David Luria

Point Mutation in the HCN4 Cardiac Ion Channel Pore Affecting Synthesis, Trafficking, and Functional Expression Is Associated With Familial Asymptomatic Sinus Bradycardia

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 in Xenopus oocytes 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.

Programmable multiple pacing configurations help to overcome high left ventricular pacing thresholds and avoid phrenic nerve stimulation.

Background: High left ventricular pacing (LVP) thresholds and phrenic nerve stimulation (PNS) are common problems with cardiac resynchronization (CRT). Newer systems capable of multiple LVP configurations may help overcome these problems without the need for reoperation.

Do abandoned leads pose risk to implantable cardioverter-defibrillator patients?

BACKGROUND With the increased number of implantable cardioverter-defibrillator (ICD) recipients and the frequent need for device upgrading, lead malfunction is a concern, but the optimal approach to managing nonfunctioning leads is unknown. OBJECTIVE The purpose of this study was to determine the rate and characteristics of complications related to abandoned ICD leads. METHODS Patients with abandoned leads were identified by retrospective review of the Mayo Clinic ICD database from August 1993 to May 2002. We reviewed the medical records to assess long-term follow-up for venous thromboembolic complications, device sensing malfunction, appropriateness of delivered shocks, defibrillation threshold (DFT) values before and after lead abandonment, and subsequent surgical procedures related to devices or leads. RESULTS We identified 78 ICD patients (81% males; mean age 63 +/- 14 years) with 101 abandoned leads (69 in the right ventricle, 31 in the right atrium or superior vena cava, 1 in the coronary sinus). During a mean follow-up of 3.1 +/- 2.0 years, neither sensing malfunction nor venous thromboembolic complications were detected. DFT values were high in 13 patients (17%), but there was no significant increase in mean DFT values before and after lead abandonment in 43 patients for whom both values were available (16.2 +/- 9.2 J before abandonment vs 14.1 +/- 5.5 J after; P = .24). Fourteen patients (18%) required further ICD-related surgery; none of these operations were attributed to abandoned leads. Five-year rates of appropriate and inappropriate shocks were 25.9% and 20.5%, respectively. CONCLUSION Abandoning a nonfunctioning lead appears to be safe and does not pose a clinically significant additional risk of future complications.

Predictors and mode of detection of transvenous lead malfunction in implantable defibrillators

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Left Atrial Contractile Function Following a Successful Modified Maze Procedure at Surgery and the Risk for Subsequent Thromboembolic Stroke

OBJECTIVES The aim of this study was to evaluate whether certain post-Maze left atrial (LA) contractile profiles may pose a risk for ischemic stroke. BACKGROUND The mechanical contraction of the left atrium may be modified after the Maze procedure. Whether this imposes a risk for stroke, even in the presence of sinus rhythm and after removal of the LA appendage, is not known. METHODS Clinical, surgery-related, and echocardiographic data from 150 patients who underwent radiofrequency and cryoablation Maze procedures without the use of atrial incisions between 2004 and 2009 and were in sustained sinus rhythm were collected and analyzed. The occurrence of stroke was evaluated by reviewing clinical records. All stroke events were adjudicated by a neurologist. RESULTS At a mean follow-up time of 24.5 months, 15 patients (10%) had experienced ischemic strokes. Forty-seven patients (31%) had no evidence of LA mechanical contraction at 3 months after surgery (baseline assessment) and on follow-up echocardiography. Multivariate analysis showed that a lack of LA mechanical contraction at baseline was associated with a 5-fold increase in the risk for stroke (p = 0.02) during follow-up. Larger atria imposed a significant risk as well; LA volume index ≥33 ml/m(2) was associated with a 3-fold risk increase (p = 0.03). These effects were maintained regardless of the lack of mechanical valve implantation and anticoagulation treatment. CONCLUSIONS Absence of LA contraction and LA volume index ≥33 ml/m(2) result in a significant increase in the risk for thromboembolic stroke after the Maze procedure for patients in sinus rhythm.

