A comprehensive meta-analysis of randomized controlled trials comparing drug-eluting stents with bare-metal stents in saphenous vein graft interventions.

BACKGROUND: Several large randomized controlled trials (RCTs) have proven the superiority of drug-eluting stents (DESs) over bare-metal stents (BMSs) for native coronary stenosis. However, RCTs comparing DESs with BMSs for SVG lesions have predominantly been small in size and have yielded conflicting results. Therefore, we conducted an updated comprehensive meta-analysis of RCTs comparing DESs versus BMSs for SVG interventions using the largest sample size to date. METHODS: Scientific databases and websites were searched to find RCTs. Data from six RCTs involving 1,582 patients were included. Pooled risk ratios (RRs) were calculated using random-effects models. The primary outcome of this meta-analysis was target vessel revascularization (TVR). The secondary outcomes were major adverse cardiac events (MACEs), myocardial infarction (MI), stent thrombosis, all-cause mortality, and cardiac mortality. RESULTS: Data from six RCTs involving 1,582 patients were included. Saphenous vein graft interventions with DESs reduced TVR (RR, 0.52; 95% CI, 0.30-0.88; P = 0.017) and MACE rate (RR, 0.60; 95% CI, 0.42-0.87; P = 0.007) compared to BMSs. No difference between the stents were found in rates of MI (RR, 0.69; 95% CI, 0.43-1.10; P = 0.123), stent thrombosis (RR, 0.61; 95% CI, 0.27-1.41; P = 0.255), all-cause mortality (RR, 1.13; 95% CI, 0.74-1.71; P = 0.554), or cardiac mortality. CONCLUSION: For SVG intervention, the MACE rate was lower for DESs compared to BMSs, driven primarily by decreased non-MI-related TVR. Rates of MI, all-cause mortality, cardiac mortality, and stent thrombosis were not different between the stents.

Chrna4 A529 knock-in mice exhibit altered nicotine sensitivity.

The reasons why people smoke are varied, but research has shown that genetic influences on various aspects of nicotine addiction are a major factor. There also is a strong genetic influence on measures of nicotine sensitivity in mice. Despite the established contribution of genetics to nicotine sensitivity in mice and humans, no naturally occurring genetic variation has been identified that demonstrably alters sensitivity to nicotine in either species. However, one genetic variant has been implicated in altering nicotine sensitivity in mice is a T529A polymorphism in Chrna4, the gene that encodes the nicotinic receptor (nAChR) alpha4 subunit. The Chrna4 T529A polymorphism leads to a threonine to alanine substitution at position 529 of the alpha4 subunit. To more definitively address whether the Chrna4 T529A polymorphism does, in fact, influence sensitivity to nicotine, knock-in mice were generated in which the threonine codon at position 529 was mutated to an alanine codon. Compared with Chrna4 T529 littermate controls, the Chrna4 A529 knock-in mice exhibited greater sensitivity to the hypothermic effects of nicotine, reduced oral nicotine consumption and did not develop conditioned place preference to nicotine. The Chrna4 A529 knock-in mice also differed from T529 littermates for two parameters of acetylcholine-stimulated Rb+ efflux in midbrain: maximal efflux and the percentage of alpha4beta2* receptors with high sensitivity to activation by agonists. Results indicate that the polymorphism affects the function of midbrain alpha4beta2* nAChRs and contributes to individual differences in several behavioral and physiological responses to nicotine thought to be modulated by midbrain alpha4beta2* nAChRs.

A Meta-Analysis Comparing Aspirin Alone Versus Dual Antiplatelet Therapy for the Prevention of Venous Graft Failure Following Coronary Artery Bypass Surgery.

BACKGROUND: Aspirin (ASA) monotherapy is the current standard of care after coronary artery bypass grafting (CABG) to prevent saphenous vein graft (SVG) failure. Several small, randomized clinical trials (RCTs) have suggested that dual antiplatelet therapy (DAPT) may be more effective at preventing SVG failure than ASA alone; however, it is unclear whether some P2Y12 inhibitors are more effective than others for the prevention of SVG failure. METHODS: Scientific databases and websites were searched to find RCTs. Both traditional pairwise meta-analysis using random-effect model and network meta-analysis using mixed-treatment comparison models were performed to compare the efficacy of various anti-platelet strategies for the prevention of SVG failure. RESULTS: Nine RCTs, which included a total of 1677 patients, were analyzed. Compared to ASA alone, DAPT decreased the risk of graft failure by 37% (RR: 0.63, 95% CI: 0.47-0.86; p = 0.003). In the moderator analysis, the decreased risk of graft failure with DAPT was not significantly different in the ASA + clopidogrel group than in the ASA + ticagrelor group (P-interaction = 0.17). The results of the network meta-analysis were consistent with those from pairwise analyses. The risk of major bleeding was not statistically significantly different between DAPT and ASA alone (RR: 1.35, 95% CI: 0.62-2.94; p = 0.45). CONCLUSION: In post-CABG patients, DAPT seems to be more effective at preventing graft failure than ASA alone. This strategy does not seem to significantly increase major bleeding risk. Clopidogrel- and ticagrelor-based DAPT seem to be equally effective for this indication.

The dopamine D Receptor (DRD4) gene exon III polymorphism, problematic alcohol use and novelty seeking: direct and mediated genetic effects.

