Cardiac MRI improves identification of etiology of acute ischemic stroke.

BACKGROUND: An accurate subtype classification of acute ischemic stroke is important in clinical practice as it can greatly influence patient care in terms of acute management and devising secondary stroke prevention strategies. Approximately, one third of ischemic strokes are cryptogenic despite a comprehensive workup. Diagnostic workup for detecting cardioaortic sources of cerebral embolism commonly includes transthoracic echocardiography (TTE). However, TTE has a limited diagnostic power to detect some of the cardioaortic abnormalities and additional imaging modalities are often needed to accurately assess such abnormalities. PURPOSE: We evaluated the feasibility of cardiovascular magnetic resonance (CMR) imaging to detect the cardioaortic sources of ischemic stroke. METHODS: A total of 106 patients were included, of which 85 had an ischemic stroke and 21 had a transient ischemic attack (TIA). Routine diagnostic workup (RDW) included brain diffusion-weighted image MRI, telemetry, magnetic resonance angiography/CT angiography of head and neck, carotid duplex ultrasonography, laboratory studies and TTE. Patients additionally underwent CMR. Subtype assignment was performed in accordance with the Stop Stroke Study of the Trial of Org 10172 in Acute Stroke Treatment classification system by a stroke neurologist after reviewing the admission notes and diagnostic test results. A second subtype classification was assigned with an additional criterion defined based on delayed enhancement (DE)-CMR findings. Additionally, the presence of non-coronary artery disease (CAD) scarring was assessed in ischemic stroke patients and compared with the TIA patients as the control group. RESULTS: RDW detected cardioaortic embolism (CAE) stroke in 32 (37.6%) patients and cryptogenic stroke in 23 patients (27.1%). Addition of CMR resulted in a 26.1% reduction in the rate of cryptogenic strokes (6 patients). Furthermore, DE-CMR findings allowed for reclassification of three additional cryptogenic subtypes, resulting in a 39.1% reduction of cryptogenic stroke rate. Non-CAD scarring was detected in 13 (15.3%) stroke patients as opposed to only 1 (4.8%) TIA patient. CONCLUSIONS: CMR is a valuable tool for the detection of CAE sources in patients with cryptogenic ischemic stroke and provides clinicians with a unique set of information that may substantially change the long-term management of these patients. DE-CMR also detects non-CAD scarring, which may indicate a predisposition to ischemic stroke. Further studies with larger samples and long-term follow-up are needed to further evaluate the clinical significance of our findings.

CD11c expression in adipose tissue and blood and its role in diet-induced obesity.

OBJECTIVE: To examine CD11c, a beta(2)-integrin, on adipose tissue (AT) leukocytes and blood monocytes and its role in diet-induced obesity. METHODS AND RESULTS: High-fat diet-induced obese C57BL/6 mice, CD11c-deficient mice, and obese humans were studied. CD11c, leukocytes, and chemokines/cytokines were examined in AT and/or blood by flow cytometry, RNase protection assay, quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. Obese C57BL/6 mice had increased CD11c in AT and blood compared with lean controls. CD11c messenger RNA positively correlated with monocyte chemoattractant protein 1 in human visceral AT. Obese humans with metabolic syndrome had a higher CD11c level on blood monocytes compared with lean humans. Low-fat diet-induced weight loss reduced blood monocyte CD11c in obese mice and humans. Mouse and human monocyte CD11c levels and mouse AT CD11c messenger RNA correlated with insulin resistance. CD11c deficiency in mice did not alter weight gain but decreased inflammation, evidenced by a lower T-cell number and reduced levels of major histocompatibility complex class II, C-C chemokine ligand 2 (CCL5), CCL4, and interferon gamma in AT, and ameliorated insulin resistance and glucose intolerance associated with diet-induced obesity. CONCLUSIONS: Diet-induced obesity increased CD11c in both AT and blood in mice and humans. CD11c plays an important role in T-cell accumulation and activation in AT, and contributes to insulin resistance associated with obesity.

Lipid management: considerations in acute coronary syndrome.

Managing dyslipidemia is an important part of the primary and secondary prevention of coronary heart disease. Low-density lipoprotein cholesterol reduction remains the primary lipid goal. Patients who have experienced an acute coronary syndrome (ACS) are at very high risk of recurrent adverse cardiovascular events. A growing body of literature supports the concept that early and intensive treatment with statins after an ACS event decreases recurrent adverse cardiovascular events. We review available evidence pertaining to lipid alterations in ACS.

