Patients With Transthyretin Cardiac Amyloidosis, Heart Failure With Preserved Ejection Fraction Have Similar All-Cause Death Rates

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Notably, patients with transthyretin cardiac amyloidosis had higher rates of heart failure hospitalizations, including patients treated with tafamidis.

Patients who have transthyretin cardiac amyloidosis (ATTR-CM) have similar rates of all-cause death compared with patients with heart failure with preserved ejection fraction (HFpEF), the results of a study published in the Journal of the American Heart Association shows.

Image credit: blacksalmon - stock.adobe.com

Image credit: blacksalmon - stock.adobe.com

Although rates of all-cause death were similar between the 2 groups, worse outcomes in ATTR-CM as compared with HFpEF were driven by high rates of heart failure hospitalizations, according to the study. This was observed even after restricting the ATTR-CM population to tafamidis-treated patients.

ATTR-CM has long been thought of as a rare disease with poor prognosis for those diagnosed, according to the study authors. However, the investigators noted that increasing use of noninvasive diagnostic tools has revealed ATTR-CM to be an underdiagnosed cause of heart failure. Prior studies have reported on the natural history of ATTR-CM in consecutive cohorts, but not in comparison with a HFpEF cohort, according to the study.

Therefore, the investigators sought to compare the clinical characteristics and outcomes between a single-center cohort of patients with ATTR-CM and patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. The primary outcome was a composite of all-cause death, heart failure hospitalizations, myocardial infarctions, and stroke. Secondary outcomes consisted of individual components of the primary outcome, in addition to death from cardiovascular causes and hospitalizations for any reason.

Participants in the study included 114 patients with ATTR-CM who received care at the Oregon Health and Science University Amyloidosis Clinic and 1763 patients enrolled in the TOPCAT trial. Shifting to analysis of the primary and secondary outcomes, a total of 689 patients in the TOPCAT cohort (39.1%) and 53 patients in the ATTR-CM cohort (46.5%) had at least 1 primary-outcome event. This result correlates to incidence rates of 15.6 events per 100 person-years in the TOPCAT cohort and 23.1 events per 100 person-years in the ATTR-CM cohort (HR, 1.44; 95% CI, 1.09-1.91; P = 0.01).

All-cause death was not found to be significantly different between the 2 cohorts, occurring in 387 patients in TOPCAT (22%) and 31 patients in ATTR-CM (27.2%). Additionally, hospitalization for heart failure occurred more frequently in ATTR-CM compared with TOPCAT (31.6% versus 22.6%; HR, 1.62 [95% CI, 1.15-2.28]; P = 0.005).

Although death from cardiovascular cases occurred more frequently in ATTR-CM compared with TOPCAT (6.64 versus 4.25 deaths per 100 person-years; HR, 1.8 [95% CI, 1.00-2.49]; P = 0.049), there was no difference in the rate of hospitalization for any reason (28.65 versus 33.75 events per 100 person-years; HR, 0.84 [95% CI, 0.65-1.10]; P = 0.20).

Tafamidis therapy was used to treat 79 patients among the 114 with ATTR-CM. Compared with patients enrolled in the TOPCAT trial, tafamidis-treated patients had similar rates of the primary composite outcome (HR, 1.30; 95% CI, 0.86-1.96; P = 0.21), all-cause death (HR, 1.10; 95% CI, 0.57-2.14; P = 0.78), and cardiovascular deaths (HR, 1.43; 95% CI, 0.67-3.06; P = 0.36).

In both the unadjusted and adjusted analyses, survival in ATTR-CM was found to be comparable with that of HFpEF over the short-term follow-up. They noted that patients with ATTR-CM who fared worse in the primary composite outcome were primarily driven by the higher rates of heart failure hospitalizations.

Continuing, the tafamidis-treated patient subgroup showed no significant difference in either the primary or composite outcome or all-cause death. The study authors noted that they continued to have higher rates of heart failure hospitalizations compared with patients enrolled in the TOPCAT trial even after adjusting for known confounders, but that efforts to identify ATTR-CM and begin treatment with tafamidis earlier may narrow these differences.

“Clinicians must stay vigilant and consider ATTR‐CM in patients with new diagnoses of heart failure with suspicious features,” the study authors concluded.

Reference

Kim M, Prasad M, Burton Y, et al. Comparative outcomes of a transthyretin amyloid cardiomyopathy cohort versus patients with heart failure with preserved ejection fraction enrolled in the TOPCAT trial. J Am Health Assoc.2023;12:e029705. doi:10.1161/JAHA.123.029705

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