Right Heart Adaptation to Pulmonary Arterial Hypertension: Physiology and Pathobiology: A Systematic Review
Keywords:
Pulmonary Arterial Hypertension, Right Ventricular Dysfunction, Right Heart Failure, RV RemodelingAbstract
Background Pulmonary arterial hypertension (PAH) is a chronic disease affecting the pulmonary vasculature and right ventricular (RV) function, leading to right heart failure (RHF). Effective management of RHF in PAH patients is critical due to its impact on prognosis and survival. Objective To evaluate the current knowledge on RV pathobiology in PAH and highlight the importance of managing RHF in these patients. Methodology A comprehensive review of existing literature was conducted, focusing on RV function, adaptive and maladaptive remodeling, clinical presentation, prognostic indicators, and therapeutic strategies for RHF in PAH. Key sources included peer-reviewed journals, clinical trials, and expert guidelines. Results The review indicates that RV dysfunction in PAH is characterized by adaptive and maladaptive remodeling, leading to progressive RHF. Clinical indicators of RHF include elevated systemic venous pressure, fluid retention, and exercise limitation. Prognostic factors such as RV ejection fraction, tricuspid annular plane systolic excursion, and cardiac biomarkers are crucial for outcome prediction. Current therapies focus on pulmonary vasodilation and targeted RV treatment, with potential benefits from metabolic regulation and novel interventions. Conclusion Effective management of right heart failure in pulmonary arterial hypertension patients is crucial for improving prognosis and survival. Understanding the pathobiology of right ventricular dysfunction and its clinical implications can guide the development of targeted therapies. Future research should focus on novel treatment strategies and metabolic regulation to optimize patient outcomes in PAH-associated RHF.References
Chesler NC, Roldan A, Vanderpool RR, Naeije R. How to measure pulmonary vascular and right ventricular function. In: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society. New York, NY: IEEE, 2009: 177–80.
Dell’Italia LJ. Anatomy and physiology of the right ventricle. Cardiol Clin. 2012;30:167–87.
Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004;351:1655–65.
Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. 2008;117(11):1436-48.
Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary circulation unit: state of the art and clinical and research implications. Circulation. 2009;120:992–1007.
Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circ. 2006;114(17):1883-91.
D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med. 1991;115(5):343-9.
Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, et al. Predicting survival in pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL). Circ. 2010;122(2):164-72.
Campo A, Mathai SC, Le Pavec J, Zaiman AL, Hummers LK, Boyce D, et al. Hemodynamic predictors of survival in scleroderma-related pulmonary arterial hypertension. Am J Respir Crit Care Med. 2010 Jul 15;182(2):252-60.
Forfia PR, Fisher MR, Mathai SC, Housten-Harris T, Hemnes AR, Borlaug BA, et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med. 2006;174(9):1034-41.11.
Gan CT, Lankhaar JW, Westerhof N, Marcus JT, Becker A, Twisk JW, et al. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest. 2007;132(6):1906-12.
Ghio S, Klersy C, Magrini G, D'Armini AM, Scelsi L, Raineri C, et al. Prognostic relevance of the echocardiographic assessment of right ventricular function in patients with idiopathic pulmonary arterial hypertension. Int J Cardiol. 2010 Apr 30;140(3):272-8.
Ghio S, Pazzano AS, Klersy C, Scelsi L, Raineri C, Camporotondo R, et al. Clinical and prognostic relevance of echocardiographic evaluation of right ventricular geometry in patients with idiopathic pulmonary arterial hypertension. Am J Cardiol. 2011 Feb 15;107(4):628-32.
Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circ. 2010;122(2):156-63.
Mahapatra S, Nishimura RA, Sorajja P, Cha S, McGoon MD. Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension. J Am Coll Cardiol. 2006;47:799–803.
Raymond RJ, Hinderliter AL, Willis PW, Ralph D, Caldwell EJ, Williams W, et al. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol. 2002;39(7):1214-9.
Sachdev A, Villarraga HR, Frantz RP, McGoon MD, Hsiao JF, Maalouf JF, et al. Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension. Chest. 2011;139(6):1299-309.
Van Wolferen SA, Marcus JT, Boonstra A, Marques KM, Bronzwaer JG, Spreeuwenberg MD, et al. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J. 2007;28(10):1250-7.
