Amyloidosis is a rare disorder characterized by the deposition of amyloid proteins in various organs, including the heart, which is affected in 30%–75% of cases.1,2 Among patients with heart failure with preserved ejection fraction (HFpEF), the prevalence of CA is approximately 13%.3 Increased awareness and advances in diagnostic modalities, such as noninvasive imaging techniques like the PYP scan,4 have improved the detection of CA.5 Multiple molecular and genetic factors are involved in the formation of amyloid proteins. Certain mutations, such as Val122Ile and Leu111Met, can influence tissue tropism, often leading to cardiac involvement.6 The pathophysiology of CA differs between subtypes, with AL amyloidosis involving the deposition of light chains that not only disrupt cardiac structure but also exert direct toxicity, contributing to its more severe cardiac manifestations compared to transthyretin (TTR) amyloidosis.7, 8, 9

Advances in diagnostic strategies, gene sequencing techniques, and a deeper understanding of the mutations and pathophysiology underlying amyloidosis have shifted medical management toward tailored therapies rather than a one-size-fits-all approach.10 This personalized approach has provided a foundation for the development of disease-modifying treatments.11, 12, 13, 14, 15

In transthyretin amyloid cardiomyopathy (ATTR-CM), several classes of therapies are emerging, with tetramer stabilizers and transthyretin silencers demonstrating significant efficacy. Tafamidis and acoramidis are currently approved for ATTR-CM, while vutrisiran may soon gain approval, offering new hope for patients with this challenging condition.16 New treatment strategies like gene editing, antisense oligonucleotides and monoclonal antibodies are currently being tested with promising preliminary results in trials.

Treatment of cardiac amyloidosis is mainly focused on managing cardiac manifestations particularly heart failure and atrial fibrillation and preventing the progression of organ dysfunction. Advanced cardiac support such as with heart transplantation and mechanical cardiac support can also be considered in certain cases.

This review examines the advancements in understanding the pathophysiology of cardiac amyloidosis and the development of new therapies, providing a detailed approach to managing its cardiac manifestations and addressing persistent challenges in treatment.