Skip to main content

Advertisement

SpringerLink
Log in

The right ventricle and pulmonary hypertension

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

In patients with pulmonary hypertension (PH), the primary cause of death is right ventricular (RV) failure. Improvement in RV function is therefore one of the most important treatment goals. In order to be able to reverse RV dysfunction and also prevent RV failure, a detailed understanding of the pathobiology of RV failure and the underlying mechanisms concerning the transition from a pressure-overloaded adapted right ventricle to a dilated and failing right ventricle is required. Here, we propose that insufficient RV contractility, myocardial fibrosis, capillary rarefaction, and a disturbed metabolism are important features of a failing right ventricle. Furthermore, an overview is provided about the potential direct RV effects of PH-targeted therapies and the effects of RV-directed medical treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Mohammed SF, Hussain I, AbouEzzeddine OF et al (2014) Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation 130:2310–2320. doi:10.1161/CIRCULATIONAHA.113.008461

    Article  PubMed  PubMed Central  Google Scholar 

  2. Meyer P, Filippatos GS, Ahmed MI et al (2010) Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure. Circulation 121:252–258. doi:10.1161/CIRCULATIONAHA.109.887570

    Article  PubMed  PubMed Central  Google Scholar 

  3. Pasque MK, Trulock EP, Cooper JD et al (1995) Single lung transplantation for pulmonary hypertension. Single institution experience in 34 patients. Circulation 92:2252–2258

    Article  CAS  PubMed  Google Scholar 

  4. Reesink HJ, Marcus JT, Tulevski II et al (2007) Reverse right ventricular remodeling after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: utility of magnetic resonance imaging to demonstrate restoration of the right ventricle. J Thorac Cardiovasc Surg 133:58–64

    Article  PubMed  Google Scholar 

  5. Oakley C (1988) Importance of right ventricular function in congestive heart failure. Am J Cardiol 62:14A–19A

    Article  CAS  PubMed  Google Scholar 

  6. Sandoval J, Bauerle O, Palomar A et al (1994) Survival in primary pulmonary hypertension. Validation of a prognostic equation. Circulation 89:1733–1744

    Article  CAS  PubMed  Google Scholar 

  7. D’Alonzo GE, Barst RJ, Ayres SM et al (1991) Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115:343–349

    Article  PubMed  Google Scholar 

  8. Fuster V, Steele PM, Edwards WD et al (1984) Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 70:580–587

    Article  CAS  PubMed  Google Scholar 

  9. Hopkins WE, Ochoa LL, Richardson GW, Trulock EP (1996) Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome. J Heart Lung Transplant 15:100–105

    CAS  PubMed  Google Scholar 

  10. Simonneau G, Gatzoulis MA, Adatia I et al (2013) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62:D34–D41. doi:10.1016/j.jacc.2013.10.029

    Article  PubMed  Google Scholar 

  11. Galiè N, Corris PA, Frost A et al (2013) Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol 62:D60–D72. doi:10.1016/j.jacc.2013.10.031

    Article  PubMed  Google Scholar 

  12. Vonk-Noordegraaf A, Haddad F, Chin KM et al (2013) Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 62:D22–D33. doi:10.1016/j.jacc.2013.10.027

    Article  PubMed  Google Scholar 

  13. van de Veerdonk MC, Marcus JT, Bogaard HJ, Vonk Noordegraaf A (2015) Cardiac MRI and PET scanning in right ventricular failure. In: Voelkel NF, Schranz D (eds) The right ventricle in health and disease, 1st edn. Springer, New York, pp 265–281

    Google Scholar 

  14. van de Veerdonk MC, Marcus JT, Westerhof N et al (2015) Signs of right ventricular deterioration in clinically stable patients with pulmonary arterial hypertension. Chest 147:1063–1071. doi:10.1378/chest.14-0701