Novel markers of inflammation in atherosclerosis.

Inflammation plays a key role in the pathogenesis of atherosclerosis. Understanding the process of inflammation as it pertains to atherosclerosis has provided researchers with multiple opportunities to identify novel markers for use in cardiovascular disease management. This article discusses the inflammatory cascade as it pertains to atherosclerosis and some of the well-studied markers of inflammation. It also discusses the limitations of current risk stratification models and characteristics of a good biomarker.

Lipid management: considerations in acute coronary syndrome.

Managing dyslipidemia is an important part of the primary and secondary prevention of coronary heart disease. Low-density lipoprotein cholesterol reduction remains the primary lipid goal. Patients who have experienced an acute coronary syndrome (ACS) are at very high risk of recurrent adverse cardiovascular events. A growing body of literature supports the concept that early and intensive treatment with statins after an ACS event decreases recurrent adverse cardiovascular events. We review available evidence pertaining to lipid alterations in ACS.

Non-high-density lipoprotein cholesterol calculation and goal awareness among physicians-in-training.

BACKGROUND: Non-high density lipoprotein cholesterol (non-HDL-C) goal attainment per Adult Treatment Panel III (ATP III) guidelines remains low. OBJECTIVE: To understand gaps in knowledge and practices of physicians-in-training (internal medicine, family medicine, cardiology, endocrinology) towards non-HDL-C. METHODS: A survey based on a conceptual model to assess the trainee's knowledge, attitudes, and practice regarding non-HDL-C was developed and administered to physicians-in-training (n = 655) at 26 training programs in the United States. Responses of those in internal medicine and family medicine (residents-in-training; n = 418) were compared with those in cardiology and endocrinology (fellows-in-training; n = 124). RESULTS: Response rate was 83.7%. Fifty-three percent of residents and 31% of fellows-in-training had not read the ATP III guidelines (P < .001). Thirty-three percent of the residents and 35% fellows-in-training could not calculate non-HDL-C from a standard lipid panel (P = .7). Sixty-seven percent of the residents and 52% of fellows were not aware of treatment goals for non-HDL-C (P = .004 for comparison between residents and fellows). Both residents and fellows reported infrequent calculation of non-HDL-C levels in patients with elevated triglycerides (≥200 mg/dL; 32.5% vs 35.4%, respectively, P = .6). Lack of familiarity with ATP III guidelines, lack of knowledge regarding importance of non-HDL-C, lack of institutional mandate to calculate non-HDL-C, and lack of emphasis on non-HDL-C by teaching staff were reported as barriers to non-HDL-C use in routine clinical practice. CONCLUSIONS: At least one-third of physicians-in-training could not calculate non-HDL-C from a standard lipid panel, and a large number were not aware of ATP III treatment goals pertaining to non-HDL-C. This area represents one for improvement if non-HDL-C is to be retained as a treatment target in the forthcoming ATP-IV guidelines.

Real-time co-registration using novel ultrasound technology: ex vivo validation and in vivo applications.

OBJECTIVE: The study objective was to evaluate whether a novel global position system (GPS)-like position-sensing technology will enable accurate co-registration of images between imaging modalities. Co-registration of images obtained by different imaging modalities will allow for comparison and fusion between imaging modalities, and therefore has significant clinical and research implications. We compared ultrasound (US) and magnetic resonance imaging (MRI) scans of carotid endarterectomy (CEA) specimens using a novel position-sensing technology that uses an electromagnetic (EM) transmitter and sensors mounted on a US transducer. We then evaluated in vivo US-US and US-MRI co-registration. METHODS: Thirteen CEA specimens underwent 3.0 Tesla MRI, after which images were uploaded to a LOGIQ E9 3D (GE Healthcare, Wauwatosa, WI) US system and registered by identifying two to three common points. A similar method was used to evaluate US-MRI co-registration in patients with carotid atherosclerosis. For carotid intima-media thickness (C-IMT) measurements, 10 volunteers underwent bilateral carotid US scans co-registered to three-dimensional US maps created on the initial visit, with a repeat scan 2 days later. RESULTS: For the CEA specimens, there was a mean of 20 (standard error [SE] 2.0) frames per MRI slice. The mean frame difference, over 33 registration markers, between MRI and US scans for readers 1 and 2 was -2.82 ± 19.32 and 2.09 ± 14.68 (mean ± 95% CI) frames, respectively. The US-MRI intraclass correlation coefficients (ICCs) for the first and second readers were 0.995 and 0.997, respectively. For patients with carotid atherosclerosis, the mean US frames per MRI slice (9 [SE 2.3]) was within range of that observed with CEA specimens. Inter-visit, intra-reader, and inter-reader reproducibility of C-IMT measurements were consistently high (side-averaged ICC >0.9). CONCLUSION: Accurate co-registration between US and other modalities is feasible with a GPS-like technology, which has significant clinical and research applicability.

