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BACKGROUND: A significant number of women with signs and symptoms of ischemia with no obstructive coronary artery disease (INOCA) have coronary vascular dysfuncton, detected by invasive coronary reactivity testing (CRT). However, the noninvasive assessment of coronary vascular dysfunction has been limited. METHODS: The Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) was a prospective study of women with suspected INOCA, aimed to investigate whether: 1) cardiac magnetic resonance imaging (CMRI) abnormalities in left ventricular morphology and function and myocardial perfusion predicted CRT measured coronary microvascular dysfunction; 2) these persistent CMRI abnormalities at 1-year follow-up predict persistent symptoms of ischemia; and 3) these CMRI abnormalities predict cardiovascular outcomes. By design a sample size of 375 women undergoing clinically indicated invasive coronary angiography for suspected INOCA was projected to complete baseline CMRI, a priori subgroup of 200 clinically indicated CRT, and a priori subgroup of 200 repeat 1-year follow-up CMRI. RESULTS: A total of 437 women enrolled between 2008 to 2015, 374 completed baseline CMRI, 279 completed CRT, and 214 completed 1-year follow-up CMRI. Mean age was 55 ± 11 years, 93% had 20-50% coronary stenosis and 7% had

Women presenting with signs and symptoms of myocardial ischemia frequently have no or nonobstructive coronary artery disease (CAD).This study aimed to investigate the associations between angiographic measures and longer-term clinical outcomes among women with signs and symptoms of ischemia referred for coronary angiography.A prospective cohort analysis of women referred for coronary angiography and enrolled in the National Heart, Lung, and Blood Institute-sponsored WISE was performed. An angiographic severity score was prospectively developed, assigning points for any stenosis weighted by stenosis severity, location, and collaterals and was then tested for prediction for adverse outcome in 917 women, over a median of 9.3 years.The study was conducted in referral centers.Women with signs and/or symptoms of myocardial ischemia referred for coronary angiography were consecutively consented and enrolled in a prospective study.Main outcomes included first occurrence of cardiovascular death or nonfatal myocardial infarction. Hospitalization for angina was a secondary outcome.Cardiovascular death or myocardial infarction at 10 years occurred in 6.7%, 12.8%, and 25.9% of women with no, nonobstructive, and obstructive CAD (P.0001), respectively. Cumulative 10-year cardiovascular death or myocardial infarction rates showed progressive, near-linear increases for each WISE CAD severity score range of 5, 5.1 to 10, 10.1 to 20, 20.1 to 50, and50. The optimal threshold in the WISE severity score classifications for predicting cardiovascular mortality was10 (eg, 5.0-10 vs 10.1-89), with both a sensitivity and specificity of 0.64 and an area under the curve of 0.64 (P = .02, 95% CI 0.59-0.68).Among women with signs and symptoms of ischemia, nonobstructive CAD is common and associated with adverse outcomes over the longer term. The new WISE angiographic score appears to be useful for risk prediction in this population.

Background We investigated the role of the renin-angiotensin system in women with signs and symptoms of ischemia without obstructive coronary artery disease (CAD). Although microvascular dysfunction has been suggested to explain this syndrome and recently was found to predict adverse outcomes, the mechanisms and treatments remain unclear. Methods In a substudy within the WISE, 78 women with microvascular dysfunction (coronary flow reserve [CFR] Results A total of 61 women completed the 16-week treatment period with repeat CFR measurements, and treatment was well tolerated. For the primary outcome, at 16 weeks, CFR improved more with ACE-I than placebo ( P P = .037) and CFR increase ( P = .008) both contributed. Conclusions Microvascular function improves with ACE-I therapy in women with signs and symptoms of ischemia without obstructive CAD. This improvement is associated with reduction in angina. The beneficial response of the coronary microvasculature was limited to women with lower baseline CFR values, suggesting that the renin-angiotensin system may be more involved among women with more severe microvascular defects.

