The Role of Chronotropic Incompetence in Heart Failure With Normal Ejection Fraction (HFNEF)

Summary

What is heart failure with normal ejection fraction? The heart contracts (pumps) and relaxes with each heartbeat. In some people with heart failure, the heart contracts normally but there is reduced relaxation of the heart. As a result, people notice a feeling of breathlessness, ankle swelling and fatigue especially on exertion. The investigators feel that patients with reduced or impaired relaxation of the heart have less heart filling time and poor energy utilisation during exercise. Therefore, the investigators are conducting a study to more thoroughly understand the disease condition by giving a drug called ivabradine to reduce the heart rate and hence to increase the heart filling time in these patients.

Timeline

Start

2011-12

Primary completion

2014-01

Completion

2014-01

Publications

• Background 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. doi: 10.1056/NEJMoa052256.
• Background Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, Gong Y, Liu PP. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9. doi: 10.1056/NEJMoa051530.
• Background De Keulenaer GW, Brutsaert DL. The heart failure spectrum: time for a phenotype-oriented approach. Circulation. 2009 Jun 23;119(24):3044-6. doi: 10.1161/CIRCULATIONAHA.109.870006. Epub 2009 Jun 8. No abstract available.
• Background Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure--abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004 May 6;350(19):1953-9. doi: 10.1056/NEJMoa032566.
• Background Westermann D, Kasner M, Steendijk P, Spillmann F, Riad A, Weitmann K, Hoffmann W, Poller W, Pauschinger M, Schultheiss HP, Tschope C. Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation. 2008 Apr 22;117(16):2051-60. doi: 10.1161/CIRCULATIONAHA.107.716886. Epub 2008 Apr 14.
• Background Yip GW, Frenneaux M, Sanderson JE. Heart failure with a normal ejection fraction: new developments. Heart. 2009 Oct;95(19):1549-52. doi: 10.1136/hrt.2009.176222. Epub 2009 Jul 29. No abstract available.
• Background Kindermann M, Reil JC, Pieske B, van Veldhuisen DJ, Bohm M. Heart failure with normal left ventricular ejection fraction: what is the evidence? Trends Cardiovasc Med. 2008 Nov;18(8):280-92. doi: 10.1016/j.tcm.2008.12.003.
• Background Phan TT, Abozguia K, Nallur Shivu G, Mahadevan G, Ahmed I, Williams L, Dwivedi G, Patel K, Steendijk P, Ashrafian H, Henning A, Frenneaux M. 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. 2009 Jul 28;54(5):402-9. doi: 10.1016/j.jacc.2009.05.012.
• Background Wachter R, Schmidt-Schweda S, Westermann D, Post H, Edelmann F, Kasner M, Luers C, Steendijk P, Hasenfuss G, Tschope C, Pieske B. Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure. Eur Heart J. 2009 Dec;30(24):3027-36. doi: 10.1093/eurheartj/ehp341.
• Background Bergstrom A, Andersson B, Edner M, Nylander E, Persson H, Dahlstrom U. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler-echocardiographic study (SWEDIC). Eur J Heart Fail. 2004 Jun;6(4):453-61. doi: 10.1016/j.ejheart.2004.02.003.
• Background Liu CP, Ting CT, Lawrence W, Maughan WL, Chang MS, Kass DA. Diminished contractile response to increased heart rate in intact human left ventricular hypertrophy. Systolic versus diastolic determinants. Circulation. 1993 Oct;88(4 Pt 1):1893-906. doi: 10.1161/01.cir.88.4.1893.
• Background Fox K, Ford I, Steg PG, Tendera M, Ferrari R; BEAUTIFUL Investigators. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Sep 6;372(9641):807-16. doi: 10.1016/S0140-6736(08)61170-8. Epub 2008 Aug 29.
• Background Shivu GN, Abozguia K, Phan TT, Ahmed I, Henning A, Frenneaux M. (31)P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy: Experiences at 3T. Eur J Radiol. 2010 Feb;73(2):255-9. doi: 10.1016/j.ejrad.2008.10.018. Epub 2008 Dec 3.
• Background Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation. 2000 Oct 10;102(15):1788-94. doi: 10.1161/01.cir.102.15.1788.
• Background Pennell DJ, Sechtem UP, Higgins CB, Manning WJ, Pohost GM, Rademakers FE, van Rossum AC, Shaw LJ, Yucel EK; European Society of cardiology; Soceity for Cardiovascular Magnetic Resonance. Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report. J Cardiovasc Magn Reson. 2004;6(4):727-65. doi: 10.1081/jcmr-200038581. No abstract available.
• Background Hudsmith LE, Neubauer S. Magnetic resonance spectroscopy in myocardial disease. JACC Cardiovasc Imaging. 2009 Jan;2(1):87-96. doi: 10.1016/j.jcmg.2008.08.005.
• Background Scardovi AB, Coletta C, De Maria R, Perna S, Aspromonte N, Feola M, Rosso G, Greggi M, Ceci V. The cardiopulmonary exercise test is safe and reliable in elderly patients with chronic heart failure. J Cardiovasc Med (Hagerstown). 2007 Aug;8(8):608-12. doi: 10.2459/01.JCM.0000281698.53983.4e.
• Background Bacharach SL, Green MV, Borer JS, Hyde JE, Farkas SP, Johnston GS. Left-ventricular peak ejection rate, filling rate, and ejection fraction--frame rate requirements at rest and exercise: concise communication. J Nucl Med. 1979 Mar;20(3):189-93.
• Pal N, Sivaswamy N, Mahmod M, Yavari A, Rudd A, Singh S, Dawson DK, Francis JM, Dwight JS, Watkins H, Neubauer S, Frenneaux M, Ashrafian H. Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction. Circulation. 2015 Nov 3;132(18):1719-25. doi: 10.1161/CIRCULATIONAHA.115.017119. Epub 2015 Sep 2.

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Indications