Advertisement

Current Heart Failure Reports

, Volume 13, Issue 6, pp 281–294 | Cite as

Pulmonary Hypertension in Heart Failure Patients: Pathophysiology and Prognostic Implications

  • Marco GuazziEmail author
  • Valentina Labate
Pathophysiology of Myocardial Failure (I Anand and M Patarroyo-Aponte, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pathophysiology of Myocardial Failure

Abstract

Pulmonary hypertension (PH) due to left heart disease (LHD), i.e., group 2 PH, is the most common reason for increased pressures in the pulmonary circuit. Although recent guidelines incorporate congenital heart disease in this classification, left-sided heart diseases of diastolic and systolic origin including valvular etiology are the vast majority. In these patients, an increased left-sided filling pressure triggers a multistage hemodynamic evolution that ends into right ventricular failure through an initial passive increase in pulmonary artery pressure complicated over time by pulmonary vasoconstriction, endothelial dysfunction, and remodeling of the small-resistance pulmonary arteries. Regardless of the underlying left heart pathology, when present, PH-LHD is associated with more severe symptoms, worse exercise tolerance, and outcome, especially when right ventricular dysfunction and failure are part of the picture. Compared with group 1 and other forms of pulmonary arterial hypertension, PH-LHD is more often seen in elderly patients with a higher prevalence of cardiovascular comorbidities and most, if not all, of the features of metabolic syndrome, especially in case of HF preserved ejection fraction. In this review, we provide an update on current knowledge and some potential challenges about the pathophysiology and established prognostic implications of group 2 PH in patients with HF of either preserved or reduced ejection fraction.

Keywords

Heart failure Pulmonary hypertension 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict 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

  1. 1.
    Murad K, Goff Jr DC, Morgan TM, Burke GL, Bartz TM, Kizer JR, et al. Burden of comorbidities and functional and cognitive impairments in elderly patients at the initial diagnosis of heart failure and their impact on total mortality: the cardiovascular health study. JACC Heart Fail. 2015;3:542–50.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    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;37:67–119.PubMedCrossRefGoogle Scholar
  3. 3.
    Kjaergaard J, Akkan D, Iversen KK, Kjoller E, Kober L, Torp-Pedersen C, et al. Prognostic importance of pulmonary hypertension in patients with heart failure. Am J Cardiol. 2007;99:1146–50.PubMedCrossRefGoogle Scholar
  4. 4.
    Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37:183–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Meyer P, Filippatos GS, Ahmed MI, Iskandrian AE, Bittner V, Perry GJ, et al. Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure. Circulation. 2010;121:252–8.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Guazzi M, Villani S, Generati G, Ferraro OE, Pellegrino M, Alfonzetti E, et al. Right ventricular contractile reserve and pulmonary circulation uncoupling during exercise challenge in heart failure: pathophysiology and clinical phenotypes. JACC Heart Fail. 2016.Google Scholar
  7. 7.
    Merlos P, Nunez J, Sanchis J, Minana G, Palau P, Bodi V, et al. Echocardiographic estimation of pulmonary arterial systolic pressure in acute heart failure. Prognostic implications. Eur J Intern Med. 2013;24:562–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Kalogeropoulos AP, Siwamogsatham S, Hayek S, Li S, Deka A, Marti CN, et al. Echocardiographic assessment of pulmonary artery systolic pressure and outcomes in ambulatory heart failure patients. J Am Heart Assoc. 2014;3:e000363.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the 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 the International Society of Heart And Lung Transplantation (ISHLT). Eur Heart J. 2009;30:2493–537.PubMedCrossRefGoogle Scholar
  10. 10.
    Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62:D42–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Gerges C, Gerges M, Lang MB, Zhang Y, Jakowitsch J, Probst P, et al. Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in “out-of-proportion” pulmonary hypertension. Chest. 2013;143:758–66.PubMedCrossRefGoogle Scholar
  12. 12.
    Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012;126:975–90.PubMedCrossRefGoogle Scholar
  13. 13.
    Rosenkranz S, Gibbs JS, Wachter R, De Marco T, Vonk-Noordegraaf A, Vachiery JL. Left ventricular heart failure and pulmonary hypertensiondagger. Eur Heart J. 2016;37:942–54.PubMedCrossRefGoogle Scholar
  14. 14.
