Phospholamban cardiomyopathy: a Canadian perspective on a unique population.

INTRODUCTION: Phospholamban cardiomyopathy is an inherited cardiomyopathy, characterised by a defect in regulation of the sarcoplasmic reticulum Ca2+ pump, often presenting with malignant arrhythmias and progressive cardiac dysfunction occurring at a young age. METHODS: Phospholamban R14del mutation carriers and family members were identified from inherited arrhythmia clinics at 13 sites across Canada. Cardiac investigations, including electrocardiograms, Holter monitoring (premature ventricular complexes, PVCs), and imaging results were summarised. RESULTS: Fifty patients (10 families) were identified (median age 30 years, range 3-71, 46% female). Mutation carriers were more likely to be older, have low-voltage QRS, T­wave inversion, frequent PVCs, and cardiac dysfunction, compared to unaffected relatives. Increasing age, low-voltage QRS, T­wave inversion, late potentials, and frequent PVCs were predictors of cardiac dysfunction (p < 0.05 for all). Older carriers (age ≥45 years) were more likely to have disease manifestations than were their younger counterparts, with disease onset occurring at an older age in Canadian patients and their Dutch counterparts. DISCUSSION: Among Canadian patients with phospholamban cardiomyopathy, clinical manifestations resembled those of their Dutch counterparts, with increasing age a major predictor of disease manifestation. Older mutation carriers were more likely to have electrical and structural abnormalities, and may represent variable expressivity, age-dependent penetrance, or genetic heterogeneity among Canadian patients.

Exercise and the multidisciplinary holistic approach to adolescent dysautonomia.

AIM: To determine whether an eight-week strength training programme as part of a multidisciplinary approach would minimise symptoms and improve quality of life in patients with dysautonomia. METHODS: Adolescents referred to a tertiary-level cardiology service from May 2014-December 2015 with symptoms of dysautonomia were eligible. Participants completed an exercise test and a quality of life (QoL) questionnaire (PedsQL) prior to the intervention. Participants were asked to complete exercises five times per week. After eight weeks, participants returned for follow-up testing. Parents completed a proxy report of their child's QoL at both time points. RESULTS: A total of 17 participants completed the study protocol with an adherence rate of up to 50%. Post-intervention, QoL scores improved across all levels in the participants [total 65.2 (50.4-74.7) vs 48.9 (37.5-63.0); p = 0.006; psychosocial 65.8 (56.1-74.6) vs 50.0 (41.7-65.8); p = 0.010; physical 62.5 (37.5-76.6) vs 43.8 (25-68.5); p = 0.007] and their parent proxy reports [total 63.5 (48.7-81.3) vs 50.0 (39.3-63.0); p = 0.004; psychosocial 62.1 (52.1-81.3) vs 50.0 (39.6-59.2); p = 0.001; physical 62.5 (51.6-80.0) vs 50.0 (27.5-70.3); p = 0.003]. Treadmill time also improved (9.1 vs 8.0 minutes; p = 0.005). CONCLUSION: Following an eight-week strength training programme, dysautonomia patients report a significant improvement in both their quality of life and endurance time.

Recurrent congestive heart failure in a child due to probable myocarditis.

Recurrent congestive heart failure (CHF) attributable to myocarditis is a seldom-discussed entity in the scientific literature. This report describes the case of an 8-year-old girl who had three clinically identical episodes of CHF, beginning at the age of 5 years, with each episode preceded by a viral prodrome. The clinical features and the echocardiography and electrocardiogram findings were most supportive of myocarditis. Symptoms and investigations completely normalized between episodes. The third episode, associated with influenza A (strain H1N1) infection, led to cardiac arrest and death on day 2 after admission. Autopsy showed mild cardiomegaly with microscopic foci of myocardial fibrosis and extensive contraction band necrosis. This report is the first to describe recurrent CHF due to probable myocarditis in a pediatric patient.

At-home determination of 24-h urine sodium excretion: Validation of chloride test strips and multiple spot samples.

