Heart failure with mildly reduced ejection fraction. Challenges, realities and future


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Insuficiencia Cardíaca
Imagen por Resonancia Magnética
Inhibidores del Cotransportador de Sodio-Glucosa 2
Ecocardiografía Heart failure
Magnetic Resonance Imaging
Sodium-Glucose Transporter 2 Inhibitors

How to Cite

Aristizabal, D., Pineda Moreno, M., & Moreno Soto, K. J. (2023). Heart failure with mildly reduced ejection fraction. Challenges, realities and future. Interdisciplinary Journal of Epidemiology and Public Health, 5(2), e–9885. https://doi.org/10.18041/2665-427X/ijeph.2.9885 (Original work published December 30, 2022)


Introduction: Heart failure with mildly reduced ejection fraction has been a sensitive point in cardiology throughout its history, since it has had multiple names and a pathophysiology that can belong to both heart failure with Heart failure with reduced ejection fraction (less than 40%) and heart failure Heart failure with preserved ejection fraction (greater than 50%), which makes it difficult to generate standard  recommendations for this entity.

Objective: Recognize Heart failure with mildly reduced ejection fraction as an individual entity both for its diagnosis and follow-up, for which currently efforts are being made to develop phenotypes that allow us to go beyond the ejection fraction, mainly consolidated from characteristics valued by cardiac magnetic resonance imaging, as well as for its management

Methods: Narrative review of the literature

Results: Traditional therapies such as beta-blockers, ACE (Angiotensin converting enzyme) inhibitors, ARBs (Angiotensin receptor blockers), mineralocorticoid receptor antagonists, barely manage to give rise to guidelines for their use for medical consideration (IIb recommendation), as a novelty, iSGLT2 have been positioned as the standard therapy in heart failure syndrome regardless of the left ventricular ejection fraction.

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Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, Adamopoulos S, Albert N, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. 2021; 27:387-413. Doi: 10.1016/j.cardfail.2021.01.022.

Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387:1089-98. Doi: 10.1056/NEJMoa2206286.

Anker SD, Butler J, Filippatos GS, Jamal W, Salsali A, Schnee J, et al. Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial. Eur J Heart Fail. 2019;21:1279-87. Doi: 10.1002/ejhf.1596.

Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384:117-28. Doi: 10.1056/NEJMoa2030183.

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 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. 2013; 62: e147-239. Doi: 10.1016/j.jacc.2013.05.019.

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129-200. Doi: 10.1093/eurheartj/ehw128.

Rickenbacher P, Kaufmann BA, Maeder MT, Bernheim A, Goetschalckx K, Pfister O, et al. Heart failure with mid-range ejection fraction: a distinct clinical entity? Insights from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF). Eur J Heart Fail. 2017;19:1586-96. Doi: 10.1002/ejhf.798.

Savarese G, Stolfo D, Sinagra G, Lund LH. Heart failure with mid-range or mildly reduced ejection fraction. Nat Rev Cardiol. 2022;19:100-16. Doi: 10.1038/s41569-021-00605-5.

Nauta JF, Hummel YM, van Melle JP, van der Meer P, Lam CSP, Ponikowski P, et al. What have we learned about heart failure with mid-range ejection fraction one year after its introduction? Eur J Heart Fail. 2017;19:1569-73. Doi: 10.1002/ejhf.1058.

Rastogi A, Novak E, Platts AE, Mann DL. Epidemiology, pathophysiology and clinical outcomes for heart failure patients with a mid-range ejection fraction. Eur J Heart Fail. 2017;19:1597-605. Doi: 10.1002/ejhf.879.

Cheng RK, Cox M, Neely ML, Heidenreich PA, Bhatt DL, Eapen ZJ, et al. Outcomes in patients with heart failure with preserved, borderline, and reduced ejection fraction in the Medicare population. Am Heart J. 2014;168:721-30. Doi: 10.1016/j.ahj.2014.07.008.

Coles AH, Tisminetzky M, Yarzebski J, Lessard D, Gore JM, Darling CE, et al. Magnitude of and Prognostic Factors Associated With 1-Year Mortality After Hospital Discharge for Acute Decompensated Heart Failure Based on Ejection Fraction Findings. J Am Heart Assoc. 2015;4:e002303. Doi: 10.1161/JAHA.115.002303.