Background Resolution of ST-segment elevation after thrombolysis for acute myocardial infarction has been shown to have prognostic significance 3 hours (180 minutes) after the initiation of therapy. Whether prognostically useful information can be achieved as early as 90 minutes after thrombolysis is unknown. Methods An electrocardiographic substudy of 2352 patients from the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial was undertaken to compare outcomes according to ST-segment resolution at 90 minutes versus 180 minutes after administration of thrombolytic therapy. Results Of 2352 patients in the substudy, 2241 had a baseline and 90-minute electrocardiogram, and 2218 had a baseline and 180-minute ECG. Complete ST-segment resolution occurred in 44.2% of patients at 90 minutes and 56.5% of patients at 180 minutes. ST-segment resolution at both 90 and 180 minutes was associated with lower 30-day and 1-year mortality. Multivariate analysis revealed ST-segment resolution at 90 minutes to be an equally strong predictor of 30-day mortality as resolution at 180 minutes. Patients who were at particularly high risk for mortality were those aged >70 years, those who presented with Killip class >1, and those with anterior infarctions. Conclusions The presence of ST-segment resolution on standard 12-lead electrocardiographic monitoring 90 minutes after thrombolysis is a useful independent predictor of mortality at 30 days and 1 year. The potential for obtaining prognostic results as early as 90 minutes after thrombolysis sets a new precedent for optimum electrocardiographic monitoring times in these patients. (Am Heart J 2002;144:81-8.)

Resolution of ST-segment elevation after thrombolysis for acute myocardial infarction has been shown to have prognostic significance 3 hours (180 minutes) after the initiation of therapy. Whether prognostically useful information can be achieved as early as 90 minutes after thrombolysis is unknown.An electrocardiographic substudy of 2352 patients from the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial was undertaken to compare outcomes according to ST-segment resolution at 90 minutes versus 180 minutes after administration of thrombolytic therapy.Of 2352 patients in the substudy, 2241 had a baseline and 90-minute electrocardiogram, and 2218 had a baseline and 180-minute ECG. Complete ST-segment resolution occurred in 44.2% of patients at 90 minutes and 56.5% of patients at 180 minutes. ST-segment resolution at both 90 and 180 minutes was associated with lower 30-day and 1-year mortality. Multivariate analysis revealed ST-segment resolution at 90 minutes to be an equally strong predictor of 30-day mortality as resolution at 180 minutes. Patients who were at particularly high risk for mortality were those aged70 years, those who presented with Killip class1, and those with anterior infarctions.The presence of ST-segment resolution on standard 12-lead electrocardiographic monitoring 90 minutes after thrombolysis is a useful independent predictor of mortality at 30 days and 1 year. The potential for obtaining prognostic results as early as 90 minutes after thrombolysis sets a new precedent for optimum electrocardiographic monitoring times in these patients.

Peripheral artery disease (PAD) is recognized as a public health issue because of its prevalence, functional limitations, and increased risk of systemic ischemic events. Current treatments for claudication, the primary symptom in patients with PAD, have limitations. Cells identified using cytosolic enzyme aldehyde dehydrogenase (ALDH) may benefit patients with severe PAD but has not been studied in patients with claudication. PACE is a randomized, double-blind, placebo-controlled clinical trial conducted by the Cardiovascular Cell Therapy Research Network to assess the safety and efficacy of autologous bone marrow–derived ALDH br cells delivered by direct intramuscular injections in 80 patients with symptom-limiting intermittent claudication. Eligible patients will have a significant stenosis or occlusion of infrainguinal arteries and a resting ankle-brachial index less than 0.90 and will be randomized 1:1 to cell or placebo treatment with a 1-year follow-up. The primary end points are the change in peak walking time and leg collateral arterial anatomy, calf muscle blood flow, and tissue perfusion as determined by magnetic resonance imaging at 6 months compared with baseline. The latter 3 measurements are new physiologic lower extremity tissue perfusion and PAD imaging–based end points that may help to quantify the biologic and mechanistic effects of cell therapy. This trial will collect important mechanistic and clinical information on the safety and efficacy of ALDH br cells in patients with claudication and provide valuable insight into the utility of advanced magnetic resonance imaging end points.