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Background Coronary microvascular dysfunction (CMD) is associated with heart failure with preserved ejection fraction (HFpEF); however, pathophysiology is not well described. Hypothesis We hypothesized that CMD in women with suspected ischemia with no obstructive coronary artery disease (INOCA) is associated with cardiomyocyte dysfunction reflected by plasma levels of a cardiomyocyte calcium handling protein, cardiac bridge integrator 1 (cBIN1). Methods Women with suspected INOCA undergoing coronary function testing were included. Coronary flow reserve, vasodilation to nitroglycerin, change in coronary blood flow (ΔCBF), and vasodilation to acetylcholine (ΔAch) were evaluated. cBIN1 score (CS) levels in these women (n = 39) were compared to women with HFpEF (n = 20), heart failure with reduced ejection fraction (HFrEF) (n = 36), and reference controls (RC) (n = 50). Higher CS indicates cardiomyocyte tubule dysfunction. Results INOCA, HFpEF, and HFrEF women were older than RC (p

Aim Heart failure following myocardial infarction (MI) is a potentially lethal problem with a staggering incidence. The CardiAMP Heart Failure trial represents the first attempt to personalize marrow-derived cell-based therapy to individuals with cell characteristics associated with beneficial responses in prior trials. Before the initiation of the randomized pivotal trial, an open-label “roll-in cohort” was completed to ensure the feasibility of the protocol's procedures. Methods Patients with chronic post-MI heart failure (NYHA class II-III) receiving stable, guideline-directed medical therapy with a left ventricular ejection fraction between 20 and 40% were eligible. Two weeks prior to treatment, a ~ 5 mL bone marrow aspiration was performed to examine “cell potency”. On treatment day, a 60 mL bone marrow aspiration, bone marrow mononuclear cell (BM MNC) enrichment and transendocardial injection of 200 million BM MNC's was performed in a single, point of care encounter. Patients were then followed to assess clinical outcomes. Results The cell potency small volume bone marrow aspirate, the 60 mL bone marrow aspirate, and transendocardial injections were well tolerated in 10 patients enrolled. There were no serious adverse events related to bone marrow aspiration or cell delivery. Improvement in 6-min walk distance was observed at 6 months (+47.8 m, P = 0.01) and trended to improvement at 12 months (+46.4, P = 0.06). Similarly, trends to improved NYHA heart failure functional class, quality of life, left ventricular ejection fraction and recruitment of previously akinetic left ventricular wall segments were observed. Conclusion All CardiAMP HF protocol procedures were feasible and well tolerated. Favorable functional, echo and quality of life trends suggest this approach may offer promise for patients with post MI heart failure. The randomized CardiAMP Heart Failure pivotal trial is underway to confirm the efficacy of this approach. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02438306

It is clear that existing cardiovascular disease is a major risk factor for COVID-19 and related adverse outcomes. In addition to acute respiratory syndrome, a large cohort also develop myocardial or vascular dysfunction, in part from inflammation and renin angiotensin system activation with increased sympathetic outflow, cardiac arrhythmias, ischemia, heart failure, and thromboembolic complications that portend poor outcomes related to COVID-19. We summarize recent information for hospitalists and internists on the front line of this pandemic regarding its cardiovascular impacts and management and the need for cardiovascular consultation.

Objectives The aim of this study was to investigate the impact of spontaneous coronary artery dissection (SCAD) on 30-day readmission rates following hospitalization with acute myocardial infarction (AMI) using a national database. Background AMI in the setting of SCAD represents an uncommon type of myocardial infarction with limited data on short-term outcomes. Methods All hospitalizations with primary or index diagnoses of AMI from 2010 to 2015 in the Nationwide Readmissions Database were queried. The primary outcome was overall 30-day readmission rates in both SCAD and non-SCAD cohorts. Propensity score matching (1:2) was conducted. Results A total of 2,654,087 patients with AMI were included in the final analysis, of whom 1,386 (0.052%) were diagnosed with SCAD. SCAD was associated with a higher readmission rate in the SCAD cohort (12.3% vs. 9.9%; p = 0.022). The main causes of readmissions in the SCAD cohort were cardiac causes (80.6%), and AMI was the most common cardiac cause (44.8%), followed by chest pain (20.1%) and arrhythmia (12.7%). Among the SCAD readmissions, 50.6% patients were readmitted in the first week post-discharge, with 54.5% of AMI readmissions occurring in the first 2 days post-discharge. Conclusions The incidence of 30-day readmission following AMI and SCAD is nontrivial and occurs early post-discharge. Most readmissions are due to cardiac causes, especially AMI. Targeted management approaches are needed to diminish the high rates of readmission and early recurrent AMI.