Improvement of Congestive Heart Failure by Upgrading of Conventional to Resynchronization Pacemakers

Aims: To compare the clinical response of patients with right ventricular apical pacing (RVAP) upgraded to cardiac resynchronization therapy (CRT) to that of previously nonpaced heart failure (HF) patients who had de novo CRT implantation.

Effects of Sex on the Incidence of Cardiac Tamponade After Catheter Ablation of Atrial Fibrillation Results From a Worldwide Survey in 34 943 Atrial Fibrillation Ablation Procedures

Background—Cardiac tamponade is the most dramatic complication observed during atrial fibrillation (AF) ablation and the leading cause of procedure-related mortality. Female sex is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. Methods and Results—A systematic Medline search was used to locate academic electrophysiological centers that reported cases of tamponade occurring during AF ablation. Centers were asked to provide information on cases of acute tamponade according to sex and their mode of management including any case of related mortality. Nineteen electrophysiological centers provided information on 34 943 ablation procedures involving 25 261 (72%) men. Overall, 289 (0.9%) cases of tamponade were reported: 120 (1.24%) in women and 169 (0.67%) in men (odds ratio, 1.83; P<0.001). There was a reciprocal association between center volume and the occurrence of tamponade with substantially lower risk in high-volume centers. Most cases of tamponade occurred during catheter manipulation or ablation; women tended to develop more tamponades during transseptal catheterization. No sex difference in the mode of management was observed. However, 16% cases of tamponade required surgery with lower rates in high-volume centers. Three cases of tamponade (1%) culminated in death. Conclusions—Tamponade during AF ablation procedures is relatively rare. Women have an ≈2-fold higher risk for developing this complication. The risk of tamponade among women decreases substantially in high-volume centers. Surgical backup and acute management skills for treating tamponade are important in centers performing AF ablation.

Risk of Recurrent Cardiac Events After Onset of Menopause in Women With Congenital Long-QT Syndrome Types 1 and 2

Background— Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population. Methods and Results— We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the Long-QT Syndrome Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause transition (hazard ratio, 3.38; P=0.005) and the postmenopausal period (hazard ratio, 8.10; P<0.001) compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19; P=0.05; P=0.02 for genotype-by-menopause interaction). Only 22 women (8%) experienced aborted cardiac arrest or sudden cardiac death during follow-up. The frequency of aborted cardiac arrest/sudden cardiac death showed a similar genotype-specific association with the onset of menopause. Conclusions— The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population.

Effects of Gender on the Incidence of Cardiac Tamponade Following Catheter Ablation of Atrial Fibrillation: Results from a Worldwide Survey in 34,943 AF Ablation Procedures.

Background—Cardiac tamponade is the most dramatic complication observed during atrial fibrillation (AF) ablation and the leading cause of procedure-related mortality. Female sex is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. Methods and Results—A systematic Medline search was used to locate academic electrophysiological centers that reported cases of tamponade occurring during AF ablation. Centers were asked to provide information on cases of acute tamponade according to sex and their mode of management including any case of related mortality. Nineteen electrophysiological centers provided information on 34 943 ablation procedures involving 25 261 (72%) men. Overall, 289 (0.9%) cases of tamponade were reported: 120 (1.24%) in women and 169 (0.67%) in men (odds ratio, 1.83; P<0.001). There was a reciprocal association between center volume and the occurrence of tamponade with substantially lower risk in high-volume centers. Most cases of tamponade occurred during catheter manipulation or ablation; women tended to develop more tamponades during transseptal catheterization. No sex difference in the mode of management was observed. However, 16% cases of tamponade required surgery with lower rates in high-volume centers. Three cases of tamponade (1%) culminated in death. Conclusions—Tamponade during AF ablation procedures is relatively rare. Women have an ≈2-fold higher risk for developing this complication. The risk of tamponade among women decreases substantially in high-volume centers. Surgical backup and acute management skills for treating tamponade are important in centers performing AF ablation.

Tilt training: does it have a role in preventing vasovagal syncope?

Background: Vasovagal syncope is one of the most common medical conditions in young adults. Previous trials have shown effectiveness of tilt training in treating this condition. We conducted a prospective, randomized study in order to evaluate the role of tilt‐training in young adults with vasovagal syncope.