    Fang JC, DeMarco T, Givertz MM, Borlaug BA, Lewis GD, Rame JE, et al. World health organization pulmonary hypertension group 2: pulmonary hypertension due to left heart disease in the adult—a summary statement from the pulmonary hypertension council of the international society for heart and lung transplantation. J Heart Lung Transplant. 2012;31:913–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Naeije R, Vachiery JL, Yerly P, Vanderpool R. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J. 2013;41:217–23.PubMedCrossRefGoogle Scholar
  16. 16.
    Rapp AH, Lange RA, Cigarroa JE, Keeley EC, Hillis LD. Relation of pulmonary arterial diastolic and mean pulmonary arterial wedge pressures in patients with and without pulmonary hypertension. Am J Cardiol. 2001;88:823–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Vachiery JL, Adir Y, Barbera JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol. 2013;62:D100–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Opitz CF, Hoeper MM, Gibbs JS, Kaemmerer H, Pepke-Zaba J, Coghlan JG, Scelsi L, D'Alto M, Olsson KM, Ulrich S, Scholtz W, Schulz U, Grünig E, Vizza CD, Staehler G, Bruch L, Huscher D, Pittrow D, Rosenkranz S. Pre-capillary, combined, and post-capillary pulmonary hypertension: a pathophysiological continuum. J Am Coll Cardiol. 2016 Jul 26;68(4):368–78.Google Scholar
  19. 19.
    Tedford RJ, Beaty CA, Mathai SC, Kolb TM, Damico R, Hassoun PM, et al. 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. 2014;33:289–97.PubMedCrossRefGoogle Scholar
  20. 20.
    Tampakakis E, Leary PJ, Selby VN, De Marco T, Cappola TP, Felker GM, et al. The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. JACC Heart Fail. 2015;3:9–16.PubMedCrossRefGoogle Scholar
  21. 21.
    Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary circulation unit: state of the art and clinical and research implications. Circulation. 2009;120:992–1007.PubMedCrossRefGoogle Scholar
  22. 22.
    Enson Y, Wood JA, Mantaras NB, Harvey RM. The influence of heart rate on pulmonary arterial-left ventricular pressure relationships at end-diastole. Circulation. 1977;56:533–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Dupont M, Mullens W, Skouri HN, Abrahams Z, Wu Y, Taylor DO, et al. Prognostic role of pulmonary arterial capacitance in advanced heart failure. Circ Heart Fail. 2012;5:778–85.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Tedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, et al. Pulmonary capillary wedge pressure augments right ventricular pulsatile loading. Circulation. 2012;125:289–97.PubMedCrossRefGoogle Scholar
  25. 25.
    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;192:1234–46.PubMedCrossRefGoogle Scholar
  26. 26.
    Saouti N, Westerhof N, Postmus PE, Vonk-Noordegraaf A. The arterial load in pulmonary hypertension. Eur Respir Rev. 2010;19:197–203.PubMedCrossRefGoogle Scholar
  27. 27.
    Lankhaar JW, Westerhof N, Faes TJ, Marques KM, Marcus JT, Postmus PE, et al. Quantification of right ventricular afterload in patients with and without pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2006;291:H1731–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Lankhaar JW, Westerhof N, Faes TJ, Gan CT, Marques KM, Boonstra A, et al. Pulmonary vascular resistance and compliance stay inversely related during treatment of pulmonary hypertension. Eur Heart J. 2008;29:1688–95.PubMedCrossRefGoogle Scholar
  29. 29.
    Dragu R, Rispler S, Habib M, Sholy H, Hammerman H, Galie N, et al. Pulmonary arterial capacitance in patients with heart failure and reactive pulmonary hypertension. Eur J Heart Fail. 2015;17:74–80.PubMedCrossRefGoogle Scholar
  30. 30.
    Al-Naamani N, Preston IR, Paulus JK, Hill NS, Roberts KE. Pulmonary arterial capacitance is an important predictor of mortality in heart failure with a preserved ejection fraction. JACC Heart Fail. 2015;3:467–74.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Pellegrini P, Rossi A, Pasotti M, Raineri C, Cicoira M, Bonapace S, et al. Prognostic relevance of pulmonary arterial compliance in patients with chronic heart failure. Chest. 2014;145:1064–70.PubMedCrossRefGoogle Scholar
  32. 32.
    Malhotra R, Dhakal BP, Eisman AS, Pappagianopoulos PP, Dress A, Weiner RB, et al. Pulmonary vascular distensibility predicts pulmonary hypertension severity, exercise capacity, and survival in heart failure. Circ Heart Fail. 2016;9.Google Scholar
  33. 33.