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.), Graphical abstract, Women with myocardial infarction with no obstructive coronary artery disease (MINOCA) are increasingly recognized…

Purpose We investigated the outcomes of patients who underwent Transcatheter Aortic Valve Replacement (TAVR) with and without Balloon Aortic Valvuloplasty (BAV) using the SAPIEN 3 (S3) valve. Methods All patients who underwent TAVR using S3 valve were included. The primary outcomes were the incidence of stroke and significant paravalvular leak (PVL). Secondary outcomes were the incidence of mortality, balloon post dilation, and need for permanent pacemaker . Results From July-2014 to April-2018, 34 (9%) patients underwent BAV prior to TAVR and 344 (91%) patients underwent direct TAVR without BAV using the S3 valve. The Society of Thoracic Surgeons (STS) risk score was similar between two groups; 5.8 ± 3.5 in no BAV group and 5.4 ± 3.3 in BAV group, p = 0.53. After TAVR, 6 (1.7%) patients in no BAV group but no patient in BAV group developed stroke (p = 1.0). No patient had severe PVL and only 5 patients (1.3%) had moderate PVL at 30-day; 4 (1.2%) in no BAV group and 1 (2.9%) in BAV group (p = 0.38). Forty-six patients (13.4%) in the no BAV group and 4 (11.8%) patients in the BAV group needed balloon post dilation (p = 1.0). Six (1.6%) patients died during hospitalization, all in the no BAV group (p = 1.0). Forty-five (11.9%) patients needed new pacemaker implantation ; 44 (12.8%) patients in no BAV group and 1 (2.9%) patient in BAV group ( p = 0.1). Two-year survival rate was 85% in no BAV group and 84% in BAV group (p = 0.46). Conclusions TAVR using S3 valves is associated with very low rates of post-TAVR stroke and significant PVL. Outcomes of direct TAVR are similar to the outcomes of TAVR with BAV, without an increased rate of stroke, significant PVL, or balloon post dilation.

Objective Elevated red blood cell distribution width (RDW) level has been shown to be associated with poor outcomes in patients with cardiovascular disease. Limited data are available regarding the prognostic value of RDW in transcatheter aortic valve replacement (TAVR) patients. Therefore, we aimed to investigate the impact of RDW variation on outcomes of TAVR patients. Methods From March 20, 2012, to February 20, 2020, the pre-TAVR RDW levels of 1,163 consecutive TAVR patients were examined. Receiver operating curves were set to define the most accurate cut-point, which was subsequently validated in our validation set. Associations of RDW levels with early and long-term outcomes were investigated. Results A total of 988 patients were eligible for the analysis. Patients with 30-day, 1-year, and 7-year mortality had significantly higher pre-TAVR RDW levels (15.8% [12.9-19.1] vs 14.7% [11.6-26.3], P = 0.01; 16% [12.3-26.3] vs 14.7% [11.6-24.3], P < 0.001; 15.6% [12.3-26.3] vs 14.6% [11.6-24.3], P < 0.001, respectively). A RDW of 14.5% was found as the most sensitive and specific cut-point for mortality at 1 and 7 years (HR = 2.6, 95% CI: 1.6-4.2, P < 0.001; HR = 1.8, 95% CI: 1.3-2.4, P < 0.001), with mortality of 22% versus 10% at 1 year ( P < 0.001) and 37% versus 27% at 7 years ( P < 0.001) in patients with RDW ≥14.5% versus those with RDW Conclusions RDW is an important prognostic factor in TAVR patients. A RDW level higher than 14.5% is significantly associated with post-TAVR early and late mortality. RDW levels should be incorporated into current risk assessment models as an additional variable to predict post-TAVR outcomes.

Objectives Individual randomized trials comparing drug-eluting balloons (DEB) versus everolimus-eluting stents (EES) for in-stent restenosis (ISR) were underpowered for clinical end-points. The objective of this study was to compare the clinical outcomes of DEB versus EES for any ISR. Materials & methods Electronic databases were searched for randomized trials which compared DEB versus EES for any ISR (i.e., drug eluting or bare metal stents). Summary estimate risk ratios (RRs) were constructed using a DerSimonian and Laird random effects model. Results Five trials with 962 patients were included. In-segment minimum lumen diameter (MLD) was lower with DEB (standardized mean difference −0.24, 95% confidence interval [CI] −0.46 – −0.01) on angiographic follow-up at a mean of 8.6 months. There was no statistically significant difference in the risk of target vessel revascularization (TVR) at 1 year (RR 1.15, 95% CI 0.60–2.19), but TVR was increased with DEB at 3 years (RR 1.87, 95% CI 1.15–3.03). The risk of target lesion revascularization (TLR) was statistically increased with DEB (RR 2.17, 95% CI 1.13–4.19) at a mean of 24.4 months. There was no difference in the risk of MI, stent thrombosis , cardiac mortality and all-cause mortality between both groups. Conclusion In patients with any type of ISR, DEB was associated a similar risk of TVR at 1-year, but increased risk of TVR and TLR at longer follow-up, as compared with EES. The quality of evidence was moderate, suggesting the need for further randomized trials with longer follow-up to confirm the role of DEB in the management of ISR.

Symptomatic non-obstructive coronary artery disease (NOCAD) is an increasingly recognised entity that is associated with poor cardiovascular outcomes. Nearly half of those undergoing coronary angiography for appropriate indications, such as typical angina, or a positive stress test have no obstructive lesion. There are no guideline recommendations as to how to care properly for these patients. Physiologic assessment of the coronary arteries beyond two-dimensional angiography is not standardised, yet it can provide valuable information in patients presenting with typical angina in the setting of NOCAD. In this consensus document, we detail steps for the interventional cardiologist to evaluate the patient with symptomatic NOCAD in the cardiac catheterisation laboratory, first with the assessment of coronary flow reserve (CFR), and then with delineation of deficiencies in non-endothelium-dependent CFR (CFRne) versus endothelium-dependent CFR (CFRe) using provocative agents such as adenosine and acetylcholine, respectively, followed by the evaluation of smooth muscle function with nitroglycerine (NTG). Once the mechanism behind the anginal symptoms is established, one can identify the appropriate treatment strategies to address the physiologic deficiency that is present. Despite an established safety profile, a comprehensive assessment may be considered for selected patients which requires an understanding of the appropriate invasive evaluation by the practising interventional cardiologist when evaluating not only patients with obstructive CAD but also those with NOCAD.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

