Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy.

BACKGROUND: Genetic defects in the RAS/mitogen-activated protein kinase pathway are an important cause of hypertrophic cardiomyopathy (RAS-HCM). Unlike primary HCM (P-HCM), the risk of sudden cardiac death (SCD) and long-term survival in RAS-HCM are poorly understood. OBJECTIVES: The study's objective was to compare transplant-free survival, incidence of SCD, and implantable cardioverter-defibrillator (ICD) use between RAS-HCM and P-HCM patients. METHODS: In an international, 21-center cohort study, we analyzed phenotype-positive pediatric RAS-HCM (n = 188) and P-HCM (n = 567) patients. The between-group differences in cumulative incidence of all outcomes from first evaluation were compared using Gray's tests, and age-related hazard of all-cause mortality was determined. RESULTS: RAS-HCM patients had a lower median age at diagnosis compared to P-HCM (0.9 years [IQR: 0.2-5.0 years] vs 9.8 years [IQR: 2.0-13.9 years], respectively) (P < 0.001). The 10-year cumulative incidence of SCD from first evaluation was not different between RAS-HCM and P-HCM (4.7% vs 4.2%, respectively; P = 0.59). The 10-year cumulative incidence of nonarrhythmic deaths or transplant was higher in RAS-HCM compared with P-HCM (11.0% vs 5.4%, respectively; P = 0.011). The 10-year cumulative incidence of ICD insertions, however, was 5-fold lower in RAS-HCM compared with P-HCM (6.9% vs 36.6%; P < 0.001). Nonarrhythmic deaths occurred primarily in infancy and SCD primarily in adolescence. CONCLUSIONS: RAS-HCM was associated with a higher incidence of nonarrhythmic death or transplant but similar incidence of SCD as P-HCM. However, ICDs were used less frequently in RAS-HCM compared to P-HCM. In addition to monitoring for heart failure and timely consideration of advanced heart failure therapies, better risk stratification is needed to guide ICD practices in RAS-HCM.

The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, abnormal results on exercise stress testing are predictive of heart failure outcomes. Our goal was to determine whether an abnormal exercise response is associated with adverse outcomes in pediatric patients with HCM. METHODS: In an international cohort study including 20 centers, phenotype-positive patients with primary HCM who were <18 years of age at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response and new or worsened ST- or T-wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of abnormal exercise test results with transplant and SCD event-free survival. RESULTS: Of 724 eligible patients, 630 underwent at least 1 exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8 years (interquartile range, 4.7 years); 78% were male and 39% were receiving beta-blockers. A total of 175 (28%) had abnormal test results. Patients with abnormal test results had more severe septal hypertrophy, higher left atrial diameter z scores, higher resting left ventricular outflow tract gradient, and higher frequency of myectomy compared with participants with normal test results (P<0.05). Compared with normal test results, abnormal test results were independently associated with lower 5-year transplant-free survival (97% versus 88%, respectively; P=0.005). Patients with exercise-induced ischemia were most likely to experience all-cause death or transplant (hazard ratio, 4.86 [95% CI, 1.69-13.99]), followed by those with an abnormal blood pressure response (hazard ratio, 3.19 [95% CI, 1.32-7.71]). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (hazard ratio, 3.32 [95% CI, 1.27-8.70]). Exercise-induced ectopy was not associated with survival. CONCLUSIONS: Exercise abnormalities are common in childhood HCM. An abnormal exercise test result was independently associated with lower transplant-free survival, especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.

Pulmonary Autograft Coronary-Cameral Fistula Leading to LVOT Pseudoaneurysm Post Ross Procedure.

We report the case of a presumed coronary-cameral fistula arising directly below the commissures of the noncoronary cusp (NCC) and left coronary cusp (LCC) of the pulmonary autograft, leading to left ventricular outflow tract pseudoaneurysm and late tamponade post Ross procedure.

