{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:09:43Z","timestamp":1789229383391,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Despite considerable advances in contemporary pharmacotherapy for heart failure (HF), residual congestion continues to drive adverse outcomes in a substantial proportion of patients. Goreisan, a traditional Kampo herbal formulation, has seen growing clinical application as an adjunct for refractory fluid retention; yet the prognostic implications of sustaining versus withdrawing goreisan among patients on tolvaptan-based regimens have not been adequately characterized. Methods: We conducted a retrospective single-center observational analysis enrolling patients with HF who received goreisan alongside tolvaptan-incorporated medical therapy between April 2022 and November 2025. Enrolled patients were classified into a continuation group or a termination group based on their subsequent goreisan treatment course. The primary endpoint was defined as a composite of all-cause death and HF-related hospitalization requiring intravenous diuretic therapy. Results: Among 25 patients, 12 maintained goreisan throughout the observation period while 13 underwent treatment termination. Baseline clinical profiles were broadly similar across the two groups. The continuation group exhibited a significantly reduced cumulative incidence of the primary endpoint relative to the termination group (p = 0.036). Negative binomial regression revealed a markedly elevated event rate in the termination group (incidence rate ratio 9.27; 95% confidence interval 2.05\u201342.0; p = 0.004), with adverse events demonstrating a pronounced temporal clustering in the immediate post-discontinuation period. Conclusions: Among patients with HF and refractory congestion on tolvaptan-incorporated therapy, maintaining goreisan was associated with a trend toward fewer clinical events and longer periods of hemodynamic stability, whereas its withdrawal appeared to be followed by early adverse outcomes. Given the small sample size and observational design, no definitive conclusions can be drawn, and these findings should be regarded strictly as preliminary and hypothesis generating; prospective controlled studies with larger cohorts are needed before any clinical implications can be established.<\/jats:p>","DOI":"10.3390\/jcm15103659","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:17:42Z","timestamp":1778519862000},"page":"3659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mid-Term Impact of Kampo Goreisan in Patients with Congestive Heart Failure Receiving Tolvaptan-Incorporated Medical Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Yuki","family":"Hida","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-7637","authenticated-orcid":false,"given":"Teruhiko","family":"Imamura","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Kinugawa","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"ref_1","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","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ccep.2018.11.001","article-title":"The Many Faces of Heart Failure","volume":"11","author":"Snipelisky","year":"2019","journal-title":"Card. Electrophysiol. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1016\/j.jacc.2021.12.011","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: Executive Summary","volume":"79","author":"Heidenreich","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/ejhf.3024","article-title":"2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"26","author":"McDonagh","year":"2024","journal-title":"Eur. J. Heart Fail."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41569-020-0379-7","article-title":"Congestion in heart failure: A contemporary look at physiology, diagnosis and treatment","volume":"17","author":"Boorsma","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1056\/NEJMra1703100","article-title":"Diuretic Treatment in Heart Failure","volume":"377","author":"Ellison","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.amjcard.2005.12.072","article-title":"Relation of loop diuretic dose to mortality in advanced heart failure","volume":"97","author":"Eshaghian","year":"2006","journal-title":"Am. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1001\/jama.297.12.1319","article-title":"Effects of oral tolvaptan in patients hospitalized for worsening heart failure: The EVEREST Outcome Trial","volume":"297","author":"Konstam","year":"2007","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1253\/circj.CJ-17-0179","article-title":"Effects of Additive Tolvaptan vs Increased Furosemide on Heart Failure With Diuretic Resistance and Renal Impairment: Results From the K-STAR Study","volume":"82","author":"Inomata","year":"2017","journal-title":"Circ. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1253\/circrep.CR-19-0064","article-title":"Long-Term Tolvaptan Treatment in Refractory Heart Failure","volume":"1","author":"Imamura","year":"2019","journal-title":"Circ. