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Neue Therapiekonzepte zur Herzinsuffizienz mit erhaltener Ejektionsfraktion

New therapy concepts for heart failure with preserved ejection fraction

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Zusammenfassung

Das Management von Patienten mit Herzinsuffizienzsymptomen und erhaltener Ejektionsfraktion (HFpEF) bleibt eine Herausforderung und setzt zunächst eine akkurate Diagnostik voraus. Obwohl es zurzeit keine überzeugenden und bewiesenen Therapieansätze für das Überleben von HFpEF-Patienten gibt, stellen die Behandlung der Flüssigkeitretention, die Einstellung der Herzfrequenz und die Therapie der Komorbiditäten wichtige Eckpfeiler zur Symptomverbesserung und Lebensqualität dar. In den letzten Jahren wurden zahlreiche neue Therapieziele für die Entwicklung erfolgreicher Interventionsstrategien bei HFpEF erforscht. Dabei scheint möglicherweise die Dysregulation des NO-cGMP-PK-Signalwegs bei HFpEF einen aktuellen neuen therapeutisch nutzbaren Ansatz darzustellen. Substanzen wie der Neprilysininhibitor LCZ 696 oder der lösliche Guanylatzyklasestimulator Vericiguat, die beide den cGMP-Signalweg optimieren können, werden zurzeit in Studien dazu untersucht. Daneben existieren zahlreiche weitere neue Ansätze, wie die zur Regulation des Matrix-, des intrazellulären Kalzium- oder des Energiehaushalts und die zur Rolle von microRNAs und Devices, die im Folgenden vorgestellt und diskutiert werden.

Abstract

The management of patients with heart failure and preserved ejection fraction (HFpEF) remains challenging and requires an accurate diagnosis. Although currently no convincing therapy that can prolong survival in patients with HFpEF has been established, treatment of fluid retention, heart rate and control of comorbidities are important cornerstones to improve the quality of life and symptoms. In recent years many new therapy targets have been tested for development of successful interventional strategies for HFpEF. Insights into new mechanisms of HFpEF have shown that heart failure is associated with dysregulation of the nitric oxide-cyclic guanosine monophosphate-protein kinase (NO-cGMP-PK) pathway. Two new drugs are currently under investigation to test whether this pathway can be significantly improved by either the neprilysin inhibitor LCZ 696 due to an increase in natriuretic peptides or by the soluble guanylate cyclase stimulator vericiguat, which is also able to increase cGMP. In addition, several preclinical or early phase studies which are currently investigating new mechanisms for matrix, intracellular calcium and energy regulation including the role of microRNAs and new devices are presented and discussed.

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Literatur

  1. Bhatia RS, Tu JV, Lee DS et al (2006) Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 355(3):260–269

    Article  CAS  PubMed  Google Scholar 

  2. Lam CS, Donal E, Kraigher-Krainer E et al (2011) Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail 13(1):18–28

    Article  PubMed Central  PubMed  Google Scholar 

  3. Owan TE, Hodge DO, Herges RM et al (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355(3):251–259

    Article  CAS  PubMed  Google Scholar 

  4. Go AS, Mozaffarian D, Roger VL et al (2014) American Heart Association Statistics Committee, Stroke Statistics Subcommittee. Heart disease and stroke statistics – 2014 update: a report from the American Heart Association. Circulation 129(3):e28–e292

    Article  PubMed  Google Scholar 

  5. Paulus WJ, Tschöpe C, Sanderson JE et al (2007) How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 28(20):2539–2550

    Article  PubMed  Google Scholar 

  6. Tschöpe C, Lam CS (2012) Diastolic heart failure: What we still don’t know. Looking for new concepts, diagnostic approaches, and the role of comorbidities. Herz 37(8):875–879

    Article  PubMed  Google Scholar 

  7. McMurray JJ, Adamopoulos S, Anker SD et al (2012) ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 33(14):1787–1847

    Article  PubMed  Google Scholar 

  8. Yancy CW, Jessup M, Bozkurt B et al (2013) American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidlines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 62(16):e147–e239

    Article  PubMed  Google Scholar 

  9. López B, Querejeta R, González A et al (2009) Impact of treatment on myocardial lysyl oxidase expression and collagen cross-linking in patients with heart failure. Hypertension 53(2):236–242

    Article  PubMed  Google Scholar 

  10. Yip GW, Wang M, Wang T et al (2008) The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart 94(5):573–580

    Article  CAS  PubMed  Google Scholar 

  11. Ather S, Chan W, Bozkurt B et al (2012) Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol 59(11):998–1005

    Article  PubMed  Google Scholar 

  12. Beckett NS, Peters R, Fletcher AE et al (2008) Treatment of hypertension in patients 80 years of age or older. N Engl J Med 358(18):1887–1898

