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The Right Ventricle: From Embryologic Development to RV Failure

  • Focus on the Right Heart (S. Rosenkranz, Section Editor)
  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The right ventricle (RV) and left ventricle (LV) have different developmental origins, which likely plays a role in their chamber-specific response to physiological and pathological stress. RV dysfunction is encountered frequently in patients with congenital heart disease (CHD) and right heart abnormalities emerge from different causes than increased afterload alone as is observed in RV dysfunction due to pulmonary hypertension (PH). In this review, we describe the developmental, structural, and functional differences between ventricles while highlighting emerging therapies for RV dysfunction.

Recent Findings

There are new insights into the role of fibrosis, inflammation, myocyte contraction, and mitochondrial dynamics in the pathogenesis of RV dysfunction. We discuss the current state of therapies that may potentially improve RV function in both experimental and clinical trials.

Summary

A clearer understanding of the differences in molecular alterations in the RV compared to the LV may allow for the development of better therapies that treat RV dysfunction.

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References

Papers of particular interest, published recently, have been highlighted as: •Of importance  

  1. • Sanz J, Sánchez-Quintana D, Bossone E, Bogaard HJ, Naeije R. Anatomy, function, and dysfunction of the right ventricle: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(12):1463–82. In this article, the authors provide a contemporaneous review of right ventricular anatomy, physiology, and hemodynamics while highlighting how the right ventricle plays an essential role in determining prognosis in nearly all cardiovascular disorders.

  2. Srivastava D, Olson EN. A genetic blueprint for cardiac development. Nature. 2000;407(6801):221–6. https://doi.org/10.1038/35025190.

    Article  CAS  PubMed  Google Scholar 

  3. Thomas T, Yamagishi H, Overbeek PA, Olson EN, Srivastava D. The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Dev Biol. 1998;196(2):228–36. https://doi.org/10.1006/dbio.1998.8849.

    Article  CAS  PubMed  Google Scholar 

  4. Rudolph AM. Congenital cardiovascular malformations and the fetal circulation. Arch Dis Child Fetal Neonatal Ed. 2010;95(2):F132–6. https://doi.org/10.1136/adc.2007.128777.

    Article  CAS  PubMed  Google Scholar 

  5. • Friedberg MK, Redington AN. Right versus left ventricular failure: differences, similarities, and interactions. Circulation. 2014;129(9):1033–44. The authors emphasize the differences between the left and right ventricle but also appropriately acknowledge that both ventricles share similar features in adaptation when faced with pressure or volume overloading conditions.

  6. Walker LA, Buttrick PM. The right ventricle: biologic insights and response to disease: updated. Curr Cardiol Rev. 2013;9(1):73–81. https://doi.org/10.2174/157340313805076296.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Guimaron S, Guihaire J, Amsallem M, Haddad F, Fadel E, Mercier O. Current knowledge and recent advances of right ventricular molecular biology and metabolism from congenital heart disease to chronic pulmonary hypertension. Biomed Res Int. 2018;17(2018):1981568. https://doi.org/10.1155/2018/1981568.

    Article  CAS  Google Scholar 

  8. Konstam MA, Kiernan MS, Bernstein D, Bozkurt B, Jacob M, Kapur NK, et al. American Heart Association Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular Surgery and Anesthesia. Evaluation and Management of Right-Sided Heart Failure: a scientific statement from the American Heart Association. Circulation. 2018;137(20):e578–e622. https://doi.org/10.1161/CIR.0000000000000560.

  9. Warnes CA. Adult congenital heart disease importance of the right ventricle. J Am Coll Cardiol. 2009; 17;54(21):1903–10. https://doi.org/10.1016/j.jacc.2009.06.048.

  10. Redington AN. Right ventricular function. Cardiol Clin. 2002;20(3):341–9. https://doi.org/10.1016/s0733-8651(02)00005-x.

  11. Sathananthan G, Grewal J. The complex relationship that is RV-PA coupling and its relevance to managing congenital heart disease. Can J Cardiol. 2019;35(7):816–8. https://doi.org/10.1016/j.cjca.2019.04.027.

    Article  PubMed  Google Scholar 

  12. Egbe AC, Kothapalli S, Miranda WR, Pislaru S, Ammash NM, Borlaug BA, et al. Assessment of right ventricular-pulmonary arterial coupling in chronic pulmonary regurgitation. Can J Cardiol. 2019;35(7):914–22. https://doi.org/10.1016/j.cjca.2019.03.009.

