Systemic primary carnitine deficiency induces severe arrhythmia due to shortening of QT interval.

BACKGROUND: Systemic primary carnitine deficiency (PCD) is characterized by cardiomyopathy and arrhythmia. Without carnitine supplementation, progression is usually towards fatal cardiac decompensation. While the cardiomyopathy is most likely secondary to energy deficiency, the mechanism of arrhythmia is unclear, and may be related to a short QT interval. OBJECTIVE: We aim to describe rhythmic manifestations at diagnosis and with carnitine supplementation. METHODS: French patients diagnosed for PCD were retrospectively included. Clinical and para clinical data at diagnosis and during follow-up were collected. Electrocardiograms with QT interval measurements were blinded reviewed by two paediatric cardiologists. RESULTS: Nineteen patients (median age at diagnosis 2.3 years (extremes 0.3-28.9)) followed in 8 French centres were included. At diagnosis, 21% of patients (4/19) had arrhythmia (2 ventricular fibrillations, 1 ventricular tachycardia and 1 sudden death), and 84% (16/19) had cardiomyopathy. Six electrocardiograms before treatment out of 11 available displayed a short QT (QTc < 340 ms). Median corrected QTc after carnitine supplementation was 404 ms (extremes 341-447) versus 350 ms (extremes 282-421) before treatment (p < 0.001). The whole QTc was prolonged, and no patient reached the criterion of short QT syndrome with carnitine supplementation. Three patients died, probably from rhythmic cause without carnitine supplementation (two extra-hospital sudden deaths and one non-recoverable rhythmic storm before carnitine supplementation), whereas no rhythmic complication occurred in patients with carnitine supplementation. CONCLUSION: PCD is associated with shortening of the QT interval inducing severe arrhythmia. A potential explanation would be a toxic effect of accumulated fatty acid and metabolites on ionic channels embedded in the cell membrane. Carnitine supplementation normalizes the QTc and prevents arrhythmia. Newborn screening of primary carnitine deficiency would prevent avoidable deaths.

Distal-to-proximal delay for ablation of premature ventricular contractions.

INTRODUCTION: Ablation of premature ventricular contractions (PVCs) has emerged as a safe and effective treatment in patients experiencing a high PVCs burden. Mapping of PVCs origin may sometimes be challenging. We sought to evaluate the accuracy of a new electrophysiological criterion, the distal-to-proximal (DP) delay, at localizing the optimal site for ablation of ventricular ectopic foci. METHODS AND RESULTS: Consecutive patients with ablation attempts of symptomatic PVCs were included. Prematurity and DP delay-that is, the time duration between the onset of ablation catheter distal bipolar electrogram and the onset of proximal bipolar electrogram-were measured at successful and unsuccessful ablation sites by three blinded experienced electrophysiologists. Mean DP delay at effective ablation sites (N = 30) was significantly higher than at ineffective sites ( N = 55) (23 ± 9 vs 11 ± 8 milliseconds; P < 0.0001). DP delay had good-to-excellent interrater reliability. A DP delay greater than or equal to 15 milliseconds had the highest accuracy at predicting a successful ablation site (sensitivity 0.97, the area under receiver operating characteristic curve 0.87; P < 0.0001). CONCLUSION: DP delay is an additional, simple, and effective electrophysiological parameter to accurately localize PVCs foci.

Carnitine deficiency induces a short QT syndrome.

