{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:16:19Z","timestamp":1788156979481,"version":"build-2803163510"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Aijinkai Clinical Research Grant"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cardiovasc Disord"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sodium\u2013glucose co-transporter 2 inhibitors (SGLT2i) have become essential in the management of heart failure. Their prognostic benefits are consistent across older adults, frail, and underweight patients, but there may be potential adverse effects on the skeletal muscle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective single-centre observational study, 117 patients with stable congestive heart failure received 10\u00a0mg of empagliflozin daily between February 2023 and October 2024. At baseline and again after 6 months, we measured the following nutritional, frailty, and quality-of-life indices (GNRI, CONUT, mini nutritional assessment (MNA), KCCQ-12, Barthel index, clinical frailty scale) and urinary titin N-fragment (U-titin), a biomarker of skeletal muscle degradation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After exclusion, 93 patients (median age 79 years; 40% women) were analysed. Baseline U-titin showed weak correlations with GNRI, MNA, and KCCQ-12 scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Median U-titin increased significantly from 1.7 (IQR 1.1\u20133.5) at baseline to 2.4 (IQR 1.3\u20134.2) pmol\/mg Cr at 6 months (p = 0.040). The GNRI, MNA, KCCQ-12, body mass index, and NT-proBNP levels improved significantly, whereas the CONUT, Barthel index, and frailty scores remained unchanged. Left ventricular ejection fraction\u2009\u226550% independently predicted \u2009\u226550% U-titin increase (OR 3.31, 95% CI 1.23\u20139.52,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Baseline U-titin levels seem to reflect nutritional and functional status in patients with heart failure. U-titin levels increased during empagliflozin treatment, suggesting a possible association with skeletal muscle degradation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12872-026-06003-4","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:46:37Z","timestamp":1788155197000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between empagliflozin exposure and skeletal muscle degeneration in patients with heart failure"],"prefix":"10.1186","volume":"26","author":[{"given":"Tatsuya","family":"Nishikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuto","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Osawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaki","family":"Shirahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Hirabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Shiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryohei","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsuki","family":"Kanemitsuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Hoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hodaka","family":"Noda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hibiki","family":"Kadohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Ohga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Shingu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Osumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Ishibashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimitsu","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mana","family":"Hiraishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuo","family":"Kinugasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Hirayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Shimokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Matuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tamita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"10254","key":"6003_CR1","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S0140-6736(20)31824-9","volume":"396","author":"F Zannad","year":"2020","unstructured":"Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, Brueckmann M, Ofstad AP, Pfarr E, Jamal W, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396(10254):819\u201329.","journal-title":"Lancet"},{"issue":"16","key":"6003_CR2","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","volume":"385","author":"SD Anker","year":"2021","unstructured":"Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, B\u00f6hm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, et al. EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451\u201361.","journal-title":"N Engl J Med"},{"issue":"12","key":"6003_CR3","doi-asserted-by":"publisher","first-page":"3538","DOI":"10.1111\/dom.15249","volume":"25","author":"D Yabe","year":"2023","unstructured":"Yabe D, Shiki K, Homma G, Meinicke T, Ogura Y, Seino Y, EMPA-ELDERLY, Investigators. Efficacy and safety of the sodium-glucose co-transporter-2 inhibitor empagliflozin in elderly Japanese adults (\u2265\u200965 years) with type 2 diabetes: A randomized, double-blind, placebo-controlled, 52-week clinical trial (EMPA-ELDERLY). Diabetes Obes Metab. 2023;25(12):3538\u201348.","journal-title":"Diabetes Obes Metab"},{"issue":"4","key":"6003_CR4","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1002\/ejhf.3221","volume":"26","author":"N Sattar","year":"2024","unstructured":"Sattar N, Butler J, Lee MMY, Harrington J, Sharma A, Zannad F, Filippatos G, Verma S, Januzzi JL, Ferreira JP, et al. Body mass index and cardiorenal outcomes in the EMPEROR-Preserved trial: Principal findings and meta-analysis with the DELIVER trial. Eur J Heart Fail. 2024;26(4):900\u20139.","journal-title":"Eur J Heart Fail"},{"issue":"1","key":"6003_CR5","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1002\/jcsm.13393","volume":"15","author":"AJS Coats","year":"2024","unstructured":"Coats AJS, Butler J, Tsutsui H, Doehner W, Filippatos G, Ferreira JP, B\u00f6hm M, Chopra VK, Verma S, Nordaby M, et al. Efficacy of empagliflozin in heart failure with preserved ejection fraction according to frailty status in EMPEROR-Preserved. J Cachexia Sarcopenia Muscle. 2024;15(1):412\u201324.","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"9","key":"6003_CR6","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1002\/ejhf.2971","volume":"25","author":"D Stolfo","year":"2023","unstructured":"Stolfo D, Lund LH, Benson L, Lindberg F, Ferrannini G, Dahlstr\u00f6m U, Sinagra G, Rosano GMC, Savarese G. Real-world use of sodium-glucose cotransporter 2 inhibitors in patients with heart failure and reduced ejection fraction: Data from the Swedish Heart Failure Registry. Eur J Heart Fail. 2023;25(9):1648\u201358.","journal-title":"Eur J Heart Fail"},{"issue":"1","key":"6003_CR7","doi-asserted-by":"publisher","first-page":"8940","DOI":"10.1038\/s41598-025-94172-1","volume":"15","author":"S Kwast","year":"2025","unstructured":"Kwast S, Hoffmann J, P\u00f6kel C, Falz R, Schulze A, Schr\u00f6ter T, Borger MA, Busse M. Cardiopulmonary exercise capacity markers and their link to symptom burden in patients at risk for heart failure with non-reduced ejection fraction. Sci Rep. 2025;15(1):8940.","journal-title":"Sci Rep"},{"issue":"2","key":"6003_CR8","doi-asserted-by":"publisher","first-page":"709","DOI":"10.3390\/ijerph19020709","volume":"19","author":"A Vale-Lira","year":"2022","unstructured":"Vale-Lira A, Turri-Silva N, Verboven K, Durigan JLQ, de Lima ACGB, Bottaro M, Chiappa GR, Hansen D, Cipriano G Jr. Muscle-skeletal abnormalities and muscle oxygenation during isokinetic strength exercise in heart failure with preserved ejection fraction phenotype: A cross-sectional study. Int J Environ Res Public Health. 2022;19(2):709.","journal-title":"Int J Environ Res Public Health"},{"issue":"10","key":"6003_CR9","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.amjcard.2018.01.046","volume":"121","author":"A Yoshihisa","year":"2018","unstructured":"Yoshihisa A, Kimishima Y, Kiko T, Sato Y, Watanabe S, Kanno Y, Abe S, Miyata M, Sato T, Suzuki S, et al. Usefulness of urinary N-terminal fragment of titin to predict mortality in dilated cardiomyopathy. Am J Cardiol. 2018;121(10):1260\u20135.","journal-title":"Am J Cardiol"},{"issue":"4","key":"6003_CR10","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1007\/s40618-024-02490-4","volume":"48","author":"Y Takiguchi","year":"2025","unstructured":"Takiguchi Y, Tsutsumi R, Shimabukuro M, Tanabe H, Kawakami A, Hyodo M, Shiroma K, Saito H, Matsuo M, Sakaue H. Urinary titin as a biomarker of sarcopenia in diabetes: a propensity score matching analysis. J Endocrinol Invest. 