BACKGROUND:While disturbed wall shear stress (WSS) is associated with coronary plaque progression and vulnerability, its influence on stent neointimal healing is not well characterized. We designed a prospective, randomized trial to investigate the influence of WSS on neointimal healing in angulated arteries undergoing percutaneous coronary intervention (PCI). METHODS:Eighty-six patients were randomized to Xience Xpedition® (X-EES) or Resolute® Integrity/Onyx (R-ZES) drug-eluting stents. Patients underwent serial OCT imaging post PCI and at 12-months. Angiography was combined with OCT to generate post-stent vessel reconstructions. WSS was calculated using computational fluid dynamics. Post-stent WSS was related to strut, frame and patient level neointimal thickness (NIT) at 12-months. RESULTS:Sixty patients met inclusion criteria and had adequate OCT image quality for analysis. Mean age was 62.7 years, 78 % were men, and 37 % had diabetes. NIT at 12-months was 0.09 mm (0.05-0.15). There was no difference in frame level NIT (p = 0.08) or post-stent WSS (p = 0.75) between X-EES or R-ZES. Patient level analysis demonstrated correlation coefficients between WSS and NIT ranging from -0.78 to 0.67. Of these, 33 % were significantly positive, indicating an association between high WSS and increased NIT, while 31.6 % were significantly negative signifying an association between low WSS and increased NIT. Age, gender, hyperlipidemia, diabetes, renal insufficiency or prior MI was not associated with the distribution of correlation coefficients. CONCLUSIONS:The SHEAR-STENT study demonstrated no significant differences in WSS or NIT at 12 months between R-ZES and X-EES. A wide range of patient level correlation coefficients between WSS and NIT were observed, with some patients showing increased NIT was associated with low WSS and others associated with high WSS. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT02098876.

Coronary stent underexpansion is associated with restenosis and stent thrombosis. In clinical studies of atherosclerosis, high wall shear stress (WSS) has been associated with activation of prothrombotic pathways, upregulation of matrix metalloproteinases, and future myocardial infarction. We hypothesized that stent underexpansion is predictive of high WSS. WSS distribution was investigated in patients enrolled in the prospective randomized controlled study of angulated coronary arteries randomized to undergo percutaneous coronary intervention with R-ZES or X-EES. WSS was calculated from 3D reconstructions of arteries from intravascular ultrasound (IVUS) and angiography using computational fluid dynamics. A logistic regression model investigated the relationship between WSS and underexpansion and the relationship between underexpansion and stent platform. Mean age was 63±11, 78

Purpose of Review Obstructive coronary artery disease is a major cause of ischemia in both men and women; however, women are more likely to present with ischemia in the setting of no obstructive coronary arteries (INOCA) and myocardial infarction with no obstructive coronary arteries (MINOCA), conditions that are associated with adverse cardiovascular prognosis despite absence of coronary stenosis. In this review, we focus on mechanisms of coronary ischemia that should be considered in the differential diagnosis when routine anatomic clinical investigation leads to the finding of non-obstructive coronary artery disease on coronary angiography in the setting of acute myocardial infarction. Recent Findings There are multiple mechanisms that contribute to MINOCA, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction (CMD), coronary embolism and/or thrombosis, and spontaneous coronary artery dissection. Non-coronary causes such as myocarditis or supply–demand mismatch should also be considered on the differential when there is an unexplained troponin elevation. Use of advanced imaging and diagnostic techniques to determine the underlying etiology of MINOCA is feasible and helpful, as this has the potential to guide management and secondary prevention. Failure to identify the underlying cause(s) may result in inappropriate treatment and inaccurate counseling to patients. Summary MINOCA predominates in young women and is associated with a guarded prognosis. The diagnosis of MINOCA should prompt further investigation to determine the underlying cause of troponin elevation. Patients with INOCA and MINOCA are heterogeneous, and response to treatments can be variable. Large randomized controlled trials to determine longer-term optimal medical therapy for management of these conditions are under investigation.

