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Because there has been a significant push toward His bundle pacing (HBP), multiple studies and advancements are underway to provide new and improved delivery tools and lead designs, allowing one to apply this technology in daily practice. A better understanding of the pacing configurations and ultimately development of dedicated algorithms will alleviate some of these aforementioned challenges. Ultimately, with such technological advances and mounting clinical evidence, one can surely anticipate HBP to revolutionize the field of cardiac pacing.

Over the last decades, the clinical need for managing the consequences of chronically implanted intravascular cardiac pacemaker or defibrillator leads has grown exponentially. Lead failure and new indications for an upgraded device therapy often requires new lead implantation in a limited central venous “real estate”. In addition, device implantation in patients with increasing comorbidities resulted in higher infection rates and cure in these cases is unlikely without complete system removal. While removal with simple traction of recently implanted leads is often sufficient, once significant fibrosis takes place around the lead (usually after 6 -12 months), use of special extraction tools often becomes necessary as traction may cause complications or incomplete lead removal. Among the numerous older and newer advanced lead management modalities, the most extensive clinical experience and supporting data from multicenter trials has come from the use of the excimer laser technology.

Background— Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2 ), 1q21 (rs13376333 in KCNN3 ), and 16q22 (rs7193343 in ZFHX3 ) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results— Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1–1.6]; P =0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions— Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.

Cardiomyopathies are a heterogeneous group of disorders characterized by myocardial dysfunction that variably progress to a range of clinical symptoms including congestive heart failure, life-threatening arrhythmias, and sudden death. While previously conceived as the general sequelae of ischemic heart disease or extrinsic insults, familial studies have greatly facilitated our understanding of the molecular basis for the cardiomyopathies. In this chapter, we review our current understanding of the cardiomyopathies with a focus on the genetic mutations and molecular pathways implicated in their pathogenesis. Our goal is to underscore the complexity of the disease mechanisms, and to highlight any overlap in the molecular pathways between the cardiomyopathies that can result in distinct phenotypes. Despite our increased understanding of the molecular basis of the cardiomyopathies in the last 15 years, further research is critically necessary to develop novel therapeutic modalities for these morbid cardiovascular conditions.

Atrial fibrillation (AF) is the most common sustained arrhythmia and has significant clinical impact. Over the last decade, our understanding of the genetics of AF has expanded dramatically. After a heritable predisposition for AF was identified, many investigators have in turn identified both common and rare variants associated with AF. Ongoing work is focused on translating these variants into disease pathways and novel therapeutic modalities. In this review, we focus on our understanding of the current concepts behind the genetics of AF and outline a vision for the incorporation of genetic data into clinical practice.