Coronary Cross-sectional Area Research Articles

Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI). We measured the changes in coronary cross-sectional area (CSA) and coronary blood flow during isometric handgrip exercise (IHE), an established endothelial-dependent stressor with smaller increases in CSA and coronary blood flow indicative of impaired CEF. We included 106 PWH and 82 individuals without HIV. Differences in demographic and clinical characteristics between PWH and individuals without HIV were explored using Pearson's χ2 test for categorical variables and Welch's t test for continuous variables. Linear regression models were used to examine the association between CEF and age. CEF was significantly lower in PWH as compared with individuals without HIV. Coronary endothelial dysfunction was also present at younger ages in PWH than in the individuals without HIV and there were significant differences in CEF between the PWH and individuals without HIV across age groups. Among the individuals without HIV, the percent changes in CSA were inversely related to age in unadjusted and adjusted models. There was no significant association between CEF and age in PWH. To the best of our knowledge, this is the first study to examine the relationship between age and CEF in PWH, and our results suggest that factors other than age significantly impair CEF in PWH across the life span.NEW & NOTEWORTHY This is the first study to examine the relationship between age and coronary endothelial function (CEF) in people with human immunodeficiency virus (HIV) (PWH). CEF was assessed using magnetic resonance imaging (MRI) in people with and without HIV. Although age and CEF were significantly inversely related in individuals without HIV, there was no association between age and CEF in PWH.

The role of HIV as a risk modifier for coronary endothelial function in young adults.

People living with HIV have an increased risk of cardiovascular disease (CVD). Although coronary endothelial function (CEF) is an early direct indicator of CVD, only a few studies have been able to interrogate CEF directly. Most studies have examined vascular endothelial function through indirect assessment of brachial flow-mediated dilatation (FMD). However, peripheral arteries are significantly larger and manifest atherogenesis differently from the coronary arteries, and so produce conflicting results. Additionally, none of these studies focused on young adults who acquired HIV perinatally or in early childhood. The present study investigates CEF in a unique population of young adults with lifelong HIV using direct magnetic resonance imaging (MRI) of coronary FMD (corFMD) with an in-house developed MRI-integrated isometric handgrip exercise system with continuous feedback and monitoring mechanisms (fmIHE). Young adults who acquired HIV perinatally or in early childhood (n = 23) and group-matched healthy participants (n = 12) completed corFMD-MRI with fmIHE. CorFMD was measured as the coronary cross-sectional area response to the fmIHE. In univariable and multivariable regression analysis, HIV status was a significant risk modifier. CD8+ T-cell count and smoking pack-years and their interaction with HIV status were independently associated with impaired coronary artery response to fmIHE. In people living with HIV, corFMD was significantly inversely correlated with CD8+ T-cells and smoking pack-years. In a multivariable regression analysis adjusted for age and body mass index, CD8+ T-cells and smoking and their interaction with HIV status remained significant independent predictors of coronary endothelial dysfunction. In this unique population of young adults, HIV status was a significant risk modifier, and immune activation and smoking were associated with decreased CEF, directly measured from the coronary vascular response to fmIHE. Management of CVD risk factors such as smoking and developing strategies that target immune activation in people living with HIV are warranted.

Evaluating the Arteriotomy Size of a New Sutureless Coronary Anastomosis Using a Finite Volume Approach.

The ELANA® Heart Bypass creates a standardized sutureless anastomosis. Hereby, we investigate the influence of arteriotomy and graft size on coronary hemodynamics. A computational fluid dynamics (CFD) model was developed. Arteriotomy size (standard 1.43mm2; varied 0.94-3.6mm2) and graft diameter (standard 2.5mm; varied 1.5-5.0mm) were independent parameters. Outcome parameters were coronary pressure and flow, and fractional flow reserve (FFR). The current size ELANA (arteriotomy 1.43 mm2) presented an estimated FFR 0.65 (39mL/min). Enlarging arteriotomy increased FFR, coronary pressure, and flow. All reached a maximum once the arteriotomy (2.80 mm2) surpassed the coronary cross-sectional area (2.69 mm2, i.e. 1.85mm diameter), presenting an estimated FFR 0.75 (46mL/min). Increasing graft diameter was positively related to FFR, coronary pressure, and flow. The ratio between the required minimal coronary diameter for application and the ELANAarteriotomy size effectuates a pressure drop that could be clinically relevant. Additional research and eventual lengthening of the anastomosis is advised.

