Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: Validation of the HCM risk-kids model and predictors of events.

BACKGROUND: RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated. AIM: To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population. METHODS: Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters. RESULTS: Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis. CONCLUSION: Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further.

Cardiac outcome of pregnancy in women with a pacemaker and women with untreated atrioventricular conduction block.

AIMS: The natural history and outcome of pregnancy in patients with a pacemaker or those presenting with atrioventricular conduction block in pregnancy are unknown with only a limited number of case reports published. METHODS AND RESULTS: This study examines the progress and outcome of 25 pregnancies in 18 women who were either paced or presented with untreated atrioventricular conduction block during pregnancy. All patients were seen in a single referral centre between 1998 and 2008 and were evaluated at regular intervals with ECG, echocardiography, and 24 h Holter. Four women (4 pregnancies) had new-onset atrioventricular block, 3 women (5 pregnancies) had previously diagnosed atrioventricular block who had not undergone pacing, and 11 women (16 pregnancies) had known atrioventricular block with a pacemaker prior to pregnancy. Of the four patients presenting for the first time in pregnancy, the frequency or severity of atrioventricular conduction block increased during pregnancy. One required pacing during and one after pregnancy. In two patients the conduction disturbance resolved postpartum. In the three patients who had known but untreated atrioventricular block before pregnancy, this progressed during each pregnancy but did not require pacing. In patients paced before pregnancy, there were no complications as a result of the pacemaker, but maternal complications were seen in patients with underlying structural heart disease. CONCLUSIONS: Atrioventricular block in pregnancy is progressive; pacing is not always required but all patients should be closely monitored during and after pregnancy. In patients paced before pregnancy, pacing is well tolerated.