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Current Heart Failure Reports

, Volume 15, Issue 2, pp 94–105 | Cite as

Right Ventricular Dysfunction and Its Contribution to Morbidity and Mortality in Left Ventricular Heart Failure

  • Amresh RainaEmail author
  • Talha Meeran
Pathophysiology of Myocardia Failure (I. Anand and M. Patarroyo Aponte A., Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pathophysiology of Myocardial Failure

Abstract

Purpose

In patients with left-sided HF, there has been less emphasis on the pathophysiology of the RV in terms of diagnostic evaluation and treatment, versus focus on structural abnormalities of the LV. This review seeks to delineate the importance of RV dysfunction in terms of its contribution to symptomatic limitations and cardiovascular outcomes in patients with left-sided HF.

Recent Findings

Recent studies have demonstrated that RV dysfunction is common in both HFpEF and HFrEF, but more pronounced in HFrEF. LV dysfunction and atrial fibrillation are most commonly associated with RV dysfunction in left-sided HF. RV dysfunction may develop due to afterload-dependent and afterload-independent pathways. Regardless, RV dysfunction is strongly associated with functional limitations and worsened survival in patients with left-sided HF. In patients with HFpEF, a recent study showed that RV failure was the most common cause of overall mortality. Among LVAD patients and patients post-cardiac transplantation, RV dysfunction is also strongly associated with survival. Despite a number of previous and ongoing clinical trials that target the RV directly or decrease RV afterload in left-sided HF, there are no definitive therapies specifically targeting RV dysfunction in left-sided HF patients

Conclusions

RV dysfunction is an important determinant of symptomatic limitations and cardiovascular outcomes in patients with left-sided HF. Further research is needed to developed pharmacotherapy that may target the RV specifically in left-sided HF patients.