Yeo TC, Dujardin KS, Tei C, Mahoney DW, McGoon MD, Seward JB. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Am J Cardiol. 1998;81:1157–61.
Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circ. 2008;117:1717–31.
Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension: comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2000;161(2):487-92.
Provencher S, Herve P, Sitbon O, Humbert M, Simonneau G, Chemla D. Changes in exercise haemodynamics during treatment in pulmonary arterial hypertension. Eur Respir J. 2008;32:393–8.
Nootens M, Wolfkiel CJ, Chomka EV, Rich S. Understanding right and left ventricular systolic function and interactions at rest and with exercise in primary pulmonary hypertension. Am J Cardiol. 1995;75:374–7.
Groepenhoff H, Vonk-Noordegraaf A, Boonstra A, Spreeuwenberg MD, Postmus PE, Bogaard HJ. Exercise testing to estimate survival in pulmonary hypertension. Med Sci Sports Exerc. 2008;40:1725–32.
Tongers J, Schwerdtfeger B, Klein G, Kempf T, Schaefer A, Knapp JM, et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J. 2007;153(1):127-32.
Forfia PR, Mathai SC, Fisher MR, Housten-Harris T, Hemnes AR, Champion HC, et al. Hyponatremia predicts right heart failure and poor survival in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;177(12):1364-9.
Shah SJ, Thenappan T, Rich S, Tian L, Archer SL, Gomberg-Maitland M. Association of serum creatinine with abnormal hemodynamics and mortality in pulmonary arterial hypertension. Circ. 2008;117:2475–83.
Haddad F, Fuh E, Peterson T, Skhiri M, Kudelko KT, Perez VD, et al. Incidence, correlates, and consequences of acute kidney injury in patients with pulmonary arterial hypertension hospitalized with acute right-side heart failure. J Card Fail. 2011;17(7):533-9.
Campo A, Mathai SC, Le Pavec J, Zaiman AL, Hummers LK, Boyce D, et al. Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension. Eur Respir J. 2011;38(2):359-67.
Haddad F, Peterson T, Fuh E, Kudelko KT, de Jesus Perez V, Skhiri M, et al. Characteristics and outcome after hospitalization for acute right heart failure in patients with pulmonary arterial hypertension. Circ Heart Fail. 2011;4(6):692-9.
Sztrymf B, Souza R, Bertoletti L, Jais X, Sitbon O, Price LC et al. Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension. Eur Respir J. 2010;35(6):1286-93.
Kurzyna M, Zyłkowska J, Fijałkowska A, Florczyk M, Wieteska M, Kacprzak A, et al. Original article Characteristics and prognosis of patients with decompensated right ventricular failure during the course of pulmonary hypertension. Pol Heart J. 2008;66(10):1033-9.
Hoeper MM, Galie N, Murali S, Olschewski H, Rubenfire M, Robbins IM, et al. Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2002;165(3):341-4.
Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circ. 2009;119(14).
Belenkie I, Smith ER, Tyberg JV. Ventricular interaction: from bench to bedside. Ann Med. 2001;33(4):236-41.
Hardziyenka M, Campian ME, Verkerk AO, Surie S, van Ginneken AC, Hakim S, et al. Electrophysiologic remodelling of the left ventricle in pressure overload-induced right ventricular failure. J Am Coll Cardiol. 2012;59(24):2193-202.
Nagendran J, Michelakis ED. Mitochondrial NOS is upregulated in the hypoxic heart: implications for the function of the hypertrophied right ventricle. Am J Physiol Heart Circ Physiol. 2009;296–6.
Sutendra G, Bonnet S, Rochefort G, Haromy A, Folmes KD, Lopaschuk GD, et al. Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodelling of pulmonary hypertension. Sci Transl Med. 2010 Aug 11;2(44):44ra58-.
Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JG, Weir EK. Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol. 2008;294–8.
Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest. 2009;135:794–804.
Voelkel NF, Natarajan R, Drake JI, Bogaard HJ. Right ventricle in pulmonary hypertension. Compr Physiol. 2011;1:525–40.
Dell’Italia LJ, Walsh RA. Application of a time varying elastance model to right ventricular performance in man. Cardiovasc Res. 1988;22:864–74.