Sodium intake and compliance with dietary sodium modification are typically assessed using a 24-h urine collection analyzed using flame photometry, but this is inconvenient. Spot urine samples have been investigated as alternatives to 24-h collections, but their accuracy is poor. Since sodium and chloride are present in equal concentrations in dietary salt, chloride test strips may provide a suitable proxy for at-home measurement of urine sodium concentrations. We aimed to determine whether (i) chloride test strips provide a reliable measure of urinary sodium compared to the gold standard flame photometry and (ii) multiple spot samples accurately reflect 24-h urine sodium. We recruited 43 participants (19 males) aged 23.6 ± 0.6 years to complete multiple consecutive spot samples (morning and evening) along with a 24-h urine sodium collection. Urine 24-h sodium estimates using chloride test strips (114.6 ± 7.5 mmol/day) were highly correlated (r = 0.900, p < 0.0001) with flame photometry (121.1 ± 7.7 mmol/day) with a bias of -6.53 ± 22.2 mmol/day. Use of a three-spot sample average (both morning and evening spot samples) with a correction factor applied (122.9 ± 4.1 mmol/day) provided a good approximation of 24-h sodium measured by flame photometry (125.6 ± 9.0 mmol/day), with a bias of -2.55 ± 43.9 mmol/day. Chloride test strips applied to a 24-h urine collection provide a highly accurate measure of urinary sodium excretion, permitting convenient at-home sample collection and analysis. Their application to multiple spot samples provides a reasonable approximation of sodium excretion that can be used to conveniently monitor attempts at dietary sodium manipulation, without the inconvenience of completing a 24-h urine sample.

Early and intermediate-term complications of self-expanding stents limit its potential application in children with congenital heart disease.

OBJECTIVES: We report on the early and intermediate-term follow-up results of self-expanding Wallstent (Schneider, Switzerland) implanted in children with congenital heart disease. BACKGROUND: The inherent shortcomings of balloon-expandable stents prompted the trial of an alternative stent. METHODS: Twenty patients underwent 22 implantations of 25 self-expanding Wallstents between December 1993 and June 1997 in two institutions. The mean age and weight were 10.8+/-4.5 years and 30.5+/-14.2 kg, respectively. The patients were divided into two groups: 1) Group I comprised 17 patients with pulmonary arterial stenoses, 2) Group II comprised four patients with venous stenoses (one belonged to both groups). Sixteen patients underwent recatheterization at a median of 5.8 months (range 0.5 to 31, mean 8.1 months) after stenting. Hemodynamic and angiographic changes after the interventional procedures and complications were documented. RESULTS: All the stents were successfully deployed in the intended position. In Group I, the narrowest diameter of the stented vessel increased from 4.1+/-1.5 to 8+/-2 mm (95% increase, p < 0.0001) while the systolic pressure gradient across decreased from 24.6+/-15.8 to 12.1+/-11.4 mm Hg (51% decrease, p = 0.001). In Group II, the dimensional changes of the narrowest segment increased from 4.3+/-0.5 to 7.5+/-0.4 mm (75% increase, p = 0.003), and the pressure gradient reduced from 5.0+/-2.9 to 0.9+/-1.0 mm Hg (82% decrease, p = 0.04) across the stented venous channel. Distal migration of two optimally positioned stents occurred within 24 h of implantation. At recatheterization, significant neointimal ingrowth (>30% of the expanded diameter) was noted in 7 (28%) of the 25 implanted stents. This responded poorly to balloon dilation. Predisposing factors for the neointimal ingrowth included stents of smaller diameter (<9 mm) and longer period after implantation. CONCLUSIONS: Self-expanding Wallstent could be deployed easily and safely to relieve vascular stenoses in children. The complications of distal migration, significant neointimal ingrowth and its unyielding design to overdilation limit its application to this patient group.

Vascular abnormalities in Adams-Oliver syndrome: cause or effect?