2025;48(4):1041\u201356.","journal-title":"J Endocrinol Invest"},{"issue":"4","key":"6003_CR11","doi-asserted-by":"publisher","first-page":"614","DOI":"10.3390\/jcm10040614","volume":"10","author":"N Nakanishi","year":"2021","unstructured":"Nakanishi N, Tsutsumi R, Hara K, Matsuo M, Sakaue H, Oto J. Urinary titin N-fragment as a biomarker of muscle atrophy, intensive care unit-acquired weakness, and possible application for post-intensive care syndrome. J Clin Med. 2021;10(4):614.","journal-title":"J Clin Med"},{"key":"6003_CR12","first-page":"1","volume":"90","author":"M Matsuo","year":"2019","unstructured":"Matsuo M, Awano H, Maruyama N, Nishio H. Titin fragment in urine: A noninvasive biomarker of muscle degradation. Adv Clin Chem. 2019;90:1\u201323.","journal-title":"Adv Clin Chem"},{"issue":"3","key":"6003_CR13","doi-asserted-by":"publisher","first-page":"105561","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.105561","volume":"30","author":"M Ishihara","year":"2021","unstructured":"Ishihara M, Nakanishi N, Tsutsumi R, Hara K, Machida K, Yamamoto N, Kanematsu Y, Sakaue H, Oto J, Takagi Y. Elevated urinary titin and its associated clinical outcomes after acute stroke. J Stroke Cerebrovasc Dis. 2021;30(3):105561.","journal-title":"J Stroke Cerebrovasc Dis"},{"issue":"1","key":"6003_CR14","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/ijms25010573","volume":"25","author":"M Arase","year":"2024","unstructured":"Arase M, Nakanishi N, Tsutsumi R, Kawakami A, Arai Y, Sakaue H, Oto J. The utility of urinary titin to diagnose and predict the prognosis of acute myocardial infarction. Int J Mol Sci. 2024;25(1):573.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"6003_CR15","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/S0899-9007(98)00171-3","volume":"15","author":"B Vellas","year":"1999","unstructured":"Vellas B, Guigoz Y, Garry PJ, Nourhashemi F, Bennahum D, Lauque S, Albarede JL. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition. 1999;15(2):116\u201322.","journal-title":"Nutrition"},{"issue":"4","key":"6003_CR16","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1093\/ajcn\/82.4.777","volume":"82","author":"O Bouillanne","year":"2005","unstructured":"Bouillanne O, Morineau G, Dupont C, Coulombel I, Vincent JP, Nicolis I, Benazeth S, Cynober L, Aussel C. Geriatric Nutritional Risk Index: A new index for evaluating at-risk elderly medical patients. Am J Clin Nutr. 2005;82(4):777\u201383.","journal-title":"Am J Clin Nutr"},{"key":"6003_CR17","unstructured":"Ignacio de Ul\u00edbarri J, Gonz\u00e1lez-Madro\u00f1o A, de Villar NG, Gonz\u00e1lez P, Gonz\u00e1lez B, Mancha A, Rodr\u00edguez F, Fern\u00e1ndez G. CONUT: A tool for controlling nutritional status. First validation in a hospital population. Nutr Hosp. 2005;20(1):38\u201345."},{"issue":"5","key":"6003_CR18","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1161\/CIRCOUTCOMES.115.001958","volume":"8","author":"JA Spertus","year":"2015","unstructured":"Spertus JA, Jones PG. Development and validation of a short version of the Kansas city cardiomyopathy questionnaire. Circ Cardiovasc Qual Outcomes. 2015;8(5):469\u201376.","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"6003_CR19","first-page":"61","volume":"14","author":"FI Mahoney","year":"1965","unstructured":"Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J. 1965;14:61\u20135.","journal-title":"Md State Med J"},{"issue":"5","key":"6003_CR20","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1503\/cmaj.050051","volume":"173","author":"K Rockwood","year":"2005","unstructured":"Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489\u201395.","journal-title":"CMAJ"},{"issue":"3","key":"6003_CR21","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1253\/circj.CJ-12-1091","volume":"77","author":"Y Kinugasa","year":"2013","unstructured":"Kinugasa Y, Kato M, Sugihara S, Hirai M, Yamada K, Yanagihara K, Yamamoto K. Geriatric nutritional risk index predicts functional dependency and mortality in patients with heart failure with preserved ejection fraction. Circ J. 2013;77(3):705\u201311.","journal-title":"Circ J"},{"issue":"9","key":"6003_CR22","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1007\/s12603-020-1507-0","volume":"24","author":"A Arenas Miqu\u00e9lez","year":"2020","unstructured":"Arenas Miqu\u00e9lez A, Requena Calleja MA, Gull\u00f3n A, Pose Reino A, Formiga F, Camafort M, Cepeda Rodrigo JMO, Mostaza JM, Su\u00e1rez Fern\u00e1ndez C, D\u00edez-Manglan J. Nutritional risk and mortality at one year for elderly patients hospitalized with nonvalvular atrial fibrillation. Nonavasc Registry. J Nutr Health Aging. 