Pneumologie 2023; 77(11): 926-936
DOI: 10.1055/a-2145-4792
Übersicht

Pulmonale Hypertonie assoziiert mit Linksherzerkrankungen (Gruppe 2)

Pulmonary hypertension associated with left heart disease (group 2)
Kai Helge Schmidt
 1   Zentrum für Kardiologie, Kardiologie I, Universitätsmedizin Mainz, Mainz, Deutschland
 2   Centrum für Thrombose und Hämostase (CTH), Universitätsmedizin Mainz, Mainz, Deutschland
,
Olympia Bikou
 3   Medizinische Klinik und Poliklinik I, Klinikum der Universität München, München, Deutschland
,
Rüdiger Blindt
 4   Kardio Bremen, Rotes Kreuz Krankenhaus Bremen, Bremen, Deutschland
,
Leonhard Bruch
 5   Klinik für Innere Medizin und Kardiologie, BG Klinikum Unfallkrankenhaus Berlin, Berlin, Deutschland
,
Ralf Felgendreher
 6   Innere Medizin, Marienhospital Arnsberg, Arnsberg, Deutschland
,
Wolfgang Hohenforst-Schmidt
 7   Lungenzentrum Bamberg, Klinikum am Bruderwald Bamberg, Bamberg, Deutschland
,
Stephan Holt
 8   Praxis am Steintor, Recklinghausen, Recklinghausen, Deutschland
,
Dennis Ladage
 9   Klinik für Pneumologie, Kliniken Maria Hilf Mönchengladbach, Mönchengladbach, Deutschland
,
Elena Pfeuffer-Jovic
10   Klinikum Würzburg Mitte, Standort Missioklinik Würzburg, Würzburg, Deutschland
,
Andreas Rieth
11   Abteilung für Kardiologie, Kerckhoff-Klinik Bad Nauheim, Bad Nauheim, Deutschland
,
Alexander Schmeisser
12   Zentrum für Innere Medizin, Universitätsklinik für Kardiologie und Angiologie Magdeburg, Magdeburg, Deutschland
,
Katharina Schnitzler
 1   Zentrum für Kardiologie, Kardiologie I, Universitätsmedizin Mainz, Mainz, Deutschland
,
Stefan Stadler
13   Klinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Deutschland
,
Regina Steringer-Mascherbauer
14   Interne 2, Ordensklinikum Linz, Linz, Österreich
,
Athiththan Yogeswaran
15   Department of Internal Medicine, Member of the German Center for Lung Research, Universities of Giessen and Marburg Lung Center, Justus-Liebig-University Giessen, Giessen, Deutschland
,
Wolfgang M. Kuebler
16   Institute of Physiology, Charité – Universitätsmedizin Berlin, Berlin, Deutschland
› Author Affiliations

Zusammenfassung

Die pulmonale Hypertonie in Verbindung mit Linksherzerkrankungen (PH-LHD) bildet in der klinischen Klassifikation die Gruppe 2 der pulmonalen Hypertonie ab. Hämodynamisch zählt zu dieser Gruppe die isoliert postkapilläre pulmonale Hypertonie (IpcPH) und die gemischt post- und präkapilläre pulmonale Hypertonie (CpcPH). Die PH-LHD ist durch einen mPAP > 20 mmHg und einen PAWP > 15 mmHg definiert, zur Differenzierung zwischen IpcPH und CpcPH wird der pulmonalvaskuläre Widerstand (PVR) mit dem Grenzwert von 2 Wood Units (WU) herangezogen. Ein PVR von größer 5 WU weist auf eine dominierende präkapilläre Komponente hin. Die PH-LHD ist die häufigste Form der pulmonalen Hypertonie, ursächlich führend ist die Linksherzinsuffizienz mit erhaltener (HFpEF) oder reduzierter Ejektionsfraktion (HFmrEF, HFrEF), Herzklappenerkrankungen und seltener angeborene Herzfehler. Das Vorhandensein eines pulmonalen Hypertonus geht im gesamten Spektrum der Linksherzerkrankungen mit einer erhöhten Symptomlast und schlechterem Outcome einher. Eine besondere Herausforderung stellt die Differenzierung zwischen der pulmonalen Hypertonie der Gruppe 1 mit kardialen Komorbiditäten und der PH-LHD, besonders infolge der HFpEF dar. Therapeutisch kann zum jetzigen Zeitpunkt noch keine generelle Empfehlung für den Einsatz von PDE-5-Inhibitoren bei HFpEF-assoziierter CpcPH gegeben werden. Für die Anwendung von PAH-Medikamenten bei der IpcPH gibt es aktuell keine belastbare Rationale, ebenso wird die Therapie mit Endothelin-Rezeptor-Antagonisten oder Prostazyklin-Analoga bei allen Formen der PH-LHD nicht empfohlen.

