Ahmed AlBadri

Coronary Microvascular Dysfunction ― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

Angina has traditionally been thought to be caused by obstructive coronary artery disease (CAD). However, a substantial number of patients with angina are found to not have obstructive CAD when undergoing coronary angiography. A significant proportion of these patients have coronary microvascular dysfunction (CMD), characterized by heightened sensitivity to vasoconstrictor stimuli and limited microvascular vasodilator capacity. With the advent of non-invasive and invasive techniques, the coronary microvasculature has been more extensively studied in the past 2 decades. CMD has been identified as a cause of cardiac ischemia, in addition to traditional atherosclerotic disease and vasospastic disease. CMD can occur alone or in the presence obstructive CAD. CMD shares many similar risk factors with macrovascular CAD. Diagnosis is achieved through detection of an attenuated response of coronary blood flow in response to vasodilatory agents. Imaging modalities such as cardiovascular magnetic resonance, positron emission tomography, and transthoracic Doppler echocardiography have become more widely used, but have not yet completely replaced the traditional intracoronary vasoreactivity testing. Treatment of CMD starts with lifestyle modification and risk factor control. The use of traditional antianginal, antiatherosclerotic medications and some novel agents may be beneficial; however, clinical trials are needed to assess the efficacy of the pharmacologic and non-pharmacologic therapeutic modalities. In addition, studies with longer-term follow-up are needed to determine the prognostic benefits of these agents. We review the epidemiology, prognosis, pathogenesis, diagnosis, risk factors and current therapies for CMD.

Inflammatory biomarkers as predictors of heart failure in women without obstructive coronary artery disease: A report from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Background Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (EF) often have diastolic dysfunction and experience elevated rates of major adverse cardiac events (MACE), including heart failure (HF) hospitalization with preserved ejection fraction (HFpEF). We evaluated the predictive value of inflammatory biomarkers for long-term HF hospitalization and all-cause mortality in these women. Methods We performed a cross-sectional analysis to investigate the relationships between inflammatory biomarkers [serum interleukin-6 (IL-6), C-reactive protein (hs-CRP) and serum amyloid A (SAA)] and median of 6 years follow-up for all-cause mortality and HF hospitalization among women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF. Multivariable Cox regression analysis tested associations between biomarker levels and adverse outcomes. Results Among 390 women, mean age 56 ± 11 years, median follow up of 6 years, we observed that there is continuous association between IL-6 level and HF hospitalization (adjusted hazard ratio [AHR] 2.5 [1.2–5.0], p = 0.02). In addition, we found significant association between IL-6, SAA levels and all-cause mortality AHR (1.8 [1.1–3.0], p = 0.01) (1.5 [1.0–2.1], p = 0.04), respectively. Conclusion In women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF, elevated IL-6 predicted HF hospitalization and all-cause mortality, while SAA level was only associated with all-cause mortality. These results suggest that inflammation plays a role in the pathogenesis of development of HFpEF, as well all-cause mortality.

Typical angina is associated with greater coronary endothelial dysfunction but not abnormal vasodilatory reserve

Typical angina (TA) is defined as substernal chest pain precipitated by physical exertion or emotional stress and relieved with rest or nitroglycerin. Women and elderly patients are usually have atypical symptoms both at rest and during stress, often in the setting of nonobstructive coronary artery disease (CAD).

Intracoronary Bolus Injection Versus Intravenous Infusion of Adenosine for Assessment of Coronary Flow Velocity Reserve in Women With Signs and Symptoms of Myocardial Ischemia and No Obstructive Coronary Artery Disease

Nonobstructive coronary artery disease is increasingly recognized, and coronary microvascular dysfunction (CMD) is often implicated, but there is no established approach to the evaluation of patients with signs and symptoms of ischemia but no obstructive coronary artery disease [(1)][1]. Coronary

Poor Glycemic Control Is Associated With Increased Extracellular Volume Fraction in Diabetes

OBJECTIVE We assessed whether poor glycemic control is associated with an increase in myocardial fibrosis among adults with diabetes. RESEARCH DESIGN AND METHODS We studied 47 adults with type 2 diabetes and stratified them into three groups according to their hemoglobin A1c (HbA1c) level: <6.5% (group 1; n = 12), 6.5–7.5% (group 2; n = 20), and >7.5% (group 3; n = 15). Left ventricular (LV) mass was assessed using cardiac MRI. The extracellular volume fraction (ECVF), an index of myocardial fibrosis, was measured by using myocardial T1 mapping before and after the administration of a gadolinium-based contrast agent. RESULTS Mean HbA1c was 5.84 ± 0.16%, 6.89 ± 0.14%, and 8.57 ± 0.2% in groups 1, 2, and 3, respectively. LV mass was not significantly different between the groups. The myocardial ECVF was significantly greater in groups 2 (mean 27.6% [95% CI 24.8–30.3]) and 3 (27.6% [24.4–30.8]) than in group 1 (21.1% [17.5–24.7]; P = 0.015). After adjusting for age, sex, BMI, blood pressure, and estimated glomerular filtration rate, the myocardial ECVF was significantly greater in groups 2 (27.4% [24.4–30.4]) and 3 (28% [24.5–31.5]) than in group 1 (20.9% [17.1–24.6]; P = 0.0156, ANCOVA). CONCLUSIONS An increased myocardial ECVF, suggesting myocardial fibrosis, is independently associated with poor glycemic control among adults with diabetes. Further research should assess whether tight glycemic control can revert fibrosis to healthy myocardium or ameliorate it and its adverse clinical consequences.

