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Background: Women have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. Purpose: To investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). Methods: We analyzed 69 women with available androgen levels. Results: Group mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = −0.26, p = 0.03; r = −0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. Conclusions: In women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. Methods and Results Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P

Background The ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high‐ versus low‐dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non‐P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22–1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91–2.22]). We found no interaction in the relative effectiveness and safety of high‐ versus low‐dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high‐dose compared with low‐dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high‐ versus low‐dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

BackgroundWhile autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history.MethodsWomen with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis.ResultsOf the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups.ConclusionsAmong women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.

Women with myocardial infarction with no obstructive coronary artery disease (MINOCA) are increasingly recognized. Women with MINOCA are at high risk for major adverse cardiovascular events. In this case, we focus on the importance of early identification and management of MINOCA to improve patients’ angina and related quality of life. (Level of Difficulty: Beginner.)

Standard cardiology practice often defers preventive strategies to primary care providers. We aimed to evaluate the effectiveness of a preventive cardiology clinic focused on lifestyle and nutrition counseling combined with guideline-directed medical therapy on reducing cardiovascular disease (CVD) risk. We queried the University of Florida-Health database for patients enrolled in the preventive cardiology clinic, and a general and interventional cardiology clinic from January 2016 to October 2019. Mean change in weight and blood cholesterol including LDL cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG) were compared in the three clinics in the initial cohort and stratified into primary and secondary prevention. A propensity score-matched analysis was done to adjust for CVD risk factors and statin use. Among a cohort of 239 patients, enrollment in the preventive clinic (n = 99) was associated with greater weight loss at 6 months compared to other clinics (n = 140) (mean −1.7 vs +0.1 kg, p 0.007). Preventive clinic was also associated with greater mean reduction in LDL-C (−24.8 vs −7.1 mg/dl, p 0.021), TC (−29.3 vs −2.0, p 0.003) and TG (−19.7 vs +13.3, p 0.002) at both initial and last follow-up (median time 6 and 16 months). The association with reduction in TG was observed in both primary and secondary prevention, but reduction in LDL-C and TC was only significant in secondary prevention. In a propensity-matched linear regression analysis, preventive clinic was independently associated with LDL-C reduction (b −14.7, r −0.3, p 0.038). A preventive cardiology clinic focused on patient education can be effective in reducing CVD risk.

Background Recurrent hospitalization is prevalent in women with signs and symptoms of ischemia and no obstructive coronary artery disease. We hypothesized that rates of angina hospitalization might have changed over time, given advances in diagnostic and therapeutic approaches. Methods and Results We evaluated 551 women enrolled in the WISE (Women's Ischemia Syndrome Evaluation) study with no obstructive coronary artery disease (CAD) for a follow‐up period of 9.1 years. We analyzed angina hospitalization rates using the Kaplan‐Meier method. Univariate analysis and multivariable Cox proportional hazard models were developed for prediction of angina hospitalization in women with signs and symptoms of angina and no CAD. A total of 223 women had nonobstructive CAD (>20–50%

Objective. In a separate, contemporary cohort, we sought to confirm findings of the original Women’s Ischemia Syndrome Evaluation (WISE). Background. The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. Methods. We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or

BackgroundPrior studies have shown that survivors of acute myocardial infarction (AMI) complicated by cardiogenic shock are likely to have increased risk of readmissions in the early post‐discharge period. However, the contemporary prevalence, reasons, and predictors of 30‐day readmissions are not well known. Methods and ResultsHospitalizations for a primary diagnosis of AMI complicated by cardiogenic shock, and discharged alive, were identified in the 2013 and 2014 Nationwide Readmissions Databases. Prevalence and reasons for 30‐day unplanned readmissions were investigated. A hierarchical logistic regression model was used to identify independent predictors of 30‐day readmissions. Among 1 116 933 patient hospitalizations with AMI, 39 807 (3.6%) had cardiogenic shock and were discharged alive. Their 30‐day readmission rate was 18.6%, with a median time for readmission 10 days post discharge. Predictors of readmission included: non–ST‐segment elevation myocardial infarction, female sex, low‐income status, nonprivate insurance, chronic renal failure, long‐term ventricular assist device or intra‐aortic balloon placement, and tachyarrhythmia. The majority of readmissions were attributable to cardiac‐related causes (52%); heart failure being the most frequent cardiac cause (39% of all cardiac causes). Noncardiac‐related readmissions included infections (14.9%), bleeding (5.3%), and respiratory causes (4.9%). The median cost per readmission was $9473 US dollars ($5037–20 199). ConclusionsAmong survivors of AMI complicated by cardiogenic shock who were discharged from hospital, almost 1 in 5 are readmitted at 30 days, mainly because of cardiac reasons such as heart failure and new AMI. The risk of readmission was associated with certain baseline patient/hospital characteristics.

