{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:35:50Z","timestamp":1774917350376,"version":"3.50.1"},"reference-count":164,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Heart failure with preserved ejection fraction (HFpEF) is frequently observed in elderly physically deconditioned subjects, mainly women with hypertension, obesity, glucose intolerance\/diabetes, atrial fibrillation, anaemia, coronary artery disease, chronic pulmonary disease, and chronic renal insufficiency. In practice, these conditions represent the majority of cardiac diseases we deal with in our daily clinical practice. For this reason, the HFpEF disease does not exist as a single entity and, as such, no specific unifying therapy could be found. New classification attempts still do not consider the multifaceted aspect of the HF syndrome and appear rather as an artefactual attempt to categorize a condition which is indeed not categorizable. The aim of the present article is to critically review the construction of the concept of the HFpEF syndrome and propose the return of a pathophysiological approach in the evaluation and treatment of patients. Considering the huge economic efforts employed up to date to run awfully expensive trials and research in this field, it is time to call action and redirect such resources towards more specific pathophysiological classifications and potential specific therapeutic targets.<\/jats:p>","DOI":"10.31083\/j.rcm2407202","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T08:14:59Z","timestamp":1689927299000},"source":"Crossref","is-referenced-by-count":5,"title":["The Concept of \"Heart Failure with Preserved Ejection Fraction\": Time for a Critical Reappraisal"],"prefix":"10.31083","volume":"24","author":[{"given":"Gabriele","family":"Fragasso","sequence":"first","affiliation":[{"name":"Heart Failure Clinic, Istituto Scientifico San Raffaele, 20132 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Echeverria HH, Bilsker MS, Myerburg RJ, Kessler KM. Congestive heart failure: echocardiographic insights. The American Journal of Medicine. 1983; 75: 750\u2013755.","DOI":"10.1016\/0002-9343(83)90403-5"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Dougherty AH, Naccarelli GV, Gray EL, Hicks CH, Goldstein RA. Congestive heart failure with normal systolic function. The American Journal of Cardiology. 1984; 54: 778\u2013782.","DOI":"10.1016\/S0002-9149(84)80207-6"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Soufer R, Wohlgelernter D, Vita NA, Amuchestegui M, Sostman HD, Berger HJ, et al. Intact systolic left ventricular function in clinical congestive heart failure. The American Journal of Cardiology. 1985; 55: 1032\u20131036.","DOI":"10.1016\/0002-9149(85)90741-6"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Zile MR. Heart failure with preserved ejection fraction: is this diastolic heart failure? Journal of the American College of Cardiology. 2003; 41: 1519\u20131522.","DOI":"10.1016\/S0735-1097(03)00186-4"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Burkhoff D, Maurer MS, Packer M. Heart failure with a normal ejection fraction: is it really a disorder of diastolic function? Circulation. 2003; 107: 656\u2013658.","DOI":"10.1161\/01.CIR.0000053947.82595.03"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. ACC\/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005; 112: e154\u2013e235.","DOI":"10.1161\/CIRCULATIONAHA.105.167587"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"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. European Journal of Heart Failure. 2016; 18: 891\u2013975.","DOI":"10.1002\/ejhf.592"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Gerber Y, Weston SA, Redfield MM, Chamberlain AM, Manemann SM, Jiang R, et al. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Internal Medicine. 2015; 175: 996\u20131004.","DOI":"10.1001\/jamainternmed.2015.0924"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nature Reviews Cardiology. 2017; 14: 591\u2013602.","DOI":"10.1038\/nrcardio.2017.65"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Pfeffer MA, Shah AM, Borlaug BA. Heart Failure With Preserved Ejection Fraction In Perspective. Circulation Research. 2019; 124: 1598\u20131617.","DOI":"10.1161\/CIRCRESAHA.119.313572"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Wang TJ, Larson MG, Levy D, Leip EP, Benjamin EJ, Wilson PWF, et al. Impact of age and sex on plasma natriuretic peptide levels in healthy adults. The American Journal of Cardiology. 2002; 90: 254\u2013258.","DOI":"10.1016\/S0002-9149(02)02464-5"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Burke MA, Cotts WG. Interpretation of B-type natriuretic peptide in cardiac disease and other comorbid conditions. Heart Failure Reviews. 2007; 12: 23\u201336.","DOI":"10.1007\/s10741-007-9002-9"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Mueller C, McDonald K, de Boer RA, Maisel A, Cleland JGF, Kozhuharov N, et al. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. European Journal of Heart Failure. 2019; 21: 715\u2013731.","DOI":"10.1002\/ejhf.1494"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Alonso J, Mora-Rodr\u00edguez R, Below PR, Coyle EF. Dehydration markedly impairs cardiovascular function in hyperthermic endurance athletes during exercise. Journal of Applied Physiology (Bethesda, Md.: 1985). 1997; 82: 1229\u20131236.","DOI":"10.1152\/jappl.1997.82.4.1229"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Shah AM, Cikes M, Prasad N, Li G, Getchevski S, Claggett B, et al. Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction. Journal of the American College of Cardiology. 2019; 74: 2858\u20132873.","DOI":"10.1016\/j.jacc.2019.09.063"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"van Riet EES, Hoes AW, Wagenaar KP, Limburg A, Landman MAJ, Rutten FH. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. European Journal of Heart Failure. 