Publications (7)41.92 Total impact
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Article: QT interval and mortality: the long, the short, and the ugly. Comment on "QT interval duration and mortality rate".
Archives of internal medicine 10/2011; 171(19):1734-5. · 11.46 Impact Factor -
Article: SCN5A mutation associated with acute myocardial infarction.
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ABSTRACT: Ventricular tachycardia and fibrillation (VT/VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) have both been linked to phase 2 reentry. Because of these mechanistic similarities in arrhythmogenesis, we examined the contribution of SCN5A mutations to VT/VF complicating AMI. Nineteen consecutive patients developing VF during AMI were enrolled. Wild-type (WT) and mutant SCN5A genes were co-expressed with SCN1B in TSA201 cells and studied using whole-cell patch-clamp techniques. One missense mutation (G400A) in SCN5A was detected in a conserved region among the cohort of 19 patients. A H558R polymorphism was detected on the same allele. Unlike the other 18 patients who each developed 1-2 VF episodes during acute MI, the mutation carrier developed six episodes of VT/VF within the first 12 hours. All VT/VF episodes were associated with ST segment changes and were initiated by short-coupled extrasystoles. We describe the first sodium channel mutation to be associated with the development of an arrhythmic storm during acute ischemia. These findings suggest that a loss of function in SCN5A may predispose to ischemia induced arrhythmic storm. These results could be very useful for forensic implications regarding genetic screening in relatives.Legal Medicine 05/2009; 11 Suppl 1:S206-9. -
Article: Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia.
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ABSTRACT: The mainstay of therapy for catecholaminergic polymorphic ventricular tachycardia (CPVT) is maximal doses of beta-blockers. However, although beta-blockers prevent exercise-induced ventricular tachycardia (VT), most patients continue to have ventricular ectopy during exercise, and some studies report high mortality rates despite beta-blockade. The purpose of this study was to investigate whether combining a calcium channel blocker with beta-blockers would prevent ventricular arrhythmias during exercise better than beta-blockers alone since the mutations causing CPVT lead to intracellular calcium overload. Five patients with CPVT and one with polymorphic VT (PVT) and hypertrophic cardiomyopathy who had exercise-induced ventricular ectopy despite beta-blocker therapy were studied. Symptom-limited exercise was first performed during maximal beta-blocker therapy and repeated after addition of oral verapamil. When comparing exercise during beta-blockers with exercise during beta-blockers + verapamil, exercise-induced arrhythmias were reduced: (1) Three patients had nonsustained VT on beta-blockers, and none of them had VT on combination therapy. (2) The number of ventricular ectopics during the whole exercise test went down from 78 +/- 59 beats to 6 +/- 8 beats; the ratio of ventricular ectopic to sinus beats during the 10-second period recorded at the time of the worst ventricular arrhythmia went down from 0.9 +/- 0.4 to 0.2 +/- 0.2. One patient with recurrent spontaneous VT leading to multiple shocks from her implanted cardioverter-defibrillator (ICD) despite maximal beta-blocker therapy (14 ICD shocks over 6 months while on beta-blockers) has remained free of arrhythmias (for 7 months) since the addition of verapamil therapy. This preliminary evidence suggests that beta-blockers and calcium blockers could be better than beta-blockers alone for preventing exercise-induced arrhythmias in CPVT.Heart Rhythm 10/2007; 4(9):1149-54. · 4.10 Impact Factor -
Article: Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction.
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ABSTRACT: Ventricular tachycardia (VT) and ventricular fibrillation (VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) both have been linked to phase 2 reentry. Given the mechanistic similarities in arrhythmogenesis, the purpose of this study was to examine the contribution of SCN5A mutations to VT/VF complicating AMI. Nineteen consecutive patients developing VF during AMI were enrolled in the study. Wild-type (WT) and mutant SCN5A genes were coexpressed with SCN1B in TSA201 cells and studied using whole-cell patch clamp techniques. Among the cohort of 19 patients, one missense mutation (G400A) in SCN5A was detected in a conserved region. An H558R polymorphism was detected on the same allele. Unlike the other 18 patients, who each developed 1-2 VF episodes during AMI, the mutation carrier developed six episodes of VT/VF within the first 12 hours. All VT/VF episodes were associated with ST-segment changes and were initiated by short-coupled extrasystoles. Flecainide and adenosine challenge performed to unmask Brugada and long QT syndromes both were negative. Peak G400A and G400A+H558R current were 70.7% and 88.4% less than WT current at -35 mV (P </=.001). G400A current decay was accelerated and steady-state inactivation was shifted -6.39 mV (V(1/2) = -98.9 +/- 0.1 mV vs -92.5 +/- 0.1 mV, P </=.001). No mutations were detected in KCNH2, KCNQ1, KCNE1, or KCNE2 in the G400A patient. We describe the first sodium channel mutation to be associated with the development of an arrhythmic storm during acute ischemia. These findings suggest that a loss of function in SCN5A may predispose to ischemia-induced arrhythmic storm.Heart Rhythm 08/2007; 4(8):1072-80. · 4.10 Impact Factor -
Article: Radiofrequency ablation of accessory pathways: a 14 year experience at the Tel Aviv Medical Center in 508 patients.