To determine the relationship between coronary vascular dysfunction and history of migraines in women with suspected ischemia and no obstructive coronary arteries (INOCA).In the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study, 402 women with suspected INOCA answered baseline angina questionnaires, including the Seattle Angina Questionnaire (SAQ). Coronary function testing (CFT) performed in a subgroup of 252 women evaluated for nonendothelial and endothelial-dependent coronary vascular function. Wilcoxon rank sum test,Of the 252 women who underwent CFT, 126 (50%) women reported migraine history. Compared to women who reported no migraines, women with migraines were younger and more were premenopausal. They had more angina at rest, with strong emotions, and hot/cold temperatures, as well as angina that wakes them from sleep (Among women with suspected INOCA, migraine history is prevalent and women with migraines have worse angina compared to those without migraines. Coronary vascular dysfunction diagnosed by CFT does not appear to relate to migraine history.

BACKGROUND: Women with suspected ischemia and no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) as measured by impaired coronary flow reserve (CFR), which is associated with angina and adverse cardiovascular events. CFR is a ratio of hyperemic to baseline average peak velocity (bAPV), and the relation of baseline flow to angina is not understood. METHODS: We evaluated 259 women enrolled in the WISE-Coronary Vascular Dysfunction (WISE-CVD) project with suspected CMD who underwent invasive coronary functional testing. We analyzed variables stratified by high (e.g. ≥22 cm/sec) vs low (

Background: Relatively high left ventricular ejection fraction (EF) (>65%) in women was recently associated with higher all-cause mortality over 6 years follow-up in the CONFIRM study. We sought to evaluate high EF and major adverse cardiovascular events (MACE) in the Women’s Ischemia Syndrome Evaluation (WISE) study. Methods: The WISE original cohort (enrolled 1996-2000) is a multicenter prospective study of women with suspected ischemic heart disease undergoing clinically indicated invasive coronary angiography. We investigated the relationship between high (>65%) and normal (55-65%) EF and MACE, defined as all-cause death, nonfatal myocardial infarction (MI), stroke and heart failure (HF) hospitalization using Kaplan Meier (KM) and regression analyses. Results: A total of 653 women were included (298 high and 355 normal EF). Mean age was 58±11 years and mean EF was 68±7%. There was no significant difference in MACE by EF group over a 10-year follow-up period (log rank p=0.54, Figure ). When patients were stratified by the presence of obstructive CAD, MACE rates remained similar between high and normal EF. High EF was not associated with stroke or HF but had a lower MI risk (log rank p=0.03, Table ). EF was not associated with MACE in a multivariable regression model. Conclusions: Among women presenting with evidence of ischemia, there was no significant difference in MACE between high and normal EF groups. High EF was associated with a lower risk of myocardial infarction as an individual component of MACE.

Background: Relatively high left ventricular ejection fraction (EF) (>65%) was recently associated with higher all-cause mortality in women but not men undergoing noninvasive coronary angiography in the CONFIRM study, although this did not remain significant following adjustment for risk variables and mortality was not adjudicated. We investigated high EF and adjudicated all-cause mortality in the Women’s Ischemia Syndrome Evaluation (WISE) study. Methods: The WISE original cohort (enrolled 1996-2000), is a multicenter prospective study of women with suspected ischemic heart disease undergoing clinically indicated coronary angiography. EF was calculated by invasive left ventriculography. We investigated the relationship among high (>65%), normal (55-65%) and low ( Results: Overall 734 women included 298 (41%) high, 355 (48%) normal, and 81 (11%) low EF. The mean age was 58±11 years and mean EF was 65±11% (43%, 63% and 75% in the low, normal and high groups respectively). Over 10 years of follow-up, all-cause mortality occurred in 18% of patients, ranging from 12% in the high EF group to 41% in the low EF group. EF was associated with mortality among groups ( Figure ). Low EF remained a significant predictor of mortality compared to high EF, but normal EF compared to high EF did not in a multivariable regression model. Compared to women in the CONFIRM study, our cohort had higher mean EF (65% v. 62%), higher rates of obstructive CAD and diabetes, and lower rates of hypertension and dyslipidemia. Conclusions: Higher EF was not associated with higher all-cause mortality adjudicated predominantly cardiovascular in women with evidence of ischemia. Potential explanations for the lack of concordance with the CONFIRM study may include lack of death adjudication, differences in comorbidities, or other unknown factors.

Objective: Women with symptoms or signs of myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary vascular dysfunction and elevated risk for adverse cardiovascular events. We hypothesized that u-hscTnI (ultra-high–sensitivity cardiac troponin I), a sensitive indicator of ischemic cardiomyocyte injury, is associated with coronary vascular dysfunction in women with INOCA. Approach and Results: Women (N=263) with INOCA enrolled in the WISE-CVD study (Women’s Ischemic Syndrome Evaluation–Coronary Vascular Dysfunction) underwent invasive coronary vascular function testing and u-hscTnI measurements (Simoa HD-1 Analyzer; Quanterix Corporation, Lexington, MA). Logistic regression models, adjusted for traditional cardiovascular risk factors were used to evaluate associations between u-hscTnI and coronary vascular function. Women with coronary vascular dysfunction (microvascular constriction and limited coronary epicardial dilation) had higher plasma u-hscTnI levels (both P =0.001). u-hscTnI levels were associated with microvascular constriction (odds ratio, 1.38 per doubling of u-hscTnI [95% CI, 1.03–1.84]; P =0.033) and limited coronary epicardial dilation (odds ratio, 1.37 per doubling of u-hscTnI [95% CI, 1.04–1.81]; P =0.026). u-hscTnI levels were not associated with microvascular dilation or coronary epicardial constriction. Conclusions: Our findings indicate that higher u-hscTnI is associated with coronary vascular dysfunction in women with INOCA. This suggests that ischemic cardiomyocyte injury in the setting of coronary vascular dysfunction has the potential to contribute to adverse cardiovascular outcomes observed in these women. Additional studies are needed to confirm and investigate mechanisms underlying these findings in INOCA. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00832702.

