Akash R. Patel

Abnormal electrocardiographic findings in athletes: recognising changes suggestive of cardiomyopathy

Cardiomyopathies are a heterogeneous group of heart muscle diseases and collectively are the leading cause of sudden cardiac death (SCD) in young athletes. The 12-lead ECG is utilised as both a screening and diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of an underlying pathological cardiac disorder. This article describes ECG findings present in cardiomyopathies afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.

Abnormal electrocardiographic findings in athletes

Cardiomyopathies are a heterogeneous group of heart muscle diseases and collectively are the leading cause of sudden cardiac death (SCD) in young athletes. The 12-lead ECG is utilised as both a screening and diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of an underlying pathological cardiac disorder. This article describes ECG findings present in cardiomyopathies afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.

Use of Oral Budesonide in the Management of Protein-Losing Enteropathy After the Fontan Operation

BACKGROUND Intestinal inflammation is a component of the pathophysiology of protein-losing enteropathy after the Fontan operation. Oral controlled-release budesonide is 90% metabolized at first pass through the liver, has high enteric anti-inflammatory activity and relatively low systemic effects, and may be an ideal agent for use in treating this disease. METHODS Budesonide was administered to 9 patients (4 male) with protein-losing enteropathy after the Fontan operation. The median interval between the Fontan operation and diagnosis of protein-losing enteropathy was 4 years (range, 0.1 to 13.3). Prior interventional therapy included pulmonary artery stent (1), fenestration (3), pacemaker placement (3) and Fontan revision (2). Prior medical therapy included oral prednisone (5), heparin (4), sildenafil (2), infliximab (1), and octreotide (1), all without persistent success. The starting daily dose of budesonide was 9 mg for patients 4 years old or older, and 6 mg for patients less than 4 years of age. RESULTS Mean serum albumin level 3 months before starting budesonide was 1.9 g/dL (range, 1 to 2.4 g/dL). Serum albumin level improved in all patients within 6 months of starting budesonide (mean 2.9 g/dL; range, 2.2 to 3.8 g/dL). Albumin levels of 3 g/dL or more were achieved in 8 of 9 patients within a median of 4.3 months (range, 2 to 25). Side effects included Cushingoid features and osteoporosis (3), infection requiring antibiotic treatment (5), and acne exacerbation (1). Weaning from high initial dose to a lower dose was possible with sustained effect; however, discontinuation of budesonide resulted in recurrence of hypoalbuminemia. CONCLUSIONS Oral budesonide is an effective therapy for treating protein-losing enteropathy after the Fontan operation. To maintain response, low-dose therapy must be continued.

Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome.

Background— Exercise stress testing has shown diagnostic utility in adult patients with long-QT syndrome (LQTS); however, the QT interval adaptation in response to exercise in pediatric patients with LQTS has received little attention. Methods and Results— One-hundred fifty-eight patients were divided into 3 groups: Those with LQTS type 1 (LQT1) or LQTS type 2 (LQT2) and normal control subjects without cardiovascular disease. Each patient underwent a uniform exercise protocol with a cycle ergometer followed by a 9-minute recovery phase with continuous 12-lead ECG monitoring. Each patient underwent a baseline ECG while resting in the supine position and in a standstill position during continuous ECG recording to determine changes in the QT and RR intervals. Fifty patients were gene-positive for LQTS (n=29 for LQT1 and n=21 for LQT2), and the control group consisted of 108 patients. QT interval adaptation was abnormal in the LQT1 patients compared with LQT2 and control patients (P<0.001). A corrected QT interval (QTc) >460 ms in the late recovery phase at 7 minutes predicted LQT1 or LQT2 versus control subjects with 96% specificity, 86% sensitivity, and a 91% positive predictive value. A recovery &Dgr;QTc(7 min−1 min) >30 ms predicted LQT2 versus LQT1 with 75% sensitivity, 82% specificity, and a 75% positive predictive value. The postural &Dgr;QT was significantly different between LQTS and control groups (P=0.005). Conclusions— Genotype-specific changes in repolarization response to exercise and recovery exist in the pediatric population and are of diagnostic utility in LQTS. An extended recovery phase is preferable to assess the repolarization response after exercise in the pediatric population.

Implantable cardioverter-defibrillator lead failure in children and young adults: a matter of lead diameter or lead design?

OBJECTIVES This study aimed to investigate the impact of lead diameter and design on implantable cardioverter-defibrillator (ICD) lead survival in children and young adults. BACKGROUND Recent reports have called attention to high rates of lead failure in adults with small-diameter ICD leads, but data in the pediatric population is limited. METHODS We reviewed lead performance in consecutive subjects ≤30 years with transvenous right ventricular ICD leads implanted at our center between January 1995 and October 2011. Lead failure was defined as fracture, perforation, or sensing failure necessitating revision. RESULTS A total of 120 ICD leads were implanted in 101 patients at a mean age of 15.5 ± 4.9 years. There were 47 small-diameter (≤8-F) and 73 standard-diameter (>8-F) leads. During a median follow-up of 28.7 months (interquartile range: 14.4 to 59.2 months), there were 25 lead failures (21% prevalence), with an incidence of 5.6%/year (95% confidence interval: 3.4 to 7.8). Sprint Fidelis (SF) (Medtronic, Inc., Minneapolis, Minnesota) leads had lower 3-year (69% vs. 92%, p < 0.01) and 5-year (44% vs. 86%, p < 0.01) survival probabilities than standard-diameter leads. In multivariate Cox regression, SF design conferred the greatest hazard ratio for lead failure (hazard ratio: 4.42, 95% confidence interval: 1.73 to 11.29, p < 0.01). Age and linear growth were not significantly associated with lead failure. CONCLUSIONS In this single-center pediatric study that evaluated lead diameter, lead design, and patient factors, the SF design conferred the highest risk of lead failure, suggesting that design rather than diameter is the critical issue in ICD lead performance.