Kuehne T, Yilmaz S, Steendijk P, Moore P, Groenink M, Saaed M, et al. Magnetic resonance imaging analysis of right ventricular pressure-volume loops: in vivo validation and clinical application in patients with pulmonary hypertension. Circ. 2004;110(14):2010-6.
Michelakis ED, Wilkins MR, Rabinovitch M. Emerging concepts and translational priorities in pulmonary arterial hypertension. Circ. 2008;118:1486–95.
Tanaka Y, Takase B, Yao T, Ishihara M. Right ventricular electrical remodelling and arrhythmogenic substrate in rat pulmonary hypertension. Am J Respir Cell Mol Biol. 2013;49:426–36.
Chung L, Liu J, Parsons L, Hassoun PM, McGoon M, Badesch DB, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138(6):1383-94.
Oudiz RJ, Midde R, Hovanesyan A, Sun XG, Roveran G, Hansen JE, et al. Usefulness of right-to-left shunting and poor exercise gas exchange for predicting prognosis in patients with pulmonary arterial hypertension. Am J Cardiol. 2010;105(8):1186-91.
Dubin AM, Feinstein JA, Reddy VM, Hanley FL, Van Hare GF, Rosenthal DN. Electrical resynchronization: a novel therapy for the failing right ventricle. Circ. 2003;107:2287–9.
Handoko ML, de Man FS, Allaart CP, Paulus WJ, Westerhof N, Vonk-Noordegraaf A. Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart. Eur Respir Rev. 2010;19:72–82.
Handoko ML, Lamberts RR, Redout EM, de Man FS, Boer C, Simonides WS, 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).
Marcus JT, Gan CT, Zwanenburg JJ, Boonstra A, Allaart CP, Gotte MJ, 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):750-7.
Mauritz GJ, Vonk-Noordegraaf A, Kind T, Surie S, Kloek JJ, Bresser P, et al. Pulmonary endarterectomy normalizes interventricular dyssynchrony and right ventricular systolic wall stress. J Cardiovasc Magn Reson. 2012;14(1):9.
Vonk-Noordegraaf A, Marcus JT, Gan CT, Boonstra A, Postmus PE. Interventricular mechanical asynchrony due to right ventricular pressure overload in pulmonary hypertension plays an important role in impaired left ventricular filling. Chest. 2005;128:628S–30S.
Lumens J, Arts T, Marcus JT, Vonk-Noordegraaf A, Delhaas T. Early-diastolic left ventricular lengthening implies pulmonary hypertension-induced right ventricular decompensation. Cardiovasc Res. 2012;96:286–95.
Helderman F, Mauritz GJ, Andringa KE, Vonk-Noordegraaf A, Marcus JT. Early onset of retrograde flow in the main pulmonary artery is a characteristic of pulmonary arterial hypertension. J Magn Reson Imaging. 2011;33:1362–8.
Sanz J, Dellegrottaglie S, Kariisa M, Sulica R, Poon M, O’Donnell TP, et al. Prevalence and correlates of septal delayed contrast enhancement in patients with pulmonary hypertension. Am J Cardiol. 2007;100(4):731-5.
McCann GP, Gan CT, Beek AM, Niessen HW, Vonk Noordegraaf A, van Rossum AC. Extent of MRI delayed enhancement of myocardial mass is related to right ventricular dysfunction in pulmonary artery hypertension. AJR Am J Roentgenol. 2007;188:349–55.
Bessa LG, Junqueira FP, Bandeira ML, Garcia MI, Xavier SS, Lavall G, et al. Pulmonary arterial hypertension: use of delayed contrast-enhanced cardiovascular magnetic resonance in risk assessment. Arq Bras Cardiol. 2013;101:336-43.
Shehata ML, Lossnitzer D, Skrok J, Boyce D, Lechtzin N, Mathai SC, Girgis RE, et al. Myocardial delayed enhancement in pulmonary hypertension: pulmonary hemodynamics, right ventricular function, and remodelling. Am J Roentgenol. 2011;196(1):87-94.
Frist WH, Lorenz CH, Walker ES, Loyd JE, Stewart JR, Graham Jr TP, et al. MRI complements standard assessment of right ventricular function after lung transplantation. Ann Thorac Surg. 1995;60(2):268-71.
Kramer MR, Valantine HA, Marshall SE, Starnes VA, Theodore J. Recovery of the right ventricle after single-lung transplantation in pulmonary hypertension. Am J Cardiol 1994;73:494–500.