    Article  PubMed  Google Scholar 

  15. Mauritz GJ, Vonk-Noordegraaf A, Kind T et al (2012) Pulmonary endarterectomy normalizes interventricular dyssynchrony and right ventricular systolic wall stress. J Cardiovasc Magn Reson 12(14):5. doi:10.1186/1532-429X-14-5

    Article  Google Scholar 

  16. Greyson CR (2008) Pathophysiology of right ventricular failure. Crit Care Med 36:S57–S65. doi:10.1097/01.CCM.0000296265.52518.70

    Article  PubMed  Google Scholar 

  17. Hinderliter AL, Willis PW, Long WA et al (2003) Frequency and severity of tricuspid regurgitation determined by Doppler echocardiography in primary pulmonary hypertension. Am J Cardiol 91(1033–7):A9

    Google Scholar 

  18. Lyon RC, Zanella F, Omens JH, Sheikh F (2015) Mechanotransduction in cardiac hypertrophy and failure. Circ Res 116:1462–1476. doi:10.1161/CIRCRESAHA.116.304937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Swift AJ, Rajaram S, Campbell MJ et al (2014) Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging 7:100–106. doi:10.1161/CIRCIMAGING.113.000338

    Article  PubMed  Google Scholar 

  20. van Wolferen SA, Marcus JT, Boonstra A et al (2007) Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J 28:1250–1257

    Article  PubMed  Google Scholar 

  21. Hagger D, Condliffe R, Woodhouse N et al (2009) Ventricular mass index correlates with pulmonary artery pressure and predicts survival in suspected systemic sclerosis-associated pulmonary arterial hypertension. Rheumatology (Oxford) 48:1137–1142. doi:10.1093/rheumatology/kep187

    Article  Google Scholar 

  22. Hopkins WE, Waggoner AD (2002) Severe pulmonary hypertension without right ventricular failure: the unique hearts of patients with Eisenmenger syndrome. Am J Cardiol 89:34–38

    Article  PubMed  Google Scholar 

  23. Kawut SM, Barr RG, Lima JA et al (2012) Right ventricular structure is associated with the risk of heart failure and cardiovascular death: the Multi-Ethnic Study of Atherosclerosis (MESA)–right ventricle study. Circulation 126:1681–1688. doi:10.1161/CIRCULATIONAHA.112.095216

    Article  PubMed  PubMed Central  Google Scholar 

  24. Schranz D, Rupp S, Müller M et al (2013) Pulmonary artery banding in infants and young children with left ventricular dilated cardiomyopathy: a novel therapeutic strategy before heart transplantation. J Heart Lung Transplant 32:475–481. doi:10.1016/j.healun.2013.01.988

    Article  PubMed  Google Scholar 

  25. Brimouille S, Wauthy P, Ewalenko P et al (2003) Single-beat estimation of right ventricular end-systolic pressure–volume relationship. Am J Physiol Heart Circ Physiol 284:H1625–H1630

    Article  Google Scholar 

  26. Suga H, Sagawa K, Shoukas AA (1973) Load independence of the instantaneous pressure–volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 32:314–322

    Article  CAS  PubMed  Google Scholar 

  27. Rain S, Handoko ML, Trip P et al (2013) Right ventricular diastolic impairment in patients with pulmonary arterial hypertension. Circulation 128(2016–25):1–10. doi:10.1161/CIRCULATIONAHA.113.001873

    Google Scholar 

  28. Tedford RJ, Mudd JO, Girgis RE et al (2013) Right ventricular dysfunction in systemic sclerosis-associated pulmonary arterial hypertension. Circ Heart Fail 6:953–963

    Article  CAS  PubMed  Google Scholar 

  29. Kuehne T, Yilmaz S, Steendijk P et al (2004) Magnetic resonance imaging analysis of right ventricular pressure–volume loops: in vivo validation and clinical application in patients with pulmonary hypertension. Circulation 110:2010–2016