2016; 18: 242\u2013252.","DOI":"10.1002\/ejhf.483"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Badano LP, Albanese MC, De Biaggio P, Rozbowsky P, Miani D, Fresco C, et al. Prevalence, clinical characteristics, quality of life, and prognosis of patients with congestive heart failure and isolated left ventricular diastolic dysfunction. Journal of the American Society of Echocardiography. 2004; 17: 253\u2013261.","DOI":"10.1016\/j.echo.2003.11.002"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Persson H, Donal E, Lund LH, Matan D, Oger E, Hage C, et al. Importance of structural heart disease and diastolic dysfunction in heart failure with preserved ejection fraction assessed according to the ESC guidelines - A substudy in the Ka (Karolinska) Ren (Rennes) study. International Journal of Cardiology. 2019; 274: 202\u2013207.","DOI":"10.1016\/j.ijcard.2018.06.078"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Hammond MM, Shen C, Li S, Kazi DS, Sabe MA, Garan AR, et al. Retrospective evaluation of echocardiographic variables for prediction of heart failure hospitalization in heart failure with preserved versus reduced ejection fraction: A single center experience. PLoS ONE. 2020; 15: e0244379.","DOI":"10.1371\/journal.pone.0244379"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Kap\u0142on-Cie\u015blicka A, Laroche C, Crespo-Leiro MG, Coats AJS, Anker SD, Filippatos G, et al. Is heart failure misdiagnosed in hospitalized patients with preserved ejection fraction? From the European Society of Cardiology - Heart Failure Association EURObservational Research Programme Heart Failure Long-Term Registry. ESC Heart Failure. 2020; 7: 2098\u20132112.","DOI":"10.1002\/ehf2.12817"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Loffredo FS, Nikolova AP, Pancoast JR, Lee RT. Heart failure with preserved ejection fraction: molecular pathways of the aging myocardium. Circulation Research. 2014; 115: 97\u2013107.","DOI":"10.1161\/CIRCRESAHA.115.302929"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Kannel WB, Belanger AJ. Epidemiology of heart failure. American Heart Journal. 1991; 121: 951\u2013957.","DOI":"10.1016\/0002-8703(91)90225-7"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. The New England Journal of Medicine. 2006; 355: 251\u2013259.","DOI":"10.1056\/NEJMoa052256"},{"key":"ref24","unstructured":"Shock NW, Greulich RC, Andres RA. Normal human aging: The Baltimore Longitudinal Study of Aging. NIH Publication No. 84-2450. US Government Printing Office: Washington, DC. 1984."},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Shapiro LM, Howat AP, Crean PA, Westgate CJ. An echocardiographic study of localized subaortic hypertrophy. European Heart Journal. 1986; 7: 127\u2013132.","DOI":"10.1093\/oxfordjournals.eurheartj.a062034"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Canepa M, Malti O, David M, AlGhatrif M, Strait JB, Ameri P, et al. Prevalence, clinical correlates, and functional impact of subaortic ventricular septal bulge (from the Baltimore Longitudinal Study of Aging). The American Journal of Cardiology. 2014; 114: 796\u2013802.","DOI":"10.1016\/j.amjcard.2014.05.068"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Rockey DC, Bell PD, Hill JA. Fibrosis\u2013a common pathway to organ injury and failure. The New England Journal of Medicine. 2015; 372: 1138\u20131149.","DOI":"10.1056\/NEJMra1300575"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Conway MA, Allis J, Ouwerkerk R, Niioka T, Rajagopalan B, Radda GK. Detection of low phosphocreatine to ATP ratio in failing hypertrophied human myocardium by 31P magnetic resonance spectroscopy. Lancet (London, England). 1991; 338: 973\u2013976.","DOI":"10.1016\/0140-6736(91)91838-L"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Nathania M, Hollingsworth KG, Bates M, Eggett C, Trenell MI, Velicki L, et al. Impact of age on the association between cardiac high-energy phosphate metabolism and cardiac power in women. Heart (British Cardiac Society). 2018; 104: 111\u2013118.","DOI":"10.1136\/heartjnl-2017-311275"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Fragasso G, De Cobelli F, Spoladore R, Esposito A, Salerno A, Calori G, et al. Resting cardiac energy metabolism is inversely associated with heart rate in healthy young adult men. American Heart Journal. 2011; 162: 136\u2013141.","DOI":"10.1016\/j.ahj.2011.04.012"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Fragasso G. Age-related reduction of myocardial metabolic efficiency: Is it time to routinely measure myocardial metabolism to monitor cardiac health? Heart (British Cardiac Society). 2018; 104: 88\u201389.","DOI":"10.1136\/heartjnl-2017-311729"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circulation Research. 1991; 68: 1560\u20131568.","DOI":"10.1161\/01.RES.68.6.1560"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnab\u00e9-Heider F, Walsh S, et al. Evidence for cardiomyocyte renewal in humans. Science (New York, N.Y.). 2009; 324: 98\u2013102.","DOI":"10.1126\/science.1164680"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010; 304: 2503\u20132512.","DOI":"10.1001\/jama.2010.1768"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Cesselli D, Aleksova A, Sponga S, Cervellin C, Di Loreto C, Tell G, et al. Cardiac Cell Senescence and Redox Signaling. Frontiers in Cardiovascular Medicine. 2017; 4: 38.","DOI":"10.3389\/fcvm.2017.00038"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD. Age-related changes in normal human hearts during the first 10 decades of life. Part II (Maturity): A quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clinic Proceedings. 1988; 63: 137\u2013146.","DOI":"10.1016\/S0025-6196(12)64946-5"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Ren J, Zhang Y. Genetics and Epigenetics in Aging and Longevity: Myths and Truths. Biochimica et Biophysica Acta: Molecular Basis of Disease. 2019; 1865: 1715\u20131717.","DOI":"10.1016\/j.bbadis.2019.02.005"},{"key":"ref38","unstructured":"Boss GR, Seegmiller JE. Age-related physiological changes and their clinical significance. The Western Journal of Medicine. 