Karen McLeod

Paced ventricular electrogram fractionation predicts sudden cardiac death in hypertrophic cardiomyopathy.

AIMS Paced electrogram fractionation analysis (PEFA) has been assessed for the prediction of sudden cardiac death (SCD) in a large-scale, prospective study of patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS We determined the positive predictive value (PPV) of PEFA in relation to other risk factors for SCD and outcomes in 179 patients with HCM and no prior history of cardiac arrest. Patients were followed over a mean 4.3 years (range: 1.1-6.3 years). Thirteen patients had SCD-equivalent events: four of these patients died suddenly, three were resuscitated from ventricular fibrillation (VF), and six had implantable cardioverter-defibrillator (ICD) discharges in response to VF. PEFA identified nine of these patients and another 14 non-VF patients yielding a censored PPV of between 0.19 and 0.59 that was greater than the PPV that was the formal stopping point of the trial (0.18). Eighty per cent of patients were followed for 4 years or more. The PPV for the identification of SCD in this group was 0.38 (0.17-0.59). The use of two or more conventional markers to predict SCD identified five patients with SCD-equivalent events in the 4-year follow-up group and 42 other patients without events yielding a PPV of 0.106 (confidence limits 0.02-0.15). CONCLUSION PEFA identifies HCM patients at risk of SCD with greater accuracy than non-invasive techniques and may have an important role in determining indications for ICD prescription.

Cardiac pacing in infants and children

Paediatric pacemaker implants comprise <1% of all pacemaker implants.w1 When it is considered that the mean age of pacemaker implantation in the adult population is 75.5 years, compared with <10 years in the paediatric population, the problems of small size, growth and truly chronic pacing faced by the paediatric implanter are fully appreciated.w1 The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) 2008 guidelines for device-based therapy of cardiac rhythm abnormalities include up to date guidelines for implantation of pacemakers in children, adolescents and patients with congenital heart disease.1 The main indication for pacing in childhood is symptomatic or worrying bradycardia, the most common being complete heart block (box 1).2 Heart block may occur in children with structurally normal hearts (isolated heart block) or those with congenital heart disease. ### Box 1 Indications for pacemaker implantation in childhood* Complete atrioventricular block following cardiac surgery Symptomatic congenital complete heart block Asymptomatic congenital complete heart block in association with: Acquired heart block in myopathies Symptomatic bradycardias in: Reflex anoxic seizures with secondary anoxic epileptic seizures Isolated complete heart block in childhood can broadly be divided into two groups—antibody positive and antibody negative.3 The antibody positive group develop heart block in fetal life as a result of maternal antibodies to single stranded RNA crossing the placenta and damaging the conduction system. The antibody negative group tend to present at a later age and heart block is often progressive. Many children with isolated complete heart block are well and asymptomatic. Pacing is indicated for those with symptoms, but there is a risk of sudden death even in asymptomatic patients. …

Novel SCN5A mutation in amiodarone-responsive multifocal ventricular ectopy-associated cardiomyopathy.

BACKGROUND Mutations in SCN5A, which encodes the cardiac sodium channel NaV1.5, typically cause ventricular arrhythmia or conduction slowing. Recently, SCN5A mutations have been associated with heart failure combined with variable atrial and ventricular arrhythmia. OBJECTIVE The purpose of this study was to determine the clinical, genetic, and functional features of an amiodarone-responsive multifocal ventricular ectopy-related cardiomyopathy associated with a novel mutation in a NaV1.5 voltage sensor domain. METHODS A novel, de novo SCN5A mutation (NaV1.5-R225P) was identified in a boy with prenatal arrhythmia and impaired cardiac contractility followed by postnatal multifocal ventricular ectopy suppressible by amiodarone. We investigated the functional consequences of NaV1.5-R225P expressed heterologously in tsA201 cells. RESULTS Mutant channels exhibited significant abnormalities in both activation and inactivation leading to large, hyperpolarized window and ramp currents that predict aberrant sodium influx at potentials near the cardiomyocyte resting membrane potential. Mutant channels also exhibited significantly increased persistent (late) sodium current. This profile of channel dysfunction shares features with other SCN5A voltage sensor mutations associated with cardiomyopathy and overlapped that of congenital long QT syndrome. Amiodarone stabilized fast inactivation, suppressed persistent sodium current, and caused frequency-dependent inhibition of channel availability. CONCLUSION We determined the functional consequences and pharmacologic responses of a novel SCN5A mutation associated with an arrhythmia-associated cardiomyopathy. Comparisons with other cardiomyopathy-associated NaV1.5 voltage sensor mutations revealed a pattern of abnormal voltage dependence of activation as a shared biophysical mechanism of the syndrome.

