Santiago O. Valdes

Left ventricular non-compaction cardiomyopathy in children: characterisation of clinical status using tissue Doppler-derived indices of left ventricular diastolic relaxation

Background: Left ventricular non-compaction (LVNC) may manifest an undulating phenotype ranging from dilated to hypertrophic appearance. It is unknown whether tissue Doppler (TD) velocities can predict adverse clinical outcomes including death and need for transplantation in children with LVNC. Methods and results: 56 children (median age 4.5 years, median follow-up 26 months) with LVNC evaluated at one hospital from January 1999 to May 2004 were compared with 56 age/sex-matched controls. Children with LVNC had significantly decreased early diastolic TD velocities (Ea) at the lateral mitral (11.0 vs 17.0 cm/s) and septal (8.9 vs 11.0 cm/s) annuli compared with normal controls (p<0.001 for each comparison). Using receiver operator characteristic curves, the lateral mitral Ea velocity proved the most sensitive and specific predictor for meeting the primary end point (PEP) at 1 year after diagnosis (area under the curve = 0.888, SE = 0.048, 95% CI 0.775 to 0.956). A lateral mitral Ea cut-off velocity of 7.8 cm/s had a sensitivity of 87% and a specificity of 79% for the PEP. Freedom from death or transplantation was 85% at 1 year and 77% at 2 years. Conclusions: TD velocities are significantly reduced in patients with LVNC compared with normal controls. Reduced lateral mitral Ea velocity helps predict children with LVNC who are at risk of adverse clinical outcomes including death and need for cardiac transplantation.

Outcomes associated with amiodarone and lidocaine in the treatment of in-hospital pediatric cardiac arrest with pulseless ventricular tachycardia or ventricular fibrillation

AIM To determine the association between amiodarone and lidocaine and outcomes in children with cardiac arrest with pulseless ventricular tachycardia (pVT) and ventricular fibrillation (VF). BACKGROUND Current AHA guidelines for CPR and emergency cardiovascular care recommend amiodarone for cardiac arrest in children associated with shock refractory pVT/VF, based on a single pediatric study and extrapolation from adult data. METHODS Retrospective cohort study from the Get With the Guidelines-Resuscitation database for in-patient cardiac arrest. Patients<18 years old with pVT/VF cardiac arrest were included. Patients receiving amiodarone or lidocaine prior to arrest or whose initial arrest rhythm was unknown were excluded. Univariate analysis was performed to assess the association between patient and event factors and clinical outcomes. Multivariate analysis was performed to address independent association between lidocaine and amiodarone use and outcomes. RESULTS Of 889 patients, 171 (19%) received amiodarone, 295 (33%) received lidocaine, and 82 (10%) received both. Return of spontaneous circulation (ROSC) occurred in 484/889 (54%), 24-h survival in 342/874 (39%), and survival to hospital discharge in 194/889 (22%). Lidocaine was associated with improved ROSC (adjusted OR 2.02, 95% CI 1.36-3), and 24-h survival (adjusted OR 1.66, 95% CI 1.11-2.49), but not hospital discharge. Amiodarone use was not associated with ROSC, 24h survival, or survival to discharge. CONCLUSIONS For children with in-hospital pVT/VF, lidocaine use was independently associated with improved ROSC and 24-h survival. Amiodarone use was not associated with superior rates of ROSC, survival at 24h. Neither drug was associated with survival to hospital discharge.

Loss-of-Function SCN5A Mutations Associated With Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture

Background—Cardiac device implantation can be complicated by inability to adequately place leads because of significant lead capture issues. This study sought to determine whether there are genetic bases that underlie poor lead capture. Methods and Results—Retrospective review of all patients with structurally normal hearts who underwent new device implantation at Texas Children’s Hospital between 2009 and 2014 was performed. Patients with inability to capture at 10 V or a final capture threshold ≥3 V at 0.4 ms during implant were analyzed. Among a total of 136 patients (median age, 13 years; range, 3 days to 46 years), 11 patients (8.1%) who underwent dual chamber device implantation had elevated thresholds in the atria (4), ventricle (3), or both chambers (4; atrial-lead threshold, 4.7±4.3 versus 0.7±0.3 V; ventricular-lead, 3.0±3.3 versus 0.7±0.3 V). All 11 patients presented with sinus node dysfunction and 10 had atrial arrhythmias. At implant, inability to find atrial capture was seen in 4 patients. Three demonstrated intermittent complete loss of ventricular capture after implantation: 1 has recurrent syncope, 2 eventually died. Genetic testing performed in 10 demonstrated 7 patients with 6 distinct SCN5A mutations, all predicted to be severe loss-of-function mutations by bioinformatic analyses. In the remaining patients, although putative pathogenic mutations were not found, multiple SCN5A polymorphisms were identified in 2 and a desmin mutation in 1. Conclusions—This study suggests that significant capture issues at implant may be because of loss-of-function SCN5A mutations, providing new insights into SCN5A function. Recognition of this association may be critical for planning device implantation strategies and patient follow-up.