    Article  PubMed  Google Scholar 

  13. 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. Circulation. 2008;117(13):1717–31. https://doi.org/10.1161/CIRCULATIONAHA.107.653584.

    Article  PubMed  Google Scholar 

  14. Kürkciyan I, Meron G, Sterz F, Janata K, Domanovits H, Holzer M, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med. 2000;160(10):1529–35. https://doi.org/10.1001/archinte.160.10.1529.

    Article  PubMed  Google Scholar 

  15. Bogaard HJ, Abe K, VonkNoordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest. 2009;135(3):794–804. https://doi.org/10.1378/chest.08-0492.

    Article  CAS  PubMed  Google Scholar 

  16. Simon MA, Pinsky MR. Right ventricular dysfunction and failure in chronic pressure overload. Cardiol Res Pract. 2011;23(2011):568095. https://doi.org/10.4061/2011/568095.

    Article  Google Scholar 

  17. Anaruma CP, Pereira RM, Cristina da Cruz Rodrigues K, Ramos da Silva AS, Cintra DE, Ropelle ER, et al. Rock protein as cardiac hypertrophy modulator in obesity and physical exercise. Life Sci. 2020;254:116955. https://doi.org/10.1016/j.lfs.2019.116955.

  18. Reddy S, Bernstein D. Molecular mechanisms of right ventricular failure. Circulation. 2015;132(18):1734–42. https://doi.org/10.1161/CIRCULATIONAHA.114.012975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. van der Bruggen CEE, Tedford RJ, Handoko ML, van der Velden J, de Man FS. RV pressure overload: from hypertrophy to failure. Cardiovasc Res. 2017;113(12):1423–32. https://doi.org/10.1093/cvr/cvx145.

    Article  CAS  PubMed  Google Scholar 

  20. Davlouros PA, Niwa K, Webb G, Gatzoulis MA. The right ventricle in congenital heart disease. Heart. 2006;92 Suppl 1(Suppl 1):i27–38. https://doi.org/10.1136/hrt.2005.077438.

  21. Redington AN, Gray HH, Hodson ME, Rigby ML, Oldershaw PJ. Characterisation of the normal right ventricular pressure-volume relation by biplane angiography and simultaneous micromanometer pressure measurements. Br Heart J. 1988;59(1):23–30. https://doi.org/10.1136/hrt.59.1.23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Connelly MS, Liu PP, Williams WG, Webb GD, Robertson P, McLaughlin PR. Congenitally corrected transposition of the great arteries in the adult: functional status and complications. J Am Coll Cardiol. 1996;27(5):1238–43. https://doi.org/10.1016/0735-1097(95)00567-6.

    Article  CAS  PubMed  Google Scholar 

  23. Warnes CA. Transposition of the great arteries. Circulation. 2006;114(24):2699–709. https://doi.org/10.1161/CIRCULATIONAHA.105.592352.

    Article  PubMed  Google Scholar 

  24. Winter MM, Bouma BJ, Groenink M, Konings TC, Tijssen JG, van Veldhuisen DJ, et al. Latest insights in therapeutic options for systemic right ventricular failure: a comparison with left ventricular failure. Heart. 2009;95(12):960–3. https://doi.org/10.1136/hrt.2008.156265.

    Article  CAS  PubMed  Google Scholar 

  25. Ryan JJ, Archer SL. The right ventricle in pulmonary arterial hypertension: disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res. 2014;115(1):176–88. https://doi.org/10.1161/CIRCRESAHA.113.301129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Andersen S, Nielsen-Kudsk JE, Vonk Noordegraaf A, de Man FS. Right ventricular fibrosis. Circulation. 2019;139(2):269–85. https://doi.org/10.1161/CIRCULATIONAHA.

    Article  CAS  PubMed  Google Scholar 

  27. Sutendra G, Dromparis P, Paulin R, Zervopoulos S, Haromy A, Nagendran J, Michelakis ED. 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). 2013;91(11):1315–27. https://doi.org/10.1007/s00109-013-1059-4.

    Article  CAS  Google Scholar 

  28. 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;45(6):1239–47. https://doi.org/10.1165/rcmb.2010-0412OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Brida M, Chessa M, Celermajer D, Li W, Geva T, Khairy P, Griselli M, et al. Atrial septal defect in adulthood: a new paradigm for congenital heart disease. Eur Heart J. 2021:ehab646. https://doi.org/10.1093/eurheartj/ehab646.

