Long term Prediction of Sudden Cardiac Death Risk in Pediatric Patients with Hypertrophic Cardiomyopathy with Late Gadolinium Imaging: Results from the SCAR-C4 Multicenter Study

Background: There is evidence that late gadolinium enhancement, a cardiac magnetic resonance (CMR)imaging surrogate of myocardial scarring, may be associated with an increased sudden cardiac death (SCD) risk in children with hypertrophic cardiomyopathy (HCM) in short term studies. However, the significance of LGE in SCD in childhood HCM in the long term is unknown.

Methods: We retrospectively analyzed the CMR images and prospectively followed 701 pediatric HCM patients over a mean of 5.7+/- 4.9 years (3993 patient-years) from 38 centers who had LGE imaging.

Results: Amongst 701 patients, 74% were male, with a mean age of 14.1+/- 4.8 years. During follow up, 69 experienced a combination of SCD (n= 8) or equivalent (including 31 aborted cardiac arrests, 40 with appropriate AICD shocks, including 2 patients who experienced multiple shocks). LGE was present in 33%, with a mean burden of 2.0 +/- 5.1% of LV myocardium. In univariate analysis, presence of LGE was associated with an increased SCD risk (HR 3.6, p< 0.0001). Burden of LGE was also associated with an increased risk (HR 1.9 per 10% increase in LGE, p< 0.0001). SCD risk was also associated with history of positive genotype (HR 1.3, p=0.003), NSVT (HR 3.6, p=0.0002), and LV dysfunction (i.e. LVEF < 50%) (HR 2.9, p< 0.0001), and borderline significant for LA diameter z-score (p=0.06), but was not associated with LVOT obstruction (p=0.21), LV mass index (p=0.19), maximal wall thickness (p=0.49) or history of syncope (p=0.10). LGE burden was independently associated with SCD risk and improved risk prediction when adjusted for AHA conventional risk factors (p=< 0.001), ESC risk score (p< 0.0001), HCM Risk-Kids Score(p=0.0001), and the PRIMACY Score (p< 0.0001).

Conclusion: Quantitative LGE remains an independent risk factor for SCD in pediatric patients with HCM in the long term, and provides incremental information to improve SCD risk stratification. Its role in a multi-metric risk score will need to be further elucidated.

Kaplan Meier Analysis of SCD risk according to LGE burden