Objective: To assess the complexity of heart rate variability (HRV) dynamics in LRRK2-nonmanifesting carriers compared to healthy individuals.

Background: Cardiovascular autonomic dysfunction is an early feature of Parkinson’s disease (PD) and manifests as a reduction in the magnitude and complexity of HRV. Dysautonomic symptoms have been reported in PD patients who carry the G2019S mutation in the LRRK2 gene, although our previous work has found that HRV magnitude was not reduced in LRRK2-PD or in LRRK2-nonmanifesting carriers. However, no previous investigation has assessed the complexity of HRV in LRRK2 G2019S mutation carriers.

Methods: Shannon entropy (ShE) and permutation entropy (PE), including ordinal patterns statistics (OPS), from 5 min cardiac interbeat interval series, were analyzed in 16 LRRK2-nonmanifesting carriers and 15 healthy individuals. For PE analysis different embedding dimensions (3-4) and time delays τ (1-20) were considered. Differences between groups were assessed controlling for age, sex, and mean heart rate (HR). A forward stepwise discriminant analysis was carried out for estimating the classification functions based on OPS. Sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV and NPV, respectively) were calculated following a K-fold cross-validation strategy (k=10).

Results: There was no significant difference in PE or ShE between LRRK2-nonmanifesting carriers and healthy individuals. However, we observed a correlation between ShE and HR in LRRK2-nonmanifesting carriers such that ShE was significantly lower in those with a HR>65 bpm. This correlation was absent in healthy individuals. Furthermore, some OPS were significantly different between groups, especially those describing the HRV dynamics between 4-10 s or 0.1-0.3 Hz (τ=4). A three-dimensional feature space discrimination, represented through the classification functions, reached 93.8% Se, 86.7% Sp, 88.2% PPV, and 92.9% NPV.

Conclusions: The dynamics of cardiac rhythm determined by both sympathetic and parasympathetic autonomic branches might be selectively altered in LRRK2-nonmanifesting carriers. Replication in larger and independent samples is required to elucidate the effectiveness of OPS for the detection of early perturbations in cardiac autonomic regulation in LRRK2-nonmanifesting carriers and prodromal PD.

References: Visanji et al. (2017) “Heart rate variability in leucine-reach repeat kinase 2-associated Parkinson’s disease”. “In press” in Movement Disorders

Bandt, C. and B. Pompe (2002). “Permutation entropy: a natural complexity measure for time series.” Phys. Rev. Lett. 88(17): 174102

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MDS Abstracts - https://www.mdsabstracts.org/abstract/listen-to-your-heart-ordinal-pattern-statistics-reveal-altered-cardiac-rhythm-dynamics-in-lrrk2-nonmanifesting-carriers/