Michael DelCore

Vitamin D deficiency induces cardiac hypertrophy and inflammation in epicardial adipose tissue in hypercholesterolemic swine

INTRODUCTION Vitamin D is a sectosteroid that functions through Vitamin D receptor (VDR), a transcription factor, which controls the transcription of many targets genes. Vitamin D deficiency has been linked with cardiovascular diseases, including heart failure and coronary artery disease. Suppressor of cytokine signaling (SOCS)3 regulates different biological processes such as inflammation and cellular differentiation and is an endogenous negative regulator of cardiac hypertrophy. OBJECTIVE The purpose of this study was to test the hypothesis that vitamin D deficiency causes cardiomyocyte hypertrophy and increased proinflammatory profile in epicardial adipose tissue (EAT), and this correlates with decreased expression of SOCS3 in cardiomyocytes and EAT. METHODS Eight female Yucatan miniswine were fed vitamin D-sufficient (900 IU/d) or vitamin D-deficient hypercholesterolemic diet. Lipid profile, metabolic panel, and serum 25(OH)D levels were regularly measured. After 12 months animals were euthanized and histological, immunohistochemical and qPCR studies were performed on myocardium and epicardial fat. RESULTS Histological studies showed cardiac hypertrophy, as judged by cardiac myocyte cross sectional area, in the vitamin D-deficient group. Immunohistochemical and qPCR analyses showed significantly decreased mRNA and protein expression of VDR and SOCS3 in cardiomyocytes of vitamin D-deficient animals. EAT from vitamin D-deficient group had significantly higher expression of TNF-α, IL-6, MCP-1, and decreased adiponectin in association with increased inflammatory cellular infiltrate. Interestingly, EAT from vitamin D-deficient group had significantly decreased expression of SOCS3. CONCLUSION These data suggest that vitamin D deficiency induces hypertrophy in cardiomyocytes which is associated with decreased expression of VDR and SOCS3. Vitamin D deficiency is also associated with increased inflammatory markers in EAT. Activity of VDR in the body is controlled through regulation of vitamin D metabolites. Therefore, restoration of VDR function by supplementation of VDR ligands in vitamin D-deficient population might be helpful in reducing inflammation and cardiovascular risk.

Comparison of Fixed‐Dose Transdermal Nicotine, Tapered‐Dose Transdermal Nicotine, and Buspirone in Smoking Cessation

The authors compared the outcome of 208 smokers treated with fixed‐dose transdermal nicotine (n = 69), tapered‐dose transdermal nicotine (n = 71), or Buspirone (n = 68). At baseline, there were no significant differences among the three treatment groups with regard to age, gender, educational level, duration of smoking, number of cigarettes smoked per day, concomitant disease states or drug use, or Fagerstrom score. All smokers participated in a behavior modification program. Fixed‐dose transdermal nicotine was given at a dose of 21 or 22 mg/day for 6 weeks. Tapered‐dose transdermal nicotine was given at a dose of 21 or 22 mg/day for 4 weeks, 14 mg/day for 4 weeks and 7 mg/day for 4 weeks. Both transdermal nicotine regimens were initiated on the evening before the attempted quit date. Buspirone was started 21 days before the quit attempt and continued for 7 days after the quit attempt. Buspirone was initiated at 5 mg TID for 7 days and then 10 mg TID for 21 days. Smoking cessation was assessed by patient diaries and random plasma thiocyanate determinations. Dropouts for any reason were considered treatment failures. Quit rates were as shown in the Table I. Discontinuation of treatment for perceived side effects and dropouts for all reasons were not significantly different among the treatment groups. The authors conclude that fixed‐dose transdermal nicotine, tapered‐dose transdermal nicotine, and buspirone are associated with similar efficacy and safety when combined with behavior modification in smoking cessation.

Randomized, Controlled Trial of Transdermal Clonidine for Smoking Cessation

OBJECTIVE: To determine the efficacy and safety of clonidine versus placebo in smoking cessation. DESIGN: Single-center, randomized, double-blind, parallel-design comparison of transdermal clonidine with behavior modification, transdermal clonidine without behavior modification, placebo with behavior modification, and placebo without behavior modification. SETTING: Outpatient, university-based ambulatory care facility. PATIENTS: One hundred fifty generally healthy, highly nicotine-dependent cigarette smokers. INTERVENTION: Clonidine was given as the transdermal patch initiated 72 hours prior to smoking-cessation attempts and continued for six weeks thereafter. Clonidine was given at a dose of 0.2 mg/d for patients weighing more than 150 pounds (>67.5 kg) and at a dose of 0.1 mg/d for patients weighing less than 150 pounds (<67.5 kg). Behavior modification consisted of a total of 12 one-hour structured group training sessions. Patients not receiving behavior modification received printed material, which included the “Help Quit Kit” and the “I Quit Kit” from the American Cancer Society. MAIN OUTCOME MEASURES: Smoking-cessation rates were assessed at 6, 12, 24, and 52 weeks of follow-up. In addition, adverse reactions to clonidine or placebo were evaluated. RESULTS: Clonidine with behavior modification was statistically superior to the other three treatment groups but only at 6 weeks of follow-up. There were no differences in smoking-cessation rates among any of the treatment groups at any other follow-up intervals. Patients receiving behavior modification, regardless of whether they received clonidine, had better quit rates than patients not receiving behavior modification at all follow-up times except 52 weeks. Women receiving clonidine had significantly better quit rates than men receiving clonidine at all follow-up visits. Clonidine was associated with a significantly higher incidence of adverse effects than placebo (52 vs. 11 percent). However, the number of smokers withdrawing from the study was not greater with clonidine compared with placebo (9 vs. 7 percent, respectively). CONCLUSIONS: Clonidine is probably not effective as a pharmacologic adjunct to behavior modification in smoking cessation. It may have a potential role in women smokers who do-not respond to or cannot tolerate more traditional smoking-cessation therapies.

