Search

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

Background: Paravalvular Leak (PVL) refers to the retrograde flow of blood in the space between an implanted cardiac valve and native tissue. These are unfortunately but luckily relatively uncommon complications of prosthetic valve replacement that, especially when moderate or severe, have important clinical consequences. Objective: Addressing PVL requires a multidisciplinary team to properly diagnose this process and choose the corrective option most likely to result in success. Methods: A comprehensive literature search was undertaken to formulate this narrative review. Results: This review highlights the complex nature of PVL and the promising contemporary treatments available. Conclusion: Clinicians should be adept at recognizing PVL and characterizing it using multimodality imaging. Using the many available tools and a multidisciplinary approach should lead to favorable outcomes in patients with PVL.

Background Ischemia with no obstructed coronary arteries (INOCA) is prevalent among women and associated with an increased risk of developing heart failure with preserved ejection fraction (HFpEF), however the mechanism linking these conditions remains poorly understood. Coronary vascular dysfunction is common in INOCA, representing a putative mechanism driving heart failure progression. Purpose To evaluate the role of coronary vascular dysfunction on left ventricular (LV) function in women with INOCA. Methods Women with suspected INOCA, defined as having signs and symptoms of ischemia but no obstructive coronary artery disease, underwent LV pressure-volume assessment at rest and during 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction. Coronary function testing was performed by infusing standard doses of adenosine, acetylcholine, and nitroglycerine through a guiding catheter placed in the left main coronary artery, per our published protocols. Using standardized definitions of normal versus abnormal responses, cases with zero abnormal coronary pathways (n=12) were compared to cases with three abnormal coronary pathways (n=7). Results At rest, end-systolic pressure and end-systolic elastance were elevated in cases with abnormal coronary vascular function (Figure), while normalized peak filling rate was lower (0.45±0.15 s mmHg–1 vs 0.37±0.08 s mmHg–1). With isometric handgrip, end-systolic pressure and end-systolic elastance increased similarly between groups, remaining highest in those with abnormal coronary vascular function (Figure). End-diastolic pressure-volume declined with handgrip in those without coronary vascular dysfunction, while increasing (up and to the left) in those with coronary vascular dysfunction (Figure). Likewise, normalized peak filling rate improved with handgrip in those without coronary vascular dysfunction, but did not change in those with coronary vascular dysfunction (0.66±0.37 s mmHg–1 vs 0.38±0.15 s mmHg–1). Conclusions We show heightened ventricular and vascular stiffness in women with INOCA who have abnormal coronary vascular function. These preliminary data support the hypothesis that coronary vascular dysfunction may be a putative mechanistic pathway driving heart failure progression in INOCA. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health

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

The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD-GENE score to predict the risk for atherothrombotic events in a diverse, real-world population of clopidogrel-treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD-GENE score ≥ 10 vs. 10. The risk of major atherothrombotic events was higher in patients with an ABCD-GENE score ≥ 10 (n = 505) vs. 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient-years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23-2.25, P 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. 10 (16.7 vs. 10.1 events per 100 patient-years, adjusted HR 1.59, 95% CI 1.11-2.30, P = 0.013). Our diverse, real-world data demonstrate diminished clopidogrel effectiveness in post-PCI patients with an ABCD-GENE score ≥ 10.

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…

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.

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.

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have emerged as helpful intravascular imaging tools to guide revascularization decisions during percutaneous coronary intervention (PCI). Studies have demonstrated that intravascular imaging is associated with improved clinical

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

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.

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.

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.