Smita I. Negi

Atrial Fibrillation: The Emerging Role of Inflammation and Oxidative Stress

Atrial fibrillation (AF) remains the most commonly encountered sustained arrhythmia in clinical practice and contributes to increased morbidity and mortality. Management of AF poses a challenge due to the refractory nature of the arrhythmia and the associated thromboembolic complications. Recent studies have implicated both systemic and local cardiac inflammation in the development as well as persistence of AF. This has been validated by the occurrence of high levels of systemic markers of inflammation in patients with post operative as well as chronic AF. High levels of markers of oxidative stress have also been found in patients with chronic AF when compared with controls, indicating a role of systemic reactive oxidative species in the perpetuation of this arrhythmia. Renin angiotension system (RAS) is believed to be unregulated in AF and may contribute to the pathogenesis of AF by producing a state of cardiac or systemic oxidative stress and /or inflammation. In this review, we aim to discuss the emerging evidence linking inflammation, and oxidative stress with AF.

The Role of Carotid Intimal Thickness and Plaque Imaging in Risk Stratification for Coronary Heart Disease

Improving the 10-year coronary heart disease (CHD) risk prediction beyond its current state is important as the current risk prediction schemes classify the majority of individuals who experience an incident CHD event as low or intermediate in risk. B-mode ultrasound-based carotid intima-media thickness (CIMT) measurement and carotid plaque detection is one of the surrogate markers of atherosclerosis that has shown value in CHD risk prediction. It has been shown that adding either CIMT, plaque, or both to traditional risk prediction models improves CHD risk prediction. Carotid ultrasound-based CIMT measurement and plaque identification is noninvasive, safe, and relatively inexpensive. Recent guidelines have given CIMT and plaque-based risk prediction a class II A recommendation. This article reviews the available data related to the use of CIMT and plaque information in CHD risk prediction.

Risk factors for perforation in microbial corneal ulcers in north India.

Aim: To identify predisposing factors leading to corneal perforation in patients with microbial keratitis. Method: Two groups of 60 patients each, with perforated corneal ulcers and healed/healing corneal ulcers, respectively, were recruited in a case-control study conducted in northern India. The cases and controls were matched by age and time of presentation. A standardised proforma was used to identify potential predisposing factors for demographic, social, medical, ocular, and treatment history. All participants underwent a detailed ocular examination. Corneal scrapings were performed where relevant. Results: The characteristics associated with corneal perforation in microbial keratitis were outdoor occupation (p = 0.005), illiteracy (p = 0.02), excessive alcohol use (p = 0.03), history of “something falling into eye” (p = 0.003), trauma with vegetable matter (p = 0.008), vision less than counting fingers at referral (p<0.001), central location of ulcer (p<0.001), lack of corneal vascularisation (p<0.001), delay in starting initial treatment (p<0.001), failure to start fortified antibiotics (p<0.001), and monotherapy with fluoroquinolones (p = 0.002). The lack of corneal vascularisation (OR 6.4, 95% CI 4.2 to 13.5), delay in starting initial treatment (OR 35.6, 95% CI 6.9 to 68.2), and failure to start fortified antibiotics (OR 19.9, 95% CI 2.7 to 64.7) retained significance on a logistic regression model. Conclusions: This study characterises microbial keratitis cases at increased risk of corneal perforation and reinforces the need for standardised referral and treatment protocols for patients with corneal ulcer on their first contact at primary care level in the developing world.

A novel mutation in the ABCA1 gene causing an atypical phenotype of Tangier disease

Tangier disease is a rare autosomal-recessive disorder caused by mutation in the ATP binding cassette transporter 1 (ABCA1) gene. Typically, Tangier disease manifests with symptoms and signs resulting from the deposition of cholesteryl esters in nonadipose tissues; chiefly, in peripheral nerves leading to neuropathy and in reticulo-endothelial organs, such as liver, spleen, lymph nodes, and tonsils, causing their enlargement and discoloration. An association with early cardiovascular disease can be variable. We describe a patient with a unique phenotype of Tangier disease from a novel splice site mutation in the ABCA1 gene that is associated with a central nervous system presentation resembling multiple sclerosis, and the presence of premature atherosclerosis.

Insights from recent meta-analysis: role of high-density lipoprotein cholesterol in reducing cardiovascular events and rates of atherosclerotic disease progression.