Abstract

Pulmonary hypertension associated with left heart disease (PH-LHD) corresponds to group two of pulmonary hypertension according to clinical classification. Haemodynamically, this group includes isolated post-capillary pulmonary hypertension (IpcPH) and combined post- and pre-capillary pulmonary hypertension (CpcPH). PH-LHD is defined by an mPAP > 20 mmHg and a PAWP > 15 mmHg, pulmonary vascular resistance (PVR) with a cut-off value of 2 Wood Units (WU) is used to differentiate between IpcPH and CpcPH. A PVR greater than 5 WU indicates a dominant precapillary component. PH-LHD is the most common form of pulmonary hypertension, the leading cause being left heart failure with preserved (HFpEF) or reduced ejection fraction (HFmrEF, HFrEF), valvular heart disease and, less commonly, congenital heart disease. The presence of pulmonary hypertension is associated with increased symptom burden and poorer outcome across the spectrum of left heart disease. Differentiating between group 1 pulmonary hypertension with cardiac comorbidities and PH-LHD, especially due to HFpEF, is a particular challenge. Therapeutically, no general recommendation for the use of PDE5 inhibitors in HFpEF-associated CpcPH can be made at this time. There is currently no reliable rationale for the use of PAH drugs in IpcPH, nor is therapy with endothelin receptor antagonists or prostacyclin analogues recommended for all forms of PH-LHD.



Publication History

Article published online:
14 November 2023

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  • Literatur

  • 1 Rosenkranz S, Gibbs JS, Wachter R. et al. Left ventricular heart failure and pulmonary hypertension. Eur Heart J 2016; 37: 942-954
  • 2 Douschan P, Kovacs G, Avian A. et al. Mild elevation of pulmonary arterial pressure as a predictor of mortality. Am J Respir Crit Care Med 2018; 197: 509-516
  • 3 Kolte D, Lakshmanan S, Jankowich MD. et al. Mild pulmonary hypertension ist associated with increased mortality: a systematic review and metanalysis. J Am Heart Assoc 2018; 7: e9729
  • 4 Maron BA. et al. Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort study. Lancet Respir Med 2020; 8: 873-884 DOI: 10.1016/S2213-2600(20)30317-9.
  • 5 Vanderpool RR, Saul M, Nouraie M. et al. Association Between Hemodynamic Markers of Pulmonary Hypertension and Outcomes in Heart Failure With Preserved Ejection Fraction. JAMA Cardiol 2018; 3: 298-306 DOI: 10.1001/jamacardio.2018.0128.