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% P =0.03). Hypertension, dyslipidemia, nonobstructive CAD, use of nitrates, statins, and angiotensin‐converting enzyme inhibitors were univariate predictors of angina hospitalization. Adjusted multivariate hazard ratios for angina hospitalization were significant for use of nitrates 2.58 (1.80–3.69, P P =0.004), and angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers 1.81 (1.22–2.68, P =0.003). Conclusions Angina hospitalization rates continued at a relatively constant rate in all women with no obstructive CAD despite medical advances. Clinical trials aimed at reducing angina hospitalization rates and identifying the pathophysiological mechanisms contributing to angina symptoms in women with no CAD and women with no obstructive CAD.

BACKGROUND. Women with evidence of ischemia and no obstructive coronary arteries (INOCA) often have coronary microvascular dysfunction (CMD) indicated by impaired coronary flow reserve (CFR) to adenosine. Low CFR is associated with an adverse prognosis, including incident heart failure. Because the CFR calculation relies on the baseline intrinsic coronary vasomotor flow velocity, a major determinate of CFR and the degree of variation in baseline flow alone may be an important contributor to risk of adverse outcomes in women with CMD. A better understanding of baseline blood flow in the setting of low CFR and its association with myocardial performance would be helpful. METHODS. We evaluated 74 women who underwent invasive coronary reactivity testing in the Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study and had impaired CFR (

BACKGROUND Bicuspid aortic valve (BAV) stenosis has been considered a relative contraindication to transcatheter aortic valve replacement (TAVR). We compared the outcomes of TAVR in patients with BAV stenosis versus patients with trileaflet aortic valve stenosis. METHODS From March 2012 to September 2017, 727 patients underwent TAVR. Thirty-two patients with BAV were included in this study and compared to 96 patients with comparable risk factors (1:3) with a trileaflet aortic valve (TAV). Transesophageal echocardiography was used to estimate post-TAVR degree of paravalvular leak (PVL). RESULTS Mean ± standard deviation Society of Thoracic Surgeons risk was 6.01 ± 3.42 in the BAV group and 6.08 ± 3.76 in the TAV group (P = 0.92). Thirty-day mortality was 4.2% (N = 4) in the TAV group and 6.25% (N = 2) in the BAV group (P = 0.63). Three (3.1%) patients in the TAV group and two (6.25%) patients in the BAV group developed a post operative stroke (P = 0.59). Following TAVR, mean aortic valve gradient significantly decreased in both TAV (42.56 ± 14.93 vs 9.27 ± 5.57, 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.

Background Erectile dysfunction has been reported as an adverse effect of statin therapy. Methods We performed a meta-analysis of randomized trials and observational studies that compared statin users versus non-statin users and reported data regarding new onset of erectile dysfunction in men with established cardiovascular disease or cardiovascular disease risk factors. We used DerSimonian-Laird and Peto models to construct the summary estimates risk ratio. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the overall quality of evidence for new-onset erectile dysfunction. Results Three randomized trials and 3 observational studies were identified, with 69,448 men, of whom 24,661 were statin users. Statin use was not associated with an increased risk of new onset of erectile dysfunction by random effects model or fixed effect model (risk ratio 0.96; 95% confidence interval, 0.84-1.10; P = .58; and odds ratio 0.95; 95% confidence interval, 0.88-1.02; P = .20, respectively). This effect was similar in randomized trials and observational studies ( P interaction = .86). Randomized trials provided a moderate quality of evidence, and observational studies provided a very low quality of evidence by the GRADE assessment. Random effects meta-regression analyses revealed no difference in treatment effect according to age or diabetes mellitus ( P = .83 and P = .74, respectively). Conclusions Among men with established cardiovascular disease or cardiovascular disease risk factors, statin use does not seem to be associated with a new onset of erectile dysfunction. Adequately powered and high-quality randomized trials are recommended to confirm these findings.

