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What Cardiologists Should Know About Amyloidosis
Journal article   Open access   Peer reviewed

What Cardiologists Should Know About Amyloidosis

Rama Alashqar, Ahmad Alkhatib, Ala W Abdallah, Mahmoud Odeh, Mustafa Al-Taei, Own Khraisat, Mohammed Al-Hiari, Hazem Taifour, Amer Hammad and Ahmed Sami Abuzaid
Journal of clinical medicine, Vol.14(18), 6668
09/22/2025
DOI: 10.3390/jcm14186668
PMCID: PMC12471172
PMID: 41010872
url
https://doi.org/10.3390/jcm14186668View
Published (Version of record) Open Access

Abstract

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. 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. 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 "red flags," 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. 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.
 Heart Failure hospitalization amyloidosis

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