Epicardial Adipose Tissue Removal Potentiates Outward Remodeling and Arrests Coronary Atherogenesis.

BACKGROUND: Pericoronary epicardial adipose tissue (cEAT) serves as a metabolic and paracrine organ that contributes to inflammation and is associated with macrovascular coronary artery disease (CAD) development. Although there is a strong correlation in humans between cEAT volume and CAD severity, there remains a paucity of experimental data demonstrating a causal link of cEAT to CAD. The current study tested the hypothesis that surgical resection of cEAT attenuates inflammation and CAD progression. METHODS: Female Ossabaw miniature swine (n = 12) were fed an atherogenic diet for 8 months and randomly allocated into sham (n = 5) or adipectomy (n = 7) groups. Both groups underwent a thoracotomy, opening of the pericardial sac, and placement of radioopaque clips to mark the proximal left anterior descending artery. Adipectomy swine underwent removal of 1 to 1.5 cm2 of cEAT from the proximal artery. After sham or adipectomy, CAD severity was assessed with intravascular ultrasonography. Swine recovered for an additional 3 months on an atherogenic diet, and CAD was assessed immediately before euthanasia. Artery sections were processed for histologic and immunohistochemical analysis. RESULTS: Severity of CAD as assessed by percent stenosis was reduced in the adipectomy cohort compared with shams; however, plaque size remained unaltered, whereas larger plaque sizes developed in sham-operated swine. Adipectomy resulted in an expanded arterial diameter, similar to the Glagov phenomenon of positive outward remodeling. No differences in inflammatory marker expression were observed. CONCLUSIONS: These data indicate that cEAT resection did not alter inflammatory marker expression, but arrested CAD progression through increased positive outward remodeling and arrest of atherogenesis.

Natural History of Implantable Cardioverter-Defibrillator Implanted at or after the Age of 70 years in a Veteran Population: A Single Center Study.

BACKGROUND: The median age of patients in major Implantable Cardioverter-defibrillator (ICD)trials (MUSTT, MADIT-I, MADIT-II, and SCD-HeFT) was 63-67 years; with only 11% ≥70 years. There is little follow-up data on patients over 70 years of age who received an ICD for primary/secondary prevention of sudden cardiac death, particularly for veterans. OBJECTIVE: The aim of this study was to study the natural history of ICD implantation for veterans over 70 years of age. METHODS: We retrospectively reviewed single center ICD data in 216 patients with a mean age at implantation 76 ± 4 years. The ICD indication was primary prevention in 161 patients and secondary prevention in 55 patients. The ICD indication was unavailable in 4 patients. RESULTS: Mean duration of follow up was 1686 ± 1244 days during which 114 (52%) patients died. Of these, 31% died without receiving any appropriate ICD therapy. Overall, 60/216 (28%) received appropriate therapy and 28/216 (13%) received inappropriate therapy. Patients who had ICD implantation for secondary prophylaxis had statistically more (p= 0.02) appropriate therapies compared to patients who had ICD implantation for primary prevention. Indication for implantation and hypertension predicted appropriate therapy, while age at the time of implantation and presence of atrial fibrillation predicted inappropriate therapies. Overall, 7.7% had device related complications. CONCLUSIONS: Although 28% septuagenarians in this study received appropriate ICD therapy, they had high rates of mortality, inappropriate therapy, and device complications. ICD implantation in the elderly merits individualized consideration, with higher benefit for secondary prevention.

Steatocholecystitis: the influence of obesity and dietary carbohydrates.

INTRODUCTION: We have recently demonstrated that obese and lean mice fed a high fat diet have increased gallbladder wall fat and decreased gallbladder contractility, cholecystosteatosis. Animal and human data also suggest that diets high in refined carbohydrates lead to gallstone formation. However, no data are available on the role of dietary carbohydrates on gallbladder wall fat and inflammation. Therefore, we tested the hypothesis that both obesity and dietary carbohydrates would increase gallbladder fat and cytokines, steatocholecystitis. METHODS: At 8 wk of age, 47 lean and 22 obese female mice were fed a 45% carbohydrate (CHO) diet while an equal number of lean and obese mice were fed a 75% CHO diet for 4 wk. All mice underwent cholecystectomy, and the gallbladders were snap-frozen. Individual and total lipids were measured by gas chromatography. Interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were measured by enzyme-linked immunosorbent assay. Data were analyzed by analysis of variance and Tukey test. RESULTS: Gallbladder total fat, triglycerides, and cholesterol were maximum (P < 0.001) in obese mice on the 75% CHO diet. Gallbladder TNF-alpha and IL-1beta as well as serum cholesterol levels showed a similar pattern (P < 0.001). Gallbladder saturated free fatty acids and IL-6 levels were highest (P < 0.001) in obese mice on the 45% CHO diet. CONCLUSIONS: These data suggest that (1) both obesity and dietary carbohydrates increase gallbladder total fat, triglycerides, cholesterol, TNF-alpha, and IL-1beta and (2) obesity also increases gallbladder free fatty acids and IL-6. Therefore, we conclude that obesity is associated with steatocholecystitis and that a high carbohydrate diet exacerbates this phenomenon.