Kamran Ahmad

Prevalence and Characteristics of Early Repolarization in the CASPER Registry Cardiac Arrest Survivors With Preserved Ejection Fraction Registry

OBJECTIVES We evaluated the prevalence and characteristics of early repolarization in patients in CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry). BACKGROUND Early repolarization has been implicated in a syndrome of polymorphic ventricular tachycardia and fibrillation in patients without organic heart disease. METHODS One hundred patients with apparently unexplained cardiac arrest and preserved ejection fraction underwent extensive clinical and genetic testing to unmask subclinical electrical or structural disease. A blinded independent analysis of the 12-lead electrocardiogram (ECG) was performed. Early repolarization was defined as ≥0.1 mV QRS-ST junction (J-point) elevation with terminal QRS slurring or notching in at least 2 contiguous inferior and/or lateral leads. RESULTS One hundred cardiac arrest patients were enrolled (40 females, age 43 ± 14 years). Forty-four were diagnosed with an established cause for cardiac arrest. Significant early repolarization was found in 19 patients, including 6 with a primary diagnosis that explained their cardiac arrest (14%), compared with 23% of the 56 patients with idiopathic ventricular fibrillation (IVF) (p = 0.23). J-point elevation in IVF patients had higher amplitude (0.25 ± 0.11 mV vs. 0.13 ± 0.05 mV, p = 0.02) and wider distribution (4.3 ± 1.3 leads vs. 2.8 ± 0.8 leads; p = 0.01) than those with an established cause of cardiac arrest. J-wave amplitude was fluctuant on serial ECGs; at least 1 ECG failed to demonstrate early repolarization in 58% of patients. CONCLUSIONS Early repolarization is present in a significant proportion of causally diagnosed and idiopathic VF. It is often intermittent and more pronounced in IVF patients. (Registry of Unexplained Cardiac Arrest; NCT00292032).

Evaluation of Genes Encoding for the Transient Outward Current (Ito) Identifies the KCND2 Gene as a Cause of J-Wave Syndrome Associated With Sudden Cardiac Death

Background—J-wave ECG patterns are associated with an increased risk of sudden arrhythmic death, and experimental evidence supports a transient outward current (Ito)-mediated mechanism of J-wave formation. This study aimed to determine the frequency of genetic mutations in genes encoding the Ito in patients with J waves on ECG. Methods and Results—Comprehensive mutational analysis was performed on Ito-encoding KCNA4, KCND2, and KCND3 genes, as well as the previously described J-wave–associated KCNJ8 gene, in 51 unrelated patients with ECG evidence defining a J-wave syndrome. Only patients with a resuscitated cardiac arrest or type 1 Brugada ECG pattern were included for analysis. A rare genetic mutation of the KCND2 gene, p.D612N, was identified in a single patient. Co-expression of mutant and wild-type KCND2 with KChIP2 in HEK293 cells demonstrated a gain-of-function phenotype, including an increase in peak Ito density of 48% (P<0.05) in the heterozygous state. Using computer modeling, this increase in Ito resulted in loss of the epicardial action potential dome, predicting an increased ventricular transmural Ito gradient. The previously described KCNJ8-S422L mutation was not identified in this cohort of patients with ECG evidence of J-wave syndrome. Conclusions—These findings are the first to implicate the KCND2 gene as a novel cause of J-wave syndrome associated with sudden cardiac arrest. However, genetic defects in Ito-encoding genes seem to be an uncommon cause of sudden cardiac arrest in patients with apparent J-wave syndromes.

Epinephrine infusion in the evaluation of unexplained cardiac arrest and familial sudden death: from the cardiac arrest survivors with preserved Ejection Fraction Registry.

