Non-ischemic sudden cardiac arrest: Role of 12 lead Holter, family screening and genetic testing.

OBJECTIVE AND BACKGROUND: To evaluate the diagnostic and prognostic yield of a comprehensive protocol involving clinical and broad genetic testing in consecutive sudden cardiac arrest (SCA) population. Determining the pathogenesis of non-ischemic SCA is crucial for management and SCA prevention in other family members METHODS: Families with unexplained non-ischemic SCA event underwent rigorous clinical and genetic protocol after referral to our inherited arrhythmia clinic, during 2011-2017. RESULTS: One hundred and four index cases, 29 ± 16 years, and 421 family members were studied. After a thorough evaluation, diagnosis was made in 80 (77%) of families. The most prevalent 47/104 (45%) diagnosis was inherited channelopathy. The genetic test was positive, in 37 /69 (54%) of patients. Using the Mann Whitney test, we found that electrocardiography (ECG) (effect size 0.5, p < .001), 12 lead Holter (effect size 0.33, p = .001) and family screening (effect size 0.4, p = .001) had the highest yield in reaching the final diagnosis. Family screening, genetic testing, and cardiac MRI were the exclusive modalities for final diagnosis in 14%, 9%, and 2% of families, respectively. Among 421 family members evaluated through cascade screening, 127 (30%), were diagnosed and medically treated. Nine family members from 25 (40%) patients who underwent implantable cardioverter defibrillator (ICD) implantation have experienced appropriate ICD shock. CONCLUSIONS: A rigorous, systematic protocol in a specialized inherited arrhythmia clinic has a high diagnostic and prognostic yield. ECG, 12 lead Holter and family screening significantly increased the diagnostic yield. In nine families, without genetic testing, the diagnosis would have been missed.

Prognostic value of cardiac troponin levels in patients presenting with supraventricular tachycardias.

BACKGROUND: An association between paroxysmal supraventricular tachycardias (PSVT) and elevated cardiac troponin I (cTnI) has been reported in small studies, even in the absence of significant coronary artery or structural heart disease. We sought to explore the prognostic significance of elevated cTnI among patients presenting with PSVT. METHODS: This is a retrospective single-center observational study conducted between January 2014 and Decemebr 2016. 165 patients (60% men, mean age 55 ± 17 year-old) with an acute episode of regular supraventricular tachyarrhythmia were admitted to the emergency department at Rambam Medical Center. 131 patients had at least one serum cTnI value measured. Of those, 57 had a positive result, defined as serum cTnI of more than 0.028 ng/dL. RESULTS: Multivariate analysis showed that heart rate > 150 beats per minute (bpm) on admission (OR = 3.9; 95% CI 1.1.6-9.5; p < 0.003) and history of coronary artery disease (CAD) (OR = 3.4; 95% CI 1.2-10.1; p = 0.026) were the only independent predictors of cTnI elevation. After mean follow-up period of 23 ± 7 months, the combined primary outcome of death, coronary intervention (PCI) or myocardial infarction (MI) occurred in 7 patients (12.3%) out of 57 patients with positive cTnI and in zero patients with negative cTn (p = 0.002). Cox proportional hazard model showed that elevated cTnI on admission was an independent predictor of adverse outcomes only in patients with known coronary artery disease (CAD) (HR = 3.3, p = 0.05). CONCLUSION: Elevated cTnI among patients presenting with PSVT appears to have prognostic significance only in patients with history of CAD. In this patient group elevated cTnI is associated with increased risk of adverse cardiac outcomes. We therefore believe serum cTnI should be measured selectively, such as in patients with symptoms of ischemic chest pain and a high pretest likelihood of having CAD.

Risk of death without appropriate defibrillator shock in patients with advanced renal dysfunction.

