Optimized Response Program for Timely Treatment Needs in Pulmonary Arterial Hypertension (PRONTO-HAP)
DOI:
https://doi.org/10.63600/qkrpqg26Keywords:
Pulmonary arterial hypertension, Program, ResponseAbstract
Pulmonary arterial hypertension (PAH) is a rare condition characterized by high morbidity and mortality rates and a significant impact on patients' quality of life. To address the complexities of its management, the Comité de Insuficiencia Cardíaca e Hipertensión Pulmonar de la Federación Argentina de Cardiología developed the PRONTO-HAP program (Optimized Response Program for Timely Treatment Needs). Its principal objective is to present a structured, evidence-based care model for proactive intervention during critical stages of the clinical trajectory in PAH patients. The program proposes a multidisciplinary approach focused on eight key clinical scenarios: chest pain, supraventricular tachyarrhythmias, pregnancy, iron deficiency, right heart failure, perioperative management, and pericardial effusion.Specific diagnostic algorithms and therapeutic strategies are defined for each scenario, ranging from etiological assessment to pharmacological optimization and personalized follow-up tools.PRONTO-HAP serves as a strategic tool to standardize care, reduce clinical variability,and improve clinical outcomes through coordinated and timely management of disease-related complications.
References
1. Ling Y, Johnson MK, Kiely DG et al. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med 2012; 186:790-6.tonelli ar
2. Jing ZC, Xu XQ, Han ZY et al. Registry and survival study in Chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest 2007; 132:373-9.
3. Humbert M, Kovacs G, Hoeper MM et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2022; 43:3618-3731.
4. Galiè N, Saia F, Palazzini M et al. Left main coronary artery compression in patients with pulmonary arterial hypertension and angina. J Am Coll Cardiol 2017; 70:2808-20.
5. Rich S, Dantzker DR, Ayres SM et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med 1987; 107:216-23.
6. D’Alonzo GE, Barst RJ, Ayres SM et al. Survival in patients with primary pulmonary hypertension: results of a national prospective study. Ann Intern Med 1991; 115:343-9.
7. Gomez A, Bialostozky D, Zajarias A et al. Right ventricular ischemia in patients with primary pulmonary hypertension. J Am Coll Cardiol 2001; 38:1137-42.
8. Labin JE, Saggar R, Yang EH et al. Left main coronary artery compression in pulmonary hypertension. Catheter Cardiovasc Interv 2021;98:E566-E573.
9. Akbal OY, Kaymaz C, Tanboga IH et al. Extrinsic compression of left main coronary artery by aneurysmal pulmonary artery in severe pulmonary hypertension: its correlates, clinical impact, and management strategies. Eur Heart J Cardiovasc Imaging 2018;19:1352-1360.
10. Velázquez Martín M, Montero Cabezas JM, Huertas S et al. Clinical relevance of adding intravascular ultrasound to coronary angiography for the diagnosis of extrinsic left main coronary artery compression by a pulmonary artery aneurysm in pulmonary hypertension. Catheter Cardiovasc Interv 2021;98:1047-1055.
11. Badea R, Dorobantu DM, Sharabiani MTA et al. Left main coronary artery compression by dilated pulmonary artery in pulmonary arterial hypertension: a systematic review and meta-analysis. Clin Res Cardiol 2022;111:1359-1371.
12. Lee MS, Oyama J, Bhatia R et al. Left main coronary artery compression from pulmonary artery enlargement due to pulmonary hypertension: a contemporary review and argument for percutaneous revascularization. Catheter Cardiovasc Interv 2010;76:543-550.
13. Kagawa H, Silvester B, Smego D et al. Surgical therapy for pulmonary artery aneurysm. Ann Thorac Surg Short Rep. 2025;3:561-565.
14. Tonelli AR, Johnson S, Alkukhun L et al. Changes in main pulmonary artery diameter during follow-up have prognostic implications in pulmonary arterial hypertension. Respirology 2017;22:1649-1655.
15. Cao JY, Abdo RM, Wang N, et al. Prognostic Value of Main Pulmonary Artery Diameter in Pulmonary Arterial Hypertension. Chest. 2025 Aug;168:476-487. doi: 10.1016/j.chest.2025.02.012. Epub 2025 Feb 21. PMID: 39987965.
16. Deterling RA Jr, Clagett OT. Aneurysm of the pulmonary artery: review of the literature and report of a case. Am Heart J 1947;34:471-499.