  • 6 Vachiery JL, Tedford RJ, Rosenkranz S. et al. Pulmonary hypertension due to left heart disease. Eur Respir J 2019; 53: 1801897
  • 7 Opitz CF, Hoeper MM, Gibbs JS. et al. Pre-capillary, combined, and post-capillary pulmonary hypertension: a pathophysiological continuum. J Am Coll Cardiol 2016; 68: 368-378
  • 8 Bermejo J, Gonzalez-Mansilla A, Mombiela T. et al. Persistent pulmonary hypertension in corrected valvular heart disease: hemodynamic insights and long-term survival. J Am Heart Assoc 2021; 10: e019949
  • 9 Caravita S, Dewachter C, Soranna D. et al. Haemodynamics to predict outcome in pulmonary hypertension due to left heart disease: a meta-analysis. Eur Respir J 2018; 51: 1702427
  • 10 Crawford TC, Leary PJ, Fraser III CD. et al. Impact of the new pulmonary hypertension definition on heart transplant outcomes: expanding the hemodynamic risk profile. Chest 2020; 157: 151-161
  • 11 O’Sullivan CJ, Wenaweser P, Ceylan O. et al. Effect of pulmonary hypertension hemodynamic presentation on clinical outcomes in patients with severe symptomatic aortic valve stenosis undergoing transcatheter aortic valve implantation: insights from the new proposed pulmonary hypertension classification. Circ Cardiovasc Interv 2015; 8: e002358
  • 12 Vanderpool RR, Saul M, Nouraie M. et al. Association between hemodynamic markers of pulmonary hypertension and outcomes in heart failure with preserved ejection fraction. JAMA Cardiol 2018; 3: 298-306
  • 13 Murali S, Kormos RL, Uretsky BF. et al. Preoperative pulmonary hemodynamics and early mortality after orthotopic cardiac transplantation: the Pittsburgh experience. Am Heart J 1993; 126: 896-904
  • 14 Zimpfer D, Zrunek P, Roethy W. et al. Left ventricular assist devices decrease fixed pulmonary hypertension in cardiac transplant candidates. J Thorac Cardiovasc Surg 2007; 133: 689-695
  • 15 Al-Naamani N, Preston IR, Paulus JK. et al. Pulmonary arterial capacitance is an important predictor of mortality in heart failure with a preserved ejection fraction. JACC Heart Fail 2015; 3: 467-474
  • 16 Ho JE. et al. Exercise Pulmonary Hypertension Predicts Clinical Outcomes in Patients With Dyspnea on Effort. J Am Coll Cardiol 2020; 75: 17-26 DOI: 10.1016/j.jacc.2019.10.048.
  • 17 Lewis GD. et al. Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes. Circ Heart Fail 2011; 4: 276-285 DOI: 10.1161/CIRCHEARTFAILURE.110.959437.
  • 18 D’Alto M, Romeo E, Argiento P. et al. Echocardiographic prediction of pre- versus postcapillary pulmonary hypertension. J Am Soc Echocardiogr 2015; 28: 108-115
  • 19 D’Alto M, Romeo E, Argiento P. et al. A simple echocardiographic score for the diagnosis of pulmonary vascular disease in heart failure. J Cardiovasc Med 2017; 18: 237-243
  • 20 Hoeper MM, Kramer T, Pan Z. et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J 2017; 50: 1700740
  • 21 Hoeper MM, Lam CSP, Vachiery JL. et al. Pulmonary hypertension in heart failure with preserved ejection fraction: a plea for proper phenotyping and further research. Eur Heart J 2017; 38: 2869-2873
  • 22 Pieske B, Tschope C, de Boer RA. et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J 2019; 40: 3297-3317
  • 23 Churchill TW, Li SX, Curreri L. et al. Evaluation of 2 existing diagnostic scores for heart failure with preserved ejection fraction against a comprehensively phenotyped cohort. Circulation 2021; 143: 289-291
  • 24 Reddy YNV, Carter RE, Obokata M. et al. A simple, evidencebased approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation 2018; 138: 861-870
  • 25 Held M, Weiner S, Walthelm J. et al. Funktionelle Charakterisierung von Patienten mit isoliert postkapillärer oder kombiniert post- und präkapillärer pulmonaler Hypertonie [Functional characterization of patients with isolated post-capillary or combined post-capillary and pre-capillary pulmonary hypertension]. Dtsch Med Wochenschr 2021; 146: e88-e94
  • 26 Vasan RS, Xanthakis V, Lyass A. et al. Epidemiology of Left Ventricular Systolic Dysfunction and Heart Failure in the Framingham Study: An Echocardiographic Study Over 3 Decades. JACC Cardiovasc Imaging 2018; 11: 1-11 DOI: 10.1016/j.jcmg.2017.08.007.