Download : Download full-size image A 68-year-old female presented to the Emergency Department with substernal chest pain and shortness of breath after an episode of syncope. She had a past medical history of hypertension, diabetes, and anxiety. She reported significant stress and anxiety surrounding her family’s recent move to a new city away from friends of many years. Physical exam was pertinent for blood pressure 80/60 mmHg, pulse 130 beats per minute (bpm), respiratory rate 30 breaths per minute, and oxygen saturation 92% on room air. Other findings included jugular venous pressure (JVP) of 20 mmHg, bibasilar crackles, 2 + pitting edema bilaterally in the lower extremities, and cold extremities. Laboratory evaluation revealed a troponin 4.5 ng/mL, BNP (brain natriuretic peptide) of 500 ng/L, potassium 4.5 meQ/L, and creatinine of 2.0 mg/dL. Electrocardiogram (ECG) demonstrated ST segment elevation in leads V2–V6 with deep T-wave inversions and QTc of 500 ms. Chest X-ray was pertinent for cephalization of pulmonary vessels and bilateral Kerley B lines and was consistent with pulmonary edema. Given her presentation, she was suspected of having an acute coronary syndrome (ACS) and was taken to the cardiac catheterization laboratory. Coronary angiography revealed no obstruction of the coronary arteries and left ventricular end diastolic pressure of 30 mmHg with left ventriculography showing apical hypokinesis. Transthoracic echocardiogram revealed a dilated left ventricle with a depressed function of 30% with apical akinesis, and basal segments were hypercontractile. Moderate-to-severe mitral regurgitation was noted due to systolic anterior motion of the anterior leaflet of the mitral valve, with mild-to-moderate tricuspid regurgitation. Aortic valve was trileaflet with mild aortic regurgitation and a normal aortic root measurement. Right ventricular size and function were normal. What is the etiology of her presentation, and how would you manage her going forward? Over the past several decades, there has been an increasing awareness of sex differences in cardiovascular disease presentation and pathophysiology. Stress-induced cardiomyopathy or Takotsubo syndrome (TTS) is one such condition that overwhelmingly affects postmenopausal women who have recently experienced a physical or an emotional stressor. The stressor activates a neurohormonal cascade causing a catecholamine storm that provokes symptoms similar to those described in acute coronary syndrome and heart failure. There are characteristic echocardiographic features that can indicate that a Takotsubo event has occurred. Treatment focuses on management of acute heart failure and monitoring for arrhythmias, because these patients can be at high risk of adverse outcomes and complications during the acute phase. This review focuses on our contemporary understanding of pathophysiology, diagnosis, and management of this condition that differentially impacts women.

Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy.

The Absorb bioresorbable vascular scaffold (BVS) demonstrated higher rates of target lesion failure (TLF) at 3 years. Low wall shear stress (WSS) promotes several mechanisms related to device TLF. We aimed to investigate the mechanisms of higher event rates with BVS. We hypothesized that deployed

BACKGROUND:Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease. METHODS:In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed. RESULTS:No significant differences in ΔSAQ angina frequency scores (P=0.53) or Duke Activity Status Index (P=0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores (P=0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO2 max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 (P=0.02). CONCLUSIONS:Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.

Novel therapies for heart failure (HF) are increasingly being tested in larger, global populations.1 This trend, in large part, may be driven by logistics of global trial conduct and the ability to more expediently enrol patients from certain geographic regions.2 Consequently, these trial-level patterns may decrease relative participation from countries where patient enrolment is more difficult or expensive. Given key differences in patientlevel factors (e.g. race, diet, co-morbidities, socio-economic factors) and health care practices (e.g. baseline use of standard medical and device therapies) across geographic regions, there is potential that study results may not be generalizable to areas of the world under-represented in the trial.3 Moreover, increased regional heterogeneity may encumber site oversight and quality control, impacting the ability of the trial to include appropriately selected patients and demonstrate treatment benefit or harm, as exemplified in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial experience.4 To date, there has been limited quantitative appraisal of these aggregate triallevel patterns in geographic representation. Given the potential implications on future HF trial planning, we conducted a comprehensive systematic review of global region of enrolment in all HF trials published over the last 16 years in any peer-reviewed medical journal. We identified phase II–IV HF clinical trials with a sample size >100 (since smaller studies are by design single centre and unlikely to

Clinical trial design and execution are evolving as increasingly important considerations with respect to the success of heart failure trials. The current review highlights temporal trends in characteristics of heart failure clinical trials.

