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DOI: 10.1055/s-0033-1356460
Management of Severe Pulmonary Arterial Hypertension
Publication History
Publication Date:
13 September 2013 (online)
![](https://www.thieme-connect.de/media/srccm/201305/lookinside/thumbnails/10.1055-s-0033-1356460-1.jpg)
Abstract
Despite advances in medical therapies, pulmonary arterial hypertension (PAH), continues to cause significant morbidity and mortality. Although, the right ventricle can adapt to an increase in afterload, progression of the pulmonary vasculopathy that characterizes PAH causes many patients to develop progressive right ventricular (RV) failure. Furthermore, acute RV decompensation may develop from disorders that lead to either an acute increase in cardiac demand or an increase in ventricular afterload including interruptions in medical therapy, arrhythmia, or pulmonary embolism. The poor reserve of the right ventricle, RV ischemia, and adverse RV influence on left ventricular filling may lead to a global reduction in oxygen delivery and multiorgan failure. The authors present an approach to patients with advanced PAH focusing on both medical and surgical strategies to improve RV function based upon current evidence and physiological principles.
Keywords
pulmonary hypertension - right ventricular failure - intensive care - extracorporeal life support - lung transplantationNote
All authors contributed equally to this work. They drafted parts of the article and worked together on the complete article.
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References
- 1 Kawut SM, Horn EM, Berekashvili KK , et al. New predictors of outcome in idiopathic pulmonary arterial hypertension. Am J Cardiol 2005; 95 (2) 199-203
- 2 Rana MS, Christoffels VM, Moorman AFM. A molecular and genetic outline of cardiac morphogenesis. Acta Physiol (Oxf) 2013; 207 (4) 588-615
- 3 Sheehan F, Redington A. The right ventricle: anatomy, physiology and clinical imaging. Heart 2008; 94 (11) 1510-1515
- 4 Drake JI, Bogaard HJ, Mizuno S , et al. Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol 2011; 45 (6) 1239-1247
- 5 Hoffman D, Sisto D, Frater RW, Nikolic SD. Left-to-right ventricular interaction with a noncontracting right ventricle. J Thorac Cardiovasc Surg 1994; 107 (6) 1496-1502
- 6 Santamore WP, Dell'Italia LJ. Ventricular interdependence: significant left ventricular contributions to right ventricular systolic function. Prog Cardiovasc Dis 1998; 40 (4) 289-308
- 7 Sarnoff SJ, Mitchell JH, Gilmore JP, Remensnyder JP. Homeometric autoregulation in the heart. Circ Res 1960; 8: 1077-1091
- 8 Hon JK, Steendijk P, Khan H, Wong K, Yacoub M. Acute effects of pulmonary artery banding in sheep on right ventricle pressure-volume relations: relevance to the arterial switch operation. Acta Physiol Scand 2001; 172 (2) 97-106
- 9 Gaynor SL, Maniar HS, Bloch JB, Steendijk P, Moon MR. Right atrial and ventricular adaptation to chronic right ventricular pressure overload. Circulation 2005; 112 (9, Suppl): I212-I218
- 10 Grothoff M, Hoffmann J, Abdul-Khaliq H , et al. Right ventricular hypertrophy after atrial switch operation: normal adaptation process or risk factor? A cardiac magnetic resonance study. Clin Res Cardiol 2012; 101 (12) 963-971
- 11 Jurcut R, Giusca S, Ticulescu R , et al. Different patterns of adaptation of the right ventricle to pressure overload: a comparison between pulmonary hypertension and pulmonary stenosis. J Am Soc Echocardiogr 2011; 24 (10) 1109-1117
- 12 Sim M-M. Adaptation of the systemic right ventricle in a congenitally corrected transposition of the great arteries. Circulation 2013; 127 (7) e448-e450
- 13 Bartelds B, Borgdorff MA, Smit-van Oosten A , et al. Differential responses of the right ventricle to abnormal loading conditions in mice: pressure vs. volume load. Eur J Heart Fail 2011; 13 (12) 1275-1282
