ObjectiveBileaflet mitral valve prolapse (MVP) with either focal or diffuse myocardial fibrosis has been linked to ventricular arrhythmia and/or sudden cardiac arrest. Left ventricular (LV) mechanical dispersion by speckle-tracking echocardiography (STE) is a measure of heterogeneity of ventricular contraction previously associated with myocardial fibrosis. The aim of this study is to determine whether mechanical dispersion can identify MVP at higher arrhythmic risk.MethodsWe identified 32 consecutive arrhythmic MVPs (A-MVP) with a history of complex ventricular ectopy on Holter/event monitor (n=23) or defibrillator placement (n=9) along with 27 MVPs without arrhythmic complications (NA-MVP) and 39 controls. STE was performed to calculate global longitudinal strain (GLS) as the average peak longitudinal strain from an 18-segment LV model and mechanical dispersion as the SD of the time to peak strain of each segment.ResultsMVPs had significantly higher mechanical dispersion compared with controls (52 vs 42 ms, p=0.005) despite similar LV ejection fraction (62% vs 63%, p=0.42) and GLS (−19.7 vs −21, p=0.045). A-MVP and NA-MVP had similar demographics, LV ejection fraction and GLS (all p>0.05). A-MVP had more bileaflet prolapse (69% vs 44%, p=0.031) with a similar degree of mitral regurgitation (mostly trace or mild in both groups) (p>0.05). A-MVP exhibited greater mechanical dispersion when compared with NA-MVP (59 vs 43 ms, p=0.0002). Mechanical dispersion was the only significant predictor of arrhythmic risk on multivariate analysis (OR 1.1, 95% CI 1.02 to 1.11, p=0.006).ConclusionsSTE-derived mechanical dispersion may help identify MVP patients at higher arrhythmic risk.

The genes encoding the mevalonate-based farnesyl pyrophosphate (FPP) biosynthetic pathway were encoded in two operons and expressed in Escherichia coli to increase the production of sesquiterpenes. Inefficient translation of several pathway genes created bottlenecks and led to the accumulation of several pathway intermediates, namely, mevalonate and FPP, and suboptimal production of the sesquiterpene product, amorphadiene. Because of the difficulty in choosing ribosome binding sites (RBSs) to optimize translation efficiency, a combinatorial approach was used to choose the most appropriate RBSs for the genes of the lower half of the mevalonate pathway (mevalonate to amorphadiene). RBSs of various strengths, selected based on their theoretical strengths, were cloned 5' of the genes encoding mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate decarboxylase, and amorphadiene synthase. Operons containing one copy of each gene and all combinations of RBSs were constructed and tested for their impact on growth, amorphadiene production, enzyme level, and accumulation of select pathway intermediates. Pathways with one or more inefficiently translated enzymes led to the accumulation of pathway intermediates, slow growth, and low product titers. Choosing the most appropriate RBS combination and carbon source, we were able to reduce the accumulation of toxic metabolic intermediates, improve growth, and improve the production of amorphadiene approximately fivefold. This work demonstrates that balancing flux through a heterologous pathway and maintaining steady growth are key determinants in optimizing isoprenoid production in microbial hosts.

Several electrocardiographic criteria can help distinguish right ventricular outflow tract arrhythmias originating from ARVD/C compared with RVOT-VT patients.

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In women, elevated levels of serum resistin are significantly associated with higher rates of incident AF and partially mediate the association between BMI and AF. In the same population, leptin and adiponectin levels are not significantly associated with AF.