    Article  PubMed  Google Scholar 

  30. Spruijt OA, de Man FS, Groepenhoff H et al (2015) The effects of exercise on right ventricular contractility and right ventricular–arterial coupling in pulmonary hypertension. Am J Respir Crit Care Med 191:1050–1057. doi:10.1164/rccm.201412-2271OC

    Article  CAS  PubMed  Google Scholar 

  31. Lau EM, Chemla D, Godinas L et al (2015) Loss of vascular distensibility during exercise is an early hemodynamic marker of pulmonary vascular disease. Chest. doi:10.1378/chest.15-0125

    Google Scholar 

  32. Gan CT, Holverda S, Marcus JT et al (2007) Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients. Chest 132:11–17

    Article  CAS  PubMed  Google Scholar 

  33. Trip P, Rain S, Handoko ML et al (2015) Clinical relevance of right ventricular diastolic stiffness in pulmonary hypertension. Eur Respir J 45:1603–1612. doi:10.1183/09031936.00156714

    Article  PubMed  Google Scholar 

  34. Murch SD, La Gerche A, Roberts TJ et al (2015) Abnormal right ventricular relaxation in pulmonary hypertension. Pulm Circ 5:370–375. doi:10.1086/681268

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gomez-Arroyo J, Santos-Martinez LE, Aranda A et al (2014) Differences in right ventricular remodeling secondary to pressure overload in patients with pulmonary hypertension. Am J Respir Crit Care Med 189:603–606. doi:10.1164/rccm.201309-1711LE

    Article  PubMed  Google Scholar 

  36. Karamitsos TD, Francis JM, Myerson S et al (2009) The role of cardiovascular magnetic resonance imaging in heart failure. J Am Coll Cardiol 54:1407–1424. doi:10.1016/j.jacc.2009.04.094

    Article  PubMed  Google Scholar 

  37. McCann GP, Gan CT, Beek AM et al (2007) Extent of MRI delayed enhancement of myocardial mass is related to right ventricular dysfunction in pulmonary artery hypertension. Am J Roentgenol 188:349–355

    Article  Google Scholar 

  38. Broberg CS, Prasad SK, Carr C et al (2014) Myocardial fibrosis in Eisenmenger syndrome: a descriptive cohort study exploring associations of late gadolinium enhancement with clinical status and survival. J Cardiovasc Magn Reson 16:32. doi:10.1186/1532-429X-16-32

    Article  PubMed  PubMed Central  Google Scholar 

  39. Swift AJ, Rajaram S, Capener D et al (2014) LGE patterns in pulmonary hypertension do not impact overall mortality. JACC Cardiovasc Imaging 7:1209–1217. doi:10.1016/j.jcmg.2014.08.014

    Article  PubMed  Google Scholar 

  40. Sanz J, Dellegrottaglie S, Kariisa M et al (2007) Prevalence and correlates of septal delayed contrast enhancement in patients with pulmonary hypertension. Am J Cardiol 100:731–735

    Article  PubMed  Google Scholar 

  41. Blyth KG, Syyed R, Chalmers J et al (2005) Pulmonary arterial pulse pressure and mortality in pulmonary arterial hypertension. Respir Med 101:2495–2501

    Article  Google Scholar 

  42. Bandula S, White SK, Flett AS et al (2013) Measurement of myocardial extracellular volume fraction by using equilibrium contrast-enhanced CT: validation against histologic findings. Radiology 269:396–403. doi:10.1148/radiol.13130130

    Article  PubMed  Google Scholar 

  43. Guihaire J, Bogaard HJ, Flécher E et al (2013) Experimental models of right heart failure: a window for translational research in pulmonary hypertension. Semin Respir Crit Care Med 34:689–699. doi:10.1055/s-0033-1355444

    Article  PubMed  Google Scholar 

  44. Drake JI, Bogaard HJ, Mizuno S et al (2011) Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol 45:1239–1247. doi:10.1165/rcmb.2010-0412OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bogaard HJ, Natarajan R, Henderson SC et al (2009) Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 120:1951–1960. doi:10.1161/CIRCULATIONAHA.109.883843

