HFpEF (heart failure with preserved ejection fraction) is a prevalent condition often accompanied by ventricular wall thickening and has no effective treatment. The HFpEF clinical pattern can be caused by transthyretin amyloid cardiomyopathy (ATTR-CM), which has a highly efficient treatment and is thought to be underrecognized. In patients with HFpEF with ventricular wall thickening, the prevalence of ATTR-CM was investigated without and with comprehensive screening. The population-based cohort research looked at ATTR-CM prevalence in 1,235 consecutive patients with HFpEF in southern Minnesota, both with and without systematic screening (consenting subgroup of cohort research,n=286). Validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater were all-important entrance criteria. There were no known ATTR-CM, contraindications to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in this community cohort of 1,235 patients. Between October 5, 2017, and March 9, 2020, two hundred ninety-five of the 884 patients gave their consent, and 286 were scanned (community screening cohort). For ATTR-CM diagnosis, medical records or technetium Tc 99m pyrophosphate scintigraphy and reflex tests are used. ATTR-CM prevalence by age, sex, and technique (clinical diagnosis or systematic screening). The trial included 1,235 patients, 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). 16 patients (1.3%; 95% CI, 0.7% -2.1%) in the community cohort without screening group had clinically diagnosed ATTR-CM. Men had a prevalence of 2.5% (95% CI: 1.4% -4.0%) while women had a prevalence of 0% (95% CI: 0.0% -0.6%). In the community screening cohort of 286 patients, 18 patients (6.3%; 95% CI, 3.8% -9.8%) developed ATTR-CM. The prevalence rose with age, rising from 0% in patients 60 to 69 years old to 21% in those 90 and older (P<.001). ATTR-CM was found in a significant proportion of patients of HFpEF with ventricular wall thickening in the community-based cohort analysis, particularly in older males. For a study, the researchers imply that a thorough evaluation can improve ATTR-CM diagnosis, resulting in therapeutically meaningful HFpEF phenotyping.