Citations

Background— QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. Methods and Results— We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0–14.4) versus 7.1% (95% CI, 6.3–8.0) and 8.2% (95% CI, 6.9–9.7) versus 4.4% (95% CI, 3.7–5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03–1.56; P =0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01–1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. Conclusions— QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.

BackgroundTranscatheter aortic valve replacement (TAVR) with the balloon‐expandable Sapien transcatheter heart valve improves survival compared to standard therapy in patients with severe aortic stenosis (AS) and is noninferior to surgical aortic valve replacement (AVR) in patients at high operative risk. Nonetheless, a significant proportion of patients may require pre‐emptive or emergent support with cardiopulmonary bypass (CPB) and/or intra‐aortic balloon pump (IABP) during TAVR due to pre‐existing comorbid conditions or as a result of procedural complications. Objectives: We hypothesized that patients who required CPB or IABP would have increased periprocedural complications and reduced long‐term survival. In addition, we sought to determine whether preprocedural variables could predict the need for CPB and IABP. Methods: The study population included 2,525 patients in the PARTNER Trial (Cohort A and B) and the continuing access registry (CAR). Patients that received CPB or IABP were compared to patients that did not receive either, and then further divided into those that received support pre‐TAVR and those that were placed on support emergently. Results: One‐hundred sixty‐three patients (6.5%) were placed on CPB and/or IABP. The use of CPB or IABP was associated with higher 1 year mortality (49.1% vs. 21.6%, P < 0.001). In multivariable analysis, utilization of CPB or IABP was an independent predictor of 30 day (HR 6.95) and 1‐year (HR 2.56) mortality. Although mortality was highest in emergent cases, mortality was also greater in planned CPB and IABP cases compared with non‐CPB/IABP cases (53.3% and 40.3% vs. 21.6%, P < 0.001). Conclusions: These findings indicate that CPB and IABP use in TAVR portends a poor prognosis and its utilization, particularly in the setting of pre‐emptive use, needs reconsideration. © 2015 Wiley Periodicals, Inc.

Sudden Cardiac Arrest During Sex in Cardiac ChannelopathiesBackgroundPatients with catecholaminergic polymorphic ventricular tachycardia (CPVT) and long‐QT syndrome (LQTS) are susceptible to cardiac events during sympathetic nervous system activation. Herein, we sought to determine the risk of cardiac events associated with sex in CPVT and LQTS patients.Methods and ResultsWe reviewed the electronic medical record of patients seen in the Genetic Heart Rhythm Clinic. There were 445 patients ≥18 years diagnosed with LQTS (N = 402, age at diagnosis 30 ± 16 years) or CPVT (N = 43, age at diagnosis 25 ± 15 years). No sex‐induced cardiac events occurred in the LQTS population, and 2 occurred in the CPVT population. Sex‐induced events were more likely in CPVT (2/43, 4.7%) than LQTS (0/402, 0%, P = 0.008). One case involved a 22‐year‐old CPVT1 female with prior cardiac arrest, who experienced several appropriate implantable cardioverter defibrillator shocks during intercourse while taking β‐blockers. The second case was a 52‐year‐old CPVT1 male with history of recurrent exercise‐triggered syncope, who had syncope during sex in the setting of β‐blocker noncompliance. Extrapolating from published estimates of intercourse frequency by age, the overall event rate was only 0.0004%, and 0.005% among the CPVT cohort.ConclusionsPotentially life‐threatening cardiac events during sex in patients with CPVT are rare and even rarer in LQTS. Overall, the cardiac event per intercourse rate is extremely low. Patients and their partners should be reassured that sex is a low‐risk activity from a cardiac standpoint.

