Age and the Risk of Ventricular Tachyarrhythmia in Patients With an Implantable Cardioverter-Defibrillator.

BACKGROUND: The benefit of implantable cardioverter-defibrillators (ICDs) in elderly patients is controversial. OBJECTIVES: The aims of this study were to evaluate the risk for ventricular tachyarrhythmia (VTA) and ICD shocks by age groups and to assess the competing risk for VTA and death without prior VTA. METHODS: The study included 5,170 primary prevention ICD recipients enrolled in 5 landmark ICD trials (MADIT [Multicenter Automatic Defibrillator Implantation Trial] II, MADIT-Risk, MADIT-CRT [MADIT Cardiac Resynchronization Therapy], MADIT-RIT [MADIT Reduce Inappropriate Therapy], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillator]). Fine and Gray regression analysis was used to evaluate the risk for fast VTA (ventricular tachycardia ≥200 beats/min or ventricular fibrillation) vs death without prior fast VTA in 3 prespecified age groups: <65, 65 to <75, and ≥75 years. RESULTS: The cumulative incidence of fast VTA at 3 years was similar for patients <65 years of age and those 65 to <75 years of age (17% vs 15%) and was lowest among patients ≥75 years of age (10%) (P < 0.001). Multivariate Fine and Gray analysis showed a 40% lower risk for fast VTA in patients ≥75 years of age (HR: 0.60; 95% CI: 0.46-0.78; P < 0.001) compared with patients <65 years of age. In patients ≥75 years of age, a risk reversal was observed whereby the risk for death without prior fast VTA exceeded the risk for developing fast VTA. A history of nonsustained ventricular tachycardia, male sex, and the presence of nonischemic cardiomyopathy were identified as predictors of fast VTA in patients ≥75 years of age. CONCLUSIONS: Patients ≥75 years of age have a significantly lower risk for VTA and ICD shocks compared with younger patients. Aging is associated with a higher risk for death compared with the risk for fast VTA, the reverse of what is seen in younger patients.

Comparison of Frequency of Ventricular Tachyarrhythmia in Men-Versus-Women in Patients with Implantable Cardioverter-Defibrillator for Primary Prevention.

Current guidelines do not account for possible sex differences in the risk of ventricular tachyarrhythmia (VTA). We sought to identify specific factors associated with increased risk for VTA in women implanted with a primary prevention implantable cardioverter-defibrillator (ICD). Our study cohort consisted of 4,506 patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in the 4 landmark MADIT studies - MADIT-II, MADIT-RISK, MADIT-CRT and MADIT-RIT (1,075 women [24%]). Fine and Gray regression models were used to identify female-specific risk factors for the primary end point of VTA, defined as ICD-recorded, treated, or monitored, sustained ventricular tachycardia ≥170 beats per minute or ventricular fibrillation. At 3.5 years of follow-up, the cumulative incidence of VTA was significantly lower in women than men (17% vs 26%, respectively; p <0.001 for the entire follow-up). Use of amiodarone at enrollment, Black race, and history of previous myocardial infarction without previous revascularization was found to be independent risk factors of VTA in women. Of these factors, only Black race was associated with a statistically significant risk increase in men. At 3.5 years, the cumulative incidence of VTA in women with one or more of these risk factors was 27% compared with 14% in women with none of the risk factors (hazard ratio [confidence interval] = 2.08 [1.49 to 2.91]). In conclusion, our study, comprising 4 landmark ICD clinical trials, shows that sex and race have the potential to be used for improved risk stratification of patients who are candidates for primary prevention ICD.

Case Report: Presumed Optic Neuropathy after Amiodarone and then Dronedarone for Treatment of Atrial Fibrillation.

SIGNIFICANCE: Amiodarone and dronedarone have recognized ophthalmological adverse effects including optic neuropathy. The recognition of optic neuropathy as a complication of amiodarone and dronedarone treatment may enable withdrawing the drug and accordingly preventing permanent vision loss. PURPOSE: This study aimed to describe a case of optic neuropathy after substitution of amiodarone with dronedarone for treatment of atrial fibrillation. CASE REPORT: An 81-year-old man treated with dronedarone for atrial fibrillation after amiodarone had caused tremor developed sequential permanent vision loss in both eyes. CONCLUSIONS: The importance of timely recognition of optic neuropathy as a complication of amiodarone and dronedarone treatment may enable discontinuing the drug, thus preventing permanent vision loss.

Characteristics and outcomes of diabetic patients with an implantable cardioverter defibrillator in a real world setting: results from the Israeli ICD registry.

