Endothelial-dependent coronary artery dilation and increased blood flow in healthy subjects, and their absence in CAD patients, can now be directly visualized and quantified noninvasively. Local coronary endothelial function differs between severely and mildly diseased arteries in a given CAD patient. This novel, safe method may offer new insights regarding the importance of local coronary endothelial function and improved risk stratification in patients at risk for and with known CAD.

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Background: Knowledge gaps remain in the epidemiology and clinical implications of myocardial injury in COVID-19. Our goal was to determine the prevalence and outcomes of myocardial injury in severe COVID-19 compared to acute respiratory distress syndrome (ARDS) unrelated to COVID-19. Methods: We included intubated COVID-19 patients from 5 hospitals between March 15 and June 11, 2020 with troponin levels assessed. We compared them to patients from a cohort study of myocardial injury in ARDS. We performed survival analysis with primary outcome of in-hospital death associated with myocardial injury. We performed linear regression to identify clinical factors associated with myocardial injury in COVID-19. Results: Of 243 patients intubated with COVID-19, 51% had troponin levels > upper limit of normal (ULN). Chronic kidney disease, lactate, ferritin and fibrinogen were associated with myocardial injury. Mortality was 22.7% among COVID-19 patients with troponin < ULN and 61.5% for those with troponin levels > 10xULN (P< 0.001). The association of myocardial injury with mortality was not statistically significant after adjusting for age, sex and multi-system organ dysfunction. Compared to non-COVID ARDS patients, patients with COVID-19 were older with higher creatinine and less favorable vital signs. After adjustment, COVID-19 was associated with lower odds of myocardial injury compared to non-COVID ARDS (OR 0.55 95% CI 0.36-0.84, P=0.005). Conclusions: Myocardial injury in severe COVID-19 is a function of baseline comorbidities, advanced age and multisystem organ dysfunction similar to traditional ARDS. The adverse prognosis of myocardial injury in COVID-19 relates largely to multisystem organ involvement and critical illness.

Background and Purpose-Left ventricular dysfunction (LVD) is associated with cardiovascular mortality. Its association with ischemic stroke has been mainly documented after myocardial infarction. The stroke risk associated with LVD, especially of mild degree, in the general population is unclear. The purpose of this study was to evaluate the relationship between LVD and ischemic stroke in a multiethnic cohort. Methods-LV systolic function was assessed by transthoracic 2-dimensional echocardiography in a subset of subjects from the Northern Manhattan Study (NOMAS), 270 patients with first ischemic stroke and 288 age-, gender-and race-matched community controls. LV ejection fraction was measured by a simplified cylinder-hemiellipsoid formula, and categorized as normal (Ͼ50%), mildly (41% to 50%), moderately (31% to 40%) or severely (Յ30%) decreased. The association between impaired ejection fraction and ischemic stroke was evaluated by logistic regression analysis after adjustment for established stroke risk factors. Results-LVD of any degree was more frequent in stroke patients (24.1%) than in controls (4.9%; PϽ0.0001), as was moderate/severe LVD (13.3% versus 2.4%; PϽ0.001). A decreased ejection fraction was associated with ischemic stroke even after adjusting for other stroke risk factors. The adjusted odds ratio for any degree of LVD was 3.92 (95% CI, 1.93 to 7.97). The adjusted odds ratio for mild LVD was 3.96 (95% CI, 1.56 to 10.01) and for moderate/severe LVD 3.88 (95% CI, 1.45 to 10.39). The association between LVD of any degree and stroke was present in all age, gender and race-ethnicity subgroups. Conclusions-LVD, even of mild degree, is independently associated with an increased risk of ischemic stroke. The assessment of LV function should be considered in the assessment of the stroke risk.

Background Coronary endothelial function (endoFx) is abnormal in patients with established coronary artery disease (CAD) and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the non-invasive assessment of both anatomic and functional (endoFx) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endoFx is related to measures of early atherosclerosis such as increased coronary wall thickness (CWT). Methods and Results Seventeen arteries in fourteen healthy adults and seventeen arteries in fourteen patients with non-obstructive CAD were studied. To measure endoFx, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor and changes in coronary cross-sectional area (CSA) and flow were measured. Black blood imaging was performed to quantify CWT and other indices of arterial remodeling. The mean stress-induced change in CSA was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2±6.8%, p<0.0001, n=17). Mean CWT was lower in healthy subjects (0.9±0.2mm) than in CAD patients (1.4±0.3mm, p<0.0001). In contrast to healthy subjects, stress-induced changes in CSA, a measure of coronary endoFx, correlated inversely with CWT in CAD patients (r= -0.73, p=0.0008). Conclusions There is an inverse relationship between coronary endothelial function and local CWT in CAD patients but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.