    Article  PubMed  Google Scholar 

  46. Bishop JE, Rhodes S, Laurent GJ et al (1994) Increased collagen synthesis and decreased collagen degradation in right ventricular hypertrophy induced by pressure overload. Cardiovasc Res 28:1581–1585

    Article  CAS  PubMed  Google Scholar 

  47. Leask A (2015) Getting to the heart of the matter: new insights into cardiac fibrosis. Circ Res 116:1269–1276. doi:10.1161/CIRCRESAHA.116.305381

    Article  CAS  PubMed  Google Scholar 

  48. Farahmand F, Hill MF, Singal PK (2004) Antioxidant and oxidative stress changes in experimental cor pulmonale. Mol Cell Biochem 260:21–29

    Article  PubMed  Google Scholar 

  49. Redout EM, Wagner MJ, Zuidwijk MJ et al (2007) Right-ventricular failure is associated with increased mitochondrial complex II activity and production of reactive oxygen species. Cardiovasc Res 75:770–781

    Article  CAS  PubMed  Google Scholar 

  50. Cucoranu I, Clempus R, Dikalova A et al (2005) NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 97:900–907

    Article  CAS  PubMed  Google Scholar 

  51. Yet SF, Perrella MA, Layne MD et al (1999) Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice. J Clin Invest 103:R23–R29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hinkel R, Lange P, Petersen B et al (2015) Heme oxygenase-1 gene therapy provides cardioprotection via control of post-ischemic inflammation: an experimental study in a pre-clinical pig model. J Am Coll Cardiol 66:154–165. doi:10.1016/j.jacc.2015.04.064

    Article  CAS  PubMed  Google Scholar 

  53. Wong YY, Westerhof N, Ruiter G et al (2011) Systolic pulmonary artery pressure and heart rate are main determinants of oxygen consumption in the right ventricular myocardium of patients with idiopathic pulmonary arterial hypertension. Eur J Heart Fail 13:1290–1295. doi:10.1093/eurjhf/hfr140

    Article  CAS  PubMed  Google Scholar 

  54. Wong YY, Ruiter G, Lubberink M et al (2011) Right ventricular failure in idiopathic pulmonary arterial hypertension is associated with inefficient myocardial oxygen utilization. Circ Heart Fail 4:700–706. doi:10.1161/CIRCHEARTFAILURE.111.962381

    Article  CAS  PubMed  Google Scholar 

  55. Vogel-Claussen J, Skrok J, Shehata ML et al (2011) Right and left ventricular myocardial perfusion reserves correlate with right ventricular function and pulmonary hemodynamics in patients with pulmonary arterial hypertension. Radiology 258:119–127. doi:10.1148/radiol.10100725

    Article  PubMed  PubMed Central  Google Scholar 

  56. Wong YY, Raijmakers PG, Knaapen P et al (2011) Supine-exercise-induced oxygen supply to the right myocardium is attenuated in patients with severe idiopathic pulmonary arterial hypertension. Heart 97:2069–2074. doi:10.1136/heartjnl-2011-300237

    Article  CAS  PubMed  Google Scholar 

  57. van Wolferen SA, Marcus JT, Westerhof N et al (2008) Right coronary artery flow impairment in patients with pulmonary hypertension. Eur Heart J 29:120–127

    Article  PubMed  Google Scholar 

  58. Ruiter G, Ying Wong Y, de Man FS et al (2013) Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hypertension. J Heart Lung Transplant 32:231–240. doi:10.1016/j.healun.2012.09.025

    Article  PubMed  Google Scholar 

  59. Sutendra G, Dromparis P, Paulin R et al (2013) A metabolic remodeling in right ventricular hypertrophy is associated with decreased angiogenesis and a transition from a compensated to a decompensated state in pulmonary hypertension. J Mol Med (Berl) 91:1315–1327. doi:10.1007/s00109-013-1059-4

