Differential Response to Cardiac Resynchronization Therapy and Clinical Outcomes According to QRS Morphology and QRS Duration

ObjectivesThe goal of this study was to examine the relative impact of QRS morphology and duration in echocardiographic responses to cardiac resynchronization therapy (CRT) and clinical outcomes.BackgroundAt least one-third of all patients treated with CRT fail to derive benefit. Patients without left bundle branch block (LBBB) or patients with smaller QRS duration (QRSd) respond less or not at all to CRT.MethodsWe retrospectively assessed baseline characteristics, clinical and echocardiographic response, and outcomes of all patients who received CRT at our institution between December 2003 and July 2007. Patients were stratified into 4 groups according to their baseline QRS morphology and QRSd.ResultsA total of 496 patients were included in the study; 216 (43.5%) had LBBB and a QRSd ≥150 ms, 85 (17.1%) had LBBB and QRSd <150 ms, 92 (18.5%) had non-LBBB and a QRSd ≥150 ms, and 103 (20.8%) had non-LBBB and QRSd <150 ms. Echocardiographic response (change in ejection fraction) was better in patients with LBBB and QRSd ≥150 ms (12 ± 12%) than in those with LBBB and QRSd <150 ms (8 ± 10%), non-LBBB and QRSd ≥150 ms (5 ± 9%), and non-LBBB and QRSd <150 ms (3 ± 11%) (p < 0.0001). In a multivariate stepwise model with change in ejection fraction as the dependent variable, the presented classification was the most important independent variable (p = 0.0003). Long-term survival was better in LBBB patients with QRSd ≥150 ms (p = 0.02), but this difference was not significant after adjustment for other baseline characteristics (p = 0.15).ConclusionsQRS morphology is a more important baseline electrocardiographic determinant of CRT response than QRSd

A systematic review of intervention effects on potential mediators of children\u27s physical activity

Background : Many interventions aiming to increase children&rsquo;s physical activity have been developed and implemented in a variety of settings, and these interventions have previously been reviewed; however the focus of these reviews tends to be on the intervention effects on physical activity outcomes without consideration of the reasons and pathways leading to intervention success or otherwise. To systematically review the efficacy of physical activity interventions targeting 5-12 year old children on potential mediators and, where possible, to calculate the size of the intervention effect on the potential mediator. Methods : A systematic search identified intervention studies that reported outcomes on potential mediators of physical activity among 5-12 year old children. Original research articles published between 1985 and April 2012 were reviewed. Results : Eighteen potential mediators were identified from 31 studies. Positive effects on cognitive/psychological potential mediators were reported in 15 out of 31 studies. Positive effects on social environmental potential mediators were reported in three out of seven studies, and no effects on the physical environment were reported. Although no studies were identified that performed a mediating analysis, 33 positive intervention effects were found on targeted potential mediators (with effect sizes ranging from small to large) and 73% of the time a positive effect on the physical activity outcome was reported. Conclusions : Many studies have reported null intervention effects on potential mediators of children&rsquo;s physical activity; however, it is important that intervention studies statistically examine the mediating effects of interventions so the most effective strategies can be implemented in future programs

A case series of very slow atrioventricular nodal reentrant tachycardia resembling junctional tachycardia

IntroductionThe surface electrocardiography&nbsp;of typical atrioventricular nodal reentrant tachycardia (AVNRT) shows simultaneous ventricular-atrial (RP) activation with pseudo R'&nbsp;in V1 and typical heart rates ranging from 150 to 220/min. Slower rates are suspicious for junctional tachycardia (JT). However, occasionally we encounter typical AVNRT with slow ventricular rates. We describe a series of typical AVNRT cases with heart rates under 110/min.MethodsA total of 1972 patients with AVNRT who underwent slow pathway ablation were analyzed. Typical AVNRT was diagnosed when; (1) evidence of dual atrioventricular nodal conduction, (2) tachycardia initiation by atrial drive train with atrial-His-atrial response, (3) short septal ventriculoatrial&nbsp;time, and (4) ventricular-atrial-ventricular (V-A-V) response to ventricular overdrive (VOD) pacing with corrected post pacing interval-tachycardia cycle length (cPPI-TCL) &gt; 110 ms. JT was excluded by either termination or advancement of tachycardia by atrial extrastimuli (AES) or atrial overdrive (AOD) pacing.ResultsWe found 11 patients (age 20-78 years old, six&nbsp;female) who met the above-mentioned criteria. The TCL ranged from 560&nbsp;to 782 ms. Except for one patient showing tachycardia termination, all patients demonstrated a V-A-V response and cPPI-TCL over 110 ms with VOD. AES or AOD pacing successfully excluded JT by either advancing the tachycardia in 10 patients or by tachycardia termination in one patient. Slow pathway was successfully ablated, and tachycardia was not inducible in all patients.ConclusionsThis case series describes patients with typical AVNRT with slow ventricular rate (less than 110/min) who may mimic JT. We emphasize the importance of using pacing maneuvers to exclude JT

A Genome-Wide RNAi Screen Identifies FOXO4 as a Metastasis-Suppressor through Counteracting PI3K/AKT Signal Pathway in Prostate Cancer

Activation of the PI3K/AKT signal pathway is a known driving force for the progression to castration-recurrent prostate cancer (CR-CaP), which constitutes the major lethal phenotype of CaP. Here, we identify using a genomic shRNA screen the PI3K/AKT-inactivating downstream target, FOXO4, as a potential CaP metastasis suppressor. FOXO4 protein levels inversely correlate with the invasive potential of a panel of human CaP cell lines, with decreased mRNA levels correlating with increased incidence of clinical metastasis. Knockdown (KD) of FOXO4 in human LNCaP cells causes increased invasion in vitro and lymph node (LN) metastasis in vivo without affecting indices of proliferation or apoptosis. Increased Matrigel invasiveness was found by KD of FOXO1 but not FOXO3. Comparison of differentially expressed genes affected by FOXO4-KD in LNCaP cells in culture, in primary tumors and in LN metastases identified a panel of upregulated genes, including PIP, CAMK2N1, PLA2G16 and PGC, which, if knocked down by siRNA, could decrease the increased invasiveness associated with FOXO4 deficiency. Although only some of these genes encode FOXO promoter binding sites, they are all RUNX2-inducible, and RUNX2 binding to the PIP promoter is increased in FOXO4-KD cells. Indeed, the forced expression of FOXO4 reversed the increased invasiveness of LNCaP/shFOXO4 cells; the forced expression of FOXO4 did not alter RUNX2 protein levels, yet it decreased RUNX2 binding to the PIP promoter, resulting in PIP downregulation. Finally, there was a correlation between FOXO4, but not FOXO1 or FOXO3, downregulation and decreased metastasis-free survival in human CaP patients. Our data strongly suggest that increased PI3K/AKT-mediated metastatic invasiveness in CaP is associated with FOXO4 loss, and that mechanisms to induce FOXO4 re-expression might suppress CaP metastatic aggressiveness