Usefulness of inducible ventricular tachycardia to predict long-term adverse outcomes in arrhythmogenic right ventricular cardiomyopathy

The role of the electrophysiologic (EP) study for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy is controversial. We investigated the role of inducible sustained monomorphic ventricular tachycardia (SMVT) for the prediction of an adverse outcome (AO), defined as the occurrence of cardiac death, heart transplantation, sudden cardiac death, ventricular fibrillation, ventricular tachycardia with hemodynamic compromise or syncope. Of 62 patients who fulfilled the 2010 Arrhythmogenic Right Ventricular Cardiomyopathy Task Force criteria and underwent an EP study, 30 (48%) experienced an adverse outcome during a median follow-up of 9.8 years. SMVT was inducible in 34 patients (55%), 22 (65%) of whom had an adverse outcome. In contrast, in 28 patients without inducible SMVT, 8 (29%) had an adverse outcome. Kaplan-Meier analysis showed an event-free survival benefit for patients without inducible SMVT (log-rank p = 0.008) with a cumulative survival free of an adverse outcome of 72% (95% confidence interval [CI] 56% to 92%) in the group without inducible SMVT compared to 26% (95% CI 14% to 50%) in the other group after 10 years. The inducibility of SMVT during the EP study (hazard ratio [HR] 2.99, 95% CI 1.23 to 7.27), nonadherence (HR 2.74, 95% CI 1.3 to 5.77), and heart failure New York Heart Association functional class II and III (HR 2.25, 95% CI 1.04 to 4.87) were associated with an adverse outcome on univariate Cox regression analysis. The inducibility of SMVT (HR 2.52, 95% CI 1.03 to 6.16, p = 0.043) and nonadherence (HR 2.34, 95% CI 1.1 to 4.99, p = 0.028) remained as significant predictors on multivariate analysis. This long-term observational data suggest that SMVT inducibility during EP study might predict an adverse outcome in patients with arrhythmogenic right ventricular cardiomyopathy, advocating a role for EP study in risk stratification.

Cognitive inertia and the implicit association test

The authors review the implicit association test (IAT), its use in marketing, and the methodology and validity issues that surround it. They focus on a validity problem that has not been investigated previously, namely, the impact of cognitive inertia on IAT effects. Cognitive inertia refers to the difficulty in switching from one categorization rule to another, which causes IAT effects to depend on the order of administration of the two IAT blocks. In Study 1, the authors observe an IAT effect when the compatible block precedes the incompatible block but not when it follows the incompatible block. In Studies 2 and 3, the IAT effect changes its sign when the order of the blocks reverses. Cognitive inertia distorts individual IAT scores and diminishes the correlations between IAT scores and predictor variables when the block order is counterbalanced between subjects. Study 4 shows that counterbalancing the block order repeatedly within subjects can eliminate cognitive inertia effects on the individual level. The authors conclude that researchers should either interpret IAT scores at the aggregate level or, if individual IAT scores are of interest, counterbalance the block order repeatedly within subjects.

How do indirect measures of evaluation work? Evaluating the inference of prejudice in the Implicit Association Test

There has been significant interest in indirect measures of attitudes like the Implicit Association Test (IAT), presumably because of the possibility of uncovering implicit prejudices. The authors derived a set of qualitative predictions for people's performance in the IAT on the basis of random walk models. These were supported in 3 experiments comparing clearly positive or negative categories to nonwords. They also provided evidence that participants shift their response criterion when doing the IAT. Because of these criterion shifts, a response pattern in the IAT can have multiple causes. Thus, it is not possible to infer a single cause (such as prejudice) from IAT results. A surprising additional result was that nonwords were treated as though they were evaluated more negatively than obviously negative items like insects, suggesting that low familiarity items may generate the pattern of data previously interpreted as evidence for implicit prejudice.

Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 Pilot European Sentinel Registry.

BACKGROUND The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited. OBJECTIVES The aim of this multinational registry is to present a real-world overview of TMVR use in Europe. METHODS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective, independent, consecutive collection of individual patient data. RESULTS A total of 628 patients (mean age 74.2 ± 9.7 years, 63.1% men) underwent TMVR between January 2011 and December 2012 in 25 centers in 8 European countries. The prevalent pathogenesis was functional mitral regurgitation (FMR) (n = 452 [72.0%]). The majority of patients (85.5%) were highly symptomatic (New York Heart Association functional class III or higher), with a high logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (20.4 ± 16.7%). Acute procedural success was high (95.4%) and similar in FMR and degenerative mitral regurgitation (p = 0.662). One clip was implanted in 61.4% of patients. In-hospital mortality was low (2.9%), without significant differences between groups. The estimated 1-year mortality was 15.3%, which was similar for FMR and degenerative mitral regurgitation. The estimated 1-year rate of rehospitalization because of heart failure was 22.8%, significantly higher in the FMR group (25.8% vs. 12.0%, p[log-rank] = 0.009). Paired echocardiographic data from the 1-year follow-up, available for 368 consecutive patients in 15 centers, showed a persistent reduction in the degree of mitral regurgitation at 1 year (6.0% of patients with severe mitral regurgitation). CONCLUSIONS This independent, contemporary registry shows that TMVR is associated with high immediate success, low complication rates, and sustained 1-year reduction of the severity of mitral regurgitation and improvement of clinical symptoms.

