Bozkurt, B. et al. HF STATS 2024: heart failure epidemiology and outcomes statistics an updated 2024 report from the Heart Failure Society of America. J. Card. Fail. https://doi.org/10.1016/j.cardfail.2024.07.001 (2024).

Ng, M. et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the global burden of disease study 2013. Lancet 384, 766–781 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Maack, C. et al. Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the translational research committee of the Heart Failure Association–European Society of Cardiology. Eur. Heart J. 39, 4243–4254 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Braunwald, E. Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog. Cardiovasc. Dis. 62, 298–302 (2019).

Article  PubMed  Google Scholar 

Robertson, J. et al. Body mass index in young women and risk of cardiomyopathy: a long-term follow-up study in Sweden. Circulation 141, 520–529 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Robertson, J. et al. Higher body mass index in adolescence predicts cardiomyopathy risk in midlife. Circulation 140, 117–125 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Setoguchi, S., Stevenson, L. W. & Schneeweiss, S. Repeated hospitalizations predict mortality in the community population with heart failure. Am. Heart J. 154, 260–266 (2007).

Article  PubMed  Google Scholar 

Mamas, M. A. et al. Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. Eur. J. Heart Fail. 19, 1095–1104 (2017).

Article  PubMed  Google Scholar 

Murashige, D. et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science 370, 364–368 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neubauer, S. et al. Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96, 2190–2196 (1997).

Article  CAS  PubMed  Google Scholar 

Phan, T. T. et al. 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, 402–409 (2009).

Article  PubMed  Google Scholar 

Mahmod, M. et al. The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study. J. Cardiovasc. Magn. Reson. 20, 88 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Neubauer, S. The failing heart — an engine out of fuel. N. Engl. J. Med. 356, 1140–1151 (2007).

Article  PubMed  Google Scholar 

Bertero, E. & Maack, C. Metabolic remodelling in heart failure. Nat. Rev. Cardiol. 15, 457–470 (2018).

Article  CAS  PubMed  Google Scholar 

Bertero, E. & Maack, C. Calcium signaling and reactive oxygen species in mitochondria. Circ. Res. 122, 1460–1478 (2018).

Article  CAS  PubMed  Google Scholar 

Ardehali, H. et al. Targeting myocardial substrate metabolism in heart failure: potential for new therapies. Eur. J. Heart Fail. 14, 120–129 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Anker, S. D. et al. Empagliflozin in heart failure with a preserved ejection fraction. N. Engl. J. Med. 385, 1451–1461 (2021).

Article  CAS  PubMed  Google Scholar 

McMurray, J. J. V. et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N. Engl. J. Med. 381, 1995–2008 (2019).

Article  CAS  PubMed  Google Scholar 

Packer, M. et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N. Engl. J. Med. 383, 1413–1424 (2020).

Article  CAS  PubMed  Google Scholar 

Solomon, S. D. et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N. Engl. J. Med. 387, 1089–1098 (2022).

Article  PubMed  Google Scholar 

Kosiborod, M. N. et al. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet 404, 949–961 (2024).

Article  CAS  PubMed  Google Scholar 

Packer, M. et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N. Engl. J. Med. 392, 427–437 (2025).

Article  CAS  PubMed  Google Scholar 

Kosiborod, M. N. et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N. Engl. J. Med. 389, 1069–1084 (2023).

Article  CAS  PubMed  Google Scholar 

Kosiborod, M. N. et al. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N. Engl. J. Med. 390, 1394–1407 (2024).

Article  CAS  PubMed  Google Scholar 

Böhm, M., Bewarder, Y. & Kindermann, I. Ejection fraction in heart failure revisited- where does the evidence start? Eur. Heart J. 41, 2363–2365 (2020).

Article  PubMed  Google Scholar 

Teerlink, J. R. et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N. Engl. J. Med. 384, 105–116 (2021).

Article  CAS  PubMed  Google Scholar 

Olivotto, I. et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 396, 759–769 (2020).

Article  CAS  PubMed  Google Scholar 

Maron, M. S. et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. N. Engl. J. Med. 390, 1849–1861 (2024).

Article  CAS  PubMed  Google Scholar 

Lehman, S. J., Crocini, C. & Leinwand, L. A. Targeting the sarcomere in inherited cardiomyopathies. Nat. Rev. Cardiol. 19, 353–363 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Saks, V. et al. Cardiac system bioenergetics: metabolic basis of the Frank–Starling law. J. Physiol. 571, 253–273 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bers, D. M. Cardiac excitation-contraction coupling. Nature 415, 198–205 (2002).

Article  CAS  PubMed  Google Scholar 

Schramm, M., Klieber, H. G. & Daut, J. The energy expenditure of actomyosin-ATPase, Ca(2+)-ATPase and Na+,K(+)-ATPase in guinea-pig cardiac ventricular muscle. J. Physiol. 481, 647–662 (1994).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Balaban, R. S., Nemoto, S. & Finkel, T. Mitochondria, oxidants, and aging. Cell 120, 483–495 (2005).

Article