1981; 135: 434\u2013440."},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Peoples JN, Saraf A, Ghazal N, Pham TT, Kwong JQ. Mitochondrial dysfunction and oxidative stress in heart disease. Experimental & Molecular Medicine. 2019; 51: 1\u201313.","DOI":"10.1038\/s12276-019-0355-7"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Mar\u00edn-Garc\u00eda J. Mitochondrial DNA repair: a novel therapeutic target for heart failure. Heart Failure Reviews. 2016; 21: 475\u2013487.","DOI":"10.1007\/s10741-016-9543-x"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Moslehi J, DePinho RA, Sahin E. Telomeres and mitochondria in the aging heart. Circulation Research. 2012; 110: 1226\u20131237.","DOI":"10.1161\/CIRCRESAHA.111.246868"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Chaudhuri J, Bains Y, Guha S, Kahn A, Hall D, Bose N, et al. The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality. Cell Metabolism. 2018; 28: 337\u2013352.","DOI":"10.1016\/j.cmet.2018.08.014"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Candore G, Caruso C, Jirillo E, Magrone T, Vasto S. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Current Pharmaceutical Design. 2010; 16: 584\u2013596.","DOI":"10.2174\/138161210790883868"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Zhao C, Li G, Li J. Non-coding RNAs and Cardiac Aging. Advances in Experimental Medicine and Biology. 2020; 1229: 247\u2013258.","DOI":"10.1007\/978-981-15-1671-9_14"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Tahhan AS, Vaduganathan M, Greene SJ, Fonarow GC, Fiuzat M, Jessup M, et al. Enrollment of Older Patients, Women, and Racial and Ethnic Minorities in Contemporary Heart Failure Clinical Trials: A Systematic Review. JAMA Cardiology. 2018; 3: 1011\u20131019.","DOI":"10.1001\/jamacardio.2018.2559"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Kitzman DW, O\u2019Neill TJ, 4th, Brubaker PH. Unraveling the Relationship Between Aging and Heart Failure With Preserved Ejection Fraction: The Importance of Exercise and Normative Reference Standards. JACC: Heart Failure. 2017; 5: 356\u2013358.","DOI":"10.1016\/j.jchf.2017.01.009"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Ho JE, Enserro D, Brouwers FP, Kizer JR, Shah SJ, Psaty BM, et al. Predicting Heart Failure With Preserved and Reduced Ejection Fraction: The International Collaboration on Heart Failure Subtypes. Circulation. Heart Failure. 2016; 9.","DOI":"10.1161\/CIRCHEARTFAILURE.115.003116"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, et al. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet (London, England). 2018; 391: 572\u2013580.","DOI":"10.1016\/S0140-6736(17)32520-5"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, Ordin DL, et al. Gender, age, and heart failure with preserved left ventricular systolic function. Journal of the American College of Cardiology. 2003; 41: 217\u2013223.","DOI":"10.1016\/S0735-1097(02)02696-7"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"O\u2019Meara E, Clayton T, McEntegart MB, McMurray JJV, Pi\u00f1a IL, Granger CB, et al. Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Circulation. 2007; 115: 3111\u20133120.","DOI":"10.1161\/CIRCULATIONAHA.106.673442"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Anker SD, Butler J, Filippatos G, Shahzeb Khan M, Ferreira JP, Bocchi E, et al. Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial. European Journal of Heart Failure. 2020; 22: 2383\u20132392.","DOI":"10.1002\/ejhf.2064"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Desai RJ, Mahesri M, Chin K, Levin R, Lahoz R, Studer R, et al. Epidemiologic Characterization of Heart Failure with Reduced or Preserved Ejection Fraction Populations Identified Using Medicare Claims. The American Journal of Medicine. 2021; 134: e241\u2013e251.","DOI":"10.1016\/j.amjmed.2020.09.038"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Sotomi Y, Hikoso S, Nakatani D, Mizuno H, Okada K, Dohi T, et al. Sex Differences in Heart Failure With Preserved Ejection Fraction. Journal of the American Heart Association. 2021; 10: e018574.","DOI":"10.1161\/JAHA.120.018574"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Kitzman DW, Gardin JM, Gottdiener JS, Arnold A, Boineau R, Aurigemma G, et al. Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study. The American Journal of Cardiology. 2001; 87: 413\u2013419.","DOI":"10.1016\/S0002-9149(00)01393-X"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Oneglia A, Nelson MD, Merz CNB. Sex Differences in Cardiovascular Aging and Heart Failure. Current Heart Failure Reports. 2020; 17: 409\u2013423.","DOI":"10.1007\/s11897-020-00487-7"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"Echouffo-Tcheugui JB, Xu H, DeVore AD, Schulte PJ, Butler J, Yancy CW, et al. Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: Findings from Get With The Guidelines-Heart Failure registry. American Heart Journal. 2016; 182: 9\u201320.","DOI":"10.1016\/j.ahj.2016.07.025"},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"McHugh K, DeVore AD, Wu J, Matsouaka RA, Fonarow GC, Heidenreich PA, et al. Heart Failure With Preserved Ejection Fraction and Diabetes: JACC State-of-the-Art Review. Journal of the American College of Cardiology. 2019; 73: 602\u2013611.","DOI":"10.1016\/j.jacc.2018.11.033"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Kenchaiah S, Evans JC, Levy D, Wilson PWF, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. The New England Journal of Medicine. 2002; 347: 305\u2013313.","DOI":"10.1056\/NEJMoa020245"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"Wong CY, O\u2019Moore-Sullivan T, Leano R, Byrne N, Beller E, Marwick TH. Alterations of left ventricular myocardial characteristics associated with obesity. Circulation. 