Sofy Landes

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.

Myocardial Scar Is Prevalent and Associated With Subclinical Myocardial Dysfunction in Women With Suspected Ischemia But No Obstructive Coronary Artery Disease: From the Women’s Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction Study

Women with suspected ischemia and no obstructive coronary artery disease (INOCA) have a high prevalence of coronary microvascular dysfunction1 and an elevated rate of major adverse cardiac events, including nonfatal myocardial infarction (MI).2 Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) imaging accurately visualizes and characterizes myocardial scar, which predicts major adverse cardiac events.3 The prevalence, incidence, and scar pattern in women with INOCA is not well characterized. We evaluated LGE in women with suspected INOCA in the WISE-CVD study (Women’s Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00832702). Participants in the WISE-CVD study included women with suspected INOCA as previously described.4 The study was approved by the site institutional review committees. All participants gave informed consent. Of the 369 total women enrolled, 341 underwent baseline CMR with LGE; 1 was excluded because of inadequate quality. A subset of 145 underwent invasive coronary reactivity testing.5 The SAQ (Seattle Angina Questionnaire) was completed at baseline and 1-year follow-up. Retrospective review included clinical diagnosis of MI, electrocardiogram, and troponin levels. A subset of 200 participants underwent repeat CMR with LGE at 1-year follow-up; 179 were included with baseline CMR and follow-up within 1 year of study completion. All scans were performed on a 1.5T scanner (Magnetom Avanto, Siemens Healthcare) and analyzed by the WISE-CMR core lab.4 A total 0.2 mmol/kg gadolinium-based contrast (Optimark, gadoversetamide) in divided doses was used, and LGE images were …

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.