Can the Use of ?-Adrenergic Blockers for Treatment of HFpEF Worsen Diastolic Dysfunction? - A Review Based on Concept of MyBP-C

Muhammad Nabeel Dookhun, Pooja Doseiah, Yunshan Cao, Ji-Nan Zhang, Xin-Zheng Lu


Heart failure can be classified based on ejection fraction as reduced Heart Failure Reduced Ejection Fraction (HFrEF), moderate Heart Failure Moderate Ejection Fraction (HFmEF) and preserved Heart Failure Preserved Ejection Fraction (HFpEF). Indeed, use of beta-blockers in Heart Failure (HF) reduces mortality and morbidity. However, the controversial effect of the use of beta-blockers in HFpEF is of great concern. HFpEF is associated with a high mortality and hospitalization rate probably due to lack of evidence-based treatment. Hence a proper understanding behind the pathophysiologic mechanism of HFpEF is important. Recently Myosin Binding Protein C (MyBP-C), a cardiac-specific protein, has been shown to be involved in various cardiac pathologic conditions. Phosphorylation of MyBP-C is crucial for normal systolic and diastolic heart function. A failing heart is associated with hypophosphorylation of MyBP-C. Use of beta-blockers in HFpEF would prevent ?-Adrenergic stimulation of MyBP-C by Protein Kinase A (PKA) and can worsen diastolic dysfunction in HFpEF.


HFpEF; heart failure; beta-blocker; MyBP-C.

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. Lam, C.S.P., et al., Epidemiology and clinical course of heart failure with preserved ejection fraction. European Journal of Heart Failure, 2011. 13(1): p. 18-28.

. Owan, T., et al., Trends in prevalence and outcome of heart failure with preserved ejection fraction. The New England Journal of Medicine, 2009. 355(3): p. 251-259.

. Mathers, C., et al., Causes of international increases in older age life expectancy. The Lancet, 2015. 385(9967): p. 540-548.

. Brouwers, F.P., et al., Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND. European Heart Journal, 2013. 34(19): p. 1424-1431.

. Fonarow, G.C., et al., Characteristics, Treatments, and Outcomes of Patients With Preserved Systolic Function Hospitalized for Heart Failure. Journal of the American College of Cardiology, 2007. 50(8): p. 768-777.

. Yancy, C.W., et al., Clinical Presentation, Management, and In-Hospital Outcomes of Patients Admitted With Acute Decompensated Heart Failure With Preserved Systolic Function. Journal of the American College of Cardiology, 2006. 47(1): p. 76-84.

. Paulus, W.J., et al., 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. European Heart Journal, 2007. 28(21): p. 2686-2687.

. Nagueh, S.F., et al., Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography. Journal of The American Society of Echocardiography, 2009. 22(2): p. 107-133.

. Redfield, M.M., et al., Burden of Systolic and Diastolic Ventricular Dysfunction in the Community: Appreciating the Scope of the Heart Failure Epidemic. JAMA, 2003. 289(2): p. 194-202.

. Mcmurray, J.J.V., et al., 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. European Heart Journal, 2012. 33(14): p. 1787-1847.

. Yancy, C.W., et al., 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. Journal of the American College of Cardiology, 2013. 62(16).

. Zile, M.R., et al., Prevalence and Significance of Alterations in Cardiac Structure and Function in Patients With Heart Failure and a Preserved Ejection Fraction. Circulation, 2011. 124(23): p. 2491-2501.

. Cheng, J.M., et al., Biomarkers of heart failure with normal ejection fraction: a systematic review. European Journal of Heart Failure, 2013. 15(12): p. 1350-1362.

. Morrow, D.A. and J.A. De Lemos, Benchmarks for the Assessment of Novel Cardiovascular Biomarkers. Circulation, 2007. 115(8): p. 949-952.

. Chatterjee, S., et al., Benefits of ? blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ, 2013. 346.

. Liu, F., et al., Effects of Beta-Blockers on Heart Failure with Preserved Ejection Fraction: A Meta-Analysis. PLOS ONE, 2014. 9(3).

