2016


To access this material please log in or register

Register Authorize
2016/№2

Pulmonary hypertension associated with diastolic heart failure: pathogenesis, diagnosis, treatment

Ovchinnikov A. G., Gavryushina S. V., Ageev F. T.
Federal State Budgetary Institution, “Russian Cardiology Science and Production Center” of the RF Ministry of Health Care, 3rd Cherepkovskaya 15a, Moscow 121552

Keywords: diastolic CHF, pulmonary hypertension, right ventricle

DOI: 10.18087/rhfj.2016.2.2210

Many patients with diastolic HF have increased pulmonary artery blood pressure. This review discusses pathophysiology of developing left-sided pulmonary hypertension and principles of its diagnosis. Therapeutic actions for elimination of pulmonary hypertension are addressed.
  1. Redfield MM, Jacobsen SJ, Burnett JC, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003 Jan 8;289 (2):194–202.
  2. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355 (3):251–9.
  3. Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A et al. Outcome of heart failure with preserved ejection fraction in a popu­lation-based study. N Engl J Med. 2006 Jul 20;355 (3):260–9.
  4. Cowie MR, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, Suresh V, Sutton GC. Incidence and aetiology of heart failure; a popylation-based study. Eur Heart J. 1999 Mar;20 (6):421–8.
  5. 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 Mar 31;53 (13):1119–26.
  6. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013 Dec 24;62 (25 Suppl): D34–41.
  7. Oudiz RJ. Pulmonary hypertension associated with left-sided heart disease. Clin Chest Med. 2007 Mar;28 (1):233–41.
  8. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009 Jun 30;54 (1 Suppl): S43–54.
  9. Hoeper MM, Barbera JA, Channick RN, Hassoun PM, Lang IM, Manes A et al. Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension. J Am Coll Cardiol. 2009 Jun 30;54 (1 Suppl): S85–96.
  10. 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 adultea summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2012 Sep;31 (9):913–33.
  11. Negrini D, Passi A, de Luca G, Miserocchi G. Pulmonary interstitial pressure and proteoglycans during development of pulmonary edema. Am J Physiol. 1996 Jun;270 (6 Pt 2):H2000–7.
  12. Palestini P, Calvi C, Conforti E, Botto L, Fenoglio C, Miserocchi G. Composition, biophysical properties, and morphometry of plasma membranes in pulmonary interstitial edema. Am J Physiol Lung Cell Mol Physiol. 2002 Jun;282 (6):L1382–90.
  13. Tsutamoto T, Wada A, Maeda Y, Adachi T, Kinoshita M. Relation between endothelin-1 spillover in the lungs and pulmonary vascular resistance in patients with chronic heart failure. J Am Coll Cardiol. 1994 May;23 (6):1427–33.
  14. Deuchar GA, Docherty A, MacLean MR, Hicks MN. Pulmonary hypertension secondary to left ventricular dysfunction: the role of nitric oxide and endothelin-1 in the control of pulmonary vascular tone. Br J Pharmacol. 2002 Feb;135 (4):1060–8.
  15. Tribouilloy CM, Enriquez-Sarano M, Rossi A, Tajik AJ, Seward JB. Determinants of the pulmonary artery pressure rise in left ventricular dysfunction. Cardiologia. 1997 Oct;42 (10):1051–8.
  16. Forfia PR. Approach to patients with heart failure and pulmonary hypertension. Curr Treat Options Cardiovasc Med. 2007 Aug;9 (4):302–9.
  17. 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 Feb;20 (2):98–104.
  18. Moraes DL, Colucci WS, Givertz MM. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation. 2000 Oct 12;102 (14):1718–23.
  19. West JB, Mathieu-Costello O. Vulnerability of pulmonary capilla­ries in heart disease. Circulation. 1995 Aug 1;92 (3):622–31.
  20. Mahdyoon H, Klein R, Eyler W, Lakier JB, Chakko SC, Gheorghiade M. Radiographic pulmonary congestion in end-stage congestive heart failure. Am J Cardiol. 1989 Mar 1;63 (9):625–7.
  21. Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA. 1989 Feb 10;261 (6):884–8.
