Neth Heart J. 2026 Nov 10. doi: 10.1007/s12471-026-02096-w. Online ahead of print.

ABSTRACT

Amyloidosis comprises a group of systemic disorders caused by extracellular deposition of misfolded precursor proteins, leading to progressive organ dysfunction. Cardiac amyloidosis, particularly transthyretin-related amyloid cardiomyopathy (ATTR-CM) has transitioned from a rare and underdiagnosed condition to a treatable disease, driven by major advances in diagnostic imaging, increased disease awareness, and the approval of disease-modifying therapies. These therapies target transthyretin (TTR) stabilization and amyloid production or deposition and have led to an evolving therapeutic landscape. As therapeutic efficacy is greatest in earlier disease stages, timely recognition is crucial. Effective management of ATTR-CM requires structured screening of high-risk populations, multidisciplinary collaboration, and longitudinal follow-up. This review provides a practical, clinician-focused framework that addresses clinical presentation and "red flags" to facilitate early detection. It offers a comprehensive overview of the diagnostic pathway, including (AI-enabled) electrocardiography analysis, (non-)invasive imaging modalities, biomarkers, and genetic testing. Additionally, emerging therapeutic strategies are discussed, encompassing supportive heart failure management, amyloid-specific treatments such as TTR stabilizers and gene silencers, and novel approaches including fibril depletion and gene-editing therapies. As the therapeutic paradigm shifts from disease stabilization toward potential reversal, early diagnosis and personalized treatment strategies are essential to improve prognosis and quality of life in patients with cardiac amyloidosis.

PMID:43007390 | DOI:10.1007/s12471-026-02096-w