Prevalence and Predictors of Atrial Fibrillation and its Embolic Complications in Patients with Rheumatic Heart Disease at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

Abstract Background: Atrial fibrillation is one of the complications of rheumatic heart disease, with substantial morbidity and mortality. The prevalence and predictors of atrial fibrillation and its thrombo-embolic complications in Ethiopian patients with rheumatic heart disease are unknown. The objective of this study was to determine the prevalence and predictors of atrial fibrillation and its thromboembolic complications. Methods: A retrospective chart review of 500 patients with rheumatic heart disease at the adult cardiology clinic of Tikur Anbessa Specialized Hospital was carried out from 01 January to 31 June 2016. Data were entered into a pre-tested questionnaire and were analyzed using SPSS version 23. Results: Records of 500 patients (72% female) with electrocardiographic recordings and echocardiographic reports were available for analysis. Atrial fibrillation was found in 234 (46.8%) of the patients. Predictors of atrial fibrillation were found to be: age ≥50 years (p=0.01), left atrial size ≥45mm (p=0.01), the presence of mitral stenosis (p<0.01) and the presence of tricuspid regurgitation (p=0.01). Cardioembolic events were reported in 67 (9.2%) patients, and the presence of atrial fibrillation (p=0.02) and sub-therapeutic anticoagulation status (p<0.01) were significant predictors of cardioembolic events. Conclusions and recommendations: The study reveals a high prevalence of atrial fibrillation and cardioembolic events in Ethiopian patients with rheumatic heart disease. Hence, active screening of atrial fibrillation and optimal anticoagulation are recommended

Coronary Endothelial Dysfunction; Obesity and the Metabolic Syndrome

Objective : To define the impact of the metabolic syndrome (MetS) and obesity on coronary vascular function; with the hypothesis that subjects with MetS will have endothelial dysfunction. Background : Obesity or the metabolic syndrome is associated with a higher risk of diabetes and coronary artery disease (CAD). Endothelial dysfunction is a common causal pathway in the initiation and progression of CAD. Methods : A total of 418 patients (165 obese; 239 MetS) with and without angiographic evidence of CAD underwent coronary vascular function testing by measuring coronary blood flow (CBF) velocity in response to intracoronary infusion of acetylcholine (ACH) and sodium nitroprusside (SNP) and coronary flow reserve with adenosine. Results : Endothelium-dependent microvascular vasodilation correlated with body mass index (BMI) (r = -0.12; p = 0.02); with ACH responses significantly lower in overweight; obese and MetS subjects (p = 0.003). The number of MetS components correlated with the response to ACH in both the coronary microcirculation and the epicardial coronary arteries; and with impaired coronary microcirculatory responses to adenosine. No significant correlation was observed with SNP. In multivariable analysis; beyond age; only the total number of MetS components; and not BMI; emerged as an independent predictor of impaired microvascular response to ACH (CBF: ? = -0.18; p 0.001). Low-grade inflammation (C-reactive protein) was higher in patients with MetS; but was not associated with coronary vascular function. Conclusions : We demonstrate that the clustering of MetS components is an important and independent determinant of coronary endothelial dysfunction in subjects with and without CAD

Coronary and Peripheral Vasomotor Responses to Mental Stress.

BACKGROUND: Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation. METHODS AND RESULTS: In 38 patients aged 59±8 years undergoing coronary angiography, endothelium-dependent and endothelium-independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate-pressure product by 22% (±23%) and constricted epicardial coronary arteries by -5.9% (-10.5%, -2.6%) (median [interquartile range]), P=0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=0.001, without epicardial coronary diameter change (0.1% [-10.9%, 8.2%], P=not significant). The MS-induced CBF response correlated with endothelium-dependent CBF changes with acetylcholine (r=0.38, P=0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demand-adjusted change in CBF during MS (r=-0.60, P=0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation. CONCLUSIONS: The coronary microvascular response to MS is determined by endothelium-dependent, but not endothelium-independent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation.

Circulating progenitor cells and coronary microvascular dysfunction: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD).