BACKGROUND: Short QT syndrome is associated with an increased risk of cardiac arrhythmias and unexpected sudden death. Until now, only mutations in genes encoding the cardiac potassium and calcium channels have been implicated in early T-wave repolarization. OBJECTIVE: The purpose of this study was to confirm a relationship between a short QT syndrome and carnitine deficiency. METHODS: We report 3 patients affected by primary systemic carnitine deficiency and an associated short QT syndrome. Ventricular fibrillation during early adulthood was the initial symptom in 1 case. To confirm the relationship between carnitine, short QT syndrome, and arrhythmias, we used a mouse model of carnitine deficiency induced by long-term subcutaneous perfusion of MET88. RESULTS: MET88-treated mice developed cardiac hypertrophy associated with a remodeling of the mitochondrial network. The continuous monitoring of electrocardiograms confirmed a shortening of the QT interval, which was negatively correlated with the plasma carnitine concentration. As in humans, such alterations coincided with the genesis of ventricular premature beats and ventricular tachycardia and fibrillation. CONCLUSION: Altogether, these results suggest that long-chain fatty acid metabolism influence the morphology and the electrical function of the heart.

Unexpected low prevalence of atrial fibrillation in cryptogenic ischemic stroke: a prospective study.

PURPOSE: Ischemic stroke is a frequent pathology with high rate of recurrence and significant morbidity and mortality. There are several causes of stroke, affecting prognosis, outcomes, and management, but in many cases, the etiology remains undetermined. We hypothesized that atrial fibrillation was involved in this pathology but underdiagnosed by standard methods. The aim of the study was to determine the incidence of atrial fibrillation in cryptogenic ischemic stroke by using continuous monitoring of the heart rate over several months. The secondary objective was to test the value of atrial vulnerability assessment in predicting spontaneous atrial fibrillation. METHODS AND RESULTS: We prospectively enrolled 24 patients under 75 years of age, 15 men and 9 women of mean age 49 years, who within the last 4 months had experienced cryptogenic stroke diagnosed by clinical presentation and brain imaging and presumed to be of cardioembolic mechanism. All causes of stroke were excluded by normal 12-lead ECG, 24-h Holter monitoring, echocardiography, cervical Doppler, hematological, and inflammatory tests. All patients underwent electrophysiological study. Of the patients, 37.5% had latent atrial vulnerability, and 33.3% had inducible sustained arrhythmia. Patients were secondarily implanted with an implantable loop recorder to look for spontaneous atrial fibrillation over a mean follow-up interval of 14.5 months. No sustained arrhythmia was found. Only one patient had non-significant episodes of atrial fibrillation. CONCLUSION: In this study, symptomatic atrial fibrillation or AF with fast ventricular rate has not been demonstrated by the implantable loop recorder in patients under 75 years with unexplained cerebral ischemia. The use of this device should not be generalized in the systematic evaluation of these patients. In addition, this study attests that the assessment of atrial vulnerability is poor at predicting spontaneous arrhythmia in such patients.

Implantable loop recorder for recurrent syncope: influence of cardiac conduction abnormalities showing up on resting electrocardiogram and of underlying cardiac disease on follow-up developments.

AIMS: The implantable loop recorder is a useful diagnostic tool in dealing with recurrent syncope in patients. We tested to determine the influence of cardiac conduction abnormalities that turn up on resting electrocardiogram (ECG) and the impact of underlying cardiac disease on developments during follow-up. METHODS AND RESULTS: Ninety-five consecutive patients received an implantable loop recorder to monitor recurrent syncope (n = 4.9+/-3.8) of unknown aetiology after cardiac investigations, including an electrophysiological study. Resting ECG was abnormal, suggesting an arrhythmic syncope, in 29 (30.5%) patients, while 21 (22.1%) patients had an underlying cardiac disease. During an average follow-up period of 10.2+/-5.2 months, 43 (45.2%) patients developed a new syncope associated in 27 of them (62.8%) with an arrhythmic event. Syncope was no more frequent in the subgroup of patients with cardiac conduction abnormalities on resting ECG, while the frequency of arrhythmic events was similar whether or not the ECG was normal. In the subgroup of patients with cardiac disease with normal left ventricular ejection fraction, the occurrence of syncope was less frequent, and the number of arrhythmic events was no greater in these patients. CONCLUSION: Implantable loop recorder is a useful diagnostic tool for recurrent syncope of unknown aetiology.