The present study sought to integrate convergent lines of research on the associations among the dopamine D(4) receptor (DRD4) gene, novelty seeking and drinking behaviors with the overall goal of elucidating genetic influences on problematic drinking in young adulthood. Specifically, this study tested a model in which novelty seeking mediated the relationship between DRD4 variable number of tandem repeats (VNTR) genotype and problematic alcohol use. Participants (n = 90, 40 females) were heavy-drinking college students. Analyses using a structural equation modeling framework suggested that the significant direct path between DRD4 VNTR genotype and problematic alcohol use was reduced to a trend level in the context of a model that included novelty seeking as a mediator, thereby suggesting that the effects of DRD4 VNTR genotype on problematic alcohol use among heavy-drinking young adults were partially mediated by novelty seeking. Cross-group comparisons indicated that the relationships among the model variables were not significantly different in models for men versus women. These results extend recent findings of the association between this polymorphism of the DRD4 receptor gene, problematic alcohol use and novelty seeking. These findings may also help elucidate the specific pathways of risk associated with genetic influences on alcohol use and abuse phenotypes.

Recent Updates in the Role of Wearable Cardioverter Defibrillator for Prevention of Sudden Cardiac Death.

PURPOSE OF REVIEW: The wearable cardioverter defibrillator (WCD) or LifeVest may protect against sudden cardiac death (SCD) in patients awaiting insertion of an implantable cardioverter defibrillator (ICD). The purpose of this communication is to review the rationale behind WCD therapy and to critically analyze recent data regarding its clinical efficacy. We seek to provide evidence-based recommendations regarding the potential role of the WCD in certain populations. RECENT FINDINGS: The only randomized controlled trial that evaluated WCD therapy did not demonstrate a reduced rate of arrhythmic death in patients prescribed the WCD during the first 90-day post-myocardial infarction (MI). However, when considering trial results alongside previous retrospective data, patient noncompliance with WCD therapy-rather than ineffectiveness of WCD therapy-remains an important theme. The uncertainty of data regarding the use of WCD therapy in patients during ICD waiting periods should be considered as part of the shared decision processes between healthcare providers and patients. Higher rates of adherence are needed to ensure efficiency. Well-designed future studies with appropriate cost-effectiveness analyses are indicated to define the clinical efficacy of WCD therapy on arrhythmic and non-arrhythmic morbidity and mortality in patients who are not yet candidates for ICDs.

Is there an optimal "door to cath time" in the treatment of acute pulmonary embolism with catheter-directed thrombolysis?

Ultrasound assisted catheter-directed thrombolysis (UACT) is a relatively novel approach to treating acute pulmonary embolism (PE). It is an alternative to systemic thrombolysis with good success rates and low reported in-hospital mortality, and low rates of procedure-related major and minor bleeding. Since UACT received FDA approval for the treatment of PE in 2014, there is paucity of data regarding the optimal timing of initiation of the procedure after the initial diagnosis is made. We reviewed the available literature regarding UACT for acute PE and found six studies that included time to procedure. Based on our review, patients may benefit from early (<24-48 h after presentation) rather than delayed (>48 h) initiation. Early initiation of therapy has shown to improve pulmonary arterial pressures, right ventricular (RV) to left ventricular (LV) ratios, with low rates of bleeding and low post procedural and in hospital mortality. However, further studies are required to confirm these findings and establish the appropriate timeline for initiation of UACT.

From Tick Bite to Heart Failure: Ehrlichial Myocarditis.

Cardiac involvement in myocarditis induced by Human Monocytic Ehrlichiosis infection is an incredibly uncommon complication with sparsely available literature. Also, this case highlights the importance of early recognition as a first step in management.

Une atteinte cardiaque secondaire à une myocardite induite par une ehrlichiose monocytaire humaine constitue une complication extrêmement rare et très peu documentée. Le cas présenté fait ressortir l'importance d'une reconnaissance rapide du problème comme première étape de la prise en charge.

Severe tricuspid regurgitation due to valvular entrapment of an inferior vena cava stent.

Endovascular venous stenting is increasingly performed for a variety of conditions. Inferior vena cava stent migration has been reported up to 6 months after placement; stent migration 6 months after implantation is uncommon. To our knowledge, this is only the second reported case of late stent migration with valve entrapment 1.

Comparison of nicotine oral consumption and baseline anxiety measures in adolescent and adult C57BL/6J and C3H/Ibg mice.

Approximately 80% of smokers initiate tobacco use during adolescence, suggesting that nicotine initiation and nicotine dependence have a substantial age component. There also is a substantial genetic influence on smoking behaviors such as age of initiation and the development of nicotine dependence. The goal of this study was to examine both genetic background and age dependent effects on oral nicotine self-administration and anxiety-like behaviors in mice. Two inbred mouse strains (C3H/Ibg and C57BL/6J) were assessed for oral nicotine preference during early adolescence (postnatal day 24-35), middle adolescence (postnatal day 36-47), late adolescence (postnatal day 48-59), adulthood (postnatal day 60+) and 2 months following their initial exposure to nicotine. Mice also were assessed for innate anxiety using an elevated zero maze to determine if age and/or genetic background influenced anxiety-like behaviors. Results indicated that initial nicotine preference and nicotine preference two months after an initial exposure are both strain and age dependent. Age also had an effect on some baseline anxiety measures but strain differences for most zero maze measures were present throughout all age groups. In general, early adolescent C3H mice exhibited greater nicotine preference while C57 mice displayed greater preference during middle adolescence and upon a second exposure to nicotine. In contrast, C57 mice exhibited reduced anxiety across all ages tested. These studies indicate that genetic background should be considered when evaluating age-dependent effects of drugs of abuse and baseline anxiety-like behaviors.