Claudia Carricarte Naranjo1, Connie Marras2, Naomi P Visanji2, David J Cornforth3, Lazaro Sanchez-Rodriguez4, Birgitt Schüle5, Samuel M Goldman6, Mario Estévez7, Phyllis K Stein8, Anthony E Lang2, Herbert F Jelinek9, Andrés Machado10. 1. Facultad de Biología, Universidad de La Habana, Calle 25 No. 455, Vedado, Plaza de la Revolución, 10400, La Habana, Cuba. carri@fbio.uh.cu. 2. Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada. 3. School of Electrical Engineering and Computing, University of Newcastle, University Dr, Callaghan, NSW, 2308, Australia. 4. Department of Radiology, University of Calgary, 330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada. 5. Department of Pathology, Stanford School of Medicine, 300 Pasteur Dr, R271, Stanford, CA, 94305, USA. 6. Department of Neurology, University of California, 3333 California St, San Francisco, CA, 94118, USA. 7. Departamento de Neurofisiología Clínica, Instituto de Neurología y Neurocirugía, Calle 29 No. 139, Vedado, Plaza de la Revolución, 10400, La Habana, Cuba. 8. School of Medicine, Washington University, 660 S Euclid Ave, St. Louis, MO, 63110, USA. 9. School of Community Health, Charles Sturt University, Elizabeth Mitchell Dr, Albury, NSW, 2640, Australia. 10. Facultad de Biología, Universidad de La Habana, Calle 25 No. 455, Vedado, Plaza de la Revolución, 10400, La Habana, Cuba.
Abstract
PURPOSE: Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation. METHODS: Short-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls. RESULTS: Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls. CONCLUSIONS: Increased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD.
PURPOSE:Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PDpatients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2G2019S mutation. METHODS: Short-term electrocardiograms were recorded in 14 LRRK2-associated PDpatients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PDpatients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls. RESULTS: Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PDpatients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PDpatients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PDpatients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PDpatients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls. CONCLUSIONS: Increased beat-to-beat HRV in LRRK2G2019S mutation carriers compared with controls and idiopathic PDpatients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD.
Authors: Naomi P Visanji; Grace S Bhudhikanok; Tiago A Mestre; Taneera Ghate; Kaviraj Udupa; Amaal AlDakheel; Barbara S Connolly; Carmen Gasca-Salas; Drew S Kern; Jennifer Jain; Elizabeth J Slow; Achinoam Faust-Socher; Sam Kim; Ruksana Azhu Valappil; Farah Kausar; Ekaterina Rogaeva; J William Langston; Caroline M Tanner; Birgitt Schüle; Anthony E Lang; Samuel M Goldman; Connie Marras Journal: Mov Disord Date: 2017-01-10 Impact factor: 10.338
Authors: Konstantinos D Rizas; Christian Eick; Angela J Doller; Wolfgang Hamm; Lukas von Stuelpnagel; Christine S Zuern; Petra Barthel; Georg Schmidt; Axel Bauer Journal: Europace Date: 2018-06-01 Impact factor: 5.214
Authors: Claudia Carricarte Naranjo; Connie Marras; Naomi P Visanji; David J Cornforth; Lazaro Sanchez-Rodriguez; Birgitt Schüle; Samuel M Goldman; Mario Estévez; Phyllis K Stein; Anthony E Lang; Herbert F Jelinek; Andrés Machado Journal: Clin Auton Res Date: 2021-07-12 Impact factor: 4.435