2020;24(9):981\u20136.","journal-title":"J Nutr Health Aging"},{"issue":"6","key":"6003_CR23","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.3390\/nu15061472","volume":"15","author":"E Rinninella","year":"2023","unstructured":"Rinninella E, Borriello R, D\u2019Angelo M, Galasso T, Cintoni M, Raoul P, Impagnatiello M, Annicchiarico BE, Gasbarrini A, Mele MC. COntrolling NUTritional Status (CONUT) as predictive score of hospital Length of Stay (LOS) and mortality: A prospective cohort study in an internal medicine and gastroenterology unit in Italy. Nutrients. 2023;15(6):1472.","journal-title":"Nutrients"},{"issue":"1","key":"6003_CR24","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1253\/circj.CJ-21-0584","volume":"86","author":"S Katano","year":"2021","unstructured":"Katano S, Yano T, Ohori K, Kouzu H, Nagaoka R, Honma S, Shimomura K, Inoue T, Takamura Y, Ishigo T, et al. Barthel Index Score predicts mortality in elderly heart failure- A goal of comprehensive cardiac rehabilitation. Circ J. 2021;86(1):70\u20138.","journal-title":"Circ J"},{"issue":"3","key":"6003_CR25","doi-asserted-by":"publisher","first-page":"e027689","DOI":"10.1161\/JAHA.122.027689","volume":"12","author":"R Nakamaru","year":"2023","unstructured":"Nakamaru R, Shiraishi Y, Niimi N, Kohno T, Nagatomo Y, Takei M, Ikoma T, Nishikawa K, Sakamoto M, Nakano S, et al. Phenotyping of elderly patients with heart failure focused on noncardiac conditions: A latent class analysis from a multicenter registry of patients hospitalized with heart failure. J Am Heart Assoc. 2023;12(3):e027689.","journal-title":"J Am Heart Assoc"},{"issue":"2","key":"6003_CR26","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1161\/CIR.0b013e3181e52e69","volume":"122","author":"GJ Balady","year":"2010","unstructured":"Balady B GJ, Arena R, Sietsema K, Myers J, Coke, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, et al. Clinician\u2019s Guide to cardiopulmonary exercise testing in adults: A scientific statement from the American Heart Association. Circulation. 2010;122(2):191\u2013225. American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Interdisciplinary Council on Quality of Care and Outcomes Research.","journal-title":"Circulation"},{"key":"6003_CR27","doi-asserted-by":"publisher","first-page":"39375","DOI":"10.1038\/srep39375","volume":"6","author":"N Maruyama","year":"2016","unstructured":"Maruyama N, Asai T, Abe C, Inada A, Kawauchi T, Miyashita K, Maeda M, Matsuo M, Nabeshima YI. Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine. Sci Rep. 2016;6:39375.","journal-title":"Sci Rep"},{"issue":"3","key":"6003_CR28","doi-asserted-by":"publisher","first-page":"899","DOI":"10.3390\/nu13030899","volume":"13","author":"H Nakano","year":"2021","unstructured":"Nakano H, Hashimoto H, Mochizuki M, Naraba H, Takahashi Y, Sonoo T, Matsuishi Y, Ogawa Y, Shimojo N, Inoue Y, et al. Urinary titin N-fragment evaluation in a randomized controlled trial of beta-hydroxy-beta-methylbutyrate for acute mild trauma in older adults. Nutrients. 2021;13(3):899.","journal-title":"Nutrients"},{"key":"6003_CR29","doi-asserted-by":"crossref","unstructured":"Miyoshi K, Shimoda M, Udo R, Oshiro Y, Suzuki S. Urinary titin N-terminal fragment concentration is an indicator of preoperative sarcopenia and nutritional status in patients with gastrointestinal tract and hepatobiliary pancreatic malignancies. Nutrition. 