AIMS: Heart failure patients with advanced chronic kidney disease (CKD) may experience an increased rate of non-arrhythmic mortality due to associated comorbidities. We aimed to evaluate the risk of mortality without appropriate implantable cardioverter-defibrillator (ICD) shocks in this high-risk population. METHODS AND RESULTS: The study population comprised 3542 patients who received an ICD, were enrolled, and prospectively followed-up in the Israeli ICD registry. Study patients were categorized into two groups: those with advanced CKD [defined by a glomerular filtration rate of <30 mL/min/1.73 m2 or being on dialysis at time of implantation (n = 197)], and those without advanced CKD (n = 3344). The primary endpoint was the risk of death without receiving appropriate ICD shock. Kaplan-Meier survival analysis showed that at 5 years of follow-up the rates of death without prior ICD shock were significantly higher in the advanced kidney disease group (46%) compared with the non-advanced CKD group (19%; log-rank P-value <0.001). Consistently, multivariate analysis showed that the risk of death without receiving appropriate ICD shock therapy at 5 years was 2.5-fold (P < 0.001) higher among advanced CKD patients. In contrast, the rate of appropriate ICD shock therapy at 5 years among advanced CKD patients was only 9%, with a very high mortality rate (63%) within 3.5 years subsequent to shock therapy. CONCLUSION: Nearly one-half of ICD with advanced CKD die within 5 years without receiving an appropriate ICD shock. These findings stress the importance of appropriate patient selection for primary ICD implantation in this high-risk population.

Specific Therapy Based on the Genotype in a Malignant Form of Long QT3, Carrying the V411M Mutation.

Congenital long QT syndrome (LQTS) is a cardiac channelopathy that leads to the prolongation of the QT interval. This prolongation can lead to ventricular tachyarrhythmia, syncope, and sudden cardiac death. There are various types of LQTS. Treatment of LQT1 and LQT2 is mainly based on antiadrenergic therapy. LQT3, on the other hand, is a result of a mutation of the SCN5A gene, which encodes the sodium channels. In this type, patients are sensitive to vagal stimuli and episodes tend to occur at rest. Sodium channel blocking compounds, such as ranolazine, mexiletine, and flecainide, have been found to be effective in selective mutations.In this case report, we report the case of a child with congenital LQT3 (V411M) who presented first with sudden cardiac death and three weeks later with an implantable cardioverter defibrillator storm. Knowing the specific mutation and understanding the mechanism at the molecular level through an in vitro study yielded a clinically meaningful result. The patient's arrhythmia burden was totally eliminated following successful treatment with flecainide.

Arrhythmic Events in Brugada Syndrome: A Nationwide Israeli Survey of the Clinical Characteristics, Treatment; and Long-Term Follow-up (ISRABRU-VF).

BACKGROUND: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE). OBJECTIVES: To conduct the first nationwide survey focused on BrS patients with documented AE. METHODS: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2). RESULTS: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13-84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30-53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine. CONCLUSIONS: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

Contemporary rates and outcomes of single- vs. dual-coil implantable cardioverter defibrillator lead implantation: data from the Israeli ICD Registry.

AIMS: Dual-coil leads were traditionally considered standard of care due to lower defibrillation thresholds (DFT). Higher complication rates during extraction with parallel progression in implantable cardioverter defibrillator (ICD) technology raised questions on dual coil necessity. Prior substudies found no significant outcome difference between dual and single coils, although using higher rates of DFT testing then currently practiced. We evaluated the temporal trends in implantation rates of single- vs. dual-coil leads and determined the associated adverse clinical outcomes, using a contemporary nation-wide ICD registry. METHODS AND RESULTS: Between July 2010 and March 2015, 6343 consecutive ICD (n = 3998) or CRT-D (n = 2345) implantation patients were prospectively enrolled in the Israeli ICD Registry. A follow-up of at least 1 year of 2285 patients was available for outcome analysis. The primary endpoint was all-cause mortality. Single-coil leads were implanted in 32% of our cohort, 36% among ICD recipients, and 26% among CRT-D recipients. Secondary prevention indication was associated with an increased rate of dual-coil implantation. A significant decline in dual-coil leads with reciprocal incline of single coils was observed, despite low rates of DFT testing (11.6%) during implantation, which also declined from 31 to 2%. In the multivariate Cox model analysis, dual- vs. single-coil lead implantation was not associated with an increased risk of mortality [hazard ratio (HR) = 1.23; P= 0.33], heart failure hospitalization (HR = 1.34; P=0.13), appropriate (HR = 1.25; P= 0.33), or inappropriate ICD therapy (HR = 2.07; P= 0.12). CONCLUSION: Real-life rates of single-coil lead implantation are rising while adding no additional risk. These results of single-coil safety are reassuring and obtained, despite low and contemporary rates of DFT testing.