Keywords

Right ventricular failure Heart failure outcomes RV failure mechanisms 

Abbreviations

ARVC

Arrhythmogenic right ventricular cardiomyopathy

COPD

Chronic obstructive pulmonary disease

CPCPH

Combined pre- and post-capillary pulmonary hypertension

EF

Ejection fraction

HF

Heart failure

HFpEF

Heart failure with preserved ejection fraction

HFrEF

Heart failure with reduced ejection fraction

LV

Left ventricle, left ventricular

LVEF

left ventricular ejection fraction

LVAD

Left ventricular assist device

NYHA

New York Heart Association

PA

Pulmonary artery

PASP

Pulmonary artery systolic pressure

PAH

Pulmonary arterial hypertension

PH

Pulmonary hypertension

RV

Right ventricle, right ventricular

RVAD

Right ventricular assist device

RVEF

Right ventricular ejection fraction

RVFAC

Right ventricular fractional area change

TAPSE

Tricuspid annular plane systolic excursion

WHO

World Health Organization

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

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

  1. 1.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70(6):776–803.  https://doi.org/10.1016/j.jacc.2017.04.025.CrossRefPubMedGoogle Scholar
  2. 2.
    Bristow MR, Kao DP, Breathett KK, Altman NL, Gorcsan J 3rd, Gill EA, et al. Structural and functional phenotyping of the failing heart: Is the Left Ventricular Ejection Fraction Obsolete? JACC Heart Fail. 2017;5(11):772–81.  https://doi.org/10.1016/j.jchf.2017.09.009.CrossRefPubMedGoogle Scholar
  3. 3.
    Lewis GA, Schelbert EB, Williams SG, Cunnington C, Ahmed F, McDonagh TA, et al. Biological phenotypes of heart failure with preserved ejection fraction. J Am Coll Cardiol. 2017;70(17):2186–200.  https://doi.org/10.1016/j.jacc.2017.09.006.CrossRefPubMedGoogle Scholar
  4. 4.
    Gewillig M, Brown SC. The Fontan circulation after 45 years: update in physiology. Heart. 2016;102(14):1081–6.  https://doi.org/10.1136/heartjnl-2015-307467.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46(4):903–75.  https://doi.org/10.1183/13993003.01032-2015.CrossRefPubMedGoogle Scholar
  6. 6.
    Kormos RL, Teuteberg JJ, Pagani FD, Russell SD, John R, Miller LW, et al. Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg. 2010;139(5):1316–24.  https://doi.org/10.1016/j.jtcvs.2009.11.020.CrossRefPubMedGoogle Scholar
  7. 7.
    LaRue SJ, Raymer DS, Pierce BR, Nassif ME, Sparrow CT, Vader JM. Clinical outcomes associated with INTERMACS-defined right heart failure after left ventricular assist device implantation. J Heart Lung Transplant. 2017;36(4):475–7.  https://doi.org/10.1016/j.healun.2016.12.017.CrossRefPubMedGoogle Scholar
  8. 8.
    Gulati A, Ismail TF, Jabbour A, Alpendurada F, Guha K, Ismail NA, et al. The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy. Circulation. 2013;128(15):1623–33.  https://doi.org/10.1161/CIRCULATIONAHA.113.002518.CrossRefPubMedGoogle Scholar
  9. 9.
    Pueschner A, Chattranukulchai P, Heitner JF, Shah DJ, Hayes B, Rehwald W, et al. The prevalence, correlates, and impact on cardiac mortality of right ventricular dysfunction in nonischemic cardiomyopathy. JACC Cardiovasc Imaging. 2017;10(10 Pt B):1225–36.CrossRefPubMedGoogle Scholar
  10. 10.
    • Gorter TM, Hoendermis ES, van Veldhuisen DJ, Voors AA, Lam CS, Geelhoed B, et al. Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Eur J Heart Fail. 2016;18(12):1472–87. This is the largest systematic review of studies evaluating the prevalence and significance of RV dysfunction in patients with HFpEF and the assocation between echocardiographic parameters and survival.CrossRefPubMedGoogle Scholar
  11. 11.
    Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM. Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Cardiol. 2009;53(13):1119–26.  https://doi.org/10.1016/j.jacc.2008.11.051.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Leung CC, Moondra V, Catherwood E, Andrus BW. Prevalence and risk factors of pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved ejection fraction. Am J Cardiol. 2010;106(2):284–6.  https://doi.org/10.1016/j.amjcard.2010.02.039.CrossRefPubMedGoogle Scholar
  13. 13.
    Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119.  https://doi.org/10.1093/eurheartj/ehv317.CrossRefPubMedGoogle Scholar