We describe a young girl diagnosed with the Adams-Oliver syndrome (AOS) associated with double outlet right ventricle, portal hypertension, and pulmonary hypertension. We hypothesize that a congenital vascular abnormality is the underlying pathogenesis and that the cutaneous defects characteristically seen in AOS represent the most common manifestation of this. We suggest that AOS should not merely be considered a syndrome consisting of aplasia cutis congenita and terminal transverse limb defects but rather a constellation of clinical findings resulting from an early embryonic vascular abnormality.

Extracardiac Fontan operation with tube fenestration allowing transcatheter coil occlusion.

A fenestration may improve the immediate postoperative course after a Fontan procedure by preserving the cardiac output. We describe a simple and safe technique of fenestration amenable to coil occlusion, which can be carried out in most cardiac catheterization laboratories.

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.

Diagnosis of postoperative arrhythmias following paediatric cardiac surgery.

Arrhythmias are commonly encountered in the paediatric intensive care unit setting, most frequently in the setting of postoperative congenital heart disease. Postoperative arrhythmias are an important cause of morbidity in children in the postoperative period following cardiac surgery for congenital cardiac lesions. It is important for all paediatric critical care physicians involved in the care of these children to understand the potential mechanisms involved and how to make an accurate diagnosis. The existing literature has focused on small groups and specific arrhythmias. There is a paucity of literature to guide the clinician in approaching arrhythmias in the paediatric intensive care unit setting. Our objective was to review the recognition and diagnosis of paediatric arrhythmias in the postoperative period following congenital cardiac surgery. Timely and accurate identification of the rhythm disturbance is mandatory and allows for the institution of effective, rhythm specific management strategies.

Cardiac risk assessment before the use of stimulant medications in children and youth: A joint position statement by the Canadian Paediatric Society, the Canadian Cardiovascular Society, and the Canadian Academy of Child and Adolescent Psychiatry.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and pediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac subspecialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Cardiac risk assessment before the use of stimulant medications in children and youth.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and paediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac sub-specialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Dilated cardiomyopathy masquerading as long QT syndrome.

Atrioventricular block has been described in association with cases of long QT syndrome and mortality is increased in this subgroup. We describe an infant with congenital QT prolongation and atrioventricular block with normal cardiac function, leading to the initial diagnosis of long QT syndrome. She subsequently developed dilated cardiomyopathy requiring cardiac transplantation. We postulate that the presenting electrocardiograph abnormalities were early manifestations of the myocardial disease, preceding the development of myocardial dysfunction by several months. The need for heightened surveillance in cases of QT prolongation with atrioventricular block is amplified by the possibility of an evolving cardiomyopathy.

Medications used to manage supraventricular tachycardia in the infant a North American survey.

Supraventricular tachycardia is the most common pediatric arrhythmia, but there is no consensus and little evidence to guide its treatment. We sent a questionnaire to pediatric cardiologists in North America to assess the current practice pattern. Of 1534 surveys mailed, 352 (23%) were returned and 295 (19%) had complete data for analysis. In the acute setting, 11 different medications were chosen. The most commonly used in the infant without preexcitation were digoxin (42%), procainamide (21%), esmolol (13%), propranolol (10%), and amiodarone (8%). In the infant with preexcitation, propranolol (34%), procainamide (23%), esmolol (17%), amiodarone (11%), and digoxin (6%) were used. In the chronic setting, 8 different medications were chosen. The most commonly used in this scenario were digoxin (52%), propranolol (33%), amiodarone (4%), and sotalol (3%). In the infant with preexcitation, propranolol (70%), amiodarone (6%), digoxin (6%), atenolol (6%), and flecainide (5%) were used. Medication choices were influenced by additional electrophysiology training and preexcitation. Digoxin was used less in the setting of preexcitation. There are no comparative trials to explain the different medication choices. Although a number of medications may be efficacious, a randomized clinical trial is needed to offer further guidance.

Post-hoc diagnosis of congenital long QT syndrome in patients with tetralogy of Fallot.

