Peter Leong-Sit

A novel pacing maneuver to localize focal atrial tachycardia.

Background: Although focal atrial tachycardias cannot be entrained, we hypothesized that atrial overdrive pacing (AOP) can be an effective adjunct to localize the focus of these tachycardias at the site where the post‐pacing interval (PPI) is closest to the tachycardia cycle length (TCL).

Prediction of Arrhythmic Events in Ischemic and Dilated Cardiomyopathy Patients Referred for Implantable Cardiac Defibrillator Evaluation of Multiple Scar Quantification Measures for Late Gadolinium Enhancement Magnetic Resonance Imaging

Background— Scar signal quantification using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) identifies patients at higher risk of future events, both in ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). However, the ability of scar signal burden to predict events in such patient groups at the time of referral for implantable cardioverter-defibrillator (ICD) has not been well explored. This study evaluates the predictive use of multiple scar quantification measures in ICM and DCM patients being referred for ICD. Methods and Results— One hundred twenty-four consecutive patients referred for ICD therapy (59 with ICM and 65 with DCM) underwent a standardized LGE-CMR protocol with blinded, multithreshold scar signal quantification and, for those with ICM, peri-infarct signal quantification. Patients were followed prospectively for the primary combined outcome of appropriate ICD therapy, survived cardiac arrest, or sudden cardiac death. At a mean follow-up of 632 ± 262 days, 18 patients (15%) had suffered the primary outcome. Total scar was significantly higher among those suffering a primary outcome, a relationship maintained within each cardiomyopathy cohort (P<0.01 for all comparisons). Total scar was the strongest independent predictor of the primary outcome and demonstrated a negative predictive value of 86%. In the ICM subcohort, peri-infarct signal showed only a nonsignificant trend toward elevation among those having a primary end point. Conclusions— Myocardial scar quantification by LGE-CMR predicts arrhythmic events in patients being evaluated for ICD eligibility irrespective of cardiomyopathy etiology.

Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs

BACKGROUND Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain. METHODS We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock. RESULTS Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group. CONCLUSIONS In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).

Arrhythmia characterization and long-term outcomes in catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergically induced ventricular tachycardia (VT) associated with syncope and sudden death. OBJECTIVE This study sought to characterize arrhythmias associated with CPVT with respect to provocation by exercise and drugs, electrocardiographic characteristics, and association with long-term outcomes; and to explore the relation between age and clinical presentation. METHODS Seventy patients from 16 families were evaluated with exercise and selective adrenaline challenge, and screened for RyR2 mutations. CPVT was diagnosed in probands with symptoms and stress- or adrenaline-provoked VT, or in asymptomatic relatives with provoked VT or RyR2 mutations. Patients were followed up for recurrent syncope, VT, and sudden death. RESULTS Twenty-seven patients including 16 probands were identified (median age 35 years, 67% female). Presentation was cardiac arrest in 33% and syncope in 56%, and 11% were asymptomatic. Polymorphic or bidirectional VT was provoked with exercise in 63% and adrenaline in 82%. The initiating beat of VT was late-coupled and wide (coupling interval 418 ± 42 ms; QRSd 131 ± 17 ms), and QRS morphology suggested an outflow tract origin in 59%. During follow-up of 6.2 ± 5.7 years, 2 patients died despite an implantable cardioverter-defibrillator (ICD), 4 patients received ICD therapy for VT, and 5 patients had inappropriate therapy for supraventricular tachycardia. Patients presenting with late-onset CPVT (age > 21; n = 10) were often female (80%) and less likely to have RyR2 (Ryanodine receptor type 2) mutations (33%), and fatal events were not observed during follow-up (4.1 ± 3.6 years). CONCLUSION Ventricular arrhythmia in CPVT is often initiated from the outflow tract region. Despite β-blocker therapy and selective ICD implantation, breakthrough arrhythmias occur and may be associated with adverse outcomes.

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).

Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands

Background— Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. Methods and Results— Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers. QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers). Mean age was 35±18 years, and resting corrected QT interval (QTc) was 466±39 ms. Abnormal resting QTc (females ≥480 ms; males ≥470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc ≥445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (n=152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc=443±47 ms), sensitivity was 0.92 and specificity was 0.82. Conclusions— A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relatives.

Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study): Six-Month Follow-Up Study

Background—We previously demonstrated that treatment with antiarrhythmic drugs (AADs) during the first 6 weeks after atrial fibrillation (AF) ablation reduces the incidence of clinically significant atrial arrhythmias and need for cardioversion or hospitalization for arrhythmia management. Whether early rhythm suppression decreases longer-term arrhythmia recurrence is unknown. We now report the 6-month follow-up data from this study. Methods and Results—The Antiarrhythmics After Ablation of Atrial Fibrillation study prospectively randomized patients with paroxysmal AF undergoing ablation to either receive (AAD group) or not receive (no-AAD group) AAD treatment for the first 6 weeks after ablation; all patients received atrioventricular nodal blockers. Physicians were encouraged to stop the AADs after the 6-week treatment period. All patients underwent 4 weeks of transtelephonic monitoring to document asymptomatic AF and an evaluation at 6 weeks and 6 months. A total of 110 patients (71% men) aged 55±9 years were randomized, with 53 to AAD and 57 to no AAD. At 6 months, there was no difference in freedom from AF between the early AAD and no-AAD groups (38/53 [72%] versus 39/57 [68%]; P=0.84). Lack of early AF recurrence during the initial 6-week period was the only independent predictor of 6-month freedom from AF (64/76 [84%] without early recurrence versus 13/34 [38%] with early recurrence; P=0.0001). Conclusions—Although short-term use of AADs after AF ablation decreases early recurrence of atrial arrhythmias, early use of AADs does not prevent arrhythmia recurrence at 6 months. Early AF recurrence on or off AADs during the initial 6-week blanking period is a strong independent predictor of long-term AF recurrence. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00408200.