  14. 14.
    Gerges M, Gerges C, Pistritto AM, Lang MB, Trip P, Jakowitsch J, et al. Pulmonary hypertension in heart failure. Epidemiology, right ventricular function, and survival. Am J Respir Crit Care Med. 2015;192(10):1234–46.  https://doi.org/10.1164/rccm.201503-0529OC.CrossRefPubMedGoogle Scholar
  15. 15.
    Gorter TM, van Veldhuisen DJ, Bauersachs J, Borlaug BA, Celutkiene J, Coats AJS, Crespo-Leiro MG, Guazzi M, Harjola VP, Heymans S, Hill L, Lainscak M, Lam CSP, Lund LH, Lyon AR, Mebazaa A, Mueller C, Paulus WJ, Pieske B, Piepoli MF, Ruschitzka F, Rutten FH, Seferovic PM, Solomon SD, Shah SJ, Triposkiadis F, Wachter R, Tschöpe C, de Boer RA Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the heart failure Association of the European Society of cardiology. Eur J Heart Fail. 2017.  https://doi.org/10.1002/ejhf.1029.
  16. 16.
    Thenappan T, Shah SJ, Gomberg-Maitland M, Collander B, Vallakati A, Shroff P, et al. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circ Heart Fail. 2011;4(3):257–65.  https://doi.org/10.1161/CIRCHEARTFAILURE.110.958801.CrossRefPubMedGoogle Scholar
  17. 17.
    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.  https://doi.org/10.1161/CIRCULATIONAHA.107.653576.CrossRefPubMedGoogle Scholar
  18. 18.
    Kasner M, Westermann D, Steendijk P, Drose S, Poller W, Schultheiss HP, 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):181–9.  https://doi.org/10.1164/rccm.201110-1860OC.CrossRefPubMedGoogle Scholar
  19. 19.
    • Gorter TM, van Melle JP, Rienstra M, Borlaug BA, Hummel YM, Van Gelder IC, et al. Right heart dysfunction in heart failure with preserved ejection fraction: the impact of atrial fibrillation. J Card Fail. 2017. Recent study demonstrating strong association between atrial fibrillation and RV dysfunction as well as right atrial function in 102 patients with HFpEF. RV dysfunction was interestingly associated with atrial fibrillation independent of pulmonary artery pressures.Google Scholar
  20. 20.
    Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. 2014;35(48):3452–62.  https://doi.org/10.1093/eurheartj/ehu193.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mohammed SF, Hussain I, AbouEzzeddine OF, Takahama H, Kwon SH, Forfia P, et al. Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation. 2014;130(25):2310–20.  https://doi.org/10.1161/CIRCULATIONAHA.113.008461.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Alam M, Samad BA, Hedman A, Frick M, Nordlander R. Cardioversion of atrial fibrillation and its effect on right ventricular function as assessed by tricuspid annular motion. Am J Cardiol. 1999;84(10):1256–8, A8.  https://doi.org/10.1016/S0002-9149(99)00542-1.CrossRefPubMedGoogle Scholar
  23. 23.
    Sivak JA, Raina A, Forfia PR. Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension. Pulm Circ. 2016;6(3):322–8.  https://doi.org/10.1086/687767.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hwang SJ, Melenovsky V, Borlaug BA. Implications of coronary artery disease in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2014;63(25 Pt A):2817–27.CrossRefPubMedGoogle Scholar
  25. 25.
    • Srivaratharajah K, Coutinho T, deKemp R, Liu P, Haddad H, Stadnick E, et al. Reduced myocardial flow in heart failure patients with preserved ejection fraction. Circ Heart Fail. 2016;9(7). Study of 78 HFpEF patients without obstructive CAD who underwent Rubidium PET scanning to assess quantitative myocardial flow reserve. Flow reserved was substantially reduced in HFpEF patients vs. 298 hypertensive control patients, illustrating the presence of microvascular disease in these patients.Google Scholar
  26. 26.
    Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation. 2017;136(1):6–19.  https://doi.org/10.1161/CIRCULATIONAHA.116.026807.CrossRefPubMedGoogle Scholar
  27. 27.
    Minai OA, Ricaurte B, Kaw R, Hammel J, Mansour M, McCarthy K, et al. Frequency and impact of pulmonary hypertension in patients with obstructive sleep apnea syndrome. Am J Cardiol. 2009;104(9):1300–6.  https://doi.org/10.1016/j.amjcard.2009.06.048.CrossRefPubMedGoogle Scholar
  28. 28.