17. Khattar RS, Fox DJ, Alty JE et al. Pulmonary artery aneurysms: a review. Pulm Circ 2011;1:317-327.
18. Byrne R, Rossello X, Coughlan J et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3720-3826.
19. Middleton JT, Maulik A, Lewis R et al. Arrhythmic Burden and Outcomes in Pulmonary Arterial Hypertension. Front Med (Lausanne). 2019;6:169.
20. Price LC, Dimopoulos K, Marino P, et al. The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension. Thorax. 2017;72:1035-1045.
21. Hoeper MM, Granton J. Intensive care unit management of patients with severe pulmonary hypertension and right heart failure. Am J Respir Crit Care Med. 2011;184:1114-24.
22. Temple IP. Arrhythmias in pulmonary arterial hypertension. J Congenit Heart Dis 2017;1:1-6.
23. Zhang A, Ding L, Zhang H, et al. Radiofrequency catheter ablation for pulmonary hypertension patients with atrial flutter. ESC Heart Fail. 2024;11:883-892.
24. Lane CR, Trow TK. Pregnancy and Pulmonary Hypertension. Clin Chest Med. 2011;32:165-74.
25. Sliwa K, van Hagen IM, Budts W, et al. Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology. Eur J Heart Fail. 2016;18:1119-28.
26. Meng ML, Landau R, Viktorsdottir O, et al. Pulmonary Hypertension in Pregnancy: A Report of 49 Cases at Four Tertiary North American Sites. Obstet Gynecol. 2017;129:511-520.
27. Low TT, Guron N, Ducas R, et al. Pulmonary arterial hypertension in pregnancy—a systematic review of outcomes in the modern era. Pulm Circ. 2021;11:20458940211013671.
28. Silva Croome N, Lema L, Stewart Harris A, et al. Pulmonary hypertension and pregnancy. Experience in Argentina (ARGEN-HP). Eur Heart J. 2025; 46 (Suppl 1):ehaf784.2913
29. Wander G, Montanaro C, Dixit P, et al. Pregnancy and pulmonary artery hypertension: Management challenges. Int J Cardiol Congenit Heart Dis. 2025;19:100566
30. Preston IR, Howard LS, Langleben D, et al. Management of pulmonary hypertension in special conditions. Eur Respir J. 2024;64:2401180.
31. De Backer J, Haugaa KH, Hasselberg NE, et al. 2025 ESC Guidelines for the management of cardiovascular disease and pregnancy: Developed by the task force on the management of cardiovascular disease and pregnancy of the European Society of Cardiology (ESC)Endorsed by the European Society of Gynecology (ESG). Eur Heart J. 2025;46:4462-568.
32. Olsson KM, Fuge J, Park DH, et al. Right heart function during and after pregnancy in women with pulmonary arterial hypertension. Eur Respir J. 2024;64:2400179
33. Muñoz L, Coronel ML, Perna E, et al. Deficit de hierro: una comorbilidad emergente en HAP. Rev Fed Arg Cardiol 2024;53: 9-13
34. Loncar G, Obradovic D, Thiele H, et al. Iron deficiency in heart failure. ESC Heart Fail. 2021;8:2368-79.
35. Rizzo C, Carbonara R, Ruggieri R, et al. Iron Deficiency: A New Target for Patients With Heart Failure. Front Cardiovasc Med 2021; 8:709872
36. Viatte L, Vaulont S. Hepcidin, the iron watcher. Biochimie 2009;91:1223-8
37. Rhodes CJ, Howard LS, Busbridge M, et al. Iron Deficiency and Raised Hepcidin in Idiopathic Pulmonary Arterial Hypertension: Clinical Prevalence, Outcomes, and Mechanistic Insights. J Am Coll Cardiol 2011;58:300-9.
38. Martens P, Yu S, Larive B, et al; PVDOMICS Study Group. Iron deficiency in pulmonary vascular disease: pathophysiological and clinical implications. Eur Heart J. 2023;44:1979-1991.
39. Albulushi A, Kashoub M, Al-Saidi K, et al. Iron Deficiency in Pulmonary Hypertension. Int Heart J. 2024, 65:593-600.
40. Von Haehling S, Jankowska EA, van Veldhuisen DJ, et al. Iron deficiency and cardiovascular disease. Nat Rev Cardiol. 2015;12:659-69.