Risk of Arrhythmia and Sudden Death in Patients With Asymptomatic Preexcitation A Meta-Analysis

Background— The incidence of sudden cardiac death (SCD) and the management of this risk in patients with asymptomatic preexcitation remain controversial. The purpose of this meta-analysis was to define the incidence of SCD and supraventricular tachycardia in patients with asymptomatic Wolff-Parkinson-White ECG pattern. Methods and Results— We performed a systematic search of prospective, retrospective, randomized, or cohort English-language studies in EMBASE and Medline through February 2011. Studies reporting asymptomatic patients with preexcitation who did not undergo ablation were included. Twenty studies involving 1869 patients met our inclusion criteria. Participants were primarily male with a mean age ranging from 7 to 43 years. Ten SCDs were reported involving 11 722 person-years of follow-up. Seven studies originated from Italy and reported 9 SCDs. The risk of SCD is estimated at 1.25 per 1000 person-years (95% confidence interval [CI], 0.57–2.19). A total of 156 supraventricular tachycardias were reported involving 9884 person-years from 18 studies. The risk of supraventricular tachycardia was 16 (95% CI, 10–24) events per 1000 person-years of follow-up. Children had numerically higher SCD (1.93 [95% CI, 0.57–4.1] versus 0.86 [95% CI, 0.28–1.75]; P=0.07) and supraventricular tachycardia (20 [95% CI, 12–31] versus 14 [95% CI, 6–25]; P=0.38) event rates compared with adults. Conclusion— The low incidence of SCD and low risk of supraventricular tachycardia argue against routine invasive management in most asymptomatic patients with the Wolff-Parkinson-White ECG pattern.

Efficacy and Risk of Atrial Fibrillation Ablation Before 45 Years of Age

Background—Young patients with atrial fibrillation (AF) tend to be more symptomatic and less willing to take long-term medications, yet catheter ablation remains recommended as second-line therapy for AF regardless of age. This study seeks to characterize the effectiveness and risk of AF ablation in the young. Methods and Results—Consecutive (n=1548) patients who underwent 2038 AF ablation procedures were included. Major procedural complications and efficacy were analyzed on the basis of age at the initial procedure: <45 years (group 1), 45 to 54 years (group 2), 55 to 64 years (group 3), and ≥65 years (group 4). AF control was defined as no or rare AF on or off antiarrhythmic drugs. The primary outcome of AF control was similar in all groups; it was achieved in 87% in group 1, 88% in group 2, 88% in group 3, and 82% in group 4 (P=0.06). However, more group 1 patients demonstrated freedom from AF off antiarrhythmic drugs (76%) compared with group 2 at 68%, group 3 at 65%, and group 4 at 53% (P<0.001). There were no major complications in group 1, 10 (1.7%) in group 2, 14 (1.4%) in group 3, and 10 (2.6%) in group 4 (P=0.01). Conclusions—In patients younger than 45 years, there is a lower major complication rate and a comparable efficacy rate, with a greater chance of being AF free without antiarrhythmic drugs. These findings suggest that it may be appropriate to consider ablative therapy as first-line therapy in this age group.

Utility of Cardiovascular Magnetic Resonance in Identifying Substrate for Malignant Ventricular Arrhythmias

Background— Sudden cardiac death (SCD) and sustained monomorphic ventricular tachycardia (SMVT) are frequently associated with prior or acute myocardial injury. Cardiovascular magnetic resonance (CMR) provides morphological, functional, and tissue characterization in a single setting. We sought to evaluate the diagnostic yield of CMR-based imaging versus non–CMR-based imaging in patients with resuscitated SCD or SMVT. Methods and Results— Eighty-two patients with resuscitated SCD or SMVT underwent routine non-CMR imaging, followed by a CMR protocol with comprehensive tissue characterization. Clinical reports of non-CMR imaging studies were blindly adjudicated and used to assign each patient to 1 of 7 diagnostic categories. CMR imaging was blindly interpreted using a standardized algorithm used to assign a patient diagnosis category in a similar fashion. The diagnostic yield of CMR-based and non–CMR-based imaging, as well as the impact of the former on diagnosis reclassification, was established. Relevant myocardial disease was identified in 51% of patients using non–CMR-based imaging and in 74% using CMR-based imaging (P=0.002). Forty-one patients (50%) were reassigned to a new or alternate diagnosis using CMR-based imaging, including 15 (18%) with unsuspected acute myocardial injury. Twenty patients (24%) had no abnormality by non-CMR imaging but showed clinically relevant myocardial disease by CMR imaging. Conclusions— CMR-based imaging provides a robust diagnostic yield in patients presenting with resuscitated SCD or SMVT and incrementally identifies clinically unsuspected acute myocardial injury. When compared with non–CMR-based imaging, a new or alternate myocardial disease process may be identified in half of these patients.