2004; 110: 3081\u20133087.","DOI":"10.1161\/01.CIR.0000147184.13872.0F"},{"key":"ref60","doi-asserted-by":"crossref","unstructured":"Russo C, Sera F, Jin Z, Palmieri V, Homma S, Rundek T, et al. Abdominal adiposity, general obesity, and subclinical systolic dysfunction in the elderly: A population-based cohort study. European Journal of Heart Failure. 2016; 18: 537\u2013544.","DOI":"10.1002\/ejhf.521"},{"key":"ref61","doi-asserted-by":"crossref","unstructured":"Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation. 2017; 136: 6\u201319.","DOI":"10.1161\/CIRCULATIONAHA.116.026807"},{"key":"ref62","doi-asserted-by":"crossref","unstructured":"Prenner SB, Mather PJ. Obesity and heart failure with preserved ejection fraction: A growing problem. Trends in Cardiovascular Medicine. 2018; 28: 322\u2013327.","DOI":"10.1016\/j.tcm.2017.12.003"},{"key":"ref63","doi-asserted-by":"crossref","unstructured":"Rusinaru D, Houpe D, Szymanski C, L\u00e9vy F, Mar\u00e9chaux S, Tribouilloy C. Coronary artery disease and 10-year outcome after hospital admission for heart failure with preserved and with reduced ejection fraction. European Journal of Heart Failure. 2014; 16: 967\u2013976.","DOI":"10.1002\/ejhf.142"},{"key":"ref64","doi-asserted-by":"crossref","unstructured":"Vedin O, Lam CSP, Koh AS, Benson L, Teng THK, Tay WT, et al. Significance of Ischemic Heart Disease in Patients With Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction: A Nationwide Cohort Study. Circulation: Heart Failure. 2017; 10: e003875.","DOI":"10.1161\/CIRCHEARTFAILURE.117.003875"},{"key":"ref65","doi-asserted-by":"crossref","unstructured":"Rahimi G, Tecson KM, Elsaid O, McCullough PA. Role of Ischemic Heart Disease in Major Adverse Renal and Cardiac Events Among Individuals With Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial). The American Journal of Cardiology. 2021; 142: 91\u201396.","DOI":"10.1016\/j.amjcard.2020.11.034"},{"key":"ref66","doi-asserted-by":"crossref","unstructured":"Hwang SJ, Melenovsky V, Borlaug BA. Implications of coronary artery disease in heart failure with preserved ejection fraction. Journal of the American College of Cardiology. 2014; 63: 2817\u20132827.","DOI":"10.1016\/j.jacc.2014.03.034"},{"key":"ref67","doi-asserted-by":"crossref","unstructured":"Obokata M, Reddy YNV, Melenovsky V, Kane GC, Olson TP, Jarolim P, et al. Myocardial Injury and Cardiac Reserve in Patients With Heart Failure and Preserved Ejection Fraction. Journal of the American College of Cardiology. 2018; 72: 29\u201340.","DOI":"10.1016\/j.jacc.2018.04.039"},{"key":"ref68","doi-asserted-by":"crossref","unstructured":"Lam CSP, Brutsaert DL. Endothelial dysfunction: a pathophysiologic factor in heart failure with preserved ejection fraction. Journal of the American College of Cardiology. 2012; 60: 1787\u20131789.","DOI":"10.1016\/j.jacc.2012.08.004"},{"key":"ref69","doi-asserted-by":"crossref","unstructured":"Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation. 2015; 131: 550\u2013559.","DOI":"10.1161\/CIRCULATIONAHA.114.009625"},{"key":"ref70","doi-asserted-by":"crossref","unstructured":"Franssen C, Chen S, Unger A, Korkmaz HI, De Keulenaer GW, Tsch\u00f6pe C, et al. Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction. JACC: Heart Failure. 2016; 4: 312\u2013324.","DOI":"10.1016\/j.jchf.2015.10.007"},{"key":"ref71","doi-asserted-by":"crossref","unstructured":"Paulus WJ, Tsch\u00f6pe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. Journal of the American College of Cardiology. 2013; 62: 263\u2013271.","DOI":"10.1016\/j.jacc.2013.02.092"},{"key":"ref72","doi-asserted-by":"crossref","unstructured":"Tona F, Montisci R, Iop L, Civieri G. Role of coronary microvascular dysfunction in heart failure with preserved ejection fraction. Reviews in Cardiovascular Medicine. 2021; 22: 97\u2013104.","DOI":"10.31083\/j.rcm.2021.01.277"},{"key":"ref73","doi-asserted-by":"crossref","unstructured":"Shah SJ, Lam CSP, Svedlund S, Saraste A, Hage C, Tan RS, et al. Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF. European Heart Journal. 2018; 39: 3439\u20133450.","DOI":"10.1093\/eurheartj\/ehy531"},{"key":"ref74","doi-asserted-by":"crossref","unstructured":"Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996; 275: 1557\u20131562.","DOI":"10.1001\/jama.275.20.1557"},{"key":"ref75","doi-asserted-by":"crossref","unstructured":"Moser M, Hebert PR. Prevention of disease progression, left ventricular hypertrophy and congestive heart failure in hypertension treatment trials. Journal of the American College of Cardiology. 1996; 27: 1214\u20131218.","DOI":"10.1016\/0735-1097(95)00606-0"},{"key":"ref76","doi-asserted-by":"crossref","unstructured":"Redfield MM, Jacobsen SJ, Burnett JC, Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003; 289: 194\u2013202.","DOI":"10.1001\/jama.289.2.194"},{"key":"ref77","doi-asserted-by":"crossref","unstructured":"Nadruz W, Shah AM, Solomon SD. Diastolic Dysfunction and Hypertension. The Medical Clinics of North America. 2017; 101: 7\u201317.","DOI":"10.1016\/j.mcna.2016.08.013"},{"key":"ref78","doi-asserted-by":"crossref","unstructured":"Verdecchia P, Schillaci G, Guerrieri M, Boldrini F, Gatteschi C, Benemio G, et al. Prevalence and determinants of left ventricular diastolic filling abnormalities in an unselected hypertensive population. European Heart Journal. 1990; 11: 679\u2013691.","DOI":"10.1093\/oxfordjournals.eurheartj.a059783"},{"key":"ref79","doi-asserted-by":"crossref","unstructured":"Sorrentino MJ. The Evolution from Hypertension to Heart Failure. Heart Failure Clinics. 2019; 15: 447\u2013453.","DOI":"10.1016\/j.hfc.2019.06.005"},{"key":"ref80","unstructured":"World Health Organization. 2023. Available at: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hypertension (Accessed: 9 June 2023)."},{"key":"ref81","doi-asserted-by":"crossref","unstructured":"Whelton PK, Carey RM, Aronow WS, Casey DE, Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; 138: e484\u2013e594.","DOI":"10.1161\/CIR.0000000000000597"},{"key":"ref82","doi-asserted-by":"crossref","unstructured":"Kannel WB. Incidence and epidemiology of heart failure. Heart Failure Reviews. 