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES Survival, stroke, and New York Heart Association functional class. RESULTS Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

The association between implicit alcohol attitudes and drinking behavior is moderated by baseline activation in the lateral prefrontal cortex

OBJECTIVE Intense alcohol consumption is a risk factor for a number of health problems. Dual-process models assume that self-regulatory behavior such as drinking alcohol is guided by both reflective and impulsive processes. Evidence suggests that (a) impulsive processes such as implicit attitudes are more strongly associated with behavior when executive functioning abilities are low, and (b) higher neural baseline activation in the lateral prefrontal cortex (PFC) is associated with better inhibitory control. The present study integrates these 2 strands of research to investigate how individual differences in neural baseline activation in the lateral PFC moderate the association between implicit alcohol attitudes and drinking behavior. METHOD Baseline cortical activation was measured with resting electroencephalography (EEG) in 89 moderate drinkers. In a subsequent behavioral testing session they completed measures of implicit alcohol attitudes and self-reported drinking behavior. RESULTS Implicit alcohol attitudes were related to self-reported alcohol consumption. Most centrally, implicit alcohol attitudes were more strongly associated with drinking behavior in individuals with low as compared with high baseline activation in the right lateral PFC. CONCLUSIONS These findings are in line with predictions made on the basis of dual-process models. They provide further evidence that individual differences in neural baseline activation in the right lateral PFC may contribute to executive functioning abilities such as inhibitory control. Moreover, individuals with strongly positive implicit alcohol attitudes coupled with a low baseline activation in the right lateral PFC may be at greater risk of developing unhealthy drinking patterns than others.

There is more than "more is up": Hand and foot responses reverse the vertical association of number magnitudes

Recent research in cognitive sciences shows a growing interest in spatial-numerical associations. The horizontal SNARC (spatial-numerical association of response codes) effect is defined by faster left-sided responses to small numbers and faster right-sided responses to large numbers in a parity judgment task. In this study we investigated whether there is also a SNARC effect for upper and lower responses. The grounded cognition approach suggests that the universal experience of "more is up" serves as a robust frame of reference for vertical number representation. In line with this view, lower hand responses to small numbers were faster than to large numbers (Experiment 1). Interestingly, the vertical SNARC effect reversed when the lower responses were given by foot instead of the hand (Experiments 2, 3, and 4). We found faster upper (hand) responses to small numbers and faster lower (foot) responses to large numbers. Additional experiments showed that spatial factors cannot account for the reversal of the vertical SNARC effect (Experiments 4 and 5). Our results question the view of "more is up" as a robust frame of reference for spatial-numerical associations. We discuss our results within a hierarchical framework of numerical cognition and point to a possible link between effectors and number representation.

Effect of B-type Natriuretic Peptides on Long-Term Outcomes After Transcatheter Aortic Valve Implantation.

B-type natriuretic peptide (BNP) levels are elevated in patients with aortic stenosis (AS) and decrease acutely after replacement of the stenotic valve. The long-term prognostic value of BNP after transcatheter aortic valve implantation (TAVI) and the relative prognostic utility of single versus serial peri-interventional measurements of BNP and N-terminal prohormone BNP (NT-pro-BNP) are unknown. This study sought to determine the impact of BNP levels on long-term outcomes after TAVI and to compare the utility of BNP versus NT-pro-BNP measured before and after intervention. We analyzed 340 patients with severe AS and baseline pre-TAVI assessment of BNP. In 219 patients, BNP and NT-pro-BNP were measured serially before and after intervention. Clinical outcomes over 2 years were recorded. Patients with high baseline BNP (higher tertile ≥591 pg/ml) had increased risk of all-cause mortality (adjusted hazard ratio 3.16, 95% confidence interval 1.84 to 5.42; p <0.001) and cardiovascular death at 2 years (adjusted hazard ratio 3.37, 95% confidence interval 1.78 to 6.39; p <0.001). Outcomes were most unfavorable in patients with persistently high BNP before and after intervention. Comparing the 2 biomarkers, NT-pro-BNP levels measured after TAVI showed the highest prognostic discrimination for 2-year mortality (area under the curve 0.75; p <0.01). Baseline-to-discharge reduction, but not baseline levels of BNP, was related to New York Heart Association functional improvement. In conclusion, high preintervention BNP independently predicts 2-year outcomes after TAVI, particularly when elevated levels persist after the intervention. BNP and NT-pro-BNP and their serial periprocedural changes provide complementary prognostic information for symptomatic improvement and survival.

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and associate with increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes mellitus and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (p=2.4*10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. SNPs at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in average UACR per minor allele was 21% for HS6ST1 and 13% for RAB38/CTSC (p=6.3*10(-7) and 5.8*10(-7), respectively). Experiments using streptozotocin-treated diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout vs. control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared to controls. The loci identified here confirm known and highlight novel pathways influencing albuminuria.