Interpreting Incidentally Identified Variants in Genes Associated With Catecholaminergic Polymorphic Ventricular Tachycardia in a Large Cohort of Clinical Whole-Exome Genetic Test Referrals

Background— The rapid expansion of genetic testing has led to increased utilization of clinical whole-exome sequencing (WES). Clinicians and genetic researchers are being faced with assessing risk of disease vulnerability from incidentally identified genetic variants which is typified by variants found in genes associated with sudden death-predisposing catecholaminergic polymorphic ventricular tachycardia (CPVT). We sought to determine whether incidentally identified variants in genes associated with CPVT from WES clinical testing represent disease-associated biomarkers. Methods and Results— CPVT-associated genes RYR2 and CASQ2 variants were identified in one of the world’s largest collections of clinical WES referral tests (N=6517, Baylor Miraca Genetics Laboratories) and compared with a control cohort of ostensibly healthy individuals (N=60 706) and a case cohort of CPVT cases (N=155). Within the WES cohort, the rate of rare variants in CPVT-associated genes was 8.8% compared with 6.0% among controls and 60.0% among cases. There was a predominance of variants of undetermined significance (97.7%). After protein topology mapping, WES variants colocalized more frequently to residues with variants found in controls compared with cases. Retrospective clinical evaluation of individuals referred to our institution with WES-positive variants demonstrated no evidence of clinical CPVT in individuals with a low pretest clinical suspicion for CPVT. Conclusions— The prevalence of incidentally identified CPVT-associated variants is ≈9% among WES tests. Variants of undetermined significances in CPVT-associated genes in WES genetic testing, in the absence of clinical suspicion for CPVT, are unlikely to represent markers of CPVT pathogenicity.

Utility and Safety of Combined Interventional Catheterization and Electrophysiology Procedures in a Children's Hospital: COMBINED PROCEDURES IN PEDIATRIC PATIENTS

Interventional cardiac catheterization (cath) and electrophysiology (EP) procedures are not routinely performed together. There are several perceived barriers affecting this practice, though there are also advantages for both the patient and practitioner to a combined approach.

Efficacy of digoxin in comparison with propranolol for treatment of infant supraventricular tachycardia: analysis of a large, national database.

INTRODUCTION Digoxin or propranolol are used as first-line enteral agents for treatment of infant supraventricular tachycardia. We used a large national database to determine whether enteral digoxin or propranolol was more efficacious as first-line infant supraventricular tachycardia therapy. MATERIALS AND METHODS The Pediatric Health Information System database was queried over 10 years for infants with supraventricular tachycardia initiated on enteral digoxin or propranolol monotherapy. Patients were excluded for Wolff-Parkinson-White, intravenous antiarrhythmics (other than adenosine), or death. Success was considered as discharge on the initiated monotherapy. Risk factors for successful monotherapy and risk factors for readmission for supraventricular tachycardia for patients discharged on monotherapy were determined. RESULTS A total of 374 patients (59.6% male) met the study criteria. Median length of stay was 7 days (interquartile range of 3-16 days). Patients had CHD (n=199, 53.2%) and underwent cardiac surgery (n=123, 32.9%), ICU admission (n=238, 63.6%), mechanical ventilation (n=146, 39.0%), and extracorporeal membrane oxygenation (n=3, 0.8%). Pharmacotherapy initiation was at median 37 days of life (interquartile range of 12-127 days) and 47.3% were initiated on digoxin. Success was similar between digoxin (73.1%) and propranolol (73.5%). Initial therapy with digoxin was not associated with success (odds ratio 1.01, 95% CI 0.64-1.61, p=0.93). Multivariable analysis demonstrated hospital length of stay (odds ratio 0.98, 95% CI 0.98-1.00) and involvement of a paediatric cardiologist (odds ratio 0.46, 95% CI 0.29-0.75) associated with monotherapy failure, and male gender (odds ratio 1.66, 95% CI 1.03-2.67) associated with monotherapy success. No variables were significant for readmission on multivariable analysis. DISCUSSION Digoxin or propranolol may be equally efficacious for inpatient treatment of infant supraventricular tachycardia.

Apical Hypertrophic Cardiomyopathy in an Adolescent

To our knowledge, this is one of the few reported cases of apical hypertrophic cardiomyopathy in an adolescent patient in the United States. We describe a clinical presentation of an adolescent male who presented for cardiac evaluation and was found to have an apical variant of hypertrophic cardiomyopathy.

Isolated Junctional Tachycardia in a Patient with Pheochromocytoma: An Unusual Presentation of an Uncommon Disease

Pheochromocytoma is a rare disease, which often presents a diagnostic challenge due to a variable symptom presentation complex. We report the case of a child who presented with isolated symptoms of palpitations and was found to have junctional tachycardia with subsequent development of cardiomyopathy. Further evaluation revealed that she had an extra-adrenal pheochromocytoma, which was the cause of her arrhythmia and subsequent symptomatology.

Reassessing Risk Factors in Pediatric Patients With Pacemakers Implanted for Atrioventricular Block: The Impact of Nonsustained Ventricular Tachycardia

In pediatric patients with pacemakers implanted for atrioventricular block (AVB), nonsustained ventricular tachycardia (NSVT) detected during routine surveillance is a finding of unknown significance. We sought to describe the incidence of NSVT and determine if there was an association between NSVT and adverse outcomes in these patients.

Intravenous sotalol for the management of postoperative junctional ectopic tachycardia

Junctional ectopic tachycardia (JET) is a common postoperative arrhythmia seen in children undergoing surgery to repair congenital heart defects.1, 2 If conservative interventions such as cooling, sedation, weaning of inotropic therapy, and atrial overdrive pacing3, 4 are not adequate, intravenous (IV) antiarrhythmic drugs are used. The most commonly used antiarrhythmic drugs for the treatment of JET include amiodarone and procainamide.4, 5, 6 Recently IV sotalol has become available, and initial studies and case reports have shown it to be safe and effective in the management of supraventricular and ventricular arrhythmias in children.7, 8, 9 We report the first use of IV sotalol for the treatment of postoperative JET.