Dizziness and syncope in adolescence

“The only difference between syncope and sudden death is that in syncope you wake up”— G L Engels 1 Syncope is a common problem in adolescence, with up to one in five experiencing an episode of syncope before adulthood.2 Whereas the vast majority of syncope is benign, a minority is caused by something potentially more serious or even life threatening. For this reason and also because syncope has such a death-like quality, it often generates extreme anxiety and is often extensively, inappropriately, and unfruitfully investigated. There are many causes of syncope and therefore it can be helpful to categorise them. One way of categorising syncope is to divide the causes into three main groups.2 Neurally mediated syncopes occur when there is a disturbance in the autonomic nervous systems control of heart rate and blood pressure. Generally they can be considered as benign. Cardiovascular causes of syncope are rare in adolescence, but it is important to be aware of them, as they are potential causes of sudden death. Non-cardiovascular syncopes can broadly be divided into the epilepsies and the psychogenic causes. In the latter the child actually fakes the syncope. It is beyond the scope of this article to discuss all the causes of syncope and the aim will be to concentrate on the most common form of syncope, the neurally mediated syncopes. Although neurally mediated syncope can occur at any age in childhood, the peak age groups are in toddlers and in adolescents. Neurally mediated syncopes are a heterogeneous group of autonomic disorders, which result in orthostatic intolerance. Grubb suggests dividing them into four main groups: the reflex syncopes, postural orthostatic tachycardia syndrome, pure autonomic failure. and multiple system atrophy.3 #### Classification of syncope in adolescence

Stenting of stenosed aortopulmonary collaterals: a new approach to palliation in pulmonary atresia with multifocal aortopulmonary blood supply.

A patient with complex pulmonary atresia and increasing cyanosis due to stenoses of aortopulmonary collateral vessels improved after implantation of balloon expandable stents into the stenosed vessels. Stent implantation may provide an alternative to surgical palliation in this group of patients.

Lead-induced tricuspid stenosis--successful management by balloon angioplasty.

We describe a case of tricuspid stenosis in a young woman 11 years after endocardial ventricular lead implantation. The cause of the stenosis appears to have been perforation of the septal leaflet by the lead at the time of insertion. We further describe successful management with percutaneous balloon valvuloplasty without the need for lead removal.

Morphology of the elastic pulmonary arteries in pulmonary hypertension: a quantitative study.

Recent studies of intravascular ultrasound of the pulmonary arteries suggest that the technique can detect intimal and medial thickening in patients with pulmonary hypertension, potentially providing a method of assessing severity of pulmonary vascular disease in life. A major drawback of the technique is that only the elastic pulmonary arteries are accessible to current ultrasound catheters. The aim of this study was to determine whether morphological changes in vessels accessible to intravascular imaging reflect severity of pulmonary vascular disease and are of a sufficient degree to be detectable by current ultrasound catheters. Morphometric studies of the elastic pulmonary arteries were performed in specimens of lungs from 24 patients who had died with pulmonary hypertension (aged 3 weeks-9 years) and compared with measurements from infants who had died from sudden infant death syndrome. Morphological changes evident in the elastic pulmonary arteries in pulmonary hypertension included luminal dilation and medial thickening but these changes were too variable to be predictive of the severity of peripheral pulmonary vascular disease. Intimal thickening and atherosclerosis were present only in those with advanced pulmonary hypertensive disease. The changes of medial thickening and luminal dilation, nonetheless, are too variable to be predictive of the severity of peripheral pulmonary vascular disease. Thus, imaging by intravascular ultrasound may help confirm advanced pulmonary vascular disease, but is unlikely to differentiate less severe pulmonary vascular disease when the patient may still potentially be operable.

