Pulmonary hypertension and right ventricular remodeling in HFpEF and HFrEF

  • Stefano GhioEmail author
  • Claudia Raineri
  • Laura Scelsi
  • Milika Ašanin
  • Marija Polovina
  • Petar Seferovic


Right ventricular function has long been neglected by heart failure specialists. We have now learnt that it is strongly associated with morbidity and mortality in all patients with heart failure, regardless of the degree of left ventricular dysfunction. Importantly, right ventricular function is tightly linked with pulmonary hypertension, and only a thorough understanding of how the right ventricle couples with the pulmonary circulation can provide an improved knowledge of the pathophysiology and possibly a more efficient treatment and a better prognosis in patients with heart failure.


Heart failure Pulmonary hypertension Right ventricle 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Yock PG, Popp RL (1984) Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 70:657–662CrossRefGoogle Scholar
  2. 2.
    Brecker SJ, Gibbs JS, Fox KM, Yacoub MH, Gibson DG (1994) Comparison of Doppler derived haemodynamic variables and simultaneous high fidelity pressure measurements in severe pulmonary hypertension. Br Heart J 72:384–389CrossRefGoogle Scholar
  3. 3.
    Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K et al (2010) 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 23:685–713CrossRefGoogle Scholar
  4. 4.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 28(1):1–39.e14CrossRefGoogle Scholar
  5. 5.
    Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M, ESC Scientific Document Group (2016) 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 37:67–119CrossRefGoogle Scholar
  6. 6.
    Chemla D, Castelain V, Humbert M, Hébert JL, Simonneau G, Lecarpentier Y, Hervé P (2004) New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure. Chest 126:1313–1317CrossRefGoogle Scholar
  7. 7.
    Aduen JF, Castello R, Daniels JT, Diaz JA, Safford RE, Heckman MG, Crook JE, Burger CD (2011) Accuracy and precision of three echocardiographic methods for estimating mean pulmonary artery pressure. Chest 139:347–352CrossRefGoogle Scholar
  8. 8.
    Abbas AE, Fortuin FD, Schiller NB, Appleton CP, Moreno CA, Lester SJ (2003) Echocardiographic determination of mean pulmonary artery pressure. Am J Cardiol 92:1373–1376CrossRefGoogle Scholar
  9. 9.
    Reuben SR (1971) Compliance of the pulmonary arterial system in disease. Circ Res 29:40–50CrossRefGoogle Scholar
  10. 10.
    Ghio S, Schirinzi S, Pica S (2015) Pulmonary arterial compliance: how and why should we measure it? Glob Cardiol Sci Pract 2015(4):58CrossRefGoogle Scholar
  11. 11.
    McLaughlin VV, Shah SJ, Souza R, Humbert M (2015) Management of pulmonary arterial hypertension. J Am Coll Cardiol 65:1976–1997CrossRefGoogle Scholar
  12. 12.
    D'Alto M, Bossone E, Opotowsky AR, Ghio S, Rudski LG, Naeije R (2018) Strengths and weaknesses of echocardiography for the diagnosis of pulmonary hypertension. Int J Cardiol 263:177–183CrossRefGoogle Scholar
  13. 13.
    D'Alto M, Romeo E, Argiento P, Di Salvo G, Badagliacca R, Cirillo AP, Kaemmerer H, Bossone E, Naeije R (2015) Pulmonary arterial hypertension: the key role of echocardiography. Echocardiography 32(Suppl 1):S23–S37CrossRefGoogle Scholar
  14. 14.
    Ghio S, Recusani F, Klersy C, Sebastiani R, Laudisa ML, Campana C, Gavazzi A, Tavazzi L (2000) Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy. Am J Cardiol 85:837–842CrossRefGoogle Scholar
  15. 15.
