Emerging therapeutic avenues in cardiac amyloidosis

Cardiac Amyloidosis (CA) is a toxic infiltrative cardiomyopathy occurred by the deposition of the amyloid fibres in the extracellular matrix of the myocardium. This results in severe clinical complications such as increased left ventricular wall thickness and interventricular stiffness, a decrease in left ventricular stroke volume and cardiac output, diastolic dysfunction, arrhythmia, etc. In a prolonged period, this condition progresses into heart failure. The amyloid fibres affecting the heart include immunoglobulin light chain (AL - amyloidosis) and transthyretin protein (ATTR - amyloidosis) misfolded amyloid fibres. ATTRwt has the highest prevalence of 155 to 191 cases per million while ATTRv has an estimated prevalence of 5.2 cases per million. The pathological findings and therapeutic approaches developed recently have aided in the treatment regimen of cardiac amyloidosis patients. In recent years, understanding the pathophysiology of amyloid fibres formation and mechanistic pathways triggered in both types of cardiac amyloidosis has led to the development of new therapeutic approaches and agents. This review focuses on the current status of emerging therapeutic agents in clinical trials. Earlier, melphalan and bortezomib in combination with alkylating agents and immunomodulatory drugs were used as a standard therapy for AL amyloidosis. Tafamidis, approved recently by FDA is used as a standard for ATTR amyloidosis. However, the emerging therapeutic agents under development for the treatment of AL and ATTR cardiac amyloidosis have shown a potent and rapid effect with a safety profile.