  • 27 Hoeper MM, Pausch C, Grünig E. et al. Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry. J Heart Lung Transplant 2020; 39: 1435-1444
  • 28 McDonagh TA, Metra M, Adamo M. et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42: 3599-3726
  • 29 Ho JE, Zern EK, Lau ES. et al. Exercise pulmonary hypertension predicts clinical outcomes in patients with dyspnea on effort. J Am Coll Cardiol 2020; 75: 17-26
  • 30 Eisman AS, Shah RV, Dhakal BP. et al. Pulmonary capillary wedge pressure patterns during exercise predict exercise capacity and incident heart failure. Circ Heart Fail 2018; 11: e004750
  • 31 Andersen MJ, Ersboll M, Bro-Jeppesen J. et al. Exercise hemodynamics in patients with and without diastolic dysfunction and preserved ejection fraction after myocardial infarction. Circ Heart Fail 2012; 5: 444-451
  • 32 Andersen MJ, Olson TP, Melenovsky V. et al. Differential hemodynamic effects of exercise and volume expansion in people with and without heart failure. Circ Heart Fail 2015; 8: 41-48
  • 33 Borlaug BA, Nishimura RA, Sorajja P. et al. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail 2010; 3: 588-595
  • 34 Fujimoto N, Borlaug BA, Lewis GD. et al. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation 2013; 127: 55-62
  • 35 Ho JE, Zern EK, Wooster L. et al. Differential clinical profiles, exercise responses, and outcomes associated with existing HFpEF definitions. Circulation 2019; 140: 353-365
  • 36 Baratto C, Caravita S, Soranna D. et al. Current limitations of invasive exercise hemodynamics for the diagnosis of heart failure with preserved ejection fraction. Circ Heart Fail 2021; 14: e007555
  • 37 Fox BD, Shimony A, Langleben D. et al. High prevalence of occult left heart disease in scleroderma-pulmonary hypertension. Eur Respir J 2013; 42: 1083-1091
  • 38 Lewis GD, Bossone E, Naeije R. et al. Pulmonary vascular hemodynamic response to exercise in cardiopulmonary diseases. Circulation 2013; 128: 1470-1479
  • 39 Maor E, Grossman Y, Balmor RG. et al. Exercise haemodynamics may unmask the diagnosis of diastolic dysfunction among patients with pulmonary hypertension. Eur J Heart Fail 2015; 17: 151-158
  • 40 Robbins IM, Hemnes AR, Pugh ME. et al. High prevalence of occult pulmonary venous hypertension revealed by fluid challenge in pulmonary hypertension. Circ Heart Fail 2014; 7: 116-122
  • 41 D’Alto M, Romeo E, Argiento P. et al. Clinical relevance of fluid challenge in patients evaluated for pulmonary hypertension. Chest 2017; 151: 119-126
  • 42 Borlaug BA. Invasive assessment of pulmonary hypertension: time for a more fluid approach?. Circ Heart Fail 2014; 7: 2-4
  • 43 Obokata M, Reddy YNV, Melenovsky V. et al. Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction. Eur Heart J 2019; 40: 689-697
  • 44 Selim AM, Wadhwani L, Burdorf A. et al. Left ventricular assist devices in pulmonary hypertension group 2 with significantly elevated pulmonary vascular resistance: a bridge to cure. Heart Lung Circ 2019; 28: 946-952
  • 45 Al-Kindi SG, Farhoud M, Zacharias M. et al. Left ventricular assist devices or inotropes for decreasing pulmonary vascular resistance in patients with pulmonary hypertension listed for heart transplantation. J Card Fail 2017; 23: 209-215
  • 46 Imamura T, Chung B, Nguyen A. et al. Decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure as a prognostic factor after continuous flow ventricular assist device implantation. Circ Heart Fail 2017; 10: e003882
  • 47 Kaluski E, Cotter G, Leitman M. et al. Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension–a multi-center randomized study. Cardiology 2008; 109: 273-280
  • 48 Lewis GD, Shah R, Shahzad K. et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007; 116: 1555-1562
