BACKGROUND: Cardiac amyloidosis (CA) results from the deposition of abnormally folded protein fibrils, leading to restrictive cardiomyopathy, valvular heart disease, and arrhythmias. Up to 15 % of patients with severe aortic stenosis (AS) have concomitant CA (AS-CA). We conducted this systematic review and meta-analysis to compare medical management, transcatheter aortic valve replacement (TAVR), and surgical AVR (SAVR) in AS-CA. METHODS: A comprehensive literature search was conducted for relevant studies from inception through January 20, 2024. Studies exploring outcomes in adult AS patients with and without CA receiving medical therapy, TAVR, or SAVR were included in this analysis. RESULTS: Fifteen studies including 253,334 patients (AS-CA 6704
AS alone 246,630) were identified. AS-CA patients had significantly higher all-cause mortality (RR = 2.60, 95 % CI 1.48-4.57, P = 0.0009) compared to AS alone. Among patients with AS-CA, TAVR was associated with lower all-cause mortality compared to both medical therapy (RR = 0.50, 95 % CI 0.29-0.89, P = 0.02) and SAVR (RR = 0.41, 95 % CI 0.22-0.78, P = 0.007). AS-CA patients undergoing TAVR were more likely to have paradoxical low-flow, low-gradient AS (RR = 1.56, 95 % CI 1.15-2.12, P = 0.04) at baseline and had a higher risk of post-TAVR acute kidney injury (RR = 1.95, 95 % CI 1.35-2.80, P = 0.0003) compared to patients undergoing TAVR for AS alone. There were similar risks of other post-TAVR complications, including major bleeding, vascular complications, stroke, and new pacemaker implantation between AS-CA and AS alone. CONCLUSION: CA is associated with a higher mortality in patients with severe AS. In patients with concomitant AS and CA, TAVR is safe and associated with better survival than medical therapy or SAVR. SOCIAL MEDIA ABSTRACT: #Meta-Analysis: Cardiac amyloidosis is associated with increased mortality in severe AS. #TAVR is safe in amyloidosis & improves survival more than medical therapy or SAVR.