Importance of Increased Arterial Resistance in Risk Prediction in Patients with Cardiovascular Risk Factors and Degenerative Aortic Stenosis

Background: Cardiovascular disease is a leading cause of heart failure (HF) and major adverse cardiac and cerebral events (MACCE). Objective: To evaluate impact of vascular resistance on HF and MACCE incidence in subjects with cardiovascular risk factors (CRF) and degenerative aortic valve stenosis (DAS). Methods: From January 2016 to December 2018, in 404 patients with cardiovascular disease, including 267 patients with moderate-to-severe DAS and 137 patients with CRF, mean values of resistive index (RI) and pulsatile index (PI) were obtained from carotid and vertebral arteries. Patients were followed-up for 2.5 years, for primary outcome of HF and MACCE episodes. Results: RI and PI values in patients with DAS compared to CRF were significantly higher, with optimal cut-offs discriminating arterial resistance of ≥0.7 for RI (sensitivity: 80.5%, specificity: 78.8%) and ≥1.3 for PI (sensitivity: 81.3%, specificity: 79.6%). Age, female gender, diabetes, and DAS were all independently associated with increased resistance. During the follow-up period, 68 (16.8%) episodes of HF-MACCE occurred. High RI (odds ratio 1.25, 95% CI 1.13–1.37) and PI (odds ratio 1.21, 95% CI 1.10–1.34) were associated with risk of HF-MACCE. Conclusions: An accurate assessment of vascular resistance may be used for HF-MACCE risk stratification in patients with DAS.

Abstract 13764: Chronic Electronic Cigarette Vapor Exposure Leads to Impaired Cardiac Function in Experimental Rat Myocardial Ischemia/reperfusion Model

Background: We investigated the effects of long-term electronic cigarettes with nicotine (eC) vaping on cardiac function and structure in rats subjected to myocardial infarction (MI). Methods: After 8 weeks of exposure to either pure air (n=20) or eC (n=20), rats were anesthetized, and were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Cardiac function was assessed by echocardiogram and pressure measurements of the aorta and left ventricle (LV). Cardiac output (CO) was measured using a thermodilution catheter. At 3 hours of reperfusion, ischemic risk zone, no-reflow and infarct areas were determined. Results: Prior to coronary artery occlusion, chronic eC exposure was associated with a lower CO (45 ± 2 ml/min ) compared to air (55 ± 4 ml/min; p<0.05)) and a decrease in +dP/dt (5226 ± 294 mmHg/s versus 6062 ± 271 mmHg/s; p=0.05). After 30 minutes of coronary occlusion and 2.5 hours of reperfusion, CO and LV + dp/dt fell in both groups, but remained significantly lower in eC compared to the pure air group (Table). LV systolic and diastolic dimensions were significantly smaller in the E-Cig group compared to the air group. Systolic and diastolic anterior LV wall thickness were significantly thicker in the eC group after reperfusion. The ischemic risk size was comparable between the 2 groups. MI size was 48.8 ± 4.8% of the ischemic risk zone in the air group and 45.4 ± 4.4 % in the eC group (p=0.603). The area of no reflow was 26.7 ± 4.0% of the ischemic risk zone in the air group and 21.1 ± 3.5% in the E-C group (p=0.298). Chronic eC exposure did not change heart rate and blood pressure, but the significantly increased the systemic arterial resistance. Conclusions: Chronic exposure to eC significantly impaired cardiac function in rats prior to and during ischemia/reperfusion, increased arterial resistance, but did not increase infarct size or no-reflow zone. Increased LV wall thickness of the risk zone suggested that eC may have increased edema.

Abstract WP267: Association Between Arterial Resistance and Subtypes of Cerebral Small Vessel Disease