Mean Coronary Cross-Sectional Area as a Measure of Arterial Remodeling Using Noncontrast CT Imaging in Persons With HIV.

Background Persons with HIV have a higher prevalence of coronary artery disease compared with their HIV-negative counterparts. Earlier identification of subclinical atherosclerosis may provide a greater opportunity for cardiovascular disease risk reduction. We investigated coronary cross-sectional area (CorCSA) by noncontrasted computed tomography imaging as a noninvasive measure of arterial remodeling among virally suppressed persons with HIV. Methods and Results We assessed 105 persons with HIV with a spectrum of cardiometabolic health. All participants underwent computed tomography imaging to assess the mean corCSA of the proximal left anterior descending artery and 28 participants underwent additional coronary computed tomography angiography. Partial Spearman rank correlations adjusted for cardiovascular disease risk factors were used to assess relationships of corCSA with anthropometric measurements, HIV-related factors, and plasma cytokines. Mean corCSA measured by noncontrast computed tomography and coronary computed tomography angiography were strongly correlated (ρ=0.91, P<0.0001). Higher mean corCSA was present in those with coronary artery calcium (P=0.005) and it correlated with participants' atherosclerotic cardiovascular disease risk score (ρ=0.35, P=0.01). After adjusting for established cardiovascular disease risk factors, we observed an inverse relationship between corCSA and CD4+ T-cell count (ρ=-0.2, P=0.047). Removal of age from the model strengthened the relationships between corCSA and antiretroviral therapy duration (from ρ=0.19, P=0.08 to ρ=0.3, P=0.01). CorCSA was also inversely correlated with plasma IL-10 (ρ=-0.25, P=0.03) but had no relationship with IL-6 (ρ=0.11, P=0.4) or IL-1β (ρ=0.08, P=0.5). Conclusions Positive coronary arterial remodeling, an imaging marker of subclinical atherosclerosis, is associated with a lower CD4 T-cell count, lower circulating IL-10, and possibly a longer antiretroviral therapy duration in persons with HIV. Registration Clinicaltrials.gov; Unique identifier: NCT04451980.

Coronary Endothelial Dysfunction in People Living With HIV Is Related to Body Fat Distribution.

People living with HIV (PLWH) on antiretroviral therapy (ART) are at increased risk of atherosclerotic disease. Abnormal adipose distribution is common in PLWH and may contribute to atherosclerosis. Because coronary artery endothelial function (CEF) is impaired in early atherosclerosis, predicts future cardiovascular events, and is reduced in PLWH, we investigated associations between body fat distribution and CEF in PLWH. Prospective cohort study. PLWH on stable ART underwent MRI to quantify CEF, measured as change in coronary cross-sectional area from rest to that during isometric handgrip exercise, an endothelial-dependent stressor. Abdominal visceral and subcutaneous fat area (axial L4 level) and liver fat fraction were quantified using MRI. Linear regression was used to determine associations between CEF and independent variables. Among 84 PLWH (52 ± 11 years; 33% women), mean cross-sectional area change was 0.74 ± 11.7%, indicating impaired CEF. On univariable regression analysis, CEF was inversely related to waist circumference (R = -0.31, P = 0.014), hip circumference (R = -0.27, P = 0.037), and subcutaneous fat area (R = -0.25, P = 0.031). We did not observe significant relationships between CEF and liver fat fraction, waist/hip ratio, or visceral fat area. On multivariable regression adjusted for age, sex, and race, CEF was associated with waist circumference, hip circumference, subcutaneous fat, and liver fat fraction. Waist and hip circumference and subcutaneous fat area are associated with impaired CEF, an established metric of abnormal vascular health in PLWH on stable ART, and may contribute to the increased rate of heart disease in this population.

Abstract EP65: Left Coronary Artery Cross-sectional Area And Traditional Cardiovascular Risk Factors Among Asymptomatic South Asians: Results From The MASALA Study

