IMPORTANCE Hereditary transthyretin (TTR) amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant is an autosomal-dominant disorder that causes heart failure in elderly individuals of African ancestry. The clinical associations of carrying the variant, its effect in other African ancestry populations including Hispanic/Latino individuals, and the rates of achieving a clinical diagnosis in carriers are unknown. OBJECTIVE To assess the association between the TTR V122I variant and heart failure and identify rates of hATTR-CM diagnosis among carriers with heart failure. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of carriers and noncarriers of TTR V122I of African ancestry aged 50 years or older enrolled in the Penn Medicine Biobank between 2008 and 2017 using electronic health record data from 1996 to 2017. Case-control study in participants of African and Hispanic/Latino ancestry with and without heart failure in the Mount Sinai BioMe Biobank enrolled between 2007 and 2015 using electronic health record data from 2007 to 2018. EXPOSURES TTR V122I carrier status. MAIN OUTCOMES AND MEASURES The primary outcome was prevalent heart failure. The rate of diagnosis with hATTR-CM among TTR V122I carriers with heart failure was measured. RESULTS The cross-sectional cohort included 3724 individuals of African ancestry with a median age of 64 years (interquartile range, 57-71); 1755 (47%) were male, 2896 (78%) had a diagnosis of hypertension, and 753 (20%) had a history of myocardial infarction or coronary revascularization. There were 116 TTR V122I carriers (3.1%); 1121 participants (30%) had heart failure. The case-control study consisted of 2307 individuals of African ancestry and 3663 Hispanic/Latino individuals; the median age was 73 years (interquartile range, 68-80), 2271 (38%) were male, 4709 (79%) had a diagnosis of hypertension, and 1008 (17%) had a history of myocardial infarction or coronary revascularization. There were 1376 cases of heart failure. TTR V122I was associated with higher rates of heart failure (cross-sectional cohort: n = 51/116 TTR V122I carriers [44%], n = 1070/3608 noncarriers [30%], adjusted odds ratio, 1.7 [95% CI, 1.2-2.4], P = .006; case-control study: n = 36/1376 heart failure cases [2.6%], n = 82/4594 controls [1.8%], adjusted odds ratio, 1.8 [95% CI, 1.2-2.7], P = .008). Ten of 92 TTR V122I carriers with heart failure (11%) were diagnosed as having hATTR-CM; the median time from onset of symptoms to clinical diagnosis was 3 years. CONCLUSIONS AND RELEVANCE Among individuals of African or Hispanic/Latino ancestry enrolled in 2 academic medical center-based biobanks, the TTR V122I genetic variant was significantly associated with heart failure.

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Stress Rb-82 PET provides significant and clinically meaningful effective risk stratification of women and men, supporting this modality as an alternative to comparative imaging modalities. Rb-82 PET findings were particularly helpful at identifying high-risk, older women.

SUMMARY1. The breathing pattern, that is the relation between tidal volume (VT) and the inspiratory (T1) and expiratory (TE) durations, has been studied for individual breaths (forty in each steady state).2. Five healthy subjects were studied in steady-state exercise on a bicycle ergometer breathing air; three of them were also studied in hypercapnia, at rest and during exercise, and two of them also during exercise on a treadmill.3. Tidal volume and respiratory frequency both increased with work load. The increase in frequency was largely due to a progressive decrease in TE; T, also decreased. 5. A simple model of the respiratory cycle which fits both the observed mean and breath-by-breath patterns and which involves no new assumptions is presented.

Objective Minimal data are available regarding the long-term mortality risk of subclinical atherosclerosis using coronary artery calcium (CAC) scoring among patients with a family history (FH) of coronary artery disease (CAD). The aim of the present analysis was to assess the prognostic utility of CAC scoring among cohorts of young and older patients with and without a FH of CAD. Methods A total of 9715 consecutive asymptomatic patients, free of known CAD, underwent CAC scoring for cardiovascular risk assessment. The primary end point was all-cause mortality, with a median follow-up of 14.6 years. Unadjusted and risk-factor adjusted Cox proportional hazard modelling was employed. We calculated the area under the curve (AUC) from receiver operating characteristics analysis.Results 15-year all-cause mortality rates ranged from 4.7% to 25.0% for FH patients and from 5.0% to 38.0% for non-FH patients with CAC scores of 0 to >400 ( p<0.0001). Effect modification by age altered the mortality risk of CAC among FH patients. For patients aged >60 years with FH of CAD, there was a significant improvement in the AUC with CAC over CAD risk factors (AUC: 0.539 vs 0.725, p<0.001). No such improvement was observed in FH patients aged <60 years (AUC: 0.636 vs 0.626, p=0.67). Conclusion CAC effectively stratified mortality risk of patients with and without FH of CAD. However, for younger and lower-risk FH cohorts, CAC screening did not provide additive prognostic information beyond that of the traditional cardiac risk factors.