Kasimir MT, Seebacher G, Jaksch P, Winkler G, Schmid K, Marta GM, et al. Reverse cardiac remodelling in patients with primary pulmonary hypertension after isolated lung transplantation. Eur J Cardiothorac Surg. 2004;26:776–81.
Conte JV, Borja MJ, Patel CB, Yang SC, Jhaveri RM, Orens JB. Lung transplantation for primary and secondary pulmonary hypertension. Ann Thorac Surg. 2001;72:1673–9.
Fadel E, Mercier O, Mussot S, Leroy-Ladurie F, Cerrina J, Chapelier A, et al. Long-term outcome of double-lung and heart–lung transplantation for pulmonary hypertension: a comparative retrospective study of 219 patients. Eur J Cardiothorac Surg. 2010;38:277–84.
Guihaire J, Haddad F, Boulate D, Decante B, Denault AY, Wu J, et al. Non-invasive indices of right ventricular function are markers of ventricular–arterial coupling rather than ventricular contractility: insights from a porcine model of chronic pressure overload. Eur Heart J Cardiovasc Imaging. 2013;14:1140–9.
Chesler NC, Argiento P, Vanderpool R, D’Alto M, Naeije R. How to measure peripheral pulmonary vascular mechanics. In: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society. New York, NY: IEEE; 2009. p. 173–6.
Tedford RJ, Mudd JO, Girgis RE, Mathai SC, Zaiman AL, Housten-Harris T, et al. Right ventricular dysfunction in systemic sclerosis–associated pulmonary arterial hypertension. Circ Heart Fail. 2013;6:953–63.
Saouti N, Westerhof N, Helderman F, Marcus JT, Boonstra A, Postmus PE, Vonk-Noordegraaf A. Right ventricular oscillatory power is a constant fraction of total power irrespective of pulmonary artery pressure. Am J Respir Crit Care Med. 2010;182:1315–20.
Saouti N, Westerhof N, Helderman F, Marcus JT, Stergiopulos N, Westerhof BE, et al. RC time constant of single lung equals that of both lungs together: a study in chronic thromboembolic pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2009;297–60.
Lankhaar JW, Westerhof N, Faes TJ, Tji-Joong Gan C, Marques KM, Boonstra A, et al. Pulmonary vascular resistance and compliance stay inversely related during treatment of pulmonary hypertension. Eur Heart J. 2008;29:1688–95.
Saouti N, Westerhof N, Postmus PE, Vonk-Noordegraaf A. The arterial load in pulmonary hypertension. Eur Respir Rev 2010;19:197–203.
Tedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, et al. Pulmonary capillary wedge pressure augments right ventricular pulsatile loading. Circulation. 2012;125(2):289-97.
Ryan JJ, Rich JD, Thiruvoipati T, Swamy R, Kim GH, Rich S. Current practice for determining pulmonary capillary wedge pressure predisposes to serious errors in the classification of patients with pulmonary hypertension. Am Heart J. 2012;163(4):589-94.
Mitchell JR, Doig CJ, Whitelaw WA, Tyberg JV, Belenkie I. Volume loading reduces pulmonary vascular resistance in ventilated animals with acute lung injury: evaluation of RV afterload. Am J Physiol Regul Integr Comp Physiol. 2011;300(3).
Norton JM. Toward consistent definitions for preload and afterload. Adv Physiol Educ. 2001;25(1):53-61.
Lumens J, Delhaas T. Cardiovascular modeling in pulmonary arterial hypertension: focus on mechanisms and treatment of right heart failure using the CircAdapt model. Am J Cardiol. 2012;110:39S–48S.
Arts T, Lumens J, Kroon W, Delhaas T. Control of whole heart geometry by intramyocardial mechano-feedback: a model study. PLoS Comput Biol. 2012;8.
Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ, Nicolls MR. Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J. 2012;40:1555–65.
Guihaire J, Bogaard HJ, Flécher E, Noly PE, Mercier O, Haddad F, et al. Experimental models of right heart failure: a window for translational research in pulmonary hypertension. Semin Respir Crit Care Med. 2013;34(5):689-99.
Bogaard HJ, Natarajan R, Henderson SC, Long CS, Kraskauskas D, Smithson L, et al. Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation. 2009;120(20):1951-60.81.