    Borlaug BA, Nishimura RA, Sorajja P, Lam CSP, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail. 2010;3:588-+.Google Scholar
  34. 34.
    Fujimoto N, Borlaug BA, Lewis GD, Hastings JL, Shafer KM, Bhella PS, et al. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation. 2013;127:55–62.PubMedCrossRefGoogle Scholar
  35. 35.
    Shim CY, Kim SA, Choi D, Yang WI, Kim JM, Moon SH, et al. Clinical outcomes of exercise-induced pulmonary hypertension in subjects with preserved left ventricular ejection fraction: implication of an increase in left ventricular filling pressure during exercise. Heart. 2011;97:1417–24.PubMedCrossRefGoogle Scholar
  36. 36.
    Dorfs S, Zeh W, Hochholzer W, Jander N, Kienzle RP, Pieske B, et al. Pulmonary capillary wedge pressure during exercise and long-term mortality in patients with suspected heart failure with preserved ejection fraction. Eur Heart J. 2014;35:3103–12.PubMedCrossRefGoogle Scholar
  37. 37.
    Bevegard S, Holmgren A, Jonsson B. The effect of body position on the circulation at rest and during exercise, with special reference to the influence on the stroke volume. Acta Physiol Scand. 1960;49:279–98.PubMedCrossRefGoogle Scholar
  38. 38.
    Fishman AP. Pulmonary circulation. Handbook of physiology. The respiratory system. Circulation and nonrespiratory functions. Bethesda (MD): American Physiology Society;. 1985;sect 3, vol 1:93-166.Google Scholar
  39. 39.
    Granath A, Jonsson B, Strandell T. Circulation in healthy old men, studied by right heart catheterization at rest and during exercise in supine and sitting position. Acta Med Scand. 1964;176:425–46.PubMedCrossRefGoogle Scholar
  40. 40.
    Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34:888–94.PubMedCrossRefGoogle Scholar
  41. 41.
    Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107:216–23.PubMedCrossRefGoogle Scholar
  42. 42.
    Argiento P, Chesler N, Mule M, D’Alto M, Bossone E, Unger P, et al. Exercise stress echocardiography for the study of the pulmonary circulation. Eur Respir J. 2010;35:1273–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Reeves JT, Dempsey J, Grover RF. Pulmonary circulation during exercise. In: Wei EK, Reeves JT, editors. Pulmonary vascular physiology and physiopathology. New York: Marcel dekker; 1989. p. 107–33.Google Scholar
  44. 44.
    Donal E, Thebault C, Lund LH, Kervio G, Reynaud A, Simon T, et al. Heart failure with a preserved ejection fraction additive value of an exercise stress echocardiography. Eur Heart J Cardiovasc Imaging. 2012;13:656–65.PubMedCrossRefGoogle Scholar
  45. 45.
    Tan YT, Wenzelburger F, Lee E, Heatlie G, Leyva F, Patel K, et al. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J Am Coll Cardiol. 2009;54:36–46.PubMedCrossRefGoogle Scholar
  46. 46.
    Reeves JT, Moon RE, Grover RF, Groves BM. Increased wedge pressure facilitates decreased lung vascular resistance during upright exercise. Chest. 1988;93:97S–9S.PubMedCrossRefGoogle Scholar
  47. 47.
    Naeije R. Pulmonary vascular resistance. A meaningless variable? Intensive Care Med. 2003;29:526–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Lewis GD, Bossone E, Naeije R, Grunig E, Saggar R, Lancellotti P, et al. Pulmonary vascular hemodynamic response to exercise in cardiopulmonary diseases. Circulation. 2013;128:1470–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Grossman W. Blood flow measurement. In: Baim DS, Grossman W, editors. Grossman’s cardiac catheterization, angiography, and intervention. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 158–9.Google Scholar
  50. 50.
    Naeije R, Vanderpool R, Dhakal BP, Saggar R, Saggar R, Vachiery JL, et al. Exercise-induced pulmonary hypertension: physiological basis and methodological concerns. Am J Respir Crit Care Med. 2013;187:576–83.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Robbins IM, Hemnes AR, Pugh ME, Brittain EL, Zhao DX, Piana RN, et al. High prevalence of occult pulmonary venous hypertension revealed by fluid challenge in pulmonary hypertension. Circ Heart Fail. 2014;7:116–22.PubMedCrossRefGoogle Scholar
  52. 52.
