{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:05:10Z","timestamp":1791446710987,"version":"4.3.3"},"reference-count":93,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heart failure with preserved ejection fraction (HFpEF) is a major driver of cardiac morbidity and mortality in developed countries, due to ageing populations and the increasing prevalence of comorbidities. While heart failure with reduced ejection fraction is dominated by left ventricular impairment, HFpEF results from a complex interplay of cardiac remodelling, peripheral circulation, and concomitant features including age, hypertension, obesity, and diabetes. In an important subset, however, HFpEF is subtended by specific diseases of the myocardium that are genetically determined, have distinct pathophysiology, and are increasingly amenable to targeted, innovative treatments. While each of these conditions is rare, they collectively represent a relevant subset within HFpEF cohorts, and their prompt recognition has major consequences for clinical practice, as access to dedicated, disease-specific treatments may radically change the quality of life and outcome. Furthermore, response to standard heart failure treatment will generally be modest for these individuals, whose inclusion in registries and trials may dilute the perceived efficacy of treatments targeting mainstream HFpEF. Finally, a better understanding of the molecular underpinnings of monogenic myocardial disease may help identify therapeutic targets and develop innovative treatments for selected HFpEF phenotypes of broader epidemiological relevance. The field of genetic cardiomyopathies is undergoing rapid transformation due to recent, groundbreaking advances in drug development, and deserves greater awareness within the heart failure community. The present review addressed existing and developing therapies for genetic causes of HFpEF, including hypertrophic cardiomyopathy, cardiac amyloidosis, and storage diseases, discussing their potential impact on management and their broader implications for our understanding of HFpEF at large.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehac764","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T07:32:32Z","timestamp":1672385552000},"page":"656-667","source":"Crossref","is-referenced-by-count":36,"title":["Genetic causes of heart failure with preserved ejection fraction: emerging pharmacological treatments"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1751-9266","authenticated-orcid":false,"given":"Iacopo","family":"Olivotto","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Meyer University Children Hospital and Careggi University Hospital , Viale Pieraccini 24, 50139 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2998-910X","authenticated-orcid":false,"given":"James E","family":"Udelson","sequence":"additional","affiliation":[{"name":"Division of Cardiology and The CardioVascular Center, Tufts Medical Center, and the Tufts University School of Medicine , 800 Washington St, Boston, MA 02111 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-4292","authenticated-orcid":false,"given":"Maurizio","family":"Pieroni","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital San Donato , Via Pietro Nenni, 20 - 52100 Arezzo , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9198-2657","authenticated-orcid":false,"given":"Claudio","family":"Rapezzi","sequence":"additional","affiliation":[{"name":"Cardiology Centre, University of Ferrara , Via Fossato di Mortara, 64\/B - 44121 Ferrara , Italy"},{"name":"Maria Cecilia Hospital, GVM Care & Research , Via Corriera, 1, 48033 Cotignola, Emilia-Romagna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"2023022023593544600_","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J"},{"key":"2023022023593544600_","first-page":"e895","article-title":"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","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"2023022023593544600_","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1136\/heartjnl-2021-319605","article-title":"Heart failure with preserved ejection fraction: recent concepts in diagnosis, mechanisms and management","volume":"108","author":"Gevaert","year":"2022","journal-title":"Heart"},{"key":"2023022023593544600_","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1093\/eurheartj\/ehy301","article-title":"Heart failure with preserved ejection fraction: from mechanisms to therapies","volume":"39","author":"Lam","year":"2018","journal-title":"Eur Heart J"},{"key":"2023022023593544600_","doi-asserted-by":"crossref","first-page":"e007555","DOI":"10.1161\/CIRCHEARTFAILURE.120.007555","article-title":"Current limitations of invasive exercise hemodynamics for the diagnosis of heart failure with preserved ejection fraction","volume":"14","author":"Baratto","year":"2021","journal-title":"Circ Heart Fail"},{"key":"2023022023593544600_","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1093\/eurheartj\/ehz641","article-title":"How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)","volume":"40","author":"Pieske","year":"2019","journal-title":"Eur Heart J"},{"key":"2023022023593544600_","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.jacc.2016.10.078","article-title":"Mode of death in heart failure with preserved ejection fraction","volume":"69","author":"Vaduganathan","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2023022023593544600_","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1093\/eurheartj\/ehs397","article-title":"Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. 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