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jjcc.2018.10.003","article-title":"Update of acute and long-term tolvaptan therapy","volume":"73","author":"Imamura","year":"2019","journal-title":"J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.jjcc.2021.12.011","article-title":"Kampo medicine for the holistic approach to older adults with heart failure","volume":"80","author":"Yaku","year":"2022","journal-title":"J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117127","DOI":"10.1016\/j.jep.2023.117127","article-title":"Efficacy and safety of the traditional herbal medication Chai-Ling-Tang (in China), Siryung-tang (in Republic of Korea) or Sairei-To (in Japan)","volume":"319","author":"Bailly","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ahj.2023.02.013","article-title":"Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial","volume":"260","author":"Yaku","year":"2023","journal-title":"Am. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, Z., Zeng, Y., Hu, J., Huang, X., Zhang, H., and Liu, Y. (2024). Effectiveness of traditional herbal Kampo medicine Goreisan on chronic subdural hematoma recurrence: A meta-analysis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1412190"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.10.010","article-title":"Goreisan Prevents Brain Edema after Cerebral Ischemic Stroke by Inhibiting Aquaporin 4 Upregulation in Mice","volume":"27","author":"Nakano","year":"2018","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"29650","DOI":"10.1038\/s41598-024-81324-y","article-title":"Goreisan promotes diuresis by regulating the abundance of aquaporin 2 phosphorylated at serine 269 through calcium-sensing receptor activation","volume":"14","author":"Ogura","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1253\/circj.CJ-20-0947","article-title":"Clinical Characteristics and Outcomes of Hospitalized Patients With Heart Failure From the Large-Scale Japanese Registry Of Acute Decompensated Heart Failure (JROADHF)","volume":"85","author":"Ide","year":"2021","journal-title":"Circ. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion: A position statement from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"Mullens","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/eurheartj\/ehv010","article-title":"The kidney in heart failure: An update","volume":"36","author":"Damman","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.15420\/cfr.2024.07","article-title":"Pathophysiology of Congestion in Heart Failure: A Contemporary Review","volume":"10","author":"Kumric","year":"2024","journal-title":"Card. Fail. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Weerts, J., Mourmans, S.G.J., Barandiar\u00e1n Aizpurua, A., Schroen, B.L.M., Knackstedt, C., Eringa, E., Houben, A.J.H.M., van Empel, V.P.M., Duncker, D.J., and Heymans, S. (2022). The Role of Systemic Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction. Biomolecules, 12.","DOI":"10.3390\/biom12020278"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gevaert, A.B., Boen, J.R.A., Segers, V.F.M., and Van Craenenbroeck, E.M. (2019). Heart Failure With Preserved Ejection Fraction: A Review of Cardiac and Noncardiac Pathophysiology. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00638"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.jchf.2019.10.005","article-title":"Frailty Is Intertwined With Heart Failure: Mechanisms, Prevalence, Prognosis, Assessment, and Management","volume":"7","author":"Pandey","year":"2019","journal-title":"JACC Heart Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jjcc.2024.09.010","article-title":"Association between complementary use of Goreisan (a Japanese herbal Kampo medicine) and heart failure readmission: A nationwide propensity score-matched study","volume":"85","author":"Isogai","year":"2025","journal-title":"J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/ejhf.1236","article-title":"Advanced heart failure: A position statement of the Heart Failure Association of the European Society of Cardiology","volume":"20","author":"Metra","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ruiz, F., Vallet, T., Dufa\u00ff Wojcicki, A., Belissa, \u00c9., Fontan, J.E., de Pontual, L., Nathanson, S., Chevallier, A., Laribe-Caget, S., and Boudy, V. (2019). Dosage form suitability in vulnerable populations: A focus on paracetamol acceptability from infants to centenarians. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221261"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3659\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:40:54Z","timestamp":1778521254000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,10]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcm15103659"],"URL":"https:\/\/doi.org\/10.3390\/jcm15103659","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,10]]}}}