzeskaki F, Konstantonis D, Rizos M, et al. 2026. Primary report reviewed 2 November 2026.
  10. PROSERA phase 3 results: ATS 2026 primary poster Ghofrani HA, McLaughlin VV, Meyer G, et al. ATS International Conference, May 2026. Safety Tables 2–3; as-treated kit-exposure denominators.
  11. Targeting ZIP12-mediated Zn2+ signaling as a treatment for pulmonary hypertension Science Translational Medicine. 2026. DOI 10.1126/scitranslmed.aee0680. Primary abstract checked; full paper/supplement access restricted.
  12. APL-9796 primary publication and healthy-volunteer phase 1 summary Apollo Therapeutics. 22 October 2026. Sponsor report; human phase 1 safety is distinct from efficacy in PH patients.
  13. Activin pathway inhibition and rapid progression of malignancy in pulmonary arterial hypertension: A case series and hypothesis Tonelli AR, Aulak KS, Berro J, Highland KB. Respir Med. 2026;263:109151. DOI 10.1016/j.rmed.2026.109151. Accessible primary abstract; denominator and full methods awaiting verification.
  14. Partial Echocardiographic Remission After Sotatercept: Expanding Treatment Goals in Pulmonary Arterial Hypertension Gutiérrez-Ortiz E, Martín de Miguel I, Cruz Utrilla A, et al. Arch Bronconeumol. 2026. DOI 10.1016/j.arbres.2026.09.004. No abstract/full results accessible in this review.
  15. Sustained improvement of systemic lupus erythematosus-associated pulmonary arterial hypertension by CD19 CAR T-cell therapy: 1-year haemodynamic follow-up Qian J, Zhao J, Wang Q, et al. Ann Rheum Dis. 2026. DOI 10.1016/j.ard.2026.09.009. Results source awaiting full-text verification.
  16. Insmed CHEST 2026 respiratory portfolio presentations Insmed. 14 October 2026. Official titles and congress links for TPIP PAH imaging, PAH OLE and PH-ILD OLE; announcement alone does not establish results.
  17. SATISFY-JP registration jRCT2031210626. Japanese Registry of Clinical Trials. Target enrollment and protocol only; not an observed outcome report.
  18. NCT03626688 · PAH journal-watch registry verification ClinicalTrials.gov. Registration and posted-result status checked 2 November 2026; no outcome inferred from a protocol or recruitment status.
  19. NCT05587712 · PAH journal-watch registry verification ClinicalTrials.gov. Registration and posted-result status checked 2 November 2026; no outcome inferred from a protocol or recruitment status.
  20. NCT05679570 · PAH journal-watch registry verification ClinicalTrials.gov. Registration and posted-result status checked 2 November 2026; no outcome inferred from a protocol or recruitment status.
  21. NCT05649748 · PAH journal-watch registry verification ClinicalTrials.gov. Registration and posted-result status checked 2 November 2026; no outcome inferred from a protocol or recruitment status.
  22. NCT06846554 · PAH journal-watch registry verification ClinicalTrials.gov. Registration and posted-result status checked 2 November 2026; no outcome inferred from a protocol or recruitment status.
  23. KCNK3-associated PAH during amlodipine treatment 2026. Primary case report; PMID42781697. Reviewed 2 November 2026.
  24. EXCEL: switching beraprost to selexipag 2024. Primary prospective Japanese study; PMID38794126. Reviewed 2 November 2026.
  25. Safety of chronic high-dose calcium channel blockers exposure in children with PAH 2022. Primary pediatric cohort; PMID36158824. Reviewed 2 November 2026.
  26. Pulmonary edema with nifedipine in primary pulmonary hypertension 1985. Primary fatal adverse-event case; PMID4001571. Reviewed 2 November 2026.
  27. Reversibility of primary pulmonary hypertension during six years of treatment with oral diazoxide 1987. Primary clinical case; PMID3814459. Reviewed 2 November 2026.
  28. A case of primary pulmonary hypertension treated with prazosin and isosorbide dinitrate 1984. Primary case; PMID6530750. Reviewed 2 November 2026.
  29. Adverse effect of hydralazine in patients with primary pulmonary hypertension 1982. Primary historical report; results and denominator awaiting full-text verification. Reviewed 2 November 2026.
  30. Failure of nifedipine treatment in primary pulmonary hypertension 1982. Primary historical report; accessible indexed record has no abstract. Reviewed 2 November 2026.
  31. Death in a patient with primary pulmonary hypertension after 20 mg of nifedipine 1993. Primary adverse-event report; full methods awaiting verification. Reviewed 2 November 2026.
  32. Pulmonary oedema and pleural effusion in two patients with primary pulmonary hypertension treated with calcium channel blockers 1996. Primary adverse-event report; full source awaiting extraction. Reviewed 2 November 2026.