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. METHODS: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy <18 years of age at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest, and aborted SCD, that is, appropriate shock following primary prevention implantable cardioverter defibrillators. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with 10 repeated 4-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized by using the c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe [Sarcomeric Human Cardiomyopathy Registry], n=285). RESULTS: Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated sudden cardiac arrests, and 14 aborted SCD). Risk predictors included age at diagnosis, documented nonsustained ventricular tachycardia, unexplained syncope, septal diameter z-score, left ventricular posterior wall diameter z score, left atrial diameter z score, peak left ventricular outflow tract gradient, and presence of a pathogenic variant. Unlike in adults, left ventricular outflow tract gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated between patients with and without SCD events with a c-statistic of 0.75 and 0.76, respectively, and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72, respectively). CONCLUSION: Our study provides a validated SCD risk prediction model with >70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.

Sensitivity, specificity, and reliability of the Get Active Questionnaire for identifying children with medically necessary special considerations for physical activity.

Physical activity is promoted for optimal health but may carry risks for children who require medically necessary activity restrictions. The sensitivity, specificity, and reliability of the Get Active Questionnaire (GAQ) for identifying children needing special considerations during physical activity was evaluated among parents of 207 children aged 3 to 14 years (97 (47%) female, mean age of 8.4 ± 3.7 years). GAQ responses were compared with reports obtained directly from the treating physician (n = 192/207) and information in the medical chart (clinic notes/physician letter, n = 111/207). Parent GAQ responses (either "No to all questions" or "Yes to 1 or more questions") agreed with physician (κ = 0.16, p = 0.003) and medical record (κ = 0.15, p = 0.003) reports regarding the need for special consideration during physical activity (Yes/No). Sensitivity was 71% (20/28) and specificity was 59% (96/164), with few false-negative responses. The GAQ was most effective for rheumatology and cardiology patients. False positives were 29% to 46%, except among chronic pain (80%) and rehabilitation (75%) patients. Test-retest reliability was moderate (Cronbach's α = 0.70) among 57 parents who repeated the GAQ 1 week later. The GAQ effectively identified children not requiring physical activity restrictions and those with medical conditions similar to those of concern among adults. Additional questions from a qualified exercise professional, as recommended for a "Yes" response on the GAQ, should reduce the false-positive burden. Indicating the timeframe of reference for each question and including an option to describe other special considerations (e.g., medication, supervision) are recommended.

Presentation, diagnosis, and medical management of heart failure in children: Canadian Cardiovascular Society guidelines.

Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.

Long-term pediatric outcome of isolated discrete subaortic stenosis.

BACKGROUND: The management of pediatric discrete subaortic stenosis remains controversial. OBJECTIVES: Document the natural history and surgical outcomes for discrete subaortic stenosis to adolescence. METHODS: Retrospective review of clinical and echocardiographic findings in 74 patients diagnosed in childhood between 1985 and 1998. RESULTS: Twenty-five patients were followed only medically for 9.4 ± 0.9 years to 15.9 ± 0.6 years of age. Their echocardiographic left ventricular outflow peak gradient did not progress, 19 ± 1.4 (SEM) vs 20 ± 2.3 mm Hg. The proportion with aortic insufficiency (AI) increased (4% to 52%). Forty-nine patients were operated for discrete subaortic stenosis at 7.8 ± 0.6 years. Their peak gradient at diagnosis was 36 ± 3 mm Hg with AI in 33%. Preoperatively their peak gradient progressed to 60 ± 5 mm Hg with AI in 82%. Assessment 6.2 ± 0.5 years postoperativly showed a peak gradient of 14 ± 2 mm Hg with AI in 88%. Ten patients required reoperation for recurrent discrete subaortic stenosis, 3 acquired complete heart block, and 1 developed endocarditis. There was no mortality. At diagnosis, surgical patients were younger, had greater peak gradients, and greater incidence of AI, than those followed only medically. The progression of discrete subaortic stenosis was positively associated with severity of obstruction and negatively associated with older age at diagnosis. The risk of having surgery over time was associated with greater preoperative obstruction and presence of AI. CONCLUSIONS: Many pediatric patients with mild discrete subaortic stenosis exhibit little progression of obstruction and need not undergo immediate surgery. Others with more severe stenosis may progress precipitously and will benefit from early resection.