The efficacy of second‐generation drug‐eluting stents (DES; eg, everolimus and zotarolimus) compared with bare‐metal stents (BMS) in patients undergoing percutaneous coronary intervention was challenged recently by new evidence from large clinical trials. Thus, we aimed to conduct an updated systematic review and meta‐analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of second‐generation DES compared with BMS. Electronic databases were systematically searched for all RCTs comparing second‐generation DES with BMS and reporting clinical outcomes. The primary efficacy outcome was major adverse cardiac events (MACE); the primary safety outcome was definite stent thrombosis. The DerSimonian and Laird method was used for estimation of summary risk ratios (RR). A total of 9 trials involving 17 682 patients were included in the final analysis. Compared with BMS, second‐generation DES were associated with decreased incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69‐0.88), driven by the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48‐0.95), target‐lesion revascularization (RR: 0.47, 95% CI: 0.42‐0.53), definite stent thrombosis (RR: 0.57, 95% CI: 0.41‐0.78), and definite/probable stent thrombosis (RR: 0.54, 95% CI: 0.38‐0.80). The incidence of all‐cause mortality was similar between groups (RR: 0.94, 95% CI: 0.79‐1.10). Meta‐regression showed lower incidences of MI with DES implantation in elderly and diabetic patients (P = 0.026 and P

Objectives The authors sought to determine the clinical characteristics and in-hospital survival of women presenting with acute myocardial infarction (AMI) and spontaneous coronary artery dissection (SCAD). Background The clinical presentation and in-hospital survival of women with AMI and SCAD remains unclear. Methods The National Inpatient Sample (2009 to 2014) was queried for all women with a primary diagnosis of AMI and concomitant SCAD. Iatrogenic coronary dissection was excluded. The main outcome was in-hospital mortality. Propensity score matching and multivariable logistic regression analyses were performed. Results Among 752,352 eligible women with AMI, 7,347 had a SCAD diagnosis. Women with SCAD were younger (61.7 vs. 67.1 years of age) with less comorbidity. SCAD was associated with higher incidence of in-hospital mortality (6.8% vs. 3.4%). In SCAD patients, a decrease in in-hospital mortality was evident with time (11.4% in 2009 vs. 5.0% in 2014) and concurred with less percutaneous coronary intervention (PCI) (82.5% vs. 69.1%). Propensity score yielded 7,332 SCAD and 14,352 patients without SCAD. The odds ratio (OR) of in-hospital mortality remained higher with SCAD after propensity matching (OR: 1.87, 95% confidence interval [CI]: 1.65 to 2.11) and on multivariable regression analyses (OR: 2.41, 95% CI: 2.07 to 2.80). PCI was associated with higher mortality in SCAD patients presenting with non–ST-segment elevation myocardial infarction (OR: 2.01; 95% CI: 1.00 to 4.47), but not with STEMI (OR: 0.62; 95% CI: 0.41 to 0.96). Conclusions Women presenting with AMI and SCAD appear to be at higher risk of in-hospital mortality. Lower rates of PCI were associated with improved survival, with evidence of worse outcomes when PCI was performed for SCAD in the setting of non with ST-segment elevation myocardial infarction.

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 Recent trials comparing PCI with CABG for unprotected left main disease yielded discrepant evidence. Objectives To perform an updated meta-analysis of randomized trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease. Methods Randomized trials comparing PCI versus CABG for patients with unprotected left main coronary artery disease were included. Summary estimates risk ratios (RRs) were performed with a DerSimonian and Laird model at short-term, intermediate and long-term follow-up periods (i.e., 30-days, 1-year, and >1-year). Outcomes evaluated were major adverse cardiac and cerebrovascular events (MACCE), all-cause mortality, myocardial infarction, stroke, revascularization and stent thrombosis or symptomatic graft occlusion. Results Six trials with 4,700 patients and a mean SYNTAX score of 23 were included. At short-term follow-up, the risk of MACCE was lower with PCI (RR 0.55, 95% confidence interval [CI] 0.39-0.76) driven by the lower risk of myocardial infarction (RR 0.67, 95% CI 0.46-0.99), and stroke (RR 0.38, 95% CI 0.16-0.90). The risk of MACCE was similar at the intermediate follow-up (RR 1.21, 95% CI 0.97-1.51). At long-term follow-up, PCI was associated with a higher risk of MACCE (RR 1.19, 95% CI 1.01-1.41), due to a higher risk of revascularization (RR 1.62, 95% CI 1.34-1.94), while the risk of all-cause mortality, myocardial infarction, and stroke were similar. Conclusions In patients with unprotected left main coronary disease and low to intermediate SYNTAX score, PCI might be an acceptable alternative to CABG. © 2017 Wiley Periodicals, Inc.

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

ObjectiveLimited data is available about the effect of implanted valve size on prosthesis–patient mismatch (PPM) incidence and aortic gradient (AG) after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). We compared PPM incidence and postprocedural AG between TAVR and SAVR patients considering the impact of implanted valve size.MethodsFrom March 20, 2012, to September 30, 2015, 563 consecutive patients underwent TAVR ( n = 419) or isolated SAVR ( n = 144). Postprocedural transthoracic echocardiography was obtained within 30 days; AG, effective orifice area (EOA), and EOA index were calculated.ResultsA total of 381 patients in TAVR group and 82 patients in SAVR group were included. Mean preoperative AG and mean aortic valve area were not significantly different between the 2 groups. Postprocedural AG was significantly lower in TAVR than SAVR group, 7.74 ± 5.39 versus 14.27 ± 8.16 ( P < 0.001). Between patients who had TAVR and SAVR with a valve size ≤23 mm, SAVR patients were 3 times more likely to have greater than mild AG after the procedure, OR: 3.1 (95% CI, 1.1 to 8.9) ( P < 0.001). PPM incidence was significantly higher in SAVR group than TAVR group, 44 (53.7%) versus 112 (29.4%), OR = 2.8 (95% CI, 1.7 to 4.5) ( P < 0.001). The PPM incidence was also higher in SAVR group than TAVR group among those who had the procedures with a valve size ≤23 mm, 35 (64.8%) versus 56 (47.9%), OR = 2 (95% CI, 1.1 to 3.9) ( P = 0.048). Postprocedural outcomes were comparable between the 2 groups.ConclusionsIn comparison to SAVR, TAVR is associated with less PPM and lower AG, especially in patients receiving a valve size ≤23 mm.