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42:3599-726. Doi: 10.1093/eurheartj/ehab368.

Schwartzenberg 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;59:442-51. Doi: 10.1016/j.jacc.2011.09.062.

Dzau VJ. Renal and circulatory mechanisms in congestive heart failure. Kidney Int 1987;31:1402-15. Doi: 10.1038/ki.1987.156.

Francis GS, Goldsmith SR, Levine TB, Olivari MT, Cohn JN. The neurohumoral axis in congestive heart failure. Ann Intern Med. 1984; 101(3): 370-7.

doi: 10.7326/0003-4819-101-3-370.

Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Zhang H, et al. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest. 2007;117:2431-44. Doi: 10.1172/JCI31060.

Bhargava V, Shabetai R, Mathiäsen RA, Dalton N, Hunter JJ, Ross J. Loss of adrenergic control of the force-frequency relation in heart failure secondary to idiopathic or ischemic cardiomyopathy. Am J Cardiol. 1998;81:1130-7. Doi: 10.1016/s0002-9149(98)00133-7.

Fullerton MJ, Funder JW. Aldosterone and cardiac fibrosis: in vitro studies. Cardiovasc Res. 1994;28:1863-7. Doi: 10.1093/cvr/28.12.1863.

Lijnen P, Petrov V. Induction of cardiac fibrosis by aldosterone. J Mol Cell Cardiol. 2000;32:865-79. Doi: 10.1006/jmcc.2000.1129.

Koh AS, Tay WT, Teng THK, Vedin O, Benson L, Dahlstrom U, et al. A comprehensive population-based characterization of heart failure with mid-range ejection fraction. Eur J Heart Fail. 2017;19:1624-34. Doi: 10.1002/ejhf.945.

Kim Y-J, Kim RJ. The role of cardiac MR in new-onset heart failure. Curr Cardiol Rep. 2011;13:185-93. Doi: 10.1007/s11886-011-0179-0.

Quarta G, Gori M, Iorio A, D'Elia E, Moon JC, Iacovoni A, et al. Cardiac magnetic resonance in heart failure with preserved ejection fraction: myocyte, interstitium, microvascular, and metabolic abnormalities. Eur J Heart Fail. 2020;22:1065-75. Doi: 10.1002/ejhf.1961.

Treibel TA, Kozor R, Schofield R, Benedetti G, Fontana M, Bhuva AN, et al. Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis. J Am Coll Cardiol. 2018;71:860-71. Doi: 10.1016/j.jacc.2017.12.035.

Plata-Mosquera CA, Bernal-Tórres W, Herrera-Escandón ÁA, Uribe-Posso LP, Rodríguez-Casanova ÁM, Casanova-Valderrama ME, et al. Sacubitril/valsartan reduces levels of procollagen types I and III and correlates with reverse cardiac remodeling. REC CardioClinics. 2021;56:14-21. Doi: 10.1016/j.rccl.2020.06.002.

Fonarow GC, Abraham WT, Albert NM, Gattis WA, Gheorghiade M, Greenberg B, et al. Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF): rationale and design. Am Heart J. 2004;148:43-51. Doi: 10.1016/j.ahj.2004.03.004.

Flather MD, Shibata MC, Coats AJS, Van Veldhuisen DJ, Parkhomenko A, Borbola J, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005;26:215-25. Doi: 10.1093/eurheartj/ehi115.

Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777-81. Doi: 10.1016/S0140-6736(03)14285-7.

Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2014;370:1383-92. Doi: 10.1056/NEJMoa1313731.

Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, et al. Angiotensin-Neprilysin inhibition in Heart failure with preserved ejection fraction. N Engl J Med. 2019;381:1609-20. Doi: 10.1056/NEJMoa1908655.

Bozkurt B, Fonarow GC, Goldberg LR, Guglin M, Josephson RA, Forman DE, et al. Cardiac rehabilitation for patients with heart failure: JACC Expert Panel. J Am Coll Cardiol. 2021;77:1454-69. Doi: 10.1016/j.jacc.2021.01.030.

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