Substantial prevalence of transthyretin amyloid cardiomyopathy present in patients with heart failure with preserved ejection fraction

1. Transthyretin amyloid cardiomyopathy was present in a substantial number of patients with heart failure with preserved ejection fraction and ventricular wall thickening in a community-based cohort, especially among older men.

2. With effective therapy available to treat transthyretin amyloid cardiomyopathy, targeted systematic evaluation in patients with heart failure with preserved ejection fraction may aid in its early diagnosis and offer therapeutically relevant phenotyping of the clinical syndrome.

Evidence Rating Level: 2 (Good)

Study Rundown: Approximately half of patients with heart failure (HF) have preserved ejection fraction (HFpEF). Increased left ventricular wall thickness is commonly observed in these patients. Although ventricular wall thickening in HFpEF is more commonly associated with hypertension-induced or volume-overload myocardial hypertrophy, a smaller group of patients have been found to have cardiac amyloid fibril infiltration, also known as transthyretin amyloid cardiomyopathy (ATTR-CM), which can mimic HFpEF clinically. However, where HFpEF caused by most other etiologies has no effective curative treatment, HFpEF due to ATTR-CM has highly effective therapy and is believed to be underrecognized in patients with heart failure. This cohort study sought to determine the prevalence of ATTR-CM among consecutive patients with HFpEF clinical syndrome and left ventricular wall thickening in southeastern Minnesota. The main endpoint of the analysis was ATTR-CM prevalence overall and stratified by strategy (clinical diagnosis or systematic screening), age, and sex. Prevalence was defined with or without screening using technetium Tc 99m pyrophosphate scintigraphy and appropriate reflex testing to exclude light chain amyloidosis. Among 1,235 consecutive patients with HFpEF, only 16 patients (1.3%; all men) had clinically recognized ATTR-CM. Subsequently, in 286 patients where systematic screening was performed using pyrophosphate scanning and reflex testing, 18 of 286 patients (6.3%; 10.0% of men and 2.2% of women) had ATTR-CM. These findings suggested that within a community-based cohort, ATTR-CM was present in a substantial number of patients with HFpEF and ventricular wall thickening, especially among older men. With effective therapy available to treat ATTR-CM, systematic evaluation in such patients may significantly aid in its early diagnosis and offer therapeutically relevant phenotyping of HFpEF. A limitation of this study was the predominance of mainly White participants, which does not accurately reflect the demographic characteristics of the US population overall, especially in more ethnically diverse urban centers. Thus, this may have underestimated the prevalence of ATTR-CM in the general US population and decreased the generalizability of the study findings.

Click to read the study in JAMA Cardiology

Relevant Reading: Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction

In-Depth [prospective cohort]: This population-based cohort study assessed 1,235 prospectively identified consecutive patients (median age, 80 years; IQR, 72-87 years; 630 [51%] male) with HFpEF from southeastern Minnesota, including 286 patients in a community systematic screening subcohort (median age, 78 years; IQR, 71-84 years; 150 [52%] male). Inclusion criteria included patients with a HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In total, 286 subjects underwent technetium Tc 99m pyrophosphate scanning between October 2017 and March 2020, where 884 individuals did not have ATTR-CM, contraindications to technetium Tc 99mpyrophosphate scintigraphy, or other barriers to study participation. Within the non-screening community cohort, 16 of 1,235 patients (1.3%; 95%CI, 0.7%-2.1%) had ATTR-CM, where the prevalence was 2.5% (95%CI, 1.4%-4.0%) in men and 0% (95%CI, 0.0%-0.6%) in women. Within the community screening cohort, 18 of 286 patients (6.3%; 95%CI, 3.8%-9.8%) had ATTR-CM, where the prevalence was 10.0% (15 of 150 men; 95%CI, 5.7%-16.1%) in men and 2.2% (3 of 136 women; 95%CI, 0.4%-6.3%) in women. Furthermore, prevalence increased with age from 0% in patients 60 to 69 years to 21% in patients 90 years and older (P < .001).

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