  • 49 Dumitrescu D, Seck C, Mohle L. et al. Therapeutic potential of sildenafil in patients with heart failure and reactive pulmonary hypertension. Int J Cardiol 2012; 154: 205-206
  • 50 Wu X, Yang T, Zhou Q. et al. Additional use of a phosphodiesterase 5 inhibitor in patients with pulmonary hypertension secondary to chronic systolic heart failure: a meta-analysis. Eur J Heart Fail 2014; 16: 444-453
  • 51 Anker SD, Butler J, Filippatos G. et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021; 385: 1451-1461
  • 52 Koller B, Steringer-Mascherbauer R, Ebner CH. et al. Pilot study of endothelin receptor blockade in heart failure with diastolic dysfunction and pulmonary hypertension (BADDHY-trial). Heart Lung Circ 2017; 26: 433-441
  • 53 Vachiery JL, Delcroix M, Al-Hiti H. et al. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J 2018; 51: 1701886
  • 54 Hoendermis ES, Liu LC, Hummel YM. et al. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J 2015; 36: 2565-2573
  • 55 Guazzi M, Vicenzi M, Arena R. et al. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation 2011; 124: 164-174
  • 56 Kramer T, Dumitrescu D, Gerhardt F. et al. Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension. Int J Cardiol 2019; 283: 152-158
  • 57 Solomon SD, McMurray JV, Claggett B. et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med 2022; 387: 1089-1098
  • 58 Redfield MM, Borlaug BA. Heart Failure with Preserved Ejection Fraction. A Review. JAMA 2023; 329: 827-833
  • 59 Dachs TM, Duca F, Rettl R. et al. Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial. EUR Heart J 2022; 43: 3402-3413
  • 60 Codina P, Domingo M, Barcelo E. et al. Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension. ESC Heart Fail 2022; 9: 2170-2180
  • 61 Obokata M, Reddy YNV, Shah SJ. et al. Effects of interatrial shunt on pulmonary vascular function in heart failure with preserved ejection fraction. J Am Coll Cardiol 2019; 74: 2539-2550
  • 62 Shah SJ, Borlaug BA, Chung ES. et al. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet 2022; 399: 1130-1140
  • 63 Borlaug BA, Blair J, Bergmann MW. et al. Latent pulmonary vascular disease may alter the response to therapeutic atrial shunt device in heart failure. Circulation 2022; 145: 1592-1604
  • 64 Abraham WT, Stevenson LW, Bourge RC. et al. Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial. Lancet 2016; 387: 453-461
  • 65 Angermann CE, Assmus B, Anker SD. et al. Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Eur J Heart Fail 2020; 22: 1891-1901
  • 66 Shavelle DM, Desai AS, Abraham WT. et al. Lower rates of heart failure and all-cause hospitalizations during pulmonary artery pressure-guided therapy for ambulatory heart failure: one-year outcomes from the CardioMEMS Post-Approval Study. Circ Heart Fail 2020; 13: e006863
  • 67 Lindenfeld J, Zile MR, Desai AS. et al. Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial. Lancet 2021; 398: 991-1001
  • 68 Gaemperli O, Moccetti M, Surder D. et al. Acute haemodynamic changes after percutaneous mitral valve repair: relation to mid-term outcomes. Heart 2012; 98: 126-132
  • 69 Tigges E, Blankenberg S, Bardeleben R vonS. et al. Implication of pulmonary hypertension in patients undergoing MitralClip therapy: results from the German transcatheter mitral valve interventions (TRAMI) registry. Eur J Heart Fail 2018; 20: 585-594
  • 70 Le Tourneau T, Richardson M, Juthier F. et al. Echocardiography predictors and prognostic value of pulmonary artery systolic pressure in chronic organic mitral regurgitation. Heart 2010; 96: 1311-1317
  • 71 Ghoreishi M, Evans CF, DeFilippi CR. et al. Pulmonary hypertension adversely affects short- and long-term survival after mitral valve operation for mitral regurgitation: implications for timing of surgery. J Thorac Cardiovasc Surg 2011; 142: 1439-1452 DOI: 10.1016/j.jtcvs.2011.08.030.