BACKGROUND AND AIMS: Ischemia stimulates a reparative response resulting in mobilization of circulating progenitor cells (CPCs). We hypothesized that women with chronic myocardial ischemia from coronary microvascular disease (CMD) will mobilize CPCs. METHODS: In 123 women with ischemic symptoms and signs but no obstructive coronary artery disease (CAD) enrolled in the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD), we measured coronary flow reserve (CFR) in response to intracoronary adenosine. Peripheral blood CPCs were measured using flow cytometry for expression of CD34, CD133, CXCR4, and VEGFR2. RESULTS: Subjects were 53 ± 11 years, BMI 30 ± 8; 44% hypertensive, 11% diabetic, 23% hyperlipidemic and 7% smokers. Lower CFR correlated inversely with higher levels of hematopoietic-enriched CD34+ (r = -0.23, p = 0.011), CD34+/CD133+ (r = -0.24, p = 0.008), and CD34+/CXCR4+ (r = -0.19, p = 0.036) cells. In multivariable regression analyses, after adjusting for traditional cardiovascular risk factors, lower CFR remained significantly associated with elevated levels of CD34+ (ß -0.18, p = 0.042), CD34+/CD133+ (ß -0.24, p = 0.036), and CD34+/CXCR4+ (ß -0.22, p = 0.050) cells. We found no association between CFR and CD34+/VEGFR2+ cells. CONCLUSIONS: In women with non-obstructive CAD, impaired CFR is associated with higher levels of CPCs, suggesting that chronic myocardial ischemia from CMD stimulates CPC mobilization. The functional significance of elevated CPCs in these subjects requires further investigation as a potential biomarker and treatment target.

Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core.

BACKGROUND: Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. METHODS AND RESULTS: Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47-63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. CONCLUSIONS: In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC.

Mediterranean Dietary Patterns and Cardiovascular Health.

The Mediterranean dietary pattern has been linked with reduced cardiovascular disease incidence and mortality. Components of the Mediterranean diet associated with better cardiovascular health include low consumption of meat and meat products, moderate consumption of ethanol (mostly from wine), and high consumption of vegetables, fruits, nuts, legumes, fish, and olive oil. Increasing evidence indicates that the synergy among these components results in beneficial changes in intermediate pathways of cardiometabolic risk, such as lipids, insulin sensitivity, oxidative stress, inflammation, and vasoreactivity. As a result, consumption of a Mediterranean dietary pattern favorably affects numerous cardiovascular disease risk factors, such as dyslipidemia, hypertension, metabolic syndrome, and diabetes. Moreover, strong evidence links this dietary pattern with reduced cardiovascular disease incidence, reoccurrence, and mortality. This review evaluates the current evidence behind the cardioprotective effects of a Mediterranean dietary pattern.

Computational fluid dynamics applied to virtually deployed drug-eluting coronary bioresorbable scaffolds: Clinical translations derived from a proof-of-concept.

BACKGROUND: Three-dimensional design simulations of coronary metallic stents utilizing mathematical and computational algorithms have emerged as important tools for understanding biomechanical stent properties, predicting the interaction of the implanted platform with the adjacent tissue, and informing stent design enhancements. Herein, we demonstrate the hemodynamic implications following virtual implantation of bioresorbable scaffolds using finite element methods and advanced computational fluid dynamics (CFD) simulations to visualize the device-flow interaction immediately after implantation and following scaffold resorption over time. METHODS AND RESULTS: CFD simulations with time averaged wall shear stress (WSS) quantification following virtual bioresorbable scaffold deployment in idealized straight and curved geometries were performed. WSS was calculated at the inflow, endoluminal surface (top surface of the strut), and outflow of each strut surface post-procedure (stage I) and at a time point when 33% of scaffold resorption has occurred (stage II). The average WSS at stage I over the inflow and outflow surfaces was 3.2 and 3.1 dynes/cm(2) respectively and 87.5 dynes/cm(2) over endoluminal strut surface in the straight vessel. From stage I to stage II, WSS increased by 100% and 142% over the inflow and outflow surfaces, respectively, and decreased by 27% over the endoluminal strut surface. In a curved vessel, WSS change became more evident in the inner curvature with an increase of 63% over the inflow and 66% over the outflow strut surfaces. Similar analysis at the proximal and distal edges demonstrated a large increase of 486% at the lateral outflow surface of the proximal scaffold edge. CONCLUSIONS: The implementation of CFD simulations over virtually deployed bioresorbable scaffolds demonstrates the transient nature of device/flow interactions as the bioresorption process progresses over time. Such hemodynamic device modeling is expected to guide future bioresorbable scaffold design.

Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker released from leukocytes and endothelial cells that has been associated with atherosclerotic cardiovascular disease. We hypothesized that plasma suPAR level is an independent predictor of coronary microvascular function. METHODS: Coronary blood flow velocity and plasma suPAR levels were evaluated in patients with non-obstructive coronary artery disease. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal average peak blood flow velocity and coronary microvascular dysfunction was defined as CFR ≤ 2.0 in the setting of a fractional flow reserve value of ≥0.75. Plasma suPAR levels were measured using ELISA technique. The association between suPAR and CFR was investigated using univariate and multivariate regression analyses. RESULTS: In 66 patients, 47% were men, 26% had diabetes, 68% had hypertension and 76% had dyslipidemia. Mean age was 55 ± 12 years and median suPAR level 2.82 (2.08-3.40) ng/mL. Plasma suPAR levels correlated with age (r = 0.31, p = 0.01), body mass index (r = 0.25, p = 0.04) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.33, p = 0.009). While median suPAR level was not significantly different in patients with different cardiovascular risk factors, patients on statin therapy had significantly higher suPAR level (p = 0.03). SuPAR correlated negatively with CFR and, after multivariate adjustment for established cardiovascular risk factors, medications profiles and hs-CRP, suPAR remained an independent predictor of CFR (B = -0.30, p = 0.04), indicating an independent association between suPAR level and coronary microvascular function. CONCLUSIONS: In this cross-sectional study, plasma suPAR level was an independent predictor of coronary microvascular function. Larger prospective clinical trials are warranted to investigate the prognostic value of this novel biomarker and the role of immune dysregulation in coronary microvascular disease.

Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies.

Patients with myocardial bridging are often asymptomatic, but this anomaly may be associated with exertional angina, acute coronary syndromes, cardiac arrhythmias, syncope, or even sudden cardiac death. This review presents our understanding of the pathophysiology of myocardial bridging and describes prevailing diagnostic modalities and therapeutic options for this challenging clinical entity.

Combination of plaque burden, wall shear stress, and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability.

AIMS: Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability. METHODS: Twenty patients with CAD underwent baseline and 6-month follow-up coronary virtual histology-intravascular ultrasound (VH-IVUS) and computational fluid dynamics modeling for calculation of WSS. Low WSS was defined as <10 dynes/cm(2) and high WSS as ≥25 dynes/cm(2). Baseline plaque characteristics and WSS were related to plaque progression and vulnerability. RESULTS: In 2249 VH-IVUS frames analyzed, coronary segments with both plaque burden >40% and low WSS had significantly greater change in plaque area at follow-up (+0.68 ± 1.05 mm(2)), compared to segments with plaque burden >40% without low WSS (-0.28 ± 1.32 mm(2)) or segments with low WSS and plaque burden ≤40% (+0.05 ± 0.71 mm(2)) (p = 0.047). Among plaque phenotypes, pathologic intimal thickening (PIT) had the greatest increase in necrotic core (NC) area (p = 0.06) and greatest decrease in fibro-fatty (FF) area (p < 0.0001). At follow-up, compared to segments with either plaque burden >60%, PIT, or high WSS, those with a combination of plaque burden >60%, PIT, and high WSS developed greater increase in NC area (p = 0.002), greater decrease in FF (p = 0.004) and fibrous areas (p < 0.0001), and higher frequency of expansive remodeling (p = 0.019). CONCLUSION: Combination of plaque burden, WSS, and plaque phenotype has incremental value for prediction of coronary plaque progression and increased plaque vulnerability in patients with non-obstructive CAD.