A Simulation Study of the Effects of His Bundle Pacing in Left Bundle Branch Block.

His bundle pacing (HBP) has emerged as a feasible alternative to right (RVP) and biventricular pacing (BVP) for Cardiac Resynchronization Therapy (CRT). This study sought to assess, in ex-vivo experimental models, the optimal setup for HBP in terms of electrode placement and pacing protocol to achieve superior electrical synchrony in the case of complete His-Purkinje block and left bundle branch block (LBBB). We developed a 3D model of His bundle and bundle branches, embedded in a patient-specific biventricular heart model reconstructed from CT images. A monodomain reaction-diffusion model was adopted to describe the propagation of cardiac action potential, and a custom procedure was developed to compute pseudo-ECGs. Experimental measurements of tip electrode potential waveforms have been performed on ex-vivo swine myocardium to determine the appropriate boundary condition for delivering the electrical stimulus in the numerical model. An extended parametric analysis, investigating the effect of the electrode orientation and helix length, pacing protocol, and atrioventricular delay, allowed us to determine the optimal setup for HBP therapy. Both selective (S-HBP) and non-selective (NS-HBP) His bundle pacing were tested, as the variable anatomical location of the His bundle can result in the activation of the surrounding myocardium. Our study indicates a perpendicular placement of the electrode as the most advantageous for restoring the physiological function of the His-Purkinje system. We found that higher-energy protocols can compensate for the effects of an angled placement though concurring to potential tip fibrosis. Promisingly, we also revealed that an increased electrode helix length can provide optimal resynchronization even with low-energy pacing protocols. Our results provide informative guidance for implant procedure and therapy optimization, which will hopefully have clinical implications further improving the procedural success rates and patients' quality of life, due to reduced incidence of lead revision and onset of complications.

Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis.

PURPOSE OF REVIEW: Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. RECENT FINDINGS: Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.

Efficacy of different doses of omega-3 fatty acids on cardiovascular outcomes: rationale and design of a network meta-analysis.

INTRODUCTION: The impact of omega-3 fatty acids (O3FA) supplementation on cardiovascular risk is still in debate, largely due to the heterogeneity of population enrolled and variable dose and composition of the formulations used in the previous studies. Yet, O3FA may favorably impact on cardiovascular risk by reducing major cardiovascular events (including cardiac death and ischemic events). EVIDENCE ACQUISITION: We aim to perform a comprehensive review of the topic of O3FA for cardiovascular prevention, stemming from a systematic review, to pairwise meta-analysis and network meta-analysis, limiting our inclusion only to randomized clinical trials comparing low dose (LD) (<1 g per day) O3FA and high dose (HD) (>1 g per day) O3FA versus placebo. The efficacy outcomes of interest are total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina and major vascular events. Safety outcomes of interest are bleeding, gastrointestinal disturbances and atrial fibrillation events. EVIDENCE SYNTHESIS: This meta-analysis is expected to include several important studies on cardiovascular primary and secondary prevention and detail on important cardiovascular outcomes. Furthermore, we intend to highlight safety outcomes related to O3FA supplementation. CONCLUSIONS: The present network meta-analysis results will aid physicians in the decision to prescribe O3FA in patients with or at risk of cardiovascular events. In particular, it will be able to solve controversies emerged from previous randomized clinical trials and meta-analyses regarding the benefit of different doses of O3FA supplementation in the cardiovascular prevention.