Heart failure (HF)
Heart failure (HF) is a complex clinical syndrome caused by changes in cardiac structure and/or function, resulting in ventricular systolic and/or diastolic dysfunction.
HF is mainly manifested as dyspnea, fatigue, and fluid retention (pulmonary congestion, systemic congestion and peripheral edema). It is also a serious manifestation or advanced stage of various heart diseases.
HF affects approximately 64 million people worldwide. In China, the prevalence of HF among population ≥25 years old was 1.10%, which meant that the estimated total number of individuals ≥25 years old with HF in China was more than 12 million and the prevalence increases with age.
According to the left ventricular ejection fraction (LVEF), HF is classified as HF with reduced LVEF (HFrEF, LVEF≤40%), HF with improved LVEF (HFimpEF, previous LVEF≤40% and a follow-up measurement of LVEF>40%), HF with mildly reduced LVEF (HFmrEF, LVEF 41%- 49%), and HF with preserved LVEF (HFpEF, LVEF≥50%). In a Chinese cohort, the 5-year mortality rate in HFrEF patients is significantly higher than in other types.
Although remarkable achievements have been made in the prevention and treatment of HF, the overall prognosis of HF is still poor. Data showed that the 30-day and 1-year readmission rates of patients with HF after discharge in China are 19% and 53%, while the mortality rates are 14% and 29%, respectively. Given the number of patients with HF, repeated hospitalizations and death place a significant burden on both families and the health care system.
Aficamten can potentially serve as a drug candidate for heart failure with preserved ejection fraction (HFpEF). As a myosin inhibitor, aficamten modulates sarcomere dysfunction by improving cardiac muscle contractility and has the potential to increase lifespan of patients with heart failure.
Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator, the first of a novel class of myotropes designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction (HFrEF). Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.
- Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes, Myotropes, and Mitotropes. JACC. 2019; 73:2345-53.
- Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat Commun. 2017;8:190.
- Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010; 3: 522-27.
- Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439-43.
- Yang et al., Heart Failure Group of the Cardiovascular Diseases Branch of the Chinese Medical Association, Heart Failure Specialty Committee of Chinese Physicians Association, Editorial Board of Chinese Journal of Cardiology. 2018 Chinese guidelines for the diagnosis and treatment of heart failure. Chin J Cardiol. 2018;46(10):760-789.
- GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet.2018; 392: 1789–1858.
- Wang H, Chai K, Du M, et al. Prevalence and Incidence of Heart Failure Among Urban Patients in China: A National Population-Based Analysis. Circ Heart Fail. 2021;14(10):e008406.
- Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol.2022;79(17):e263-e421.
- Chen SQ, Huang ZD, Liang Y, et al. Five-year mortality of heart failure with preserved, mildly reduced, and reduced ejection fraction in a 4880 Chinese cohort. ESC Heart Fail. 2022;9(4):2336-2347.
- Lan T, Liao Y, Zhang J, et al. Mortality and readmission rates after heart failure: A systematic review and meta-analysis. Therapeutics and Clinical Risk Management. 2021;17: 1307–1320.