Holter-Based Heart Rate Variability Distinguishes Adolescent Postural Orthostatic Tachycardia Syndrome from Healthy Controls

Postural orthostatic tachycardia syndrome (POTS) is associated with autonomic dysregulation, but ambulatory markers that capture autonomic phenotype remain incompletely defined. To compare Holter-derived heart rate variability (HRV) metrics between adolescents with POTS and healthy controls and to derive candidate discriminatory thresholds. Retrospective case-control analysis of an existing Holter dataset (POTS n = 19, controls n = 44). Heart rate variability was processed in Kubios HRV Premium. Between-group comparisons used Welch's t-test with Benjamini-Hochberg false discovery rate adjustment. Nonparametric sensitivity analyses yielded similar results. Discrimination was assessed using receiver operating characteristic analysis; optimal thresholds were defined by the Youden index. An exploratory penalized logistic regression model (L1 regularization) was fit with standardized candidate HRV predictors and internal cross-validation. Among 19 POTS patients and 44 control subjects, POTS demonstrated lower time- and frequency-based HRV, higher rate-related and sympathetic composite indices, and lower parasympathetic composite measures. The strongest univariate discriminator was PNSi (Parasympathetic Nervous System index; AUROC 0.874; threshold ≤ -1.10; sensitivity 77.8%; specificity 88.6%). Other high-performing discriminators included SNSi, mean RR, mean heart rate, and SDNNi. Holter-derived HRV metrics demonstrate a reproducible pattern consistent with reduced parasympathetic modulation and relative sympathetic predominance in POTS. Several variables yield candidate discriminatory thresholds that may support physiologic phenotyping and warrant validation in independent cohorts.