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Molecular Mechanisms of Diastolic Dysfunction

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Diastolic Heart Failure

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Abstract

Heart failure is a clinical syndrome characterized by symptoms and signs of decreased tissue perfusion and increased tissue water. Defining the cause of this syndrome requires measurements of both systolic and diastolic functions. When abnormalities in diastolic function are predominant and abnormalities in hemodynamic pump function are absent or mild (e.g., preserved ejection fraction [EF]), this syndrome is called “diastolic heart failure” (DHF) or “heart failure with preserved ejection fraction.”

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References

  1. Brutsaert DL. Cardiac dysfunction in heart failure: the cardiologist’s love affair with time. Prog Cardiovasc Dis 2006:49:157–181.

    Article  PubMed  Google Scholar 

  2. Brutsaert DL, Sys SU. Relaxation and diastole of the heart. Physiol Rev 1989;69:1228–1315.

    PubMed  CAS  Google Scholar 

  3. Brutsaert DL, Rademakers FE, Sys SU. Triple control of relaxation: implications in cardiac disease. Circulation 1984;69:190–196.

    PubMed  CAS  Google Scholar 

  4. Frank KF, Bolck B, Brixius K, Kranias EG, Schwinger RH. Modulation of SERCA: implications for the failing human heart. Basic Res Cardiol 2002;97(Suppl 1):I72–I78.

    PubMed  Google Scholar 

  5. del Monte F, Harding SE, Dec GW, Gwathmey JK, Hajjar RJ. Targeting phospholamban by gene transfer in human heart failure. Circulation 2002;105:904–907.

    Article  PubMed  CAS  Google Scholar 

  6. MacLennan DH, Kranias EG. Phospholamban: a crucial regulator of cardiac contractility. Nat Rev Mol Cell Biol 2003;4:566–577.

    Article  PubMed  CAS  Google Scholar 

  7. Hasenfuss G, Pieske B. Calcium cycling in congestive heart failure. J Mol Cell Cardiol 2002;34:951–969.

    Article  PubMed  CAS  Google Scholar 

  8. Miyamoto MI, del Monte F, Schmidt U, DiSalvo TS, Kang ZB, Matsui T, Guerrero JL, Gwathmey JK, Rosenzweig A, Hajjar RJ. Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc Natl Acad Sci USA 2000;97:793–798.

    Article  PubMed  CAS  Google Scholar 

  9. Hoshijima M, Ikeda Y, Iwanaga Y, Minamisawa S, Date MO, Gu Y, Iwatate M, Li M, Wang L, Wilson JM, Wang Y, Ross J Jr, Chien KR. Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med 2002;8:864–871.

    PubMed  CAS  Google Scholar 

  10. Mercadier JJ. Progression from cardiac hypertrophy to heart failure. In Hosenpud D, Greenberg BH, eds. Congestive Heart Failure, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2000:83–100.

    Google Scholar 

  11. Kiss E, Ball NA, Kranias EG, Walsh RA. Differential changes in cardiac phospholamban and sarcoplasmic reticular Ca(2+)-ATPase protein levels. Effects on Ca2+ transport and mechanics in compensated pressure-overload hypertrophy and congestive heart failure. Circ Res 1995;77:759–764.

    PubMed  CAS  Google Scholar 

  12. Ginsburg KS, Bers DM. Modulation of excitation-contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca load and ICa trigger. J Physiol 2004;556:463–480.

    Article  PubMed  CAS  Google Scholar 

  13. Li Y, Kranias EG, Mignery GA, Bers DM. Protein kinase A phosphorylation of the ryanodine receptor does not affect calcium sparks in mouse ventricular myocytes. Circ Res 2002;90:309–316.

    Article  PubMed  CAS  Google Scholar 

  14. Bodor S, Oakeley AE, Allen PD. Troponin I phosphorylation in the normal and failing adult human heart. Circulation 1997;96:1495–1500.

    PubMed  CAS  Google Scholar 

  15. Borbely A, van der Velden J, Papp Z, Bronzwaer JG, Edes I, Stienen GJ, Paulus WJ. Cardiomyocyte stiffness in diastolic heart failure. Circulation 2005;111:774–781.

    Article  PubMed  Google Scholar 

  16. Bronzwaer JG, Paulus WJ. Matrix, cytoskeleton, or myofilaments: which one to blame for diastolic left ventricular dysfunction? Prog Cardiovasc Dis 2005;47:276–284.

    Article  PubMed  Google Scholar 

  17. Geisterfer-Lowrance AA, Christe M, Conner DA, Ingwall JS, Schoen FJ, Seidman CE, Seidman JG. A mouse model of familial hypertrophic cardiomyopathy. Science 1996;272:731–734.