Background: South Asians have a higher atherosclerotic cardiovascular disease (ASCVC) burden than other race/ethnic groups that is not fully explained by traditional risk factors. Smaller coronary artery luminal diameter has been proposed as a potential reason for this higher risk among South Asians. A few studies have measured coronary artery diameter in South Asians demonstrating smaller coronary luminal diameter explained by smaller body size. However, these studies were done symptomatic individuals with high burden of coronary plaque, and stenosis and vascular tone is known to impact lumen diameter. No studies have measured coronary artery external diameters in asymptomatic South Asians. Methods: We analyzed data from 513 participants, between ages of 42 and 68 years, enrolled in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study (2016-2018). We analyzed coronary cross-sectional area (CSA) with thin slice non-contrast cardiac CT scans. This is equivalent to the outermost (adventitial) boundary measured with intravascular ultrasound of the coronary arteries. We computed mean CSA in the proximal and mid LAD segments perpendicular to the centerline of the vessel. We examined bivariate associations of traditional cardiovascular risk factors and coronary artery calcium (CAC) with LAD CSA. We then created multivariable models adjusted for age and sex to determine independent correlations with LAD CSA. Results: We used data from 285 men and 228 women with mean age 56±7 years. The overall mean LAD CSA was 22.8±6.8 mm 2 for men and 17.6±6.2 mm 2 for women. In bivariate analysis, higher LAD CSA was associated with male sex, and higher age, BMI, waist circumference, systolic and diastolic blood pressures, fasting glucose, total and LDL-cholesterol, CAC scores, statin medication use, and lower HDL-cholesterol. In multivariable models, only male sex (β 0.044, p&lt;0.001), hypertension (β 0.024, p&lt;0.001), and BMI (β 0.003 per kg/m 2 , p &lt;0.001) were significantly associated with LAD CSA. High CAC was marginally associated with LAD CSA (CAC&gt;100: B 0.015 p = 0.065) while age, diabetes, and cholesterol levels were not independently associated with LAD CSA. Conclusion: These preliminary results suggest that LAD CSA is highly correlated with sex, body size, and hypertension, but not other metabolic risk factors that are more aberrant among South Asians. Long-term follow-up will determine whether LAD CSA is an important contributor to cardiovascular disease events among South Asians.

Transluminal attenuation gradient derived from coronary CT angiography to predict ischemia in SPECT myocardial perfusion imaging: Effect of coronary cross-sectional area

BackgroundCoronary computed tomography angiography (CCTA)-based transluminal attenuation gradient (TAG) was suggested to determine the functional significance of a stenosis. However, evidence that TAG acquired by wide-volume scanners can assess the hemodynamic significance of stenosis assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is lacking. Moreover, coronary cross-sectional area may influence TAG. Hence, we aimed at assessing the diagnostic value of TAG to predict ischemia in SPECT-MPI and the correlation between TAG and the transluminal cross-sectional area gradient (TCG). MethodsPatients undergoing CCTA and SPECT-MPI for suspected coronary artery disease were included. TAG and TCG were calculated measuring the mean vessel attenuation and the cross-sectional area along major coronary vessels at 5-mm intervals. ResultsA total of 255 coronary arteries of 87 patients were included. TAG and TCG did not discriminate between coronary arteries with or without ischemia as assessed by SPECT-MPI (p = .44 and p = .25, respectively). The area under the curve to predict ischemia was not increased by adding TAG (0.88, 95% CI 0.83-0.92) or TCG (0.87, 95% CI 0.81-0.90) to CCTA alone (0.85, 95% CI 0.80-0.89). There was a significant correlation between TAG and TCG (r = 0.43; p < .001). ConclusionsCCTA-derived TAG and TCG do not offer any value in predicting ischemia assessed by SPECT-MPI. TAG is partly affected by differences in the coronary luminal area.

Abstract 11727: Sex Differences in Coronary Endothelial Dysfunction Among Women and Men Living With HIV

Introduction: Impaired coronary endothelial function (CEF) is a known predictor of cardiovascular (CV) events and occurs in people living with HIV. HIV+ women compared to men have worse CV outcomes, but prior studies include very few women. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to endothelial cell inflammation and is elevated in HIV+ men. CEF and PCSK9 are not well studied in women with HIV. Hypothesis: We hypothesize that HIV+ women have worse CEF and higher PCSK9 levels compared to risk factor matched HIV- women, and that CEF will be associated with PCSK9 in HIV+ women, similar to prior findings in HIV+ men. Methods: A total of 34 HIV+ women and 75 HIV+ men on stable highly active antiretroviral therapy and 17 HIV- women and 8 HIV- men underwent MRI to measure CEF (%change in coronary artery cross-sectional area (%CSA) and coronary blood flow (CBF) during isometric handgrip exercise, an endothelial dependent stressor). Serum PCSK9 samples were obtained on the day of MRI. Comparisons were performed using student’s t-test for normally distributed and Kruskal-Wallis test for data not normally distributed. Robust regression was used for the association of PCSK9 with CEF. Results: CEF was significantly reduced in HIV+ women compared to age-, race- and BMI-matched HIV- women (p&lt;0.001 for both %CSA and %CBF change Fig. 1A-B). Both HIV+ men and women had similarly impaired CEF. Women with HIV had significantly higher PCSK9 levels than women without HIV (Figure 1C). Further, PCSK9 was significantly inversely associated with %CSA (ß -0.03(-0.06,0.00); p=0.038) in men but not in women (ß -0.02(-0.04,0.01); p=0.26). Conclusions: Coronary endothelial dysfunction is present among HIV+ women as compared to risk factor matched HIV- women. HIV+ women have similarly depressed CEF as HIV+ men. With HIV, PCSK9 is not significantly associated with CEF, suggesting potential alternative mechanisms of impaired CEF in men and women with HIV.