Pulmonary hypertension: additional primary reports reviewed 2 November 202669
  1. Same Class, Different Risk? Dapagliflozin versus Empagliflozin and Genitourinary Safety in Heart Failure with Preserved Ejection Fraction: A Retrospective Comparative Cohort Study Danau RA, Munteanu MA, Muraru M, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  2. Early Changes in Left Atrial Mechanics During Sodium-Glucose Cotransporter-2 Inhibitor Therapy in Heart Failure with Preserved Ejection Fraction Altun SC, Özyüncü N, Akbulut Koyuncu İM, Tan TS. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  3. Effect of dapagliflozin on left ventricular longitudinal strain and atrioventricular coupling in heart failure with preserved ejection fraction and chronic kidney disease Chen F, Xu C, Chen Y, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  4. SGLT-2 inhibitor dapagliflozin improves left ventricular diastolic function and reduces circulating inflammatory markers in HFpEF patients: a retrospective cohort study Ye JF, Zhang J, Wang X, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  5. Dapagliflozin in phenotypically stratified HFpEF without myocardial fibrosis: the STADIA-HFpEF randomized crossover trial Scheffer M, van Maarschalkerwaart W, Dong C, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  6. Stratified Treatment of Heart Failure with preserved Ejection Fraction: rationale and design of the STADIA-HFpEF trial Scheffer M, Driessen-Waaijer A, Hamdani N, et al. 2020. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  7. Effects of Fasudil on Patients with Pulmonary Hypertension Associated with Left Ventricular Heart Failure with Preserved Ejection Fraction: A Prospective Intervention Study Zhang X, Zhang X, Wang S, et al. 2018. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  8. Sotatercept as a Treatment for Pulmonary Hypertension Associated With Connective Tissue Disease and ILD Vargas-Ursúa F, Cruz-Utrilla A, Tenes A. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  9. Captopril effects on pulmonary and systemic hemodynamics in chronic cor pulmonale Zieliński J, Hawrylkiewicz I, Górecka D, et al. 1986. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  10. Haemodynamic and endocrine effects of type 1 angiotensin II receptor blockade in patients with hypoxaemic cor pulmonale Kiely DG, Cargill RI, Wheeldon NM, et al. 1997. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  11. Comparison of levosimendan, NO, and inhaled iloprost for pulmonary hypertension reversibility assessment in heart transplant candidates Tavares-Silva M, Saraiva F, Pinto R, et al. 2021. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  12. Short- and long-term hemodynamic effects of oral nifedipine in patients with pulmonary hypertension secondary to COPD and lung fibrosis. Deleterious effects in patients with restrictive disease. Domenighetti GM, Saglini VG. 1992. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  13. One-year clinical study on nifedipine in the treatment of pulmonary hypertension in chronic obstructive lung disease Vestri R, Philip-Joet F, Surpas P, Arnaud A, Saadjian A. 1988. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  14. Nesiritide for secondary pulmonary hypertension in patients with end-stage heart failure O’Dell KM, Kalus JS, Kucukarslan S, Czerska B. 2005. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  15. A Novel Insight Into Luspatercept: Therapeutic Implications in Myelodysplastic Syndrome Patients With Elevated Pulmonary Artery Systolic Pressure. Jin Q, Tian D, Chen D, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  16. Luspatercept Treatment in a β-Thalassemia Patient with Pulmonary Arterial Hypertension: A Case Report. Yang B, Liu D, Yang C, et al. 2025. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  17. Clinical Study to Evaluate the Possible Efficacy and Safety of L-Arginine in Children with Sickle Cell Disease and Increased Tricuspid Regurgitant Jet Velocity: a Randomized Controlled Trial. Gomaa DA, El-Haggar SM, El-Shanshory MR, et al. 2025. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  18. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Morris CR, Morris SM, Hagar W, et al. 2003. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  19. Efficacy and safety of inhaled nitrite in addition to sildenafil in thalassemia patients with pulmonary hypertension: A 12-week randomized, double-blind placebo-controlled clinical trial. Sasiprapha T, Pussadhamma B, Sibmooh N, et al. 2022. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  20. Randomized Clinical and Biochemical Study Comparing the Effect of L-arginine and Sildenafil in Beta Thalassemia Major Children With High Tricuspid Regurgitant Jet Velocity. El-Khateeb E, El-Haggar SM, El-Razaky O, et al. 2022. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  21. Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial. Gladwin MT, Gordeuk VR, Desai PC, et al. 2024. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  22. Safety of macitentan in sarcoidosis-associated pulmonary hypertension: a case-series. Mathijssen H, Huitema MP, Bakker ALM, et al. 2020. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  23. Treatment of newly diagnosed sarcoid-associated pulmonary hypertension with ambrisentan and tadalafil combination therapy. Abston E, Hon S, Lawrence R, et al. 2020. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  24. Long-term outcomes of epoprostenol therapy in sarcoid associated pulmonary hypertension. Abston E, Moll M, Hon S, et al. 2020. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  25. Riociguat use in sickle cell related chronic thromboembolic pulmonary hypertension: A case series. Weir NA, Conrey A, Lewis D, et al. 2018. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  26. Prostacyclin-analog therapy in sickle cell pulmonary hypertension. Weir NA, Saiyed R, Alam S, et al. 2017. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  27. Long-term tolerability of phosphodiesterase-5 inhibitors in pulmonary hypertension of sickle cell disease. Cramer-Bour C, Ruhl AP, Nouraie SM, et al. 2021. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  28. Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Machado RF, Martyr S, Kato GJ, et al. 2005. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  29. Clinical characteristics, haemodynamics and treatment of pulmonary hypertension in sarcoidosis in a single centre, and meta-analysis of the published data. Dobarro D, Schreiber BE, Handler C, et al. 2013. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  30. Treatment of sarcoidosis-associated pulmonary hypertension: A single centre retrospective experience using targeted therapies. Keir GJ, Walsh SL, Gatzoulis MA, et al. 2014. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  31. Direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension patients: A retrospective cohort study. Chong LT, Hu S, Guo TT, et al. 2024. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  32. Direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension and the presence of recent thrombus during pulmonary endarterectomy. Jeong I, Alotaibi M, Fernandes TM, et al. 2022. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  33. Use of direct anticoagulants in chronic thromboembolic pulmonary hypertension: An anatomopathological study of endarterectomy material. Salibe-Filho W, Nascimento YPP, Tatagiba LS, et al. 2025. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  34. Real-life data of direct anticoagulant use, bleeding risk and venous thromboembolism recurrence in chronic thromboembolic pulmonary hypertension patients: an observational retrospective study. Sena S, Bulent M, Derya K, et al. 2020. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  35. Safety and efficacy of direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension. Benzidia I, Robitaille C, Abualsaud A, et al. 2023. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  36. Association Between Anticoagulation Outcomes and Venous Thromboembolism History in Chronic Thromboembolic Pulmonary Hypertension. Zhu YJ, Zhou YP, Wei YP, et al. 2021. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  37. The anticoagulant effects of warfarin and the bleeding risk associated with its use in patients with chronic thromboembolic pulmonary hypertension at a specialist center in Japan: a retrospective cohort study. Jujo-Sanada T, Tanabe N, Sakao S, et al. 2017. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  38. Pulmonary artery fresh floating thrombus in patients with chronic thromboembolic pulmonary hypertension on low-dose direct oral anticoagulants: A single-center angiographic observational study. Suetomi T, Shimokawahara H, Kuronuma K, et al. 2025. