K. Gibbs

The Study of Antiarrhythmic Medications in Infancy (SAMIS) A Multicenter, Randomized Controlled Trial Comparing the Efficacy and Safety of Digoxin Versus Propranolol for Prophylaxis of Supraventricular Tachycardia in Infants

Background—Supraventricular tachycardia (SVT) is one of the most common conditions requiring emergent cardiac care in children, yet its management has never been subjected to a randomized controlled clinical trial. The purpose of this study was to compare the efficacy and safety of the 2 most commonly used medications for antiarrhythmic prophylaxis of SVT in infants: digoxin and propranolol. Methods and Results—This was a randomized, double-blind, multicenter study of infants <4 months with SVT (atrioventricular reciprocating tachycardia or atrioventricular nodal reentrant tachycardia), excluding Wolff-Parkinson-White, comparing digoxin with propranolol. The primary end point was recurrence of SVT requiring medical intervention. Time to recurrence and adverse events were secondary outcomes. Sixty-one patients completed the study, 27 randomized to digoxin and 34 to propranolol. SVT recurred in 19% of patients on digoxin and 31% of patients on propranolol (P=0.25). No first recurrence occurred after 110 days of treatment. The 6-month recurrence-free status was 79% for patients on digoxin and 67% for patients on propranolol (P=0.34), and there were no first recurrences in either group between 6 and 12 months. There were no deaths and no serious adverse events related to study medication. Conclusions—There was no difference in SVT recurrence in infants treated with digoxin versus propranolol. The current standard practice may be treating infants longer than required and indicates the need for a placebo-controlled trial. Clinical Trial Registration Information—http://clinicaltrials.gov; NCT-00390546.

Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry

Background—The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease to identify the pathogenesis of cardiac arrest through systematic clinical testing. Exercise testing, drug provocation, advanced cardiac imaging, and genetic testing may be useful when a cause is not apparent. Methods and Results—The first 200 survivors of unexplained cardiac arrest from 14 centers across Canada were evaluated to determine the results of investigation and follow-up (age, 48.6±14.7 years, 41% female). Patients were free of evidence of coronary artery disease, left ventricular dysfunction, or evident repolarization syndromes. Advanced testing determined a diagnosis in 34% of patients at baseline, with a diagnosis emerging during follow-up in 7% of patients. Of those who were diagnosed, 28 (35%) had an underlying structural condition and 53 (65%) had a primary electric disease. During a mean follow-up of 3.15±2.34 years, 23% of patients had either a shock or an appropriate antitachycardia pacing from their implantable cardioverter defibrillator, or both. The implantable cardioverter defibrillator appropriate intervention rate was 8.4% at 1 year and 18.1% at 3 years, with no clear difference between diagnosed and undiagnosed subjects, or between those diagnosed with a primary electric versus structural pathogenesis. Conclusions—Obtaining a diagnosis in previously unexplained cardiac arrest patients requires systematic clinical testing and regular follow-up to unmask the cause. Nearly half of apparently unexplained cardiac arrest patients ultimately received a diagnosis, allowing for improved treatment and family screening. A substantial proportion of patients received appropriate implantable cardioverter defibrillator therapy during medium-term follow-up. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.

A review of sudden unexpected death in the young in British Columbia

BACKGROUND Since 2008, all pediatric deaths in British Columbia have been reported to the coroner. The cause of death in pediatric sudden unexpected death (SUD) remains undetermined in 10% to 30% of cases. Before 2008, there was no standardized approach for referring relatives of SUD victims for follow-up medical testing to determine whether they were affected by the same condition. In the current era, genetic testing for primary electrical diseases can be used in cases of undetermined SUD when existing diagnostic methods fail. OBJECTIVE To improve the clinical care of surviving relatives of SUD victims, the current practice of assessment of SUD in British Columbia was reviewed. The study also aimed to determine the prevalence of SUD and sudden cardiac death, types of postmortem investigations performed in SUD, and the use of genetic testing for primary electrical diseases in SUD from 2005 to 2007. METHODS Cases involving individuals zero to 35 years of age, with a death due to natural disease or an undetermined cause were compiled from the British Columbia Coroners Service database. Cases were determined to be either sudden death due to a previously diagnosed condition or SUD. RESULTS In individuals zero to 35 years of age, the prevalence of SUD was 9.21 per 100,000 and the prevalence of sudden cardiac death was 5.26 per 100,000. There were 35 cases of SUD in which a cause of death was unidentified after autopsy (autopsy- negative SUD). Specimens were collected, and specialists were consulted in 86% of these cases in the pediatric population and 14% in the adult population. A suggestion was made to relatives to seek medical attention in 26% of the autopsy-negative SUDs, and molecular autopsy was discussed in 9% of cases but performed in none. CONCLUSION Currently, SUD in British Columbia is not managed in a way that optimizes a timely diagnosis for surviving relatives. A standardized protocol for SUD is needed to ensure optimization of diagnosis, genetic testing and referral of surviving relatives.