Watts JA, Marchick MR, Kline JA. Right ventricular heart failure from pulmonary embolism: key distinctions from chronic pulmonary hypertension. J Card Fail. 2010;16:250–9.
Wrigley BJ, Lip GY, Shantsila E. The role of monocytes and inflammation in the pathophysiology of heart failure. Eur J Heart Fail. 2011;13:1161–71.
Tuder RM, Davis LA, Graham BB. Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension. Am J Respir Crit Care Med. 2012;185:260–6.
Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet. 2005;6:826–35.
Drake JI, Bogaard HJ, Mizuno S, Clifton B, Xie B, Gao Y, et al. Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol. 2011 Dec;45(6):1239-47.
Raizada V, Thakore K, Luo W, McGuire PG. Cardiac chamber-specific alterations of ANP and BNP expression with advancing age and with systemic hypertension. Mol Cell Biochem. 2001;216:137–40.
Michaels AD, Chatterjee K, De Marco T. Effects of intravenous nesiritide on pulmonary vascular hemodynamics in pulmonary hypertension. J Card Fail. 2005;11:425–31.
Klinger JR, Thaker S, Houtchens J, Preston IR, Hill NS, Farber HW. Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension. Chest. 2006;129:417–25.
Lowes BD, Minobe W, Abraham WT, Rizeq MN, Bohlmeyer TJ, Quaife RA, et al. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest. 1997;100(9):2315-24.
Urashima T, Zhao M, Wagner R, Fajardo G, Farahani S, Quertermous T, Bernstein D. Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis. Am J Physiol Heart Circ Physiol. 2008;295(3).
Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A, 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):238-48.
Nagendran J, Gurtu V, Fu DZ, Dyck JR, Haromy A, Ross DB, Rebeyka IM, Michelakis ED. A dynamic and chamber-specific mitochondrial remodeling in right ventricular hypertrophy can be therapeutically targeted. J Thorac Cardiovasc Surg. 2008;136(1):168-78.
Reddy S, Zhao M, Hu DQ, Fajardo G, Hu S, Ghosh Z, et al. Dynamic microRNA expression during the transition from right ventricular hypertrophy to failure. Physiol Genomics. 2012;44(10):562-75.
Ruiter G, Wong YY, de Man FS, Handoko ML, Jaspers RT, Postmus PE, et al. Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hypertension. J Heart Lung Transplant. 2013;32(2):231-40.
Rain S, Handoko ML, Trip P, Gan CT, Westerhof N, Stienen GJ, et al. Right ventricular diastolic impairment in patients with pulmonary arterial hypertension. Circulation. 2013;128(18):2016-25.
Von Haehling S, von Bardeleben RS, Kramm T, Thiermann Y, Niethammer M, Doehner W, et al. Inflammation in right ventricular dysfunction due to thromboembolic pulmonary hypertension. Int J Cardiol. 2010;144(2):206-11.
Watts JA, Zagorski J, Gellar MA, Stevinson BG, Kline JA. Cardiac inflammation contributes to right ventricular dysfunction following experimental pulmonary embolism in rats. J Mol Cell Cardiol. 2006;41:296–307.
Sanz J, Conroy J, Narula J. Imaging of the right ventricle. Cardiol Clin. 2012;30:189–203.
Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography: endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713.
Kawut SM, Lima JA, Barr RG, Chahal H, Jain A, Tandri H, et al. Sex and race differences in right ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis–Right Ventricle Study. Circulation. 2011;123(22):2542-51.
Blumberg FC, Arzt M, Lange T, Schroll S, Pfeifer M, Wensel R. Impact of right ventricular reserve on exercise capacity and survival in patients with pulmonary hypertension. Eur J Heart Fail 2013;15:771–5.
Lewis GD, Murphy RM, Shah RV, Pappagianopoulos PP, Malhotra R, Bloch KD, et al. Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes. Circ Heart Fail. 2011;4(3):276-85.
Riley RL, Himmelstein A, Motley HL, Weiner HM, Cournand A. Studies of the pulmonary circulation at rest and during exercise in normal individuals and in patients with chronic pulmonary disease. Am J Physiol. 1948;152(2):372-82.
