{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T03:51:00Z","timestamp":1794282660306,"version":"4.9.0"},"reference-count":21,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:sec id=\"ab-hoi220030-4\"><jats:title>Importance<\/jats:title><jats:p>Transthyretin amyloid cardiomyopathy (ATTR-CM) is a form of heart failure (HF) with preserved ejection fraction (HFpEF). Technetium Tc 99m pyrophosphate scintigraphy (PYP) enables ATTR-CM diagnosis. It is unclear which patients with HFpEF have sufficient risk of ATTR-CM to warrant PYP.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi220030-5\"><jats:title>Objective<\/jats:title><jats:p>To derive and validate a simple ATTR-CM score to predict increased risk of ATTR-CM in patients with HFpEF.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi220030-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>Retrospective cohort study of 666 patients with HF (ejection fraction\u2009\u2265\u200940%) and suspected ATTR-CM referred for PYP at Mayo Clinic, Rochester, Minnesota, from May 10, 2013, through August 31, 2020. These data were analyzed September 2020 through December 2020. A logistic regression model predictive of ATTR-CM was derived and converted to a point-based ATTR-CM risk score. The score was further validated in a community ATTR-CM epidemiology study of older patients with HFpEF with increased left ventricular wall thickness ([WT]\u2009\u2265\u200912 mm) and in an external (Northwestern University, Chicago, Illinois) HFpEF cohort referred for PYP. Race was self-reported by the participants. In all cohorts, both case patients and control patients were definitively ascertained by PYP scanning and specialist evaluation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi220030-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Performance of the derived ATTR-CM score in all cohorts (referral validation, community validation, and external validation) and prevalence of a high-risk ATTR-CM score in 4 multinational HFpEF clinical trials.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi220030-8\"><jats:title>Results<\/jats:title><jats:p>Participant cohorts included were referral derivation (n\u2009=\u2009416; 13 participants [3%] were Black and 380 participants [94%] were White; ATTR-CM prevalence\u2009=\u200945%), referral validation (n\u2009=\u2009250; 12 participants [5%]were Black and 228 participants [93%] were White; ATTR-CM prevalence\u2009=\u200948% ), community validation (n\u2009=\u2009286; 5 participants [2%] were Black and 275 participants [96%] were White; ATTR-CM prevalence\u2009=\u20096% ), and external validation (n\u2009=\u200966; 23 participants [37%] were Black and 36 participants [58%] were White; ATTR-CM prevalence\u2009=\u200939%). Score variables included age, male sex, hypertension diagnosis, relative WT more than 0.57, posterior WT of 12 mm or more, and ejection fraction less than 60% (score range \u22121 to 10). Discrimination (area under the receiver operating characteristic curve [AUC] 0.89; 95% CI, 0.86-0.92; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) and calibration (Hosmer-Lemeshow; \u03c7<jats:sup>2<\/jats:sup>\u2009=\u20094.6; <jats:italic>P<\/jats:italic>\u2009=\u2009.46) were strong. Discrimination (AUC \u2265 0.84; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001 for all) and calibration (Hosmer-Lemeshow \u03c7<jats:sup>2<\/jats:sup> \u2009=\u20092.8; <jats:italic>P<\/jats:italic>\u2009=\u2009.84; Hosmer-Lemeshow \u03c7<jats:sup>2<\/jats:sup> \u2009=\u20094.4; <jats:italic>P<\/jats:italic>\u2009=\u2009.35; Hosmer-Lemeshow \u03c7<jats:sup>2<\/jats:sup>\u2009=\u20092.5; <jats:italic>P<\/jats:italic>\u2009=\u2009.78 in referral, community, and external validation cohorts, respectively) were maintained in all validation cohorts. Precision-recall curves and predictive value vs prevalence plots indicated clinically useful classification performance for a score of 6 or more (positive predictive value \u226525%) in clinically relevant ATTR-CM prevalence (\u226510% of patients with HFpEF) scenarios. In the HFpEF clinical trials, 11% to 35% of male and 0% to 6% of female patients had a high-risk (\u22656) ATTR-CM score.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi220030-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>A simple 6 variable clinical score may be used to guide use of PYP and increase recognition of ATTR-CM among patients with HFpEF in the community. Further validation in larger and more diverse populations is needed.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2022.1781","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T15:02:34Z","timestamp":1662562954000},"page":"1036","source":"Crossref","is-referenced-by-count":130,"title":["A Simple Score to Identify Increased Risk of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1001","volume":"7","author":[{"given":"Daniel R.","family":"Davies","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Redfield","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Scott","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Minamisawa","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Department of Cardiovascular Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Grogan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Dispenzieri","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panithaya","family":"Chareonthaitawee","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amil M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramsey M.","family":"Wehbe","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh N. 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