  22. Chen Y1, 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 Jun;59 (6):1170–8.
  23. Kerem A, Yin J, Kaestle SM, Hoffmann J, Schoene AM, Singh B et al. Lung endothelial dysfunction in congestive heart failure: role of impaired Ca2+ signaling and cytoskeletal reorganization. Circ Res. 2010 Apr 2;106 (6):1103–16.
  24. Kapanci Y, Burgan S, Pietra GG, Conne B, Gabbiani G. Modulation of actin isoform expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension. Am J Pathol. 1990 Apr;136 (4):881–9.
  25. Guazzi M1. Alveolar gas diffusion abnormalities in heart failure. J Card Fail. 2008 Oct;14 (8):695–702.
  26. Solomonica A, Burger AJ, Aronson D. Hemodynamic determinants of dyspnea improvement in acute decompensated heart failure. Circ Heart Fail. 2013 Jan;6 (1):53–60.
  27. 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 Int Med. 2013 Sep;24 (6):562–7.
  28. Овчинников А. Г. Роль нарушения баланса коллагена в формировании диастолической дисфункции и оптимизация лечения больных с диастолической дисфункцией с учётом её тяжести и выраженности клинических проявлений. Автореф. дис. … докт. мед. наук. –М., 2012. – 54с [Ovchinnikov A. G. Rol` narushe­niya balansa kollagena v formirovanii diastolicheskoj disfunkczii i optimizacziya lecheniya bol`ny`x s diastolicheskoj disfunkcziej s uchyotom eyo tyazhesti i vy`razhennosti klinicheskix proyavlenij. Avtoref. dis. … dokt. med. nauk. – M., 2012. – 54s].
  29. Azarbar S, Dupuis J. Lung capillary injury and repair in left heart disease: a new target for therapy? Clin Sci (Lond). 2014 Jul;127 (2):65–76.
  30. 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 Jan 17;125 (2):289–97.
  31. 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 Mar 8;117 (11):1436–48.
  32. Kerbaul F, Brimioulle S, Rondelet B, Dewachter C, Hubloue I, Naeije R. How prostacyclin improves cardiac output in right heart failure in conjunction with pulmonary hypertension. Am J Respir Crit Care Med. 2007 Apr 15;175 (8):846–50.
  33. Kuehne T, Yilmaz S, Steendijk P, Moore P, Groenink M, Saaed M et al. Magnetic resonance imaging analysis of right ventricular pressure-volume loops: in vivo validation and clinical application in patients with pulmonary hypertension. Circulation. 2004 Oct 5;110 (14):2010–6.
  34. Otto C. Practice of Clinical Echocardiography, 4th ed. – Philadelphia, PA: Elsevier / Saunders, 2012. – P629–45.
  35. Tei C, Dujardin KS, Hodge DO, Bailey KR, McGoon MD, Tajik AJ, Seward SB. Doppler echocardiographic index for assessment of global right ventricular function. J Am Soc Echocardiogr. 1996 Nov-Dec;9 (6):838–47.
  36. Sallach JA, Tang WH, Borowski AG, Tong W, Porter T, Martin MG et al. Right atrial volume index in chronic systolic heart failure and prognosis. JACC Cardiovasc Imaging. 2009 May;2 (5):527–34.
  37. Guazzi M, Gatto P, Giusti G, Pizzamiglio F, Previtali I, Vignati C, Arena R. Pathophysiology of cardiorenal syndrome in decompensated heart failure: role of lung – right heart – kidney interaction. Int J Cardiol. 2013 Nov 30;169 (6):379–84.
  38. Atherton JJ, Moore TD, Lele SS, Thomson HL, Galbraith AJ, Belenkie I et al. Diastolic ventricular interaction in chronic heart failure. Lancet. 1997 Jun 14;349 (9067):1720–4.
  39. Douglas PS, Morrow R, Ioli A, Reichek N. Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1989 Feb;13 (2):311–5.
  40. 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 Jan;7 (1):116–22.
  41. 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 Nov 1;305 (9):H1373–81.
  42. Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet. 1999 May 29;353 (9167):1838–42.
  43. Melenovsky V, Kotrc M, Borlaug BA, Marek T, Kovar J, Malek I, Kautzner J. Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. J Am Coll Cardiol. 2013 Oct 29;62 (18):1660–70.
