Background—The hyperpolarization-activated nucleotide-gated channel-HCN4 plays a major role in the diastolic depolarization of sinus atrial node cells. Mutant HCN4 channels have been found to be associated with inherited sinus bradycardia.Methods and Results—Sixteen members of a family with sinus bradycardia were evaluated. Evaluation included a clinical questionnaire, 12-lead ECGs, Holter monitoring, echocardiography, and treadmill exercise testing. Eight family members (5 males) were classified as affected. All affected family members were asymptomatic with normal exercise capacity during long-term follow-up. Electrophysiological testing performed on 2 affected family members confirmed significant isolated sinus node dysfunction. Segregation analysis suggested autosomal-dominant inheritance. Direct sequencing of the exons encoding HCN4 revealed a missense mutation, G480R, in the ion channel pore domain in all affected family members. Function analysis, including expression of HCN4 wild-type and G480R inXenopusoocytes and human embryonic kidney 293 cells, revealed that mutant channels were activated at more negative voltages compared with wild-type channels. Synthesis and expression of the wild-type and mutant HCN4 channel on the plasma membrane tested in human embryonic kidney 293 cells using biotinylation and Western blot analysis demonstrated a reduction in synthesis and a trafficking defect in mutant compared with wild-type channels.Conclusions—We describe an inherited, autosomal-dominant form of sinus node dysfunction caused by a missense mutation in the HCN4 ion channel pore. Despite its critical location, this mutation carries a favorable prognosis without the need for pacemaker implantation during long-term follow-up.

Managing patients with cardiac implantable electrophysiological devices (CIED) infections can be challenging. The first step should be prevention, which involves patient selection, timing of implantation, and the procedure itself. After implantation, a high degree of suspicion should be applied in order to correctly diagnose patients with infected implanted devices. It is necessary to recognize that patients can present with a wide variety of signs and symptoms. Once diagnosed, the next step is determining if it is a local pocket infection or system infection. In almost every patient, in addition to antibiotics, complete removal of ALL hardware is required. Transvenous lead extraction is now safe and effective, but should only be performed at experienced centres with a practiced extraction team, all possible needed equipment, and cardiothoracic surgical backup. After extraction, the indication for CIED therapy should be re-evaluated to determine re-implantation is warranted. Timing of re-implantation depends on a variety of factors such as type of infection or valvular involvement and should be made in concordance with an infectious disease specialist. This review is aimed at introducing the steps needed to manage patients with infected cardiac devices.

Background: The past decade has brought major advances in therapy of patients presenting with acute coronary syndromes (ACS).Hypothesis: The outcomes of ACS patients with atrial fibrillation (AF) has improved over the years.Methods: We evaluated time‐dependent changes in clinical characteristics, management strategies, and outcomes associated with AF observed during ACS hospitalization in patients enrolled in the biannual ACS Israeli Surveys (ACSIS) between 2000 and 2013. We divided the surveys into early (2000–2006) and late (2008–2013) time periods.Results: The study population comprised 13 297 ACS patients, of whom 755 (5.7%) either presented with or developed AF during the index hospitalization. The incidence of AF observed during ACS hospitalization was lower during the later period (6.2% vs 4.9%; P < 0.01). Kaplan‐Meier survival analysis showed that 1‐year mortality rates were significantly lower among ACS patients with and without AF who were enrolled during the later vs early survey period (log‐rank P < 0.01 for the overall difference). However, AF observed among ACS patients was still associated with increased risk for in‐hospital complications and 30‐day and 1‐year mortality during both the early and late survey periods (P < 0.05 for all comparisons).Conclusions: In 10 years, rates of AF among ACS patients have declined significantly. Yet, despite improved overall 1‐year survival for patients with AF, the development of AF in this population remains an independent predictor of mortality that has not changed appreciably over the years.