Autism Spectrum Disorder and Cardiovascular Risk: The Role of Frontal QRS-T Angle and Systemic Immune-Inflammation...

Autism spectrum disorder (ASD) has been linked to autonomic dysregulation and low-grade systemic inflammation, but their expression on routine electrocardiography (ECG) in pediatric samples remains unclear. We examined whether inflammatory indices relate to ECG markers, particularly the frontal QRS-T angle (fQRS-T), in youths with ASD.

In this case-control study, children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition- confirmed ASD and age- and sex-matched healthy controls (HC) were enrolled. Sociodemographic data, complete blood counts, biochemistry/hormones, and standard 12-lead ECGs were obtained. Inflammatory composites included the systemic immune-inflammation index (SII), systemic inflammatory response index, and pan-immune-inflammation value. fQRS-T was derived from the automated ECG report as the absolute difference between frontal QRS and T axes (0°-180°) and verified by clinician review.

Eighty-four ASD participants and 82 HC were analyzed, with no age or sex differences. Compared with HC, ASD showed higher heart rate (97.56±21.20 bpm vs. 84.63±17.02 bpm; p=0.004) and a wider fQRS-T (median 23.5° [IQR 5.75-43.25] vs. 18° [IQR 3.5-31.5]; p=0.005). SII was modestly higher in ASD (539.66 vs. 453.14; p=0.030). Autism Behavior Checklist scores correlated with SII (r=0.387; p=0.041) and fQRS-T (r=0.566; p=0.002), but not with heart rate (r=0.117; p=0.546). SII also correlated with fQRS-T (r=0.424; p=0.010).

ASD was associated with increased fQRS-T and SII despite largely normal conventional ECG intervals, and behavioral severity tracked with both inflammatory tone and repolarization heterogeneity, suggesting a possible association between inflammatory, autonomic, and electrophysiological processes.