- 14 Szabó G, Soós P, Bährle S , et al. Adaptation of the right ventricle to an increased afterload in the chronically volume overloaded heart. Ann Thorac Surg 2006; 82 (3) 989-995
- 15 Grignola JC, Ginés F, Bia D, Armentano R. Improved right ventricular-vascular coupling during active pulmonary hypertension. Int J Cardiol 2007; 115 (2) 171-182
- 16 Piazza G, Goldhaber SZ. The acutely decompensated right ventricle: pathways for diagnosis and management. Chest 2005; 128 (3) 1836-1852
- 17 Rich S. Right ventricular adaptation and maladaptation in chronic pulmonary arterial hypertension. Cardiol Clin 2012; 30 (2) 257-269
- 18 Benza RL, Miller DP, Gomberg-Maitland M , et al. Predicting survival in pulmonary arterial hypertension: Insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management (reveal). Circulation 2010; 122 (2) 164-172
- 19 Swiston JR, Johnson SR, Granton JT. Factors that prognosticate mortality in idiopathic pulmonary arterial hypertension: a systematic review of the literature. Respir Med 2010; 104 (11) 1588-1607
- 20 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 (10) 1114-1124
- 21 Balik M, Pachl J, Hendl J, Martin B, Jan P, Jan H. Effect of the degree of tricuspid regurgitation on cardiac output measurements by thermodilution. Intensive Care Med 2002; 28 (8) 1117-1121
- 22 Fares WH, Blanchard SK, Stouffer GA , et al. Thermodilution and Fick cardiac outputs differ: impact on pulmonary hypertension evaluation. Can Respir J 2012; 19 (4) 261-266
- 23 Nuñez S, Maisel A. Comparison between mixed venous oxygen saturation and thermodilution cardiac output in monitoring patients with severe heart failure treated with milrinone and dobutamine. Am Heart J 1998; 135 (3) 383-388
- 24 van de Veerdonk MC, Kind T, Marcus JT , et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol 2011; 58 (24) 2511-2519
- 25 Forfia PR, Vachiéry J-L. Echocardiography in pulmonary arterial hypertension. Am J Cardiol 2012; 110 (6, Suppl): 16S-24S
- 26 Howard LS, Grapsa J, Dawson D , et al. Echocardiographic assessment of pulmonary hypertension: standard operating procedure. Eur Respir Rev 2012; 21 (125) 239-248
- 27 Denault AY, Haddad F, Jacobsohn E, Deschamps A. Perioperative right ventricular dysfunction. Curr Opin Anaesthesiol 2013; 26 (1) 71-81
- 28 Haddad F, Peterson T, Fuh E , et al. Characteristics and outcome after hospitalization for acute right heart failure in patients with pulmonary arterial hypertension. Circ Heart Fail 2011; 4 (6) 692-699
- 29 Huynh TN, Weigt SS, Sugar CA, Shapiro S, Kleerup EC. Prognostic factors and outcomes of patients with pulmonary hypertension admitted to the intensive care unit. J Crit Care 2012; 27 (6) e7-e13
- 30 Sztrymf B, Souza R, Bertoletti L , et al. Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension. Eur Respir J 2010; 35 (6) 1286-1293
- 31 Lahm T, McCaslin CA, Wozniak TC , et al. Medical and surgical treatment of acute right ventricular failure. J Am Coll Cardiol 2010; 56 (18) 1435-1446
- 32 Belenkie I, Dani R, Smith ER, Tyberg JV. Effects of volume loading during experimental acute pulmonary embolism. Circulation 1989; 80 (1) 178-188
- 33 Mercat A, Diehl JL, Meyer G, Teboul JL, Sors H. Hemodynamic effects of fluid loading in acute massive pulmonary embolism. Crit Care Med 1999; 27 (3) 540-544
- 34 Benoist D, Stones R, Drinkhill MJ , et al. Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension. Am J Physiol Heart Circ Physiol 2012; 302 (11) H2381-H2395
- 35 Medi C, Kalman JM, Ling L-H , et al. Atrial electrical and structural remodeling associated with longstanding pulmonary hypertension and right ventricular hypertrophy in humans. J Cardiovasc Electrophysiol 2012; 23 (6) 614-620
- 36 Mak S, Witte KK, Al-Hesayen A, Granton JJ, Parker JD. Cardiac sympathetic activation in patients with pulmonary arterial hypertension. Am J Physiol Regul Integr Comp Physiol 2012; 302 (10) R1153-R1157