    Article  CAS  Google Scholar 

  60. Bogaard HJ, Natarajan R, Mizuno S et al (2010) Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med 182:652–660. doi:10.1164/rccm.201003-0335OC

    Article  CAS  PubMed  Google Scholar 

  61. Handoko ML, de Man FS, Happé CM et al (2009) Opposite effects of training in rats with stable and progressive pulmonary hypertension. Circulation 120:42–49. doi:10.1161/CIRCULATIONAHA.108.829713

    Article  CAS  PubMed  Google Scholar 

  62. May D, Gilon D, Djonov V et al (2008) Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation. Proc Natl Acad Sci USA 105:282–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Potus F, Ruffenach G, Dahou A et al (2015) Downregulation of miR-126 contributes to the failing right ventricle in pulmonary arterial hypertension. Circulation 132:932–943. doi:10.1161/CIRCULATIONAHA.115.016382

    Article  CAS  PubMed  Google Scholar 

  64. Al-Husseini A, Kraskauskas D, Mezzaroma E et al (2015) Vascular endothelial growth factor receptor 3 signaling contributes to angioobliterative pulmonary hypertension. Pulm Circ 5:101–116. doi:10.1086/679704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kivelä R, Bry M, Robciuc MR et al (2014) VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart. EMBO Mol Med 6:307–321. doi:10.1002/emmm.201303147

    PubMed  PubMed Central  Google Scholar 

  66. Dávila-Román VG, Vedala G, Herrero P et al (2002) Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 40:271–277

    Article  PubMed  Google Scholar 

  67. Nagaya N, Goto Y, Satoh T, Uematsu M et al (1998) Impaired regional fatty acid uptake and systolic dysfunction in hypertrophied right ventricle. J Nucl Med 39:1676–1680

    CAS  PubMed  Google Scholar 

  68. Lundgrin EL, Park MM, Sharp J et al (2013) Fasting 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year. Ann Am Thorac Soc 10:1–9. doi:10.1513/AnnalsATS.201206-029OC

    Article  PubMed  PubMed Central  Google Scholar 

  69. Oikawa M, Kagaya Y, Otani H et al (2005) Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol. J Am Coll Cardiol 45:1849–1855

    Article  CAS  PubMed  Google Scholar 

  70. Graham BB, Kumar R, Mickael C et al (2015) Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake. Am J Physiol Lung Cell Mol Physiol. doi:10.1152/ajplung.00169.2015

    PubMed  Google Scholar 

  71. Fang YH, Piao L, Hong Z et al (2012) Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle’s cycle. J Mol Med (Berl) 90:31–43. doi:10.1007/s00109-011-0804-9

    Article  CAS  Google Scholar 

  72. Piao L, Fang YH, Cadete VJ et al (2010) The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: resuscitating the hibernating right ventricle. J Mol Med (Berl) 88:47–60. doi:10.1007/s00109-009-0524-6

    Article  CAS  Google Scholar 

  73. Ventetuolo CE, Baird GL, Barr RG et al (2015) Higher estradiol and lower dehydroepiandrosterone-sulfate levels are associated with pulmonary arterial hypertension in men. Am J Respir Crit Care Med. doi:10.1164/rccm.201509-1785OC

    Google Scholar 

  74. Ventetuolo CE, Ouyang P, Bluemke DA et al (2011) Sex hormones are associated with right ventricular structure and function: the MESA-right ventricle study. Am J Respir Crit Care Med 183:659–667. doi:10.1164/rccm.201007-1027O

    Article  PubMed  PubMed Central  Google Scholar 

  75. Jacobs W, van de Veerdonk MC, Trip P et al (2014) The right ventricle explains sex differences in survival in idiopathic pulmonary arterial hypertension. Chest 145:1230–1236. doi:10.1378/chest.13-1291