Fowler NO. The normal pulmonary arterial pressure-flow relationships during exercise. Am J Med. 1969;47:1–6.
Kovacs G, Olschewski A, Berghold A, Olschewski H. Pulmonary vascular resistances during exercise in normal subjects: a systematic review. Eur Respir J. 2012;39:319–28.
D'Alto M, Ghio S, D'Andrea A, Pazzano AS, Argiento P, Camporotondo R, et al. Inappropriate exercise-induced increase in pulmonary artery pressure in patients with systemic sclerosis. Heart. 2011;97(2):112-7.
Reeves JT, Linehan JH, Stenmark KR. Distensibility of the normal human lung circulation during exercise. Am J Physiol Lung Cell Mol Physiol. 2005;288–25.
Kovacs G, Maier R, Aberer E, Brodmann M, Scheidl S, Hesse C, Troester N, Salmhofer W, Stauber R, Fuerst FC, Thonhofer R. Assessment of pulmonary arterial pressure during exercise in collagen vascular disease: echocardiography vs right-sided heart catheterization. Chest. 2010 Aug 1;138(2):270-8.
Argiento P, Chesler N, Mulè M, D'Alto M, Bossone E, Unger P, et al. Exercise stress echocardiography for the study of the pulmonary circulation. Eur Respir J. 2010;35(6):1273-8.
D'Andrea A, Naeije R, D'Alto M, Argiento P, Golia E, Cocchia R, et al. Range in pulmonary artery systolic pressure among highly trained athletes. Chest. 2011;139(4):788-94.
Kovacs G, Maier R, Aberer E, Brodmann M, Scheidl S, Tröster N, et al. Borderline pulmonary arterial pressure is associated with decreased exercise capacity in scleroderma. Am J Respir Crit Care Med. 2009;180(9):881-6.
Whyte K, Hoette S, Hervé P, Montani D, Jaïs X, Parent F, et al. The association between resting and mild-to-moderate exercise pulmonary artery pressure. Eur Respir J. 2012;39(2):313-8.
Saggar R, Lewis GD, Systrom DM, Champion HC, Naeije R. Pulmonary vascular responses to exercise: a haemodynamic observation. Eur Respir J. 2012;39:231–4.
Tamborini G, Muratori M, Brusoni D, Celeste F, Maffessanti F, Caiani EG, et al. Is right ventricular systolic function reduced after cardiac surgery? A two-and three-dimensional echocardiographic study. Eur J Echocardiogr. 2009;10(5):630-4.
Hagger D, Condliffe R, Woodhouse N, Elliot CA, Armstrong IJ, Davies C, et al. Ventricular mass index correlates with pulmonary artery pressure and predicts survival in suspected systemic sclerosis-associated pulmonary arterial hypertension. Rheumatology. 2009;48(9):1137-42.
Van de Veerdonk MC, Kind T, Marcus JT, Mauritz GJ, Heymans MW, Bogaard HJ, et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol. 2011;58(24):2511-9.
Thenappan T, Glassner C, Gomberg-Maitland M. Validation of the pulmonary hypertension connection equation for survival prediction in pulmonary arterial hypertension. Chest. 2012;141:642–50.
Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltrán M, Guerrero ML. Survival in primary pulmonary hypertension. Validation of a prognostic equation. Circulation. 1994;89(4):1733-44.
Nagaya N, Nishikimi T, Uematsu M, Satoh T, Kyotani S, Sakamaki F, Kakishita M, Fukushima K, Okano Y, Nakanishi N, Miyatake K. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation. 2000;102(8):865-70.
Haeck ML, Scherptong RW, Marsan NA, Holman ER, Schalij MJ, Bax JJ, Delgado V. Prognostic value of right ventricular longitudinal peak systolic strain in patients with pulmonary hypertension. Circ Cardiovasc Imaging. 2012;5:628–36.
Haeck ML, Scherptong RW, Antoni ML, Marsan NA, Vliegen HW, Holman ER, et al. Right ventricular longitudinal peak systolic strain measurements from the subcostal view in patients with suspected pulmonary hypertension: a feasibility study. J Am Soc Echocardiogr. 2012;25(6):674-81.
Vonk Noordegraaf A, Galie N. The role of the right ventricle in pulmonary arterial hypertension. Eur Respir Rev. 2011;20:243–53.