    Ghio S, Guazzi M, Scardovi AB, Klersy C, Clemenza F, Carluccio E, Temporelli PL, Rossi A, Faggiano P, Traversi E, Vriz O, Dini FL, on behalf of all investigators (2017) Different correlates but similar prognostic implications for right ventricular dysfunction in heart failure patients with reduced or preserved ejection fraction. Eur J Heart Fail 19:873–879CrossRefGoogle Scholar
  16. 16.
    Focardi M, Cameli M, Carbone SF, Massoni A, de Vito R, Lisi M, Mondillo S (2015) Traditional and innovative echocardiographic parameters for the analysis of right ventricular performance in comparison with cardiac magnetic resonance. Eur Heart J Cardiovasc Imaging 16:47–52CrossRefGoogle Scholar
  17. 17.
    Haeck ML, Scherptong RW, Marsan NA, Holman ER, Schalij MJ, Bax JJ et al (2012) Prognostic value of right ventricular longitudinal peak systolic strain in patients with pulmonary hypertension. Circ Cardiovasc Imaging 5:628–636CrossRefGoogle Scholar
  18. 18.
    Fine NM, Chen L, Bastiansen PM, Frantz RP, Pellikka PA, Oh JK, Kane GC (2013) Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging 6:711–721CrossRefGoogle Scholar
  19. 19.
    Puwanant S, Park M, Popovic ZB, Tang WH, Farha S, George D et al (2010) Ventricular geometry, strain, and rotational mechanics in pulmonary hypertension. Circulation 121:259–266CrossRefGoogle Scholar
  20. 20.
    D’Hooge J, Barbosa D, Gao H, Claus P, Prater D, Hamilton J et al (2016) Two-dimensional speckle tracking echocardiography: standardization efforts based on synthetic ultrasound data. Eur Heart J Cardiovasc Imaging 17:693–701CrossRefGoogle Scholar
  21. 21.
    Verhaert D, Mullens W, Borowski A, Popovic ZB, Curtin RJ, Thomas JD et al (2010) Right ventricular response to intensive medical therapy in advanced decompensated heart failure. Circ Heart Fail 3:340–346CrossRefGoogle Scholar
  22. 22.
    Grant AD, Smedira NG, Starling RC, Marwick TH (2012) Independent and incremental role of quantitative right ventricular evaluation for the prediction of right ventricular failure after left ventricular assist device implantation. J Am Coll Cardiol 60:521–528CrossRefGoogle Scholar
  23. 23.
    Sugeng L, Mor-Avi V, Weinert L, Niel J, Ebner C, Steringer-Mascherbauer R, Bartolles R, Baumann R, Schummers G, Lang RM, Nesser HJ (2010) Multimodality comparison of quantitative volumetric analysis of the right ventricle. JACC Cardiovasc Imaging 3:10–18CrossRefGoogle Scholar
  24. 24.
    Drazner MH, Hamilton MA, Fonarow G, Creaser J, Flavell C, Stevenson LW (1999) Relationship between right and left-sided filling pressures in 1000 patients with advanced heart failure. J Heart Lung Transplant 18:1126–1132CrossRefGoogle Scholar
  25. 25.
    Magne J, Lancellotti P, Piérard LA (2010) Exercise pulmonary hypertension in asymptomatic degenerative mitral regurgitation. Circulation 122:33–41CrossRefGoogle Scholar
  26. 26.
    Harvey RM, Enson Y, Ferrer MI (1971) A reconsideration of the origins of pulmonary hypertension. Chest 59:82–94CrossRefGoogle Scholar
  27. 27.
    Mikhail G, Chester AH, Gibbs JS, Borland JA, Banner NR, Yacoub MH (1998) Role of vasoactive mediators in primary and secondary pulmonary hypertension. Am J Cardiol 82:254–255CrossRefGoogle Scholar
  28. 28.
    Moraes DL, Colucci WS, Givertz MM (2000) Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation 102:1718–1723CrossRefGoogle Scholar
  29. 29.