AIMS: There are limited data regarding the effect of diabetes mellitus (DM) on the risks of both appropriate and inappropriate implantable cardioverter defibrillator (ICD) therapy. The present study was designed to compare the outcome of appropriate and inappropriate ICD therapy in patients with or without DM. METHODS AND RESULTS: The risk of a first appropriate ICD therapy for ventricular tachyarrhythmias (including anti tachycardia pacing and shock) was compared between 764 DM and 1346 non-DM patients enrolled in the national Israeli ICD registry. We also compared the risks of inappropriate ICD therapy, and death or cardiac hospitalization between diabetic and non-diabetic patients. Diabetic patients were older, were more likely to have ischemic cardiomyopathy, lower ejection fraction, atrial fibrillation, and other co-morbidities. The 3-year cumulative incidence of appropriate ICD therapy was similar in the DM and non-DM groups (12 and 13%, respectively, p = 0.983). Multivariate analysis showed that DM did not affect the risk of appropriate ICD therapy (HR = 1.07, 95% CI 0.78-1.47, p = 0.694) or inappropriate therapy (HR = 0.72, 95% CI 0.42-1.23, p = 0.232). However, DM was associated with a 31% increased risk for death or cardiac hospitalization (p = 0.005). Results were similar in subgroup analyses including ICD and defibrillators with cardiac resynchronization therapy function recipients, primary or secondary prevention indication for an ICD. CONCLUSIONS: Despite a significant excess of cardiac hospitalizations and mortality in the diabetic population, there was no difference in the rate of ICD treatments, suggesting that the outcome difference is not related to arrhythmias.

Association between second-hand smoking and acute coronary heart disease among Arab women with multiple risk factors.

BACKGROUND: Active smoking is a well-established risk factor for coronary heart disease (CHD). However, the role of second-hand smoking (SHS) needs further investigation. We aimed to study the association between SHS and CHD in Arab women in Israel. METHODS: A matched case-control study among non-smoking Arab women. The case group included women discharged from hospital after having acute coronary event. The control group was women without CHD who were individually matched for age and type-2 diabetes. The women were interviewed with structured questionnaires on exposure to SHS and on attitudes towards such exposure, and underwent anthropometric measurements. RESULTS: A total of 146 women were included, the majority had type-2 diabetes (68.5%) and were overweight or obese (89.4% of cases and 93.2% of controls, P = 0.727). The prevalence of exposure to domestic-SHS after marriage was higher among the cases than controls (91.8% vs. 53.4%, P < 0.001). After adjustment for hypertension, body mass index > 25 and family history, exposure to domestic-SHS after marriage was an independent risk factor for CHD (OR = 6.1, 95% CI 1.93-19.3). Compared with no exposure, the exposed for 2-6 h a day had an OR of 5.68 (1.48-21.73), and for >6 h a day the OR reached 26.12 (4.26-159.92). Women with CHD felt less comfortable voicing their concern about smoking near them and more highly agreed with prohibition of smoking. CONCLUSIONS: Exposure to domestic-SHS is independently associated with CHD in Arab women, with a strong dose-response relationship, emphasizing the need for public health initiatives to reduce exposure to domestic-SHS.

Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel.

BACKGROUND: The etiology of conduction disturbances necessitating permanent pacemaker (PPM) implantation is often unknown, although familial aggregation of PPM (faPPM) suggests a possible genetic basis. We developed a pan-cardiovascular next generation sequencing (NGS) panel to genetically characterize a selected cohort of faPPM. MATERIALS AND METHODS: We designed and validated a custom NGS panel targeting the coding and splicing regions of 246 genes with involvement in cardiac pathogenicity. We enrolled 112 PPM patients and selected nine (8%) with faPPM to be analyzed by NGS. RESULTS: Our NGS panel covers 95% of the intended target with an average of 229x read depth at a minimum of 15-fold depth, reaching a SNP true positive rate of 98%. The faPPM patients presented with isolated cardiac conduction disease (ICCD) or sick sinus syndrome (SSS) without overt structural heart disease or identifiable secondary etiology. Three patients (33.3%) had heterozygous deleterious variants previously reported in autosomal dominant cardiac diseases including CCD: LDB3 (p.D117N) and TRPM4 (p.G844D) variants in patient 4; TRPM4 (p.G844D) and ABCC9 (p.V734I) variants in patient 6; and SCN5A (p.T220I) and APOB (p.R3527Q) variants in patient 7. CONCLUSION: FaPPM occurred in 8% of our PPM clinic population. The employment of massive parallel sequencing for a large selected panel of cardiovascular genes identified a high percentage (33.3%) of the faPPM patients with deleterious variants previously reported in autosomal dominant cardiac diseases, suggesting that genetic variants may play a role in faPPM.

Ethnic differences among implantable cardioverter defibrillators recipients in Israel.

Heart failure is an increasingly common condition arising from a variety of different pathophysiological processes. Little is known about the unique features of Israeli Arabs who present with heart failure and who undergo cardiac device implantation. The study population comprised of 4,671 patients who were enrolled in the national Israeli Implantable Cardioverter Defibrillator registry. We compared demographic, clinical, and echocardiographic characteristics; device-related indications; and outcomes between Israeli Arabs (n = 733) and Jews (n = 3,938), who were enrolled in the registry from July 2010 through December 2013. Israeli Arabs constituted 15.7% of the study population. They were younger at presentation compared with Jews (57 ± 15 vs 66 ± 12 years, respectively; p <0.001), with a greater burden of co-morbidities, including diabetes mellitus and chronic obstructive lung disease and smoking. In addition, Arab patients had a greater frequency of non-ischemic cardiomyopathy (40.2% vs 24.6%, respectively; p <0.001), which was associated with a greater frequency of familial history of sudden cardiac death. During 15 ± 9 month follow-up, the mortality rates and appropriate device therapy were similar in both ethnic groups. In conclusion, Israeli Arab patients implanted with implantable cardioverter defibrillators display unique clinical features with greater prevalence of non-ischemic cardiomyopathy characterized by an early-onset and rapid deterioration.