    Article  PubMed  CAS  Google Scholar 

  18. Paulus WJ, Bronzwaer JG, Felice H, Kishan N, Wellens F. Deficient acceleration of left ventricular relaxation during exercise after heart transplantation [abstr]. Circulation 1992;86:1175–1185.

    PubMed  CAS  Google Scholar 

  19. Vantrimpont PJ, Felice H, Paulus WJ. Does dobutamine prevent the rise in left ventricular filling pressures observed during exercise after heart transplantation? Eur Heart. 1995;16:1300–1306a.

    CAS  Google Scholar 

  20. Hori M, Inoue M, Kitakaze M, Tsujioka K, Ishida Y, Fukunami M, Nakajima S, Kitabatake A, Abe H. Loading sequence is a major determinant of after-load-dependent relaxation in intact canine heart. Am J Physiol 1985;249:H747–H754.

    PubMed  CAS  Google Scholar 

  21. Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation 2003;107:714–720.

    Article  PubMed  Google Scholar 

  22. Granzier HL, Irving TC. Passive tension in cardiac muscle: contribution of collagen, titin, microtubules and intermediate filaments. Biophys J 1995;68:1027–1044.

    Article  PubMed  CAS  Google Scholar 

  23. Wu Y, Cazorla O, Labeit D, et al. Changes in titin and collagen underlie diastolic stiffness diversity of cardiac muscle. J Mol Cell Cardiol 2000;32:2151–2162.

    Article  PubMed  CAS  Google Scholar 

  24. Wu Y, Bell SP, Trombitas K, et al. Changes in titin isoform expression in pacing-induced cardiac failure give rise to increased passive muscle stiffness. Circulation 2002;106:1384–1389.

    Article  PubMed  CAS  Google Scholar 

  25. Yamamoto K, Masuyama T, Sakata Y, et al. Myocardial stiffness is determined by ventricular fibrosis but not by compensatory or excessive hypertrophy in hypertensive heart. Cardiovasc Res 2002;55:76–82.

    Article  PubMed  CAS  Google Scholar 

  26. Neagoe C, Kulke M, del Monte F, et al. Titin isoform switch in ischemic human heart. Circulation 2002;106:1333–1341.

    Article  PubMed  Google Scholar 

  27. Yamasaki R, Wu Y, McNabb M, et al. Protein kinase A phosphorylates titin’s cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes. Circ Res 2002;90:1181–1188.

    Article  PubMed  CAS  Google Scholar 

  28. Jalil JE, Doering CW, Janicki JS, Pick R, Shroff SG, Weber KT. Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle. Circ Res 1989;64:1041–1050.

    PubMed  CAS  Google Scholar 

  29. Weber KT, Janicki JS, Pick R, Capasso J, Anversa P. Myocardial fibrosis and pathologic hypertrophy in the rat with renovascular hypertension. Am J Cardiol 1990;65:1G–7G.

    Article  PubMed  CAS  Google Scholar 

  30. Kato S, Spinale FG, Tanaka R, Johnson W, Cooper G 4th, Zile MR. Inhibition of collagen crosslinking: effects on fibrillar collagen and ventricular diastolic function. Am J Physiol 1995;269:H863–H868.

    PubMed  CAS  Google Scholar 

  31. Stroud JD, Baicu CF, Barnes MA, Spinale FG, Zile MR. Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment. Am J Physiol Heart Circ Physiol 2002;282:H2324–H2335.

    PubMed  CAS  Google Scholar 

  32. Brower GL, Janicki JS. Contribution of ventricular remodeling to pathogenesis of heart failure in rats. Am J Physiol Heart Circ Physiol 2001;280:H674–H683.

    PubMed  CAS  Google Scholar 

  33. Kass DA, Bronzwaer JG, Paulus WJ. What mechanisms underlie diastolic dysfunction in heart failure? Circ Res 2004;94:1533–1542.

    Article  PubMed  CAS  Google Scholar 

  34. Paulus WJ, Vantrimpont PJ, Shah AM. Paracrine coronary endothelial control of left ventricular function in humans. Circulation. 1995;92:2119–2126.

    PubMed  CAS  Google Scholar 

  35. Pinsky DJ, Patton S, Mesaros S, Brovkovych V, Kubaszewski E, Grunfeld S, Malinski T. Mechanical transduction of nitric oxide synthesis in the beating heart. Circ Res 1997;81:372–379.

    PubMed  CAS  Google Scholar 

  36. Paulus WJ. Beneficial effects of nitric oxide on cardiac diastolic function: “the flip side of the coin.” Heart Fail Rev 2000;5:337–344.