Morbidity and mortality with cardiac resynchronization therapy with pacing vs. with defibrillation in octogenarian patients in a real-world setting.

AIMS: Cardiac resynchronization therapy (CRT) with a defibrillator (CRT-D) has downsides of high cost and inappropriate shocks compared to CRT without a defibrillator (CRT-P). Recent data suggest that the survival benefit of implantable cardioverter defibrillator (ICD) therapy is attenuated in the older age group. We hypothesized that, among octogenarians eligible for cardiac resynchronization therapy, CRT-P confers similar morbidity and mortality benefits as CRT-D. METHODS AND RESULTS: We compared morbidity and mortality outcomes between consecutive octogenarian patients eligible for CRT therapy who underwent CRT-P implantation at Barzilai MC (n = 142) vs. those implanted with CRT-D for primary prevention indication who were prospectively enrolled in the Israeli ICD Registry (n = 104). Among the 246 study patients, mean age was 84 ± 3 years, 74% were males, and 66% had ischaemic cardiomyopathy. Kaplan-Meier survival analysis showed that at 5 years of follow-up the rate of all-cause mortality was 43% in CRT-P vs. 57% in the CRT-D group [log-rank P = 0.13; adjusted hazard ratio (HR) = 0.79, 95% CI 0.46-1.35, P = 0.37]. Kaplan-Meier analysis also showed no significant difference in the rates of the combined endpoint of heart failure or death (46 vs. 60%, respectively, log-rank P = 0.36; adjusted HR was 0.85, 95% CI 0.51-1.44, P = 0.55). A Cox proportional hazard with competing risk model showed that re-hospitalizations for cardiac cause were not different for the two groups (adjusted HR 1.35, 95% CI 0.7-2.6, P = 0.37). CONCLUSION: Our data suggest that, in octogenarians with systolic heart failure, CRT-P therapy is associated with similar morbidity and mortality outcomes as CRT-D therapy.

Red cell distribution width predicts death and appropriate therapy in patients with implantable cardioverter defibrillator: A simple measurement with prognostic value in a variety of diseases, may help in better selection of patients who will benefit the most from this device.

BACKGROUND: Red cell distribution width (RDW) is a measure of the size variation of erythrocytes. Its prognostic value has been described in a variety of cardiac and noncardiac diseases. Implantable cardioverter defibrillator (ICD) is useful in preventing sudden cardiac death in high-risk patients, but many of these patients continue to survive without needing ICD therapy. We sought to examine whether RDW, with its prognostic values, can benefit in risk stratification of patients with ICD by predicting death and ICD therapy, and thus help in the selection of patients who will benefit the most from ICD, and minimizing its implantation in others at low risk of death and arrhythmias. METHODS: In a retrospective study, we enrolled patients with ICD implanted for both primary and secondary prevention of sudden cardiac death. Baseline RDW values, demographics, and clinical characteristics, as well as the occurrence of death or first appropriate ICD therapy in postimplantation follow-up were collected. We examined whether RDW can predict higher-risk ICD-implanted patients prone to death and first appropriate ICD therapy (the combined outcome). RESULTS: Final population included 432 patients. Compared to others, patients in the upper RDW tertile were older and had more comorbidities and outcomes. In multivariate analysis including RDW, age, gender, and ejection fraction, RDW was the only predictor of the combined outcome. CONCLUSION: RDW may be useful in risk stratification of patients selected for ICD implantation. But larger prospective randomized trials are needed.

Clinical Outcomes of Single- versus Dual-Chamber Implantable Cardioverter Defibrillators: Lessons from the Israeli ICD Registry.

