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Structure and function abnormalities can include all four cardiac chambers. The left ventricle has abnormal systolic and diastolic functions which can be examined by invasive and non-invasive measurements. In addition, the left atrium enlarges with abnormal left atrial function, pulmonary hypertension occurs, and the right ventricle can develop hypertrophy, enlargement, and systolic dysfunction. There are a paucity of data on calcium handling in HFpEF patients. Growing literature supports the presence of abnormalities in titin and its phosphorylation, and increased interstitial fibrosis contributing to increased chamber stiffness. A systemic inflammatory state causing reduced myocardial cyclic guanosine monophosphate along with defects in the unfolded protein response have been recently reported. Diagnosis relies on signs and symptoms of heart failure, preserved ejection fraction, and detection of diastolic function abnormalities based on echocardiographic findings and abnormally elevated natriuretic peptide levels or invasive measurements of wedge pressure at rest or with exercise. There are currently two diagnostic algorithms: H2FPEF, and HFA-PEFF with limited data comparing their performance head to head in the same patient population. Despite the growing understanding of the syndrome\u2019s pathophysiology, there have been little success in developing specific treatment for patients with HFpEF.<\/jats:p>","DOI":"10.1093\/cvr\/cvaa228","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T15:15:47Z","timestamp":1595430947000},"page":"999-1014","source":"Crossref","is-referenced-by-count":81,"title":["Heart failure with preserved ejection fraction: insights into diagnosis and pathophysiology"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-8056","authenticated-orcid":false,"given":"Sherif F","family":"Nagueh","sequence":"first","affiliation":[{"name":"Methodist DeBakey Heart and Vascular Center, 6550 Fannin, SM-1801, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"2021032208561309800_cvaa228-B1","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1161\/CIRCRESAHA.119.313572","article-title":"Heart failure with preserved ejection fraction in perspective","volume":"124","author":"Pfeffer","year":"2019","journal-title":"Circ Res"},{"key":"2021032208561309800_cvaa228-B2","doi-asserted-by":"crossref","first-page":"H1364","DOI":"10.1152\/ajpheart.00004.2014","article-title":"Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction","volume":"306","author":"Kitzman","year":"2014","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2021032208561309800_cvaa228-B3","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1093\/eurheartj\/ehm037","article-title":"How to diagnose diastolic heart failure: a consensus statement on the 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