Van Wolferen SA, Van De Veerdonk MC, Mauritz GJ, Jacobs W, Marcus JT, Marques KM, et al. Clinically significant change in stroke volume in pulmonary hypertension. Chest. 2011;139(5):1003-9.
Thenappan T, Shah SJ, Rich S, Tian L, Archer SL, Gomberg-Maitland M. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J. 2010;35:1079–87.
Vonk MC, Sander MH, van den Hoogen FH, van Riel PL, Verheugt FW, van Dijk AP. Right ventricle Tei-index: a tool to increase the accuracy of non-invasive detection of pulmonary arterial hypertension in connective tissue diseases. Eur J Echocardiogr. 2007;8:317–21.
Mauritz GJ, Kind T, Marcus JT, Bogaard HJ, van de Veerdonk M, Postmus PE, et al. Progressive changes in right ventricular geometric shortening and long-term survival in pulmonary arterial hypertension. Chest. 2012 Apr 1;141(4):935-43.
McCann GP, Beek AM, Vonk-Noordegraaf A, van Rossum AC. Delayed contrast-enhanced magnetic resonance imaging in pulmonary arterial hypertension. Circulation. 2005;112:115–22.
Torbicki A, Kurzyna M, Kuca P, Fijałkowska A, Sikora J, Florczyk M, et al. Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation. 2003;108(7):844-8.
Vélez-MartÃnez M, Ayers C, Mishkin JD, Bartolome SB, GarcÃa CK, Torres F, et al. Association of cardiac troponin I with disease severity and outcomes in patients with pulmonary hypertension. Am J Cardiol. 2013;111(12):1812-7.
Filusch A, Giannitsis E, Katus HA, Meyer FJ. High-sensitive troponin T: a novel biomarker for prognosis and disease severity in patients with pulmonary arterial hypertension. Clin Sci. 2010;119:207–13.
Heresi GA, Tang WH, Aytekin M, Hammel J, Hazen SL, Dweik RA. Sensitive cardiac troponin I predicts poor outcomes in pulmonary arterial hypertension. Eur Respir J. 2012;39:939–44.
Fijalkowska A, Kurzyna M, Torbicki A, Szewczyk G, Florczyk M, Pruszczyk P, et al. Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension. Chest. 2006;129(5):1313-21.
Kerbaul F, Brimioulle S, Rondelet B, Dewachter C, Hubloue I, Naeije R. How prostacyclin improves cardiac output in right heart failure in conjunction with pulmonary hypertension. Am J Respir Crit Care Med. 2007;175:846–50.
Rich S, Seidlitz M, Dodin E, Osimani D, Judd D, Genthner D, et al. The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest. 1998;114(3):787-92.
De Man FS, Handoko ML, van Ballegoij JJ, Schalij I, Bogaards SJ, Postmus PE, et al. Bisoprolol delays progression towards right heart failure in experimental pulmonary hypertension. Circ Heart Fail. 2012;5(1):97-105.
Bogaard HJ, Natarajan R, Mizuno S, Abbate A, Chang PJ, Chau VQ, et al. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med. 2010;182(5):652-60.
Provencher S, Herve P, Jais X, Lebrec D, Humbert M, Simonneau G, Sitbon O. Deleterious effects of β-blockers on exercise capacity and hemodynamics in patients with aortopulmonary hypertension. Gastroenterol. 2006;130(1):120-6.
Haddad F, Ashley E, Michelakis ED. New insights for the diagnosis and management of right ventricular failure, from molecular imaging to targeted right ventricular therapy. Curr Opin Cardiol. 2010;25:131–40.
Lambermont B, D’Orio V. The role of right ventricular-pulmonary arterial coupling to differentiate between effects of inotropic agents in experimental right heart failure. Crit Care Med. 2006;34:2864–5.
Kerbaul F, Rondelet B, Motte S, Fesler P, Hubloue I, Ewalenko P, Naeije R, Brimioulle S. Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure. Crit Care Med. 2004 Apr 1;32(4):1035-40.
Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galié N, et al. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013;127(10):1128-38.
Ghofrani HA, Morrell NW, Hoeper MM, Olschewski H, Peacock AJ, Barst RJ, et al. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am J Respir Crit Care Med. 2010;182(9):1171-7.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Pakistan Journal of Chest Medicine
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