  44. Anjan VY, Loftus TM, Burke MA, Akhter N, Fonarow GC, Gheorghiade M, Shah SJ. Prevalence, clinical phenotype, and outcomes associated with normal b-type natriuretic peptide levels in heart failure with preserved ejection fraction. Am J Cardiol. 2012 Sep 15;110 (6):870–6.
  45. Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. 2014 Dec 21;35 (48):3452–62.
  46. 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 Dec 23;130 (25):2310–20.
  47. 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 Mar 1;7 (2):288–99.
  48. Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail. 2010 Sep;3 (5):588–95.
  49. Scwartzenberg S, Redfield MM, From AM, Sorajja P, Nishimura RA, Borlaug BA. Effects of vasodilation in heart failure with preserved or reduced ejection fraction implications of distinct pathophysiologies on response to therapy. J Am Coll Cardiol. 2012 Jan 31;59 (5):442–51.
  50. Gavazzi A, Ghio S, Scelsi L, Campana C, Klersy C, Serio A et al. Response of the right ventricle to acute pulmonary vasodilation predicts the outcome in patients with advanced heart failure and pulmonary hypertension. Am Heart J. 2003 Feb;145 (2):310–6.
  51. 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 Jan;37 (1):183–8.
  52. Salamon JN, Kelesidis I, Msaouel P, Mazurek JA, Mannem S, Adzic A, Zolty R. Outcomes in World Health Organization group II pulmonary hypertension: mortality and readmission trends with systolic and preserved ejection fraction induced pulmonary hypertension. J Card Fail. 2014 Jul;20 (7):467–75.
  53. Aronson D, Eitan A, Dragu R, Burger AJ. Relationship between reactive pulmonary hypertension and mortality in patients with acute decompensated heart failure. Circ Heart Fail. 2011 Sep;4 (5):644–50.
  54. Rabinovitz A, Raiszadeh F, Zolty R. Association of hyponatremia and outcomes in pulmonary hypertension. J Card Fail. 2013 Aug;19 (8):550–6.
  55. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Faber HW, Lindner JR et al. ACCF / AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009 Apr 28;53 (17):1573–619.
  56. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009 Feb;22 (2):107–33.
  57. Gallagher RC, Kormos RL, Gasior T, Murali S, Griffith BP, Hardesty RL. Univentricular supportresults in reduction of pulmonary resistance and improved right ventricular function. ASAIO Trans. 1991 Jul-Sep;37 (3):M287–8.
  58. Zimpfer D, Zrunek P, Roethy W, Czerny M, Schima H, Huber L et al. Left ventricular assist devices decrease fixed pulmonary hypertension in cardiac transplant candidates. J Thorac Cardiovasc Surg. 2007 Mar;133 (3):689–95.
  59. John R, Liao K, Kamdar F, Eckman P, Boyle A, Colvin-Adams M. Effects on pre- and posttransplant pulmonary hemodynamics in patients with continuous-flow left ventricular assist devices. J Thorac Cardiovasc Surg. 2010 Aug;140 (2):447–52.
  60. Wharton J, Strange JW, Møller GM, Growcott EJ, Ren X, Franklyn AP et al. Antiproliferative effects of phosphodiesterase type 5 Inhibition in human pulmonary artery cells. Am J Respir Crit Care Med. 2005 Jul 1;172 (1):105–13.
  61. Li B, Yang L, Shen J, Wang C, Jiang Z. The antiproliferative effect of sildenafil on pulmonary artery smooth muscle cells is mediated via upregulation of mitogen-activated protein kinase phosphatase-1 and degradation of extracellular signal-regulated kinase 1 / 2 phosphorylation. Anesth Analg. 2007 Oct;105 (4):1034–41.
  62. Schermuly RT, Pullamsetti SS, Kwapiszewska G, Dumitrascu R, Tian X, Weissmann N et al. Phosphodiesterase 1 upregulation in pulmonary arterial hypertension: target for reverse-remodeling therapy. Circulation. 2007 May 1;115 (17):2331–9.
  63. Jones DA, Benjamin CW, Linseman DA. Activation of thrombo­xane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol Pharmacol. 1995 Nov;48 (5):890–6.