. Bavishi, C., et al., Beta-blockers in heart failure with preserved ejection fraction: a meta-analysis. Heart Failure Reviews, 2014. 20(2): p. 193-201.

. Starr, E.R., et al., Phosphorylation of cardiac myosin binding protein-C regulates heart contraction and dilatation in vivo during ?-adrenergic receptor activation. The Journal of Physiology, 2016. 594(14): p. 4015-4016.

. Previs, M.J., et al., Phosphorylation and calcium antagonistically tune myosin-binding protein C's structure and function. Proceedings of the National Academy of Sciences of the United States of America, 2016. 113(12): p. 3239-3244.

. Fu, Q., X. Chen, and Y.K. Xiang, Compartmentalization of ?-adrenergic signals in cardiomyocytes. Trends in Cardiovascular Medicine, 2013. 23(7): p. 250-256.

. Gresham, K.S. and J.E. Stelzer, The contributions of cardiac myosin binding protein C and troponin I phosphorylation to ??adrenergic enhancement of in vivo cardiac function. The Journal of Physiology, 2016. 594(3): p. 669-686.

. Moss, R.L., D.P. Fitzsimons, and J.C. Ralphe, Cardiac MyBP-C Regulates the Rate and Force of Contraction in Mammalian Myocardium. Circulation Research, 2015. 116(1): p. 183-192.

. Tong, C.W., et al., Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or ?1-Adrenergic Stimulation. Circulation-heart Failure, 2015. 8(3): p. 595-604.

. Biesiadecki, B.J., et al., Tri-modal regulation of cardiac muscle relaxation; intracellular calcium decline, thin filament deactivation, and cross-bridge cycling kinetics. Biophysical Reviews, 2014. 6: p. 273-289.

. Tong, C.W., et al., Acceleration of Crossbridge Kinetics by Protein Kinase A Phosphorylation of Cardiac Myosin Binding Protein C Modulates Cardiac Function. Circulation Research, 2008. 103(9): p. 974-982.

. Frey, N., M. Luedde, and H.A. Katus, Mechanisms of disease: hypertrophic cardiomyopathy. Nature Reviews Cardiology, 2012. 9(2): p. 91-100.

. Van Dijk, S.J., et al., Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function. Circulation-heart Failure, 2012. 5(1): p. 36-46.

. Rosas, P.C., et al., Phosphorylation of Cardiac Myosin-Binding Protein-C Is a Critical Mediator of Diastolic Function. Circulation-heart Failure, 2015. 8(3): p. 582-594.

. Figueroa, M.S. and J.I. Peters, Congestive Heart Failure: Diagnosis, Pathophysiology, Therapy, and Implications for Respiratory Care. Respiratory Care, 2006. 51(4): p. 403-412.

. Borlaug, B.A. and W.J. Paulus, Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. European Heart Journal, 2011. 32(6): p. 670-679.

. Borlaug, B.A., et al., Impaired Chronotropic and Vasodilator Reserves Limit Exercise Capacity in Patients With Heart Failure and a Preserved Ejection Fraction. Circulation, 2006. 114(20): p. 2138-2147.

. Kawaguchi, M., et al., 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(5): p. 714-720.

. Lam, C.S.P., et al., Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology, 2009. 53(13): p. 1119-1126.

. Maurer, M.S., et al., Ventricular Structure and Function in Hypertensive Participants With Heart Failure and a Normal Ejection Fraction : The Cardiovascular Health Study. Journal of the American College of Cardiology, 2007. 49(9): p. 972-981.

. Maurer, M.S. and S.L. Hummel, Heart Failure With a Preserved Ejection Fraction: What Is in a Name? Journal of the American College of Cardiology, 2011. 58(3): p. 275-277.

. Prasad, A., et al., Characterization of Static and Dynamic Left Ventricular Diastolic Function in Patients With Heart Failure With a Preserved Ejection Fraction. Circulation-heart Failure, 2010. 3(5): p. 617-626.


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