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  39. Haemodynamic and clinical impacts of switching phosphodiesterase-5 inhibitors to riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after balloon pulmonary angioplasty (BPA) - a prospective cohort study. Kam THH, Kam KKH, Wong MKL, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  40. Upfront combination therapy with sildenafil and ambrisentan in patients with chronic thromboembolic pulmonary hypertension. Salibe-Filho W, Vieira TM, Leonidas Alves-Junior J, et al. 2025. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  41. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Ghofrani HA, Schermuly RT, Rose F, et al. 2003. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  42. Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension. Skoro-Sajer N, Bonderman D, Wiesbauer F, et al. 2007. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  43. Long-term efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension. Post MC, Plokker HW, Kelder JC, et al. 2009. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  44. Use of direct oral anticoagulants for chronic thromboembolic pulmonary hypertension. Gavilanes-Oleas FA, Alves JL, Fernandes CJC, et al. 2018. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  45. Beneficial effects of riociguat on hemodynamic responses to exercise in CTEPH patients after balloon pulmonary angioplasty - A randomized controlled study. Aoki T, Sugimura K, Terui Y, et al. 2020. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  46. Riociguat as inpatient rescue therapy for acute decompensation of inoperable chronic thromboembolic pulmonary hypertension. Alsufyani RH, Imran S, Mccullagh B, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  47. The Effects of Hydroxyurea Therapy on the Six-Minute Walk Distance in Patients with Adult Sickle Cell Anemia: An Echocardiographic Study. Garadah T, Mandeel F, Jaradat A, et al. 2019. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  48. Comparative study of pulmonary circulation and myocardial function in patients with β-thalassemia intermedia with and without hydroxyurea, a case-control study. Amoozgar H, Farhani N, Khodadadi N, et al. 2011. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  49. Macitentan Administration for Pulmonary Hypertension Due to β-thalassemia with Multiple Organ Failure. Takagi K, Kasai H, Tani H, et al. 2023. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  50. Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies. Derchi G, Forni GL, Formisano F, et al. 2005. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  51. Sequential treatment with sildenafil and riociguat in patients with persistent or inoperable chronic thromboembolic pulmonary hypertension improves functional class and pulmonary hemodynamics. Darocha S, Banaszkiewicz M, Pietrasik A, et al. 2018. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  52. Bosentan or Macitentan Therapy in Chronic Thromboembolic Pulmonary Hypertension? van Thor MCJ, Ten Klooster L, Snijder RJ, et al. 2019. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  53. Haemodynamic benefit of bridging use of bosentan prior to pulmonary endarterectomy. Kunihara T, Wilkens H, Halank M, et al. 2021. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  54. Long-term advanced therapy with bosentan improves symptoms and prevents deterioration of inoperable chronic thromboembolic pulmonary hypertension. Nishikawa-Takahashi M, Ueno S, Kario K. 2014. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  55. Bosentan treatment is associated with improvement of right ventricular function and remodeling in chronic thromboembolic pulmonary hypertension. Surie S, Reesink HJ, Marcus JT, et al. 2013. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  56. The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study. Hughes RJ, Jais X, Bonderman D, et al. 2006. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  57. Bosentan for patients with chronic thromboembolic pulmonary hypertension. Vassallo FG, Kodric M, Scarduelli C, et al. 2008. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  58. Bosentan therapy for chronic thromboembolic pulmonary hypertension. A national open label study assessing the effect of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study). Ulrich S, Speich R, Domenighetti G, et al. 2007. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  59. Bosentan therapy for inoperable chronic thromboembolic pulmonary hypertension. Hoeper MM, Kramm T, Wilkens H, et al. 2005. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  60. Bosentan therapy for inoperable chronic thromboembolic pulmonary hypertension. Bonderman D, Nowotny R, Skoro-Sajer N, et al. 2005. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  61. Long-term bosentan in chronic thromboembolic pulmonary hypertension. Seyfarth HJ, Hammerschmidt S, Pankau H, et al. 2006. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  62. [Role of bosentan in patients with chronic venous thromboembolic pulmonary hypertension]. Segovia Cubero J, Ortiz Uribe JC, Gómez Bueno M, et al. 2007. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  63. Pulmonary hypertensive medical therapy in chronic thromboembolic pulmonary hypertension before pulmonary thromboendarterectomy. Jensen KW, Kerr KM, Fedullo PF, et al. 2009. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  64. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Ghofrani HA, Hoeper MM, Halank M, et al. 2010. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  65. PVRI 2026 A092: Features of Right Heart Remodeling and Effects of Comprehensive Therapy in Patients with Pulmonary Hypertension Rahimova D, Rakhimova DA, Alyavi AL, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  66. PVRI 2026 A179: Selective Pulmonary Vasodilation by Intravenous PDNO in Patients With Pulmonary Hypertension After Cardiac Surgery Nilsson K, Adding C, Seilitz J, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  67. OPTION registration and actual olaparib product ClinicalTrials.gov. Route verification for the OPTION primary conference report. Accessed 2 November 2026.
  68. ARTISAN registration and treprostinil transition regimen ClinicalTrials.gov. Study-specific IV/SC to oral transition route verification. Accessed 2 November 2026.
  69. Lynparza product information European Medicines Agency. Formulation verification for the named oral tablet product used in OPTION; not a PH treatment indication. Accessed 2 November 2026.
Pulmonary hypertension: reproducible literature retrieval1
  1. Documented PH journal-watch database and source queries · 2 November 2026 PubMed/MEDLINE, Europe PMC, ClinicalTrials.gov and primary proceedings. Exact query text, source counts, timestamps and pagination status are retained in the source-coverage manifest. These links document retrieval, not verified efficacy.cteph-update-windowcteph-windowCTEPH and group5 registry updated overlapexact-primary-chasesgroup5-drug-historygroup5-update-windowgroup5-windowTargeted registry recheck NCT02633397Targeted registry recheck NCT03814317Targeted study-specific administration recheckTargeted registry recheck NCT07886554sapphire-lam-definitive-searchHistorical primary PH and PAH: CCB, sitaxsentan, beraprost and older vasodilators; unrestricted datesNamed PAH verification queue and antiZIP12 registry refreshPAH, historical primary PH, portopulmonary and Eisenmenger: publication or entry overlapacronyms-any-datefamily-followups-updatedfamily-followups-windowhf-drugs-updatedhf-drugs-windowhistorical-lefthistorical-lungleft-updatedleft-windowlung-updatedlung-window
Pulmonary hypertension: further primary reports reviewed 2 November 202631
