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Published on: July 20, 2022
Atrial Fibrillation as a Prognostic Factor for All-Cause Mortality in Patients With Transthyretin Amyloid
Ronald Witteles1, John L Jefferies2, Suraj Kapa3
1Stanford University School of Medicine, Stanford, California, USA.
Insights
Atrial fibrillation/flutter (AF/AFL) in transthyretin amyloid cardiomyopathy (ATTR-CM) predicts mortality with limited adjustments but not with broader disease severity factors. AF/AFL did not affect tafamidis treatment efficacy.
Area of Science:
- Cardiology
- Genetics
- Pharmacology
Background:
- Atrial fibrillation/atrial flutter (AF/AFL) are common in transthyretin amyloid cardiomyopathy (ATTR-CM).
- Previous findings suggest AF/AFL is not a mortality predictor in ATTR-CM.
- This study investigates AF/AFL as a prognostic factor for mortality in ATTR-CM.
Purpose of the Study:
- To determine if baseline or historical AF/AFL predicts all-cause mortality in ATTR-CM patients.
- To explore the impact of AF/AFL on the efficacy of tafamidis treatment.
Main Methods:
- Analysis of the ATTR-ACT trial data, a 30-month study of tafamidis versus placebo in ATTR-CM.
- Cox proportional hazards modeling to assess AF/AFL as an independent prognostic factor for all-cause mortality.
- Exploration of treatment interaction with AF/AFL status for mortality and clinical outcomes.
Main Results:
- AF/AFL was an independent predictor of all-cause mortality in ATTR-ACT (HR: 0.550; 95% CI: 0.368-0.821) with limited covariate adjustment.
- AF/AFL lost prognostic significance in an expanded model including 23 covariates, indicating disease severity is a stronger factor.
- No significant interactions were found between tafamidis treatment and AF/AFL for mortality, quality of life (KCQ), or 6-minute walk test distance.
Conclusions:
- Baseline or historical AF/AFL is prognostic for mortality in ATTR-CM with limited adjustment but not when accounting for broader disease severity indicators.
- AF/AFL status does not influence the efficacy of tafamidis in treating ATTR-CM.
- The findings highlight the importance of comprehensive assessment of disease severity in ATTR-CM prognosis.
Background:
Atrial fibrillation/atrial flutter (AF/AFL) are common manifestations of transthyretin amyloid cardiomyopathy (ATTR-CM) but have not been found to be predictive of mortality.
Objectives:
This analysis aimed to examine whether baseline or historical AF/AFL at enrollment was prognostic for all-cause mortality.
Methods:
In the ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), a 30-month study of tafamidis vs placebo for ATTR-CM, AF/AFL was evaluated as an independent prognostic factor for all-cause mortality using Cox proportional hazards modelling. The impact of AF/AFL on tafamidis efficacy was explored by adding an interaction term for AF/AFL status and treatment.
Results:
ATTR-ACT enrolled 441 patients with ATTR-CM (median age 75 years; 90% male); 314 (71.2%) had baseline or historical AF/AFL at enrollment. AF/AFL was an independent prognostic factor for all-cause mortality after adjusting for covariates prespecified in the ATTR-ACT model (treatment, genotype, New York Heart Association functional class; HR: 0.550; 95% CI: 0.368-0.821) but not in an expanded stepwise model selection analysis including 23 covariates (blood urea nitrogen and N-terminal pro-B-type natriuretic peptide concentration, 6-minute walk test distance, genotype, treatment, and global longitudinal strain were prognostic [P < 0.01]). The interactions between tafamidis treatment and AF/AFL for all-cause mortality (P = 0.33) and changes in Kansas City Cardiomyopathy Questionnaire Overall Summary score (P = 0.83) and 6-minute walk test distance (P = 0.82) were not significant.
Conclusions:
In ATTR-ACT, baseline or historical AF/AFL was prognostic for all-cause mortality in analyses with limited adjustment but not after accounting for additional indicators of disease severity. Baseline or historical AF/AFL did not impact the efficacy of tafamidis treatment. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889).