OBJECTIVE: To compare the clinical outcomes of a single- versus dual-chamber ICD for primary prevention of sudden cardiac death in a large, national ICD registry. METHODS: Data were collected from the prospective Israeli ICD Registry. Baseline characteristics and clinical outcomes including mortality, admissions for heart failure (HF), and ICD therapy were compared between the two groups. RESULTS: A total of 1,125 subjects, 37% with a single-chamber and 63% with a dual-chamber ICD, constructed the baseline cohort. Approximately 80% had ischemic heart disease (IHD). Mean follow-up was 22 months, mean ejection fraction was 30%, and mean QRS width was 103 milliseconds in both groups. During follow-up, there were no significant differences in the rate of mortality, admissions for HF, appropriate or inappropriate therapy, or in time to any of the clinical outcomes. Using multivariate analysis, single-chamber ICD was not associated with increased risk of death or admission for HF. In a subgroup of patients with IHD, single-chamber ICD was associated with a higher rate of inappropriate therapy. CONCLUSIONS: In this large retrospective population-based cohort, dual-chamber ICD showed no benefit in reducing the incidence of death or HF admissions, whereas in a subgroup of patients with IHD, single-chamber ICD was associated with increased inappropriate therapy. Further prospective studies are necessary to assess the benefit of dual-chamber ICD in reducing the rate of inappropriate therapy.

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.

Clinical Outcomes in Patients with Severe Renal Dysfunction Including Dialysis Following Defibrillator Implantation.

BACKGROUND: Renal dysfunction is associated with increased mortality in heart failure (HF) patients. However, there are limited data regarding clinical and arrhythmic outcomes associated with implantable cardioverter defibrillator (ICD) therapy in this population. METHODS: We evaluated outcomes associated with the severity of renal dysfunction with or without dialysis among 2,289 patients who were enrolled and prospectively followed up in the Israeli ICD Registry. The primary endpoint of the study was all-cause mortality. Secondary endpoints included cardiac mortality, HF hospitalization, non-cardiac hospitalization, and appropriate and inappropriate ICD therapy. RESULTS: Severe renal dysfunction patients (estimated glomerular filtration rate<30 ml/min/1.73 m2; n=144 patients; 6%) were older, with higher comorbidities prevalence, and more likely to suffer from advanced HF. Among severe renal dysfunction patients, those on dialysis had a lower prevalence of wide QRS and complete left bundle branch morphology, resulting in lower cardiac resynchronization therapy defibrillator (CRTD) implantation rates. Dialysis was associated with an overall increased risk for all-cause mortality (hazard ratio (HR) 3.22; 95% CI 1.69-6.13; p<0.01) and for noncardiac hospitalizations (HR 2.80; p<0.001) compared to all other study patients. However, within the subgroup of patients with severe renal dysfunction, the presence of dialysis was not an independent risk factor for all-cause mortality (HR 0.99; p=0.97) as compared to non-dialysis. The rate of appropriate ICD therapy for ventricular tachyarrhythmias increased with declining renal function, with the highest rate observed among those undergoing dialysis. CONCLUSIONS: The present findings suggest that dialysis does not significantly modify the adverse outcomes associated with severe renal dysfunction following ICD/CRTD implantation.

Novel Clinical Manifestation of the Known SCN5A D1790G Mutation.

The D1790G mutation was found in all 24 patients of an extended long QT family but not in 200 chromosomes carried by healthy individuals. We describe a 37-year-old man presenting with a typical spontaneous type 1 Brugada pattern who in electrophysiological testing had easily inducible ventricular fibrillation. At the age of 47 years he had an atrial ventricular type 2 block documented by an exercise test and a Holter monitor. Genetic analysis revealed a known D1790G mutation in the gene encoding of the sodium channel (SCN5A) that until now has been associated only with the long QT phenotype. Although this mutation has not been associated with a reduction of sodium channel expression, we hypothesize that sodium currents are further diminished due to the 20-mV shift of the steady-state inactivation curve, and this could contribute to the Brugada phenotype. This case is important as it allows a better understanding of the underlying molecular mechanisms of Brugada syndrome. Moreover, this observation raises concern about the safety of class IC drug therapy in long QT type 3 patients and quinidine therapy in Brugada patients, and emphasizes the importance of a thorough clinical and genetic evaluation.

