{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:01:48Z","timestamp":1779915708313,"version":"3.53.1"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder marked by myocardial hypertrophy, leading to diastolic and systolic dysfunction and heart failure. Traditionally, the burn-out stage is defined by systolic dysfunction, but we propose expanding its definition to include advanced diastolic dysfunction. Methods: We retrospectively analyzed HCM patients (2004\u20132023) with either systolic dysfunction (left ventricular ejection fraction [LVEF] &lt; 50%) or advanced diastolic dysfunction (preserved LVEF with left atrial enlargement and elevated filling pressures: E\/A \u2265 2 or E\/e\u2032 \u2265 14). Both subgroups were included under the term \u201cend-stage HCM\u201d and compared to HCM controls with preserved LVEF and impaired relaxation. Results: Of 696 HCM patients, 94 had end-stage HCM (23 with systolic dysfunction, 71 with advanced diastolic dysfunction). Median age was 56.5 years, and 55.3% were male. End-stage HCM patients were more symptomatic at follow-up than controls (91.5% vs. 75.0%, p-value = 0.006), with higher rates of dyspnea and advanced heart failure (38.3% vs. 6.3%, p-value &lt; 0.001). Advanced diastolic dysfunction was associated with a more symptomatic profile (p-value = 0.013) and a high annual mortality rate (2.34%, p = 0.014). Male sex, older age, lower LVEF, and higher E\/A predicted systolic dysfunction. Conclusions: Advanced diastolic dysfunction represents an alternative progression pathway in burn-out HCM, requiring distinct management strategies alongside systolic dysfunction.<\/jats:p>","DOI":"10.3390\/diagnostics15091134","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"1134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical Characteristics and Prognosis of Patients with End-Stage Hypertrophic Cardiomyopathy from a Tertiary Center Cohort: Systolic Dysfunction and Advanced Diastolic Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0318-734X","authenticated-orcid":false,"given":"Andreea Sorina","family":"Afana","sequence":"first","affiliation":[{"name":"Expert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, Romania"},{"name":"Emergency Clinical County Hospital Craiova, 1 Tabaci Street, 200642 Craiova, Romania"},{"name":"Cardiology Department, University of Medicine and Pharmacy Craiova, 2 Petru Rares Street, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5018-1482","authenticated-orcid":false,"given":"Robert Daniel","family":"Adam","sequence":"additional","affiliation":[{"name":"Expert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, Romania"},{"name":"Cardiology Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania"},{"name":"Emerald Medical Center, 75 Nicolae G. Caramfil Street, 077190 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2578-6356","authenticated-orcid":false,"given":"Sebastian","family":"Militaru","sequence":"additional","affiliation":[{"name":"Emergency Clinical County Hospital Craiova, 1 Tabaci Street, 200642 Craiova, Romania"},{"name":"Cardiology Department, University of Medicine and Pharmacy Craiova, 2 Petru Rares Street, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1729-0126","authenticated-orcid":false,"given":"Sebastian","family":"Onciul","sequence":"additional","affiliation":[{"name":"Cardiology Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania"},{"name":"Emerald Medical Center, 75 Nicolae G. Caramfil Street, 077190 Bucharest, Romania"},{"name":"Emergency Clinical Hospital Floreasca, 8 Calea Floreasca, 014461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Andrei","sequence":"additional","affiliation":[{"name":"Expert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, Romania"},{"name":"Cardiology Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-4625","authenticated-orcid":false,"given":"Adela","family":"Chirita Emandi","sequence":"additional","affiliation":[{"name":"Regional Center of Medical Genetics Timi\u0219, Part of ERN ITHACA, Clinical Emergency Hospital for Children \u201cLouis \u021aurcanu\u201d Timisoara, 2 Doctor Iosif Nemoianu Street, 300011 Timisoara, Romania"},{"name":"Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, University of Medicine and Pharmacy \u201cVictor Babes\u201d Timisoara, 2 Piata Eftimie Murgu Street, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Puiu","sequence":"additional","affiliation":[{"name":"Institute for Research and Development in Genomics, 37 Dionisie Lupu, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Militaru","sequence":"additional","affiliation":[{"name":"Emergency Clinical County Hospital Craiova, 1 Tabaci Street, 200642 Craiova, Romania"},{"name":"Cardiology Department, University of Medicine and Pharmacy Craiova, 2 Petru Rares Street, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3438-2612","authenticated-orcid":false,"given":"Ruxandra","family":"Jurcut","sequence":"additional","affiliation":[{"name":"Expert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, Romania"},{"name":"Cardiology Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1093\/eurheartj\/ehad194","article-title":"2023 ESC Guidelines for the management of cardiomyopathies","volume":"44","author":"Arbelo","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1146\/annurev.med.55.091902.104417","article-title":"Left Ventricular Diastolic Dysfunction and Diastolic Heart Failure","volume":"55","author":"Gaasch","year":"2004","journal-title":"Annu. Rev. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1016\/j.jacc.2013.05.019","article-title":"2013 ACCF\/AHA Guideline for the Management of Heart Failure","volume":"62","author":"Yancy","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1239","DOI":"10.1161\/CIR.0000000000001250","article-title":"2024 AHA\/ACC\/AMSSM\/HRS\/PACES\/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association\/American College of Cardiology Joint Committee on Clinical Practice Guidelines","volume":"149","author":"Ommen","year":"2024","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e003090","DOI":"10.1161\/CIRCHEARTFAILURE.116.003090","article-title":"Histological and Histometric Characterization of Myocardial Fibrosis in End-Stage Hypertrophic Cardiomyopathy","volume":"9","author":"Galati","year":"2016","journal-title":"Circ. Heart Fail."