The sinoatrial node (SAN) is the primary pacemaker of the heart. Normal SAN function is crucial in maintaining proper cardiac rhythm and contraction. Sinus node dysfunction (SND) is due to abnormalities within the SAN which can affect the heartbeat frequency, regularity, and the propagation of electrical pulses through the cardiac conduction system. As a result, SND often increases the risk of cardiac arrhythmias. SND is most commonly seen as a disease of the elderly given the role of degenerative fibrosis as well as other age-dependent changes in its pathogenesis. Despite the prevalence of SND, current treatment is limited to pacemaker implantation, which is associated with substantial medical costs and complications. Emerging evidence has identified various genetic abnormalities that can cause SND, shedding light on the molecular underpinnings of SND. Identification of these molecular mechanisms and pathways implicated in the pathogenesis of SND is hoped to identify novel therapeutic targets for the development of more effective therapies for this disease. In this review article, we examine the anatomy of the SAN and the pathophysiology and epidemiology of SND. We then discuss in detail the most common genetic mutations correlated with SND and provide our perspectives on future research and therapeutic opportunities in this field.
Purpose of reviewAtrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments. Recent findingsGenome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many implicated genes. Genetic variants at identified loci also help predict individual atrial fibrillation risk and response to different therapies. SummaryContinued advances in the field of genetics and molecular biology have led to significant insight into the genetic underpinnings of atrial fibrillation. Potential clinical applications of these studies include the identification of new therapeutic targets and development of genetic risk scores to optimize management of this common cardiac arrhythmia.
IntroductionConduction system pacing (CSP) is observed to produce greater improvements in echocardiographic and hemodynamic parameters as compared to conventional biventricular pacing (BiVP). However, whether these surrogate endpoints directly translate to improvements in hard clinical outcomes such as death and heart failure hospitalization (HFH) with CSP remains uncertain as studies reporting these outcomes are scarce. The aim of this meta‐analysis was to analyze the existing data to compare the clinical outcomes of CSP versus BiVP.MethodsA systematic search of the Embase and PubMed database was performed for studies comparing CSP and BiVP for patients indicated to receive a CRT device. The coprimary endpoints were all‐cause mortality and HFH. Other secondary outcomes included change in left ventricular ejection fraction (LVEF), change in NYHA class, and increase in NYHA class ≥1. A random‐effects model was chosen a priori to analyze the composite effects given the anticipated heterogeneity of included trials.ResultsTwenty‐one studies (4 randomized and 17 observational) were identified reporting either primary outcome and were included in the meta‐analysis. In total 1960 patients were assigned to CSP and 2367 to BiVP. Median follow‐up time was 10.1 months (ranging 2–33 months). CSP was associated with a significant reduction in all‐cause mortality (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.56–0.83) and HFH (OR 0.52, 95% CI: 0.44–0.63). Mean improvement in LVEF was also greater with CSP (mean difference 4.26, 95% CI: 3.19–5.33). Reduction in NYHA class was significantly greater with CSP (mean difference −0.36, 95% CI: −0.49 to −0.22) and the number of patients with an increase in NYHA class ≥1 was significantly greater with CSP (OR 2.02, 95% CI: 1.70–2.40).ConclusionsCSP was associated with a significant reduction in all‐cause mortality and HFH when compared to conventional BiVP for CRT. Further large‐scale randomized trials are needed to verify these observations.
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