    Article  PubMed  PubMed Central  Google Scholar 

  76. Rafikova O, Rafikov R, Meadows ML et al (2015) The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype. Pulm Circ 5:184–197. doi:10.1086/679724

    Article  PubMed  PubMed Central  Google Scholar 

  77. Hemnes AR, Maynard KB, Champion HC et al (2012) Testosterone negatively regulates right ventricular load stress responses in mice. Pulm Circ 2:352–358. doi:10.4103/2045-8932.101647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lahm T, Albrecht M, Fisher AJ et al (2012) 17β-Estradiol attenuates hypoxic pulmonary hypertension via estrogen receptor-mediated effects. Am J Respir Crit Care Med 185:965–980. doi:10.1164/rccm.201107-1293OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu A, Schreier D, Tian L et al (2014) Direct and indirect protection of right ventricular function by estrogen in an experimental model of pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 307:H273–H283. doi:10.1152/ajpheart.00758.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Nadadur RD, Umar S, Wong G et al (2012) Reverse right ventricular structural and extracellular matrix remodeling by estrogen in severe pulmonary hypertension. J Appl Physiol 113:149–158. doi:10.1152/japplphysiol.01349.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Umar S, Iorga A, Matori H, Nadadur RD et al (2011) Estrogen rescues preexisting severe pulmonary hypertension in rats. Am J Respir Crit Care Med 184:715–723. doi:10.1164/rccm.201101-0078OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wood J, Albrecht M, Fisher A et al (2013) 17Beta-estradiol (E2) improves right ventricular (RV) function and exercise capacity in Su5416/Hypoxia (SuHx)-induced pulmonary hypertension (thoracic). Am J Respir Crit Care Med 187:A1028

    Article  Google Scholar 

  83. Witt H, Schubert C, Jaekel J et al (2008) Sex-specific pathways in early cardiac response to pressure overload in mice. J Mol Med (Berl) 86:1013–1024. doi:10.1007/s00109-008-0385-4

    Article  Google Scholar 

  84. Galiè N, Manes A, Negro L et al (2009) A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 30:394–403. doi:10.1093/eurheartj/ehp022

    Article  PubMed  PubMed Central  Google Scholar 

  85. Peacock AJ, Crawley S, McLure L et al (2014) Changes in right ventricular function measured by cardiac magnetic resonance imaging in patients receiving pulmonary arterial hypertension-targeted therapy: the EURO-MR study. Circ Cardiovasc Imaging. 7:107–114. doi:10.1161/CIRCIMAGING.113.000629

    Article  PubMed  Google Scholar 

  86. Nagendran J, Sutendra G, Paterson I et al (2013) Endothelin axis is upregulated in human and rat right ventricular hypertrophy. Circ Res 112:347–354. doi:10.1161/CIRCRESAHA.111.300448

    Article  CAS  PubMed  Google Scholar 

  87. Jasmin JF, Cernacek P, Dupuis J (2003) Activation of the right ventricular endothelin (ET) system in the monocrotaline model of pulmonary hypertension: response to chronic ETA receptor blockade. Clin Sci (Lond) 105:647–653

    Article  CAS  Google Scholar 

  88. Nagendran J, Archer SL, Soliman D et al (2007) Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation 116:238–248

    Article  CAS  PubMed  Google Scholar 

  89. Borgdorff MA, Bartelds B, Dickinson MG et al (2012) Sildenafil enhances systolic adaptation, but does not prevent diastolic dysfunction, in the pressure-loaded right ventricle. Eur J Heart Fail 14:1067–1074. doi:10.1093/eurjhf/hfs094

    Article  CAS  PubMed  Google Scholar 

  90. Borgdorff MA, Bartelds B, Dickinson MG et al (2014) Sildenafil treatment in established right ventricular dysfunction improves diastolic function and attenuates interstitial fibrosis independent from afterload. Am J Physiol Heart Circ Physiol 307:H361–H369. doi:10.1152/ajpheart.00843.2013