    Article  PubMed  CAS  Google Scholar 

  37. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure. Part II: causal mechanisms and treatment. Circulation 2002;105:1503–1508.

    Article  PubMed  Google Scholar 

  38. Yu CM, Lin H, Yang H, Kong SL, Zhang Q, Lee SW. Progression of systolic abnormalities in patients with “isolated” diastolic heart failure and diastolic dysfunction. Circulation 2002;105:1195–1201.

    Article  PubMed  Google Scholar 

  39. Yip G, Wang M, Zhang Y, Fung JW, Ho PY, Sanderson JE. Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition? Heart 2002;87:121–125.

    Article  PubMed  CAS  Google Scholar 

  40. Bruch C, Gradaus R, Gunia S, Breithardt G, Wichter T. Doppler tissue analysis of mitral annular velocities: evidence for systolic abnormalities in patients with diastolic heart failure. J Am Soc Echocardiogr 2003;16:1031–1036.

    Article  PubMed  Google Scholar 

  41. Sanderson JE. Diastolic heart failure: fact or fiction? Heart 2003;89:1281–1282.

    Article  PubMed  CAS  Google Scholar 

  42. Petrie MC, Caruana L, Berry C, McMurray JJ. “Diastolic heart failure” or heart failure caused by subtle left ventricular systolic dysfunction? Heart 2002;87:29–31.

    Article  PubMed  CAS  Google Scholar 

  43. Nikitin NP, Witte KK, Clark AL, Cleland JG. Color tissue Doppler-derived long-axis left ventricular function in heart failure with preserved global systolic function. Am J Cardiol 2002;90:1174–1177.

    Article  PubMed  Google Scholar 

  44. Vinereanu D, Nicolaides E, Tweddel AC, Fraser AG. “Pure” diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure. Eur J Heart Fail 2005;7:820–828.

    Article  PubMed  Google Scholar 

  45. Vinereanu D, Lim PO, Frenneaux MP, Fraser AG. Reduced myocardial velocities of left ventricular long-axis contraction identify both systolic and diastolic heart failure-a comparison with brain natriuretic peptide. Eur J Heart Fail 2005;7:512–519.

    Article  PubMed  CAS  Google Scholar 

  46. Hasegawa H, Little WC, Ohno M, Brucks S, Morimoto A, Cheng HJ, Cheng CP. Diastolic mitral annular velocity during the development of heart failure. J Am Coll Cardiol. 2003;41:1590–1597.

    Article  PubMed  Google Scholar 

  47. Baicu CF, Zile MR, Aurigemma GP, Gaasch WH. Left ventricular systolic performance, function, and contractility in patients with diastolic heart failure. Circulation 2005;111:2306–2312.

    Article  PubMed  Google Scholar 

  48. Wiggers CJ. Determinants of cardiac performance. Circulation 1951;4:485–495.

    PubMed  CAS  Google Scholar 

  49. Rushmer RF. Anatomy and physiology of ventricular function. Physiol Rev 1956;36:400–425.

    PubMed  CAS  Google Scholar 

  50. Sarnoff SJ. Related myocardial contractility as described by ventricular function curves; observations on Starling’s law of the heart. Physiol Rev 1955;35:107–122.

    PubMed  CAS  Google Scholar 

  51. Abbott BC, Mommaerts WF. A study of inotropic mechanisms in the papillary muscle preparation. J Gen Physiol 1959;42:533–551.

    Article  PubMed  CAS  Google Scholar 

  52. Sonnenblick EH. Force-velocity relations in mammalian heart muscle. Am J Physiol 1962;202:931–939.

    PubMed  CAS  Google Scholar 

  53. Brutsaert DL. Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Physiol Rev 2003;83:59–115.

    PubMed  CAS  Google Scholar 

  54. Yotti R, Bermejo J, Antoranz JC, Desco MM, Cortina C, Rojo-Alvarez JL, Allue C, Martin L, Moreno M, Serrano JA, Munoz R, Garcia-Fernandez MA. A noninvasive method for assessing impaired diastolic suction in patients with dilated cardiomyopathy. Circulation 2005;112:2921.

    Article  PubMed  Google Scholar 

  55. Little WC. Related diastolic dysfunction beyond distensibility: adverse effects of ventricular dilatation. Circulation 2005;112:2888–2890.

    PubMed  Google Scholar 

  56. De Keulenaer GW, Brutsaert DL. Systolic and diastolic heart failure: different phenotypes of the same disease? Eur J Heart Fail 2007;9:136–143.