- 37 McGowan CL, Swiston JS, Notarius CF , et al. Discordance between microneurographic and heart-rate spectral indices of sympathetic activity in pulmonary arterial hypertension. Heart 2009; 95 (9) 754-758
- 38 Tongers J, Schwerdtfeger B, Klein G , et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J 2007; 153 (1) 127-132
- 39 Olsson KM, Nickel NP, Tongers J, Hoeper MM. Atrial flutter and fibrillation in patients with pulmonary hypertension. Int J Cardiol 2012;
- 40 Gan CT, Lankhaar JW, Marcus JT , et al. Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 2006; 290 (4) H1528-H1533
- 41 Marcus JT, Vonk Noordegraaf A, Roeleveld RJ , et al. Impaired left ventricular filling due to right ventricular pressure overload in primary pulmonary hypertension: noninvasive monitoring using MRI. Chest 2001; 119 (6) 1761-1765
- 42 Nelson GS, Sayed-Ahmed EY, Kroeker CA , et al. Compression of interventricular septum during right ventricular pressure loading. Am J Physiol Heart Circ Physiol 2001; 280 (6) H2639-H2648
- 43 Kasner M, Westermann D, Steendijk P , et al. Left ventricular dysfunction induced by nonsevere idiopathic pulmonary arterial hypertension: a pressure-volume relationship study. Am J Respir Crit Care Med 2012; 186 (2) 181-189
- 44 Grant DA, Kondo CS, Maloney JE, Tyberg JV. Pulmonary and pericardial limitations to diastolic filling of the left ventricle of the lamb. Am J Physiol 1994; 266 (6 Pt 2) H2327-H2333
- 45 Marcus JT, Gan CT-J, Zwanenburg JJM , et al. Interventricular mechanical asynchrony in pulmonary arterial hypertension: left-to-right delay in peak shortening is related to right ventricular overload and left ventricular underfilling. J Am Coll Cardiol 2008; 51 (7) 750-757
- 46 Aqel RA, Aljaroudi W, Hage FG, Tallaj J, Rayburn B, Nanda NC. Left ventricular collapse secondary to pericardial effusion treated with pericardicentesis and percutaneous pericardiotomy in severe pulmonary hypertension. Echocardiography 2008; 25 (6) 658-661
- 47 Hemnes AR, Gaine SP, Wiener CM. Poor outcomes associated with drainage of pericardial effusions in patients with pulmonary arterial hypertension. South Med J 2008; 101 (5) 490-494
- 48 Handoko ML, Lamberts RR, Redout EM , et al. Right ventricular pacing improves right heart function in experimental pulmonary arterial hypertension: a study in the isolated heart. Am J Physiol Heart Circ Physiol 2009; 297 (5) H1752-H1759
- 49 Hardziyenka M, Surie S, de Groot JR , et al. Right ventricular pacing improves haemodynamics in right ventricular failure from pressure overload: an open observational proof-of-principle study in patients with chronic thromboembolic pulmonary hypertension. Europace 2011; 13 (12) 1753-1759
- 50 Ciarka A, Vachièry J-L, Houssière A , et al. Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension. Chest 2007; 131 (6) 1831-1837
- 51 Diller G-P, Lammers AE, Haworth SG , et al. A modelling study of atrial septostomy for pulmonary arterial hypertension, and its effect on the state of tissue oxygenation and systemic blood flow. Cardiol Young 2010; 20 (1) 25-32
- 52 Koeken Y, Kuijpers NHL, Lumens J, Arts T, Delhaas T. Atrial septostomy benefits severe pulmonary hypertension patients by increase of left ventricular preload reserve. Am J Physiol Heart Circ Physiol 2012; 302 (12) H2654-H2662
- 53 Rothman A, Beltran D, Kriett JM, Smith C, Wolf P, Jamieson SW. Graded balloon dilation atrial septostomy as a bridge to lung transplantation in pulmonary hypertension. Am Heart J 1993; 125 (6) 1763-1766
- 54 Sandoval J, Gaspar J, Peña H , et al. Effect of atrial septostomy on the survival of patients with severe pulmonary arterial hypertension. Eur Respir J 2011; 38 (6) 1343-1348
- 55 Doyle RL, McCrory D, Channick RN, Simonneau G, Conte J. American College of Chest Physicians. Surgical treatments/interventions for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126 (1, Suppl): 63S-71S