    Article  CAS  PubMed  Google Scholar 

  13. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (2002) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288(23):2981–2997

    Article  Google Scholar 

  14. Wachtell K, Bella JN, Rokkedal J et al (2002) Change in diastolic left ventricular filling after one year of antihypertensive treatment: the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Circulation 105(9):1071–1076

    Article  PubMed  Google Scholar 

  15. Klingbeil AU, Schneider M, Martus P et al (2003) A metaanalysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 115(1):41–46

    Article  PubMed  Google Scholar 

  16. James PA, Oparil S, Carter BL et al (2014) 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311(5):507–520

    Article  CAS  PubMed  Google Scholar 

  17. Butt M, Dwivedi G, Shantsila A et al (2012) Left ventricular systolic and diastolic function in obstructive sleep apnea: impact of continuous positive airway pressure therapy. Circ Heart Fail 5(2):226–233

    Article  PubMed  Google Scholar 

  18. Anker SD, Comin Colet J, Filippatos G et al (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361(25):2436–2448

    Article  CAS  PubMed  Google Scholar 

  19. Kasner M, Aleksandrov AS, Westermann D et al (2013) Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. Int J Cardiol 168(5):4652–4657

    Article  PubMed  Google Scholar 

  20. Senni M, Paulus WJ, Gavazzi A et al (2014) New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur Heart J 35(40):2797–2815

    Article  PubMed  Google Scholar 

  21. Westermann D, Kasner M, Steendijk P et al (2008) Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation 117(16):2051–2060

    Article  PubMed  Google Scholar 

  22. Benedict CR, Johnstone DE, Weiner DH et al (1994) Relation of neurohumoral activation to clinical variables and degree of ventricular dysfunction: a report from the Registry of Studies of Left Ventricular Dysfunction. SOLVD Investigators. J Am Coll Cardiol 23(6):1410–1420

    Article  CAS  PubMed  Google Scholar 

  23. Yusuf S, Pfeffer MA, Swedberg K et al (2003) Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-PRESERVED Trial. Lancet 362(9386):777–781

    Article  CAS  PubMed  Google Scholar 

  24. Cleland JG, Tendera M, Adamus J et al (2006) The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 27(19):2338–2345

    Article  CAS  PubMed  Google Scholar 

  25. Massie BM, Carson PE, McMurray JJ et al (2008) Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 359(23):2456–2467

    Article  CAS  PubMed  Google Scholar 

  26. Bonow RO, Udelson JE (1992) Left ventricular diastolic dysfunction as a cause of congestive heart failure. Mechanisms and management. Ann Intern Med 117(6):502–510

    Article  CAS  PubMed  Google Scholar 

  27. Borlaug BA, Olson TP, Lam CS et al (2010) Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol 56(11):845–854

    Article  PubMed Central  PubMed  Google Scholar 

  28. Phan TT, Abozguia K, Nallur Shivu G et al (2009) Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency. J Am Coll Cardiol 54(5):402–409

    Article  PubMed  Google Scholar 

  29. Phan TT, Shivu GN, Abozguia K et al (2010) Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction. Circ Heart Fail 3(1):29–34

    Article  PubMed  Google Scholar 

  30. Flather MD, Shibata MC, Coats AJ et al (2005) Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 26(3):215–225

    Article  CAS  PubMed  Google Scholar 

  31. Veldhuisen DJ van, Cohen-Solal A, Bohm M et al (2009) Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol 53(23):2150–2158

    Article  PubMed  Google Scholar 

  32. Conraads VM, Metra M, Kamp O et al (2012) Effects of the long-term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study. Eur J Heart Fail 14(2):219–225

    Article  CAS  PubMed  Google Scholar 

  33. Hernandez AF, Hammill BG, O’Connor CM et al (2009) Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) Registry. J Am Coll Cardiol 53(2):184–192

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Massie BM, Nelson JJ, Lukas MA et al (2007) Comparison of outcomes and usefulness of carvedilol across a spectrum of left ventricular ejection fractions in patients with heart failure in clinical practice. Am J Cardiol 99(9):1263–1268

    Article  CAS  PubMed  Google Scholar 

  35. Lund L, Benson L, Dahlström U et al (2014) Association between use of β-blockers and outcomes in patients with heart failure and preserved ejection fraction. JAMA 312(19):2008–2018