Randomized Trial of Anti-inflammatory Medications and Coronary Endothelial Dysfunction in Patients With Stable Coronary Disease.

Aims: Inflammation plays a critical role in the pathogenesis of coronary artery disease (CAD), however the impact of anti-inflammatory therapies to reduce those processes which promote atherosclerosis in CAD patients is unknown. We aimed to test the hypothesis that anti-inflammatory approaches improve impaired coronary endothelial function (CEF), a driver of coronary atherosclerosis, in stable CAD patients.Methods and Results: We performed a single-center, randomized, placebo-controlled, double-blinded trial to assess whether low dose methotrexate (MTX), low dose colchicine (LDC), and/or their combination (MTX+LDC), improves CEF using non-invasive MRI measures in patients with stable CAD (N = 94). The primary endpoint was the MRI-detected change in coronary cross-sectional area from rest to isometric handgrip exercise (IHE), a predominantly nitric oxide-dependent endothelial dependent stressor. Coronary and systemic endothelial endpoints, and serum inflammatory markers, were collected at baseline, 8 and 24 weeks. Anti-inflammatory study drugs were well-tolerated. There were no significant differences in any of the CEF parameters among the four groups (MTX, LDC, MTX+LDC, placebo) at 8 or 24 weeks. Serum markers of inflammation and systemic endothelial function measures were also not significantly different among the groups.Conclusion: This is the first study to examine the effects of the anti-inflammatory approaches using MTX, LDC, and/or the combination in stable CAD patients on CEF, a marker of vascular health and the primary endpoint of the study. Although these anti-inflammatory approaches were relatively well-tolerated, they did not improve coronary endothelial function in patients with stable CAD.Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT02366091.

4313Evolocumab rapidly reverses impaired coronary endothelial function in six weeks in people living with HIV and in patients with dyslipidemia

Abstract Background/Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) is well recognized for its importance in cholesterol metabolism. Elevated levels are associated with increased cardiovascular risk and inhibition with PCSK9 antibodies lowers cardiovascular events in patients with known coronary disease. PCSK9 levels are also elevated in people living with HIV (PLWH), and we previously reported that increased PCSK9 in PLWH is associated with impaired coronary endothelial function (CEF), a major driver for the development, progression, and clinical manifestations of coronary artery disease. Purpose Here we investigate the hypothesis that PCSK9 inhibition improves impaired CEF in PLWH and in patients with dyslipidemia (DL). Methods Cine 3T MRI was used to noninvasively measure CEF, assessed as the change in coronary cross-sectional area (CSA) from rest to isometric handgrip exercise (IHE), a known endothelial-dependent vasodilator. Eight HIV+ subjects on stable highly active antiretroviral therapy and with undetectable HIV RNA (mean age 53±9 yrs, LDLC 98±18 mg/dL, 38% on statins) and ten patients with dyslipidemia (DL) without HIV receiving evolocumab for clinical reasons (mean age 56±10 yrs, LDLC 130±28 mg/dL, 50% on statins) underwent MRI studies before and six weeks following the initiation of evolocumab 420 mg. MRI readers were blinded to group and timepoint. MRI data are presented as mean±SD for % change rest vs IHE. Results Prior to evolucumab, resting CSA in the two groups did not differ and IHE did not induce normal coronary vasodilation in either group; mean stress-induced CSA changes were −2.1±6.4% in HIV (p=0.27) and −0.6±4.1% in DL (p=0.46). Notably, CEF significantly improved following six weeks of evolocumab with IHE-induced CSA changes of 7.6±5.7% (p=0.006) and 5.0±3.6% (p=0.002) in the HIV and DL groups, respectively. The %-LDLC reduction with evolocumab was profound and comparable in the HIV and DL groups, 73±5% and 60±6% (p=0.19 HIV vs. DL). There was no significant correlation between the extents of LDLC reduction and of CEF improvement in either of these modest sized groups. Conclusion PCSK9 inhibition with evolocumab significantly improves abnormal coronary endothelial function after only six weeks in HIV+ people with normal LDLC and in HIV- people with DL. To our knowledge, these data represent the earliest (6 weeks) evidence for improvement in human coronary artery health by PCSK9 inhibition. Acknowledgement/Funding Amgen provided the PCSK9 monoclonal antibody (evolocumab) for this study.

