Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis

Abstract

Cardiac amyloidosis is a progressive disease characterized by the buildup of amyloid fibrils in the extracellular space of the heart. It is divided in 2 main types, immunoglobulin light chain amyloidosis and transthyretin amyloidosis (ATTR), and ATTR amyloidosis is further divided in 2 subtypes, non-hereditary wild type ATTR and hereditary mutant variant amyloidosis. Incidence and prevalence of ATTR cardiac amyloidosis is increasing over the last years due to the improvements in diagnostic methods. Survival rates are improving due to the development of novel therapeutic strategies. Tafamidis is the only disease-modifying approved therapy in ATTR amyloidosis so far. However, the most recent advances in medical therapies have added more options with the potential to become part of the therapeutic armamentarium of the disease. Agents including acoramidis, eplontersen, vutrisiran, patisiran and anti-monoclonal antibody NI006 are being investigated on cardiac function in large, multicenter controlled trials which are expected to be completed within the next 2-3 years, providing promising results in patients with ATTR cardiac amyloidosis. However, further and ongoing research is required in order to improve diagnostic methods that could provide an early diagnosis, as well as survival and quality of life of these patients.

Keywords: Acoramidis; Eplontersen; Patisiran; Tafamidis; Transthyretin cardiac amyloidosis; Vutrisiran.

Figure 1

Diagnostic approach and therapeutic strategies in transthyretin amyloidosis cardiac amyloidosis. ACEi: Angiotensin-converting enzyme inhibitors; AL: Immunoglobulin light chain amyloidosis; ARBs: Angiotensin receptor blockers; ATTR: Transthyretin amyloidosis; ATTRv: Mutant variant transthyretin amyloidosis; ATTRwt: Wild type transthyretin amyloidosis; AV: Atrioventricular; CMR: Cardiac magnetic resonance; ECG: Electrocardiogram; HCL: Heart/contralateral; HF: Heart failure; LV: Left ventricular; LVH: Left ventricular hypertrophy; RV: Right ventricular; sFLC: Serum free light chain; SGLT2i: Sodium-glucose cotransporter-2 inhibitors; SIFE: Serum immunofixation electrophoresis; SPECT: Single-photon emission computed tomography; UIFE: Urine immunofixation electrophoresis.