    Article  CAS  PubMed  Google Scholar 

  36. Ahmed A, Rich MW, Fleg JL et al (2006) Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation 114(5):397–403

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Setaro JF, Zaret BL, Schulman DS et al (1990) Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol 66(12):981–986

    Article  CAS  PubMed  Google Scholar 

  38. Dietz JD, Du S, Bolten CW et al (2008) A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension 51(3):742–748

    Article  CAS  PubMed  Google Scholar 

  39. Lijnen P, Petrov V (2000) Induction of cardiac fibrosis by aldosterone. J Mol Cell Cardiol 32(6):865–879

    Article  CAS  PubMed  Google Scholar 

  40. Edelmann F, Wachter R, Schmidt AG et al (2013) Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 309(8):781–791

    Article  CAS  PubMed  Google Scholar 

  41. Pitt B, Pfeffer MA, Assmann SF et al (2014) Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370(15):1383–1392

    Article  CAS  PubMed  Google Scholar 

  42. Colussi G, Catena C, Sechi LA (2013) Spironolactone, eplerenone and the new aldosterone blockers in endocrine and primary hypertension. J Hypertens 31(1):3–15

    Article  CAS  PubMed  Google Scholar 

  43. Hattori T, Shimokawa H, Higashi M et al (2004) Long-term inhibition of Rho-kinase suppresses left ventricular remodeling after myocardial infarction in mice. Circulation 109(18):2234–2239

    Article  CAS  PubMed  Google Scholar 

  44. Fukuta H, Sane DC, Brucks S, Little WC (2005) Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 112(3):357–363

    Article  CAS  PubMed  Google Scholar 

  45. Tavazzi L, Maggioni AP, Marchioli R et al (2008) Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo controlled trial. Lancet 372(9645):1231–1239

    Article  PubMed  Google Scholar 

  46. Sossalla S, Maurer U, Schotola H et al (2011) Diastolic dysfunction and arrhythmias caused by over expression of CaMKIIdelta(C) can be reversed by inhibition of late Na(+) current. Basic Res Cardiol 106(2):263–272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Song Y, Shryock J, Wagner S et al (2006) Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther 318(1):214–222

    Article  CAS  PubMed  Google Scholar 

  48. Maier LS, Layug B, Karwatowska-Prokopczuk E et al (2013) Ranolazine for the treatment of diastolic heart failure in patients with preserved Β ejection fraction: the RALI-DHF proof-of-concept study. JACC Heart Fail 1(2):115–122

    Article  PubMed  Google Scholar 

  49. Colin P, Ghaleh B, Hittinger L et al (2002) Differential effects of heart rate reduction and beta-blockade on left ventricular relaxation during exercise. Am J Physiol Heart Circ Physiol 282(2):H672–H679

    Article  CAS  PubMed  Google Scholar 

  50. Reil JC, Hohl M, Reil GH et al (2013) Heart rate reduction by If inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction. Eur Heart J 34(36):2839–2849

    Article  PubMed Central  PubMed  Google Scholar 

  51. Becher PM, Lindner D, Miteva K et al (2012) Role of heart rate reduction in the prevention of experimental heart failure: comparison between If-channel blockade and β-receptor blockade. Hypertension 59(5):949–957

    Article  CAS  PubMed  Google Scholar 

  52. Kosmala W, Holland DJ, Rojek A et al (2013) Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial. J Am Coll Cardiol 62(15):1330–1338

    Article  CAS  PubMed  Google Scholar 

  53. Komajda M, Lam CS (2014) Heart failure with preserved ejection fraction: a clinical dilemma. Eur Heart J 35(16):1022–1032

    Article  CAS  PubMed  Google Scholar 

  54. Tschöpe C, Van Linthout S (2014) New insights in (inter)cellular mechanisms by heart failure with preserved ejection fraction. Curr Heart Fail Rep 11(4):436–444

    Article  PubMed Central  PubMed  Google Scholar 

  55. Heerebeek L van, Hamdani N, Falcão-Pires I et al (2012) Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 126(7):830–839

    Article  PubMed  Google Scholar 

  56. Westermann D, Riad A, Richter U et al (2009) Enhancement of the endothelial NO synthase attenuates experimental diastolic heart failure. Basic Res Cardiol 104(5):499–509

    Article  CAS  PubMed  Google Scholar 

  57. Solomon SD, Zile M, Pieske B et al; Prospective comparison of ARNI with ARB on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) Investigators (2012) The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet 380(9851):1387–1395