In vitro optimization and comparison of CT angiography versus radial cardiovascular magnetic resonance for the quantification of cross-sectional areas and coronary endothelial function

BackgroundOur objectives were first to determine the optimal coronary computed tomography angiography (CTA) protocol for the quantification and detection of simulated coronary artery cross-sectional area (CSA) differences in vitro, and secondly to quantitatively compare the performance of the optimized CTA protocol with a previously validated radial coronary cardiovascular magnetic resonance (CMR) technique.Methods256-multidetector CTA and radial coronary CMR were used to obtain images of a custom in vitro resolution phantom simulating a range of physiological responses of coronary arteries to stress. CSAs were automatically quantified and compared with known nominal values to determine the accuracy, precision, signal-to-noise ratio (SNR), and circularity of CSA measurements, as well as the limit of detection (LOD) of CSA differences. Various iodine concentrations, radiation dose levels, tube potentials, and iterative image reconstruction algorithms (ASiR-V) were investigated to determine the optimal CTA protocol. The performance of the optimized CTA protocol was then compared with a radial coronary CMR method previously developed for endothelial function assessment under both static and moving conditions.ResultsThe iodine concentration, dose level, tube potential, and reconstruction algorithm all had significant effects (all p < 0.001) on the accuracy, precision, LOD, SNR, and circularity of CSA measurements with CTA. The best precision, LOD, SNR, and circularity with CTA were achieved with 6% iodine, 20 mGy, 100 kVp, and 90% ASiR-V. Compared with the optimized CTA protocol under static conditions, radial coronary CMR was less accurate (− 0.91 ± 0.13 mm2 vs. -0.35 ± 0.04 mm2, p < 0.001), but more precise (0.08 ± 0.02 mm2 vs. 0.21 ± 0.02 mm2, p < 0.001), and enabled the detection of significantly smaller CSA differences (0.16 ± 0.06 mm2 vs. 0.52 ± 0.04 mm2; p < 0.001; corresponding to CSA percentage differences of 2.3 ± 0.8% vs. 7.4 ± 0.6% for a 3-mm baseline diameter). The same results held true under moving conditions as CSA measurements with CMR were less affected by motion.ConclusionsRadial coronary CMR was more precise and outperformed CTA for the specific task of detecting small CSA differences in vitro, and was able to reliably identify CSA changes an order of magnitude smaller than those reported for healthy physiological vasomotor responses of proximal coronary arteries. However, CTA yielded more accurate CSA measurements, which may prove useful in other clinical scenarios, such as coronary artery stenosis assessment.

Regional coronary endothelial dysfunction is related to the degree of local epicardial fat in people with HIV

Background and aimsCoronary artery disease (CAD) is now an important cause of premature death in people with HIV but the causes of accelerated CAD are poorly understood. Epicardial adipose tissue (EAT) is metabolically-active and thought to contribute to CAD development. We tested the hypothesis that abnormal coronary endothelial function (CEF), an early marker and mediator of atherosclerosis, is related to the amount of local pericoronary EAT in HIV. MethodsWe studied 36 participants with HIV and no CAD (HIV+ CAD-), 15 participants with HIV and known CAD (HIV+ CAD+), and 14 age-matched, healthy participants without HIV (HIV-CAD-). To measure CEF, coronary MRI was performed before and during isometric handgrip exercise (IHE), an endothelial-dependent stressor. EAT was measured with MRI at the same imaging plane as CEF. ResultsCEF was significantly depressed, as measured by IHE-induced % coronary cross sectional area (CSA) change, in HIV+ CAD- and HIV+ CAD+ as compared to HIV-CAD-participants (p<0.0001). EAT thickness was significantly greater in HIV+ CAD- and HIV+ CAD+ participants as compared to HIV-CAD-participants (p=0.001). There was a significant inverse relationship between CEF and local EAT thickness and area (R = −0.48 and R = −0.51 respectively, p<0.0001 for both) among participants with HIV even after adjustment for cardiovascular risk factors. In participants with multiple CEF measures, CEF was lower in segments with higher EAT, other factors being equivalent. ConclusionsThere is a significant relationship between increased metabolically-active EAT and depressed local CEF in people with HIV, consistent with the hypothesis that increased epicardial fat contributes to accelerated CAD in persons with HIV.