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ABSTRACT: Radiofrequency ablation has been suggested as first-line therapy in the management of accessory pathways. There are limited data on the results of ablation over years of experience. To assess the results and complications following RFA of APs performed in our institution over a 14 year period. RFA was performed using deflectable electrode catheters positioned at the mitral or tricuspid annulus. The site of the AP was localized by electrophysiological study and radiofrequency energy was applied via the tip of the catheter. The study cohort comprised 508 consecutive patients (64.2% males, mean age 33.6 +/- 15.1 years) who underwent 572 RFA procedures for ablating 534 APs. A single AP was found in 485 (95.5%) patients while multiple APs were noted in 23 patients (4.5%). The APs were manifest, concealed or intermittent in 46.8%, 44.4% and 8.8% of cases, respectively. AP distribution was as follows: left free wall (56.6%), posteroseptal (23%), right anteroseptal (7.9%), right free wall (6.2%), midseptal (3.4%) and right atriofascicular (3.0%). Acute successful rates for a first or multiple ablation attempts were 93.1% and 95.3%, respectively. At a first ablation attempt, acute success and failure rates were the highest for midseptal (100%) and right atriofascicular (12.5%) APs respectively. Right anteroseptal APs were associated with the highest rate (23.9%) of discontinued or non-attempted procedures. Recurrent conduction in an AP after an initial successful ablation was observed in 9.9% of cases; it was the highest (24.2%) for right free wall APs and the lowest (5.0%) for left free wall APs. During follow-up (85 +/- 43 months), definite cure of the AP was achieved in 94.9% of cases following a single or multiple procedures: midseptal (100%), left free wall (98%), right free wall (97%), posteroseptal (92.7%), right atriofascicular (87.5%) and right anteroseptal (78.5%). A non-fatal complication occurred in 18 patients (3.5%), more frequently in females (6.6%) than in males (1.8%) (P < 0.01). The two major complications (pericardial effusion and myocardial ischemic events) mainly occurred during RFA of a left free wall AP using a retrograde aortic approach. Catheter-induced mechanical trauma to APs was observed in 56 cases (10.5%). Mechanical trauma mainly involved right atriofascicular (43.8%) and right anteroseptal (38.1%) APs and contributed to the low success rate of RFA at these AP locations. During the 14 year period, our learning curve was achieved quickly in terms of success rate, although the most significant complications were observed at the beginning of our experience. The results of this study confirm the efficacy and safety of RFA and suggest that it is a reasonable first-line therapy for the management of APs at any location.The Israel Medical Association journal: IMAJ 04/2007; 9(4):265-70. · 1.02 Impact Factor -
Article: The morphology of the QT interval predicts torsade de pointes during acquired bradyarrhythmias.
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ABSTRACT: The purpose of this study was to define the electrocardiographic (ECG) predictors of torsade de pointes (TdP) during acquired bradyarrhythmias. Complete atrioventricular block (CAVB) might lead to downregulation of potassium channels, QT interval prolongation, and TdP. Because potassium-channel malfunction causes characteristic T-wave abnormalities in the congenital long QT syndrome (LQTS), we reasoned that T-wave abnormalities like those described in the congenital LQTS would identify patients at risk for TdP during acquired bradyarrhythmias. In a case-control study, we compared 30 cases of bradyarrhythmias complicated by TdP with 113 cases of uncomplicated bradyarrhythmias. On the basis of the criteria used for the congenital LQTS, T waves were defined as LQT1-like (long QT interval with broad T waves), LQT2-like (notched T waves), and LQT3-like (small and late) T waves. Neither the ventricular rate nor the QRS width at the time of worst bradyarrhythmia predicted the risk of TdP. However, the QT, corrected QT (QTc), and T(peak)-T(end) intervals correlated with the risk of TdP. The best single discriminator was a T(peak)-T(end) of 117 ms. LQT1-like and LQT3-like morphologies were rare during bradyarrhythmias. In contrast, LQT2-like "notched T waves" were observed in 55% of patients with TdP but in only 3% of patients with uncomplicated bradyarrhythmias (p < 0.001). A 2-step model based on QT duration and the presence of LQT2-like T waves identified patients at risk for TdP with a positive predictive value of 84%. Prolonged QT interval, QTc interval, and T(peak)-T(end) correlate with increased risk for TdP during acquired bradyarrhythmias, particularly when accompanied by LQT2-like notched T waves.Journal of the American College of Cardiology 02/2007; 49(3):320-8. · 14.16 Impact Factor -
Article: Serum levels of interleukin-18 in patients with stable and unstable angina pectoris.
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ABSTRACT: Recent evidence suggests that atherosclerosis is an inflammatory disorder in which cytokines appear to play an important role. Special attention centered over the possible contribution of cytokines to the destabilization of the plaque. IL-18 is a proinflammatory cytokine of the IL-1 family, recognized for its ability to promote IFN-gamma secretion. It has recently been detected in human plaques and its administration was associated with increased atherosclerosis in apolipoprotein E (apoE) mice concomitant with an increase in plaque infiltrating inflammatory cells. In our study, we investigated whether patients with established atherosclerosis, with either stable or unstable angina, possessed high levels of IL-18. Patients with stable angina (n=48) were from the outpatient clinic whereas patients with unstable angina (n=73) were recruited upon admission and prior to performance of coronary angiography. Control patients (n=19) were healthy subjects with no evidence of coronary artery disease. Serum levels of IL-18 were assayed by ELISA. Patients with stable and unstable angina exhibited higher serum levels of IL-18 (77.1+/-7.2 and 61.5+/-5.1 pg/ml, respectively) in comparison to control subjects (p=0.002 and p=0.02, respectively). However, levels of IL-18 did not differ significantly between patients with stable and unstable angina. No differences were evident in the serum concentrations of IL-18 in patients with unstable angina (n=17) upon admission and 1-3 months later when the angina was already controlled. Although IL-18 serum levels appear elevated in the presence of coronary atherosclerosis, there is no evidence to associate this progression towards plaque instability.International Journal of Cardiology 02/2005; 98(1):45-8. · 7.08 Impact Factor
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2005
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Tel Aviv University
Tel Aviv, Tel Aviv, Israel
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