    Article  CAS  PubMed  Google Scholar 

  58. Kasner M, Westermann D, Steendijk P et al (2012) Left ventricular dysfunction induced by nonsevere idiopathic pulmonary arterial hypertension: a pressure-volume relationship study. Am J Respir Crit Care Med 186(2):181–189

    Article  PubMed  Google Scholar 

  59. Guazzi M, Vicenzi M, Arena R, Guazzi MD (2011) 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 4(1):8–17

    Article  CAS  PubMed  Google Scholar 

  60. Redfield MM, Chen HH, Borlaug BA et al (2013) Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 309(12):1268–1277

    Article  CAS  PubMed  Google Scholar 

  61. Pieske B, Butler J, Filippatos G et al (2014) Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail 16(9):1026–1038

    Article  CAS  PubMed  Google Scholar 

  62. Westermann D, Lindner D, Kasner M et al (2011) Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail 4(1):44–52

    Article  PubMed  Google Scholar 

  63. Lindner D, Zietsch C, Tank J et al (2014) Cardiac fibroblasts support cardiac inflammation in heart failure. Basic Res Cardiol 109(5):428

    Article  PubMed  Google Scholar 

  64. Van Linthout S, Miteva K, Tschöpe C (2014) Crosstalk between fibroblasts and inflammatory cells. Cardiovasc Res 102(2):258–269

    Article  Google Scholar 

  65. Van Tassell BW, Seropian IM, Toldo S et al (2013) Interleukin-1β induces a reversible cardiomyopathy in the mouse. Inflamm Res 62(7):637–640

    Article  Google Scholar 

  66. Van Tassell BW, Arena R, Biondi-Zoccai G et al (2014) Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and reserved ejection fraction (from the D-HART pilot study). Am J Cardiol 113(2):321–327

    Article  Google Scholar 

  67. Lompre AM, Hajjar RJ, Harding SE et al (2010) Ca2+ cycling and new therapeutic approaches for heart failure. Circulation 121(6):822–830

    Article  PubMed Central  PubMed  Google Scholar 

  68. Currie S, Elliott EB, Smith GL, Loughrey CM (2011) Two candidates at the heart of dysfunction: the ryanodine receptor and calcium/calmodulin protein kinase II as potential targets for therapeutic intervention – an in vivo perspective. Pharmacol Ther 131(2):204–220

    Article  CAS  PubMed  Google Scholar 

  69. Hasenfuss G, Pieske B (2002) Calcium cycling in congestive heart failure. J Mol Cell Cardiol 34(8):951–969

    Article  CAS  PubMed  Google Scholar 

  70. Sacherer M, Sedej S, Wakuła P et al (2012) JTV519 (K201) reduces sarcoplasmic reticulum Ca2+ leak and improves diastolic function in vitro in murine and human non-failing myocardium. Br J Pharmacol 167(3):493–504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Kamimura D, Ohtani T, Sakata Y et al (2012) Ca2+ entry mode of Na+/Ca2+ exchanger as a new therapeutic target for heart failure with preserved ejection fraction. Eur Heart J 33(11):1408–1416

    Article  CAS  PubMed  Google Scholar 

  72. Sedej S, Schmidt A, Denegri M et al (2014) Subclinical abnormalities in sarcoplasmic reticulum Ca(2+) release promote eccentric myocardial remodeling and pump failure death in response to pressure overload. J Am Coll Cardiol 63(15):1569–1579

    Article  CAS  PubMed  Google Scholar 

  73. Ashrafian H, Frenneaux MP, Opie LH (2007) Metabolic mechanisms in heart failure. Circulation 116(4):434–448

    Article  CAS  PubMed  Google Scholar 

  74. Reasner CA II (1999) Promising new approaches. Diabetes Obes Metab 1(Suppl 1):S41–S48

    Article  CAS  PubMed  Google Scholar 

  75. Meer RW van der, Rijzewijk LJ, Jong HW de et al (2009) Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation 119(15):2069–2077

    Article  PubMed  Google Scholar 

  76. Drucker DJ (1998) Glucagon-like peptides. Diabetes 47(2):159–169

    Article  CAS  PubMed  Google Scholar 

  77. Wei Y, Mojsov S (1995) Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acidsequences. FEBS Lett 358(3):219–224

    Article  CAS  PubMed  Google Scholar 

  78. Inzucchi SE, McGuire DK (2008) New drugs for the treatment of diabetes: part II: incretin-based therapy and beyond. Circulation 117(4):574–584

    Article  PubMed  Google Scholar 

  79. Witteles RM, Keu KV, Quon A et al (2012) Dipeptidyl peptidase inhibition increases myocardial glucose uptake in nonischemic cardiomyopathy. J Card Fail 18(10):804–809