AbstractBackground. The long-term outcome of patients with pyogenic vertebral osteomyelitis (PVO) has not been fully assessed.Methods. We conducted a retrospective cohort study to describe the long-term outcome of PVO and to assess risk factors for treatment failure in patients evaluated at our institution between 1994 and 2002. Patients were observed until July 1, 2013.Results. Two hundred sixty patients with PVO were included in this study. Twenty-seven percent (70) of patients developed their infection after an invasive spinal procedure. Staphylococcus aureus accounted for 40% (103) of infections. Forty-nine percent (128) of patients underwent spinal surgery as part of their initial therapy. The median duration of parenteral antimicrobial therapy was 42 days (interquartile range, 38–53). The estimated 2-, 5-, and 10-year cumulative probability of treatment failure-free survival was 72%, 69%, and 69%, respectively. Seventy-five percent of patients who developed treatment failure did so within 4.7 months of diagnosis. Residual neurological defects and persistent back pain were seen in 16% and 32% of patients, respectively. In a multivariate analysis, longer duration of symptoms before diagnosis and having an infection with S. aureus were associated with increased risk of treatment failure.Conclusions. Increasing duration of symptoms and infection with S. aureus were associated with treatment failure in patients with PVO. Most treatment failures occurred early after initiation of treatment. Pyogenic vertebral osteomyelitis is associated with a high 2-year failure rate. Persistent neurological deficits and back pain are common after therapy.

ASPP2 is an important tumor suppressor protein promoting p53‐dependent and‐independent apoptosis. However, it has been unclear how ASPP2 protein is regulated. Here, we identified Itch as the E3 ubiquitin ligase for ASPP2. Itch interacts with ASPP2 and mediates its degradation and ubiquitination in vivo. The PPXY motif of ASPP2 interacts with the WW domains of Itch. Yap1 competes with Itch for binding to ASPP2, and prevents Itch‐mediated degradation and ubiquitination of ASPP2. Together, these observations reveal that Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability through competing post‐translational regulatory mechanism of ASPP2.

Abstract Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS in patients with taxol- and platinum-resistant ovarian cancer. MV-NIS was given intraperitoneally every 4 weeks for up to 6 cycles. Treatment was well tolerated and associated with promising median overall survival in these patients with heavily pretreated ovarian cancer; no dose-limiting toxicity was observed in 16 patients treated at high-dose levels (108–109 TCID50), and their median overall survival of 26.5 months compared favorably with other contemporary series. MV receptor CD46 and nectin-4 expression was confirmed by immunohistochemistry in patient tumors. Sodium iodide symporter expression in patient tumors after treatment was confirmed in three patients by 123I uptake on SPECT/CTs and was associated with long progression-free survival. Immune monitoring posttreatment showed an increase in effector T cells recognizing the tumor antigens IGFBP2 and FRα, indicating that MV-NIS treatment triggered cellular immunity against the patients' tumor and suggesting that an immune mechanism mediating the observed antitumor effect. Our findings support further clinical evaluation of MV-NIS as an effective immunovirotherapy. Cancer Res; 75(1); 22–30. ©2014 AACR.

BackgroundPatent foramen ovale (PFO) is common and may predispose to paradoxical embolism. Transcatheter device closure of PFO can be challenging in certain cases of “long‐tunnel” PFO morphology. We report our experience with device closure of long‐tunnel PFO using transseptal puncture.MethodsWe retrospectively reviewed all cases of PFO device closure using transseptal puncture at the Mayo Clinic from January 1, 2010 to September 30, 2013. We arbitrarily defined a PFO tunnel configuration as a tunnel length ≥ 12 mm as observed in intracardiac echocardiography (ICE) at the time of device closure.ResultsTwelve patients (mean age 40.8 [range 15–67] years; 7 males [58%]) underwent PFO device closure with transseptal puncture. The most common indication for PFO closure was previous stroke (n = 7, 58%). Median tunnel length measured by ICE was 15 mm (12–20 mm). GORE® HELEX® Septal Occluder was used for closure in all but one patient. The only significant procedural complication was a minor perforation of the left atrial wall during attempted septal puncture, which resulted in a trivial pericardial effusion that resolved without intervention. At latest follow‐up (mean 543 days, [range 170–1162]) one patient had a residual shunt and subsequently died due to complications during surgical PFO closure. No recurrent strokes or TIAs were reported.ConclusionThough not without risk, transseptal puncture can be a valuable tool for facilitating device closure of long‐tunnel type PFOs. GORE® HELEX® Septal Occluder may be an effective option for facilitating device closure for patients with long‐tunnel type PFO. © 2014 Wiley Periodicals, Inc.