  64. Lin H, Lee JL, Hou HH, Chung CP, Hsu SP, Juan SH. Molecular mechanisms of the antiproliferative effect of beraprost, a prostacyclin agonist, in murine vascular smooth muscle cells. J Cell Physiol. 2008 Feb;214 (2):434–41.
  65. Guazzi M, Agostoni P. Angiotensin-converting enzyme inhibition restores the diffusing capacity for carbon monoxide in patients with chronic heart failure by improving the molecular diffusion across the alveolar capillary membrane. Clin Sci (Lond). 1999 Jan;96 (1):17–22.
  66. Agostoni P, Magini A, Andreini D, Contini M, Apostolo A, Bussotti M et al. Spironolactone improves lung diffusion in chronic heart failure. Eur Heart J. 2005 Jan;26 (2):159–64.
  67. Guazzi M. Pulmonary hypertension in heart failure preserved ejection fraction: prevalence, pathophysiology, and clinical perspectives. Circ Heart Fail. 2014 Mar 1;7 (2):367–77.
  68. Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012 Aug 21;126 (8):975–90.
  69. Gottlieb SS. The impact of finally publishing a negative study: new conclusions about endothelin antagonists. J Card Fail. 2005 Feb;11 (1):21–2.
  70. 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 Jul;134 (1):44–54.
  71. Kalra PR, Moon JC, Coats AJ. Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure? Int J Cardiol. 2002 Oct;85 (2-3):195–7.
  72. Anand I, McMurray J, Cohn JN, Konstam MA, Notter T, Quitzau K et al. Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial. Lancet. 2004 Jul 24–30;364 (9431):347–54.
  73. Kaluski E, Cotter G, Leitman M, Milo-Cotter O, Krakover R, Kobrin I et al. Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension – a multi-center randomized study. Cardiology. 2008;109 (4):273–80.
  74. Kaluski E, Kobrin I, Zimlichman R, Marmor A, Krakov O, Milo O et al. RITZ-5: randomized intravenous TeZosentan (an endothelin-A / B antagonist) for the treatment of pulmonary edema: a prospective, multicenter, double-blind, placebo-controlled study. J Am Coll Cardiol. 2003 Jan 15;41 (2):204–10.
  75. Ardehali A, Hughes K, Sadeghi A, Esmailian F, Marelli D, Moriguchi J et al. Inhaled nitric oxide for pulmonary hypertension after heart transplantation. Transplantation. 2001 Aug 27;72 (4):638–41.
  76. Zhuang XD, Long M, Li F, Hu X, Liao XX, Du ZM. PDE5 inhibitor sildenafil in the treatment of heart failure: a meta-analysis of randomized controlled trials. Int J Cardiol. 2014 Apr 1;172 (3):581–7.
  77. Lewis GD, Shah RV, Pappagianopoulos 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 Nov;1 (4):227–33.
  78. Murphy RM, Shah RV, Malhotra R, Pappagianopoulos PP, Hough SS, Systrom DM et al. Exercise oscillatory ventilation in systolic heart failure: An indicator of impaired hemodynamic response to exercise. Circulation. 2011 Sep 27;124 (13):1442–51.
  79. Gomez-Sanchez AM, De La Calzada SC, Subias EP, Jimenez JF, Salvador ML, Gonzalez AA, Calvo LC. Pilot assessment of the response of several pulmonary hemodynamic variables to sublingual sildenafil in candidates for heart transplantation. Eur J Heart Fail. 2004 Aug;6 (5):615–7.
  80. Jabbour A, Keogh A, Hayward C, Macdonald P. Chronic sildenafil lowers transpulmonary gradient and improves cardiac output allowing successful heart transplantation. Eur J Heart Fail. 2007 Jun-Jul;9 (6-7):674–7.
  81. Lewis GD, Lachmann J, Camuso J, Lepore JJ, Shin J, Martinovic ME et al. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure. Circulation. 2007 Jan 2;115 (1):59–66.
  82. Behling A, Rohde LE, Colombo FC, Goldraich LA, Stein R, Clausell N. Effects of 5’ – phosphodiesterase four-week long inhibition with sildenafil in patients with chronic heart failure: a double-blind, placebo-controlled clinical trial. J Card Fail. 2008 Apr;14 (3):189–97.
  83. Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol. 2004 Dec 21;44 (12):2339–48.