Background There are limited data on the merits of an early invasive strategy in diabetics with non‐ST‐elevation acute coronary syndrome, with unclear influence of this strategy on survival. The aim of this study was to evaluate the in‐hospital survival of diabetics with non‐ST‐elevation acute coronary syndrome treated with an early invasive strategy compared with an initial conservative strategy. Methods and Results The National Inpatient Sample database, years 2012–2013, was queried for diabetics with a primary diagnosis of non‐ST‐elevation acute coronary syndrome defined as either non‐ST‐elevation myocardial infarction or unstable angina (unstable angina). An early invasive strategy was defined as coronary angiography±revascularization within 48 hours of admission. Propensity scores were used to assemble a cohort managed with either an early invasive or initial conservative strategy balanced on >50 baseline characteristics and hospital presentations. Incidence of in‐hospital mortality was compared in both groups. In a cohort of 363 500 diabetics with non‐ST‐elevation acute coronary syndrome, 164 740 (45.3%) were treated with an early invasive strategy. Propensity scoring matched 21 681 diabetics in both arms. Incidence of in‐hospital mortality was lower with an early invasive strategy in both the unadjusted (2.0% vs 4.8%; odds ratio [OR], 0.41; 95% CI, 0.39–0.42; P

There are several techniques for performing coronary atherosclerotic plaque modification, known as atherectomy . Historically, clinical trials show mostly equivalence between various coronary atherectomy techniques, balloon angioplasty, and percutaneous coronary stenting. In the last several years the use of a given atherectomy technique has been mostly as a means of facilitating stent delivery in vessels that are heavily calcified. No clinical trials have shown superiority of any atherectomy method over more standard techniques of percutaneous coronary intervention. This review begins with a discussion of directional atherectomy, which is no longer available. The rotational atherectomy technique and its clinical trial data are presented. Orbital atherectomy is then discussed in detail, including the relevant clinical trials. Finally, laser atherectomy techniques are reviewed, and the pertinent trial data are presented. Lastly, future directions are detailed.

Over the past decade, percutaneous renal denervation has been vigorously investigated as a treatment for resistant hypertension. The SYMPLICITY radiofrequency catheter system (Medtronic CardioVascular Inc., Santa Rosa, CA, USA) is the most tested device in clinical trials. After the positive results of small phase I and II clinical trials, SYMPLICITY HTN-3 (a phase III, multi-center, blinded, sham-controlled randomized clinical trial) was completed in 2014, but did not show significant blood pressure lowering effect with renal denervation compared to medical therapy and caused the investigators and industry to revisit both the basic science elements of renal denervation as well as the design of related clinical trials. This review summarizes the SYMPLICITY trials, analyzes the SYMPLICITY HTN-3 data, and provides insights gained from this trial in the design of the most recent clinical trial, the SPYRAL HTN Global clinical trial. Other than hypertension, the role of renal denervation in the management of other disease processes such as systolic and diastolic heart failure, metabolic syndrome, arrhythmia, and obstructive sleep apnea with the common pathophysiologic pathway of sympathetic overactivity is also discussed.

Coronary artery chronic total occlusion (CTO) is defined as an occluded coronary artery segment without anterograde flow for at least three months. It can be classified as a “true” or “functional” CTO based on flow characteristics. In “true” CTO, there is no anterograde flow. In “functional” CTO, there is minimal anterograde flow through the occluded segment of the coronary artery. CTO is a common finding during coronary angiography and its prevalence may vary depending on the reported literature. Among patients without previous coronary artery bypass grafting (CABG), CTO is found in about 20–30% of the patients. CTO may develop insidiously over a period of time and involve a complex interplay between intracellular and extracellular factors, smooth muscle and foam cells, calcification, and neovascularization. There is a growing body of evidence to support that CTO revascularization may improve clinical outcome when compared to medical management. Both the European and American cardiovascular societies support CTO revascularization with a class 2a recommendation (level of evidence B). Historically, due to low procedural success rate, apparent inefficient resource utilization, potential increase in complication rates and uncertain clinical benefits, only about 10–20% of patients with CTO are treated with percutaneous coronary intervention (PCI). Recent advances using novel and innovative techniques with dedicated equipment have significantly improved the procedural success rate for CTO PCI to about 90% in the hands of experienced operators. With increasing interest in CTO PCI coupled with increased educational effort, CTO PCI likely will become more accessible to patients in need of CTO revascularization. Ongoing advancement in innovative techniques and equipment will continue to improve procedural success rates and reduce procedural complication rate for CTO PCI. Furthermore, there are a number of prospective clinical trials on the horizon which should help define the clinical benefits and limitations of CTO PCI in the near future.

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).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.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

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.

TIMI frame count (TFC) predicts outcomes in patients with obstructive coronary artery disease (CAD); it remains unclear whether TFC predicts outcomes in patients without obstructive CAD.TFC was determined in a sample of women with no obstructive CAD enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study. Because TFC is known to be higher in the left anterior descending artery (LAD), TFC determined in the LAD was divided by 1.7 to provide a corrected TFC (cTFC).A total of 298 women, with angiograms suitable for TFC analysis and long-term (6-10 year) follow up data, were included in this sub-study. Their age was 55±11 years, most were white (86%), half had a history of smoking, and half had a history of hypertension. Higher resting cTFC was associated with a higher rate of hospitalization for angina (34% in women with a cTFC >35, 15% in women with a cTFC ≤35, P