2000; 5: 167\u2013173.","DOI":"10.1023\/A:1009884820941"},{"key":"ref83","doi-asserted-by":"crossref","unstructured":"Yamasaki N, Kitaoka H, Matsumura Y, Furuno T, Nishinaga M, Doi Y. Heart failure in the elderly. Internal Medicine (Tokyo, Japan). 2003; 42: 383\u2013388.","DOI":"10.2169\/internalmedicine.42.383"},{"key":"ref84","doi-asserted-by":"crossref","unstructured":"Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure-lowering treatment. 6. Prevention of heart failure and new-onset heart failure\u2013meta-analyses of randomized trials. Journal of Hypertension. 2016; 34: 373\u2013384.","DOI":"10.1097\/HJH.0000000000000848"},{"key":"ref85","doi-asserted-by":"crossref","unstructured":"Fragasso G, Maranta F, Montanaro C, Salerno A, Torlasco C, Margonato A. Pathophysiologic therapeutic targets in hypertension: a cardiological point of view. Expert Opinion on Therapeutic Targets. 2012; 16: 179\u2013193.","DOI":"10.1517\/14728222.2012.655724"},{"key":"ref86","doi-asserted-by":"crossref","unstructured":"Fragasso G, Margonato A, Spoladore R, Lopaschuk GD. Metabolic effects of cardiovascular drugs. Trends in Cardiovascular Medicine. 2019; 29: 176\u2013187.","DOI":"10.1016\/j.tcm.2018.08.001"},{"key":"ref87","doi-asserted-by":"crossref","unstructured":"Zafrir B, Lund LH, Laroche C, Ruschitzka F, Crespo-Leiro MG, Coats AJS, et al. Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry. European Heart Journal. 2018; 39: 4277\u20134284.","DOI":"10.1093\/eurheartj\/ehy626"},{"key":"ref88","doi-asserted-by":"crossref","unstructured":"Packer M, Lam CSP, Lund LH, Redfield MM. Interdependence of Atrial Fibrillation and Heart Failure With a Preserved Ejection Fraction Reflects a Common Underlying Atrial and Ventricular Myopathy. Circulation. 2020; 141: 4\u20136.","DOI":"10.1161\/CIRCULATIONAHA.119.042996"},{"key":"ref89","doi-asserted-by":"crossref","unstructured":"Son MK, Park JJ, Lim NK, Kim WH, Choi DJ. Impact of atrial fibrillation in patients with heart failure and reduced, mid-range or preserved ejection fraction. Heart (British Cardiac Society). 2020; 106: 1160\u20131168.","DOI":"10.1136\/heartjnl-2019-316219"},{"key":"ref90","doi-asserted-by":"crossref","unstructured":"Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004; 110: 1042\u20131046.","DOI":"10.1161\/01.CIR.0000140263.20897.42"},{"key":"ref91","doi-asserted-by":"crossref","unstructured":"Mou L, Norby FL, Chen LY, O\u2019Neal WT, Lewis TT, Loehr LR, et al. Lifetime Risk of Atrial Fibrillation by Race and Socioeconomic Status: ARIC Study (Atherosclerosis Risk in Communities). Circulation. Arrhythmia and Electrophysiology. 2018; 11: e006350.","DOI":"10.1161\/CIRCEP.118.006350"},{"key":"ref92","doi-asserted-by":"crossref","unstructured":"Kornej J, B\u00f6rschel CS, Benjamin EJ, Schnabel RB. Epidemiology of Atrial Fibrillation in the 21st Century: Novel Methods and New Insights. Circulation Research. 2020; 127: 4\u201320.","DOI":"10.1161\/CIRCRESAHA.120.316340"},{"key":"ref93","doi-asserted-by":"crossref","unstructured":"Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstr\u00f6m-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. European Heart Journal. 2021; 42: 373\u2013498.","DOI":"10.1093\/eurheartj\/ehab648"},{"key":"ref94","doi-asserted-by":"crossref","unstructured":"Unger ED, Dubin RF, Deo R, Daruwalla V, Friedman JL, Medina C, et al. Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction. European Journal of Heart Failure. 2016; 18: 103\u2013112.","DOI":"10.1002\/ejhf.445"},{"key":"ref95","doi-asserted-by":"crossref","unstructured":"Joslin JR, Lioudaki E, Androulakis E. Interrelation between heart failure with preserved ejection fraction and renal impairment. Reviews in Cardiovascular Medicine. 2022; 23: 69.","DOI":"10.31083\/j.rcm2302069"},{"key":"ref96","doi-asserted-by":"crossref","unstructured":"Nayor M, Larson MG, Wang N, Santhanakrishnan R, Lee DS, Tsao CW, et al. The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction. European Journal of Heart Failure. 2017; 19: 615\u2013623.","DOI":"10.1002\/ejhf.778"},{"key":"ref97","doi-asserted-by":"crossref","unstructured":"Hung SC, Lai YS, Kuo KL, Tarng DC. Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies. Journal of the American Heart Association. 2015; 4: e001918.","DOI":"10.1161\/JAHA.115.001918"},{"key":"ref98","doi-asserted-by":"crossref","unstructured":"L\u00f6fman I, Szummer K, Dahlstr\u00f6m U, Jernberg T, Lund LH. Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction. European Journal of Heart Failure. 2017; 19: 1606\u20131614.","DOI":"10.1002\/ejhf.821"},{"key":"ref99","doi-asserted-by":"crossref","unstructured":"Muchtar E, Blauwet LA, Gertz MA. Restrictive Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circulation Research. 2017; 121: 819\u2013837.","DOI":"10.1161\/CIRCRESAHA.117.310982"},{"key":"ref100","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-L\u00f3pez E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. European Heart Journal. 2015; 36: 2585\u20132594.","DOI":"10.1093\/eurheartj\/ehv338"},{"key":"ref101","doi-asserted-by":"crossref","unstructured":"Madan N, Kalra D. Clinical evaluation of infiltrative cardiomyopathies resulting in heart failure with preserved ejection fraction. Reviews in Cardiovascular Medicine. 2020; 21: 181\u2013190.","DOI":"10.31083\/j.rcm.2020.02.65"},{"key":"ref102","doi-asserted-by":"crossref","unstructured":"Holmboe ES, Durning SJ. Assessing clinical reasoning: moving from in vitro to in vivo. Diagnosis (Berlin, Germany). 2014; 1: 111\u2013117.","DOI":"10.1515\/dx-2013-0029"},{"key":"ref103","doi-asserted-by":"crossref","unstructured":"Mohammed SF, Hussain I, AbouEzzeddine OF, Takahama H, Kwon SH, Forfia P, et al. Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation. 