The influence of febuxostat on coronary artery endothelial dysfunction in patients with coronary artery disease: A phase 4 randomized, placebo-controlled, double-blind, crossover trial

The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.

Local coronary wall eccentricity and endothelial function are closely related in patients with atherosclerotic coronary artery disease

BackgroundCoronary endothelial function (CEF) in patients with coronary artery disease (CAD) varies among coronary segments in a given patient. Because both coronary vessel wall eccentricity and coronary endothelial dysfunction are predictors of adverse outcomes, we hypothesized that local coronary endothelial dysfunction is associated with local coronary artery eccentricity.MethodsWe used 3 T coronary CMR to measure CEF as changes in coronary cross-sectional area (CSA) and coronary blood flow (CBF) during isometric handgrip exercise (IHE), a known endothelial-dependent stressor, in 29 patients with known CAD and 16 healthy subjects. Black-blood MRI quantified mean coronary wall thickness (CWT) and coronary eccentricity index (EI) and CEF was determined in the same segments.ResultsIHE-induced changes in CSA and CBF in healthy subjects (10.6 ± 6.6% and 38.3 ± 29%, respectively) were greater than in CAD patients 1.3 ± 7.7% and 6.5 ± 19.6%, respectively, p < 0.001 vs. healthy for both measures), as expected. Mean CWT and EI in healthy subjects (1.1 ± 0.3 mm 1.9 ± 0.5, respectively) were less than those in CAD patients (1.6 ± 0.4 mm, p < 0.0001; and 2.6 ± 0.6, p = 0.006 vs. healthy). In CAD patients, we observed a significant inverse relationship between stress-induced %CSA change and both EI (r = -0.60, p = 0.0002), and CWT (r = -0.54, p = 0.001). Coronary EI was independently and significantly related to %CSA change with IHE even after controlling for mean CWT (adjusted r = -0.69, p = 0.0001). For every unit increase in EI, coronary CSA during IHE is expected to change by -6.7 ± 9.4% (95% confidence interval: -10.3 to -3.0, p = 0.001).ConclusionThere is a significant inverse and independent relationship between coronary endothelial macrovascular function and the degree of local coronary wall eccentricity in CAD patients. Thus anatomic and physiologic indicators of high-risk coronary vascular pathology are closely related. The noninvasive identification of coronary eccentricity and its relationship with underlying coronary endothelial function, a marker of vascular health, may be useful in identifying high-risk patients and culprit lesions.

Prognostic Value of Area Flow Index in Patients with Acute st Elevation Myocardial Infarction: Clinical and Echocardiographic Outcomes

Background: Early restoration of patency of infarct related artery is a universally accepted goal in the treatment of acute myocardial infarction. These could be achieved by Primary PCI or fibrinolysis. Primary PCI is preferred reperfusion strategy over fibrinolysis. Identifying initial area at risk in patients with acute myocardial infarction had been shown to have a direct impact on patients adverse clinical outcomes as well as prediction of systolic dysfunction. Area flow index (AFI) calculation in patients with acute myocardial infarction may predict initial area at risk during primary PCI. Aim: To investigate the clinical utility of Area flow index to predict systolic dysfunction and adverse clinical outcomes in patients with acute anterior ST elevation myocardial infarction Patients: 250 consecutive patients with acute anterior ST elevation myocardial infarction treated with primary PCI presenting to Alexandria main university hospital and ICC hospital from June 2013 till December 2014. Methods: Echocardiographic assessment of LV systolic function 5-7 days after myocardial infarction by calculation of ejection fraction using modified simpson method. Area flow index was calculated by dividing culprit segment cross sectional area to total coronary cross sectional area. Where DC is the culprit segment diameter, D1 left anterior descending diameter, D2 left circumflex diameter, D3 right coronary diameter. All patients were followed one month for the occurrence of MACE. Results: Patients were grouped according to their ejection fraction following myocardial infarction into 3 groups: -Group I: severe LV systolic dysfunction EF 45% There was a significant negative correlation between AFI and LVEF (r=-0. 58, P 28.4% had a 75.6% sensitivity and 78.1% specificity in predicting severe LV systolic dysfunction. Also the composite one month MACE was higher in the group with AFI>28.4% (p<0. 001). Conclusion: Area flow index calculated from coronary angiography at time of primary PCI is a new strong independent predictor of LV systolic dysfunction and 1month MACE in patients with acute anterior myocardial infarction.

Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function.

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(-1)·min(-1)), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies ~8 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 ± 2.5 (mean ± SE, placebo) vs. -0.3 ± 1.6% (l-NMMA); P < 0.001] and significantly blunted the increase in flow [%CBF, 47.7 ± 6.4 (placebo) vs. 10.6 ± 4.6% (l-NMMA); P < 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA (P < 0.0001) and CBF (P < 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.

Abstract 15980: Regional Coronary Endothelial Function is Related to Coronary Wall Eccentricity on MRI

Introduction: Coronary endothelial function (CEF) in patients with coronary artery disease (CAD) varies among coronary segments in a given patient for reasons that are incompletely understood. Hypothesis: Because both plaque eccentricity and coronary endothelial dysfunction are associated with adverse outcomes, we used noninvasive MRI to test the hypothesis that local coronary endothelial dysfunction is associated with local plaque eccentricity. Methods: We studied 13 healthy subjects (mean age±SEM: 55±7 years) and 21 patients with known CAD or CAD risk factors (61±4 years). To measure CEF, 3T coronary MRI was performed before and during isometric hand-grip exercise (IHE), a known endothelial-dependent stressor and % coronary cross-sectional area (CSA) and % coronary flow velocity (CFV) changes were measured. Black blood imaging of the coronaries was performed at the same cross sectional plane to quantify mean coronary wall thickness (CWT) and coronary eccentricity index (EI=max wall thickness (WT)-min WT)/max WT). Results: The changes in stress-induced CSA and CFV were significantly higher in healthy subjects (11.0±4.9% and 32.2±10.6% respectively) than in patients (2.2±1.5%, 12.8±4.9%, p&lt;0.01 vs. healthy for both measures). Both mean CWT (1.11±0.06mm) and EI (0.47±0.2) were significantly lower in the healthy group than in the patients (CWT=1.59±0.07mm,p&lt;0.001; EI= 0.57±0.02,p=0.006 vs. healthy). In the patient group, we observed a strong inverse relationship between stress-induced %CSA change and EI (r 2 =0.65, p&lt;0.0001), but no significant relationship between %CFV change with stress and EI (r 2 =0.007,p=0.7). CWT was also significantly related to %CSA change (r 2 =0.47,p=0.002). Conclusion: We observed a strong inverse relationship between coronary endothelial macrovascular reactivity as measured by stress-induced %CSA change and the degree of coronary wall eccentricity in CAD patients. These findings indicate that an eccentric pattern of coronary wall remodeling is associated with abnormal local CEF, and therefore that anatomic and physiologic early indicators of coronary vascular pathology are closely related in atherosclerosis.

Abstract 13292: A Novel Reproducible Noninvasive Imaging Approach to Quantify Nitric Oxide-mediated Coronary Endothelial Function in Humans

Endothelial release of nitric oxide (NO) is a defining characteristic of non-diseased vascular tissue. Healthy coronary arteries respond to endothelial-dependent stressors with vasodilatation but those with endothelial dysfunction respond with paradoxical vasoconstriction. The combination of new non-invasive 3T coronary MRI methods and isometric handgrip exercise (IHE), has been suggested as a means to noninvasively quantify coronary endothelial function (CEF). However, IHE may trigger neural, neuro-hormonal and other vasoreactive responses; thus, it is unknown whether the IHE-induced coronary response is, in fact, primarily mediated by NO. Furthermore, it is not known whether the MRI-IHE test is reproducible over time.To test the hypothesis that the IHE-induced coronary response is NO-mediated, we performed MRI-IHE studies before and during the infusion of monomethyl-L-arginine (L-NMMA, 0.3mg/kg/min), a NO synthase inhibitor in 8 healthy subjects. To study reproducibility we performed 2 MRI-IHE studies ~8 weeks apart in 8 coronary artery disease (CAD) patients and 9 healthy subjects. Changes from rest to IHE in coronary cross-sectional area (%CSA) and coronary blood flow (%CBF) were measured with cine MRI. L-NMMA completely blocked coronary vasodilation during IHE (%CSA change 15.4%±2.8% with placebo vs -1.6%±1.3% with L-NMMA; p&lt;0.0001) and the normal increase in coronary blood flow (%CBF change 50.2%±6.7% with placebo vs -2.1%±6.7% with L-NMMA; p&lt; 0.0001). Moreover, there was a strong correlation between repeated measures for %CSA change with IHE at the two exams (R=0.91, p&lt;0.0001) and %CBF change with IHE (R=0.80; p&lt;0.001). Bland-Altman analysis and intra-class correlation coefficients for %CSA and %CBF change with IHE (0.90 and 0.80, respectively) indicated good agreement and little variability between repeated measures. In summary the coronary response to IHE is largely mediated by endothelial-derived NO and is reproducible over several weeks. Thus MRI-IHE is a noninvasive, reproducible tool to assess CEF, arguably the first to noninvasively measure macro- and micro-vascular NO-mediated coronary responses. This noninvasive tool may be useful in future studies of the impact of interventions on CAD pathogenesis.