    Article  CAS  PubMed  Google Scholar 

  91. Gomez-Arroyo J, Sakagami M, Syed AA et al (2015) Iloprost reverses established fibrosis in experimental right ventricular failure. Eur Respir J 45:449–462. doi:10.1183/09031936.00188013

    Article  CAS  PubMed  Google Scholar 

  92. Wensel R, Jilek C, Dörr M et al (2009) Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension. Eur Respir J 34:895–901. doi:10.1183/09031936.00145708

    Article  CAS  PubMed  Google Scholar 

  93. Velez-Roa S, Ciarka A, Najem B et al (2004) Increased sympathetic nerve activity in pulmonary artery hypertension. Circulation 110:1308–1312

    Article  PubMed  Google Scholar 

  94. Holverda S, Gan CT, Marcus JT et al (2006) Impaired stroke volume response to exercise in pulmonary arterial hypertension. J Am Coll Cardiol 47:1732–1733

    Article  PubMed  Google Scholar 

  95. Okumura K, Kato H, Honjo O et al (2015) Carvedilol improves biventricular fibrosis and function in experimental pulmonary hypertension. J Mol Med (Berl). 93:663–674. doi:10.1007/s00109-015-1251-9

    Article  CAS  PubMed  Google Scholar 

  96. Perros F, Ranchoux B, Izikki M et al (2015) Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension. J Am Coll Cardiol 65:668–680. doi:10.1016/j.jacc.2014.11.050

    Article  CAS  PubMed  Google Scholar 

  97. de Man FS, Handoko ML, van Ballegoij JJ et al (2012) Bisoprolol delays progression towards right heart failure in experimental pulmonary hypertension. Circ Heart Fail 5:97–105. doi:10.1161/CIRCHEARTFAILURE.111.964494

    Article  PubMed  CAS  Google Scholar 

  98. Andersen S, Schultz JG, Andersen A et al (2014) Effects of bisoprolol and losartan treatment in the hypertrophic and failing right heart. J Card Fail 20:864–873. doi:10.1016/j.cardfail.2014.08.003

    Article  CAS  PubMed  Google Scholar 

  99. So PP, Davies RA, Chandy G et al (2012) Usefulness of beta-blocker therapy and outcomes in patients with pulmonary arterial hypertension. Am J Cardiol 109:1504–1509. doi:10.1016/j.amjcard.2012.01.368

    Article  CAS  PubMed  Google Scholar 

  100. Bandyopadhyay D, Bajaj NS, Zein J et al (2015) Outcomes of β-blocker use in pulmonary arterial hypertension: a propensity-matched analysis. Eur Respir J. doi:10.1183/09031936.00215514

    PubMed  Google Scholar 

  101. Grinnan D, Bogaard HJ, Grizzard J et al (2014) Treatment of group I pulmonary arterial hypertension with carvedilol is safe. Am J Respir Crit Care Med 189:1562–1564. doi:10.1164/rccm.201311-2025LE

    Article  PubMed  Google Scholar 

  102. Wang L, Li W, Yang Y et al (2015) Quantitative assessment of right ventricular glucose metabolism in idiopathic pulmonary arterial hypertension patients: a longitudinal study. Eur Heart J Cardiovasc Imaging. doi:10.1093/ehjci/jev297

  103. Cucci AR, Kline JA, Lahm T (2015) Acute right ventricular failure. In: Voelkel NF, Schranz D (eds) The right ventricle in health and disease. Springer, New York, pp 161–205

    Google Scholar 

  104. Swaminathan AC, Dusek AC, McMahon TJ (2015) Treatment-related biomarkers in pulmonary hypertension. Am J Respir Cell Mol Biol 52:663–673. doi:10.1165/rcmb.2014-0438TR