Frequencies of C282Y and H63D alleles in the HFE gene among various Jewish ethnic groups in Israel: a change of concept required.

PURPOSE: Hereditary hemochromatosis has not been fully evaluated in the non-Ashkenazi population and is considered to be relatively rare. After ascertaining three unrelated hereditary hemochromatosis families of North African Jewish origin with the HFE C282Y/C282Y genotype, we evaluated the C282Y and H63D allele frequencies among the different Jewish ethnic groups in Israel, in particular North African Jews. METHODS: Data were collected from three Israeli Medical Centers. North African, Oriental, Yemenite, and Sephardic Jewish healthy individuals were assessed for the C282Y and H63D alleles. RESULTS: The C282Y allele frequency was 1.02% (6/586 chromosomes), and the H63D allele frequency was 13.82% (81/586 chromosomes) in the North African Jewish group. The C282Y allele was not detected in the other non-Ashkenazi groups. The H63D allele frequency was 12.5% (38/304 chromosomes) in Oriental Jews, 14.9% (14/94 chromosomes) in Yemenite Jews, and 9.3% (11/118 chromosomes) in Sephardic Jews. DISCUSSION: Hereditary hemochromatosis is underrecognized among North African Jews, who have carrier frequencies of 1/58 and 1/4 for C282Y and H63D, respectively. HFE-hereditary hemochromatosis is not rare among this population as currently thought and merits increased awareness to prevent endpoint disease. The frequent occurrence of beta-thalassemia trait and HFE-H63D in non-Ashkenazi Jews raises the possibility of genetic interactions contributing to iron overload when coinherited and requires further evaluation.

Modern pacemakers: hope or hype?

In recent years, the role of implantable pacing devices has expanded beyond the arrhythmia horizon and contemporary pacemakers' attempt to meet the physiological needs of patients. Modern pacemakers' functions include various modes of dual-chamber pacing, rate-response algorithms with dual sensors for optimum physiological response, cardiac resynchronization therapy (CRT), arrhythmia-prevention algorithms, antitachycardia pacing, and hemodynamic monitoring. The automaticity features of pacemakers enable continuous or intermittent monitoring of various pacemaker parameters including battery voltage, pacing impedance, sensing levels, pacing thresholds, and daily activity log. Modern pacemakers offer "physiological pacing" algorithms that minimize ventricular pacing and reduce the incidence of atrial fibrillation significantly. Ventricular pacing in patients with intact atrioventricular (AV) conduction or intermittent advanced AV block should be minimized with a hope to reduce heart failure hospitalization and mortality. A reduction in all-cause mortality due to physiological pacing, except for the CRT, has yet to be demonstrated in a randomized trial. Overall, modern pacemakers have acceptable performances to fulfill the clinical needs and have a reasonable safety margin. Promising new technologies are currently under development and offer hope to patients who may one day derive both symptomatic and mortality benefit from these devices.

Disparity in utilization of implantable cardioverter-defibrillators in treatment of heart failure based on sex and race.

Evaluation of: Hernandez AF, Fonarow GC, Lang L et al.:Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure.JAMA298(13), 1525-1532 (2007) [1] . Disparity of utilization of proven therapies for treatment of cardiac disease according to gender and ethnicity has been well documented in various aspects of cardiac care. Implanted cardiac defibrillators (ICDs) are devices that have been proven to prevent sudden cardiac death. This retrospective study examined ICD use in heart-failure patients who had an indication for ICD implantation, from the "Get with the Guidelines" program. The patients were stratified by gender and ethnicity (Black vs White). The overall rate of utilization (or intention for utilization) of ICDs was 35%, while among women and Black people the rate was significantly lower, at 27 and 23%, respectively, with the lowest rate being for Black women (28%). These findings suggest a bias against implantation of such devices in women and Black people, which is not explained by clinical variables.

Role of ablation therapy in ventricular arrhythmias.

Catheter ablation is an effective therapy for symptomatic ventricular arrhythmia (VA) in patients with and without structural heart disease. It is the treatment of choice to cure or reduce recurrent VA in patients who have an implantable cardioverter defibrillator and can be a life-saving procedure in patients who have electrical storm. Catheter ablation for VAs remains a challenging procedure and requires a precise understanding of cardiac electrophysiology, the arrhythmia mechanisms, and mapping techniques. Various mapping techniques such as pace mapping, activation mapping, entrainment mapping, and substrate mapping are used. These techniques complement each other in localizing the critical isthmus of a reentrant VT or the source of origin of a focal VT. Most VAs can be ablated endocardially. Epicardial ablation is needed for VAs with an epicardial circuit or a focal source.