{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:09:40Z","timestamp":1789229380941,"version":"build-2803163510"},"reference-count":22,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Public Health Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Telemonitoring aimed at detecting subclinical heart failure and facilitating medication up-titration offers a promising approach to reducing heart failure hospitalizations. Our team has recently developed a non-invasive metric called \u201crespiratory stability time (RST)\u201d, which quantifies respiratory instability, a surrogate marker of subclinical worsening heart failure. A decrease in RST below 20 s predicts the onset of worsening heart failure within 28 days. However, the clinical utility of RST-guided management in reducing mortality and heart failure hospitalizations remains uncertain. Methods: The Innovative Tele-Monitoring Environment To Halt Ongoing Deterioration of Heart Failure-III (ITMETHOD-HF-III) is a non-blinded, interventional, multicenter, single-arm study. Eighty heart failure patients with a history of at least two prior hospitalizations for heart failure will be enrolled. After validating the robustness of RST measurements, participants will be monitored for 1.5 years through daily RST measurements. Mandatory up-titration of heart failure medications will be started if RST values decrease below 20 s for two consecutive days or decrease progressively below 30 s over 10\u201390 days from RST values above 45 s maintained for over 1 month, irrespective of the presence of heart failure signs\/symptoms. Medication adjustment will continue until RST exceeds 30 s. The study will compare a composite endpoint of heart failure hospitalization and cardiac death between the present RST-guided group and a historical control group from the ITMETHOD-HF-II trial, in which management was based on patients\u2019 symptoms. Results: We anticipate that the precent ITMETHOD-HF-III study will demonstrate that mandatory, RST-guided heart failure management significantly reduces the incidence of the primary composite endpoint\u2014heart failure hospitalization and cardiac death\u2014compared with symptom-guided standard care in the historical control group (ITMETHOD-HF-II). Conclusions: The ITMETHOD-HF-III study aims to demonstrate the clinical efficacy of RST-guided management in reducing heart failure hospitalization rates and cardiac mortality by enabling early detection of subclinical heart failure and facilitating timely medication adjustments, irrespective of heart failure signs\/symptoms. If successful, RST-guided management could establish a new standard for telemonitoring heart failure patients in outpatient settings.<\/jats:p>","DOI":"10.3390\/jcm14134653","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"4653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Usefulness of Respiratory Stability Time-Guided Management to Prevent Readmission of Chronic Heart Failure Patients at Home: A Multicenter, Single-Arm, Open-Label Clinical Study (ITMETHOD-HF-III)"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-7637","authenticated-orcid":false,"given":"Teruhiko","family":"Imamura","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Akazawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0829-2891","authenticated-orcid":false,"given":"Shunsuke","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5855-8897","authenticated-orcid":false,"given":"Tomomi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Medical Innovation, Osaka University Hospital, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetsugu","family":"Asanoi","sequence":"additional","affiliation":[{"name":"Toyama Nishi General Hospital, Toyama 939-2716, 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":[[2025,7,1]]},"reference":[{"key":"ref_1","first-page":"e895","article-title":"2022 AHA\/ACC\/HFSA Guideline for the management of heart failure","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e014949","DOI":"10.1161\/JAHA.119.014949","article-title":"Prognostic Implications of Early and Midrange Readmissions After Acute Heart Failure Hospitalizations: A Report From a Japanese Multicenter Registry","volume":"9","author":"Kitakata","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1002\/ehf2.13646","article-title":"\u2018Time is prognosis\u2019 in heart failure: Time-to-treatment initiation as a modifiable risk factor","volume":"8","author":"Abdin","year":"2021","journal-title":"ESC Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e002606","DOI":"10.1161\/JAHA.115.002606","article-title":"Medication Adherence Interventions Improve Heart Failure Mortality and Readmission Rates: Systematic Review and Meta-Analysis of Controlled Trials","volume":"5","author":"Ruppar","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/dom.15166","article-title":"Assessment of the patient with heart failure symptoms and risk factors: A guide for the non-cardiologist","volume":"25","author":"Arnold","year":"2023","journal-title":"Diabetes Obes. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/ejhf.507","article-title":"Moving away from symptoms-based heart failure treatment: Misperceptions and real risks for patients with heart failure","volume":"18","author":"Butler","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0147-9563(97)90053-4","article-title":"Older adults\u2019 symptoms and their duration before hospitalization for heart failure","volume":"26","author":"Friedman","year":"1997","journal-title":"Heart Lung"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1177\/1357633X211039404","article-title":"Prognostic value of signs and symptoms in heart failure patients using remote telemonitoring","volume":"30","author":"Gingele","year":"2024","journal-title":"J. Telemed. Telecare"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1056\/NEJMoa1010029","article-title":"Telemonitoring in patients with heart failure","volume":"363","author":"Chaudhry","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1161\/CIRCULATIONAHA.111.043042","article-title":"Intrathoracic impedance monitoring, audible patient alerts, and outcome in patients with heart failure","volume":"124","author":"Braunschweig","year":"2011","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/ejhf.458","article-title":"Predicting heart failure decompensation using cardiac implantable electronic devices: A review of practices and challenges","volume":"18","author":"Hawkins","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.cardfail.2010.08.002","article-title":"Champion trial rationale and design: The long-term safety and clinical efficacy of a wireless pulmonary artery pressure monitoring system","volume":"17","author":"Adamson","year":"2011","journal-title":"J. Card. Fail."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S0140-6736(11)60101-3","article-title":"Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: A randomised controlled trial","volume":"377","author":"Abraham","year":"2011","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/HCO.0000000000001119","article-title":"Implementation of remote monitoring strategies to improve chronic heart failure management","volume":"39","author":"Chau","year":"2024","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12576-022-00847-z","article-title":"Temporal variations in the pattern of breathing: Techniques, sources, and applications to translational science","volume":"72","author":"Oku","year":"2022","journal-title":"J. Physiol. Sci."},{"key":"ref_16","first-page":"1","article-title":"Advanced ICT remote monitoring system in home healthcare: Challenges, solutions, and prospects","volume":"55","author":"Asanoi","year":"2016","journal-title":"J. Jpn. Munic. Hosp. Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1253\/circj.CJ-18-0519","article-title":"Multicenter, Prospective Study on Respiratory Stability During Recovery from Deterioration of Chronic Heart Failure","volume":"83","author":"Takagawa","year":"2018","journal-title":"Circ. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ueno, Y., Imamura, T., Oshima, A., Onoda, H., Ushijima, R., Sobajima, M., Fukuda, N., Ueno, H., and Kinugawa, K. (2022). Clinical Implications of Changes in Respiratory Instability Following Transcatheter Aortic Valve Replacement. J. Clin. Med., 11.","DOI":"10.3390\/jcm11010280"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1253\/circj.CJ-21-0590","article-title":"Early Detection of Worsening Heart Failure in Patients at Home Using a New Telemonitoring System of Respiratory Stability","volume":"86","author":"Sakoda","year":"2022","journal-title":"Circ. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1002\/ejhf.1906","article-title":"Telemonitoring versus standard care in heart failure: A randomised multicentre trial","volume":"22","author":"Galinier","year":"2020","journal-title":"Eur. J. Heart Fail."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e008335","DOI":"10.1161\/CIRCHEARTFAILURE.121.008335","article-title":"Trends in 30- and 90-day readmission rates for heart failure","volume":"14","author":"Khan","year":"2021","journal-title":"Circ. Heart Fail."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.jchf.2017.02.020","article-title":"Progression to stage D heart failure among outpatients with stage D heart failure and reduced ejection fraction","volume":"5","author":"Kalogeropoulos","year":"2017","journal-title":"JACC Heart Fail."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:15Z","timestamp":1760032935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":22,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14134653"],"URL":"https:\/\/doi.org\/10.3390\/jcm14134653","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]}}}