Abstract Body (Do not enter title and authors here): Background: Transthyretin cardiac amyloidosis (ATTR-CA) is an under-diagnosed but treatable cause of heart failure (HF) in older individuals. ATTR-CA occurs in the context of normal wild-type (ATTRwt-CA) or an abnormal inherited (ATTRv-CA) TTR gene variant. The most common inherited TTR variant (V142I, historically known as V122I) that causes ATTRv-CA occurs in 3.4% of self-identified Black Americans or approximately 1.5 million people. While V142I has definitively been associated with excess morbidity and mortality in population studies, the prevalence of ATTR-CA among older Black or Hispanic patients with HF as well as the proportions of those with ATTRv-CA and ATTRwt-CA are unknown.

Methods: The SCAN-MP study was a prospective, NIH/NHLBI-funded, observational, multi-center cohort of 650 self-identified Black or Caribbean Hispanic individuals ≥ 60 years of age with HF. Participants were enrolled between 2019 - 2024 and those with normal left ventricular (LV) wall thickness or left ventricular ejection faction (LVEF) < 30% were excluded. ATTR-CA was determined by Tc-99m-pyrophosphate scintigraphy with blood testing to exclude light-chain amyloidosis and genotyping to determine TTR gene variant. Echocardiographic, biochemical, physical performance, and symptom burden data were collected.

Results: The median age was 73 years (IQR 66-80y), 50.6% were women, 71.4% identified as Black, median LV wall thickness was 13 mm (IQR 12-14mm), and median LVEF was 61% (IQR 55-67%). Overall prevalence of ATTR-CA was 6.5% (95% CI 4.6-8.5) of whom 60.5% were ATTRwt-CA and 39.5% were ATTRv-CA due to V142I. The overall prevalence of the V142I allele was 5.6% and of those 45.5% had ATTRv-CA. Prevalence of ATTR-CA was 8.2% (95% CI 5.2-11.2) in men and was 5.0% (95% CI 2.6-7.3) in women, p=0.10. Prevalence of ATTR-CA was 8.3% (95% CI 5.8-10.9) in Black and 2.2% (95% CI 0.1-4.2) in Hispanic participants, p<0.01. Prevalence of ATTR-CA among Black participants age ≤75y was 3.9% (95% CI 1.6- 6.1) while it was 15.8% (95% CI 10.3-21.3) among those >75y, p<0.0001. Among Black male participants >75y, the prevalence of ATTR-CA was 20% (95% CI 10.6-29.4).

Conclusions: ATTR-CA is a commonly encountered cause of HF in older Black individuals with HF, and particularly in men over 75 years of age. Less than half of V142I carriers had adjudicated ATTR-CA and 60.5% of all cases were ATTRwt-CA, indicating that a genotype-first approach would miss a large portion of affected individuals.