BACKGROUND Although low-density lipoprotein cholesterol (LDL-C) traditionally has been the focus of treatment guidelines and clinical trials of lipid therapy, patients continue to have cardiovascular disease (CVD) events despite effective lowering of their LDL-C levels, suggesting the influence of other risk factors. High-density lipoprotein cholesterol (HDL-C) levels have been shown to be inversely associated with CVD risk in epidemiological studies. METHODS Meta-analyses and clinical trials that reported on the potential relation between HDL-C and CVD were reviewed. RESULTS Low HDL-C level is associated with increased CVD risk. Statins reduce CVD events in patients with low HDL-C, and fibrates benefit patients with low HDL-C and high triglyceride levels. The benefit of statins on event reduction may be related to their effects on HDL-C. However, not all therapies that increase HDL-C reduce CVD events. Imaging trials have provided evidence of the combined influence of HDL-C and LDL-C on surrogate end points. CONCLUSION Drugs in the same class may have different effects on HDL-C, and these different lipid effects may translate into different effects on atherosclerosis and CVD events. A new class of agents, cholesteryl ester transfer protein inhibitors, is being examined in ongoing trials to determine whether dalcetrapib may have different effects than torcetrapib, which increased levels of HDL-C but was associated with increased adverse events. In addition, ongoing trials are examining whether targeting both HDL-C and LDL-C, by combining a second agent such as niacin with a statin, leads to greater benefit on CVD and clinical events.

Racial Differences in Association of Elevated Interleukin-18 Levels With Type 2 Diabetes: The Atherosclerosis Risk in Communities Study

OBJECTIVE Elevated plasma interleukin-18 (IL-18) has been linked to onset of diabetes mellitus (DM) and its complications. However, so far this association has been shown only in predominantly white populations. We examined IL-18 levels and their association with incident DM in a racially heterogeneous population. RESEARCH DESIGN AND METHODS In a nested case-cohort design representing a 9-year follow-up of 9,740 middle-aged, initially healthy, nondiabetic white and African American participants of the Atherosclerosis Risk in Communities Study, we selected and measured analytes on race-stratified (50% white, 50% African American) random samples of both cases of incident diabetes (n = 548) and eligible members of the full cohort (n = 536). RESULTS Baseline IL-18 levels were significantly higher in white participants compared with African American participants (P < 0.001). Although white participants in the fourth (versus first) quartile of IL-18 levels had a significant hazard ratio (HR) for developing DM (HR: 2.1, 95% CI: 1.3–3.4), after adjustment for age, sex, and study center, no difference was seen among African Americans (HR: 1.0, 95% CI: 0.6–1.7). Unlike those in African Americans, IL-18 levels in whites had a significant correlation with age (P < 0.01); anthropometric characteristics such as waist circumference (P < 0.001), height (P = 0.04), waist-to-hip ratio (P < 0.001), and BMI (P < 0.01); and total (P < 0.001) and high-molecular-weight (P < 0.001) adiponectin. CONCLUSIONS There are racial differences in levels of IL-18 and the association of IL-18 with risk factors and incident type 2 DM. In addition, there seems to be a complex interplay of inflammation and adiposity in the development of DM.

Widespread systemic embolization with isolated tricuspid valve endocarditis

Concurrent systemic and pulmonary septic emboli from isolated right-sided infective endocarditis are rare. One mechanism described is that of intrapulmonary shunting. We describe a case of widespread pulmonary and systemic septic embolization with sequelae in an intravenous drug user with concomitant chronic hepatitis C infection and discuss possible mechanisms involved in the pathogenesis.

Large blood transfusion as a rare cause of ventricular fibrillation.

Large blood transfusions are common in clinical practice. Though several complications have been described with this procedure, cardiac arrhythmias occur uncommonly in this setting. We describe a case of a previously healthy 17-year-old girl who developed wide-complex ventricular tachycardia rapidly culminating in a ventricular fibrillation cardiac arrest several hours following an uneventful large-volume blood transfusion. Hypomagnesemia was detected on postcardiac arrest investigations. A review of this life-threatening complication and discussion on the ways to prevent it are presented.

TCT-295 Percutaneous Coronary Intervention in Chronic Total Occlusions: A Single Center Experience on the Impact and Efficacy of Using Contemporary Techniques

Withdrawn

TCT-269 Impact of Incomplete Revascularization in Diabetes Mellitus Patients with Multivessel Disease Treated with Percutaneous Coronary Intervention

TCT-267 Clinical outcomes of diabetic patients treated with an amphilimus-eluting stent and a short duration of dual antiplatelet therapy in routine clinical practice: first results of the Utrecht Cre8 (U-Cre8) Registry Rik Rozemeijer, Mera Stein, Michiel Voskuil, Adriaan Kraaijeveld, Leo Timmers, Ramon Rodríguez-Olivares, Saskia Rittersma, Pieter Stella UMC Utrecht, Utrecht, Netherlands; Utrecht, Netherlands; UMC Utrecht; UMC Utrecht, Leiden, Netherlands; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai; ErasmusMC, Rotterdam, Netherlands; University Medical Center Utrecht; University Medical Center Utrecht, Utrecht, Netherlands