  84. Guazzi M, Samaja M, Arena R, Vicenzi M, Guazzi MD. Long-term use of sildenafil in the therapeutic management of heart failure. J Am Coll Cardiol. 2007 Nov 27;50 (22):2136–44.
  85. Guazzi M, Myers J, Peberdy MA, Bensimhon D, Chase P, Arena R. Ventilatory efficiency and dyspnea on exertion improvements are related to reduced pulmonary pressure in heart failure patients receiving Sildenafil. Int J Cardiol. 2010 Oct 29;144 (3):410–2.
  86. Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geo­metry, and clinical status in patients with stable systolic heart failure: results of a 1‑year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011 Jan;4 (1):8–17.
  87. 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 Jul 12;124 (2):164–74.
  88. Guazzi M, Vicenzi M, Arena R. Phosphodiesterase 5 inhibition with sildenafil reverses exercise oscillatory breathing in chronic heart failure: a long-term cardiopulmonary exercise testing placebo-controlled study. Eur J Heart Fail. 2012 Jan;14 (1):82–90.
  89. Pons J, Leblanc MH, Bernier M, Cantin B, Bourgault C, Bergeron S et al. Effects of chronic sildenafil use on pulmonary hemodyna­mics and clinical outcomes in heart transplantation. J Heart Lung Transplant. 2012 Dec;31 (12):1281–7.
  90. Reichenbach A, Al-Hiti H, Malek I, Pirk J, Goncalvesova E, Kautzner J, Melenovsky V. The effects of phosphodiesterase 5 inhibition on hemodynamics, functional status and survival in advanced heart failure and pulmonary hypertension: a case-control study. Int J Cardiol. 2013 Sep 20;168 (1):60–5.
  91. Urbanowicz T, Straburzynska-Migaj E, Katynska I, Araszkiewicz A, Oko-Sarnowska Z, Grajek S, Jemielity M. Sustained improvement of clinical status and pulmonary hypertension in patients with severe heart failure treated with sildenafil. Ann Transplant. 2014 Jul 9;19:325–30.
  92. Alaeddini J, Uber PA, Park MH, Scott RL, Ventura HO, Mehra MR. Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in severe heart failure. Am J Cardiol. 2004 Dec 1;94 (11):1475–7.
  93. Lepore JJ, Maroo A, Bigatello LM, Dec GW, Zapol WM, Bloch KD, Semigran MJ. Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide. Chest. 2005 May;127 (5):1647–53.
  94. Dumitrescu D, Seck C, Möhle L, Erdmann E, Rosenkranz S. Therapeutic potential of sildenafil in patients with heart failure and reactive pulmonary hypertension. Int J Cardiol. 2012 Jan 26;154 (2):205–6
  95. Tedford RJ, Hemnes AR, Russell SD, Wittstein IS, Mahmud M, Zaiman AL et al. PDE5A inhibitor treatment of persistent pulmonary hypertension after mechanical circulatory support. Circ Heart Fail. 2008 Nov;1 (4):213–9.
  96. De Santo LS, Buonocore M, Agrusta F, Bancone C, Galdieri N, Romano G et al. Pattern of resolution of pulmonary hypertension, long-term allograft right ventricular function, and exercise capacity in high-risk heart transplant recipients listed under oral sildenafil. Clin Transplant. 2014 Jul;28 (7):837–43.
  97. Schmidt HH, Hofmann F, Stasch JP. Generators, Effectors and Therapeutic Implicatons Handbook of Experimental Pharmacology 191. – Berlin: Springer-Verlag, 2009. – P485–506.
  98. Hofmann F, Feil R, Kleppisch T, Schlossmann J. Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev. 2006 Jan;86 (1):1–23.
  99. van Heerebeek L, Hamdani N, Falcao-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG et al. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation. 2012 Aug 14;126 (7):830–9.
  100. Murray F, MacLean MR, Pyne NJ. Increased expression of the cGMP-inhibited cAMP-specific (PDE3) and cGMP binding cGMP-specific (PDE5) phosphodiesterases in models of pulmonary hypertension. Br J Pharmacol. 2002 Dec;137 (8):1187–94.
  101. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005 Feb;11 (2):214–22.