  1. A156 Sotatercept in High-Risk PAH Patients Under Triple Combination Therapy, in a Greek PAH centre · PVRI 2026 Dublin Frantzeskaki F, Konstantonis D, Rizos M, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  2. A165 Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Liposomal Treprostinil Inhalation Suspension (L606) in PAH and PH-ILD · PVRI 2026 Dublin Muralidhar A, Triveri M, Restrepo-Jaramillo R, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  3. A010 Sotatercept · Ohio State first-year practice · PVRI 2026 Dublin Kittel D, Garber E, Schlegel M, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  4. A029 TPIP · exploratory respiratory-imaging substudy · PVRI 2026 Dublin Preston IR, Frantz RP, Muchmore P, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  5. A044 HYPERION · RV echo secondary report · PVRI 2026 Dublin McLaughlin VV, Hoeper MM, Badesch DB, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  6. A055 OPTION · olaparib phase 1b · PVRI 2026 Dublin OPTION investigators; PVRI 2026 A055 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  7. A134 ADVANCE EXTENSION · interim risk analysis · PVRI 2026 Dublin Benza R, Botta CE, Church C, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  8. A135 ARTISAN · early treprostinil interim analysis · PVRI 2026 Dublin Benza R, Chin K, Lachant D, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  9. A138 Nebulized treprostinil · postmarketing safety cases · PVRI 2026 Dublin Kugener A, Lopchuk S, Chaar-Alvarez F, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  10. A139 Treprostinil DPI · postmarketing safety cases · PVRI 2026 Dublin Kugener A, Lopchuk S, Chaar-Alvarez F, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  11. A166 SC treprostinil · monitored home titration · PVRI 2026 Dublin Minnock C, Lennon D, Cullivan S, McCullagh B. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  12. A170 Sotatercept · two Eisenmenger cases · PVRI 2026 Dublin Lammers A, Diller GP. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  13. A175 Sotatercept · two-center US experience · PVRI 2026 Dublin Habib N, Javed H, Balasubramanian V. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  14. Dasatinib-Induced Pulmonary Arterial Hypertension. Musthafa HN, Mufti G, Sivadasanpillai H. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  15. Angiotensin Converting Enzyme Inhibition and Mortality in Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) Yogeswaran A, Fünderich M, Wendlandt K, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  16. Response Letter: ACE Inhibition in PH-COPD: Severity Stratification Unlocks a Precision Medicine Opportunity Yogeswaran A, Tello K, Seeger W. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  17. A021: Safety and Exploratory Efficacy Data of LIQ861 Dry Powder Inhaled Treprostinil in PH-ILD Patients: ASCENT to Week 24 Saggar R, Ravichandran A, Kolaitis N, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  18. ASCENT to Week 24: primary PVRI 2026 poster 83, including paired analysis denominators and adverse-event severity Saggar R, Ravichandran A, Kolaitis N, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  19. A020: Changes in Cardiac Effort in Pulmonary Hypertension–Interstitial Lung Disease: Insights from the ASCENT Trial Lachant D, Galloway A, Fleming D, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  20. A071: Evaluating the Effect of Increasing Dose of Sildenafil on Pulmonary Haemodynamics in ILD-PH Using Remote Monitoring Burney R, Paula-Ribeiro M, Goh ZM, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  21. A099: Effect of High Dose Inhaled Treprostinil On Mortality In Patients Enrolled in the Open-Label Extension of the INCREASE Trial Shlobin O, Bajwa A, Deng C, et al. 2026. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  22. Prevalence of potential drug-drug interactions with disease-specific treatments in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: A registry study. Norell PN, Ivarsson B, Selin M, et al. 2022. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  23. Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Hirashiki A, Adachi S, Nakano Y, et al. 2016. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  24. Cardiopulmonary exercise testing to evaluate the exercise capacity of patients with inoperable chronic thromboembolic pulmonary hypertension: an endothelin receptor antagonist improves the peak PETCO2. Hirashiki A, Adachi S, Nakano Y, et al. 2014. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  25. Bosentan in pulmonary arterial hypertension: a comparison between congenital heart disease and chronic pulmonary embolism. Duffels MG, van der Plas MN, Surie S, et al. 2009. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  26. Improved survival in medically treated chronic thromboembolic pulmonary hypertension. Nishimura R, Tanabe N, Sugiura T, et al. 2013. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  27. Secondary pulmonary arterial hypertension: treated with endothelin receptor blockade. Sharma S, Kashour T, Philipp R. 2005. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  28. Right ventricular function predicts clinical response to specific vasodilator therapy in patients with pulmonary hypertension. Giusca S, Jurcut R, Coman IM, et al. 2012. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  29. Long-term experience with oral or inhaled vasodilator combination therapy in patients with pulmonary hypertension. Beyer S, Speich R, Fischler M, et al. 2006. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  30. [Pulmonary arterial hypertension--experience of Centro Hospitalar de Vila Nova de Gaia]. Oliveira A, Ferreira D, Caiado A, et al. 2007. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
  31. Characteristics and risk profiles of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension living permanently at >2500 m of high altitude in Ecuador. Hoyos R, Lichtblau M, Cajamarca E, et al. 2024. Primary report reviewed 2 November 2026; design, population and uncertainty are retained in its PH evidence appraisal.
PH journal watch: additional source retrieval provenance1
  1. PH supplemental queries and primary bibliographic records Documented source searches and metadata snapshots completed 2 November 2026. Retrieval is not eligibility appraisal or proof of worldwide completeness.Exact verified and unresolved primary report identifiersStudy-specific primary report, safety, historical route and notice verificationExact protocol/product administration verificationExact protocol/product administration verificationPAH and historical phenotypes updated-record overlap, not publication-date limitedCOR-PH primary ESC protocol metadata and results-pending checkExact DOI primary-publisher metadata retentionExact DOI primary-publisher metadata retentionExact DOI primary-publisher metadata retentionPrimary GoDeep ACE-inhibitor COPD-PH report and response clarificationPVRI ASCENT and FIT-PH registrations
PH historical and perioperative primary reports reviewed 2 November 202610
  1. Short-Term Effect of Levosimendan in Acute Right Heart Failure Caused by Pulmonary Hypertension: A Pilot Study. Wang YQ, Deng QY, Zhang ZZ, Wang GL, Zhao Z, Su CF, Wang L, Ge X, Wang GX, Xiao H. 2026. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  2. Intravenous Levosimendan versus Inhalational Milrinone in the Management of Pulmonary Hypertension during Adult Cardiac Surgery: A Randomized Clinical Trial. Ftikos P, Gkantinas G, Karageorgos V, Smirli A, Kogerakis N, Leontiadis E, Petsios K, Antoniou T, Theodoraki K. 2024. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  3. Comparative Effect of Levosimendan and Milrinone in Cardiac Surgery Patients With Pulmonary Hypertension and Left Ventricular Dysfunction. Mishra A, Kumar B, Dutta V, Arya VK, Mishra AK. 2016. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  4. Sodium Nitroprusside in Patients With Mixed Pulmonary Hypertension and Left Heart Disease: Hemodynamic Predictors of Response and Prognostic Implications. Lim HS, Zaphiriou A. 2016. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  5. Long-term treatment of chronic obstructive lung disease by Nifedipine: an 18-month haemodynamic study. Saadjian AY, Philip-Joet FF, Vestri R, Arnaud AG. 1988. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  6. Nifedipine reduces pulmonary pressure and vascular tone during short- but not long-term treatment of pulmonary hypertension in patients with chronic obstructive pulmonary disease. Agostoni P, Doria E, Galli C, Tamborini G, Guazzi MD. 1989. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  7. Effects of captopril in patients with chronic obstructive pulmonary disease and secondary pulmonary hypertension. Patakas D, Georgopoulos D, Rodini H, Christaki P. 1988. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  8. Nifedipine inhibits hypoxic pulmonary vasoconstriction during rest and exercise in patients with chronic obstructive pulmonary disease. A controlled double-blind study. Kennedy TP, Michael JR, Huang CK, Kallman CH, Zahka K, Schlott W, Summer W. 1984. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  9. Severe Pulmonary Hypertension in Critically Ill Children: A 10-Year Single-Center Case Series and Practical Management Considerations. Straka K, Polymerou I, Christakou E. 2026. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
  10. Advanced Rheumatic Heart Disease Complicated by Pregnancy, Mitral Valve Disease, Pulmonary Hypertension, and Left Atrial Thrombus: A Multidisciplinary Case Report from Resource-Limited Settings. Botan NI, Ahmed SI, Imaan FH, Madar KH. 2026. Primary report reviewed 2 November 2026; study methods, results, uncertainty and route provenance are retained in its PH appraisal.