41. Ołdakowska AK, Kamiński KA, Ptaszyńska K. Iron Deficiency in Pulmonary Hypertension-Prevalence, Impact on Prognosis and Disease Burden in Pulmonary Arterial Hypertension and Pulmonary Hypertension Related to Hypoxia: A Review. Int J Mol Sci. 2026 27:2333
42. Yu X, Luo Q, Liu Z, et al. Prevalence of iron deficiency in different subtypes of pulmonary hypertension. Heart Lung. 2018;47(4):308-13.
43. Ruiter G, Lankhorst S, Boonstra A, et al. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur Respir J. 2011;37:1386-91.
44. Kramer T, Wissmüller M, Natsina K, et al. Ferric carboxymaltose in patients with pulmonary arterial hypertension and iron deficiency: a long-term study. J Cachexia Sarcopenia Muscle. 2021;12:1501-12.
45. Viethen T, Gerhardt F, Dumitrescu D, et al. Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: A pilot study. Int J Cardiol. 2014;175:233-9.
46. Ghio S, Badagliacca R, Acquaro M, et al. Prognostic value of deep echocardiographic phenotyping in pulmonary arterial hypertension. ERJ Open Res. 2024;10:00587-2023.
47. Benjamin N, Resag C, Xanthouli P, et al. Fluid restriction in patients with pulmonary arterial hypertension and right heart failure. Respiration. 2025;104:800-813.
48. Badagliacca R, Rischard F, Papa S, et al. Clinical implications of idiopathic pulmonary arterial hypertension phenotypes defined by cluster analysis. J Heart Lung Transplant. 2020;39:310-320.
49. Vonk Noordegraaf A, Chin KM, Haddad F, et al. Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension. Eur Respir J. 2019;53:1801900.
50. Hemnes AR, Celermajer DS, D'Alto M, et al. Pathophysiology of the right ventricle and its pulmonary vascular interaction. Eur Respir J. 2024 64:2401321
51. Celestin C, Opotowsky AR, Valente AM, et al. Identifying consistent echocardiographic thresholds for risk stratification in pulmonary arterial hypertension. Pulm Circ. 2024;14:e12345.
52. Manca P, Nuzzi V, Cannatà A, et al. Gaps and knowledge in the contemporary management of acute right ventricular failure. J Clin Med. 2023;12:4987.
53. Lahm T, McCaslin CA, Wozniak TC, et al. Medical and surgical treatment of acute right ventricular failure. J Am Coll Cardiol. 2010;56:1435-1446.
54. Benjamin N, Schiffer V, Resag C, et al. Sex-specific differences in echocardiographic parameters of risk stratification in pulmonary arterial hypertension. J Am Soc Echocardiogr. 2024;37:45-56.
55. Lai HC, Lai HC, Wang KY, et al. Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery. Br J Anaesth. 2007;99:184-90.
56. Ramakrishna G, Sprung J, Ravi BS, et al. Impact of pulmonary hypertension on the outcomes of noncardiac surgery: predictors of perioperative morbidity and mortality. J Am Coll Cardiol. 2005;45:1691-9.
57. Price LC, Martinez G, Brame A, et al. Perioperative management of patients with pulmonary hypertension undergoing non-cardiothoracic, non-obstetric surgery: a systematic review and expert consensus statement. Br J Anaesth. 2021;126:774-790.
58. Rajagopal S, Ruetzler K, Ghadimi K, et al. American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, and the Council on Cardiovascular and Stroke Nursing. Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association. Circulation. 2023;147:1317-1343.
59. Minai OA, Yared JP, Kaw Ret al. Perioperative risk and management in patients with pulmonary hypertension. Chest. 2013;144:329-340.
60. Benza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest. 2019;156:323-337.
61. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;84:1869-1969.
62. McGlothlin DP, Granton J, Klepetko W, et al. ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery. J Heart Lung Transplant. 2022;41:1135-1194.
63. Hoeper MM, Preston IR, Gomberg-Maitland M, et al. Pericardial effusion in sotatercept phase 3 trials: insights from STELLAR and ZENITH. Eur Respir J 2025; 66: 2500768
64. Shimony A, Fox BD, Langleben D, et al. Incidence and significance of pericardial effusion in patients with pulmonary arterial hypertension. Can J Cardiol. 2013 29:678-82.
65. Batal O, Dardari Z, Costabile C, et al. Prognostic Value of Pericardial Effusion on Serial Echocardiograms in Pulmonary Arterial Hypertension. Echocardiography. 2015 32:1471-6
66. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the diagnosis and management of pericardial diseases of the European Society of Cardiology. European Heart Journal, 2015;42:2921-2964.