  102. Shan X, Quaile MP, Monk JK, French B, Cappola TP, Margulies KB. Differential expression of PDE5 in failing and nonfailing human myocardium. Circ Heart Fail. 2012 Jan;5 (1):79–86.
  103. Lu Z, Xu X, Hu X, Lee S, Traverse JH, Zhu G et al. Oxidative stress regulates left ventricular PDE5 expression in the failing heart. Circulation. 2010 Apr 6;121 (13):1474–83.
  104. Nagayama T, Hsu S, Zhang M, Koitabashi N, Bedja D, Gabrielson KL et al. Sildenafil stops progressive chamber, cellular, and mole­cular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J Am Coll Cardiol. 2009 Jan 13;53 (2):207–15.
  105. Bishu K, Hamdani N, Mohammed SF, Kruger M, Ohtani T, Ogut O et al. Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo. Circulation. 2011 Dec 20;124 (25):2882–91.
  106. Kohr MJ, Davis JP, Ziolo MT. Peroxynitrite increases protein phosphatase activity and promotes the interaction of phospholamban with protein phosphatase 2a in the myocardium. Nitric Oxide. 2009 Apr 15;20 (3):217–21.
  107. Selby DE, Palmer BM, LeWinter MM, Meyer M. Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction. J Am Coll Cardiol. 2011 Jul 5;58 (2):147–54.
  108. Masuyama H, Tsuruda T, Kato J, Imamura T, Asada Y, Stasch JP et al. Soluble guanylate cyclase stimulation on cardiovascular remode­ling in angiotensin II-induced hypertensive rats. Hypertension. 2006 Nov;48 (5):972–8.
  109. Masuyama H, Tsuruda T, Sekita Y, Hatakeyama K, Imamura T, Kato J et al. Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart. Hypertens Res. 2009 Jul;32 (7):597–603.
  110. Yin J, Kukucka M, Hoffmann J, Sterner-Kock A, Burhenne J, Haefeli WE et al. Sildenafil preserves lung endothelial function and prevents pulmonary vascular remodeling in a rat model of diastolic heart failure. Circ Heart Fail. 2011 Mar;4 (2):198–206.
  111. Al-Hesayen A, Floras JS, Parker JD. The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure. Eur J Heart Fail. 2006 Dec;8 (8):864–8.
  112. Melenovsky V, Al-Hiti H, Kazdova L, Jabor A, Syrovatka P, Malek I et al. Transpulmonary B-type natriuretic peptide uptake and cyclic guanosine monophosphate release in heart failure and pulmonary hypertension: the effects of sildenafil. J Am Coll Cardiol. 2009 Aug 11;54 (7):595–600.
  113. Oliver JJ, Melville VP, Webb DJ. Effect of regular phosphodieste­rase type 5 inhibition in hypertension. Hypertension. 2006 Oct;48 (4):622–7.
  114. Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol. 2000 Sep;36 (3):845–51.
  115. Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation. 2003 Aug 5;108 (5):560–5.
  116. Borlaug BA, Melenovsky V, Marhin T, Fitzgerald P, Kass DA. Sildenafil inhibits beta-adrenergic-stimulated cardiac contractility in humans. Circulation. 2005 Oct 25;112 (17):2642–9.
  117. Borlaug BA, Olson TP, Lam CS, Flood KS, Lerman A, Johnson BD, Redfield MM. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2010 Sep 7;56 (11):845–54.
  118. Redfield MM, Borlaug BA, Lewis GD, Mohammed SF, Semigran MJ, Lewinter MM et al. PhosphdiesteRasE-5 inhibition to improve CLinical status and EXercise capacity in diastolic heart failure (RELAX) Trial: rationale and design. Circ Heart Fail. 2012 Sep 1;5 (5):653–9.
  119. Hoendermis ES, Liu LC, Hummel YM, van der Meer P, Boer RA, Berger RM et al. 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. 2015 Oct 7;36 (38):2565–73.
  120. Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007 Oct 2;116 (14):1555–62.
Ovchinnikov A. G., Gavryushina S. V., Ageev F. T. Pulmonary hypertension associated with diastolic heart failure: pathogenesis, diagnosis, treatment. Russian Heart Failure Journal. 2016;17 (2):114–129

To access this material please log in or register

Register Authorize
Ru En