    Article  CAS  PubMed  Google Scholar 

  80. Hartog JW, Voors AA, Bakker SJ et al (2007) Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implication. Eur J Heart Fail 9(12):1146–1155

    Article  CAS  PubMed  Google Scholar 

  81. Little WC, Zile MR, Kitzman DW et al (2005) The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail 11(3):191–195

    Article  CAS  PubMed  Google Scholar 

  82. Ohtani K, Dimmeler S (2011) Control of cardiovascular differentiation by microRNAs. Basic Res Cardiol 106(1):5–11

    Article  CAS  PubMed  Google Scholar 

  83. Dong S, Ma W, Hao B et al (2014) microRNA-21 promotes cardiac fibrosis and development of heart failure with preserved left ventricular ejection fraction by up-regulating Bcl-2. Int J Clin Exp Pathol 7(2):565–574

    PubMed Central  PubMed  Google Scholar 

  84. Nair N, Gupta S, Gongora E et al (2014) Can microRNAs emerge as biomarkers in distinguishing HFpEF versus HFrEF? Int J Cardiol 175(3):395–399

    Article  PubMed  Google Scholar 

  85. Edelmann F, Gelbrich G, Dungen HD et al (2011) Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (Exercise training in Diastolic Heart Failure) pilot study. J Am Coll Cardiol 58(17):1780–1791

    Article  PubMed  Google Scholar 

  86. Zile MR, Bennett TD, St John Sutton M et al (2008) Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation 118(14):1433–1441

    Article  PubMed  Google Scholar 

  87. Sinning D, Kasner M, Westermann D et al (2011) Increased left ventricular stiffness impairs exercise capacity in patients with heart failure symptoms despite normal left ventricular ejection fraction. Cardiol Res Pract 2011:692862

    PubMed Central  PubMed  Google Scholar 

  88. Lutembacher R (1916) De la sténose mitrale avec communication interauirulaire. Arch Mal Coeur 9:237–260

    Google Scholar 

  89. Søndergaard L, Reddy V, Kaye D et al (2014) Transcatheter treatment of heart failure with preserved or mildly reduced ejection fraction using a novel interatrial implant to lower left atrial pressure. Eur J Heart Fail 16(7):796–801

    Article  PubMed  Google Scholar 

  90. Kasner M, Westermann D, Schultheiss HP, Tschöpe C (2012) Simultaneous estimation of NT-proBNP on top to mitral flow Doppler echocardiography as an accurate strategy to diagnose diastolic dysfunction in HFNEF. Curr Pharm Biotechnol 13(13):2539–2544

    Article  CAS  PubMed  Google Scholar 

  91. Menet A, Greffe L, Ennezat PV et al (2014) Is mechanical dyssynchrony a therapeutic target in heart failure with preserved ejection fraction? Am Heart J 168(6):909–916.e1

    Article  PubMed  Google Scholar 

  92. Borggrefe M, Burkhoff D (2012) Clinical effects of cardiac contractility modulation (CCM) as a treatment for chronic heart failure. Eur J Heart Fail 14(7):703–712

    Article  CAS  PubMed  Google Scholar 

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Danksagung

European 7th Framework Konsortium MEDIA (CT).

Einhaltung ethischer Richtlinien

Interessenkonflikt. C. Tschöpe:“Steering-committee”- oder“Speaker”-Honorare von Novartis, Berlin-Chemie, Servier, BMS, Roche, Bayer Healthcare, Impulse Dynamics. B. Pieske:“Steering-committee”- oder“Speaker”-Honorare von Bayer Healthcare, Servier, CVRx, Stealth Peptides, Novartis, Medtronic.

Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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  1. Abteilung für Kardiologie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 13353, Berlin, Deutschland

    C. Tschöpe & B. Pieske

  2. Deutsches Herzzentrum Berlin (DHZB), Berlin, Deutschland

    B. Pieske

  3. Berliner Zentrum für Regenerative Therapien (BCRT), Campus Virchow-Klinikum (CVK), Berlin, Deutschland

    C. Tschöpe

  4. Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) – Standort Berlin/Charité, Berlin, Deutschland

    C. Tschöpe & B. Pieske

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Correspondence to C. Tschöpe.

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Tschöpe, C., Pieske, B. Neue Therapiekonzepte zur Herzinsuffizienz mit erhaltener Ejektionsfraktion. Herz 40, 194–205 (2015). https://doi.org/10.1007/s00059-015-4210-x

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