Cold Pressor Stress Cardiac Magnetic Resonance Myocardial Flow Reserve Is Not Useful for Detection of Coronary Endothelial Dysfunction in Women with Signs and Symptoms of Ischemia and No Obstructive CAD

Background Coronary endothelial function testing using acetylcholine is not routinely available, while non-pharmacological cold pressor testing (CPT) is considered an endothelial stressor. Noninvasive cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) can detect coronary microvascular dysfunction (CMD). We evaluated if CPT stress CMRI MPRI could detect invasive coronary endothelial dysfunction. Methods Coronary reactivity testing was performed in 189 women with symptoms and signs of ischemic but no obstructive coronary artery disease as previously described plus CPT stress. Subjects also underwent pharmacologic and CPT stress during CMRI (1.5 T). Statistical analysis comparing CPT MPRI between groups was performed by Welch`s t-test and Mann-Whitney where appropriate. Anderson-Darling test and Levene test were considered to verify the normality and homogeneity of variances assumptions. Correlation analyses between CPT MPRI and both invasive and noninvasive measures of CMD were performed using Spearman correlation. Results While CPT MPRI correlated with pharmacological stress MPRI, it did not correlate with invasive measures of CMD including invasively measured responses to intracoronary (IC) adenosine, IC acetylcholine, CPT, or IC nitroglycerin. Additionally CPT MPRI was not significantly different between subjects with normal compared to abnormal pharm stress MPRI or normal compared to abnormal invasive CMD parameters. Conclusion Despite correlation with pharmacological stress MPRI, non-invasive CPT MPRI does not appear to be useful for detecting CMD in symptomatic women.

Acetylcholine versus cold pressor testing for evaluation of coronary endothelial function

Background Assessment of coronary endothelial function with intracoronary acetylcholine (IC-Ach) provides diagnostic and prognostic data in patients with suspected coronary microvascular dysfunction (CMD), but is often not feasible due in part to the time and expertise needed for pharmacologic mixing. Cold pressor testing (CPT) is a simple and safe stimulus useful for either invasive or non-invasive endothelial function testing and myocardial perfusion imaging but has not been specifically evaluated among symptomatic women with signs of ischemic heart disease (IHD) who have no obstructive coronary artery disease (CAD). Methods 163 women with signs and symptoms of IHD and no obstructive CAD from the NHLBI- Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study underwent coronary reactivity testing with a Doppler flow wire (FloWire® Volcano, San Diego, CA) in the proximal left anterior descending artery. Coronary artery diameter and coronary blood flow (CBF) assessed by core lab using QCA before and after IC-Ach (18.2 μg/ml infused over 3 minutes) and during CPT. Results Mean age was 55 ± 12 years. Rate pressure product (RPP) in response to IC-Ach did not change (baseline to peak, P = 0.26), but increased during CPT (363±1457; P = 0.0028). CBF in response to CPT was poorly correlated to IC-Ach CBF. Change in coronary artery diameter after IC-Ach correlated with change after CPT (r = 0.59, P<0.001). The correlation coefficient was stronger in subjects with coronary dilation to IC-Ach (r = 0.628, P<0.001) versus those without dilation (r = 0.353, P = 0.002), suggesting that other factors may be important to this relationship when endothelium is abnormal. Conclusions In women with no obstructive CAD and suspected CMD, coronary diameter changes with IC-Ach and CPT are moderately-well correlated suggesting that CPT testing may be of some use, particularly among patients with normal endothelial function, however, not an alternative to IC-Ach for diagnosis of coronary endothelial dysfunction.

Interscan reproducibility of cardiovascular magnetic resonance myocardial perfusion reserve index in women with suspected coronary microvascular dysfunction and no obstructive coronary artery disease

Background Cardiovascular magnetic resonance (CMR) myocardial perfusion reserve index (MPRI) has recently shown promise for detecting coronary microvascular dysfunction (CMD) in women with signs and symptoms of ischemia and no obstructive coronary artery disease (CAD). Prior CMR studies in CAD populations and in healthy volunteers have shown good intra and interobserver reproducibility for MPRI. However, interscan reproducibility is more variable. If MPRI is to be considered useful for the detection of CMD in women, the interscan reproducibility in this population must also be understood, such that proposed MPRI cut-off thresholds can be appropriately adjusted. Therefore, the aim of this study was to determine the interscan reproducibility of MPRI in women with suspected CMD.