Quantification of Coronary Arterial Narrowing in Autopsy Cases

Coronary artery disease (CAD) is a major cause of human mortality and morbidity in the world and has been a matter of great concern for continuing research and its management. The principle cause of CAD worldwide is coronary atherosclerosis. Various studies conducted globally have revealed marked variations in incidence and extent of CAD. The initiation of the atherosclerotic process starts at a very tender age in the aorta; however the clinical presentations and manifestations are seen later on. The basic pathological process involved in CAD is stenosis of the coronary lumen which is quantified in living patients by coronary angiography. The present study quantifies the coronary luminal stenosis with the help of necropsy histo-pathological study in autopsy cases which has distinct advantage of being able to measure cross-sectional area of the artery concerned. The findings of present study with relation to defining and quantifying the coronary artery dia and cross-sectional area in necropsy specimens of an Indian population will be discussed in this paper.

Abstract 45: Hemodynamic and Clinical Determinants of Coronary Sinus Flow in Patients Referred for Cardiac Catheterization

Background: Coronary sinus blood flow (CSBF) can be used as a measure of total coronary blood flow. Hemodynamic and clinical determinants of coronary sinus flow are not well investigated. Decreased CSBF is expected in obstructive coronary artery disease (CAD) and elevated left ventricular end-diastolic pressure (LVEDP). Material and Methods: A prospective cohort study of patients referred for cardiac catheterization was performed. CSBF (ml/min) was measured non-invasively as a product of heart rate, coronary sinus cross-sectional area (obtained in modified apical 4 chamber view), and coronary sinus time velocity integral (obtained in modified right ventricular inflow view). In patients with normal sinus rhythm and preserved atrial contraction, retrograde diastolic CSBF was subtracted from forward CSBF. Repeated measures ANOVA and chi-square analyses were used. Results: Study cohort consisted of 39 patients (19 females, 63+/-11 years old, 9 with diabetes, 30 with hypertension (HTN) and 6 with atrial fibrillation). CSBF was obtained in 24 (61%) patients. CSBF was increased in patients with normal blood pressure (1353+/-862 vs. 647+/-397 in patients with HTN, p=0.011) and in patients with right atrial (RA) pressure exceeding 5 mmHg (1228+/-654 vs. 478+/-356 in RA pressure less than 5 mmHg, p=0.002). HTN appeared to be a less important determinant of CSBF than RA pressure (RAP) in multiple ANOVA comparison (HTN p=0.643, RAP p=0.005, Figure). There was also a trend towards decreased CSBF in patients with diabetes (647 +/-507 vs. 937 +/-685 ml/min in patients without diabetes, p=0.327) and /or obstructive CAD (663+/-381 vs. 832+/-748 ml/min in non-obstructive CAD or normal coronaries, p=0.613) and females (680+/-419 vs. 1095+/-828 ml/min in males, p=0.119). There was no significant correlation between CSBF and LVEDP. Discussion and Conclusions: Coronary sinus blood flow is determined by patient morbidities and central hemodynamic parameters. CSBF tends to be lower in patients with obstructive CAD, diabetes and/or HTN. Increased RA pressure and systemic HTN are associated with augmented CSBF. We speculate that effects of RA pressure on CSBF are reflective of preload and intrathoracic pressure parameters. Increased intrathoracic pressure may augment coronary blood flow by compression of the aorta and improved coronary perfusion gradient.