    Andersen MJ, Olson TP, Melenovsky V, Kane GC, Borlaug BA. Differential hemodynamic effects of exercise and volume expansion in people with and without heart failure. Circ Heart Fail. 2015;8:41–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Thenappan T, Gomberg-Maitland M. Epidemiology of pulmonary hypertension and right ventricular failure in left heart failure. Curr Heart Fail Rep. 2014;11:428–35.PubMedCrossRefGoogle Scholar
  54. 54.
    Miller WL, Mahoney DW, Michelena HI, Pislaru SV, Topilsky Y, Enriquez-Sarano M. Contribution of ventricular diastolic dysfunction to pulmonary hypertension complicating chronic systolic heart failure. JACC Cardiovasc Imaging. 2011;4:946–54.PubMedCrossRefGoogle Scholar
  55. 55.
    Miller WL, Grill DE, Borlaug BA. 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. 2013;1:290–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Szwejkowski BR, Elder DH, Shearer F, Jack D, ChoyAM, Pringle SD, et al. Pulmonary hypertension predicts all-cause mortality in patients with heart failure: a retrospective cohort study. Eur J Heart Fail. 2012;14:162–7.Google Scholar
  57. 57.
    Cappola TP, Felker GM, Kao WH, Hare JM, Baughman KL, Kasper EK. Pulmonary hypertension and risk of death in cardiomyopathy: patients with myocarditis are at higher risk. Circulation. 2002;105:1663–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Butler J, Chomsky DB, Wilson JR. Pulmonary hypertension and exercise intolerance in patients with heart failure. J Am Coll Cardiol. 1999;34:1802–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Hurdman J, Condliffe R, Elliot CA, Davies C, Hill C, Wild JM, et al. Aspire registry: assessing the spectrum of pulmonary hypertension identified at a referral centre. Eur Respir J. 2012;39:945–55.PubMedCrossRefGoogle Scholar
  60. 60.
    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;7:288–99.PubMedCrossRefGoogle Scholar
  61. 61.
    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;53:1119–26.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    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;130:2310–20.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Anjan VY, Loftus TM, Burke MA, Akhter N, Fonarow GC, Gheorghiade M, et al. Prevalence, clinical phenotype, and outcomes associated with normal b-type natriuretic peptide levels in heart failure with preserved ejection fraction. Am J Cardiol. 2012;110:870–6.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Damy T, Goode KM, Kallvikbacka-Bennett A, Lewinter C, Hobkirk J, Nikitin NP, et al. Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure. Eur Heart J. 2010;31:2280–90.PubMedCrossRefGoogle Scholar
  65. 65.
    Shah AM, Shah SJ, Anand IS, Sweitzer NK, O’Meara E, Heitner JF, et al. Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circ Heart Fail. 2014;7:104–15.PubMedCrossRefGoogle Scholar
  66. 66.
    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;106:284–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Dalos D, Mascherbauer J, Zotter-Tufaro C, Duca F, Kammerlander AA, Aschauer S, et al. Functional status, pulmonary artery pressure, and clinical outcomes in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2016;68:189–99.PubMedCrossRefGoogle Scholar
  68. 68.
    Dupuis J, Guazzi M. Pathophysiology and clinical relevance of pulmonary remodelling in pulmonary hypertension due to left heart diseases. Can J Cardiol. 2015;31:416–29.PubMedCrossRefGoogle Scholar
  69. 69.
    West JB, Mathieu-Costello O. Vulnerability of pulmonary capillaries in heart disease. Circulation. 1995;92:622–31.PubMedCrossRefGoogle Scholar
  70. 70.
    Elliott AR, Fu Z, Tsukimoto K, Prediletto R, Mathieu-Costello O, West JB. Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure. J Appl Physiol (1985). 1992;73:1150–8.Google Scholar
  71. 71.
    Guazzi M. Alveolar gas diffusion abnormalities in heart failure. J Card Fail. 2008;14:695–702.PubMedCrossRefGoogle Scholar
  72. 72.
    Moraes DL, Colucci WS, Givertz MM. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation. 2000;102:1718–23.PubMedCrossRefGoogle Scholar
  73. 73.
    Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med. 2003;348:500–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Jasmin JF, Calderone A, Leung TK, Villeneuve L, Dupuis J. Lung structural remodeling and pulmonary hypertension after myocardial infarction: complete reversal with irbesartan. Cardiovasc Res. 2003;58:621–31.PubMedCrossRefGoogle Scholar
  75. 75.
