{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:49:42Z","timestamp":1783111782815,"version":"3.54.6"},"reference-count":77,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"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: Cardiac amyloidosis (CA) is an increasingly recognized but historically underdiagnosed cause of restrictive cardiomyopathy and heart failure with preserved ejection fraction (HFpEF). It results from the extracellular deposition of misfolded protein fibrils, most commonly transthyretin (ATTR) or immunoglobulin light chains (AL), leading to progressive myocardial dysfunction and multi-organ involvement. Objective: This review provides a comprehensive, cardiology-centered overview of cardiac amyloidosis, with an emphasis on early recognition, diagnostic strategies, subtype differentiation, and the evolving therapies. Content: We summarize the epidemiology, pathophysiology, and clinical manifestations of both ATTR and AL subtypes. Key diagnostic tools, including echocardiography, cardiac magnetic resonance imaging, bone scintigraphy, monoclonal protein screening, and endomyocardial biopsy, are reviewed in the context of a stepwise diagnostic approach. Special attention is given to clinical presentation, electrocardiographic and imaging \u201cred flags,\u201d and to differentiating CA from mimickers such as hypertrophic cardiomyopathy, hypertension-induced left ventricular hypertrophy, and aortic stenosis. Staging systems are detailed, highlighting the prognostic role of cardiac biomarkers. Therapeutic strategies are explored, including subtype-specific regimens (e.g., daratumumab-based therapy for AL; tafamidis and gene silencers for ATTR), the judicious use of conventional heart failure medications, and emerging therapies such as CRISPR-based gene editing. Conclusions: Timely recognition and accurate diagnosis of cardiac amyloidosis are critical to improving outcomes. As diagnostic tools and disease-modifying therapies evolve rapidly, cardiologists must remain at the forefront of multidisciplinary care. A structured biomarker- and imaging-guided approach can enhance diagnostic yield, inform prognosis, and optimize patient-specific management.<\/jats:p>","DOI":"10.3390\/jcm14186668","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:08:03Z","timestamp":1758542883000},"page":"6668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["What Cardiologists Should Know About Amyloidosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Rama","family":"Alashqar","sequence":"first","affiliation":[{"name":"Washington Hospital Center Program, MedStar Health, Georgetown University, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Alkhatib","sequence":"additional","affiliation":[{"name":"Baltimore Program, Department of Internal Medicine, Medstar Health, Georgetown University, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0266-2859","authenticated-orcid":false,"given":"Ala W.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV 89102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9095-2302","authenticated-orcid":false,"given":"Mahmoud","family":"Odeh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Sheikh Tahnoon Bin Mohammed Medical City, Al Ain, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0330-3336","authenticated-orcid":false,"given":"Mustafa","family":"Al-Taei","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Own","family":"Khraisat","sequence":"additional","affiliation":[{"name":"Englewood Hospital and Medical Center, Department of Medicine, Englewood, NJ 07631, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-4128","authenticated-orcid":false,"given":"Mohammed","family":"Al-Hiari","sequence":"additional","affiliation":[{"name":"Jefferson Einstein Philadelphia Hospital, Philadephia, PA 19131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem","family":"Taifour","sequence":"additional","affiliation":[{"name":"Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, NY 14626, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8568-2150","authenticated-orcid":false,"given":"Amer","family":"Hammad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Banner University Medical Center, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Sami","family":"Abuzaid","sequence":"additional","affiliation":[{"name":"Alaska Heart and Vascular Institute, Anchorage, AK 99508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.jchf.2019.04.010","article-title":"Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice","volume":"7","author":"Witteles","year":"2019","journal-title":"JACC Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1016\/j.jacc.2019.04.003","article-title":"Transthyretin Amyloid Cardiomyopathy","volume":"73","author":"Ruberg","year":"2019","journal-title":"J. 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