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Background: Circulating Angiogenic Cells (CAC) are known to aid in endothelial repair and are a promising marker of vascular function. Electronic Nicotine Delivery Systems (ENDS) have been hypothesized to impact vascular health, however the association between ENDS and CACs is unknown. Hypothesis: We hypothesize that ENDS use, sole or dual, will be significantly associated with CAC levels. Methods: We analyzed CAC levels of 314 human participants enrolled in the Cardiovascular Injury due to Tobacco Use study, which is a multi-center cross-sectional study of healthy participants 21-45 years age, without known cardiovascular disease or cardiovascular disease risk factors. Four study groups were determined a priori - non-smokers (n=62), sole cigarette users (n=207), sole ENDS users (n=17), and dual users (cigarette and ENDS) (n=28). A total of 15 CACs were measured via a standardized flowcytometry protocol using four cell surface markers - CD146 (endothelial), CD34 (stem cell), CD45 (leukocyte), and ACC133 (early progenitor/stem cell). Regression analysis was conducted using a General Linear Model with gamma distribution and log-link. Model was adjusted for age, sex, race, ethnicity, and enrollment site. Results: Among sole ENDS users, two CACs were significantly higher and four CACs were significantly lower, as compared to referent non-smokers (all P Conclusion: CACs are sensitive to ENDS use, including dual use. Although CACs with endothelial surface markers were most commonly associated with ENDS/dual use, CACs with stem and early progenitor surface markers were also associated with ENDS/dual use. CACs are promising biomarkers of vascular function and further research is needed to quantify the effect of individual CAC on vascular function.

Endothelial-dependent coronary artery vasoreactivity is an important indicator of vascular function and is traditionally measured invasively. We hypothesized that coronary vasoreactivity can be measured non-invasively and abnormal function detected using high-field MRI. We studied 16 healthy adults (mean age ± SD 41.1±14.1 years, seven men) and eight patients with coronary artery disease (CAD, mean age 56.6±11.3, two men). To measure endothelial-dependent vasoreactivity, 3T coronary MRI was performed before and during continuous isometric hand-grip exercise, a known endothelial-dependent stressor. Cross-sectional coronary artery area and peak diastolic coronary flow velocities were quantified. In healthy adults, coronary arteries significantly dilated and increased in flow velocity with stress (baseline vs. stress area: 13.0±3.0 vs.14.9±4.1mm2, p . We provide first evidence that MRI and isometric handgrip exercise, an established endothelial-dependent stressor, non-invasively detects significant changes in two common indices of coronary endothelial vasoreactivity: coronary artery area and flow velocity. This novel technique demonstrates physiologic coronary artery vasodilation and increased flow velocity in healthy subjects in response to handgrip stress, and their pathologic absence in patients with CAD. Figure 1. Percent change in coronary artery area and peak diastolic coronary flow velocity from baseline to stress (isometric handgrip exercise) in healthy adults (n=16) and CAD patients (n=8). (*,† p

Background: Prior studies demonstrate an association between specific β-adrenergic receptor polymorphisms and clinical outcomes in patients with chronic heart failure and following an acute coronary syndrome. The mechanism may relate to an effect on left ventricular (LV) remodeling. We hypothesized that β-adrenergic receptor polymorphisms predict LV remodeling after acute ST elevation myocardial infarction (STEMI). Methods: We assessed the presence of β-1 and β-2 adrenergic receptor polymorphisms in 122 patients after their first STEMI enrolled in a single-center randomized, double-blind placebo controlled trial of L-arginine vs. placebo, 91% of whom received successful early reperfusion therapy. All patients were treated with a beta-1 receptor antagonist and underwent baseline (mean 5.9 days following STEMI) and 6-month LV volume evaluation using gated blood pool imaging. Univariate and multivariate linear and logistic regressions were used to assess the relationships between the polymorphisms, β1 Arg389Gly, β1 Ser49Gly, β2 Gly16Arg and β2 Gly27Glu and the six-month changes in LV volumes. The top quintiles of LV end-systolic (ESV) and end-diastolic (EDV) 6-month volume increases and LV ejection fraction decrease were compared to the lower quintiles in the logistic regression analyses. Results: The polymorphisms β1 Arg389Gly, β1 Ser49Gly, β2 Gly16Arg were not associated LV remodeling. However, the 25% of patients homozygous for the β2 Glu27 variant were 5.2 times more likely to have an increase in 6-month ESV than those who had the Gln27 variant (OR 5.2, 95%CI 1.4 –19.0). Multiple linear regression analyses demonstrated that absolute ESV at six months was 19 ml greater (p = 0.02) and EDV was 21 ml greater (p = 0.01) in post STEMI patients with the β2 Glu27 polymorphism compared to the wild type or heterozygous patients. Conclusions: Increased LV volumes post-STEMI are associated with an increased risk of heart failure and death. The common β2 receptor polymorphism, Glu27Glu, is associated with increased odds of adverse LV remodeling in patients treated with a beta-one receptor antagonist. Whether treatment with a non-specific β-adrenergic receptor blocker guided by this genetic polymorphism ameliorates the effect requires further study.

A distressed woman hailed a car for assistance several blocks from our institution. Upon arrival at the Emergency Department, she was unresponsive. Telemetry demonstrated ventricular fibrillation, and she was defibrillated to sinus rhythm with ECG, as shown in Figure 1. She was taken for emergent cardiac catheterization with a heart rate of 117 bpm and blood pressure of 95/55 mm Hg. Coronary angiography revealed no stenosis or flow abnormalities. During catheterization, ST-segment elevation resolved and …