Prognostic Factors and Implantable Cardioverter-Defibrillator Outcomes in Transthyretin Cardiac Amyloidosis: A...

Transthyretin (TTR) cardiac amyloidosis is a progressive cardiomyopathy with high mortality; however, the role of implantable cardioverter-defibrillators (ICDs) in this population remains unclear.

This retrospective cohort study included patients with confirmed TTR cardiac amyloidosis, with or without ICDs, from January 1, 2001, to December 31, 2024, across all three Mayo Clinic sites (Arizona, Florida, and Minnesota). Diagnosis was confirmed by endomyocardial biopsy or abnormal technetium pyrophosphate (PYP) scintigraphy. A 1:4 propensity score-matched cohort of non-ischemic cardiomyopathy (NICM) patients with ICDs served as a control group. The primary outcome was all-cause mortality, comparing transthyretin cardiac amyloidosis (TTR-CA) patients by ICD status and against matched NICM patients. Secondary analyses evaluated predictors of mortality, including the use of tafamidis and the indication for ICD (primary vs. secondary prevention). Kaplan-Meier and Cox regression analyses were used to assess predictors of survival and mortality.

A total of 463 patients with confirmed TTR cardiac amyloidosis were included. The median follow-up duration was 7.4 years (interquartile range (IQR): 5.3-9.2 years) for the non-ICD group and 6.8 years (IQR: 4.5-9.0 years) for the ICD group. The median age was 74.5 years (IQR: 68.0-80.0 years), and 92.9% of patients were male. Among them, 206 (44.5%) received ICDs and 257 (55.5%) did not. ICD recipients were younger (71.0 vs. 77.0 years; p = 0.001) and had higher rates of hypertension (62.6% vs. 45.6%; p = 0.001), chronic kidney disease (CKD) (62.6% vs. 44.4%; p = 0.001), and diabetes (30.1% vs. 21.8%; p = 0.043). Median left ventricular ejection fraction was lower in the ICD groups (43% vs. 54%; p = 0.007), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the ICD group (2259.0 pg/mL vs. 1503.0 pg/mL; p = 0.007). Among ICD recipients, 157 (76.2%) received the device for primary prevention, while 48 (23.3%) received the ICD for secondary prevention. Appropriate shocks were delivered in 22 patients (10.6%), primarily for ventricular tachycardia (n = 18) and ventricular fibrillation (n = 4). Inappropriate shocks occurred in six patients (3.0%), and 12 patients (5.8%) experienced device-related complications. Over 10 years of follow-up, ICD implantation did not confer a survival benefit for patients with TTR-CA compared to those without an ICD (p = 0.74). In contrast, a 1:4 propensity-matched NICM cohort with ICDs, which had a median follow-up of 7.1 years (IQR: 4.6-8.8 years), showed significantly improved survival than TTR-CA patients with ICDs (p = 0.034). Among the TTR-CA patients with ICDs, neither the use of tafamidis (p = 0.10) nor the ICD indication (primary vs. secondary prevention; p = 0.85) influenced mortality. In the Cox regression analysis, predictors of mortality in TTR-CA patients included older age (hazard ratio (HR) 1.048; p = 0.001), CKD (HR 1.637; p = 0.029), troponin T >50 ng/L (HR 1.594; p = 0.031), NT-proBNP >3000 pg/mL (HR 1.514; p = 0.050), and ejection fraction <40% (HR 1.935; p = 0.003). ICD implantation was not associated with improved survival (HR 0.932; p = 0.763).

In conclusion, our data suggest that ICD therapy may not provide a significant overall survival benefit in older TTR-CA patients with impaired pump function; thus, prospective studies are warranted before any changes to clinical practice are considered. Key predictors of mortality included reduced ejection fraction and elevated cardiac biomarkers. Additional prospective studies are needed to clarify the role of ICDs in treatment strategies for patients with TTR-CA.