    Assad TR, Hemnes AR, Larkin EK, Glazer AM, Xu M, Wells QS, Farber-Eger EH, Sheng Q, Shyr Y, Harrell FE, Newman JH, Brittain EL (2016) Clinical and biological insights into combined post- and pre-capillary pulmonary hypertension. J Am Coll Cardiol 68:2525–2536CrossRefGoogle Scholar
  30. 30.
    Adir Y, Guazzi M, Offer A, Temporelli PL, Cannito A, Ghio S (2017) Pulmonary hemodynamics in heart failure patients with reduced or preserved ejection fraction and pulmonary hypertension: similarities and disparities. Am Heart J 192:120–127CrossRefGoogle Scholar
  31. 31.
    Paulus WJ, Tschope C (2013) A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 62:263–271CrossRefGoogle Scholar
  32. 32.
    Dorfmuller P, Humbert M (2012) Progress in pulmonary arterial hypertension pathology: relighting a torch inside the tunnel. Am J Respir Crit Care Med 186:210–212CrossRefGoogle Scholar
  33. 33.
    Fayyaz AU, Edwards WD, Maleszewski JJ, Konik EA, DuBrock HM, Borlaug BA, Frantz RP, Jenkins SM, Redfield MM (2018) Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction. Circulation 137:1796–1810CrossRefGoogle Scholar
  34. 34.
    Vachiéry JL, Tedford RJ, Rosenkranz S et al (2018) Pulmonary hypertension due to left heart disease. Eur Respir J Dec 13Google Scholar
  35. 35.
    Gerges C, Gerges M, Lang MB, Zhang Y, Jakowitsch J, Probst P, Maurer G, Lang IM (2013) Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in “out-of-proportion” pulmonary hypertension. Chest 143:758–766CrossRefGoogle Scholar
  36. 36.
    Tedford RJ, Beaty CA, Mathai SC, Kolb TM, Damico R, Hassoun PM, Leary PJ, Kass DA, Shah AS (2014) Prognostic value of the pre-transplant diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension. J Heart Lung Transplant 33:289–297CrossRefGoogle Scholar
  37. 37.
    Tampakakis E, Leary PJ, Selby VN et al (2015) The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. J Am Coll Cardiol HF 3:9–16Google Scholar
  38. 38.
    Lam CSP, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM (2009) Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Cardiol 53:1119–1126CrossRefGoogle Scholar
  39. 39.
    Bursi F, McNallan SM, Redfield MM, Nkomo VT, Lam CS, Weston SA, Jiang R, Roger VL (2012) Pulmonary pressures and death in heart failure. A community study. J Am Coll Cardiol 59:222–231CrossRefGoogle Scholar
  40. 40.
    Agarwal R, Shah SJ, Foreman AJ, Glassner C, Bartolome SD, Safdar Z, Coslet SL, Anderson AS, Gomberg-Maitland M (2012) Risk assessment in pulmonary hypertension associated with heart failure and preserved ejection fraction. J Heart Lung Transplant 31:467–477CrossRefGoogle Scholar
  41. 41.
    Damy T, Goode KM, Kallvikbacka-Bennett A, Lewinter C, Hobkirk J, Nikitin NP, Dubois-Randé JL, Hittinger L, Clark AL, Cleland JGF (2010) Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure. Eur Heart J 31:2280–2290CrossRefGoogle Scholar
  42. 42.
    Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, Arbustini E, Recusani F, Tavazzi L (2001) Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 37:183–188CrossRefGoogle Scholar
  43. 43.
    Cappola TP, Felker GM, Kao WH, Hare JM, Baughman KL, Kasper EK (2002) Pulmonary hypertension and risk of death in cardiomyopathy: patients with myocarditis are at higher risk. Circulation 105:1663–1668CrossRefGoogle Scholar
  44. 44.
    Costard-Jackle A, Fowler MB (1992) Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group. J Am Coll Cardiol 19:48–54CrossRefGoogle Scholar
  45. 45.
