Progression of Autonomic Dysfunction in Neurogenic Orthostatic Hypotension Patients

Abstract

Previous studies in diabetic patients have confirmed use of prolonged QT intervals, corrected for HR by Bazett’ sF ormula (QTc) on electrocardiograms, as a surrogate marker for cardiac autonomic neuropathy. However, progressive changes ove r time have not been measured in patients with other etiologies of Autonomic Dysfunction and Neurogenic Orthostatic Hypotension (NOH). The goal of the present study was to characterize the change in autonomic function over time. We conducted a retrospective chart review of 25 NOH due to various etiologies [(PAF, AI, PD, MSA) (BMI = 25.62 ± 2.73 kg/m) (HR = 69.8 ± 8.2 bpm)] followed for 7.2 ± 5.4 yrs. pre-diagnosis and 5.5 ± 3.1 yrs. post-diagnosis. QTc ≥440 mm were considered prolonged. These values were standardized from the time of diagnosis for evaluation of changes. The rate of prolongation over time was measured by the slope (m) of linear regression analysis. Results: Prior to diagnosis, NOH displayed a modest rate of progressive QTc prolongation (m = 1.6197; r 2 =0 .29). Postdiagnosis, there was a 2.7-fold increase over time in the rate of QTc prolongation (m = 4.3334; r 2 = 0.50). Additionally, the percent of prolonged QTc intervals ≥ 440 mm increased from 8% pre-diagnosis to 68% post-diagnosis (P b 0.01). Conclusion: Our results suggest that autonomic dysfunction may be predicted at an earlier stage by progression of QTc prolongation, which then increases progressively post-diagnosis by 2.7-fold. A chronologic association may also exist between the extent of QTc prolongation and the duration of NOH. Thus, prolongation of QTc interval may represent the progressive loss of adrenergic neurons over time, which later predisposes NOH to cardiac arrhythmias and sudden death.