PH watch final source reconciliation1
  1. Europe PMC primary report identifier reconciliation Europe PMC / EMBL-EBI. Exact primary report metadata retrieval completed 2 November 2026; query traversal is separate from clinical appraisal.
Echo: acquisition and interpretation14
  1. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults Mitchell, Rahko et al. ASE. 2019. Adult comprehensive TTE. Consulted for Echo; synthetic coefficients are not guideline values.Rechecked 6 November 2026 for the Echo anatomy and workspace revision. Standard views guide anatomical relationships; synthetic surfaces, acoustic material values and display quality are implementation assumptions.
  2. Guidelines for Performing a Comprehensive Transesophageal Echocardiography Examination Hahn et al. ASE/SCA. 2013. Adult comprehensive TEE. Rechecked 6 November 2026 for transgastric levels, LAA coverage and aortic sections: descending thoracic aorta lies posterior/left of the oesophagus (sections 25–26, printed pages 940–941 and 947). Fixed synthetic starting coordinates are not universal clinical positions. Rechecked for the visible mitral apparatus: leaflets, annulus, papillary muscles and chordae (specific structural imaging, mitral valve section). The teaching mesh follows existing reduced synthetic sampler geometry; its leaflet shapes, sizes and chordal arrangement are implementation assumptions, not guideline-derived dimensions.
  3. Recommended Standards for TEE Screening for Structural Heart Intervention Hahn et al. ASE. 2021. Adult structural intervention screening. Consulted for Echo; synthetic coefficients are not guideline values.
  4. Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults Lang, Badano et al. ASE/EACVI. 2015. Adults; reference cohorts and sex/body-size context specified in source. Consulted for Echo; synthetic coefficients are not guideline values.
  5. Recommendations for the Evaluation of LV Diastolic Function by Echocardiography and for HFpEF Diagnosis: An Update Nagueh et al. ASE. 2025. Adults in sinus rhythm and separately addressed special populations. Consulted for Echo; synthetic coefficients are not guideline values.
  6. Echocardiographic Assessment of Aortic Valve Stenosis: A Focused Update Baumgartner et al. EACVI/ASE. 2017. Adult native aortic stenosis. Consulted for Echo; synthetic coefficients are not guideline values.Rechecked 6 November 2026 for Echo continuity area, LVOT sampling, beam alignment, gradients and discordance. Synthetic examples demonstrate arithmetic rather than validated patient grading.
  7. Clinical Recommendations for Multimodality Cardiovascular Imaging of Patients with Pericardial Disease Klein et al. ASE/SCMR/SCCT. 2013. Pericardial imaging; adult clinical context. Consulted for Echo; synthetic coefficients are not guideline values.
  8. Recommendations for the Identification and Mitigation of Cardiac Ultrasound Artifacts Saric, Sadeghpour et al. ASE. 2026. Cardiac ultrasound across 2D, colour, spectral and 3D modes. Rechecked for Echo image formation: attenuation, specular dropout, acoustic shadowing and focus-dependent resolution. Synthetic coefficients are not guideline values.Rechecked 6 November 2026 for the cleaner Echo image renderer: representative attenuation, finite resolution, specular interfaces, shadowing and dropout. Texture is deterministic and synthetic; numerical appearance settings are not validated scanner parameters.
  9. Recommendations for Image Acquisition and Display Using Three-Dimensional Echocardiography Lang et al. EAE/ASE. 2012. TTE and TEE 3D acquisition. Consulted for Echo; synthetic coefficients are not guideline values.
  10. Three-dimensional transoesophageal echocardiography: how to use and when to use Faletra et al. EACVI. 2023. Clinical 3D TEE. Consulted for Echo; synthetic coefficients are not guideline values.
  11. Recommendations for Multimodality Cardiovascular Imaging of Patients with Hypertrophic Cardiomyopathy: An Update Nagueh et al. ASE/ASNC/SCMR/SCCT. 2022. HCM imaging. Consulted for Echo; synthetic coefficients are not guideline values.
  12. Recommendations for the Use of Echocardiography in the Evaluation of Rheumatic Heart Disease Pandian et al. ASE. 2023. Rheumatic valve disease. Consulted for Echo; synthetic coefficients are not guideline values.Rechecked 6 November 2026 for rheumatic MS planimetry, PHT compliance/loading limitations and selected continuity use. The empirical PHT constant does not generalize to every mitral lesion.
  13. 2023 ESC Guidelines for the management of endocarditis Delgado et al. ESC. 2023. Suspected and confirmed infective endocarditis. Consulted for Echo; synthetic coefficients are not guideline values.
  14. 2025 ESC Guidelines for the management of myocarditis and pericarditis Schulz-Menger, Imazio et al. ESC. 2025. Inflammatory myocardial/pericardial syndromes. Consulted for Echo; synthetic coefficients are not guideline values.
Echo: valve quantification methods3
  1. Multi-modality imaging assessment of native valvular regurgitation Lancellotti P, Pibarot P, et al. EACVI / ESC Council of Valvular Heart Disease. Eur Heart J Cardiovasc Imaging. 2022. Consulted 6 November 2026 for PISA geometry/timing, vena contracta and integrated interpretation.