    Hilde JM, Skjorten I, Grotta OJ, Hansteen V, Melsom MN, Hisdal J, et al. Right ventricular dysfunction and remodeling in chronic obstructive pulmonary disease without pulmonary hypertension. J Am Coll Cardiol. 2013;62(12):1103–11.  https://doi.org/10.1016/j.jacc.2013.04.091.CrossRefPubMedGoogle Scholar
  29. 29.
    Burke MA, Katz DH, Beussink L, Selvaraj S, Gupta DK, Fox J, et al. Prognostic importance of pathophysiologic markers in patients with heart failure and preserved ejection fraction. Circ Heart Fail. 2014;7(2):288–99.  https://doi.org/10.1161/CIRCHEARTFAILURE.113.000854.CrossRefPubMedGoogle Scholar
  30. 30.
    • Borlaug BA, Kane GC, Melenovsky V, Olson TP. Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction. Eur Heart J. 2016;37(43):3293–302. Invasive cardiopulmonary exercise study of 50 patients with HFpEF vs. 24 controls which demonstrated increased in biventicular filling pressures, blunted increased in cardiac output, stroke volume and cardiac output relative to O2 consumption in HFpEF patients with exercsie. This provided insight into limited RV reserve with activity as well as LV reserve as a driver of symptomatic limitations.CrossRefPubMedGoogle Scholar
  31. 31.
    • Guazzi M, Dixon D, Labate V, Beussink-Nelson L, Bandera F, Cuttica MJ, et al. RV contractile function and its coupling to pulmonary circulation in heart failure with preserved ejection fraction: stratification of clinical phenotypes and outcomes. JACC Cardiovasc Imaging. 2017;10(10 Pt B):1211–21. This large study stratified 378 HFpEF patients into tertiles based upon TAPSE/PASP ratio, a measure of RV/PA coupling derived from echocardiography. This study confirmed the utility of this simply measured echocardiographic metric in risk stratification of HFpEF patients above and beyond standard demographic factors.CrossRefPubMedGoogle Scholar
  32. 32.
    • Mukherjee M, Sharma K, Madrazo JA, Tedford RJ, Russell SD, Hays AG. Right-sided cardiac dysfunction in heart failure with preserved ejection fraction and worsening renal function. Am J Cardiol. 2017;120(2):274–8. This study is one of the first to demonstrate an association between decreased RV function and increased RV wall thickness and worsening renal function among patients with HFpEF hospitalized for acute decompensated HF.CrossRefPubMedGoogle Scholar
  33. 33.
    • Aschauer S, Zotter-Tufaro C, Duca F, Kammerlander A, Dalos D, Mascherbauer J, et al. Modes of death in patients with heart failure and preserved ejection fraction. Int J Cardiol. 2017;228:422–6. Important, prospective registry of 230 patients with HFpEF which delineated the cause of death in these patients over close follow up. The study demonstrated that right heart failure was not only the most common cause of cardiovascular death in HFpEF patients, but was also the leading cause of mortality overall.CrossRefPubMedGoogle Scholar
  34. 34.
    Agarwal R, Shah SJ, Foreman AJ, Glassner C, Bartolome SD, Safdar Z, et al. Risk assessment in pulmonary hypertension associated with heart failure and preserved ejection fraction. J Heart Lung Transplant. 2012;31(5):467–77.  https://doi.org/10.1016/j.healun.2011.11.017.CrossRefPubMedGoogle Scholar
  35. 35.
    Cenkerova K, Dubrava J, Pokorna V, Kaluzay J, Jurkovicova O. Right ventricular systolic dysfunction and its prognostic value in heart failure with preserved ejection fraction. Acta Cardiol. 2015;70(4):387–93.CrossRefPubMedGoogle Scholar
  36. 36.
    Raeisi-Giglou P, Lam L, Tamarappoo BK, Newman J, Dweik RA, Tonelli AR. Evaluation of left ventricular diastolic function profile in patients with pulmonary hypertension due to heart failure with preserved ejection fraction. Clin Cardiol. 2017;40(6):356–63.  https://doi.org/10.1002/clc.22664.CrossRefPubMedGoogle Scholar
  37. 37.
    Guazzi M, Bandera F, Pelissero G, Castelvecchio S, Menicanti L, Ghio S, et al. Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis. Am J Physiol Heart Circ Physiol. 2013;305(9):H1373–81.  https://doi.org/10.1152/ajpheart.00157.2013.CrossRefPubMedGoogle Scholar
  38. 38.
    • Bosch L, Lam CSP, Gong L, Chan SP, Sim D, Yeo D, et al. Right ventricular dysfunction in left-sided heart failure with preserved versus reduced ejection fraction. Eur J Heart Fail. 2017. Echocardiographic study of 657 patients with either HFpEF, HFrEF or normal controls, demonstrating that RV dysfunction is more pronounced in HFrEF than HFpEF and is associated with LV dysfunction and atrial fibrillation. This study also confirmed that echocardiographic measures of RV/PA coupling were prognostically important.Google Scholar