Background—Epinephrine infusion may unmask latent genetic conditions associated with cardiac arrest, including long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia (VT). Methods and Results—Patients with unexplained cardiac arrest (normal left ventricular function and QT interval) and selected family members from the Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) registry underwent epinephrine challenge at doses of 0.05, 0.10, and 0.20 &mgr;g/kg per minute. A test was considered positive for long-QT syndrome if the absolute QT interval prolonged by ≥30 ms at 0.10 &mgr;g/kg per minute and borderline if QT prolongation was 1 to 29 ms. Catecholaminergic polymorphic VT was diagnosed if epinephrine provoked ≥3 beats of polymorphic or bidirectional VT and borderline if polymorphic couplets, premature ventricular contractions, or nonsustained monomorphic VT was induced. Epinephrine infusion was performed in 170 patients (age, 42±16 years; 49% men), including 98 patients with unexplained cardiac arrest. Testing was positive for long-QT syndrome in 31 patients (18%) and borderline in 24 patients (14%). Exercise testing provoked an abnormal QT response in 42% of tested patients with a positive epinephrine response. Testing for catecholaminergic polymorphic VT was positive in 7% and borderline in 5%. Targeted genetic testing of abnormal patients was positive in 17% of long-QT syndrome patients and 13% of catecholaminergic polymorphic VT patients. Conclusions—Epinephrine challenge provoked abnormalities in a substantial proportion of patients, most commonly a prolonged QT interval. Exercise and genetic testing replicated the diagnosis suggested by the epinephrine response in a small proportion of patients. Epinephrine infusion combined with exercise testing and targeted genetic testing is recommended in the workup of suspected familial sudden death syndromes. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.Background— Epinephrine infusion may unmask latent genetic conditions associated with cardiac arrest, including long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia (VT). Methods and Results— Patients with unexplained cardiac arrest (normal left ventricular function and QT interval) and selected family members from the Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) registry underwent epinephrine challenge at doses of 0.05, 0.10, and 0.20 μg/kg per minute. A test was considered positive for long-QT syndrome if the absolute QT interval prolonged by ≥30 ms at 0.10 μg/kg per minute and borderline if QT prolongation was 1 to 29 ms. Catecholaminergic polymorphic VT was diagnosed if epinephrine provoked ≥3 beats of polymorphic or bidirectional VT and borderline if polymorphic couplets, premature ventricular contractions, or nonsustained monomorphic VT was induced. Epinephrine infusion was performed in 170 patients (age, 42±16 years; 49% men), including 98 patients with unexplained cardiac arrest. Testing was positive for long-QT syndrome in 31 patients (18%) and borderline in 24 patients (14%). Exercise testing provoked an abnormal QT response in 42% of tested patients with a positive epinephrine response. Testing for catecholaminergic polymorphic VT was positive in 7% and borderline in 5%. Targeted genetic testing of abnormal patients was positive in 17% of long-QT syndrome patients and 13% of catecholaminergic polymorphic VT patients. Conclusions— Epinephrine challenge provoked abnormalities in a substantial proportion of patients, most commonly a prolonged QT interval. Exercise and genetic testing replicated the diagnosis suggested by the epinephrine response in a small proportion of patients. Epinephrine infusion combined with exercise testing and targeted genetic testing is recommended in the workup of suspected familial sudden death syndromes. Clinical Trial Registration— URL: . Unique identifier: [NCT00292032][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00292032&atom=%2Fcircae%2F5%2F5%2F933.atom

Prevalence and Risk Factors for Cervical and Lumbar Spondylosis in Interventional Electrophysiologists

Cervical and Lumbar Spondylosis in Electrophysiologists. Introduction: The volume and complexity of interventional electrophysiology procedures have increased greatly over the last 20 years. Anecdotal reports from Canada and elsewhere have suggested an important prevalence of neck and back problems in interventional electrophysiologists.

Role of antiarrhythmic drugs in patients with implantable cardioverter defibrillators

The transvenous implantable cardioverter defibrillator (ICD) has emerged as the primary therapy for patients at high risk of life-threatening ventricular arrhythmias. A high number of ICD recipients will require subsequent adjunctive treatment with antiarrhythmic drugs (AADs). This review provides an overview of potential reasons for AAD initiation, candidates for treatment, current medical options, and possible drug-device interactions.

Efficacy and safety of dofetilide in the treatment of frequent ventricular tachyarrhythmias after amiodarone intolerance or failure.

To the Editor: Many patients with an implantable cardioverter-defibrillator (ICD) require concomitant antiarrhythmic drug (AAD) therapy at some point. Sotalol and especially amiodarone have been shown to reduce the number of ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes and

Rate control in atrial fibrillation: looking beyond the average heart rate.