  2. Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice Baumgartner H, Hung J, et al. EAE/ASE. 2009. Historical technical methods only; current catalogue flags partial updates by AS 2017 and RHD 2023. Superseded severity ranges are not reused.
  3. Echocardiographic assessment of aortic stenosis: a practical guideline from the British Society of Echocardiography Ring L, Shah BN, et al. British Society of Echocardiography. Echo Res Pract. 2021;8:G19–G59. Consulted 6 November 2026 for practical Bernoulli, continuity and acquisition limitations; diagnostic cutoffs are not mixed across guidance.
Connective tissue disease: screening, classification and lung involvement6
  1. The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study Thakkar V, Stevens W, Prior D, et al. Arthritis Res Ther. 2013;15:R193. Primary ASIG cohort and exact screening thresholds consulted 7 November 2026.ASIG screening is not PAH diagnosis or mortality prediction; the implementation retains missing data, Hb-corrected DLCO and separate pulmonary/biomarker arms. Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Small, referral-enriched cohort; not all patients in a general screening population underwent RHC. A negative screen cannot override unexplained symptoms, and NPV changes with prevalence.
  2. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study Coghlan JG, Denton CP, Grünig E, et al. Ann Rheum Dis. 2014;73:1340–1349. Primary study and Figure 3 nomogram consulted 7 November 2026.The app checks guideline eligibility and interprets manually supplied nomogram totals (>300 and >35); it does not reconstruct raw-variable DETECT points or impute missing variables. Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Enriched population, internal model validation and older haemodynamic definitions. This was neither a treatment trial nor evidence that screening independently improves survival.
  3. 2013 classification criteria for systemic sclerosis: an ACR/EULAR collaborative initiative van den Hoogen F, Khanna D, Fransen J, et al. Arthritis Rheum. 2013;65:2737–2747. Original classification criteria consulted 7 November 2026.Classification, not a diagnostic exclusion test or PH probability. Category maxima, sufficient criterion and applicability exclusions remain explicit.
  4. Interstitial lung disease in systemic sclerosis: a simple staging system Goh NSL, Desai SR, Veeraraghavan S, et al. Am J Respir Crit Care Med. 2008;177:1248–1254. Original HRCT/FVC staging study consulted 7 November 2026.Goh extent is SSc-ILD prognostic context. Indeterminate HRCT uses the FVC 70% threshold; this does not establish PH group or PAH prognosis. Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. A prognostic staging study, not a PH classification standard or treatment trial. Goh stage alone cannot establish whether PH is group 1, group 3 or mixed.
  5. ERS/EULAR clinical practice guidelines for connective tissue disease-associated interstitial lung disease Antoniou KM, Distler O, Gheorghiu AM, et al. Eur Respir J. 2026;67:2402533. Published online 2025. Current CTD-ILD screening and monitoring recommendations consulted 7 November 2026.All-SSc HRCT screening, PFT-based monitoring and multidisciplinary interpretation; clinical recommendations do not validate the software calculators. Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Many recommendations are conditional with low-certainty evidence. These ILD therapies should not be presented as treatment for PAH; reassessment intervals require individual clinical judgement.
  6. EULAR recommendations for the treatment of systemic sclerosis: 2023 update Del Galdo F, Lescoat A, Conaghan PG, et al. Ann Rheum Dis. 2025;84:29–40. SSc-PAH treatment recommendations consulted 7 November 2026.Confirmed SSc-PAH treatment context; concurrent ILD and left-heart disease must be phenotyped before applying PAH therapy. Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. This is a guideline, not a new trial; CTD/SSc subgroup analyses contribute substantially. The PAH anticoagulation recommendation does not remove anticoagulation for a separate established indication.
CTD and systemic sclerosis: focused literature review6
  1. A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis Hao Y, Thakkar V, Stevens W, et al. A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis. Arthritis Res Ther. 2015;17:7. Primary publication consulted 7 November 2026.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Small, referral-selected sample; absent TR jets limited the older echocardiography approach. Observed 100% sensitivity is not a guarantee in routine practice or proof of better survival.
  2. Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival Humbert M, Yaici A, de Groote P, et al. Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival. Arthritis Rheum. 2011;63:3522–3530. Primary publication consulted 7 November 2026.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Small, nonrandomised cohorts; lead-time and length-time bias may partly explain longer survival measured from diagnosis. Do not interpret this as proof that screening itself prolongs life.
  3. Long-Term Outcomes in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS) Kolstad KD, Li S, Steen V, Chung L; PHAROS Investigators. Long-Term Outcomes in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension From the PHAROS Registry. Chest. 2018;154:862–871. Primary publication consulted 7 November 2026.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Selected registry population with relatively mild disease at diagnosis. Cohort survival is not an individual prediction, and treatment comparisons are vulnerable to confounding.
  4. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II). Lancet Respir Med. 2016;4:708–719. Primary publication consulted 7 November 2026.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. No placebo-only group. Failure to demonstrate superiority does not establish equivalence, and within-group improvement does not establish either drug's causal benefit for PAH.
  5. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease Distler O, Highland KB, Gahlemann M, et al. Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease. N Engl J Med. 2019;380:2518–2528. Primary publication consulted 7 November 2026.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Missing-data sensitivity analyses were less conclusive; gastrointestinal adverse effects affect tolerability. The trial did not establish a survival benefit or treatment of pulmonary arterial vasculopathy, and background mycophenolate use was not randomised.
  6. Effectiveness of oral anticoagulants in precapillary pulmonary hypertension associated with systemic sclerosis: a EUSTAR cohort study Farina N, et al. Rheumatology. 2026;65:keag516. Primary publication consulted 7 November 2026.Reviewed 7 November 2026 for the focused CTD/SSc literature reading guide. Observational exposure, residual confounding and worse baseline hemodynamics in anticoagulated patients. Drug type, prescribing indication and bleeding outcomes were unavailable. This is neither randomized evidence nor proof of equivalent benefit–risk.
Pulmonary hypertension: 9 November 2026 journal watch121
  1. Captopril as treatment for patients with pulmonary hypertension. Problem of variability in assessing chronic drug treatment. Rich S, Martinez J, Lam W, Rosen KM. (1982). Captopril as treatment for patients with pulmonary hypertension. Problem of variability in assessing chronic drug treatment.
  2. Hazards of diazoxide in pulmonary hypertension. Buch J, Wennevold A. (1981). Hazards of diazoxide in pulmonary hypertension.
  3. Effects of captopril (SQ 14,225) in a patient with primary pulmonary hypertension. Horowitz JD, Brennan JB, Oliver LE, Harding D, Goble AJ, Louis WJ. (1981). Effects of captopril (SQ 14,225) in a patient with primary pulmonary hypertension.