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa

Background— Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Methods and Results— Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8–13.9 versus 15.8; 95% confidence interval, 15.3–16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9–14.9 versus 12.3; 95% confidence interval, 11.3–13.3; P=0.026). Conclusions— Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa.

Assessing the knowledge of sudden unexpected death in the young among Canadian medical students and recent graduates: a cross-sectional study

Objective To determine the level of knowledge concerning Sudden Unexpected Death in the Young (SUDY) among Canadian medical students and recent graduates (≤5 years after graduating). Design A cross-sectional study was conducted by distributing a standardised, multiple choice, online questionnaire which assessed basic knowledge of SUDY. Setting Canadian medical schools and residency training programmes. Participants 614 Canadian medical students (in either their penultimate or final year) and recent graduates (≤5 years after graduating) completed an anonymous online questionnaire. Primary and secondary outcome measures The level of knowledge regarding molecular aetiology, clinical presentation, pharmacological management and modes of inheritance of six of the commonest conditions causing SUDY, including hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQT) and Wolff-Parkinson White syndrome (WPW), were compared between medical students and recent graduates. Questions were broken down into basic knowledge and advanced categories and analysed as a secondary outcome measure. Results Of 614 responses, approximately two-thirds were answered by recent graduates, who generally scored 10% higher on all subject categories than medical students. Overall, questions regarding HCM were best answered (40%), followed by WPW syndrome (32%), CPVT (30%), ARVC (23%), Brugada syndrome (21%) and LQT syndrome (17%). Questions categorised as basic knowledge were answered 30% and 39% correctly in medical student and recent graduate groups, respectively, and those in the advanced category were answered 20% and 25% correctly. Conclusions Survey respondents fared poorly when answering questions regarding SUDY, which may be a reflection of inadequate medical education regarding these disorders. Standardised teaching regarding SUDY needs to occupy a stronger focus in Canadian medical curricula in order to prevent more unnecessary deaths by these syndromes in the future.

Response to Letter Regarding Article, “Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry”

We would like to thank Professors Jaimez and Sanchez for their letter of response commenting on our recent summary of evaluation and outcome of our first 200 unexplained cardiac arrest probands.1 We would first like to point out that we excluded patients with a manifest diagnosis, so none of these patients had overt evidence of an ion channelopathy or cardiomyopathy that are typically both readily diagnosed and treated. This is reflected in our empirical strength of diagnosis framework, which is necessary when a classic diagnosis is not forthcoming.2 In addition, registries do not mandate care but rather capture it, and reflect the reality of practice with the vagaries of contextual clinical decision making. In response to the concerns about the incidence of shocks and the inefficacy of medical therapy, it is important to point out the difference between efficacy and effectiveness. Without …

ETIOLOGY OF CARDIAC ARREST IN THE ABSENCE OF MANIFEST STRUCTURAL HEART DISEASE - UPDATE FROM THE CASPER PROSPECTIVE COHORT

BACKGROUND: In patients requiring cardiac resynchronization therapy (CRT), the most common method of left ventricular (LV) lead implantation is percutaneous. However, in cases of poor venous access or failed transvenous LV lead placement, an epicardial approach through a mini thoracotomy is recommended. In general, the results of the two approaches are thought to be similar. To date, the indications and underlying pathology of patients requiring epicardial LV lead placement are not well known. The aim of this study is to further delineate baseline patient characteristics and long term outcomes in those receiving epicardical LV lead placement. METHODS AND RESULTS: A retrospective review of 500 consecutive CRT devices at a single center from January 2008 to March 2014 was undertaken. We identified 25 (5%) patients with epicardial LV lead placement. Median age was 61 +13 years, 19 (76%) were male 6 (24%) female. The most common underlying pathology was non-ischemic cardiomyopathy 19 (75%). The number one indication for epicardial lead placement was failed coronary sinus cannulation in 16 (64%), poor venous access in 4 (16%), and other in 5 (20%). Average hospital stay was 4.9 days + 4.6 days post implantation for patients with epicardial lead placement versus 1.1 days + 0.7 days in the age, sex matched percutaneous group (p 1⁄4 0.00041, two tailed t-test). Average follow up of patients from time of epicardial lead implantation was 595 days + 274 days. A higher mortality was observed in patient receiving an epicardial lead when compared to patients with transvenous lead (11 (44%) vs. 90 (19%), p1⁄40.0079). Patients died on average 622 + 293 days from operation date with improvement in patient functional class in 7 (28%) patients. There were no significant changes in ejection fraction (EF) pre and post epicardial lead implantation (21% versus 23%, p1⁄40.19) or the degree of mitral regurgitation (MR) pre and post epicardial LV lead placement (mild to moderate versus moderate MR). CONCLUSION: Failure to cannulate the coronary sinus is the most common indication for epicardial LV lead placement. These patients are more likely to be males with non ischemic cardiomyopathy and as such these implantations should be undertaken in centers where an epicardial approach is available. Patients receiving epicardial LV lead on average have longer hospital stays post implantation and have higher long term mortality.