Identification and electrophysiological characterization of early left atrial structural remodeling as a predictor for atrial fibrillation recurrence after pulmonary vein isolation.

BACKGROUND: Voltage-guided substrate ablation following pulmonary vein isolation (PVI) improves atrial fibrillation (AF) ablation outcomes. However, by setting an upper voltage cutoff of 0.5 mV during sinus rhythm (SR) to guided substrate ablation using electroanatomic voltage mapping (EAVM), mildly affected low-voltage area (maLVA) may be undetected. We sought to determine the optimal bipolar voltage cutoff to identify maLVA, its electrogram complexity, and the implication on ablation outcome. METHODS AND RESULTS: Left atrial (LA) EAVMs were obtained in patients without AF and structural heart disease (control) to devise a voltage cutoff to identify maLVA. Subsequently, we investigated 100 patients without low-voltage area (LVA) of < 0.5 mV who underwent PVI alone. In our 6 control cohorts, 95% of LA regional bipolar voltage was > 1.17 mV. maLVA, defined as <1.1 mV, was present in 43% of AF patients, associated with higher prevalence of abnormal electrograms (44.1% vs. 4.4%, P < 0.001). During a median of 2.4 years, patients with maLVA had higher recurrence rate (Log-rank P < 0.001), and maLVA was an independent predictor for recurrence in a multivariate analysis (hazard ratio [HR] 3.944; 95% confidence interval [CI] 1.292-12.042; P = 0.016). CONCLUSIONS: A control-derived LA voltage cutoff of <1.1 mV for EAVM in SR reveals maLVA, harboring abnormal electrograms, as an independent predictor for recurrences after PVI alone in patients without LVA (< 0.5 mV). Adjunctive maLVA-guided substrate ablation targeting mildly remodeled and potentially arrhythmogenic LA substrate may further improve the long-term outcome of AF ablation.

Safety of computed tomography in patients with cardiac rhythm management devices: assessment of the U.S. Food and Drug Administration advisory in clinical practice.

OBJECTIVES: To assess the safety of computed tomography (CT) imaging in patients with cardiac rhythm management (CRM) devices, which was subject to an advisory from the U.S. Food and Drug Administration (FDA) in 2008. BACKGROUND: The FDA warned about potential interference of CT imaging with CRM devices and made recommendations for clinical practice despite only limited evidence. METHODS: All 516 CT scans that involved direct radiation exposure of CRM devices (332 defibrillators, 184 pacemakers) at 2 large-volume centers between July 2000 and May 2010 were included. The primary outcome was a composite endpoint of death, bradycardia or tachycardia requiring termination of the scan or an immediate intervention, unplanned hospital admission, reprogramming of the device, inappropriate defibrillator shocks, or device replacement/revision thought to be due to CT imaging. Significant changes in device parameters were sought as a secondary outcome (control group 4:1 ratio). RESULTS: The main finding was that none of the CTs were associated with the primary outcome. With serial device interrogations, there were no differences in changes in battery voltage or lead parameters between devices exposed to radiation and their controls. Potentially significant changes in device parameters were observed in a small group of devices (both the CT group and control group), but no definitive link to CT was confirmed, and there were no associated clinical consequences. CONCLUSIONS: The findings suggest that the presence of CRM devices should not delay or result in cancellation of clinically indicated CT imaging procedures, and provide evidence that would be helpful when the FDA advisory is re-evaluated.

Survival after in-hospital cardiopulmonary resuscitation.

BACKGROUND: The use of postarrest variables to predict survival after discharge following in-hospital cardiopulmonary resuscitation has not been definitive. This study evaluates whether the duration of cardiopulmonary resuscitation (CPR) and other variables affect discharge rates and survival rates after discharge. METHODS: Prospective cohort survival data and arrest variables were collected, including initial observed rhythm, duration of CPR, time of arrest, and number of arrests. Arrests on unmonitored general medical units, monitored telemetry units, and critical care units were included. Outcome measures were: survival after CPR, 24 hours post-CPR, survival to discharge, and to six months postdischarge. RESULTS: At both discharge and six months after discharge, ventricular fibrillation and ventricular tachycardia were associated with better survival rates than other initial rhythms (P < 0.001). There were significantly higher survival rates (P < 0.001) for those receiving CPR for < or =10 minutes as compared with those receiving CPR >10 minutes. Multiple versus single arrests and monitored versus unmonitored arrests approached significance. The time of day of the arrest was not a significant factor. CONCLUSIONS: Duration of CPR >10 minutes was predictive of significantly decreased survival to discharge and six months postdischarge. Low six-month survival rates may reflect the relatively high proportion of initial rhythms other than ventricular in the study group.

Invariant chain and the MHC class II cytoplasmic domains regulate localization of MHC class II molecules to lipid rafts in tumor cell-based vaccines.

Cell-based tumor vaccines, consisting of MHC class I+ tumor cells engineered to express MHC class II molecules, stimulate tumor-specific CD4+ T cells to mediate rejection of established, poorly immunogenic tumors. Previous experiments have demonstrated that these vaccines induce immunity by functioning as APCs for endogenously synthesized, tumor-encoded Ags. However, coexpression of the MHC class II accessory molecule invariant chain (Ii), or deletion of the MHC class II cytoplasmic domain abrogates vaccine immunogenicity. Recent reports have highlighted the role of lipid microdomains in Ag presentation. To determine whether Ii expression and/or truncation of MHC class II molecules impact vaccine efficacy by altering MHC class II localization to lipid microdomains, we examined the lipid raft affinity of MHC class II molecules in mouse M12.C3 B cell lymphomas and SaI/A(k) sarcoma vaccine cells. Functional MHC class II heterodimers were detected in lipid rafts of both cell types. Interestingly, expression of Ii in M12.C3 cells or SaI/A(k) cells blocked the MHC class II interactions with cell surface lipid rafts. In both cell types, truncation of either the alpha- or beta-chain decreased the affinity of class II molecules for lipid rafts. Simultaneous deletion of both cytoplasmic domains further reduced localization of class II molecules to lipid rafts. Collectively, these data suggest that coexpression of Ii or deletion of the cytoplasmic domains of MHC class II molecules may reduce vaccine efficacy by blocking the constitutive association of MHC class II molecules with plasma membrane lipid rafts.