Cardiac Amyloidosis in the Real World: Clinical Presentations, Disease Overlap, and Therapeutic Imperatives.

Cardiac amyloidosis (CA) has emerged from the margins of cardiology to the forefront of research and practice on heart failure. Once regarded as rare and elusive, CA is now recognized as a significant cause of heart failure with preserved ejection fraction (HFpEF), arrhythmias, and valvular disease, especially in older patients. CA is characterized by extracellular deposition of misfolded protein fibrils, which infiltrate the myocardium and disrupt the structural and electrical integrity. Although CA can stem from multiple amyloid types, transthyretin amyloidosis (ATTR) and light-chain (AL) amyloidosis are the predominant subtypes with cardiac involvement, each carrying distinct implications for prognosis and therapy. This review explores CA as a clinical reality often obscured by more common cardiovascular syndromes. Moreover, this review focuses on the varied presentations of CA in real-world practice, how the condition overlaps with HFpEF, the subtle clues for CA amid common valvular disorders, and the complex rhythm manifestations of the condition. Particular attention is given to thromboembolic risk, microvascular dysfunction, and the evolving paradigm of preclinical or asymptomatic amyloidosis management. Furthermore, this review addresses contemporary challenges such as financial toxicity and the cost-effectiveness of screening, emphasizing the benefits of early detection and therapy. The paper also discusses risk stratification and staging, drawing from validated models to guide both prognosis and treatment decisions, and the role of histopathological characterization. Thus, this review underscores the importance of timely recognition and tailored intervention in transforming CA from a terminal diagnosis into a manageable chronic condition.