  39. 39.
    Gude E, Simonsen S, Geiran OR, Fiane AE, Gullestad L, Arora S, et al. Pulmonary hypertension in heart transplantation: discrepant prognostic impact of pre-operative compared with 1-year post-operative right heart hemodynamics. J Heart Lung Transplant. 2010;29(2):216–23.  https://doi.org/10.1016/j.healun.2009.08.021.CrossRefPubMedGoogle Scholar
  40. 40.
    Chang PP, Longenecker JC, Wang NY, Baughman KL, Conte JV, Hare JM, et al. Mild vs severe pulmonary hypertension before heart transplantation: different effects on posttransplantation pulmonary hypertension and mortality. J Heart Lung Transplant. 2005;24(8):998–1007.  https://doi.org/10.1016/j.healun.2004.07.013.CrossRefPubMedGoogle Scholar
  41. 41.
    Pfisterer M, Emmenegger H, Muller-Brand J, Burkart F. Prevalence and extent of right ventricular dysfunction after myocardial infarction—relation to location and extent of infarction and left ventricular function. Int J Cardiol. 1990;28(3):325–32.  https://doi.org/10.1016/0167-5273(90)90315-V.CrossRefPubMedGoogle Scholar
  42. 42.
    Zornoff LA, Skali H, Pfeffer MA, St John Sutton M, Rouleau JL, Lamas GA, et al. Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction. J Am Coll Cardiol. 2002;39(9):1450–5.  https://doi.org/10.1016/S0735-1097(02)01804-1.CrossRefPubMedGoogle Scholar
  43. 43.
    • Ghio S, Guazzi M, Scardovi AB, Klersy C, Clemenza F, Carluccio E, et al. Different correlates but similar prognostic implications for right ventricular dysfunction in heart failure patients with reduced or preserved ejection fraction. Eur J Heart Fail. 2017;19(7):873–9. Very large study of 1663 HF patients with HFrEF and HFpEF, delineating different correlates of RV dsyfunction in HFpEF vs. HFrEF patients. Regardless of LV function, the TAPSE/PASP ratio was a powerful independent predictor of prognosis in this cohort.CrossRefPubMedGoogle Scholar
  44. 44.
    Guazzi M, Naeije R. Pulmonary hypertension in heart failure: pathophysiology, pathobiology, and emerging clinical perspectives. J Am Coll Cardiol. 2017;69(13):1718–34.CrossRefPubMedGoogle Scholar
  45. 45.
    • Abraityte A, Lunde IG, Askevold ET, Michelsen AE, Christensen G, Aukrust P, et al. Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy. Sci Rep. 2017;7(1):3490. Novel molecular study which demonstrated an association between expression of Wnt5a, RV dysfunction and adverse outcomes in patients with dilated cardiomyopathy.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2016;68(13):1476–88.  https://doi.org/10.1016/j.jacc.2016.05.011.CrossRefPubMedGoogle Scholar
  47. 47.
    Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol. 1995;25(5):1143–53.  https://doi.org/10.1016/0735-1097(94)00511-N.CrossRefPubMedGoogle Scholar
  48. 48.
    • Kim J, Di Franco A, Seoane T, Srinivasan A, Kampaktsis PN, Geevarghese A, et al. Right ventricular dysfunction impairs effort tolerance independent of left ventricular function among patients undergoing exercise stress myocardial perfusion imaging. Circ Cardiovasc Imaging. 2016;9(11). Novel study which demonstrated an association between regional LV ischemia in patients undergoing myocardial stress perfusion imaging and increased likelihood of RV dysfunction. Interestingly, this study demonstrated that RV dysfunction impacted exercise tolerance independent of LV dysfunction.Google Scholar
  49. 49.
    Meluzin J, Spinarova L, Hude P, Krejci J, Dusek L, Vitovec J, et al. Combined right ventricular systolic and diastolic dysfunction represents a strong determinant of poor prognosis in patients with symptomatic heart failure. Int J Cardiol. 2005;105(2):164–73.  https://doi.org/10.1016/j.ijcard.2004.12.031.CrossRefPubMedGoogle Scholar
  50. 50.
    Meluzin J, Spinarova L, Hude P, Krejci J, Kincl V, Panovsky R, et al. Prognostic importance of various echocardiographic right ventricular functional parameters in patients with symptomatic heart failure. J Am Soc Echocardiogr. 2005;18(5):435–44.  https://doi.org/10.1016/j.echo.2005.02.004.CrossRefPubMedGoogle Scholar
  51. 51.
