Cardiovascular Indices As Outcome Measures in Autism Spectrum Disorder Clinical Trials

Background: Heart rate (HR) and heart rate variability (HRV) are regulated by the autonomic nervous system (ANS). Several prior studies have reported elevated HR and reduced HRV in individuals with autism spectrum disorder (ASD) in comparison to typically developing (TD) controls and other clinical populations. However, less is known about these cardiovascular indices in response to social and non-social stimuli within ASD, and how they associate with reported symptomology over time.

Objectives: Evaluate HR and HRV between ASD and TD groups at rest, and within individuals with ASD in response to presentation of a range of social and non-social stimuli, including correlation with reported symptomology over time.

Methods: Cardiovascular data was collected using Actiwave Cardio Single-Channel Electrocardiogram while participants (ASD: n=127, mean [SD] age=14.6 [7.91]; TD: n=41, mean [SD] age=16.27 [13.18]) were at rest while observing a range of dynamic and static social and non-social stimuli across three blocks lasting approximately 15 minutes each. Baseline HR was calculated during a resting state task, both eyes open (where participants watched sand flow through an hourglass) and eyes closed. ASD participants repeated the task battery at four and eight weeks during a non-interventional trial. ASD and TD participants were approximately matched for age and gender.

Results: HR and RMSSD (a time-domain measure of HRV) were distributed non-normally (Kolgomorov-Smirnov p < 0.05) and analyzed non-parametrically. Data are reported as median [IQR].

 

At baseline, HR in ASD participants was statistically significantly higher than TD controls for both eyes open [88.38 BPM [79.35-96.23] vs. 73.14 BPM [65.81-84.37]) and eyes closed (89.32 BPM [79.32-97.62] vs 74.18 BPM [65.68-84.72]), both p < 0.001). RMSSD in ASD participants was statistically significantly lower than TD controls eyes open (43.43ms [27.41-72.26] vs. 61.28ms [38.41-93.16], p=0.024) and eyes closed (42.17ms [26.95-70.44] vs. 62.13ms [41.66-108.6], p=0.022).

The following findings between baseline assessment and endpoint assessment periods were also observed: HR during the passive viewing of social and non-social dynamic visual stimuli (Kanwisher task) was statistically significantly correlated with the ABI Social Communication subscale (Spearman’s rho = -0.23, p=-0.043); RMSSD during the passive viewing of social and non-social dynamic visual stimuli (Tager-Flusberg task) statistically significantly correlated with the SRS Social Communication and Interaction subscale (Spearman’s rho =-0.25, p=0.02); and RMSSD during both the Kanwisher and Tager-Flusberg tasks statistically significantly associated with the ABI Restrictive and Repetitive Behavior subscale (rho=0.30, p=0.008; rho=0.30, p=0.009).

 Conclusions: Results confirm previous findings of statistically significant differences in cardiovascular indices between ASD and TD populations at rest. Changes in these indices between time points also significantly correlated with changes in reported symptom severity, indicating the potential of cardiovascular indices as sensitive outcome measures of clinical trial interventions.