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 Results. In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p Conclusions. This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.

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+ (β −0.18, p = 0.042), CD34+/CD133+ (β −0.24, p = 0.036), and CD34+/CXCR4+ (β −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.

Objective To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients. Background Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions. Methods The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]). Patients with an EF ≥20% but ≤45%, multivessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II–IV) or heart failure (NYHA Class II–III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping, and IM delivery of ADRCs or placebo. Results Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65 ± 8 years, baseline LVEF(%) 31.1 ± 8.7 (ADRC), 31.8 ± 7.7 (placebo) were enrolled. Change in V02 max favored ADRCs (+45.4 ± 222 vs. −9.5 ± 137 mL/min) but there was no difference in left ventricular function or volumes. At 12-months, heart failure hospitalizations occurred in 2/17 (11.7%) [ADRC] and 3/14 (21.4%) [placebo]. Differences in NYHA and CCS classes favored ADRCs at 12-months with significant improvement in MLHFQ (−21.6 + 13.9 vs. −5.5 + 23.8, P = 0.038). Conclusions A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in “no option” CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. © 2016 Wiley Periodicals, Inc.

We know that endocardial mapping reports left ventricular electrical activity (voltage) and that these data can predict outcomes in patients undergoing traditional revascularization. Because the mapping data from experimental models have also been linked with myocardial viability, we hypothesized an association between increased unipolar voltage in patients undergoing intramyocardial injections and their subsequent improvement in left ventricular performance. For this exploratory analysis, we evaluated 86 patients with left ventricular dysfunction, heart-failure symptoms, possible angina, and no revascularization options, who were undergoing endocardial mapping. Fifty-seven patients received bone marrow mononuclear cell (BMC) injections and 29 patients received cell-free injections of a placebo. The average mapping site voltage was 9.7 ± 2 mV, and sites with voltage of ≥6.9 mV were engaged by needle and injected (with BMC or placebo). For all patients, at 6 months, left ventricular ejection fraction (LVEF) improved, and after covariate adjustment this improvement was best predicted by injection-site voltage. For every 2-mV increase in baseline voltage, we detected a 1.3 increase in absolute LVEF units for all patients (P=0.038). Multiple linear regression analyses confirmed that voltage and the CD34+ count present in bone marrow (but not treatment assignment) were associated with improved LVEF (P=0.03 and P=0.014, respectively). In an exploratory analysis, higher endocardial voltage and bone marrow CD34+ levels were associated with improved left ventricular function among ischemic cardiomyopathy patients. Intramyocardial needle injections, possibly through stimulation of angiogenesis, might serve as a future therapy in patients with reduced left ventricular function and warrants investigation.

Summary Background Ixmyelocel-T is an expanded, multicellular therapy produced from a patient's own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical, functional, symptomatic, and quality-of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy. We aimed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions. Methods In this randomised, double-blind, placebo-controlled phase 2B trial (ixCELL-DCM), patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy, who had left ventricular ejection fraction 35% or less, an automatic implantable cardioverter defibrillator, and who were ineligible for revascularisation procedures were randomly assigned (1:1) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months. Randomisation was done through an interactive (voice/web) response system. The pharmacist, treating physician, and coordinator at each site were unblinded, but the the follow-up team was completely blinded. The primary endpoint was a composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01670981. Findings Between April 2, 2013, and Jan 28, 2015, 126 participants were randomly assigned to receive either ixmyelocel-T (n=66) or placebo (n=60). 114 (90%) patients comprised the modified intention-to-treat population and 109 (87%) patients were included in the per-protocol primary efficacy analysis (58 in the ixmyelocel-T group and 51 in the placebo group). The primary efficacy endpoint was observed in 47 patients: 50 events in 25 (49%) of 51 patients in the placebo group and 38 events in 22 (38%) of 58 patients in the ixmyelocel-T group, which represents a 37% reduction in cardiac events compared with placebo (risk ratio 0·63 [95% CI 0·42–0·97]; p=0·0344). 41 (75%) of 51 participants in the placebo group had serious adverse events versus 31 (53%) of 58 in the ixmyelocel-T group (p=0·0197). Interpretation To the best of our knowledge, ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far. The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy resulted in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes. Funding Vericel Corporation.

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.

Limited data are available regarding impact of mitral valve regurgitation (MR) on patient outcomes following transcatheter aortic valve replacement (TAVR). In this study, we investigated the impact of TAVR on improvement of MR and patient outcomes. Patients who underwent TAVR from March 2012 to

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

Background Prior 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 Results Hospitalizations 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). Conclusions Among 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.