2020;79\u201380:110957.","DOI":"10.1016\/j.nut.2020.110957"},{"issue":"7","key":"6003_CR30","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1002\/ejhf.3285","volume":"26","author":"M Pagnesi","year":"2024","unstructured":"Pagnesi M, Serafini L, Chiarito M, Stolfo D, Baldetti L, Inciardi RM, Tomasoni D, Adamo M, Lombardi CM, Sammartino AM, et al. Impact of malnutrition in patients with severe heart failure. Eur J Heart Fail. 2024;26(7):1585\u201393.","journal-title":"Eur J Heart Fail"},{"issue":"4","key":"6003_CR31","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1002\/ehf2.13886","volume":"9","author":"Y Kinugasa","year":"2022","unstructured":"Kinugasa Y, Sota T, Kamitani H, Nakayama N, Nakamura K, Hirai M, Yanagihara K, Kato M, Ono T, Takahashi M, et al. Diagnostic performance of nutritional indicators in patients with heart failure. ESC Heart Fail. 2022;9(4):2096\u2013106.","journal-title":"ESC Heart Fail"},{"issue":"23","key":"6003_CR32","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1016\/j.jacc.2025.03.545","volume":"85","author":"BR El-Sabawi","year":"2025","unstructured":"El-Sabawi BR, Al-Garadi MA, Steitz BD, Perkins AM, McCoy AB, Sengstack DG, Greevy RA Jr, Burnell EH, Schlendorf KH, Lindenfeld J, et al. Predicting Heart Failure Outcomes Using Patient-Reported Health Status: Real-World Validation of the KCCQ-12. J Am Coll Cardiol. 2025;85(23):2253\u201366.","journal-title":"J Am Coll Cardiol"},{"issue":"12","key":"6003_CR33","doi-asserted-by":"publisher","first-page":"e006539","DOI":"10.1161\/CIRCHEARTFAILURE.119.006539","volume":"12","author":"P Dewan","year":"2019","unstructured":"Dewan P, R\u00f8rth R, Raparelli V, Campbell RT, Shen L, Jhund PS, Petrie MC, Anand IS, Carson PE, Desai AS, et al. Sex-related differences in heart failure with preserved ejection fraction. Circ Heart Fail. 2019;12(12):e006539.","journal-title":"Circ Heart Fail"},{"issue":"1","key":"6003_CR34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jacc.2018.09.081","volume":"73","author":"P Dewan","year":"2019","unstructured":"Dewan P, R\u00f8rth R, Jhund PS, Shen L, Raparelli V, Petrie MC, Abraham WT, Desai AS, Dickstein K, K\u00f8ber L, et al. Differential impact of heart failure with reduced ejection fraction on men and women. J Am Coll Cardiol. 2019;73(1):29\u201340.","journal-title":"J Am Coll Cardiol"},{"issue":"11","key":"6003_CR35","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1038\/s41591-021-01536-x","volume":"27","author":"ME Nassif","year":"2021","unstructured":"Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, Khariton Y, Malik AO, Khumri T, Umpierrez G, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: A multicenter randomized trial. Nat Med. 2021;27(11):1954\u201360.","journal-title":"Nat Med"},{"key":"6003_CR36","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1136\/heartjnl-2022-321097","volume":"109","author":"A Jasinska-Piadlo","year":"2023","unstructured":"Jasinska-Piadlo A, Campbell P. Management of patients with heart failure and preserved ejection fraction. Heart. 2023;109:874\u201383.","journal-title":"Heart"},{"issue":"11","key":"6003_CR37","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1161\/CIRCRESAHA.119.313572","volume":"124","author":"MA Pfeffer","year":"2019","unstructured":"Pfeffer MA, Shah AM, Borlaug BA. Heart failure with preserved ejection fraction in perspective. Circ Res. 2019;124(11):1598\u2013617.","journal-title":"Circ Res"},{"issue":"2","key":"6003_CR38","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/ejhf.2408","volume":"24","author":"A Kap\u0142on-Cie\u015blicka","year":"2022","unstructured":"Kap\u0142on-Cie\u015blicka A, Benson L, Chioncel O, Crespo-Leiro MG, Coats AJS, Anker SD, Filippatos G, Ruschitzka F, Hage C, Dro\u017cd\u017c J, et al. on behalf of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the ESC Heart Failure Long-Term Registry Investigators. A comprehensive characterization of acute heart failure with preserved versus mildly reduced versus reduced ejection fraction - insights from the ESC-HFA EORP Heart Failure Long-Term Registry. Eur J Heart Fail. 2022;24(2):335\u201350.","journal-title":"Eur J Heart Fail"},{"issue":"11","key":"6003_CR39","doi-asserted-by":"publisher","first-page":"e005254","DOI":"10.1161\/CIRCHEARTFAILURE.118.005254","volume":"11","author":"HJ Warraich","year":"2018","unstructured":"Warraich HJ, Kitzman DW, Whellan DJ, Duncan PW, Mentz RJ, Pastva AM, Nelson MB, Upadhya B, Reeves GR. Physical function, frailty, cognition, depression, and quality of life in hospitalized adults\u2009\u2265\u200960 years with acute decompensated heart failure with preserved versus reduced ejection fraction. Circ Heart Fail. 2018;11(11):e005254.","journal-title":"Circ Heart Fail"},{"issue":"9","key":"6003_CR40","doi-asserted-by":"publisher","first-page":"H1364","DOI":"10.1152\/ajpheart.00004.2014","volume":"306","author":"DW Kitzman","year":"2014","unstructured":"Kitzman DW, Nicklas B, Kraus WE, Lyles MF, Eggebeen J, Morgan TM, Haykowsky M. Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2014;306(9):H1364\u201370.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"6003_CR41","doi-asserted-by":"publisher","first-page":"1016452","DOI":"10.3389\/fcvm.2022.1016452","volume":"9","author":"EL Saw","year":"2022","unstructured":"Saw EL, Werner LD, Zamani P, Chirinos JA, Valero-Mu\u00f1oz M, Sam F. Skeletal muscle phenotypic switching in heart failure with preserved ejection fraction. Front Cardiovasc Med. 2022;9:1016452.","journal-title":"Front Cardiovasc Med"},{"issue":"3","key":"6003_CR42","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/ejhf.239","volume":"17","author":"TS Bowen","year":"2015","unstructured":"Bowen TS, Rolim NP, Fischer T, Baekkerud FH, Medeiros A, Werner S, Br\u00f8nstad E, Rognmo O, Mangner N, Linke A, et al. Optimex Study Group. Heart failure with preserved ejection fraction induces molecular, mitochondrial, histological, and functional alterations in rat respiratory and limb skeletal muscle. Eur J Heart Fail. 2015;17(3):263\u201372.","journal-title":"Eur J Heart Fail"},{"issue":"7","key":"6003_CR43","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/j.amjcard.2013.12.031","volume":"113","author":"MJ Haykowsky","year":"2014","unstructured":"Haykowsky MJ, Kouba EJ, Brubaker PH, Nicklas BJ, Eggebeen J, Kitzman DW. Skeletal muscle composition and its relation to exercise intolerance in older patients with heart failure and preserved ejection fraction. Am J Cardiol. 2014;113(7):1211\u20136.","journal-title":"Am J Cardiol"},{"issue":"8","key":"6003_CR44","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.jchf.2016.03.011","volume":"4","author":"AJ Molina","year":"2016","unstructured":"Molina AJ, Bharadwaj MS, Van Horn C, Nicklas BJ, Lyles MF, Eggebeen J, Haykowsky MJ, Brubaker PH, Kitzman DW. Skeletal muscle mitochondrial content, oxidative capacity, and Mfn2 expression are reduced in older patients with heart failure and preserved ejection fraction and are related to exercise intolerance. JACC Heart Fail. 2016;4(8):636\u201345.","journal-title":"JACC Heart Fail"},{"issue":"18","key":"6003_CR45","doi-asserted-by":"publisher","first-page":"6082","DOI":"10.3390\/jcm12186082","volume":"12","author":"J Perea-Armijo","year":"2023","unstructured":"Perea-Armijo J, L\u00f3pez-Aguilera J, Gonz\u00e1lez-Manzanares R, Pericet-Rodriguez C, Castillo-Dom\u00ednguez JC, Heredia-Campos G, Rold\u00e1n-Guerra \u00c1, Urbano-S\u00e1nchez C, Barreiro-Mesa L, Aguayo-Ca\u00f1o N, et al. The worsening of heart failure with reduced ejection fraction: The impact of the number of hospital admissions in a cohort of patients. J Clin Med. 2023;12(18):6082.","journal-title":"J Clin Med"}],"container-title":["BMC Cardiovascular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-026-06003-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12872-026-06003-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-026-06003-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:46:38Z","timestamp":1788155198000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12872-026-06003-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["6003"],"URL":"https:\/\/doi.org\/10.1186\/s12872-026-06003-4","relation":{},"ISSN":["1471-2261"],"issn-type":[{"value":"1471-2261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"24 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This is a single-centre prospective cohort study, conducted in accordance with the principles of the Declaration of Helsinki. It was approved by the Akashi Medical Centre Ethics Review Board (approval number: 2022-27).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"759"}}