Transthyretin Cardiac Amyloidosis: An Evolution in Diagnosis and Management of an "Old" Disease

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, and cardiac amyloidosis (CA) is one of the causes of HFpEF, that has established and emerging treatment options. However, it remains an underdiagnosed and often overlooked cause of HFpEF. The importance of early diagnosis cannot be emphasized enough, as emerging therapies are more effective early in the course of the disease. Further, because of the unique physiologic and hemodynamic features of CA, patients poorly tolerate traditional heart failure medications and experience worse outcomes compared with other causes of HFpEF. With the aging of the population, transthyretin (ATTR) CA, once thought to be a rare disease, will become the most common type of systemic amyloidosis. ATTR-CA is increasingly recognized due to enhanced clinical awareness; advances in diagnostic imaging that have led to a diagnostic approach that does not require a biopsy, as well as the recent introduction of novel disease-modifying treatments. ATTR-CA causes restrictive and infiltrative cardiomyopathy that results in heart failure, atrial and ventricular arrhythmias, and conduction disease, and is associated with significant morbidity and mortality. Our goal in this review is to provide an overview of the historical, epidemiologic, diagnostic, and therapeutic evolution of ATTR-CA, and to emphasize the importance of early suspicion and detection of HFpEF.