Tan YT, Wenzelburger F, Lee E, Heatlie G, Leyva F, Patel K, et al. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J Am Coll Cardiol. 2009;54(1):36–46.

Article  PubMed  Google Scholar 

Rosch S, Kresoja KP, Besler C, Fengler K, Schöber AR, von Roeder M, et al. Characteristics of heart failure with preserved ejection fraction across the range of left ventricular ejection fraction. Circulation. 2022;146(7):506–18.

Article  CAS  PubMed  Google Scholar 

Pecchia B, Samuel R, Shah V, Newman E, Gibson GT. Mechanisms ofexercise intolerance in heart failure with preserved ejection fraction (HFpEF). Heart Fail Rev. 2025. https://doi.org/10.1007/s10741-025-10504-3.

Article  PubMed  PubMed Central  Google Scholar 

Miranda JJ, Barrientos-Gutiérrez T, Corvalan C, Hyder AA, Lazo-Porras M, Oni T, et al. Understanding the rise of cardiometabolic diseases in low- and middle-income countries. Nat Med. 2019;25(11):1667–79.

Article  CAS  PubMed  Google Scholar 

Shahim B, Kapelios CJ, Savarese G, Lund LH. Global public health burden of heart failure: an updated review. Card Fail Rev. 2023;9: e11.

Article  PubMed  PubMed Central  Google Scholar 

Campbell P, Rutten FH, Lee MM, Hawkins NM, Petrie MC. Heart failure with preserved ejection fraction: everything the clinician needs to know. Lancet. 2024;403(10431):1083–92.

Article  PubMed  Google Scholar 

Samson R, Jaiswal A, Ennezat PV, Cassidy M, Le Jemtel TH. Clinical phenotypes in heart failure with preserved ejection fraction. J Am Heart Assoc. 2016;5(1): e002477.

Article  PubMed  PubMed Central  Google Scholar 

Wong ND, Sattar N. Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention. Nat Rev Cardiol. 2023;20(10):685–95.

Article  PubMed  Google Scholar 

Lopez-Jimenez F, Almahmeed W, Bays H, Cuevas A, Di Angelantonio E, le Roux CW, et al. Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the world heart federation and world obesity federation. Eur J Prev Cardiol. 2022;29(17):2218–37.

Article  PubMed  Google Scholar 

Kenchaiah S, Chesebro JH. The epidemiologic association between obesity and heart failure. Am Coll Cardiol Ext Learn. 2017;49(8):4–6.

PubMed  PubMed Central  Google Scholar 

Hong Y, Gao Z, Wei H, Wei Y, Qiu Z, Xiao J, et al. Bi-directional association of body size and composition with heart failure: a Mendelian randomization study. Int J Cardiol. 2024;407: 132069.

Article  PubMed  Google Scholar 

Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069–84.

Article  CAS  PubMed  Google Scholar 

Kramer CM, Borlaug BA, Zile MR, Ruff D, DiMaria JM, Menon V,et al. Tirzepatide reduces LV mass and paracardiac adipose tissue in obesity-related heart failure: SUMMIT CMR substudy. J Am Coll Cardiol. 2025;85(7):699–706.

Article  CAS  PubMed  Google Scholar 

Hullon D, Subeh GK, Volkova Y, Janiec K, Trach A, Mnevets R. The role of glucagon-like peptide-1 receptor (GLP-1R) agonists in enhancing endothelial function: a potential avenue for improving heart failure with preserved ejection fraction (HFpEF). Cardiovasc Diabetol. 2025;24(1):70.

Article  PubMed  PubMed Central  Google Scholar 

Hall JL, Terzic A. Heart failure transcriptome. Circ Cardiovasc Genet. 2011;4(5):469–71.

Article  CAS  PubMed  Google Scholar 

Alpert MA, Karthikeyan K, Abdullah O, Ghadban R. Obesity and cardiac remodeling in adults: mechanisms and clinical implications. Prog Cardiovasc Dis. 2018;61(2):114–23.

Article  PubMed  Google Scholar 

Mishra S, Kass DA. Cellular and molecular pathobiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2021;18(6):400–23.

Article  PubMed  PubMed Central  Google Scholar 

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(10159):1789–858.

Walters GWM, Yeo JL, Bilak JM, Pepper C, Gulsin GS, Freeman SC, et al. The effectiveness of lifestyle interventions in heart failure with preserved ejection fraction: a systematic review and network meta-analysis. J Card Fail. 2024;30(8):994–1009.

Article  PubMed  Google Scholar 

Carbone S, Lavie CJ. Disparate effects of obesity on survival and hospitalizations in heart failure with preserved ejection fraction. Int J Obes (Lond). 2020;44(7):1543–5.

Article  PubMed  Google Scholar 

Hamo CE, DeJong C, Hartshorne-Evans N, Lund LH, Shah SJ, Solomon S, et al. Heart failure with preserved ejection fraction. Nat Rev Dis Primers. 2024;10(1):55.

Article  PubMed  Google Scholar 

Khan MS, Fonarow GC, Khan H, Greene SJ, Anker SD, Gheorghiade M, et al. Renin-angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta-analysis. ESC Heart Fail. 2017;4(4):402–8.

Article  PubMed  PubMed Central  Google Scholar 

Castiglione V, Gentile F, Ghionzoli N, Chiriacò M, Panichella G, Aimo A, et al. Pathophysiological rationale and clinical evidence for neurohormonal modulation in heart failure with preserved ejection fraction. Card Fail Rev. 2023;9: e09.

Article  PubMed  PubMed Central  Google Scholar 

Lund LH,Benson L, Dahlström U, Edner M. Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction. JAMA. 2012;308(20):2108–17.

Article  CAS  PubMed  Google Scholar 

Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27(11):1954–60.

Article  PubMed  PubMed Central  Google Scholar 

Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61.

Article  CAS  PubMed  Google Scholar 

Peikert A, Bart BA, Vaduganathan M, Claggett BL, Kulac IJ, Kosiborod MN, et al. Contemporary use and implications of beta-blockers in patients with HFmrEF or HFpEF: the DELIVER trial. JACC Heart Fail. 2024;12(4):631–44.

Article  CAS  PubMed  Google Scholar 

Salah HM, Fudim M, Al’Aref SJ, Khan MS, Almarzooq ZI, Devabhaktuni SR, et al. Meta-analysis of efficacy of sacubitril/valsartan in heart failure with preserved ejection fraction. Am J Cardiol. 2021;145:165–8.

Article  PubMed  Google Scholar 

Thangaraj PM, Oikonomou EK, Dhingra LS, Aminorroaya A, Jayaram R, Suchard MA, et al. Computational phenomapping of randomized clinical trial participants to enable assessment of their real-world representativeness and personalized inference. Circ Cardiovasc Qual Outcomes. 2025. https://doi.org/10.1161/CIRCOUTCOMES.124.011306.

Article  PubMed  Google Scholar 

Bozkurt B, Ezekowitz J. Substance and substrate: LVEF and sex subgroup analyses of PARAGON-HF and PARADIGM-HF trials. Circulation. 2020;141(5):362–6.

Article  PubMed  Google Scholar 

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(17):1609–20.

Article  CAS  PubMed  Google Scholar 

Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al. Finerenone in Heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2024;391(16):1475–85.

Article  CAS  PubMed  Google Scholar 

Stoicescu L, Crişan D, Morgovan C, Avram L, Ghibu S. Heart failure with preserved ejection fraction: the pathophysiological mechanisms behind the clinical phenotypes and the therapeutic ap