- 56 Reichenberger F, Pepke-Zaba J, McNeil K, Parameshwar J, Shapiro LM. Atrial septostomy in the treatment of severe pulmonary arterial hypertension. Thorax 2003; 58 (9) 797-800
- 57 Gibbons Kroeker CA, Adeeb S, Shrive NG, Tyberg JV. Compression induced by RV pressure overload decreases regional coronary blood flow in anesthetized dogs. Am J Physiol Heart Circ Physiol 2006; 290 (6) H2432-H2438
- 58 Wong YY, Ruiter G, Lubberink M , et al. Right ventricular failure in idiopathic pulmonary arterial hypertension is associated with inefficient myocardial oxygen utilization. Circ Heart Fail 2011; 4 (6) 700-706
- 59 Shehata ML, Lossnitzer D, Skrok J , et al. Myocardial delayed enhancement in pulmonary hypertension: pulmonary hemodynamics, right ventricular function, and remodeling. AJR Am J Roentgenol 2011; 196 (1) 87-94
- 60 Granton J, Moric J. Pulmonary vasodilators—treating the right ventricle. Anesthesiol Clin 2008; 26 (2) 337-353 , vii
- 61 Price LC, Wort SJ, Finney SJ, Marino PS, Brett SJ. Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Crit Care 2010; 14 (5) R169
- 62 Kwak YL, Lee CS, Park YH, Hong YW. The effect of phenylephrine and norepinephrine in patients with chronic pulmonary hypertension*. Anaesthesia 2002; 57 (1) 9-14
- 63 Evora PRB, Pearson PJ, Rodrigues AJ, Viaro F, Schaff HV. Effect of arginine vasopressin on the canine epicardial coronary artery: experiments on V1-receptor-mediated production of nitric oxide. Arq Bras Cardiol 2003; 80 (5) 483-494
- 64 Holmes CL, Landry DW, Granton JT. Science review: Vasopressin and the cardiovascular system part 1—receptor physiology. Crit Care 2003; 7 (6) 427-434
- 65 Leather HA, Segers P, Berends N, Vandermeersch E, Wouters PF. Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension. Crit Care Med 2002; 30 (11) 2548-2552
- 66 Zamanian RT, Haddad F, Doyle RL, Weinacker AB. Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit Care Med 2007; 35 (9) 2037-2050
- 67 Apitz C, Honjo O, Humpl T , et al. Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload. J Thorac Cardiovasc Surg 2012; 144 (6) 1494-1501
- 68 Nagendran J, Archer SL, Soliman D , et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation 2007; 116 (3) 238-248
- 69 Borgdorff MAJ, Bartelds B, Dickinson MG , et al. Sildenafil enhances systolic adaptation, but does not prevent diastolic dysfunction, in the pressure-loaded right ventricle. Eur J Heart Fail 2012; 14 (9) 1067-1074
- 70 Ebade AA, Khalil MA, Mohamed AK. Levosimendan is superior to dobutamine as an inodilator in the treatment of pulmonary hypertension for children undergoing cardiac surgery. J Anesth 2012;
- 71 Lee TS, Hou X. Vasoactive effects of ketamine on isolated rabbit pulmonary arteries. Chest 1995; 107 (4) 1152-1155
- 72 Williams GD, Philip BM, Chu LF , et al. Ketamine does not increase pulmonary vascular resistance in children with pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous ventilation. Anesth Analg 2007; 105 (6) 1578-1584 , table of contents
- 73 McCaul C, Kornecki A, Engelberts D, McNamara P, Kavanagh BP. Positive end-expiratory pressure improves survival in a rodent model of cardiopulmonary resuscitation using high-dose epinephrine. Anesth Analg 2009; 109 (4) 1202-1208
- 74 Barst RJ, Rubin LJ, Long WA , et al; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996; 334 (5) 296-301
- 75 Nagendran J, Sutendra G, Paterson I , et al. Endothelin axis is upregulated in human and rat right ventricular hypertrophy. Circ Res 2013; 112 (2) 347-354
- 76 Christie JD, Edwards LB, Kucheryavaya AY , et al; International Society of Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012. J Heart Lung Transplant 2012; 31 (10) 1073-1086
- 77 Lordan JL, Corris PA. Pulmonary arterial hypertension and lung transplantation. Expert Rev Respir Med 2011; 5 (3) 441-454
- 78 Orens JB, Estenne M, Arcasoy S , et al; Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. International guidelines for the selection of lung transplant candidates: 2006 update—a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2006; 25 (7) 745-755