Introduction: Increased arterial resistance is a potential pathophysiological mechanism in the pathogenesis of cerebral small vessel disease (cSVD). In this study, we aimed to investigate the association between puslatility index (PI) representing cerebral arterial resistance and subtypes of cSVD in patients with stroke due to small vessel occlusion (SVO). Hypothesis: Pattern of increased arterial resistance may be different between individual subtypes of cSVD. Methods: We included consecutive patients with SVO between 2010 and 2013. White matter hyperintensity (WMH) volume was rated using semi-automated quantitative methods. And the presence of old lacunar infarct (OLI), cerebral microbleed (CMB), or enlarged perivascular space (EPVS) was also evaluated. The relationship between PI, measured with transcranial Doppler sonography in each middle cerebral artery, and subtypes/burden of cSVD was analyzed in the relevant hemisphere. Results: A total of 206 patients with 412 hemispheres were included (mean age: 64 years, male: 68%). In multivariable analysis, PI was positively associated with the WMH volume [beta = 1.372, 95% confidence interval (CI) = 0.624 to 2.120, P < 0.001] after adjusting confounders. PI was also related to the presence of OLI (adjusted odds ratio = 11.37, 95% CI = 2.55-48.56, P = 0.001), however this relationship was not significant in CMB or EPVS. Regarding to the cSVD burden, PI increased according to the WMH tertiles ( P for trend < 0.001), and burden of OLI ( P for trend = 0.004) in a dose-response manner. Conclusion: Association of cerebral arterial resistance is different between subtypes of cSVD, which is suggestive of underlying pathophysiological difference. Simple measure of PI seems to be useful to estimate the arterial resistance and the burden of cSVD.

Fetal growth outcomes following peri-implantation exposure of Long-Evans rats to noise and ozone differ by sex

Background Exposure to air pollution and high levels of noise have both been independently associated with the development of adverse pregnancy outcomes including low birth weight. However, exposure to such environmental stressors rarely occurs in isolation and is often co-localized, especially in large urban areas. Methods The purpose of this study was to compare the effects of combined exposure to noise (N) or ozone (O3), compared to either exposure alone. Long-Evans dams were exposed to air or 0.4 ppm ozone for 4 h on gestation day (GD) 5 and 6, coinciding with implantation receptivity. A subset of dams from each exposure group was further exposed to intermittent white noise (~ 85 dB) throughout the dark cycle following each inhalation exposure (n = 14 − 16/group). Uterine artery ultrasound was performed on GD 15 and 21. Fetal growth characteristics and indicators of placental nutrient status were measured at GD 21. Results Exposure to ozone + quiet (O3 + Q) conditions reduced uterine arterial resistance at GD 15 compared to air + quiet (A + Q) exposure, with no further reduction by GD 21. By contrast, exposure to air + noise (A + N) significantly increased uterine arterial resistance at both GD 15 and 21. Notably, while peri-implantation exposure to O3 + Q conditions reduced male fetal weight at GD 21, this effect was not observed in the air + noise (A + N) or the ozone + noise (O3 + N) exposure groups. Fetal weight in female offspring was not reduced by ozone exposure alone (O3 + Q), nor was it affected by air + noise (A + N) or by combined ozone + noise (O3 + N) exposure. Conclusions These data indicate that exposure to ozone and noise differentially impact uterine blood flow, particularly at mid-gestation, with only ozone exposure being associated with sex-dependent fetal growth retardation in male offspring.

Pressure and Volume Characteristics of the Left Ventriclе in Its Diastolic and Systolic Dysfunction

The Aimof the study was a detailed investigation of pressure volume-loop (PV-loop) curves in the rat heart during development of doxorubicin cardiomyopathy.Materials and methods. Cardiomyopathy in rats has been developed after 4 weeks doxorubicin administration (2 mg / kg weekly).Results. Echocardiographic study of rats in 8 weeks from onset of doxorubicin administration showed preponderance of systolic dysfunction (67 %) with decrease of left ventricular (LV) ejection fraction (EF) by 30 %. Simultaneous registration of LV pressure and volume showed that diastolic LV volume was preserved in doxorubicin-treated rats due to considerable lengthening of the diastole, the heart rate was reduced by 22 %. These hearts also showed slowing of relaxation, reduced maximal rate of pressure development and stroke work, as well as significant reduction in peripheral arterial resistance. Diastolic dysfunction differed from the systolic one by normal systolic EF and preserved LV contractility index as well as lower diastolic LV pressure throughout the diastole.Conclusions. Based on these data, four compensatory mechanisms associated with cardiomyopathy were distinguished - 1) slowing of myocardial relaxation, prolonging myofibrillar active state, 2) reduction of peripheral arterial resistance for easier LV ejection, 3) heart rate reduction, prolonging diastolic pause and thus facilitating better LV filling and 4) increased pressure in the small circle, also contributing to the LV rapid filling.