Electrocardiographic comparison of ventricular premature complexes during exercise test in patients with CPVT and healthy subjects.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but highly malignant inherited arrhythmic disorder. Although a standardized exercise stress test (ST) is the most reliable way to diagnose CPVT, in 30% only single ventricular premature beats (VPCs) were recorded. OBJECTIVE: To evaluate whether electrocardiographic characteristics of VPCs during ST distinguish patients with CPVT from healthy subjects. METHODS: Electrocardiographic characteristics of VPCs during ST in 16 calsequestrin-2 (CASQ2) mutation carriers CPVT patients were compared with that in 36 healthy subjects. RESULTS: CPVT patients had more VPCs (31 ± 14 vs 3 ± 4, P < 0.0001), longer QRS duration (139 ± 18 ms vs 121 ± 21, P = 0.004), and coupling interval (CI; 476 ± 58 ms vs 355 ± 61 ms, P < 0.0001). The most sensitive characteristics for CPVT were >10 VPCs/test (100% sensitivity, 100% negative predictive value [NPV]), left bundle branch block (LBBB) pattern with inferior axis (88% sensitivity, 94% NPV), and CI longer than 400 ms (88% sensitivity, 94% NPV). Bigeminy or trigeminy or LBBB pattern with inferior axis was most specific for CPVT at 100% (100% positive predictive value PPV, 92% NPV). First VPC during the recovery period and VPC recording more than 1 minute during the recovery period were most specific for healthy subjects (100% specificity, 100% PPV). In multivariate analysis, QRS duration >120 ms (odds ratio 4.2, 95% confidence interval 1-17.6, P = 0.04) and first VPC at ≥10 mets (odds ratio 9.1, 95% confidence interval 2.01-41.1, P = 0.004) each predicted the presence of CPVT. CONCLUSIONS: Several electrocardiographic criteria can help distinguish VPCs originating from CPVT compared with healthy subjects.

Outcome of Patients with Advanced Heart Failure Who Receive Device-Based Therapy for Primary Prevention of Sudden Cardiac Death: Insights from the Israeli ICD Registry.

BACKGROUND: Randomized clinical trials have shown conflicting data on the benefit of implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death in patients with more advanced heart failure (HF) symptoms. Using the Israeli ICD Registry data, we sought to examine the effect of HF functional class on the outcome of patients who receive device therapy in a real-world setting. METHODS: The association between HF functional class (categorized as baseline New York Heart Association [NYHA] functional class I and II in [61%] vs class III and IV in [39%]) and clinical outcomes was assessed among 913 patients who received an ICD (n = 514) or a cardiac resynchronization therapy with a defibrillator (CRT-D; n = 399) device and were prospectively followed in the Israeli ICD Registry between July 2011 and June 2013. RESULTS: The risk associated with advanced HF functional class was significantly different in ICD and CRT-D recipients. In the former group, patients with NYHA classes III and IV experienced >3-fold increased risk of HF or death (hazard ratio [HR] = 3.28; P < 0.001), whereas among CRT-D recipients the risk was similar between patients with NYHA III/IV and those with less advanced HF symptoms (HR = 0.97 [95% confidence interval (CI) 0.54-1.78]; P = 0.42; P value for NYHA functional class by device type interaction = 0.002). The risk for ventricular arrhythmia (VA) was significantly lower among patients with more advanced NYHA functional class, regardless of device type (overall HR = 0.52; 95% CI 0.33-0.91; P = 0.04). CONCLUSION: Our findings suggest that patients with less advanced HF symptoms experience a greater risk for VA and the development of HF is attenuated in CRT-D recipients with more advanced NYHA functional class.