    Kingsbury MP, Huang W, Donnelly JL, Jackson E, Needham E, Turner MA, et al. Structural remodelling of lungs in chronic heart failure. Basic Res Cardiol. 2003;98:295–303.PubMedCrossRefGoogle Scholar
  76. 76.
    Chen Y, Guo H, Xu D, Xu X, Wang H, Hu X, et al. Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease. Hypertension. 2012;59:1170–8.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Guazzi M, Arena R. Pulmonary hypertension with left-sided heart disease. Nat Rev Cardiol. 2010;7:648–59.PubMedCrossRefGoogle Scholar
  78. 78.
    Kutty RS, Parameshwar J, Lewis C, Catarino PA, Sudarshan CD, Jenkins DP, et al. Use of centrifugal left ventricular assist device as a bridge to candidacy in severe heart failure with secondary pulmonary hypertension. Eur J Cardiothorac Surg. 2013;43:1237–42.PubMedCrossRefGoogle Scholar
  79. 79.
    ten Freyhaus H, Dagnell M, Leuchs M, Vantler M, Berghausen EM, Caglayan E, et al. Hypoxia enhances platelet-derived growth factor signaling in the pulmonary vasculature by down-regulation of protein tyrosine phosphatases. Am J Respir Crit Care Med. 2011;183:1092–102.PubMedCrossRefGoogle Scholar
  80. 80.
    Guazzi MD, Berti M, Doria E, Fiorentini C, Galli C, Pepi M, et al. Enhancement of the pulmonary vasoconstriction reaction to alveolar hypoxia in systemic high blood pressure. Clin Sci (Lond). 1991;80:403.CrossRefGoogle Scholar
  81. 81.
    Azarbar S, Dupuis J. Lung capillary injury and repair in left heart disease: a new target for therapy? Clin Sci (Lond). 2014;127:65–76.CrossRefGoogle Scholar
  82. 82.
    Guazzi M, Pontone G, Brambilla R, Agostoni P, Reina G. Alveolar-capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure. Eur Heart J. 2002;23:467–76.PubMedCrossRefGoogle Scholar
  83. 83.
    Kitzman DW, Guazzi M. Impaired alveolar capillary membrane diffusion: a recently recognized contributor to exertional dyspnea in heart failure with preserved ejection fraction. JACC Heart Fail. 2016;4:499–501.PubMedCrossRefGoogle Scholar
  84. 84.
    Hoeper MM, Meyer K, Rademacher J, Fuge J, Welte T, Olsson KM. Diffusion capacity and mortality in patients with pulmonary hypertension due to heart failure with preserved ejection fraction. JACC Heart Fail. 2016;4:441–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Borlaug BA, Olson TP. The lungs in heart failure: Not an innocent bystander. JACC Heart Fail. 2016;4:450–2.PubMedCrossRefGoogle Scholar
  86. 86.
    Olson TP, Johnson BD, Borlaug BA. Impaired pulmonary diffusion in heart failure with preserved ejection fraction. JACC Heart Fail. 2016;4:490–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Patel JB, Borgeson DD, Barnes ME, Rihal CS, Daly RC, Redfield MM. Mitral regurgitation in patients with advanced systolic heart failure. J Card Fail. 2004;10:285–91.PubMedCrossRefGoogle Scholar
  88. 88.
    van Empel VP, Kaufmann BA, Bernheim AM, Goetschalckx K, Min SY, Muzzarelli S, et al. Interaction between pulmonary hypertension and diastolic dysfunction in an elderly heart failure population. J Card Fail. 2014;20:98–104.PubMedCrossRefGoogle Scholar
  89. 89.
    Ennezat PV, Marechaux S, Bouabdallaoui N, Le Jemtel TH. Dynamic nature of pulmonary artery systolic pressure in decompensated heart failure with preserved ejection fraction: role of functional mitral regurgitation. J Card Fail. 2013;19:746–52.PubMedCrossRefGoogle Scholar
  90. 90.
    Marechaux S, Neicu DV, Braun S, Richardson M, Delsart P, Bouabdallaoui N, et al. Functional mitral regurgitation: a link to pulmonary hypertension in heart failure with preserved ejection fraction. J Card Fail. 2011;17:806–12.PubMedCrossRefGoogle Scholar
  91. 91.
    Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol. 2013;62:D22–33.PubMedCrossRefGoogle Scholar
  92. 92.
    Delgado JF. The right heart and pulmonary circulation (iii). The pulmonary circulation in heart failure. Rev Esp Cardiol. 2010;63:334–45.PubMedCrossRefGoogle Scholar
  93. 93.