    Article  PubMed  Google Scholar 

  57. Brutsaert DL, De Keulenaer GW. Diastolic heart failure: a myth. Curr Opin Cardiol 2006;21:240–248.

    Article  PubMed  Google Scholar 

  58. Klapholz M, Maurer M, Lowe AM, Messineo F, Meisner JS, Mitchell J, Kalman J, Phillips RA, Steingart R, Brown EJ Jr, Berkowitz R, Moskowitz R, Soni A, Mancini D, Bijou R, Sehhat K, Varshneya N, Kukin M, Katz SD, Sleeper LA, Le Jemtel TH. Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol 2004;43:1432–1438.

    Article  PubMed  Google Scholar 

  59. CHARM Investigators and Committees, Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003;362:777–781.

    Article  PubMed  CAS  Google Scholar 

  60. The Merit-HF study group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–2007.

    Article  Google Scholar 

  61. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol 1999;33:1948–1955.

    Article  PubMed  CAS  Google Scholar 

  62. Chen HH, Lainchbury JG, Senni M, Bailey KR, Redfield MM. Diastolic heart failure in the community: clinical profile, natural history, therapy, and impact of proposed diagnostic criteria. J Card Fail 2002;8:279–287.

    Article  PubMed  Google Scholar 

  63. Kalantar-Zadeh K, Block G, Horwich T, Fonarow GC. Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J Am Coll Cardiol 2004;43:1439–1444.

    Article  PubMed  Google Scholar 

  64. Solomon SD, St John Sutton M, Lamas GA, Plappert T, Rouleau JL, Skali H, Moye L, Braunwald E, Pfeffer MA. Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction. Circulation 2002;106:1251–1255.

    Article  PubMed  Google Scholar 

  65. Kenchaiah S, Evans JC, Levy D, Wilson PWF, Benjamin EJ, Larson MG, Kannel WB, Vasan RS. Obesity and the risk of heart failure. N Engl J Med 2002;347:305–313.

    Article  PubMed  Google Scholar 

  66. Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Woo MA, Tillisch JH. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol 2001;38:789–795.

    Article  PubMed  CAS  Google Scholar 

  67. Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002;8:216–224.

    Article  PubMed  CAS  Google Scholar 

  68. Poole-Wilson PA, Uretsky BF, Thygesen K, Cleland JG, Massie BM, Ryden L; Atlas Study Group. Assessment of treatment with lisinopril and survival. Mode of death in heart failure: findings from the ATLAS trial. Heart 2003;89:42–48.

    Article  PubMed  CAS  Google Scholar 

  69. Weinberg EO, Mirotsou M, Gannon J, Dzau VJ, Lee RT, Pratt RE. Sex dependence and temporal dependence of the left ventricular genomic response to pressure overload. Physiol Genomics 2003;12:113–127.

    PubMed  CAS  Google Scholar 

  70. Haghighi K, Schmidt AG, Hoit BD, Brittsan AG, Yatani A, Lester JW, Zhai J, Kimura Y, Dorn GW 2nd, MacLennan DH, Kranias EG. Superinhibition of sarcoplasmic reticulum function by phospholamban induces cardiac contractile failure. J Biol Chem 2001;276:24145–24152.

    Article  PubMed  CAS  Google Scholar 

  71. Dash R, Schmidt AG, Pathak A, Gerst MJ, Biniakiewicz D, Kadambi VJ, Hoit BD, Abraham WT, Kranias EG. Differential regulation of p38 mitogen-activated protein kinase mediates gender-dependent catecholamine-induced hypertrophy. Cardiovasc Res 2003;57:704–714.

    Article  PubMed  CAS  Google Scholar 

  72. Leinwand LA. Sex is a potent modifier of the cardiovascular system. J Clin Invest 2003;112:302–307.

    PubMed  CAS  Google Scholar 

  73. Hay I, Rich J, Ferber P, Burkhoff D, Maurer MS. The role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure. Am J Physiol Heart Circ Physiol 2005;288:H1203–H1208.

    Article  PubMed  CAS  Google Scholar 

  74. Skaluba SJ, Litwin SE. Mechanisms of exercise intolerance: insights from tissue Doppler imaging. Circulation 2004;109:972–977.

    Article  PubMed  Google Scholar 

  75. Fischer M, Baessler A, Hense HW, Hengstenberg C, Muscholl M, Holmer S, Doring A, Broeckel U, Riegger G, Schunkert H. Prevalence of left ventricular diastolic dysfunction in the community. Results from a Doppler echocardiographic-based survey of a population sample. Eur Heart J 2003;24:320–328.