Comparison of percutaneous device closure versus surgical closure of peri‐membranous ventricular septal defects: A systematic review and meta‐analysis

While percutaneous device closure (PDC) is a first‐line therapy for isolated muscular ventricular septal defects (mVSD), surgery is still the preferred approach for peri‐membranous ventricular septal defects (pmVSD).

Calphostin C as a rapid and strong inducer of apoptosis in human coronary artery smooth muscle cells

Vascular smooth muscle cells (VSMCs) play a major role in the development of atherosclerotic and restenotic lesions. The apoptotic process has been implicated in the development of this pathology. In this study, we characterized the induction of apoptosis by calphostin C (CC), a protein kinase C (PKC) inhibitor, in primary human coronary artery smooth muscle cells in the presence and absence of insulin-like growth factor-I (IGF-I). Additionally, we investigated the signal transduction pathways important for IGF-I mediated protection. Calphostin C induced apoptosis, as measured by terminal deoxy-UTP nick-end labeling (TUNEL), in a time- and dose-dependent manner, approaching 20% within 6 h of 50 nM calphostin C treatment. The amount of apoptosis increased to 44.58+/-8.08%, 47.54+/-1.66% and 78.1+/-11.9% after 8, 10 and 12 h of treatment, respectively (p<0.01 vs. control). IGF-I offered significant protection (p<0.05) at 8 and 10 h of treatment (60.6% and 52.5% protection, respectively). DNA ELISA confirmed the apoptotic effect of calphostin C and the protective effect of IGF-I. After 6 h of calphostin C treatment, DNA ELISA revealed 11.20+/-1.53 fold greater apoptosis as compared to baseline values. IGF-I treatment offered a level of protection of 46.6% as measured by DNA ELISA (p=0.06). Apoptosis was further qualitatively confirmed by time-lapse video microscopy and scanning electron microscopy. Interestingly, inhibitors of phosphatidylinositol-3-kinase (PI-3-K), p38 and extracellular regulated kinase (ERK) activation significantly (p<0.05 vs. calphostin C only treatment) increased apoptosis when used in conjunction with calphostin C. Inhibitors of phospatidylinositol-3-kinase and ERK activation reversed IGF-I protection. However, the p38 inhibitor SB203580 failed to reverse IGF-I protection. This study characterized an apoptotic system for human coronary artery smooth muscle cells offering a rapid and strong induction of programmed cell death (PCD) that remains responsive to the survival effects of IGF-I. Studies utilizing this system may prove useful in understanding the apoptotic response of VSMCs in the arterial wall.

TCT-816 Trend of Utilization & Procedural Outcomes of Endomyocardial Biopsy in United States: A Nationwide Inpatient Sample Based Study

There is limited data on recent trends of utilization and procedural outcomes of endomyocardial biopsy (EMB) in the United States. In this report we aim to study the nationwide trends in the performance EMB and in-hospital outcomes using the National Inpatient Sample (NIS) database. NIS data was

TCT-186 Delayed versus immediate stenting strategy in ST segment elevation myocardial infarction - A meta analysis.

TCT-185 Influence of total ischemic time on clinical outcomes and efficacy of manual thrombus aspiration during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Analysis from the POST trial Ji-Hoon Jang, Dong-Kie Kim, Pil Sang Song, Doo-Il Kim, Joo-Yong Hahn Inje University Haeundae Paik Hospital, Busan, Korea, Republic of; Inje University Haeundae Paik Hospital, Busan, Korea, Republic of; INJE, Busan, Korea, Republic of; Inje University Haeundae Paik Hospital; Samsung Medical Center, Seoul, Korea, Republic of

ZOTAROLIMUS ELUTING STENT VERSUS EVEROLIMUS ELUTING STENT IN PERCUTANEOUS CORONARY INTERVENTION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Zotarolimus eluting stents (ZES) and Everolimus eluting stents (EES) with durable polymer are the most commonly used second and third generation drug-eluting stents (DES) during percutaneous coronary revascularization (PCI). Previously conducted randomized (RCTs) and observational trials have shown

A SYSTEMATIC REVIEW OF PERCUTANEOUS CLOSURE OF RUPTURED SINUS OF VALSALVA ANEURYSM IN ADULTS

Sinus of Valsalva aneurysm (SVA) is a rare anomaly and is mostly congenital. It can rupture into one of the cardiac chambers leading to aorto-cardiac fistula. Urgent repair is recommended to prevent heart failure. Surgical repair with patch closure has been the treatment of choice. Percutaneous