  30. Walker RE, Moran AM, Gauvreau K, Colan SD. Evidence of adverse ventricular interdependence in patients with atrial septal defects. Am J Cardiol. 2004;93(11):1374–7, A6. https://doi.org/10.1016/j.amjcard.2004.02.033.

  31. Valente AM, Geva T. How to image repaired tetralogy of Fallot. Circ Cardiovasc Imaging. 2017;10(5):e004270. https://doi.org/10.1161/CIRCIMAGING.116.004270.

    Article  PubMed  Google Scholar 

  32. Modesti PA, Vanni S, Bertolozzi I, Cecioni I, Lumachi C, Perna AM, et al. Different growth factor activation in the right and left ventricles in experimental volume overload. Hypertension. 2004;43(1):101–8. https://doi.org/10.1161/01.HYP.0000104720.76179.18.

    Article  CAS  PubMed  Google Scholar 

  33. Babu-Narayan SV, Kilner PJ, Li W, Moon JC, Goktekin O, Davlouros PA, et al. Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of Fallot and its relationship to adverse markers of clinical outcome. Circulation. 2006;113(3):405–13. https://doi.org/10.1161/CIRCULATIONAHA.

    Article  CAS  PubMed  Google Scholar 

  34. Wald RM, Haber I, Wald R, Valente AM, Powell AJ, Geva T. Effects of regional dysfunction and late gadolinium enhancement on global right ventricular function and exercise capacity in patients with repaired tetralogy of Fallot. Circulation. 2009;119(10):1370–7. https://doi.org/10.1161/CIRCULATIONAHA.108.816546.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bossers GPL, Hagdorn QAJ, Ploegstra MJ, Borgdorff MAJ, Silljé HHW, Berger RMF, et al. Volume load-induced right ventricular dysfunction in animal models: insights in a translational gap in congenital heart disease. Eur J Heart Fail. 2018;20(4):808–12. https://doi.org/10.1002/ejhf.931.

    Article  PubMed  Google Scholar 

  36. Cui Q, Sun S, Zhu H, Xiao Y, Jiang C, Zhang H, et al. Volume overload initiates an immune response in the right ventricle at the neonatal stage. Front Cardiovasc Med. 2021;16(8):772336. https://doi.org/10.3389/fcvm.2021.772336.

    Article  CAS  Google Scholar 

  37. Felner JM. The Second Heart Sound. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations. 3rd ed. Boston: Butterworths; 1990. Chapter 23.

  38. Surawicz B, Knilans T (2008) Chou’s electrocardiography in clinical practice: adult and pediatric, 6th ed. W.B. Saunders, Philadelphia.

  39. Cepkova M, Kapur V, Ren X, Quinn T, Zhuo H, Foster E, et al. Clinical significance of elevated B-type natriuretic peptide in patients with acute lung injury with or without right ventricular dilatation: an observational cohort study. Ann Intensive Care. 2011;1(1):18. https://doi.org/10.1186/2110-5820-1-18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hayek S, Sims DB, Markham DW, Butler J, Kalogeropoulos AP. Assessment of right ventricular function in left ventricular assist device candidates. Circ Cardiovasc Imaging. 2014;7(2):379–89. https://doi.org/10.1161/CIRCIMAGING.113.001127.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Tadic M, Nita N, Schneider L, Kersten J, Buckert D, Gonska B, et al. The predictive value of right ventricular longitudinal strain in pulmonary hypertension, heart failure, and valvular diseases. Front Cardiovasc Med. 2021;17(8):698158. https://doi.org/10.3389/fcvm.2021.698158.

    Article  Google Scholar 

  42. Shaddy RE, Boucek MM, Hsu DT, Boucek RJ, Canter CE, Mahony L, Ross RD, et al. Pediatric Carvedilol Study Group. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA. 2007;298(10):1171–9. https://doi.org/10.1001/jama.298.10.1171.

  43. Book WM, Shaddy RE. Medical therapy in adults with congenital heart disease. Heart Fail Clin. 2014;10(1):167–78. https://doi.org/10.1016/j.hfc.2013.09.006.

    Article  PubMed  Google Scholar 

  44. Graham TP Jr, Bernard YD, Mellen BG, Celermajer D, Baumgartner H, Cetta F, et al. Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study. J Am Coll Cardiol. 2000;36(1):255–61. https://doi.org/10.1016/s0735-1097(00)00682-3.