This editorial refers to ‘How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST elevation myocardial infarction?’, by G.L. De Maria et al ., doi:10.1093/eurheartj/ehv353. There have been significant reductions in the mortality associated with ST elevation myocardial infarction (STEMI) over the last several decades. On the background of declining coronary heart disease mortality in the USA and Western Europe, the use of prompt reperfusion strategies and adjunctive pharmacotherapy, mortality in STEMI patients has continued to improve. The 30-day mortality from four French registries over 15 years decreased from 11.3 to 4.4% between 1995 and 2010.1 Data from the American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR) reveal a risk-adjusted in-hospital mortality of 5.5% among STEMI patients in 2009.2 A large registry of STEMI patients in Sweden demonstrated a reduction in 30-day and 1-year mortality from 15.0 to 8.6% ( P < 0.001) and 21.0 to 13.3% ( P < 0.001), respectively.3 The reperfusion era was ushered in during the 1980s with mortality reductions obtained using thrombolytic therapy.4 This was followed by the use of mechanical reperfusion with percutaneous coronary intervention (PCI). Subsequent meta-analyses of randomized trials comparing thrombolytic therapy and PCI documented PCI as the preferred strategy leading to reductions in mortality, stroke and re-infarction. In longer-term (>1 year) follow-up, PCI for STEMI patients was found to lower mortality and re-infarction rates.5 This has led to PCI as the preferred strategy in patients presenting with STEMI and is endorsed by guidelines internationally.6 Despite prompt restoration of epicardial coronary flow, however, normalization of flow at the myocardial or microcirculatory level …

Objective In women, metabolic syndrome (MetS) is associated with higher risk of ischemic heart disease-related adverse outcomes versus individual components. We examined the relationship of MetS to subclinical coronary atherosclerosis. Methods Women (n = 100) undergoing coronary angiography for suspected ischemia but without obstructive coronary artery disease (CAD) underwent intravascular ultrasound (IVUS) of a segment of the left coronary artery. A core lab, masked to other findings, assessed IVUS measures and normalized volume measures to pull-back length. MetS [defined using ATPIII criteria (fasting glucose ≥ 100 mg/dl per revised NCEP guideline)] and its components were entered into multiple regression models to assess associations with IVUS measures. Results Detailed IVUS measurements were available in 87 women. Mean age was 54 ± 10 years, 36% had MetS, and 78% had atheroma. Comparing women with MetS versus without MetS, significant differences were observed for seven IVUS atherosclerosis measures, but were not significant after adjusting for the MetS components. Systolic blood pressure and waist circumference components remained independently positively associated with the IVUS measures after adjusting for age, diabetes, CAD family history, dyslipidemia, smoking, and hormone replacement. Conclusion In women with signs and symptoms of ischemia and no obstructive CAD, MetS is associated with coronary atherosclerosis presence and severity. However, these associations appear largely driven by components of waist circumference and systolic blood pressure versus MetS cluster. This supports the concept that MetS is a convenient clustering of risk factors rather than an independent risk predictor, and emphasizes that the critical factors for coronary atherosclerosis are potentially modifiable.

Despite the progress made over the past several decades, coronary artery disease remains one of the most significant health issues worldwide. Data in 2012 from the American Heart Association estimated coronary artery disease prevalence to be 15.5 million or 6.2% of U.S. adults older than 20 years of

Objectives This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype–guided antiplatelet therapy after percutaneous coronary intervention (PCI). Background CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. Methods After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. Results Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). Conclusions These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Background Women represent approximately half of heart failure hospitalizations and are disproportionately affected by heart failure with preserved ejection fraction (HFpEF). Women with signs and symptoms of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD) often have elevated left ventricular end-diastolic pressure (LVEDP). However, isolated elevated LVEDP in the absence of coronary microvascular dysfunction (CMD) is not understood. Methods Among 244 women with signs and symptoms of ischemia, no obstructive CAD, and preserved LVEF who underwent invasive coronary reactivity testing (CRT), 43 (18%) women had no evidence of CMD. LVEDP was measured at time of CRT, and left ventricular (LV) volumes and mass were assessed by cardiac magnetic resonance (CMR) imaging. Results Of the 43 women without CMD, 24 (56%) had elevated LVEDP [mean 18 mm Hg (SD = 3)] compared to 19 (44%) with normal LVEDP [11 mm Hg (SD = 3)]. The elevated LVEDP group had a comparatively higher systolic and diastolic blood pressure, lower LV end-diastolic volume index (EDVI), and higher mass-to-volume ratio. Other functional parameters were not significantly different. Conclusions Among women with signs and symptoms of ischemia without obstructive CAD, absence of CMD, and preserved LVEF, isolated elevated LVEDP is associated with a significantly higher systolic and diastolic blood pressure, higher LV mass-to-volume ratio and lower LV EDVI. These results suggest these women have maladaptive remodeling to blood pressure. Given the relatively high prevalence of HFpEF in women, these hypothesis-generating results suggest that further study of ventricular remodeling is warranted.

Although aspirin monotherapy is considered the standard of care after coronary artery bypass grafting (CABG), more recent evidence has suggested a benefit with dual antiplatelet therapy (DAPT) after CABG. We performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of aspirin monotherapy with DAPT in patients after CABG. Subgroup analyses were conducted according to surgical technique (i.e., on vs off pump) and clinical presentation (acute coronary syndrome vs no acute coronary syndrome). Random effects overall risk ratios (RR) were calculated using the DerSimonian and Laird model. Eight randomized control trials and 9 observational studies with a total of 11,135 patients were included. At a mean follow-up of 23 months, major adverse cardiac events (10.3% vs 12.1%, RR 0.84, confidence interval [CI] 0.71 to 0.99), all-cause mortality (5.7% vs 7.0%, RR 0.67, CI 0.48 to 0.94), and graft occlusion (11.3% vs 14.2%, RR 0.79, CI 0.63 to 0.98) were less with DAPT than with aspirin monotherapy. There was no difference in myocardial infarction, stroke, or major bleeding between the 2 groups. In conclusion, DAPT appears to be associated with a reduction in graft occlusion, major adverse cardiac events, and all-cause mortality, without significantly increasing major bleeding compared with aspirin monotherapy in patients undergoing CABG.