  4. Prediction of favourable responses to long term vasodilator treatment of pulmonary hypertension by short term administration of epoprostenol (prostacyclin) or nifedipine. Rozkovec A, Stradling JR, Shepherd G, MacDermot J, Oakley CM, Dollery CT. (1988). Prediction of favourable responses to long term vasodilator treatment of pulmonary hypertension by short term administration of epoprostenol (prostacyclin) or nifedipine.
  5. Pulmonary hypertension in hydralazine induced systemic lupus erythematosus: association with C4 null allele. Asherson RA, Benbow AG, Speirs CJ, Jackson N, Hughes GR. (1986). Pulmonary hypertension in hydralazine induced systemic lupus erythematosus: association with C4 null allele.
  6. The CREST syndrome--successful reduction of pulmonary hypertension by captopril. Prouse PJ, Lahiri A, Gumpel JM. (1984). The CREST syndrome--successful reduction of pulmonary hypertension by captopril.
  7. Haemodynamic and hormonal effects of captopril in primary pulmonary hypertension. Ikram H, Maslowski AH, Nicholls MG, Espiner EA, Hull FT. (1982). Haemodynamic and hormonal effects of captopril in primary pulmonary hypertension.
  8. Captopril in primary pulmonary hypertension. Leier CV, Bambach D, Nelson S, Hermiller JB, Huss P, Magorien RD, Unverferth DV. (1983). Captopril in primary pulmonary hypertension.
  9. Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease. Alpert MA, Pressly TA, Mukerji V, Lambert CR, Mukerji B, Panayiotou H, Sharp GC. (1991). Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease.
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  93. Prognostic Value of Acute Vasoreactivity in Chronic Thromboembolic Pulmonary Hypertension. Uphus JAG, Hu JR, Huang S, Hofbauer TM, Panzenboeck A, Sadushi-Kolici R, Shafran I, Skoro-Sajer N, Gerges C, Brittain E, Lang IM. (2026). Prognostic Value of Acute Vasoreactivity in Chronic Thromboembolic Pulmonary Hypertension.
  94. Treatment pathways in Finnish patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). Pentikäinen M, Simonen P, Leskelä P, Harju T, Jääskeläinen P, Asseburg C, Oksanen M, Soini E, Wennerström C, Puhakka A, FINPAH study group, Kahlos K. (2025). Treatment pathways in Finnish patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).
  95. Pediatric Pulmonary Hypertension Associated With Treatment of Myeloproliferative Disorders and Malignant Tumors. Chida-Nagai A, Terashita Y, Hirabayashi S, Yamazawa H, Cho Y, Manabe A. (2025). Pediatric Pulmonary Hypertension Associated With Treatment of Myeloproliferative Disorders and Malignant Tumors.
  96. Association Between Sotatercept and Improved Lung Function in Sarcoidosis-Associated Pulmonary Hypertension. Poor HD, Eisenberg E, Saini S, Hannah-Clark S, Zhang J, Lee AG, Serrao G, Powell C, Ventetuolo CE, Padilla M. (2026). Association Between Sotatercept and Improved Lung Function in Sarcoidosis-Associated Pulmonary Hypertension.
  97. An Exploratory Study of Anticoagulation For Pulmonary Hypertension in Sickle Cell Disease — posted results University of North Carolina, Chapel Hill / ClinicalTrials.gov (2014). An Exploratory Study of Anticoagulation For Pulmonary Hypertension in Sickle Cell Disease — posted results
  98. A Pilot Study of Hydroxyurea for the Treatment of Pulmonary Hypertension in Children and Young Adults With Sickle Cell Disease — posted results Ann & Robert H Lurie Children's Hospital of Chicago / ClinicalTrials.gov (2013). A Pilot Study of Hydroxyurea for the Treatment of Pulmonary Hypertension in Children and Young Adults With Sickle Cell Disease — posted results
  99. A Phase 2, Randomised, Double-Blind, Placebo-Controlled, Multicentre, Prospective Study to Assess Efficacy of Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy With High Preoperative Pulmonary Vascular Resistance — posted results International CTEPH Association / ClinicalTrials.gov (2021). A Phase 2, Randomised, Double-Blind, Placebo-Controlled, Multicentre, Prospective Study to Assess Efficacy of Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy With High Preoperative Pulmonary Vascular Resistance — posted results
  100. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study in Participants With Sarcoidosis-Associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag. — posted results Actelion / ClinicalTrials.gov (2024). A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study in Participants With Sarcoidosis-Associated Pulmonary Hypertension (SAPH) to Assess the Efficacy and Safety of Oral Selexipag. — posted results
  101. The Safety and Efficacy of Macitentan for Treatment of Pulmonary Hypertension in Sickle Cell Disease — posted results Boston University / ClinicalTrials.gov (2020). The Safety and Efficacy of Macitentan for Treatment of Pulmonary Hypertension in Sickle Cell Disease — posted results
  102. Phase 2 Trial for Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension — posted results UCSF Benioff Children's Hospital Oakland / ClinicalTrials.gov (2021). Phase 2 Trial for Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension — posted results
  103. Long-term Open-label Extension Study in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Who Completed Protocol AC-052-366 (BENEFIT, NCT00313222) — posted results Actelion / ClinicalTrials.gov (2012). Long-term Open-label Extension Study in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Who Completed Protocol AC-052-366 (BENEFIT, NCT00313222) — posted results
  104. Multifactorial Pulmonary Hypertension: Converging Roles of Sarcoidosis, Heart Failure With Reduced Ejection Fraction, and Chronic Thromboembolic Disease. Bajouka J, Matti C, Touza G, Patel K, Affas ZR. (2026). Multifactorial Pulmonary Hypertension: Converging Roles of Sarcoidosis, Heart Failure With Reduced Ejection Fraction, and Chronic Thromboembolic Disease.
  105. Chronic Thromboembolic Pulmonary Hypertension With Cold Agglutinins Needing Pulmonary Thromboendarterectomy: The Use of Therapeutic Plasma Exchange. Naqvi B, Bautista MA, Sanchez AP, Yang JZ, Fernandes TM, Poch DS, Kerr KM, Kim NH, Madani MM, Pretorius VG, Allen ES, Kopko PM, Dilly LD, Ginsberg C, Park SJ, Choi M, Cruz DN, Papamatheakis DG. (2026). Chronic Thromboembolic Pulmonary Hypertension With Cold Agglutinins Needing Pulmonary Thromboendarterectomy: The Use of Therapeutic Plasma Exchange.