2014; 130: 2310\u20132320.","DOI":"10.1161\/CIRCULATIONAHA.113.008461"},{"key":"ref104","doi-asserted-by":"crossref","unstructured":"Gorter TM, Hoendermis ES, van Veldhuisen DJ, Voors AA, Lam CSP, Geelhoed B, et al. Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis. European Journal of Heart Failure. 2016; 18: 1472\u20131487.","DOI":"10.1002\/ejhf.630"},{"key":"ref105","doi-asserted-by":"crossref","unstructured":"Morris DA, Gailani M, Vaz P\u00e9rez A, Blaschke F, Dietz R, Haverkamp W, et al. Right ventricular myocardial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction. Journal of the American Society of Echocardiography: Official Publication of the American Society of Echocardiography. 2011; 24: 886\u2013897.","DOI":"10.1016\/j.echo.2011.04.005"},{"key":"ref106","doi-asserted-by":"crossref","unstructured":"Melenovsky V, Hwang SJ, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. European Heart Journal. 2014; 35: 3452\u20133462.","DOI":"10.1093\/eurheartj\/ehu193"},{"key":"ref107","doi-asserted-by":"crossref","unstructured":"Berglund F, Pi\u00f1a P, Herrera CJ. Right ventricle in heart failure with preserved ejection fraction. Heart (British Cardiac Society). 2020; 106: 1798\u20131804.","DOI":"10.1136\/heartjnl-2020-317342"},{"key":"ref108","doi-asserted-by":"crossref","unstructured":"Levine AR, Simon MA, Gladwin MT. Pulmonary vascular disease in the setting of heart failure with preserved ejection fraction. Trends in Cardiovascular Medicine. 2019; 29: 207\u2013217.","DOI":"10.1016\/j.tcm.2018.08.005"},{"key":"ref109","doi-asserted-by":"crossref","unstructured":"Sanderson JE. Factors related to outcome in heart failure with a preserved (or normal) left ventricular ejection fraction. European Heart Journal. Quality of Care & Clinical Outcomes. 2016; 2: 153\u2013163.","DOI":"10.1093\/ehjqcco\/qcw026"},{"key":"ref110","doi-asserted-by":"crossref","unstructured":"Parcha V, Patel N, Kalra R, Bhargava A, Prabhu SD, Arora G, et al. Clinical, Demographic, and Imaging Correlates of Anemia in Heart Failure With Preserved Ejection Fraction (from the RELAX Trial). The American Journal of Cardiology. 2020; 125: 1870\u20131878.","DOI":"10.1016\/j.amjcard.2020.03.006"},{"key":"ref111","doi-asserted-by":"crossref","unstructured":"Streng KW, Nauta JF, Hillege HL, Anker SD, Cleland JG, Dickstein K, et al. Non-cardiac comorbidities in heart failure with reduced, mid-range and preserved ejection fraction. International Journal of Cardiology. 2018; 271: 132\u2013139.","DOI":"10.1016\/j.ijcard.2018.04.001"},{"key":"ref112","doi-asserted-by":"crossref","unstructured":"Fung JWH, Li TST, Choy DKL, Yip GWK, Ko FWS, Sanderson JE, et al. Severe obstructive sleep apnea is associated with left ventricular diastolic dysfunction. Chest. 2002; 121: 422\u2013429.","DOI":"10.1378\/chest.121.2.422"},{"key":"ref113","doi-asserted-by":"crossref","unstructured":"Kirkman DL, Bohmke N, Billingsley HE, Carbone S. Sarcopenic Obesity in Heart Failure With Preserved Ejection Fraction. Frontiers in Endocrinology. 2020; 11: 558271.","DOI":"10.3389\/fendo.2020.558271"},{"key":"ref114","doi-asserted-by":"crossref","unstructured":"Packer M. HFpEF Is the Substrate for Stroke in Obesity and Diabetes Independent of Atrial Fibrillation. JACC: Heart Failure. 2020; 8: 35\u201342.","DOI":"10.1016\/j.jchf.2019.09.002"},{"key":"ref115","doi-asserted-by":"crossref","unstructured":"Sandesara PB, Hammadah M, Samman-Tahhan A, Kelli HM, O\u2019Neal WT. Peripheral artery disease and risk of adverse outcomes in heart failure with preserved ejection fraction. Clinical Cardiology. 2017; 40: 692\u2013696.","DOI":"10.1002\/clc.22716"},{"key":"ref116","doi-asserted-by":"crossref","unstructured":"Reddy YNV, Obokata M, Jones AD, Lewis GD, Shah SJ, Abouezzedine OF, et al. Characterization of the Progression From Ambulatory to Hospitalized Heart Failure With Preserved Ejection Fraction. Journal of Cardiac Failure. 2020; 26: 919\u2013928.","DOI":"10.1016\/j.cardfail.2020.08.008"},{"key":"ref117","doi-asserted-by":"crossref","unstructured":"Fragasso G, Sanvito F, Monaca G, Ardizzone V, De Bonis M, Pappalardo F, et al. Myocardial fibrosis in asymptomatic patients undergoing surgery for mitral and aortic valve regurgitation. Journal of Cardiovascular Medicine (Hagerstown, Md.). 2022; 23: 505\u2013512.","DOI":"10.2459\/JCM.0000000000001347"},{"key":"ref118","doi-asserted-by":"crossref","unstructured":"Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nature Reviews. Nephrology. 2020; 16: 223\u2013237.","DOI":"10.1038\/s41581-019-0244-2"},{"key":"ref119","doi-asserted-by":"crossref","unstructured":"Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus\u2013present and future perspectives. Nature Reviews. Endocrinology. 2011; 8: 228\u2013236.","DOI":"10.1038\/nrendo.2011.183"},{"key":"ref120","unstructured":"World Health Organization: Obesity and overweight. 2021. Available at: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight (Accessed: 9 June 2023)."},{"key":"ref121","doi-asserted-by":"crossref","unstructured":"Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. Journal of the American College of Cardiology. 2020; 76: 2982\u20133021.","DOI":"10.1016\/j.jacc.2020.11.010"},{"key":"ref122","doi-asserted-by":"crossref","unstructured":"Blanco I, Diego I, Bueno P, Casas-Maldonado F, Miravitlles M. Geographic distribution of COPD prevalence in the world displayed by Geographic Information System maps. The European Respiratory Journal. 2019; 54: 1900610.","DOI":"10.1183\/13993003.00610-2019"},{"key":"ref123","unstructured":"United Nations, Department of economic and social affairs. World population ageing-2019. Available at: https:\/\/www.un.org\/en\/development\/desa\/population\/publications\/pdf\/ageing\/WorldPopulationAgeing2019-Highlights.pdf (Accessed: 9 June 2023)."},{"key":"ref124","doi-asserted-by":"crossref","unstructured":"Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge. International Journal of Stroke: Official Journal of the International Stroke Society. 