The Absorb bioresorbable vascular scaffold (BVS) is associated with higher rates of target lesion failure and device thrombosis at 3 years. Low wall shear stress (WSS) plays an important role in atherogenesis and potentially stent failure. In the prospective, multicenter, randomized ABSORB III

Given its continuous wire molding and sinusoidal design, we hypothesized that Resolute Integrity stent (R-ZES) is more conformable than the XIENCE Xpedition stent (X-EES) and therefore may induce more physiologic wall shear stress (WSS) in angulated coronary arteries. Interim analysis of

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in women. Historically, medical research has focused on male patients, and subsequently, there has been decreased awareness of the burden of ASCVD in females until recent years. The biological differences between sexes and differences in societal expectations defined by gender roles contribute to gender differences in ASCVD risk factors. With these differing risk profiles, risk assessment, risk stratification, and primary preventive measures of ASCVD are different in women and men. In this review article, clinicians will understand the risk factors unique to women, such as preeclampsia, gestational diabetes, and those that disproportionately affect them such as autoimmune disorders. With these conditions in mind, the approach to ASCVD risk assessment and stratification in women will be discussed. Furthermore, the literature behind the effects of primary preventive measures in women, including lifestyle modifications, aspirin, statins, and anticoagulation, will be reviewed. The aim of this review article was to ultimately improve ASCVD primary prevention by reducing gender disparities through education of physicians.

Background Newly developed white matter (WM) injury is common after cardiopulmonary bypass (CPB) in severe/complex congenital heart disease. Fractional anisotropy (FA) allows measurement of macroscopic organization of WM pathology but has rarely been applied after CPB. The aims of our animal study were to define CPB‐induced FA alterations and to determine correlations between these changes and cellular events after congenital heart disease surgery. Methods and Results Normal porcine WM development was first assessed between 3 and 7 weeks of age: 3‐week‐old piglets were randomly assigned to 1 of 3 CPB‐induced insults. FA was analyzed in 31 WM structures. WM oligodendrocytes, astrocytes, and microglia were assessed immunohistologically. Normal porcine WM development resembles human WM development in early infancy. We found region‐specific WM vulnerability to insults associated with CPB. FA changes after CPB were also insult dependent. Within various WM areas, WM within the frontal cortex was susceptible, suggesting that FA in the frontal cortex should be a biomarker for WM injury after CPB. FA increases occur parallel to cellular processes of WM maturation during normal development; however, they are altered following surgery. CPB‐induced oligodendrocyte dysmaturation, astrogliosis, and microglial expansion affect these changes. FA enabled capturing CPB‐induced cellular events 4 weeks postoperatively. Regions most resilient to CPB‐induced FA reduction were those that maintained mature oligodendrocytes. Conclusions Reducing alterations of oligodendrocyte development in the frontal cortex can be both a metric and a goal to improve neurodevelopmental impairment in the congenital heart disease population. Studies using this model can provide important data needed to better interpret human imaging studies.

This report describes the first confirmed case of isolated pyomyositis caused by a hypervirulent strain of Klebsiella pneumoniae. Pyomyositis is almost universally caused by gram-positive organisms and while the recent emergence of invasive disease due to hypervirulent K. pneumoniae has been well documented, the most common clinical manifestation reported is liver abscess. The K. pneumoniae isolate in our case had a hypermucousviscous phenotype as demonstrated by a positive string test and was confirmed to be hypervirulent with molecular testing. Documenting the extrahepatic manifestations of hypervirulent Klebsiella pneumoniae strains is important to increase clinical awareness and in guiding empiric antibiotic regimens.