Hays AG, Iantorno M, Soleimanifard S, Steinberg A, Schär M, Gerstenblith G, Stuber M, Weiss RG. Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function. Am J Physiol Heart Circ Physiol 308: H1343-H1350, 2015. First published March 27, 2015 doi:10.1152/ajpheart.00023.2015.-Endothelial cell release of nitric oxide (NO) is a defining characteristic of nondiseased arteries, and abnormal endothelial NO release is both a marker of early atherosclerosis and a predictor of its progression and future events. Healthy coronaries respond to endothelial-dependent stressors with vasodilatation and increased coronary blood flow (CBF), but those with endothelial dysfunction respond with paradoxical vasoconstriction and reduced CBF. Recently, coronary MRI and isometric handgrip exercise (IHE) were reported to noninvasively quantify coronary endothelial function (CEF). However, it is not known whether the coronary response to IHE is actually mediated by NO and/or whether it is reproducible over weeks. To determine the contribution of NO, we studied the coronary response to IHE before and during infusion of N G -monomethyl-L-arginine (L-NMMA, 0.3 mg·kg Ϫ1 ·min Ϫ1 ), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies ϳ8 wk apart in healthy subjects and patients with coronary artery disease (CAD). Changes from rest to IHE in coronary cross-sectional area (%CSA) and diastolic CBF (%CBF) were quantified. L-NMMA completely blocked normal coronary vasodilation during IHE [%CSA, 12.9 Ϯ 2.5 (mean Ϯ SE, placebo) vs. Ϫ0.3 Ϯ 1.6% (L-NMMA); P Ͻ 0.001] and significantly blunted the increase in flow [%CBF, 47.7 Ϯ 6.4 (placebo) vs. 10.6 Ϯ 4.6% (L-NMMA); P Ͻ 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA (P Ͻ 0.0001) and CBF (P Ͻ 0.01). In conclusion, the normal human coronary vasoactive response to IHE is primarily mediated by NO. This noninvasive, reproducible MRI-IHE exam of NO-mediated CEF promises to be useful for studying CAD pathogenesis in low-risk populations and for evaluating translational strategies designed to alter CAD in patients. endothelial function; coronary artery disease; magnetic resonance imaging ENDOTHELIAL CELL RELEASE of nitric oxide (NO) is a defining characteristic of nondiseased vascular tissue; it inhibits platelet aggregation, attenuates inflammation, decreases cellular proliferation, and induces local vascular smooth muscle vasodilation (4). Most classic and novel cardiovascular risk factors converge to impair endothelial function, including dyslipidemia, insulin resistance, inflammation, tobacco abuse, and oxidative stress, as well as hemodynamic and genetic factors (4, 33). Critically, endothelial dysfunction is a marker for subclinical disease, an independent predictor of adverse cardiovascular events, and a potential target for medical interventions (21,24,28).Traditionally, coronary endothelial function (CEF) is assessed by the directi...

COVID-19 is associated with myocardial injury caused by ischemia, inflammation, or myocarditis. Cardiovascular magnetic resonance (CMR) is the noninvasive reference standard for cardiac function, structure, and tissue composition. CMR is a potentially valuable diagnostic tool in patients with COVID-19 presenting with myocardial injury and evidence of cardiac dysfunction. Although COVID-19–related myocarditis is likely infrequent, COVID-19–related cardiovascular histopathology findings have been reported in up to 48% of patients, raising the concern for long-term myocardial injury. Studies to date report CMR abnormalities in 26% to 60% of hospitalized patients who have recovered from COVID-19, including functional impairment, myocardial tissue abnormalities, late gadolinium enhancement, or pericardial abnormalities. In athletes post–COVID-19, CMR has detected myocarditis-like abnormalities. In children, multisystem inflammatory syndrome may occur 2 to 6 weeks after infection; associated myocarditis and coronary artery aneurysms are evaluable by CMR. At this time, our understanding of COVID-19–related cardiovascular involvement is incomplete, and multiple studies are planned to evaluate patients with COVID-19 using CMR. In this review, we summarize existing studies of CMR for patients with COVID-19 and present ongoing research. We also provide recommendations for clinical use of CMR for patients with acute symptoms or who are recovering from COVID-19.

Diny et al. report a pathogenic role for eosinophils in autoimmune myocarditis and dilated cardiomyopathy. Eosinophils are required for progression of myocarditis to dilated cardiomyopathy and drive severe disease when present in large numbers. Activated cardiac eosinophils mediate this process through IL-4.