Objective: A retrospective records review of 9 patients that failed screening for a clinical trial was performed to examine the co-morbid cardiac manifestations of PD and other Parkinson’s Plus Syndromes.

Background: The pathogenesis that leads to the manifestation of dysautonomia in PD is thought to be due to deposition of alpha-synuclein in catecholaminergic neurons throughout the body. Prior studies have shown a relatively high prevalence of QT interval prolongation, neurogenic orthostatic hypotension, supine hypertension, as well as blood pressure variability.

Methods: A landmark safety study was performed at Georgetown University Hospital using Nilotinib in patients with more advanced stages of PD, Parkinson’s disease Dementia, Multi-System Atrophy, and Diffuse Lewy Body Dementia. 9 of 20 patients failed initial screening due to various cardiac conditions making them ineligible to enter the clinical trial. Data from these nine patients was reviewed and included the following parameters: demographics, PD stage, cardiac history, electrocardiogram data, and vital signs.

Results: All participants were at least in their 6^th decade of life. EKGs were performed on the initial screening visit. Five of the nine patients had EKG abnormalities other than QTc prolongation. These abnormalities included a left bundle branch block in the DLB subject, right bundle branch block in three subjects, a first degree heart block seen in one subject, and evidence of ischemia seen in one subject.

Conclusions: EKG data revealed QTc prolongation in eight out of nine screen fail patients. Seven out of eight screen fail patients had QTc prolongation of 465 or greater, which was well above the 450 cutoff. Screen fail #5 had the longest QTc prolongation of 505, and was the participant with the highest UPDRS motor score of 50. The three participants that had a UPDRS motor score of 31 or higher also exhibited the longest QTc prolongation of the sample. Our data shows a correlation between PD and cardiovascular co-morbidities. As supported in the literature, alpha-synuclein accumulation in the peripheral nerves leads to vasomotor denervation, which results in an alteration of blood pressure. Practically speaking, healthcare professionals should utilize cardiac screening tools to assess PD patients for cardiac comorbidities and other autonomic symptoms, since our data suggests that many of these patients have underlying undiagnosed cardiac conditions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lessons-learned-from-the-nilotinib-trial-cardio-vascular-conditions-in-parkinsonism/