    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;128:1623–33.PubMedCrossRefGoogle Scholar
  94. 94.
    La Vecchia L, Zanolla L, Varotto L, Bonanno C, Spadaro GL, Ometto R, et al. Reduced right ventricular ejection fraction as a marker for idiopathic dilated cardiomyopathy compared with ischemic left ventricular dysfunction. Am Heart J. 2001;142:181–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Puwanant S, Priester TC, Mookadam F, Bruce CJ, Redfield MM, Chandrasekaran K. Right ventricular function in patients with preserved and reduced ejection fraction heart failure. Eur J Echocardiogr. 2009;10:733–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Damy T, Kallvikbacka-Bennett A, Goode K, Khaleva O, Lewinter C, Hobkirk J, et al. Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (tapse) among out-patients referred for the evaluation of heart failure. J Card Fail. 2012;18:216–25.PubMedCrossRefGoogle Scholar
  97. 97.
    Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23:685–713. quiz 786-688.PubMedCrossRefGoogle Scholar
  98. 98.
    Naeije R, D’Alto M. The diagnostic challenge of group 2 pulmonary hypertension. Prog Cardiovasc Dis. 2016;59:22–9.Google Scholar
  99. 99.
    Arkles JS, Opotowsky AR, Ojeda J, Rogers F, Liu T, Prassana V, et al. Shape of the right ventricular doppler envelope predicts hemodynamics and right heart function in pulmonary hypertension. Am J Respir Crit Care Med. 2011;183:268–76.PubMedCrossRefGoogle Scholar
  100. 100.
    Claessen G, La Gerche A, Voigt JU, Dymarkowski S, Schnell F, Petit T, et al. Accuracy of echocardiography to evaluate pulmonary vascular and rv function during exercise. JACC Cardiovasc Imaging. 2016;9:532–43.PubMedCrossRefGoogle Scholar
  101. 101.
    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:H1373–81.PubMedCrossRefGoogle Scholar
  102. 102.
    Sanz J, Garcia-Alvarez A, Fernandez-Friera L, Nair A, Mirelis JG, Sawit ST, et al. Right ventriculo-arterial coupling in pulmonary hypertension: a magnetic resonance study. Heart. 2012;98:238–43.PubMedCrossRefGoogle Scholar
  103. 103.
    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. doi: 10.1093/eurheartj/ehw241.
  104. 104.
    Hussain I, Mohammed SF, Forfia PR, Lewis GD, Borlaug BA, Gallup DS, et al. Impaired right ventricular-pulmonary arterial coupling and effect of sildenafil in heart failure with preserved ejection fraction: an ancillary analysis from the phosphodiesterase-5 inhibition to improve clinical status and exercise capacity in diastolic heart failure (relax) trial. Circ Heart Fail. 2016;9.Google Scholar
  105. 105.
    Frea S, Pidello S, Bovolo V, Iacovino C, Franco E, Pinneri F, et al. Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure. Eur J Heart Fail. 2016;18:564–72.PubMedCrossRefGoogle Scholar
  106. 106.
    Dandel M, Knosalla C, Kemper D, Stein J, Hetzer R. Assessment of right ventricular adaptability to loading conditions can improve the timing of listing to transplantation in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2015;34:319–28.Google Scholar
  107. 107.
    Andersen MJ, Nishimura RA, Borlaug BA. The hemodynamic basis of exercise intolerance in tricuspid regurgitation. Circ Heart Fail. 2014;7:911–7.PubMedCrossRefGoogle Scholar
  108. 108.
    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;31:467–77.PubMedCrossRefGoogle Scholar
  109. 109.
    Lewis GD, Shah RV, Pappagianopolas PP, Systrom DM, Semigran MJ. Determinants of ventilatory efficiency in heart failure: the role of right ventricular performance and pulmonary vascular tone. Circ Heart Fail. 2008;1:227–33.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Guazzi M, Naeije R, Arena R, Corra U, Ghio S, Forfia P, et al. Echocardiography of right ventriculoarterial coupling combined with cardiopulmonary exercise testing to predict outcome in heart failure. Chest. 2015;148:226–34.PubMedCrossRefGoogle Scholar
  111. 111.
    Melenovsky V, Kotrc M, Borlaug BA, Marek T, Kovar J, Malek I, et al. Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. J Am Coll Cardiol. 2013;62:1660–70.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.University Cardiology Department, IRCCS Policlinico San DonatoUniversity of MilanoMilanItaly

Personalised recommendations