    Juilliere Y, Barbier G, Feldmann L, Grentzinger A, Danchin N, Cherrier F. Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy. Eur Heart J. 1997;18(2):276–80.  https://doi.org/10.1093/oxfordjournals.eurheartj.a015231.CrossRefPubMedGoogle Scholar
  52. 52.
    Kjaergaard J, Akkan D, Iversen KK, Kober L, Torp-Pedersen C, Hassager C. Right ventricular dysfunction as an independent predictor of short- and long-term mortality in patients with heart failure. Eur J Heart Fail. 2007;9(6–7):610–6.  https://doi.org/10.1016/j.ejheart.2007.03.001.CrossRefPubMedGoogle Scholar
  53. 53.
    • Dini FL, Carluccio E, Simioniuc A, Biagioli P, Reboldi G, Galeotti GG, et al. Right ventricular recovery during follow-up is associated with improved survival in patients with chronic heart failure with reduced ejection fraction. Eur J Heart Fail. 2016;18(12):1462–71. Important mechanistic study that showed that in patients with HFrEF and RV dysfunction at baseline, patients who improved RV function with medical therapy had better survival than those who had persistently abnormal or worsened RV function (based on TAPSE). This lends support to the concept that RV function is an independent determinate of survival in HFrEF.CrossRefPubMedGoogle Scholar
  54. 54.
    Drakos SG, Janicki L, Horne BD, Kfoury AG, Reid BB, Clayson S, et al. Risk factors predictive of right ventricular failure after left ventricular assist device implantation. Am J Cardiol. 2010;105(7):1030–5.  https://doi.org/10.1016/j.amjcard.2009.11.026.CrossRefPubMedGoogle Scholar
  55. 55.
    Fitzpatrick JR 3rd, Frederick JR, Hsu VM, Kozin ED, O'Hara ML, Howell E, et al. Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support. J Heart Lung Transplant. 2008;27(12):1286–92.  https://doi.org/10.1016/j.healun.2008.09.006.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Patlolla B, Beygui R, Haddad F. Right-ventricular failure following left ventricle assist device implantation. Curr Opin Cardiol. 2013;28(2):223–33.  https://doi.org/10.1097/HCO.0b013e32835dd12c.CrossRefPubMedGoogle Scholar
  57. 57.
    Kato TS, Farr M, Schulze PC, Maurer M, Shahzad K, Iwata S, et al. Usefulness of two-dimensional echocardiographic parameters of the left side of the heart to predict right ventricular failure after left ventricular assist device implantation. Am J Cardiol. 2012;109(2):246–51.  https://doi.org/10.1016/j.amjcard.2011.08.040.CrossRefPubMedGoogle Scholar
  58. 58.
    Neyer J, Arsanjani R, Moriguchi J, Siegel R, Kobashigawa J. Echocardiographic parameters associated with right ventricular failure after left ventricular assist device: a review. J Heart Lung Transplant. 2016;35(3):283–93.  https://doi.org/10.1016/j.healun.2015.12.018.CrossRefPubMedGoogle Scholar
  59. 59.
    Puwanant S, Hamilton KK, Klodell CT, Hill JA, Schofield RS, Cleeton TS, et al. Tricuspid annular motion as a predictor of severe right ventricular failure after left ventricular assist device implantation. J Heart Lung Transplant. 2008;27(10):1102–7.  https://doi.org/10.1016/j.healun.2008.07.022.CrossRefPubMedGoogle Scholar
  60. 60.
    Raina A, Seetha Rammohan HR, Gertz ZM, Rame JE, Woo YJ, Kirkpatrick JN. Postoperative right ventricular failure after left ventricular assist device placement is predicted by preoperative echocardiographic structural, hemodynamic, and functional parameters. J Card Fail. 2013;19(1):16–24.  https://doi.org/10.1016/j.cardfail.2012.11.001.CrossRefPubMedGoogle Scholar
  61. 61.
    Vivo RP, Cordero-Reyes AM, Qamar U, Garikipati S, Trevino AR, Aldeiri M, et al. Increased right-to-left ventricle diameter ratio is a strong predictor of right ventricular failure after left ventricular assist device. J Heart Lung Transplant. 2013;32(8):792–9.  https://doi.org/10.1016/j.healun.2013.05.016.CrossRefPubMedGoogle Scholar
  62. 62.
    Denault AY, Couture P, Beaulieu Y, Haddad F, Deschamps A, Nozza A, et al. Right ventricular depression after cardiopulmonary bypass for Valvular surgery. J Cardiothorac Vasc Anesth. 2015;29(4):836–44.  https://doi.org/10.1053/j.jvca.2015.01.011.CrossRefPubMedGoogle Scholar
  63. 63.
