Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that includes distinct subtypes with different pathophysiologies, genetics, and treatment. Distinguishing HFpEF due to transthyretin cardiac amyloidosis (ATTR-CA) is critical given its specific treatable pathophysiology. Obesity is a common driver of HFpEF, but it has been noted clinically that low body mass index (BMI) is a common finding in ATTR-CA. Methods: A single center, retrospective study of patients undergoing 99mTc-pyrophosphate (PYP) scans from 2010-2019 was analyzed for BMI association with ATTR-CA and the Val122Ile variant. BMI differences were prospectively evaluated in the ongoing multicenter Screening for Cardiac Amyloidosis Using Nuclear Imaging for Minority Populations (SCAN-MP) study. The association of BMI with ATTR-CA/Val122Ile was compared by Wilcoxon rank sum analysis and combined with age, sex, and maximum LV wall thickness in a multivariable logistic regression in both the retrospective and SCAN-MP cohorts. Results: In the retrospective analysis, BMI (in kg/m 2 ) among those with ATTR-CA/Val122Ile (n=198, 40%) was lower (25.8, IQR 23.4-28.9) than in other patients (27.1, IQR 23.9-32.0) (p<0.001). In multivariable logistic regression, BMI < 30 (OR 2.60, 95% CI 1.49-4.54), remained independently associated with ATTR-CA/Val122Ile. In the first 221 patients enrolled in SCAN-MP, 18 (8%) had ATTR-CA (n=11) or were carriers of the Val122Ile variant (n=7) with negative PYP scans. Among those subjects, BMI was significantly lower (25.6 [IQR 24.3-28.3]) than in other patients (32.6 [27.9-38.1]) (p<0.001). BMI did not differ between ATTR-CA patients (27.5 [25.3-28.9]) and Val122Ile allele carriers with negative 99mTc-pyrophosphate scans (25.3 [24.3-28.2]). When combined with age, sex, and maximum LV wall thickness, BMI<30 (OR 11.8 [CI 2.47-56.14]) and maximum LV wall thickness (OR 1.38/mm [95% CI 1.10-1.74]) were associated with ATTR-CA/Val122Ile. Conclusions: Lower BMI is associated with a diagnosis of ATTR-CA/Val122Ile in heart failure with increased LV wall thickness and may be useful in selecting patients benefiting from evaluation for ATTR-CA.
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