67. Imazio M, Pedrotti P, Quattrocchi G, et al. Multimodality imaging of pericardial diseases. J Cardiovasc Med 2016;17:774-782.
68. Klein A, Abbara S, Agler D, et al. American Society of Echocardiography Clinical Recommendations for Multimodality Cardiovascular Imaging of Pa- tients with Pericardial Disease. J Am Soc Echocardiogr 2013;26:965-1.012
69. Klein AL, Wang TKM, Cremer P C, et al. International Position Statement on New Concepts and Advances in Multimodality Cardiac Imaging: Pericardial Diseases. JACC: Cardiovascular Imaging. 2024; 17:937–988.
70. Sahay S, Tonelli AR. Pericardial effusion in pulmonary arterial hypertension. Pulm Circ. 2013; 3:467-477.
71. Luo Y, Gordon JK, Xu J, et al. PHAROS Investigators. Prognostic significance of pericardial effusion in systemic sclerosis-associated pulmonary hypertension: analysis from the PHAROS Registry. Rheumatology (Oxford). 2024;63:1251-1258.
72. Neupane R, Sivakumar B, Mathew E, et al. Cardiac Complications in Systemic Lupus Erythematosus: A Systematic Review of Diagnostic and Prognostic Gaps. Cureus. 2026 18:e102966
73. Hoeper MM. Sotatercept in pulmonary arterial hypertension: revolution, risk and the road ahead. Eur Respir J. 2025;66:2501633.
74. Preston IR, Badesch D, Ghofrani HA, et al. A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA. Eur Respir J. 2025;66:2401435.
75. Sahay S, Hernandez NV, Al Aaraj Y, et al., Pericardial Effusions and Sotatercept Therapy in Pulmonary Arterial Hypertension: A Multicenter Real‐World Experience. Eur Respiratory J 2025;66:2501040
76. Cabada-Garcia MJ, Rodriguez-Rivera J, Jerjes-Sanchez C, et al. Safety of pericardiocentesis in pulmonary arterial hypertension: a systematic review. Front Cardiovasc Med. 2025;12:1610419.
77. Reddy YNV, Frantz RP, Miranda WR, et al. Elevated Pulmonary Artery Wedge Pressure in Group 1 Pulmonary Hypertension. Circulation. 2026 153(13):948-962.
78. Borlaug BA, Reddy YNV. The role of the pericardium in heart failure: implications for pathophysiology and treatment. JACC Heart Fail. 2019;7:574-585.
79. Obokata M, Reddy YNV, Pislaru SV, et al. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation. 2017;136:6-19.
80. Tada A, Omote K, Fayyaz AU, et al. Pulmonary arterial wedge pressure exceeding left atrial pressure: clinical implications. Eur Heart J. 2025;46:4123-4126.
81. Manders E, Bogaard HJ, Handoko ML, et al. Contractile dysfunction of left ventricular cardiomyocytes in patients with pulmonary arterial hypertension. J Am Coll Cardiol. 2014;64:28-37
82. Kovacs G, Bartolome S, Denton CP, et al. Definition, classification and diagnosis of pulmonary hypertension. Eur Respir J. 2024;64:2401324
83. Maron BA, Bortman G, De Marco T, et al. Pulmonary hypertension associated with left heart disease. Eur Respir J. 2024 64(4):2401344
84. Khan MS, Borlaug BA, Butler J, et al. Pulmonary Hypertension Associated With Left Heart Disease: Challenges, Emerging Strategies, and Future Directions. J Am Coll Cardiol. 2026:S0735-1097(26)00134-8.
85. Coronel ML, Diez M, Lema L, et al. Recomendaciones para la realización de cateterismo cardíaco derecho en hipertensión pulmonar: Documento conjunto de la Federación Argentina de Cardiología y la Sociedad Argentina de Cardiología. Rev. Fed. Arg. Cardiol. [Internet]. 2022 Aug. 26
86. Kovacs G, Moutchia J, Zeder K, et al. Clinical response to pulmonary arterial hypertension treatment does not depend on pulmonary arterial wedge pressure: a meta-analysis using individual participant data from randomized clinical trials. Am J Respir Crit Care Med. 2024;210:844-847
87. Botelli Dagum V, Lobo Marquez L, Guzman JF, et al. Programa de Respuesta Optimizada para Necesidades de Tratamiento Oportuno en Insuficiencia Cardíaca (PRONTO – IC): Una visión integradora del paciente vulnerable con Insuficiencia Cardíaca. Rev Fed Arg Cardiol. 2025; 54 (Suplemento 8): 5-26