A transesophageal echocardiography examination clarifies the cause of cardiovascular collapse during scoliosis surgery in a child.

PURPOSE: The prone position is required for posterior spinal fusion surgery and may be associated with cardiovascular changes, including a decrease in venous return and cardiac index. We report a case of a patient who developed cardiovascular collapse, increased central venous pressure (CVP), and massive bleeding during posterior spinal fusion surgery. A transesophageal echocardiography examination (TEE) documented a right ventricular outflow tract (RVOT) obstruction associated with the use of transverse bolsters. CLINICAL FEATURES: We describe a case of a healthy 14-yr-old male with idiopathic scoliosis who developed severe intraoperative cardiovascular instability and massive bleeding. The surgery was suspended, and the patient was transferred to the intensive care unit. The patient subsequently underwent TEE in the supine and prone positions. The echocardiogram appeared normal in the supine position; however, in the prone position with transverse bolsters, we identified a significant decrease in the diameter of the RVOT that worsened with pressure applied against the thoracic spine. The central venous pressure increased from 10-24 mmHg simultaneously. We found appreciably less impact to the RVOT, RV size and flow, and CVP (10 to 14 mmHg) using longitudinal bolsters both with and without pressure to the back. This position was recommended for the patient's reoperation, which was uneventful. CONCLUSION: A TEE confirmed a RVOT obstruction in the prone position that was associated, in this case, with the use of transverse bolsters. The RVOT obstruction was explained by the chest deformity, compliant chest cage, bolstering, and pressure applied to the patient's back by the surgeon. This positional RVOT obstruction may explain the increase in the CVP and the secondary massive bleeding during the first operation. The TEE was useful to diagnose the patient's condition and to guide his positioning for the second operation.

The measurement of the QT and QTc on the neonatal and infant electrocardiogram: a comprehensive reliability assessment.

BACKGROUND: An electrocardiogram has been proposed to screen for prolonged QT interval that may predispose infants to sudden death in the first year of life. Understanding the reliability of QT interval measurement will inform the design of a screening program. METHODS: Three pediatric cardiologists measured the QT/RR intervals on 60 infant electrocardiograms (median age 46 days), from leads II, V5 and V6 on three separate occasions, 7 days apart, according to a standard protocol. The QTc was corrected by Bazett's (QTcB), Fridericia's (QT(CFrid)), and Hodges' (QTcH) formulae. Intraobserver and interobserver reliability were assessed by intraclass correlation coefficients (ICC), limits of agreement and repeatability coefficients for single, average of two and average of three measures. Agreement for QTc prolongation (> 440 msec) was assessed by kappa coefficients. RESULTS: QT interval intraobserver ICC was 0.86 and repeatability coefficient was 25.9 msec; interobserver ICC increased from 0.88 for single observations to 0.94 for the average of 3 measurements and repeatability coefficients decreased from 22.5 to 16.7 msec. For QTcB, intraobserver ICC was 0.67, and repeatability was 39.6 msec. Best interobserver reliability for QTcB was for the average of three measurements (ICC 0.83, reproducibility coefficient 25.8 msec), with further improvement for QTcH (ICC 0.92, reproducibility coefficient 16.69 msec). Maximum interobserver kappa for prolonged QTc was 0.77. Misclassification around specific cut points occurs because of the repeatability coefficients. CONCLUSIONS: Uncorrected QT measures are more reliable than QTcB and QT(CFrid). An average of three independent measures provides the most reliable QT and QTc measurements, with QTcH better than QTcB.