Systematic review: Functional outcomes and complications of intramedullary nailing versus plate fixation for both-bone diaphyseal forearm fractures in children

BACKGROUND Both-bone diaphyseal forearm fractures constitute up to 5.4% of all fractures in children in the United Kingdom. Most can be managed with closed reduction and cast immobilisation. Surgical fixation options include flexible intramedullary nailing and plating. However, the optimal method is controversial. The main purpose of this study was to systematically search for and critically appraise articles comparing functional outcomes, radiographic outcomes and complications of nailing and plating for both-bone diaphyseal forearm fractures in children under 18 years. METHODS A comprehensive search of Medline, Embase and Cochrane databases using specific search terms and limits was conducted. Articles identified were thoroughly screened using strict eligibility criteria and eight retrospective non-randomised comparative studies were identified and reviewed. RESULTS There were no statistically significant differences in functional outcome or time to fracture union between plating and IM nailing. No consistent difference was found in complication rate, fracture angulation, shortening or rotation. Better cosmesis and shorter duration of surgery was noted in the IM nailing group. Post-operative radial bow was significantly abnormal in the IM nailing groups, but did not affect forearm movement. CONCLUSION Based on similar functional and radiographic outcomes, nailing seems to be a safe and effective option when compared to plating for paediatric forearm fractures. However, critical appraisal of the studies in this review identified some methodological deficiencies and further prospective, randomised trials are recommended.

Junctional Tachycardia in a Child with Lyme Carditis

A 3-year-old girl presented with fatigue, fever, and rash. Tachycardia was noted and an ECG showed junctional tachycardia. Lyme titers were positive and the arrhythmia resolved with intravenous ceftriaxone.

Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small cell lung cancer with FLT-PET imaging

Inhibition of thymidylate synthase (TS) results in a transient flare in DNA thymidine salvage pathway activity measurable with FLT ([18F]thymidine)-positron emission tomography (PET). Here we characterize this imaging strategy for potential clinical translation in non-small cell lung cancer (NSCLC). Since pemetrexed acts by inhibiting TS, we defined the kinetics of increases in thymidine salvage pathway mediated by TS inhibition following treatment with pemetrexed in vitro. Next, using a mouse model of NSCLC, we validated the kinetics of the pemetrexed-mediated flare in thymidine salvage pathway activity in vivo using FLT-PET imaging. Finally, we translated our findings into a proof-of-principle clinical trial of FLT-PET in a human NSCLC patient. In NSCLC cells in vitro, we identified a burst in pemetrexed-mediated thymidine salvage pathway activity, assessed by 3H-thymidine assays, thymidine kinase 1 (TK1) expression, and equilibrative nucleoside transporter 1 (ENT1) mobilization to the cell membrane, that peaked at 2hrs. This 2hr time-point was also optimal for FLT-PET imaging of pemetrexed-mediated TS inhibition in murine xenograft tumors and was demonstrated to be feasible in a NSCLC patient. FLT-PET imaging of pemetrexed-induced TS inhibition is optimal at 2hrs from therapy start; this timing is feasible in human clinical trials.

Acquired ventricular septal aneurysm in a patient with pulmonary atresia with intact ventricular septum

Myocardial ischaemia and infarction in pulmonary atresia and intact ventricular septum with right ventricular-dependent coronary circulation is a well-established complication. We report an interesting case of an acquired aneurysm in the ventricular septum in a patient who underwent staged palliation.

Utility of Electrocardiogram in the Assessment and Monitoring of Pulmonary Hypertension (Idiopathic or Secondary to Pulmonary Developmental Abnormalities) in Patients ≤18 Years of Age

Electrocardiograms have utility in disease stratification and monitoring in adult pulmonary arterial hypertension (PAH). We examined the electrocardiographic findings that are common in pediatric PAH and assessed for correlation with disease severity and progression. We retrospectively identified patients aged≤18 years followed at a single institution from January 2001 to June 2012 with catheterization-confirmed diagnosis of idiopathic PAH and PAH secondary to pulmonary developmental abnormalities. Patients with an electrocardiography performed within 60 days of catheterization were included. Primary and secondary outcomes are the prevalence of abnormal electrocardiographic findings at the time of catheterization and the association between electrocardiographic and hemodynamic findings and electrocardiographic changes with disease progression on follow-up catheterization, respectively. Of the 100 electrocardiography-catheterization pairs derived from the 46 patients identified, 93% had an electrocardiographic abnormality: 78% had right ventricular hypertrophy (RVH) and 52% had right axis deviation (RAD) for age. In patients with idiopathic PAH, the presence of RVH and RAD correlated with pulmonary vascular resistance and transpulmonary gradient. RAD and RVH on baseline electrocardiogram was associated with an increased risk of disease progression on subsequent catheterization (odds ratio 11.0, 95% confidence interval 1.3 to 96.2, p=0.03) after adjusting for PAH subgroup. The sensitivity, specificity, and positive and negative predictive values of RAD and RVH on baseline electrocardiogram for disease progression were 92%, 48%, 33%, and 95%, respectively. In conclusion, electrocardiographic abnormalities are common in pediatric PAH. RAD and RVH on electrocardiogram were associated with worse hemodynamics, whereas their absence is suggestive of a lack of disease progression.