    Article  CAS  PubMed  Google Scholar 

  105. Bensley JG, Stacy VK, De Matteo R et al (2010) Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease. Eur Heart J 31:2058–2066. doi:10.1093/eurheartj/ehq104

    Article  CAS  PubMed  Google Scholar 

  106. Ruiter G, van de Veerdonk MC, Bogaard HJ et al (2014) The interventricular septum in pulmonary hypertension does not show features of right ventricular failure. Int J Cardiol 173:509–512. doi:10.1016/j.ijcard.2014.03.064

    Article  PubMed  Google Scholar 

  107. Voelkel NF, Quaife RA, Leinwand LA et al (2006) 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. Circulation 114:1883–1891

    Article  PubMed  Google Scholar 

  108. Voelkel NF, Bogaard HJ, Gomez-Arroyo J (2015) The need to recognize the pulmonary circulation and the right ventricle as an integrated functional unit: facts and hypotheses (2013 Grover Conference series). Pulm Circ 5:81–89. doi:10.1086/679702

    Article  PubMed  PubMed Central  Google Scholar 

  109. Voelkel NF, Gomez-Arroyo J, Abbate A et al (2012) Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J 40:1555–1565. doi:10.1183/09031936.00046612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Lahm T, Tuder RM, Petrache I (2014) Progress in solving the sex hormone paradox in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 307:L7–L26. doi:10.1152/ajplung.00337.2013

    Article  CAS  PubMed  Google Scholar 

  111. Thum T, Borlak J (2000) Gene expression in distinct regions of the heart. Lancet 355:979–983

    Article  CAS  PubMed  Google Scholar 

  112. Gomez-Arroyo J, Mizuno S, Szczepanek K et al (2013) Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 6:136–144. doi:10.1161/CIRCHEARTFAILURE.111.966127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Berman M, Tsui S, Vuylsteke A et al (2008) Successful extracorporeal membrane oxygenation support after pulmonary thromboendarterectomy. Ann Thorac Surg 86:1261–1267. doi:10.1016/j.athoracsur.2008.06.037

    Article  PubMed  Google Scholar 

  114. Hoopes CW, Kukreja J, Golden J et al (2013) Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation. J Thorac Cardiovasc Surg. 145:862–867. doi:10.1016/j.jtcvs.2012.12.022 (discussion 867–8)

    Article  PubMed  Google Scholar 

  115. Toyoda Y, Bhama JK, Shigemura N et al (2013) Efficacy of extracorporeal membrane oxygenation as a bridge to lung transplantation. J Thorac Cardiovasc Surg. 145:1065–1070. doi:10.1016/j.jtcvs.2012.12.067 (discussion 1070–1)

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the support from the Netherlands CardioVascular Research Initiative, the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences.

Author information

Authors and Affiliations

  1. Department of Pulmonary Diseases, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands

    Mariëlle C. van de Veerdonk & Harm J. Bogaard

  2. The Victoria Johnson Pulmonary Research Laboratory, Virginia Commonwealth University, 1220 East Broad Street, Richmond, VA, 23298, USA

    Norbert F. Voelkel

Authors
  1. Mariëlle C. van de Veerdonk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Harm J. Bogaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Norbert F. Voelkel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norbert F. Voelkel.

Ethics declarations

Conflict of interest

Dr. M.C. van de Veerdonk declares that she has no conflicts of interest or financial ties to disclose. Dr. H.J. Bogaard receives speaker fees form Actelion, Pfizer, Bayer and is part of the advisory board of United Therapeutics and has received grant support from Boehringer Ingelheim and the Lung Foundation. Dr. N.F. Voelkel is part of the advisory board of Actelion and is a consultant at Insmed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van de Veerdonk, M.C., Bogaard, H.J. & Voelkel, N.F. The right ventricle and pulmonary hypertension. Heart Fail Rev 21, 259–271 (2016). https://doi.org/10.1007/s10741-016-9526-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-016-9526-y

Keywords

Search

Navigation