{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T21:51:50Z","timestamp":1768081910513,"version":"3.49.0"},"reference-count":20,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCDD"],"abstract":"<jats:p>Background: Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy that frequently progresses to symptomatic heart failure (HF), often with mildly reduced or reduced ejection fraction (EF). Standard therapies are limited in NYHA III\u2013IV, and Tafamidis is approved only for the early stages. Cardiac contractility modulation (CCM) therapy has shown promise in HF with reduced EF, but its role in ATTR-CM remains unexplored. Methods: This multicentric, prospective pilot study evaluated the safety and efficacy of CCM therapy in ten patients (n = 10) with ATTR-CM, EF between 25 and 45%, and NYHA class III\u2013IV symptoms refractory to optimal medical therapy. All patients underwent implantation of the Optimizer CCM system and were followed for at least 12 months. The primary endpoint was the incidence of worsening heart failure (WHF); secondary endpoints included changes in EF, NYHA class, 6-minute walk test (6MWT), and quality of life metrics. Results: In this cohort (n = 10), CCM therapy significantly reduced WHF episodes (from 0.18 \u00b1 0.09 to 0.025 \u00b1 0.08 hospitalizations\/patient-year, p &lt; 0.001) and improved NYHA class and 6MWT (p &lt; 0.001). EF increased by an average of 4.8 \u00b1 6.1%, and 6MWT improved by 31.3 \u00b1 53.3%. Importantly, all patients became eligible for Tafamidis after CCM therapy due to improved functional status. Conclusion: This pilot study suggests that CCM therapy is a feasible and potentially effective option for ATTR-CM patients with advanced HF who are not candidates for existing disease-modifying treatments. These findings support the rationale for larger studies, including the ongoing AMY-CCM registry (NCT05167799), to validate CCM\u2019s therapeutic role in this population.<\/jats:p>","DOI":"10.3390\/jcdd12100380","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:05:13Z","timestamp":1758801913000},"page":"380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of Contractility Modulation Therapy in Patients with Transthyretin Amyloid Cardiomyopathy, Mildly Reduced to Reduced EF and NYHA III and IV: A Multicentric, Prospective Pilot Study for AMY-CCM Registry"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2677-9214","authenticated-orcid":false,"given":"Procolo","family":"Marchese","sequence":"first","affiliation":[{"name":"Cardiology Unit, Mazzoni Civil Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Gennaro","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Mazzoni Civil Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Mazzotta","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Mazzoni Civil Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierfrancesco","family":"Grossi","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Mazzoni Civil Hospital, AST Ascoli Piceno, 63100 Ascoli Piceno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6604-1756","authenticated-orcid":false,"given":"Luigi","family":"Cocchiara","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Guarracini","sequence":"additional","affiliation":[{"name":"Department of Cardiology, \u201cPierangeli\u201d Hospital, 65129 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Mazzocchetti","sequence":"additional","affiliation":[{"name":"Department of Cardiology, \u201cPierangeli\u201d Hospital, 65129 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3617-2739","authenticated-orcid":false,"given":"Matteo","family":"Ziacchi","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Giuseppe Massarenti 9, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4590-8584","authenticated-orcid":false,"given":"Mauro","family":"Biffi","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Giuseppe Massarenti 9, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Magnano","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Ospedale Civile Santo Spirito, 65100 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Ospedale Civile Santo Spirito, 65100 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-2621","authenticated-orcid":false,"given":"Matteo","family":"Ruzzolini","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Sciences, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-4948","authenticated-orcid":false,"given":"Antonio","family":"Bisignani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Sciences, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6751-6437","authenticated-orcid":false,"given":"Matteo","family":"Bianco","sequence":"additional","affiliation":[{"name":"SCDO Cardiology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, 10043 Orbassano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-9155","authenticated-orcid":false,"given":"Paolo","family":"Garrone","sequence":"additional","affiliation":[{"name":"SCDO Cardiology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, 10043 Orbassano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4554-1110","authenticated-orcid":false,"given":"Walter","family":"Grosso Marra","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ivrea Hospital, ASLTO4, 10015 Ivrea, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6579-9040","authenticated-orcid":false,"given":"Margherita","family":"Cannillo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ivrea Hospital, ASLTO4, 10015 Ivrea, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Lavalle","sequence":"additional","affiliation":[{"name":"Department of Internal Clinical, Anesthesiological and Cardiovascular Sciences, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6781-7424","authenticated-orcid":false,"given":"Daniele","family":"Masarone","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Department of Cardiology, AORN dei Colli\/Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Chimenti","sequence":"additional","affiliation":[{"name":"Department of Internal Clinical, Anesthesiological and Cardiovascular Sciences, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1161\/CIRCRESAHA.117.310643","article-title":"Amyloid Cardiomyopathy: Disease on the Rise","volume":"120","author":"Liao","year":"2017","journal-title":"Circ. 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