ATTR-ACT Post Hoc Analysis: AFib/AFL Not Predictive of Mortality in Patients With ATTR-CM

Although atrial fibrillation/atrial flutter (AFib/AFL) are common manifestations of transthyretin amyloid cardiomyopathy (ATTR-CM), a post hoc analysis of the ATTR-ACT study, published April 30 in JACC: CardioOncology, found they do not predict all-cause mortality. Furthermore, baseline or historical AFib/AFL did not impact the efficacy of treatment with tafamidis.

The ATTR-ACT trial with 441 patients (median age, 75 years; 90% men; 81% White, 14% Black) with biopsy-confirmed ATTR-CM and a history of heart failure found that tafamidis (20 mg and 80 mg doses pooled) compared with placebo reduced the primary outcome of all-cause mortality at 30 months. For the post hoc analysis, using medical and medication history as well as ECG findings, the researchers found that 314 patients (71.2%) had baseline or historical AFib/AFL

Ronald Witteles, MD, FACC, et al., found that baseline or historical AFib/AFL was common among patients with ATTR-CM and the patients who had it were more likely to have advanced disease. Patients with AFib/AFL were more likely to be White and to have a wild-type TTR genotype, shorter median 6MWT distance, and higher median NT-proBNP and BUN concentrations.

Results of the Cox proportional hazards model showed that TTR genotype, baseline or historical AFib/AFL and NYHA functional class were each a significant independent predictor of all-cause mortality. However, using an expanded stepwise selection model with 23 baseline demographic and clinical covariates, baseline or historical AFib/AFL were no longer a statistically significant independent prognostic factor. Prognostic factors identified by the expanded analysis included TTR genotype (variant vs. wild-type), NT-proBNP concentration (log-transformed), global longitudinal strain, BUN concentration, 6MWT distance and treatment (tafamidis vs. placebo). Moreover, they found no significant interaction between the treatment effect of tafamidis in ATTR-ACT and baseline or historical AFib/AFL for all-cause mortality.

The authors note that the relationship between AFib/AFL and mortality found in the analysis with the limited adjustment analysis “could prove useful in the clinical setting where only limited data such as [left ventricular] ejection fraction or NYHA functional class may be available, in which case AFib/AFL could be a valuable indicator of disease severity for the clinician.” They also note that because the study was conducted before any treatments were approved for ATTR-CM it provides information on the natural history of arrhythmias in the study population.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Electrocardiography, Cardiomyopathies, Heart Failure, Ventricular Function, Left, Cardio-oncology, Atrial Flutter, Atrial Fibrillation

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