    Article  PubMed  Google Scholar 

  45. Dubin AM, Janousek J, Rhee E, Strieper MJ, Cecchin F, Law IH, et al. Resynchronization therapy in pediatric and congenital heart disease patients: an international multicenter study. J Am Coll Cardiol. 2005;46(12):2277–83. https://doi.org/10.1016/j.jacc.2005.05.096.

    Article  PubMed  Google Scholar 

  46. Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(12):e81–192. https://doi.org/10.1016/j.jacc.2018.08.1029.

    Article  PubMed  Google Scholar 

  47. Muliawan HS, Widyantoro B, Soerarso R, Hersunarti N, Sahara E, Atmadikoesoemah CA, et al. P194 Trimetazidine preserves right ventricular function on pulmonary arterial hypertension patients in National Cardiovascular Center Harapan Kita Hospital Indonesia. Eur Heart J. 2020. https://doi.org/10.1093/ehjci/ehz872.068.

    Article  Google Scholar 

  48. Vonk Noordegraaf A, Channick R, Cottreel E, Kiely DG, Marcus JT, Martin N, et al. The REPAIR study: effects of macitentan on RV structure and function in pulmonary arterial hypertension. JACC Cardiovasc Imaging. 2022;15(2):240–53. https://doi.org/10.1016/j.jcmg.2021.07.027.

    Article  PubMed  Google Scholar 

  49. Grinnan D, Bogaard HJ, Grizzard J, Van Tassell B, Abbate A, DeWilde C, et al. Treatment of group I pulmonary arterial hypertension with carvedilol is safe. Am J Respir Crit Care Med. 2014;189(12):1562–4. https://doi.org/10.1164/rccm.201311-2025LE.

    Article  PubMed  Google Scholar 

  50. Andersen S, Birkmose Axelsen J, Ringgaard S, Randel Nyengaard J, Holm Nielsen S, Genovese F, et al. Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone. Pulm Circ. 2019;9(2):2045894019848659. https://doi.org/10.1177/2045894019848659.

  51. Gorr MW, Sriram K, Chinn AM, Muthusamy A, Insel PA. Transcriptomic profiles reveal differences between the right and left ventricle in normoxia and hypoxia. Physiol Rep. 2020;8(2):e14344. https://doi.org/10.14814/phy2.14344.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Rain S, Andersen S, Najafi A, Gammelgaard Schultz J, da Silva Gonçalves Bós D, Handoko ML, et al. Right ventricular myocardial stiffness in experimental pulmonary arterial hypertension: relative contribution of fibrosis and myofibril stiffness. Circ Heart Fail. 2016;9(7):e002636. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002636.

  53. Bernal-Ramírez J, Silva-Platas C, Jerjes-Sánchez C, Ramos-González MR, Vázquez-Garza E, Chapoy-Villanueva H, et al. Resveratrol prevents right ventricle dysfunction, calcium mishandling, and energetic failure via SIRT3 stimulation in pulmonary arterial hypertension. Oxid Med Cell Longev. 2021;20(2021):9912434. https://doi.org/10.1155/2021/9912434.

    Article  CAS  Google Scholar 

  54. 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, 178.e1–3. https://doi.org/10.1016/j.jtcvs.2008.01.040.

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Funding

B.A.M.: NIH 1R01HL139613-01, R01HL153502, R01HL155096-01, 2021A007243 BWH/MIT-Broad Institute; Cardiovascular Medical Research Foundation.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Brigham and Women’s Hospital, 77 Ave. Louis Pasteur, NRB 0630-N, Boston, MA, 02115, USA

    Matthew R. Lippmann & Bradley A. Maron

  2. Department of Cardiology, VA Boston Healthcare System, West Roxbury, MA, USA

    Bradley A. Maron

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Correspondence to Bradley A. Maron.

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Conflict of Interest

B.A.M., Deerfield Corporation (beyond the scope of this work); Actelion Sciences (beyond the scope of this work), Tenax Company (beyond the scope of this work), and Regeneron (beyond the scope of this work); patent or patent pending (beyond the scope of this work): patent 9,605,047; PCT/US2019/059890; PCT/US2020/066886.

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Lippmann, M.R., Maron, B.A. The Right Ventricle: From Embryologic Development to RV Failure. Curr Heart Fail Rep 19, 325–333 (2022). https://doi.org/10.1007/s11897-022-00572-z

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