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ilated cardiomyopathy (DCM) is a nonischemic, nontoxic, noninfectious, or nonvalvular heart muscle disease characterized by left ventricular or biventricular systolic dysfunction. 1,2 Typical onset of the disease is in the fourth or fifth decade of life and it affects predominantly male individuals with a male-to-female ratio of 3:1. 2 Although a specific cause might be unknown in a non-negligible number of patients, to date, more than one-third of familial forms and approximately 25% of sporadic cases have positive genetic testing for pathogenic (P) or likely pathogenic (LP) variants. [3][4][5][6] Recent evidence highlights the importance of specific genotypes in determining the prognosis of patients with DCM, either alone or in combination with environmental factors. [7][8][9][10][11] Contemporary analyses highlight that DCM is increasingly diagnosed in older patients 12 and a late-onset (ie, age >60 years) form of DCM could differ from more typical-onset DCM presentations. 13 However, the genetic background and the prognostic impact of genetic characterization among patients with DCM presenting who are older than 60 years are largely unknown.The aim of the present study was to investigate the genetic background and the natural history of a large international cohort of individuals with DCM presenting in individuals older than 60 years to assess the importance of genetic testing in those patients. Methods Study PopulationFor the present study, we included all consecutive patients with DCM older than 60 years at the time of diagnosis (ie, lateonset DCM), with available genetic testing analysis, from 7 international tertiary centers worldwide: Cardiovascular IMPORTANCE Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM).OBJECTIVE To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM. DESIGN, SETTING, AND PARTICIPANTSA population of patients with late-onset DCM who had undergone genetic testing in 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as the presence of pathogenic or likely pathogenic (P/LP) variants. MAIN OUTCOMES AND MEASURESThe study outcome was all-cause mortality.RESULTS A total of 184 patients older than 60 years (103 female [56%]; mean [SD] age, 67 [6] years; mean [SD] left ventricular ejection fraction, 32% [10%]) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin-truncating variants were the most prevalent (present in 46 [25%] of the total population and accounting for 46 [69%] of all genotype-positive patients). During a median (interquartile range) follow-up of 42 (10-115) months, 23 patients (13%) died; 17 (25%) of these were carriers o...

SUMMARY The morphologic characteristics at coronary arteriography of systolic narrowing of the left anterior descending coronary artery (LAD) were evaluated in 14 patients. Six patients had systolic narrowing of the LAD not associated with other cardiac abnormalities (group A) and eight patients had systolic narrowing of the LAD associated with hypertrophic cardiomyopathy (group B). Patients in group A showed a smooth and progressive constriction of the vessel up to the point of maximal stenosis, giving it a "rat-tail" appearance. There was no systolic narrowing of septal branches or of other epicardial vessels in this group. In patients of group B, systolic narrowing of the LAD had a "saw-fish" appearance. Seven patients had systolic narrowing of the septal branches, and five had systolic narrowing of other epicardial vessels. These data indicate that systolic narrowing of the LAD in patients with hypertrophic cardiomyopathy differs angiographically from systolic narrowing due to an intramural course of a part of the vessel (as in group A patients). We postulate that in patients with hypertropic cardiomyopathy, fiber hypertrophy and disarray in the vicinity of the coronary vessels is responsible for the morphology and the widespread distribution of systolic narrowing. SYSTOLIC NARROWING ("milking" or "bridging") of the left anterior descending coronary artery (LAD) at angiography is a well-known phenomenon.'-5 It occurs both as an isolated finding at cardiac catheterization and in patients with arteriosclerotic coronary artery disease, left ventricular hypertrophy and hypertrophic cardiomyopathy. The angiographic morphology of systolic narrowing of the LAD has not been analyzed in relation to the underlying heart disease, and it is not known whether the same pathologic basis accounts for systolic narrowing of the LAD in patients with or without heart disease. We studied the morphologic aspect at angiography of systolic narrowing of the LAD in six patients without hypertrophic cardiomyopathy, left ventricular hypertrophy or any other form of heart disease and in eight patients with hypertrophic cardiomyopathy. Methods PatientsWe reviewed the records of 520 patients who underwent cardiac catheterization and coronary angiography. In six patients with otherwise normal coronary arteries and no associated cardiovascular abnormalities part of the LAD had an intramural course that produced systolic narrowing (group A. patients 1-6). In eight of 15 patients with hypertrophic cardiomyopathy and otherwise normal coronary arteries, systolic narrowing of the LAD was demonstrated by selective coronary arteriograms (group B, patients 7-14). Hypertrophic cardiomyopathy was diagnosed from the characteristic echocardiogram, left ventriculogram and an intraventricular pressure gradient at rest or after provocation by induced extrasystoles. In one patient with characteristic electrocardiographic and angiographic findings of hypertrophic cardiomyopathy and no gradient at rest, provocation was not attempted. In one patient, an intra...

ObjectiveWe examined the association between stay-at-home order implementation and the incidence of COVID-19 infections and deaths in rural versus urban counties of the United States.DesignWe used an interrupted time-series analysis using a mixed effects zero-inflated Poisson model with random intercept by county and standardised by population to examine the associations between stay-at-home orders and county-level counts of daily new COVID-19 cases and deaths in rural versus urban counties between 22 January 2020 and 10 June 2020. We secondarily examined the association between stay-at-home orders and mobility in rural versus urban counties using Google Community Mobility Reports.InterventionsIssuance of stay-at-home orders.Primary and secondary outcome measuresCo-primary outcomes were COVID-19 daily incidence of cases (14-day lagged) and mortality (26-day lagged). Secondary outcome was mobility.ResultsStay-at-home orders were implemented later (median 30 March 2020 vs 28 March 2020) and were shorter in duration (median 35 vs 54 days) in rural compared with urban counties. Indoor mobility was, on average, 2.6%–6.9% higher in rural than urban counties both during and after stay-at-home orders. Compared with the baseline (pre-stay-at-home) period, the number of new COVID-19 cases increased under stay-at-home by incidence risk ratio (IRR) 1.60 (95% CI, 1.57 to 1.64) in rural and 1.36 (95% CI, 1.30 to 1.42) in urban counties, while the number of new COVID-19 deaths increased by IRR 14.21 (95% CI, 11.02 to 18.34) in rural and IRR 2.93 in urban counties (95% CI, 1.82 to 4.73). For each day under stay-at-home orders, the number of new cases changed by a factor of 0.982 (95% CI, 0.981 to 0.982) in rural and 0.952 (95% CI, 0.951 to 0.953) in urban counties compared with prior to stay-at-home, while number of new deaths changed by a factor of 0.977 (95% CI, 0.976 to 0.977) in rural counties and 0.935 (95% CI, 0.933 to 0.936) in urban counties. Each day after stay-at-home orders expired, the number of new cases changed by a factor of 0.995 (95% CI, 0.994 to 0.995) in rural and 0.997 (95% CI, 0.995 to 0.999) in urban counties compared with prior to stay-at-home, while number of new deaths changed by a factor of 0.969 (95% CI, 0.968 to 0.970) in rural counties and 0.928 (95% CI, 0.926 to 0.929) in urban counties.ConclusionStay-at-home orders decreased mobility, slowed the spread of COVID-19 and mitigated COVID-19 mortality, but did so less effectively in rural than in urban counties. This necessitates a critical re-evaluation of how stay-at-home orders are designed, communicated and implemented in rural areas.