Renal dysfunction and clinical outcomes of patients undergoing ICD and CRTD implantation: data from the Israeli ICD registry.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) reduce mortality in patients with heart failure (HF) and left ventricular dysfunction. However, their efficacy in patients with chronic kidney disease (CKD) is controversial. OBJECTIVE: We examined the association between renal dysfunction and clinical outcomes in patients undergoing ICD and CRT defibrillator (CRTD) implantation. METHODS: Data were collected from the Israeli ICD registry. Estimated glomerular filtration rate (eGFR) at implantation was assessed using the modification of diet in renal disease formula. Primary outcome was all-cause mortality. Secondary outcomes included the composite endpoints of death or HF and death or ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]); any hospitalizations; first appropriate and inappropriate ICD therapy. RESULTS: During the study period (July 2010-November 2012), 2,811 patients were implanted with ICD or CRTD. One-year follow-up data were available for 730 ICD patients and 453 CRTD patients. Patients with eGFR < 30 mL/minute/1.73 m(2) (n = 54, 4.6%) were older, had a higher prevalence of diabetes, hypertension, or ischemic heart disease. eGFR <30 mL/minute/1.73 m(2) was associated with increased mortality risk in ICD (HR 5.4; 95% CI 1.5-19.2), but not in CRTD patients (HR 0.9; 95% CI 0.1-7.5). Renal dysfunction was associated with the composite endpoints of death or HF and death or VT/VF in ICD, but not in CRTD patients. Mean eGFR during follow-up decreased by 8.0 ± 4.3 mL/minute/1.73 m(2) in ICD patients (P = 0.06) and by 1.8 ± 1.3 mL/minute/1.73 m(2) in patients with CRTD (P = 0.2). CONCLUSION: Based on this retrospective analysis, CKD is associated with adverse prognosis after ICD implantation, but not after CRTD implantation. GFR decreased in patients with ICD, but not in CRTD patients.

Sex differences in implantable cardioverter-defibrillator implantation indications and outcomes: lessons from the Nationwide Israeli-ICD Registry.

AIMS: Implantable cardioverter-defibrillators (ICDs) improve survival in certain high arrhythmic risk populations. However, there are sex differences regarding both the utilization and the benefit of these devices. Using a prospective national ICD registry, we aim to compare the indications for ICD implantation as well as outcomes in implanted women vs. men. METHODS AND RESULTS: All subjects implanted with an ICD or cardiac resynchronization therapy with a defibrillator (CRTD) in Israel between July 2010 and February 2013 were included. A total of 3544 subjects constructed the baseline cohort, of whom 615 (17%) were women. Women had the same age (64 years) and rate of secondary prevention indication (26%) as men. However, women were more likely than men to have significant heart failure symptoms (52 vs. 45%), QRS > 120 ms (41 vs. 36%), and a higher rate of non-ischaemic cardiomyopathy (54 vs. 21%, all P values <0.05). Using multivariate analysis, women were more likely to undergo CRTD implantation (odds ratio = 1.8, P < 0.01). Follow-up data were available for 1518 subjects with a mean follow-up of 12 months. During follow-up, there were no significant differences among genders in the rate of any single or the combined outcomes of appropriate device therapies, heart failure admissions, or death. First-year re-intervention rate was double among women (5.6 vs. 3.0%, P < 0.01). CONCLUSION: In real-world setting, women implanted with an ICD differ significantly from men in their baseline characteristics and in the use of CRTD devices. These, however, did not translate into outcome differences.

The role of early cardiac resynchronization therapy implantation in dilated cardiomyopathy patients with narrow QRS carrying lamin A/C mutation.