2021; 16: 217\u2013221.","DOI":"10.1177\/1747493019897870"},{"key":"ref125","doi-asserted-by":"crossref","unstructured":"Kao DP, Lewsey JD, Anand IS, Massie BM, Zile MR, Carson PE, et al. Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response. European Journal of Heart Failure. 2015; 17: 925\u2013935.","DOI":"10.1002\/ejhf.327"},{"key":"ref126","doi-asserted-by":"crossref","unstructured":"Hedman \u00c5K, Hage C, Sharma A, Brosnan MJ, Buckbinder L, Gan LM, et al. Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning. Heart (British Cardiac Society). 2020; 106: 342\u2013349.","DOI":"10.1136\/heartjnl-2019-315481"},{"key":"ref127","doi-asserted-by":"crossref","unstructured":"Shah SJ, Katz DH, Selvaraj S, Burke MA, Yancy CW, Gheorghiade M, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015; 131: 269\u2013279.","DOI":"10.1161\/CIRCULATIONAHA.114.010637"},{"key":"ref128","doi-asserted-by":"crossref","unstructured":"Uijl A, Savarese G, Vaartjes I, Dahlstr\u00f6m U, Brugts JJ, Linssen GCM, et al. Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction. European Journal of Heart Failure. 2021; 23: 973\u2013982.","DOI":"10.1002\/ejhf.2169"},{"key":"ref129","doi-asserted-by":"crossref","unstructured":"Yamamoto K, Origasa H, Hori M, J-DHF Investigators. Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J-DHF). European Journal of Heart Failure. 2013; 15: 110\u2013118.","DOI":"10.1093\/eurjhf\/hfs141"},{"key":"ref130","doi-asserted-by":"crossref","unstructured":"Martin N, Manoharan K, Thomas J, Davies C, Lumbers RT. Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. The Cochrane Database of Systematic Reviews. 2018; 6: CD012721.","DOI":"10.1002\/14651858.CD012721.pub2"},{"key":"ref131","doi-asserted-by":"crossref","unstructured":"Vergaro G, Aimo A, Prontera C, Ghionzoli N, Arzilli C, Zyw L, et al. Sympathetic and renin-angiotensin-aldosterone system activation in heart failure with preserved, mid-range and reduced ejection fraction. International Journal of Cardiology. 2019; 296: 91\u201397.","DOI":"10.1016\/j.ijcard.2019.08.040"},{"key":"ref132","doi-asserted-by":"crossref","unstructured":"Jimenez-Marrero S, Moliner P, Rodr\u00edguez-Costoya I, Enjuanes C, Alcoberro L, Yun S, et al. Sympathetic activation and outcomes in chronic heart failure: Does the neurohormonal hypothesis apply to mid-range and preserved ejection fraction patients? European Journal of Internal Medicine. 2020; 81: 60\u201366.","DOI":"10.1016\/j.ejim.2020.07.008"},{"key":"ref133","doi-asserted-by":"crossref","unstructured":"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. The Lancet. 2003; 362: 777\u2013781.","DOI":"10.1016\/S0140-6736(03)14285-7"},{"key":"ref134","doi-asserted-by":"crossref","unstructured":"Cleland JGF, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J, et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. European Heart Journal. 2006; 27: 2338\u20132345.","DOI":"10.1093\/eurheartj\/ehl250"},{"key":"ref135","doi-asserted-by":"crossref","unstructured":"Massie M, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, et al. Irbesartan in patients with heart failure and preserved ejection fraction. New England Journal of Medicine. 2008; 359: 2456\u20132467.","DOI":"10.1056\/NEJMoa0805450"},{"key":"ref136","doi-asserted-by":"crossref","unstructured":"Patel K, Fonarow GC, Kitzman DW, Aban IB, Love TE, Allman RM, et al. Aldosterone antagonists and outcomes in real-world older patients with heart failure and preserved ejection fraction. JACC: Heart Failure. 2013; 1: 40\u201347.","DOI":"10.1016\/j.jchf.2012.08.001"},{"key":"ref137","doi-asserted-by":"crossref","unstructured":"Lund LH, Benson L, Dahlstr\u00f6m 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: 2108\u20132117.","DOI":"10.1001\/jama.2012.14785"},{"key":"ref138","doi-asserted-by":"crossref","unstructured":"Edelmann F, Wachter R, Schmidt AG, Kraigher-Krainer E, Colantonio C, Kamke W, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA. 2013; 309: 781\u2013791.","DOI":"10.1001\/jama.2013.905"},{"key":"ref139","doi-asserted-by":"crossref","unstructured":"Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. The New England Journal of Medicine. 2014; 370: 1383\u20131392.","DOI":"10.1056\/NEJMoa1313731"},{"key":"ref140","doi-asserted-by":"crossref","unstructured":"Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. The New England Journal of Medicine. 2019; 381: 1609\u20131620.","DOI":"10.1056\/NEJMoa1908655"},{"key":"ref141","doi-asserted-by":"crossref","unstructured":"Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, B\u00f6hm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. New England Journal of Medicine. 2021; 385: 1451\u20131461.","DOI":"10.1056\/NEJMoa2107038"},{"key":"ref142","doi-asserted-by":"crossref","unstructured":"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. New England Journal of Medicine. 2022; 387: 1089\u20131098.","DOI":"10.1056\/NEJMoa2206286"},{"key":"ref143","doi-asserted-by":"crossref","unstructured":"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. Nature Medicine. 2021; 27: 1954\u20131960.","DOI":"10.1038\/s41591-021-01536-x"},{"key":"ref144","doi-asserted-by":"crossref","unstructured":"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 Failure. 2017; 4: 402\u2013408.","DOI":"10.1002\/ehf2.12204"},{"key":"ref145","doi-asserted-by":"crossref","unstructured":"Fukuta H, Goto T, Wakami K, Ohte N. Effect of renin-angiotensin system inhibitors on mortality in heart failure with preserved ejection fraction: a meta-analysis of observational cohort and randomized controlled studies. Heart Failure Reviews. 2017; 22: 775\u2013782.","DOI":"10.1007\/s10741-017-9637-0"},{"key":"ref146","doi-asserted-by":"crossref","unstructured":"Kuno T, Ueyama H, Fujisaki T, Briasouli A, Takagi H, Briasoulis A. Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction. The American Journal of Cardiology. 