The impact of trans-catheter aortic valve replacement induced leftbundle branch block on cardiac reverse remodeling

Background Left bundle branch block (LBBB) is common following trans-catheter aortic valve replacement (TAVR) and has been linked to increased mortality, although whether this is related to less favourable cardiac reverse remodeling is unclear. The aim of the study was to investigate the impact of TAVR induced LBBB on cardiac reverse remodeling. Methods 48 patients undergoing TAVR for severe aortic stenosis were evaluated. 24 patients with new LBBB (LBBB-T) following TAVR were matched with 24 patients with a narrow post-procedure QRS (nQRS). Patients underwent cardiovascular magnetic resonance (CMR) prior to and 6 m post-TAVR. Measured cardiac reverse remodeling parameters included left ventricular (LV) size, ejection fraction (LVEF) and global longitudinal strain (GLS). Inter- and intra-ventricular dyssynchrony were determined using time to peak radial strain derived from CMR Feature Tracking. Results In the LBBB-T group there was an increase in QRS duration from 96 ± 14 to 151 ± 12 ms (P < 0.001) leading to inter- and intra-ventricular dyssynchrony (inter: LBBB-T 130 ± 73 vs nQRS 23 ± 86 ms, p < 0.001; intra: LBBB-T 118 ± 103 vs. nQRS 13 ± 106 ms, p = 0.001). Change in indexed LV end-systolic volume (LVESVi), LVEF and GLS was significantly different between the two groups (LVESVi: nQRS -7.9 ± 14.0 vs. LBBB-T -0.6 ± 10.2 ml/m2, p = 0.02, LVEF: nQRS +4.6 ± 7.8 vs LBBB-T -2.1 ± 6.9%, p = 0.002; GLS: nQRS -2.1 ± 3.6 vs. LBBB-T +0.2 ± 3.2%, p = 0.024). There was a significant correlation between change in QRS and change in LVEF (r = -0.434, p = 0.002) and between change in QRS and change in GLS (r = 0.462, p = 0.001). Post-procedure QRS duration was an independent predictor of change in LVEF and GLS at 6 months. Conclusion TAVR-induced LBBB is associated with less favourable cardiac reverse remodeling at medium term follow up. In view of this, every effort should be made to prevent TAVR-induced LBBB, especially as TAVR is now being extended to a younger, lower risk population

Guideline-indicated treatments and diagnostics, GRACE risk score, and survival for non-ST elevation myocardial infarction

Aim: To investigate whether improved survival from NSTEMI, according to GRACE risk score, was associated with guideline-indicated treatments and diagnostics, and persisted after hospital discharge. Methods and results: National cohort study (n=389,507 patients, n=232 hospitals, MINAP registry), 2003-13. The primary outcome was adjusted all-cause survival estimated using flexible parametric survival modelling with time-varying covariates over a median follow-up of 2.3-years. Receipt of all eligible treatments (optimal care) was inversely related to risk status: 25.6% in low, 18.6% in intermediate and 11.5% in high risk NSTEMI. At 30 days, the use of optimal care was associated with improved survival among high (adjusted hazard ratio [aHR]=0.66 [95% CI 0.53-0.86], difference in absolute mortality rate per 100 patients [AMR/100] –0.19 [95% CI –0.29 to –0.08]), and intermediate (aHR=0.74 [95% CI 0.62-0.92]; AMR/100 –0.15 [95% CI –0.23 to –0.08]) risk NSTEMI. At the end of follow-up (8.4 years), the significant association between the use of all eligible guideline-indicated treatments and improved survival remained only for high risk NSTEMI (aHR=0.66 [95% CI 0.50-0.96]; AMR/100= –0.03 [95% CI –0.06 to –0.01]). For low risk NSTEMI, there was no association between the use of optimal care and improved survival at 30 days (aHR=0.92 [95% CI 0.69-1.38] and at 8.4 years (aHR=0.71 [95% CI 0.39-3.74]). Conclusions: Optimal use of guideline-indicated care for NSTEMI was associated with greater survival gains with increasing GRACE risk, but its use decreased with increasing GRACE risk

p120 and Kaiso Regulate Helicobacter pylori-induced Expression of Matrix Metalloproteinase-7

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons develop cancer. One H. pylori constituent that augments disease risk is the cytotoxin-associated gene (cag) pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Matrix metalloproteinase (MMP)-7, a member of a family of enzymes with tumor-initiating properties, is overexpressed in premalignant and malignant gastric lesions, and H. pylori cag+ strains selectively increase MMP-7 protein levels in gastric epithelial cells in vitro and in vivo. We now report that H. pylori-mediated mmp-7 induction is transcriptionally regulated via aberrant activation of p120-catenin (p120), a component of adherens junctions. H. pylori increases mmp-7 mRNA levels in a cag- and p120-dependent manner and induces translocation of p120 to the nucleus in vitro and in a novel ex vivo gastric gland culture system. Nuclear translocation of p120 in response to H. pylori relieves Kaiso-mediated transcriptional repression of mmp-7, which is implicated in tumorigenesis. These results indicate that selective and coordinated induction of mmp-7 expression by H. pylori cag+ isolates may explain in part the augmentation in gastric cancer risk associated with these strains

Walter Deane correspondence.

Senders W-Z, 1854-192

Walter Deane correspondence.

Senders N-P, 1845-192

Walter Deane correspondence.

Sender Bailey, William W., 1888-189

Walter Deane correspondence.

Senders F-G, 1884-192