    Article  PubMed  CAS  Google Scholar 

  76. Alpert MA, Terry BE, Mulekar M, Cohen MV, Massey CV, Fan TM, Panayiotou H, Mukerji V. Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss. Am J Cardiol 1997;80:736–740.

    Article  PubMed  CAS  Google Scholar 

  77. Perhonen MA, Zuckerman JH, Levine BD. Deterioration of left ventricular chamber performance after bed rest: “cardiovascular deconditioning” or hypovolemia? Circulation 2001;103:1851–1857.

    PubMed  CAS  Google Scholar 

  78. Arbab-Zadeh A, Dijk E, Prasad A, Fu Q, Torres P, Zhang R, Thomas JD, Palmer D, Levine BD. Effect of aging and physical activity on left ventricular compliance. Circulation 2004;110:1799–1805.

    Article  PubMed  Google Scholar 

  79. Lakatta EG, Yin FC. Myocardial aging: functional alterations and related cellular mechanisms. Am J Physiol 1982;242:H927–H941.

    PubMed  CAS  Google Scholar 

  80. Yelamarty RV, Moore RL, Yu FT, Elensky M, Semanchick AM, Cheung JY. Relaxation abnormalities in single cardiac myocytes from renovascular hypertensive rats. Am J Physiol 1992;262:C980–990.

    PubMed  CAS  Google Scholar 

  81. Nishikawa N, Yamamoto K, Sakata Y, Mano T, Yoshida J, Miwa T, Takeda H, Hori M, Masuyama T. Differential activation of matrix metalloproteinases in heart failure with and without ventricular dilatation. Cardiovasc Res 2003;57:766–774.

    Article  PubMed  CAS  Google Scholar 

  82. Diamant M, Lamb HJ, Groeneveld Y, Endert EL, Smit JW, Bax JJ, Romijn JA, de Roos A, Radder JK. Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. J Am Coll Cardiol 2003;42:328–335.

    Article  PubMed  CAS  Google Scholar 

  83. Mohan P, Brutsaert DL, Paulus WJ, Sys SU. Myocardial contractile response to nitric oxide and cGMP. Circulation 1996;93:1223–1229.

    PubMed  CAS  Google Scholar 

  84. De Keulenaer GW, Andries LJ, Sys SU, Brutsaert DL. Endothelin-mediated positive inotropic effect induced by reactive oxygen species in isolated cardiac muscle. Circ Res 1995;76:878–884.

    PubMed  Google Scholar 

  85. Leite-Moreira AF, Bras-Silva C, Pedrosa CA, Rocha-Sousa AA. ET-1 increases distensibility of acutely loaded myocardium: a novel ETA and Na+/H+ exchanger-mediated effect. Am J Physiol 2003;284:H1332–H1339.

    CAS  Google Scholar 

  86. Mohan P, Brutsaert DL, Sys SU. Myocardial performance is modulated by interaction of cardiac endothelium derived nitric oxide and prostaglandins. Cardiovasc Res 1995;29:637–640.

    Article  PubMed  CAS  Google Scholar 

  87. Cote GM, Miller TA, Lebrasseur NK, Kuramochi Y, Sawyer DB. Neuregulin-1alpha and beta isoform expression in cardiac microvascular endothelial cells and function in cardiac myocytes in vitro. Exp Cell Res 2005;311:135–146.

    Article  PubMed  CAS  Google Scholar 

  88. Fransen P, Lamberts RR, Hendrickx J, De Keulenaer GW. Endocardial endothelium modulates subendocardial pH(i) of rabbit papillary muscles: role of transendothelial HCO(3)(−) transport. Cardiovasc Res 2004;63:700–708.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cardiology Department, AZ Middelheim — University of Antwerp, Antwerp, Belgium

    Gilles W. De Keulenaer MD, PhD & Dirk L. Brutsaert MD, PhD

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  1. Gilles W. De Keulenaer MD, PhD
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  2. Dirk L. Brutsaert MD, PhD
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Editors and Affiliations

  1. Heart-Lung Clinic, Department of Cardiology Rikshospitalet, University of Oslo, Oslo, Norway

    Otto A. Smiseth MD, PhD (Professor of Medicine and Head) (Professor of Medicine and Head)

  2. 3rd Division of Cardiology, Medical University of Silesia, Katowice, Poland

    Michał Tendera MD, PhD (Professor of Medicine and Head) (Professor of Medicine and Head)

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De Keulenaer, G.W., Brutsaert, D.L. (2008). Molecular Mechanisms of Diastolic Dysfunction. In: Smiseth, O.A., Tendera, M. (eds) Diastolic Heart Failure. Springer, London. https://doi.org/10.1007/978-1-84628-891-3_1

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