This report describes two patients diagnosed with congenital long QT syndrome after surgical repair of tetralogy of Fallot. Despite the fact that both patients had preoperative electrocardiograms demonstrating QT prolongation, neither was diagnosed until long after their surgeries, when they or their relatives presented with symptoms of long QT syndrome. A brief discussion highlights the reasons why long QT syndrome may be overlooked in patients with structural heart defects and the clinical importance of identifying these patients preoperatively.

Predictors of refractory tachycardia in infants with supraventricular tachycardia.

Reentrant supraventricular tachycardia (SVT) is the most common arrhythmia in infants. There are few predictors as to which patients will have recurrent or refractory SVT. We retrospectively reviewed records of all infants with SVT evaluated at The Hospital for Sick Children, Toronto, between January 1, 1995, and December 31, 1999. Patients with reentrant SVT documented in infancy and structurally normal hearts were included. Patients were placed in two groups: the "simple" group consisted of patients with SVT completely controlled by not more than one medication, and the "complex" group consisted of patients with recurrent episodes requiring at least one medication change for control. Forty-two cases were analyzed-23 in the simple group and 19 in the complex group. One patient in each group died. Age at presentation was 50.4 +/- 13.2 days for the simple group versus 10.2 +/- 2.5 days for the complex group (p <0.01). Complex patients were treated with a median of three medications and were more likely to have echocardiographically reduced ventricular function. The surface electrocardiogram RP interval during SVT was significantly longer in complex patients (p <0.001). There were no differences between the groups in gender, cycle length in SVT or sinus rhythm, the presence of pre-excitation, initial medication choice, or duration of therapy. Recurrent SVT in infancy is associated with younger age and/or ventricular dysfunction at presentation and also with slower ventriculoatrial conduction. The similar duration of therapy for simple and complex patients suggests that the early clinical course of SVT in infancy is not predictive of long-term outcome.

Evolution of heart rate control after transplantation: conduction versus autonomic innervation.

In cardiac transplantation, the donor organ is not initially innervated and demonstrates decreased heart rate variability (HRV). However, HRV may improve after several months. The mechanism for HRV improvement has not been elucidated; autonomic "reinnervation" of the donor heart has been proposed. The role of atrioatrial conduction from recipient to donor organ has not been evaluated. We prospectively evaluated cardiac transplant patients with a limited electrophysiology study at the time of their surveillance biopsies. Recordings were made of recipient and donor signals, observing conduction properties between recipient and donor atria. Holter recordings were analyzed and HRV was determined using spectral analysis techniques, recording mean RR interval, low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio. These were compared to published norms. From November 1999 to May 2000, 21 patients (6 female) who underwent cardiac transplantation participated at a median age of 101 months (range, 4.1-217 months). Time posttransplant ranged from 26 days to 71 months. Holter data were available for 20 patients and demonstrated dissociated P waves in 13 (65%). The mean heart rate on Holter was 111 beats per minute (bpm) (range, 85-161 bpm). We were able to record distinct recipient atrial signals in 16 of 21 (76%) patients. The average recipient tissue heart rate was 55% that of the donor heart rate. We documented atrioatrial association in only 1 patient. HRV did not reach normal values for most patients and did not increase with time posttransplantation. The LF values were in the normal range for most patients, whereas 3 patients had normal HF values and 2 patients had values just below normal. Recipients of heart transplantation have a predominantly sympathetic influence of HRV. These preliminary data suggest that atrioatrial conduction does not play a role in reestablishing normal heart rate control following pediatric cardiac transplantation.

Spontaneously terminating apparent ventricular fibrillation during transesophageal electrophysiological testing in infants with Wolff-Parkinson-White syndrome.

This article describes two infants with Wolff-Parkinson-White (WPW) syndrome in whom apparent VF occurred without antecedent AF or atrial flutter during routine transesophageal electrophysiological testing. Remarkably, this arrhythmia terminated spontaneously in both infants. The documentation of self-limited apparent VF, or polymorphic ventricular tachycardia close to VF, in transesophageal testing adds another dimension to the management of WPW.