BACKGROUND: Dilated cardiomyopathy (DCM) caused by Lamin A/C gene (LMNA) mutation is complicated with atrioventricular conduction disturbances, malignant ventricular arrhythmias and progressive severe heart failure. OBJECTIVE: We hypothesized that early cardiac resynchronization therapy (CRT) implantation in LMNA mutation carriers with an established indication for pacemaker or implantable cardioverter defibrillator (ICD), may preserve ejection fraction, and delay disease progression to end stage heart failure. METHODS: We compared the primary outcomes: time to heart transplantation, death due to end stage heart failure or ventricular tachycardia (VT) ablation and secondary outcomes: change in left ventricular ejection fraction (EF) and ventricular arrhythmia burden between LMNA DCM patients in the early CRT and non-CRT groups. RESULTS: Of ten LMNA DCM patients (age 51±10 years, QRS 96±14 msec, EF 55±7%) with indication for pacemaker or ICD implantation, five underwent early CRT-D implantation. After 7.2±4 years, three patients (60%) in the non-CRT group reached the primary outcome, compared to no patients in the CRT group (P=0.046). Four patients in non-CRT group (80%) experienced sustained ventricular tachycardia or received appropriate ICD shock compared to 1 patient (20%) in the CRT group (P=0.058). LMNA patients without early CRT had a higher burden of VPC/24 h in 12-lead holter (median 2352 vs 185, P=0.09). Echocardiography showed statistically lower LVEF in the non-CRT group compared to CRT group [(32±15)% vs (61±4)%, 95% CI: 32.97-61.03, P=0.016]. CONCLUSION: Early CRT implantation in LMNA cardiomyopathy patients, with an indication for pacemaker or ICD, may reduce heart failure deterioration and life-threatening heart failure complications.

The role of genetic testing in the prevention, diagnosis, and prognosis of sudden cardiac arrest in children.

Background: Determining the pathogenesis of sudden cardiac arrest (SCA) in children is crucial for its management and prognosis. Our aim is to analyze the role of broad genetic testing in the prevention, diagnosis, and prognosis of SCA in Children. Methods: ECG, 12-lead holter, exercise testing, cardiac imaging, familial study, and genetic testing were used to study 29 families, in whom a child experienced SCA. Results: After a thorough clinical and genetic evaluation a positive diagnosis was reached in 24/29 (83%) families. Inherited channelopathies (long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) were the most prevalent 20/29 (69%) diagnosis, followed by cardiomyopathy 3/29 (10%). Broad genetic testing was positive in 17/24 (71%) cases. Using the Mann-Whitney test, we found that genetic testing (effect size = 0.625, p = 0.003), ECG (effect size = 0.61, p = 0.009), and exercise test (effect size = 0.63, p = 0.047) had the highest yield in reaching the final diagnosis. Genetic testing was the only positive test available for five (17%) families. Among 155 family members evaluated through cascade screening, 73 (47%) had a positive clinical evaluation and 64 (41%) carried a pathologic mutation. During 6 ± 4.8 years of follow-up, 58% of the survived children experienced an arrhythmic event. Of nine family members who had an ICD implant for primary prevention, four experienced appropriate ICD shock. Conclusions: The major causes of SCA among children are genetic etiology, and genetic testing has a high yield. Family screening has an additional role in both the diagnosis and preventing of SCA.

Elevated thrombin generation levels in the left atrial appendage in patients with atrial fibrillation.

Background: Atrial Fibrillation (AF) is the most common sustained tachi-arrhythmia. Thrombus formation in the left atrial appendage (LAA) increases the risk of stroke and systemic embolism in patients with AF. Objectives: The aim of this study was to compare thrombin generation in the LAA to the LA among patients with AF. Methods: A cross-sectional study of consecutive patients with AF undergoing pulmonary veins catheter ablation. Blood samples from the femoral vein (FV), right atrium (RA), left atrium (LA), and LAA were collected during the catheter ablation procedures. Thrombin generation was assessed by a Calibrated Automated Thrombogram. The LAA-calibrated automated thrombogram parameters were compared with the RA, LA, and FV. Results: A total of 47 consecutive patients were enrolled in the study. The endogenous thrombin potential and peak height were significantly higher in the LAA compared with the LA, the mean differences and 95% CI between the LA and LAA were -378.9 (-680.5, -77.2) (nM∗min) and -66.7 (-119.6, -13.8) (nM) in the endogenous thrombin potential and peak height respectively. Conclusion: In patients with AF undergoing catheter ablation, the LAA demonstrated increased thrombin generation compared with the LA. This finding might contribute to the understanding of why the LAA is more predisposed to thrombus formation than the LA. Clinical Trials Registration: NCT03795883.