  • 72 Yang B, DeBenedictus C, Watt T. et al. The impact of concomitant pulmonary hypertension on early and late outcomes following surgery for mitral stenosis. J Thorac Cardiovasc Surg 2016; 152: 394-400.e1 DOI: 10.1016/j.jtcvs.2016.02.038. Erratum in: J Thorac Cardiovasc Surg 2016; 152: 1465
  • 73 Vahanian A, Beyersdorf F, Praz F. et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2022; 43: 561-632
  • 74 Zlotnick DM, Ouellette ML, Malenka DJ. et al. Effect of preoperative pulmonary hypertension on outcomes in patients with severe aortic stenosis following surgical aortic valve replacement. Am J Cardiol 2013; 112: 1635-1640
  • 75 Melby SJ, Moon MR, Lindman BR. et al. Impact of pulmonary hypertension on outcomes after aortic valve replacement for aortic valve stenosis. J Thorac Cardiovasc Surg 2011; 141: 1424-1430
  • 76 Lucon A, Oger E, Bedossa M. et al. Prognostic implications of pulmonary hypertension in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: study from the FRANCE 2 Registry. Circ Cardiovasc Interv 2014; 7: 240-247
  • 77 Faggiano P, Antonini-Canterin F, Ribichini F. et al. Pulmonary artery hypertension in adult patients with symptomatic valvular aortic stenosis. Am J Cardiol 2000; 85: 204-208
  • 78 Zuern CS, Eick C, Rizas K. et al. Prognostic value of mild-to-moderate pulmonary hypertension in patients with severe aortic valve stenosis undergoing aortic valve replacement. Clin Res Cardiol 2012; 101: 81-88
  • 79 Roques F, Nashef SA, Michel P. et al. Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients. Eur J Cardiothorac Surg 1999; 15: 816-822
  • 80 Bermejo J, Yotti R, Garcia-Orta R. et al. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial. Eur Heart J 2018; 39: 1255-1264
  • 81 Jiang G, Li B, Zhang G. et al. Effects of sildenafil on prognosis in patients with pulmonary hypertension after left-sided valvular surgery. Heart Lung Circ 2014; 23: 680-685
  • 82 Lindman BR, Zajarias A, Madrazo JA. et al. Effects of phosphodiesterase type 5 inhibition on systemic and pulmonary hemodynamics and ventricular function in patients with severe symptomatic aortic stenosis. Circulation 2012; 125: 2353-2362
  • 83 Chorin E, Rozenbaum Z, Topilsky Y. et al. Tricuspid regurgitation and long-term clinical outcomes. Eur Heart J Cardiovasc Imaging 2020; 21: 157-165
  • 84 Topilsky Y, Nkomo VT, Vatury O. et al. Clinical outcome of isolated tricuspid regurgitation. JACC Cardiovasc Imaging 2014; 7: 1185-1194
  • 85 Condello F, Gitto M, Stafanini GG. Etiology, epidemiology, pathophysiology and management of tricuspid regugitation: an overview. Rev Cardiovasc Med 2021; 22: 1115-1142
  • 86 Stocker TJ, Hertell H, Orban M. et al. Cardiopulmonary hemodynamic profile predicts mortality after transcatheter tricuspid valve repair in chronic heart failure. JACC Cardiovas Interv 2021; 14: 29-38
  • 87 Hausleiter J, Braun D, Orban M. et al. Patient selection, echocardiographic screening and treatment strategies for interventional tricuspid repair using the edge-to-edge repair technique. EuroIntervention 2018; 14: 645-653
  • 88 Lurz P, Orban M, Besler C. et al. Clinical characteristics, diagnosis, and risk stratification of pulmonary hypertension in severe tricuspid regurgitation and implications for transcatheter tricuspid valve repair. Eur Heart J 2020; 41: 2785-2795
  • 89 Sorajja P, Whisenant B, Hamid NHursh N. for the TRILUMINATE Pivotal Investigators. et al. Transcatheter Repair for Patients with Tricuspid Regurgitation. N Engl J Med 2023; 388: 1833-1842 DOI: 10.1056/NEJMoa2300525.
  • 90 Hoeper MM, Humbert M, Souza R. et al. A global view of pulmonary hypertension. Lancet Respir Med 2016; 4: 306-322
  • 91 Rosenkranz S, Gibbs JS, Wachter R. et al. Left ventricular heart failure and pulmonary hypertension. Eur Heart J 2016; 37: 942-954
  • 92 Kovacs G, Herve P, Barbera JA. et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J 2017; 50: 1700578
  • 93 Lindelow B, Andersson B, Waagstein F. et al. High and low pulmonary vascular resistance in heart transplant candidates. A 5-year follow-up after heart transplantation shows continuous reduction in resistance and no difference in complication rate. Eur Heart J 1999; 20: 148-156
  • 94 Beyersdorf F, Schlensak C, Berchtold-Herz M. et al. Regression of “fixed” pulmonary vascular resistance in heart transplant candidates after unloading with ventricular assist devices. J Thorac Cardiovasc Surg 2010; 140: 747-749
  • 95 Yin J, Kukucka M, Hoffmann J. et al. Sildenafil preserves lung endothelial function and prevents pulmonary vascular remodeling in a rat model of diastolic heart failure. Circ Heart Fail 2011; 4: 198-206
  • 96 Cao JY, Wales KM, Cordina R. et al. Pulmonary vasodilator therapies are of no benefit in pulmonary hypertension due to left heart disease: A meta-analysis. Int J Cardiol 2018; 273: 213-220