    Klotz S, Wenzelburger F, Stypmann J, Welp H, Drees G, Schmid C, Scheld HH (2006) Reversible pulmonary hypertension in heart transplant candidates: to transplant or not to transplant. Ann Thorac Surg 82:1770–1773CrossRefGoogle Scholar
  46. 46.
    Drakos SG, Kfoury AG, Gilbert EM, Horne BD, Long JW, Stringham JC, Campbell BA, Renlund DG (2007) Effect of reversible pulmonary hypertension on outcomes after heart transplantation. J Heart Lung Transplant 26:319–323CrossRefGoogle Scholar
  47. 47.
    Miller WL, Grill DE, Borlaug BA (2013) Clinical features, hemodynamics, and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction: pulmonary hypertension and heart failure. JACC Heart Fail 1:290–299CrossRefGoogle Scholar
  48. 48.
    Mohammed SF, Hussain I, AbouEzzeddine OF, Takahama H, Kwon SH, Forfia P, Roger VL, Redfield MM (2014) Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation 130:2310–2320CrossRefGoogle Scholar
  49. 49.
    Burke MA, Katz DH, Beussink L, Selvaraj S, Gupta DK, Fox J, Chakrabarti S, Sauer AJ, Rich JD, Freed BH, Shah SJ (2014) Prognostic importance of pathophysiologic markers in patients with heart failure and preserved ejection fraction. Circ Heart Fail 7:288–299CrossRefGoogle Scholar
  50. 50.
    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 (2018) 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 20:16–37CrossRefGoogle Scholar
  51. 51.
    Guazzi M, Bandera F, Pelissero G, Castelvecchio S, Menicanti L, Ghio S, Temporelli PL, Arena R (2013) 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 305:H1373–H1381CrossRefGoogle Scholar
  52. 52.
    Califf RM, Adams KF, McKenna WJ et al (1997) A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST). Am Heart J 134:44–54CrossRefGoogle Scholar
  53. 53.
    Packer M, McMurray JJV, Krum H et al (2017) 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 5:317–326CrossRefGoogle Scholar
  54. 54.
    Vachiéry JL, Delcroix M, Al-Hiti H et al (2018) Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J 51(2):1701886CrossRefGoogle Scholar
  55. 55.
    Bonderman D, Ghio S, Felix SB, Ghofrani HA, Michelakis E, Mitrovic V, Oudiz RJ, Boateng F, Scalise AV, Roessig L, Semigran MJ, Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) Study Group (2013) Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation 128:502–511CrossRefGoogle Scholar
  56. 56.
    Pieske B, Maggioni AP, Lam CSP, Pieske-Kraigher E, Filippatos G, Butler J, Ponikowski P, Shah SJ, Solomon SD, Scalise AV, Mueller K, Roessig L, Gheorghiade M (2017) Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED EF (SOCRATES-PRESERVED) study. Eur Heart J 38:1119–1127CrossRefGoogle Scholar
  57. 57.
    Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CSP, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Müller K, Roessig L, Pieske B, for the SOCRATES-REDUCED Investigators and Coordinators (2015) Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: the SOCRATES-REDUCED randomized trial. JAMA 314:2251–2262CrossRefGoogle Scholar
  58. 58.
    Guazzi M, Vicenzi M, Arena R, Guazzi MD (2011) Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation 124:164–174CrossRefGoogle Scholar
  59. 59.
    Hoendermis ES, Liu LC, Hummel YM et al (2015) Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J 36:2565–2573CrossRefGoogle Scholar
  60. 60.
    Bermejo J, Yotti R, Garcia-Orta R et al (2018) Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial. Eur Heart J 39:1255–1264CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of CardiologyFondazione I.R.C.C.S. Policlinico San MatteoPaviaItaly
  2. 2.Faculty of MedicineUniversity of BelgradeBelgradeSerbia
  3. 3.Department of CardiologyClinical Centre of SerbiaBelgradeSerbia

Personalised recommendations