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 “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. 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.

Cardiac amyloidosis, once considered a rare and untreatable disorder, is now increasingly recognized as a significant cause of heart failure, particularly in older adults. The two most clinically relevant subtypes of cardiac amyloidosis—immunoglobulin light-chain amyloidosis (AL) and transthyretin-related amyloidosis (ATTR)—differ in pathogenesis, natural history, and management strategies, thereby necessitating a tailored approach to diagnosis and therapy. Advances in multimodality cardiac imaging, including echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, have enabled earlier detection and improved differentiation between subtypes. Management of AL centers on rapid initiation of plasma cell-directed therapies to suppress light-chain production, with autologous stem cell transplantation and novel chemotherapeutic regimens improving survival. In contrast, ATTR management focuses on stabilizing or reducing transthyretin deposition through disease-modifying agents, such as stabilizers, gene-silencing therapies, and emerging fibril-disrupting approaches. Supportive care, including guideline-directed heart failure therapies and arrhythmia management, as well as advanced therapies such as transplantation, remains essential across both subtypes, albeit with unique considerations due to amyloid-related hemodynamics. This review synthesizes current evidence on the diagnosis and treatment of AL and ATTR, highlights recent therapeutic breakthroughs, and discusses ongoing challenges in optimizing patient outcomes, from equitable access to therapies to the integration of multidisciplinary care.

Takotsubo syndrome (TTS), also known as the “broken heart syndrome” or “stress cardiomyopathy,” is characterized by transient left ventricular systolic dysfunction, usually in the absence of significant obstructive coronary artery disease. The pathophysiology of TTS remains incompletely understood, though commonly proposed mechanisms include catecholamine surge, estrogen deficiency, and coronary circulation dysfunction. TTS was initially regarded as benign and reversible; however, studies indicate that it may have severe short- and long-term complications. There are several prognostic factors associated with TTS that may influence patient outcomes. In this review, we aim to explore these prognostic factors in relation to various clinical variables, including age, gender, trigger type, atrial arrhythmias, rate-corrected QT interval, baseline left ventricular systolic function, and comorbidities. While many factors are thought to influence TTS, current research findings remain inconsistent. To improve prognosis, there is an urgent need to develop better risk-assessment tools. This can be achieved through large-scale, multicenter studies and analysis of existing research. By understanding these prognostic factors, better prevention and intervention strategies can be developed for TTS, reinforcing its recognition as a serious cardiovascular condition.

Takotsubo syndrome (TTS), also known as broken heart syndrome, is an acute cardiac condition with a poorly understood pathophysiology due to its relative rarity. Once considered benign, it is now recognized as a serious disorder with severe complications and a mortality rate comparable to or exceeding that of acute coronary syndrome. This narrative review aims to summarize current knowledge on the prognostic factors associated with TTS, with a particular focus on its relationship with diabetes mellitus (DM). A thorough analysis of 57 relevant studies, selected from over 98,000 articles retrieved from PubMed and Google Scholar, was conducted based on strict inclusion criteria. The findings indicate that advanced age, female sex, pre-existing cardiovascular diseases, and systemic disorders significantly influence the prognosis and mortality of patients with the syndrome. DM plays a paradoxical role, being associated with increased long-term mortality risk while potentially providing a protective effect during the acute phase of the syndrome, possibly by modulating stress responses involved in its onset. Therefore, a deeper understanding of the prognostic implications of TTS and its interaction with diabetes is crucial for developing appropriate risk stratification tools and improving clinical management of patients.