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.amjcard.2018.08.041","article-title":"Long-Term Left Ventricular Remodeling of Patients With Hypertrophic Cardiomyopathy","volume":"122","author":"Musumeci","year":"2018","journal-title":"Am. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1016\/j.jacc.2020.05.009","article-title":"Avoiding Burnout From Hypertrophic Cardiomyopathy","volume":"75","author":"Brinkley","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131784","DOI":"10.1016\/j.ijcard.2024.131784","article-title":"Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes","volume":"400","author":"Musumeci","year":"2024","journal-title":"Int. J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.echo.2016.01.011","article-title":"Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"29","author":"Nagueh","year":"2016","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.jacc.2005.04.062","article-title":"Dilated-Hypokinetic Evolution of Hypertrophic Cardiomyopathy","volume":"46","author":"Biagini","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.cardfail.2011.01.015","article-title":"Risk of Sudden Death in End-Stage Hypertrophic Cardiomyopathy","volume":"17","author":"Kawarai","year":"2011","journal-title":"J. Card. Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1161\/CIRCULATIONAHA.105.583500","article-title":"Prevalence, Clinical Profile, and Significance of Left Ventricular Remodeling in the End-Stage Phase of Hypertrophic Cardiomyopathy","volume":"114","author":"Harris","year":"2006","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/CIRCULATIONAHA.119.044366","article-title":"Hypertrophic Cardiomyopathy With Left Ventricular Systolic Dysfunction","volume":"141","author":"Marstrand","year":"2020","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1016\/j.jacc.2020.04.045","article-title":"Outcomes in Patients With Hypertrophic Cardiomyopathy and Left Ventricular Systolic Dysfunction","volume":"75","author":"Rowin","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1001\/jamacardio.2015.0354","article-title":"How Hypertrophic Cardiomyopathy Became a Contemporary Treatable Genetic Disease With Low Mortality","volume":"1","author":"Maron","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jjcc.2012.08.010","article-title":"Clinical characteristics and outcomes of dilated phase of hypertrophic cardiomyopathy: Report from the registry data in Japan","volume":"61","author":"Goto","year":"2013","journal-title":"J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e003062","DOI":"10.1161\/CIRCGEN.120.003062","article-title":"Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy","volume":"14","author":"Lakdawala","year":"2021","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_18","first-page":"A15763","article-title":"Abstract 15763: Predictors of End-Stage Hypertrophic Cardiomyopathy","volume":"140","author":"Marstrand","year":"2019","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Buongiorno, A., Albani, S., Grilli, G., Merlo, M., Berchialla, P., Ricotti, A., Pierri, A., De Luca, A., Barbisan, D., and Mabritto, B. (2023). C81 ROLE OF RESTRICTIVE DIASTOLIC DYSFUNCTION FOR RISK STRATIFICATION OF PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY: A BAYESIAN MODEL AVERAGING. Eur. Heart J. Suppl., 25.","DOI":"10.1093\/eurheartjsupp\/suad111.079"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1016\/j.jacc.2007.02.061","article-title":"Prevalence, Clinical Significance, and Genetic Basis of Hypertrophic Cardiomyopathy With Restrictive Phenotype","volume":"49","author":"Kubo","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1161\/hc4601.097997","article-title":"Impact of Atrial Fibrillation on the Clinical Course of Hypertrophic Cardiomyopathy","volume":"104","author":"Olivotto","year":"2001","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.hlc.2017.05.116","article-title":"Atrial Fibrillation in Hypertrophic Cardiomyopathy","volume":"26","author":"Vaidya","year":"2017","journal-title":"Heart Lung Circ."},{"key":"ref_23","first-page":"1339","article-title":"Implications of left ventricular remodeling in hypertrophic cardiomyopathy","volume":"81","author":"Maron","year":"1998","journal-title":"Am. J. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1056\/NEJMoa021332","article-title":"Effect of Left Ventricular Outflow Tract Obstruction on Clinical Outcome in Hypertrophic Cardiomyopathy","volume":"348","author":"Maron","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.2214\/AJR.07.2286","article-title":"MRI of Hypertrophic Cardiomyopathy: Part I, MRI Appearances","volume":"189","author":"Hansen","year":"2007","journal-title":"Am. J. Roentgenol."},{"key":"ref_26","first-page":"140","article-title":"Predictors and Prognosis of End-Stage Hypertrophic Cardiomyopathy","volume":"16","author":"Alizadehasl","year":"2022","journal-title":"Int. Cardiovasc. Res. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1161\/CIRCHEARTFAILURE.114.001843","article-title":"Clinical Spectrum, Therapeutic Options, and Outcome of Advanced Heart Failure in Hypertrophic Cardiomyopathy","volume":"8","author":"Pasqualucci","year":"2015","journal-title":"Circ. Heart Fail."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.jcmg.2020.09.037","article-title":"Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy","volume":"14","author":"Habib","year":"2021","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ditaranto, R., Shiwani, H., Davies, R.H., Malcolmson, J., Pierce, I., Moschonas, K., Schiavo, M.A., Lorenzini, M., Lovato, L., and Biagini, E. (2024). Myocardial scar in end-stage hypertrophic cardiomyopathy: Correlation with systolic function and prognostic significance. Eur. Heart J., 45.","DOI":"10.1093\/eurheartj\/ehae666.2051"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.echo.2009.09.016","article-title":"Left Atrial Volume Index: A Predictor of Adverse Outcome in Patients with Hypertrophic Cardiomyopathy","volume":"22","author":"Yang","year":"2009","journal-title":"J. Am. Soc. Echocardiogr."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/9\/1134\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:24:06Z","timestamp":1760030646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/9\/1134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["diagnostics15091134"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15091134","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,29]]}}}