  106. Tenax Therapeutics Reports Third Quarter 2026 Financial Results and Provides Corporate Update Tenax Therapeutics, Inc. (2026). Tenax Therapeutics Reports Third Quarter 2026 Financial Results and Provides Corporate Update
  107. EU Clinical Trials Register: pulmonary hypertension query and historical results European Medicines Agency. EU Clinical Trials Register. Pulmonary Hypertension query, all 416 unique trials over 21 pages; accessed 9 November 2026. Registrations are candidates, not appraised outcomes.Example historical treprostinil result attachment; inaccessible at this checkpoint
  108. Correction to “Impact of Stress Hyperglycemia Ratio on Adverse Outcomes in Patients With Chronic Thromboembolic Pulmonary Hypertension” Clinical and Translational Science (2026). Correction to “Impact of Stress Hyperglycemia Ratio on Adverse Outcomes in Patients With Chronic Thromboembolic Pulmonary Hypertension” Clinical and Translational Science. Primary correction checked9November2026.
  109. Correction to “The Diagnostic Value of Transthoracic Echocardiography Parameters Under the New Diagnostic Criteria for Pulmonary Hypertension” Canadian Respiratory Journal (2026). Correction to “The Diagnostic Value of Transthoracic Echocardiography Parameters Under the New Diagnostic Criteria for Pulmonary Hypertension” Canadian Respiratory Journal. Primary correction checked9November2026.
  110. Expression of concern to "Post-treatment with Resolvin D1 attenuates pulmonary hypertension by inhibiting endothelial-to-mesenchymal transition" [Biomed. Pharmacother. 177 (2024) 117023]. Li X, Li H, Feng B. 2026. Expression of concern to "Post-treatment with Resolvin D1 attenuates pulmonary hypertension by inhibiting endothelial-to-mesenchymal transition" [Biomed. Pharmacother. 177 (2024) 117023]. PMID42174771. doi:10.1016/j.biopha.2026.119313.Parent experimental study
  111. A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety and Tolerability of Treprostinil Administered Via a Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) United Therapeutics. ClinicalTrials.gov NCT07923591. Registry last update 2026-11-06; checked 9 November 2026.Registration/protocol only; no posted outcomes in the checked primary record. Planned enrollment is not observed clinical findings.
  112. An Open-label Extension Study of Treprostinil Administered Via a Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) United Therapeutics. ClinicalTrials.gov NCT07923526. Registry last update 2026-11-06; checked 9 November 2026.Registration/protocol only; no posted outcomes in the checked primary record. Planned enrollment is not observed clinical findings.
  113. A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety and Efficacy of L606 (Treprostinil Liposome Inhalation Suspension) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (WHO Group 3) Liquidia Technologies, Inc.. ClinicalTrials.gov NCT07285655. Registry last update 2026-10-14; checked 9 November 2026.Registration/protocol only; no posted outcomes in the checked primary record. Planned enrollment is not observed clinical findings.
  114. A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study to Evaluate the Efficacy and Safety of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease Insmed Incorporated. ClinicalTrials.gov NCT07179380. Registry last update 2026-10-26; checked 9 November 2026.Registration/protocol only; no posted outcomes in the checked primary record. Planned enrollment is not observed clinical findings.
  115. A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of TX000045 After 24 Weeks of Treatment in Patients With Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction (PH-HFpEF) Tectonic Therapeutic. ClinicalTrials.gov NCT06616974. Registry last update 2026-07-07; checked 9 November 2026.Registration/protocol only; no posted outcomes in the checked primary record. Planned enrollment is not observed clinical findings.
  116. Effects of Sotatercept on Cardiac Structure and Function in Combined Post- and Precapillary Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: Analysis of the CADENCE Study. Tedford RJ, Badagliacca R, Asleh R, Urbinati A, Kopeć G, Langleben D, Rosenkranz S, Rubinshtein R, Silverman DN, Zamanian R, Zolty R, Miller B, Jones AD, Shi Y, Liu CC, McMullan CJ, Vachiery JL, Gomberg-Maitland M. 2026. PMID 42999959. doi:10.1161/circulationaha.126.083993.CADENCE echo companion: bibliographic identity only verified; no primary abstract and inaccessible AHA full text. Findings remain unknown.
  117. Sleep Apnea in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The FINEARTS-HF Trial. Lu H, Schneider SR, Pabón MA, Claggett BL, Miao MZ, Desai AS, Jhund PS, Henderson A, Lam CSP, Senni M, Shah SJ, Voors AA, Zannad F, Pitt B, McMurray JJV, Solomon SD, Vaduganathan M. 2026. PMID 42340295. doi:10.1016/j.jchf.2026.103187.FINEARTS-HF sleep-apnea companion: no accessible primary abstract; numerical findings remain unappraised.
  118. Corrigendum to "Long-term effects of inhaled treprostinil in Japanese patients with pulmonary hypertension associated with interstitial lung disease" [Respir Invest, Volume 64, Issue 1, January 2026, 101340]. Kondoh Y, Ogura T, Nishiyama O, Kinoshita H, Ogo T, Tanabe N, Minatsuki S, Nakayama K, Taniguchi Y, Takahashi K, Orido T, Sakao S. 2026. PMID 41500901. doi:10.1016/j.resinv.2025.101365.Corrigendum identity/parent link verified; full notice inaccessible, numerical impact unknown.
  119. Long-term effects of inhaled treprostinil in Japanese patients with pulmonary hypertension associated with interstitial lung disease. Kondoh Y, Ogura T, Nishiyama O, Kinoshita H, Ogo T, Tanabe N, Minatsuki S, Nakayama K, Taniguchi Y, Takahashi K, Orido T, Sakao S. 2026. PMID 41401567. doi:10.1016/j.resinv.2025.101340.Japanese long-term treprostinil PH-ILD primary abstract checked; numerical appraisal deferred until linked corrigendum contents are verified.
  120. A Phase 3 Study to Evaluate the Safety and Efficacy L606 in Participants With PH-ILD Health Canada. Clinical Trial Search Portal, control number 305001; protocol L606-301; updated 20 October 2026; checked 9 November 2026.Recruiting protocol links NCT07285655, without reported outcomes; another registry identity, not another independent clinical trial.
  121. Effect of enalapril on renal profile and right ventricular dimensions in chronic cor pulmonale. Mahajan SK, Sharma VK, Thakral S. (1996). Effect of enalapril on renal profile and right ventricular dimensions in chronic cor pulmonale.

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