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Prevalence of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction
Omar F AbouEzzeddine1, Daniel R Davies1, Christopher G Scott2
1Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
Insights
Transthyretin amyloid cardiomyopathy (ATTR-CM) is underrecognized in heart failure with preserved ejection fraction (HFpEF). Systematic screening identified ATTR-CM in 6.3% of patients, particularly older men, suggesting improved diagnosis and treatment opportunities.
Area of Science:
- Cardiology
- Cardiovascular Diseases
- Medical Diagnostics
Background:
- Heart failure with preserved ejection fraction (HFpEF) is a common condition often linked to ventricular wall thickening.
- Currently, effective therapies for HFpEF are limited.
- Transthyretin amyloid cardiomyopathy (ATTR-CM) can mimic the HFpEF phenotype and is treatable, but often overlooked.
Purpose of the Study:
- To determine the prevalence of ATTR-CM in patients with HFpEF and ventricular wall thickening.
- To compare ATTR-CM prevalence with and without systematic screening protocols.
- To identify demographic factors associated with ATTR-CM in this population.
Main Methods:
- A population-based cohort study involving 1235 patients with HFpEF and ventricular wall thickness ≥12 mm.
- Patients were assessed for ATTR-CM through medical record review or technetium Tc 99m pyrophosphate scintigraphy.
- A subset of 286 patients underwent systematic screening for ATTR-CM.
Main Results:
- Clinically recognized ATTR-CM was found in 1.3% of the general cohort.
- Systematic screening identified ATTR-CM in 6.3% of patients.
- Prevalence was higher in men (10.1%) than women (2.2%) and increased significantly with age, reaching 21% in those 90 years and older.
Conclusions:
- ATTR-CM is prevalent in patients presenting with HFpEF and ventricular wall thickening, especially older men.
- Systematic screening significantly increases ATTR-CM detection rates.
- Diagnosing ATTR-CM in HFpEF patients allows for targeted therapy and improved patient management.
Importance:
Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized.
Objective:
To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening.
Design, Setting, And Participants:
This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort).
Exposures:
Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis.
Main Outcomes And Measures:
The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex.
Results:
A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002).
Conclusions And Relevance:
In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.
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