2020; 125: 1187\u20131193.","DOI":"10.1016\/j.amjcard.2020.01.009"},{"key":"ref147","doi-asserted-by":"crossref","unstructured":"Gallo G, Tocci G, Fogacci F, Battistoni A, Rubattu S, Volpe M. Blockade of the neurohormonal systems in heart failure with preserved ejection fraction: A contemporary meta-analysis. International Journal of Cardiology. 2020; 316: 172\u2013179.","DOI":"10.1016\/j.ijcard.2020.05.084"},{"key":"ref148","doi-asserted-by":"crossref","unstructured":"Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah AA, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. Journal of the American College of Cardiology. 2012; 59: 998\u20131005.","DOI":"10.1016\/j.jacc.2011.11.040"},{"key":"ref149","doi-asserted-by":"crossref","unstructured":"Vergaro G, Ghionzoli N, Innocenti L, Taddei C, Giannoni A, Valleggi A, et al. Noncardiac Versus Cardiac Mortality in Heart Failure With Preserved, Midrange, and Reduced Ejection Fraction. Journal of the American Heart Association. 2019; 8: e013441.","DOI":"10.1161\/JAHA.119.013441"},{"key":"ref150","doi-asserted-by":"crossref","unstructured":"Cohen JB, Schrauben SJ, Zhao L, Basso MD, Cvijic ME, Li Z, et al. Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone. JACC. Heart Failure. 2020; 8: 172\u2013184.","DOI":"10.1016\/j.jchf.2019.09.009"},{"key":"ref151","doi-asserted-by":"crossref","unstructured":"Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH, et al. Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. The New England Journal of Medicine. 2015; 373: 2314\u20132324.","DOI":"10.1056\/NEJMoa1510774"},{"key":"ref152","doi-asserted-by":"crossref","unstructured":"Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013; 309: 1268\u20131277.","DOI":"10.1001\/jama.2013.2024"},{"key":"ref153","doi-asserted-by":"crossref","unstructured":"Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, B\u00f6hm M, et al. Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Failure Reviews. 2013; 18: 123\u2013134.","DOI":"10.1007\/s10741-012-9323-1"},{"key":"ref154","doi-asserted-by":"crossref","unstructured":"Armstrong PW, Lam CSP, Anstrom KJ, Ezekowitz J, Hernandez AF, O\u2019Connor CM, et al. Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial. JAMA. 2020; 324: 1512\u20131521.","DOI":"10.1001\/jama.2020.15922"},{"key":"ref155","doi-asserted-by":"crossref","unstructured":"Udelson JE, Lewis GD, Shah SJ, Zile MR, Redfield MM, Burnett J, Jr, et al. Effect of Praliciguat on Peak Rate of Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: The CAPACITY HFpEF Randomized Clinical Trial. JAMA. 2020; 324: 1522\u20131531.","DOI":"10.1001\/jama.2020.16641"},{"key":"ref156","doi-asserted-by":"crossref","unstructured":"Seferovi\u0107 PM, Fragasso G, Petrie M, Mullens W, Ferrari R, Thum T, et al. Heart Failure Association of the European Society of Cardiology update on sodium-glucose co-transporter 2 inhibitors in heart failure. European Journal of Heart Failure. 2020; 22: 1984\u20131986.","DOI":"10.1002\/ejhf.2026"},{"key":"ref157","doi-asserted-by":"crossref","unstructured":"McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, B\u00f6hm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2021; 42: 3599\u20133726.","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"ref158","doi-asserted-by":"crossref","unstructured":"Kitzman DW, Brubaker P, Morgan T, Haykowsky M, Hundley G, Kraus WE, et al. Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA. 2016; 315: 36\u201346.","DOI":"10.1001\/jama.2015.17346"},{"key":"ref159","doi-asserted-by":"crossref","unstructured":"Upadhya B, Haykowsky MJ, Kitzman DW. Therapy for heart failure with preserved ejection fraction: current status, unique challenges, and future directions. Heart Failure Reviews. 2018; 23: 609\u2013629.","DOI":"10.1007\/s10741-018-9714-z"},{"key":"ref160","doi-asserted-by":"crossref","unstructured":"Shah SJ. Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview. Journal of Cardiovascular Translational Research. 2017; 10: 233\u2013244.","DOI":"10.1007\/s12265-017-9756-y"},{"key":"ref161","doi-asserted-by":"crossref","unstructured":"Fragasso G. Editorial Commentary: Drug dosing optimization in heart failure: Need of a multidimensional approach (and skilled heart failure specialists). Trends in Cardiovascular Medicine. 2021; 31: 117\u2013118.","DOI":"10.1016\/j.tcm.2020.01.007"},{"key":"ref162","doi-asserted-by":"crossref","unstructured":"Infante T, Francone M, De Rimini ML, Cavaliere C, Canonico R, Catalano C, et al. Machine learning and network medicine: a novel approach for precision medicine and personalized therapy in cardiomyopathies. Journal of Cardiovascular Medicine (Hagerstown, Md.). 2021; 22: 429\u2013440.","DOI":"10.2459\/JCM.0000000000001103"},{"key":"ref163","doi-asserted-by":"crossref","unstructured":"Mesko B. The role of artificial intelligence in precision medicine. Expert Review of Precision Medicine and Drug Development. 2017; 5: 239\u2013241.","DOI":"10.1080\/23808993.2017.1380516"},{"key":"ref164","doi-asserted-by":"crossref","unstructured":"Packer M. Can brain natriuretic peptide be used to guide the management of patients with heart failure and a preserved ejection fraction? The wrong way to identify new treatments for a nonexistent disease. Circulation: Heart Failure. 2011; 4: 538\u2013540.","DOI":"10.1161\/CIRCHEARTFAILURE.111.963710"}],"container-title":["Reviews in Cardiovascular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/24\/7\/10.31083\/j.rcm2407202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T19:04:38Z","timestamp":1732734278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/24\/7\/10.31083\/j.rcm2407202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,14]]},"references-count":164,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023]]}},"alternative-id":["S1530-6550(23)01036-0"],"URL":"https:\/\/doi.org\/10.31083\/j.rcm2407202","relation":{},"ISSN":["1530-6550","2153-8174"],"issn-type":[{"value":"1530-6550","type":"print"},{"value":"2153-8174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,14]]},"article-number":"202"}}