- 79 Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest 2012; 142 (2) 448-456
- 80 Diller G-P, Dimopoulos K, Broberg CS , et al. Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: a combined retrospective and case-control study. Eur Heart J 2006; 27 (14) 1737-1742
- 81 Dimopoulos K, Inuzuka R, Goletto S , et al. Improved survival among patients with Eisenmenger syndrome receiving advanced therapy for pulmonary arterial hypertension. Circulation 2010; 121 (1) 20-25
- 82 Chen H, Shiboski SC, Golden JA , et al. Impact of the lung allocation score on lung transplantation for pulmonary arterial hypertension. Am J Respir Crit Care Med 2009; 180 (5) 468-474
- 83 Dandel M, Lehmkuhl HB, Mulahasanovic S , et al. Survival of patients with idiopathic pulmonary arterial hypertension after listing for transplantation: impact of iloprost and bosentan treatment. J Heart Lung Transplant 2007; 26 (9) 898-906
- 84 Bermudez CA, Rocha RV, Zaldonis D , et al. Extracorporeal membrane oxygenation as a bridge to lung transplant: midterm outcomes. Ann Thorac Surg 2011; 92 (4) 1226-1231 , discussion 1231–1232
- 85 Crotti S, Iotti GA, Lissoni A , et al. The organ allocation waiting time during extracorporeal bridge to lung transplantation affects outcomes. Chest 2013;
- 86 Fuehner T, Kuehn C, Hadem J , et al. Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. Am J Respir Crit Care Med 2012; 185 (7) 763-768
- 87 Hoopes CW, Kukreja J, Golden J, Davenport DL, Diaz-Guzman E, Zwischenberger JB. Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation. J Thorac Cardiovasc Surg 2013; 145 (3) 862-867 , discussion 867–868
- 88 Nosotti M, Rosso L, Tosi D , et al. Extracorporeal membrane oxygenation with spontaneous breathing as a bridge to lung transplantation. Interact Cardiovasc Thorac Surg 2013; 16 (1) 55-59
- 89 Toyoda Y, Bhama JK, Shigemura N , et al. Efficacy of extracorporeal membrane oxygenation as a bridge to lung transplantation. J Thorac Cardiovasc Surg 2013; 145 (4) 1065-1070 , discussion 1070–1071
- 90 de Perrot M, Granton JT, McRae K , et al. Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J Heart Lung Transplant 2011; 30 (9) 997-1002
- 91 Fischer S, Hoeper MM, Tomaszek S , et al. Bridge to lung transplantation with the extracorporeal membrane ventilator Novalung in the veno-venous mode: the initial Hannover experience. ASAIO J 2007; 53 (2) 168-170
- 92 Hämmäinen P, Schersten H, Lemström K , et al. Usefulness of extracorporeal membrane oxygenation as a bridge to lung transplantation: a descriptive study. J Heart Lung Transplant 2011; 30 (1) 103-107
- 93 Lang G, Taghavi S, Aigner C , et al. Primary lung transplantation after bridge with extracorporeal membrane oxygenation: a plea for a shift in our paradigms for indications. Transplantation 2012; 93 (7) 729-736
- 94 Olsson KM, Simon A, Strueber M , et al. Extracorporeal membrane oxygenation in nonintubated patients as bridge to lung transplantation. Am J Transplant 2010; 10 (9) 2173-2178
- 95 Strueber M, Hoeper MM, Fischer S , et al. Bridge to thoracic organ transplantation in patients with pulmonary arterial hypertension using a pumpless lung assist device. Am J Transplant 2009; 9 (4) 853-857
- 96 Schmid C, Philipp A, Hilker M , et al. Bridge to lung transplantation through a pulmonary artery to left atrial oxygenator circuit. Ann Thorac Surg 2008; 85 (4) 1202-1205
- 97 Javidfar J, Brodie D, Iribarne A , et al. Extracorporeal membrane oxygenation as a bridge to lung transplantation and recovery. J Thorac Cardiovasc Surg 2012; 144 (3) 716-721
- 98 Rehder KJ, Turner DA, Hartwig MG , et al. Active rehabilitation during ECMO as a bridge to lung transplantation. Respir Care 2012;
- 99 Iacono A, Groves S, Garcia J, Griffith B. Lung transplantation following 107 days of extracorporeal membrane oxygenation. Eur J Cardiothorac Surg 2010; 37 (4) 969-971