Evaluation of Pediatric Electrocardiogram Diagnosis of Ventricular Hypertrophy by Computer Program Compared with Cardiologists

This study aimed to evaluate the diagnosis of pediatric left ventricular hypertrophy (LVH) and right ventricular hypertrophy (RVH) by the Glasgow electrocardiogram (ECG) interpretation program compared to interpretations provided by two pediatric cardiologists. ECGs had all identifying information removed and were sent to the cardiologists independently with the patient’s age and sex and the clinical indication for the ECG, if known. A total of 984 ECGs were included in the study, of which 664 were reported “with clinical indication” and 320 were reported “blind.” With respect to an averaged diagnosis of the two cardiologists, the sensitivity of the program for RVH was better when the cardiologists reported blind (73.3%) than with the clinical indication (53.5%), with the same trend for the program compared with individual cardiologists. The specificity of the program was at least 94.4% in all cases. For LVH, the program had high specificity (=95.8%) for “reported blind” and “with clinical indication” cases but low sensitivities throughout (the highest was 44.4% with respect to an averaged diagnosis of the two cardiologists reporting with the clinical indication). Subsequent discussion revealed that if the cardiologists had disagreed with one another initially, their consensus opinion was twice as likely to be in agreement with the program.

Ventricular fibromas in children, arrhythmia risk, and outcomes: A multicenter study

BACKGROUND Although ventricular fibromas are rare, they are the second most common type of cardiac tumor in children. While histologically benign, they have a propensity to cause malignant arrhythmias, with cardiac arrest often being the first presentation. OBJECTIVE The purpose of this study was to evaluate the arrhythmia risk and management strategies for pediatric ventricular fibromas. METHODS Fifteen centers in the British Paediatric Arrhythmia Group network were contacted to partake in the study to contribute cases. A detailed database search was performed at 2 hospitals for cases of ventricular fibromas. RESULTS A total of 19 patients were included in the study. Arrhythmias were common, with 5 patients presenting with cardiac arrest and 5 others having documented ventricular tachycardia. Nine patients have undergone surgical resection at various hospitals, and all these patients have survived with good long-term outcomes. One patient who did not have any treatment died, presumably of a ventricular arrhythmia; another died of metastatic disease. There were no recurrences of arrhythmia after surgery, and the need for a defibrillator was alleviated in all cases. CONCLUSION Ventricular fibromas have a high propensity to cause malignant arrhythmias, and if they are not managed appropriately, mortality is high. The outcomes of surgical resection are good, regardless of size, and this represents the best therapeutic option, with most patients being symptom free in the longer term.

A multicentre study of patients with Timothy syndrome

Aims Timothy syndrome (TS) is an extremely rare multisystem disorder characterized by marked QT prolongation, syndactyly, seizures, behavioural abnormalities, immunodeficiency, and hypoglycaemia. The aim of this study was to categorize the phenotypes and examine the outcomes of patients with TS. Methods and results All patients diagnosed with TS in the United Kingdom over a 24-year period were reviewed. Fifteen centres in the British Congenital Arrhythmia Group network were contacted to partake in the study. Six patients with TS were identified over a 24-year period (4 boys and 2 girls). Five out of the six patients were confirmed to have a CACNA1C mutation (p.Gly406Arg) and the other patient was diagnosed clinically. Early presentation with heart block, due to QT prolongation was frequently seen. Four are still alive, two of these have a pacemaker and two have undergone defibrillator implantation. Five out of six patients have had a documented cardiac arrest with three occurring under general anaesthesia. Two patients suffered a cardiac arrest while in hospital and resuscitation was unsuccessful, despite immediate access to a defibrillator. Surviving patients seem to have mild developmental delay and learning difficulties. Conclusion Timothy syndrome is a rare disorder with a high attrition rate if undiagnosed. Perioperative cardiac arrests are common and not always amenable to resuscitation. Longer-term survival is possible, however, patients invariably require pacemaker or defibrillator implantation.