    • Kassis H, Cherukuri K, Agarwal R, Kanwar M, Elapavaluru S, Sokos GG, et al. Significance of residual mitral regurgitation after continuous flow left ventricular assist device implantation. JACC Heart Fail. 2017;5(2):81–8. Interesting restrospective study demonstrating that residual mitral regurgitation after LVAD implant was associated with worse RV size and function as well as with shorter time to re-hospitalization and death.CrossRefPubMedGoogle Scholar
  64. 64.
    Kiernan MS, French AL, DeNofrio D, Parmar YJ, Pham DT, Kapur NK, et al. Preoperative three-dimensional echocardiography to assess risk of right ventricular failure after left ventricular assist device surgery. J Card Fail. 2015;21(3):189–97.  https://doi.org/10.1016/j.cardfail.2014.12.009.CrossRefPubMedGoogle Scholar
  65. 65.
    Lampert BC, Teuteberg JJ. Right ventricular failure after left ventricular assist devices. J Heart Lung Transplant. 2015;34(9):1123–30.  https://doi.org/10.1016/j.healun.2015.06.015.CrossRefPubMedGoogle Scholar
  66. 66.
    Kato TS, Jiang J, Schulze PC, Jorde U, Uriel N, Kitada S, et al. Serial echocardiography using tissue Doppler and speckle tracking imaging to monitor right ventricular failure before and after left ventricular assist device surgery. JACC Heart Fail. 2013;1(3):216–22.  https://doi.org/10.1016/j.jchf.2013.02.005.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Kapelios CJ, Charitos C, Kaldara E, Malliaras K, Nana E, Pantsios C, et al. Late-onset right ventricular dysfunction after mechanical support by a continuous-flow left ventricular assist device. J Heart Lung Transplant. 2015;34(12):1604–10.  https://doi.org/10.1016/j.healun.2015.05.024.CrossRefPubMedGoogle Scholar
  68. 68.
    Takeda K, Takayama H, Colombo PC, Yuzefpolskaya M, Fukuhara S, Han J, et al. Incidence and clinical significance of late right heart failure during continuous-flow left ventricular assist device support. J Heart Lung Transplant. 2015;34(8):1024–32.  https://doi.org/10.1016/j.healun.2015.03.011.CrossRefPubMedGoogle Scholar
  69. 69.
    Takeda K, Naka Y, Yang JA, Uriel N, Colombo PC, Jorde UP, et al. Outcome of unplanned right ventricular assist device support for severe right heart failure after implantable left ventricular assist device insertion. J Heart Lung Transplant. 2014;33(2):141–8.  https://doi.org/10.1016/j.healun.2013.06.025.CrossRefPubMedGoogle Scholar
  70. 70.
    Stobierska-Dzierzek B, Awad H, Michler RE. The evolving management of acute right-sided heart failure in cardiac transplant recipients. J Am Coll Cardiol. 2001;38(4):923–31.CrossRefPubMedGoogle Scholar
  71. 71.
    Griepp RB, Stinson EB, Dong E Jr, Clark DA, Shumway NE. Determinants of operative risk in human heart transplantation. Am J Surg. 1971;122(2):192–7.  https://doi.org/10.1016/0002-9610(71)90316-3.CrossRefPubMedGoogle Scholar
  72. 72.
    Erickson KW, Costanzo-Nordin MR, O'Sullivan EJ, Johnson MR, Zucker MJ, Pifarre R, et al. Influence of preoperative transpulmonary gradient on late mortality after orthotopic heart transplantation. J Heart Transplant. 1990;9(5):526–37.PubMedGoogle Scholar
  73. 73.
    Kirklin JK, Naftel DC, Kirklin JW, Blackstone EH, White-Williams C, Bourge RC. Pulmonary vascular resistance and the risk of heart transplantation. J Heart Transplant. 1988;7(5):331–6.PubMedGoogle Scholar
  74. 74.
    Bittner HB, Chen EP, Biswas SS, Van Trigt P 3rd, Davis RD. Right ventricular dysfunction after cardiac transplantation: primarily related to status of donor heart. Ann Thorac Surg. 1999;68(5):1605–11.  https://doi.org/10.1016/S0003-4975(99)00987-X.CrossRefPubMedGoogle Scholar
  75. 75.
    Carrier M, Blaise G, Belisle S, Perrault LP, Pellerin M, Petitclerc R, et al. Nitric oxide inhalation in the treatment of primary graft failure following heart transplantation. J Heart Lung Transplant. 1999;18(7):664–7.  https://doi.org/10.1016/S1053-2498(99)00025-X.CrossRefPubMedGoogle Scholar
  76. 76.
    Raina A, Vaidya A, Gertz ZM, Susan C, Forfia PR. Marked changes in right ventricular contractile pattern after cardiothoracic surgery: implications for post-surgical assessment of right ventricular function. J Heart Lung Transplant. 2013;32(8):777–83.  https://doi.org/10.1016/j.healun.2013.05.004.CrossRefPubMedGoogle Scholar
  77. 77.