The current generation of drug eluting stents (DES) exhibit a very low risk of stent thrombosis, restenosis, and need for repeat intervention (1). However, it took almost a decade for DES to reach this degree of maturation. Yet, these devices still carry a risk of very late stent restenosis and the need for repeat revascularization, due to the persistence of the metallic backbone and/or residual polymer once the anti-proliferative agent has completely eluted. As such, bioresorbable vascular scaffolds (BVS) hold the promise of offering an early anti-proliferative effect in addition to the mechanical support similar to DES for 2–3 years followed by complete bioabsorption. These effects are theoretically appealing. Complete bioabsorption could allow for preservation of the coronary vasomotion (which has been linked to the increased risks of late stent restenosis with DES), a possible reduction in the duration of dual antiplatelet therapy (DAPT) following the stent implantation, and the preservation of native coronary architecture which would allow for future surgical therapy.

Background Complete revascularization of patients with ST-elevation myocardial infarction and multivessel coronary artery disease reduces adverse events compared to infarct-related artery only revascularization. Whether complete revascularization should be done as multivessel intervention during index procedure or as a staged procedure remains controversial. Method We performed a meta-analysis of randomized controlled trials comparing outcomes of multivessel intervention in patients with ST-elevation myocardial infarction and multivessel coronary artery disease as staged procedure versus at the time of index procedure. Composite of death or myocardial infarction was the primary outcome. Mantel-Haenszel risk ratios were calculated using random effect model. Results Six randomized studies with a total of 1126 patients met our selection criteria. At a mean follow-up of 13 months, composite of myocardial infarction or death (7.2% vs 11.7%, RR: 1.66, 95%CI: 1.09-2.52, P = 0.02), all cause mortality (RR: 2.55, 95%CI: 1.42-4.58, P

BACKGROUND We compared stroke occurrence and outcomes between Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR), both periprocedural and at follow-up. METHODS From March 2012 to December 2014, 391 consecutive patients underwent TAVR (N.=290) or isolated SAVR (N.=101), concomitantly. Patients' data were prospectively collected. RESULTS TAVR patients had more comorbidities. One (0.34%) TIA and 9 (3.11%) strokes occurred in-hospital following TAVR, but no cerebrovascular event occurred after SAVR (P=0.11). One stroke (0.99%) and one TIA (0.99%) were detected in SAVR group within 30 days. Among TAVR patients, one (0.75%) stroke at 6 months, 2 (1.9%) strokes and 2 (1.9%) TIAs at 12 months were diagnosed. Kaplan-Meier analysis revealed that 96% and 99% 12-month CVA free survival following TAVR and SAVR, respectively (P=0.67). Preoperative mean trans-aortic valve systolic pressure gradient higher than 40 mmHg remained as risk factor for stroke in TAVR patients only, OR: 4.48 (CI: 1.2-16.54, P=0.02). One intraoperative death, and 5 (4 with CVA) in-hospital deaths occurred after TAVR; whereas only one patient died in SAVR group (P=0.49). Thirty-day mortality was 3.8% (11/290) for TAVR and 0.99% (1/101) for SAVR patients. SAVR patients' survival was 99% at 6 months, 97.9% at 12, and 96.4% at 24 months, whereas survival in TAVR was 97.5% at 6, 92% at 12, and 73.6% at 24 months (HR: 8.43 (CI: 2.47-28.73), P

Choosing an antithrombotic regimen after coronary intervention in patients with concomitant indication for anticoagulation is a challenge commonly encountered by clinicians.We performed a meta-analysis of observational studies and randomized, controlled trials comparing outcomes of triple therapy (dual antiplatelet therapy and anticoagulant) with dual therapy (single antiplatelet therapy and anticoagulant) in patients taking long-term anticoagulants after percutaneous coronary intervention. Major bleeding was the primary outcome. Random effects overall risk ratios (RRs) were calculated using the DerSimonian and Laird model.Nine observational studies and 2 randomized controlled trials with a total of 7276 patients met our selection criteria. At a mean follow-up of 10.8 months major bleeding was higher in the triple therapy cohort compared with dual therapy (6.6% vs 3.8%; RR 1.54; 95% confidence interval [CI], 1.2-1.98; P .01). No difference was observed between the 2 groups for all-cause mortality (RR 0.98; 95% CI, 0.68-1.43; P = .93), major adverse cardiac events (RR 1.03; 95% CI, 0.8-1.32; P = .83), thromboembolic events (RR 1.02; 95% CI, 0.49-2.10; P = .96), myocardial infarction (RR 0.85; 95% CI, 0.67-1.09; P = .21), stent thrombosis (RR 0.77; 95% CI, 0.46-1.3; P = .33), and target vessel revascularization (RR 0.87; 95% CI, 0.66-1.15; P = .33).In patients receiving anticoagulant therapy, a strategy of single antiplatelet therapy confers a benefit of less major bleeding with no difference in all-cause mortality, cardiovascular mortality, major adverse cardiac events, myocardial infarction, stent thrombosis, or thromboembolic event rate compared with dual antiplatelet therapy.

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 P P interaction =0.02). Conclusions An early invasive strategy may be associated with a lower incidence of in‐hospital mortality in patients with diabetes. The benefit of this strategy appears to be superior in patients presenting with non‐ST‐elevation myocardial infarction compared with unstable angina.

Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P =0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P =0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P =0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01774097.

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.