Purpose of review The aim of this article is to provide a perspective on rate control in atrial fibrillation which emphasizes patient wellbeing (exercise tolerance, symptoms, quality of life) over attempts to reduce resting or exercise heart rate to an arbitrary range. Recent findings Recent trials of rhythm versus rate control strategies of treatment in patients with atrial fibrillation suggest that rate control is a viable first line strategy in many patients. The adverse consequences of atrial fibrillation with rapid ventricular response are partly due to factors other than rate itself, such as irregularity of ventricular response, and variable changes in autonomic nervous system output. Digoxin, calcium channel blockers, and β-blockers cause a similar reduction in resting heart rate. Beta blockers are the most potent at reducing exercise heart rate, followed by calcium channel blockers and digoxin. Exercise tolerance is occasionally improved by digoxin, sometimes improved by calcium channel blockers and not improved by (and sometimes decreased by) β-blockers. Information about quality of life with different rate control regimens is sparse. Summary Rate control in atrial fibrillation provides important benefits to patients in terms of symptoms, quality of life and prevention of late consequences of uncontrolled rate (such as tachycardia induced cardiomyopathy). Restricting treatment objectives to achievement of a specific heart rate range on resting or exercise electrocardiogram may result in lack of patient benefit or worsened symptoms. Understanding the nuances of rate control when treating individual patients and interpreting existing evidence allows patients to experience the most benefit from this treatment strategy.

Cost effectiveness of continued-warfarin versus heparin-bridging therapy during pacemaker and defibrillator surgery.

In patients receiving warfarin due to high risk of thromboembolic events, current guidelines recommend bridging therapy with heparin or low molecular weight heparin (LMWH) during surgery for cardiac pacemakers or implantable cardioverter-defibrillators [(1)][1]. Bridging therapy is associated with

Electrogram-Based Optimal Atrioventricular and Interventricular Delays of Cardiac Resynchronization Change Individually During Exercise

BACKGROUND Limited data suggest that optimal atrioventricular (AV) and interventricular (VV) delays are different at rest than during exercise in patients with heart failure. We assessed the feasibility and reproducibility of an electrogram-based method of optimization called QuickOpt at rest and during exercise. METHODS Patients with a St Jude Medical cardiac resynchronization therapy implantable cardioverter-defibrillator were subjected to a graded treadmill test, and QuickOpt was repeatedly measured prior to, during, and after the exercise. RESULTS Twenty-four patients (16 males, aged 67.4 ± 7.7 years) participated. At rest, delays (in ms) were 110.4 ± 20.1 for sensed AV delay and -70 (LV pacing first) to +20 (RV pacing first) for VV delay. The changes in QuickOpt-derived delays at rest were not significant despite change in body position. During exercise, QuickOpt-derived AV delays did not change in 11 patients, were shorter during peak exercise in 8 patients, and were longer in 3 patients (average value during peak exercise was 126.5 ± 15.8 ms, P = 0.04 compared to baseline). The QuickOpt-derived VV delay gradually shifted toward earlier right ventricular pacing during exercise in 19 patients, while no changes were seen in 3 patients, and a shift occurred toward earlier left ventricular pacing in 2 patients (average value during peak exercise was -30.7 ± 22.2; P = 0.001 compared to baseline). There was no correlation between changes in the QuickOpt-derived AV and VV delays and heart rate. CONCLUSIONS The application of electrogram-based algorithm is feasible both at rest and during exercise. The results are reproducible. QuickOpt-derived AV and VV delays individually change during exercise.

Pre-Hospital Cardiac Arrest in Acute Coronary Syndromes: Insights from the Global Registry of Acute Coronary Events and the Canadian Registry of Acute Coronary Events

Objectives: Cardiac arrest in acute coronary syndromes (ACS) is associated with high morbidity and mortality. We examined the clinical characteristics, contemporary management patterns and outcomes of ACS patients with pre-hospital cardiac arrest. Methods: The Global Registry of Acute Coronary Events and the Canadian Registry of Acute Coronary Events enrolled 14,010 ACS patients in 1999-2008. We compared the clinical characteristics, in-hospital treatment and outcomes between patients with and without pre-hospital cardiac arrest. Results: Overall, 206 (1.4%) patients had cardiac arrest prior to hospital presentation. ACS patients with pre-hospital cardiac arrest were less frequently treated with aspirin, β-blocker, angiotensin-converting enzyme inhibitors, and statins within the first 24 h of presentation, but the use of cardiac procedures was similar compared to the group without cardiac arrest. Patients with pre-hospital cardiac arrest had significantly higher rates of in-hospital adverse events. Factors independently associated with pre-hospital cardiac arrest included male gender, current smoker status, tachycardia, higher Killip class and ST-segment deviation. Conclusion: ACS patients with pre-hospital cardiac arrest continue to have more in-hospital complications and higher mortality. Their use of evidence-based medical therapies was lower but the use of cardiac procedures was similar compared to the group without cardiac arrest. Better utilization of evidence-based therapies in these patients may translate into improved outcomes.