    • Bianco JC, Mc Loughlin S, Denault AY, Marenchino RG, Rojas JI, Bonofiglio FC. Heart transplantation in patients >/=60 years: importance of relative pulmonary hypertension and right ventricular failure on midterm survival. J Cardiothorac Vasc Anesth. 2017. Recent single center study that demonstrated that post-transplant survival was more related to preoperative PH, cardiopulmonary bypass time and importantly post-operative RV dysfunction than to donor age.Google Scholar
  78. 78.
    • Barakat AF, Sperry BW, Starling RC, Mentias A, Popovic ZB, Griffin BP, et al. Prognostic utility of right ventricular free wall strain in low risk patients after orthotopic heart transplantation. Am J Cardiol. 2017;119(11):1890–6. Important study that showed that measurement of RV global strain and other markers of RV function were independently associated with the composite of death, rejection and vasculopathy in 96 stable transplant patients one year post transplant. Markers of RV function were independently associated with the composite outcome while LVEF and LV strain were not.CrossRefPubMedGoogle Scholar
  79. 79.
    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.CrossRefPubMedGoogle Scholar
  80. 80.
    Califf RM, Adams KF, McKenna WJ, Gheorghiade M, Uretsky BF, McNulty SE, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1997;134(1):44–54.  https://doi.org/10.1016/S0002-8703(97)70105-4.CrossRefPubMedGoogle Scholar
  81. 81.
    Grossman NL, Fiack CA, Weinberg JM, Rybin DV, Farber HW. Pulmonary hypertension associated with heart failure with preserved ejection fraction: acute hemodynamic effects of inhaled iloprost. Pulm Circ. 2015;5(1):198–203.  https://doi.org/10.1086/679725.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309(12):1268–77.  https://doi.org/10.1001/jama.2013.2024.CrossRefPubMedGoogle Scholar
  83. 83.
    Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011;124(2):164–74.  https://doi.org/10.1161/CIRCULATIONAHA.110.983866.CrossRefPubMedGoogle Scholar
  84. 84.
    Bonderman D, Pretsch I, Steringer-Mascherbauer R, Jansa P, Rosenkranz S, Tufaro C, et al. Acute hemodynamic effects of riociguat in patients with pulmonary hypertension associated with diastolic heart failure (DILATE-1): a randomized, double-blind, placebo-controlled, single-dose study. Chest. 2014;146(5):1274–85.  https://doi.org/10.1378/chest.14-0106.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    • Packer M, JJV MM, Krum H, Kiowski W, Massie BM, Caspi A, et al. Long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure: primary results of the ENABLE Trials. JACC Heart Fail. 2017;5(5):317–26. Long term follow up data from the ENABLE randomized trials of the endothelin receptor antagonist bosentan in patients with HFrEF. Bosentan did not improve survuival in this cohort of patients with HFrEF and was associated with the early development of fluid retention.CrossRefPubMedGoogle Scholar
  86. 86.
    • Koller B, Steringer-Mascherbauer R, Ebner CH, Weber T, Ammer M, Eichinger J, et al. Pilot study of endothelin receptor blockade in heart failure with diastolic dysfunction and pulmonary hypertension (BADDHY-Trial). Heart Lung Circ. 2017;26(5):433–41. Randomized, placebo controlled pilot study evaluating the impact of the endothelin receptor antagonist bosentan in HFpEF patients with PH. The study was terminated early after interim analysis favored the placebo group in terms of six minute walk testing and estimated PA pressures.CrossRefPubMedGoogle Scholar
  87. 87.
    Conraads VM, Metra M, Kamp O, De Keulenaer GW, Pieske B, Zamorano J, et al. Effects of the long-term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study. Eur J Heart Fail. 2012;14(2):219–25.  https://doi.org/10.1093/eurjhf/hfr161.CrossRefPubMedGoogle Scholar
  88. 88.
    Shah AM, Claggett B, Sweitzer NK, Shah SJ, Deswal A, Anand IS, et al. Prognostic importance of changes in cardiac structure and function in heart failure with preserved ejection fraction and the impact of spironolactone. Circ Heart Fail. 2015;8(6):1052–8.  https://doi.org/10.1161/CIRCHEARTFAILURE.115.002249.PubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cardiovascular InstituteAllegheny General HospitalPittsburghUSA
  2. 2.Pulmonary Hypertension Program, Section of Heart Failure/Transplant/MCS & Pulmonary Hypertension, Allegheny General HospitalPittsburghUSA

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