Preoperative statin therapy decreases risk of postoperative renal insufficiency.

INTRODUCTION: Although current guidelines recommend withholding statins in perioperative patients, little information is available on whether perioperative statin use increases risk for postoperative renal failure. AIMS: We examined the relation between preoperative statin therapy and postoperative risk for renal insufficiency in patients undergoing cardiac surgery. METHODS: Retrospective cohort review from the Texas Heart Institute research database was performed. Patients were divided into two groups: those who received preoperative statins and those who did not. Primary outcome was the development of postoperative renal insufficiency (requiring dialysis or not). Outcomes were assessed in the entire cohort and in subgroups undergoing isolated coronary artery bypass grafting (CABG), isolated valve surgery, or combined CABG and valve surgery. RESULTS: Of 3001 patients, 56% received preoperative statins. In multivariate logistic regression analysis, preoperative statins were associated with significant reductions in risk for postoperative renal insufficiency in the entire cohort (odds ratio [OR]= 0.60, 95% confidence interval [CI] 0.38-0.95) and in patients undergoing isolated CABG (OR = 0.34, 95% CI 0.17-0.68). In patients undergoing isolated valve surgery (OR = 1.35, 95% CI 0.61-2.96) or combined CABG and valve surgery (OR = 1.39, 95% CI 0.48-3.99), preoperative statins were not associated with decreased incidence of postoperative renal insufficiency. Age >65 years, preoperative renal insufficiency, history of congestive heart failure, preoperative intra-aortic balloon pump insertion, and total cardiopulmonary bypass time >80 min were also independent predictors associated with increased risk for postoperative renal insufficiency. CONCLUSIONS: Preoperative statin therapy was associated with decreased incidence of postoperative renal insufficiency in patients undergoing cardiac surgeries, particularly in patients undergoing isolated CABG.

Efficacy and tolerability of multidrug therapy for hypertriglyceridemia.

BACKGROUND: Although there is clinical evidence for the safety and efficacy of single-drug therapy and some two-drug combinations for the treatment of hypertriglyceridemia, information is limited on the use of more than 2 drugs. OBJECTIVE: We evaluated the efficacy and safety of multidrug regimens (≥3 agents) in the management of hypertriglyceridemia. METHODS: The study included 40 individuals in an academic lipid referral clinic with mean follow-up of 1.98 years and an average use of 3.5 medications. RESULTS: During the study, mean body mass index decreased significantly (P=.0127), from 29.2kg/m(2) to 28.7kg/m(2), and mean hemoglobin A1C showed a trend towards decreasing (P=.06), from 7.9% to 7.2% in patients with diabetes (n=17). All lipid parameters decreased significantly: total cholesterol level decreased significantly from (mean±SD) 334.3±282.9mg/dL to 183.8±54.8mg/dL (P=.001, mean reduction of 45%), mean (± SD) triglyceride level decreased significantly from 1900.9±4576.8mg/dL to 300.7±372.2mg/dL (P=.02), median (range) triglyceride level decreased from 599 (242-28,550) mg/dL to 301 (40-1960) mg/dL (P < .001, mean reduction of 50%), and mean (± SD) non-high-density lipoprotein cholesterol decreased significantly from 189.9±131.6mg/dL to 138.4±49.1mg/dL (P=.014, mean reduction of 27%). There were no serious adverse effects (rhabdomyolysis or increased liver function tests >3 times upper limit of normal). CONCLUSION: In a 2-year follow-up of 40 individuals on multidrug therapy (average of 3.5 drugs) for severe hypertriglyceridemia, combination therapy was efficacious and well tolerated.