Orthostatic hypotension in Parkinson syndromes correlates to the degree of cardiac denervation assessed by HED PET

Background: Recently we demonstrated in a small cohort of patients that assessment of (postganglionic) sympathetic myocardial innervation using C-11-hydroxyephedrine (HED) and positron emission tomography (PET) might help to differentiate Parkinson syndromes. Our findings were in line with other reports using I-123-MIBG or F-18-Fluorodopamine as markers of adrenergic innervation.

The aim of the present study was to evaluate whether the degree cardiac denervation correlates to the presence and severity of orthostatic hypotension.

Methods: 22 patients with Parkinson syndromes (male:female 1:1, mean age 63±7.3yrs, mean disease duration 6±3.8yrs; 1 PSP, 1 PDD, 2 DLB, 3 MSA, 15 IPD) underwent a Schellong-test to detect orthostatic hypotension (OH). OH was defined according to the American Autonomic Society as a decrease in systolic blood pressure (sBP) of at least 20mmHg or in diastolic pressure (dBP) of 10mmHg caused by the change of position between lying supine for 10 minutes and then standing for 5 minutes. In each patient a dynamic PET study was acquired over 45min after i.v. injection of 400 MBq C-11-hydroxyephedrine. For quantitative analysis the left ventricular myocardium was delineated using an automated rendering procedure. Mean myocardial influx of HED in the first 5min (K1) was calculated based on an one-compartment-model and using an input function generated from the cave of the left ventricle. HED uptake was quantified additionally by calculating a myocardium-to-liver maximal count (M/L) ratio measured at 5 minutes and 40 minutes after injection, respectively.

Results: Of twenty-two patients, 9 showed orthostatic hypotension. K1 values ranged from 0.198 to 0.561, M/L5min ratios from 0.39 to 1.01. Significant negative correlation was found between sBP and K1 (r=-0.61, p=0.008) as well as sBP and M/L5min ratio (r=-0.57, p=0.006). Moreover, in patients with OH, K1 and M/L5min were significantly lower than in patients without OH (K1: 0.317±0.107 vs. 0.414±0.094, p=0.04; M/L5min: 0.59±0.17 vs. 0.76±0.18, p=0.02). We did not observe a correlation between PET measurements and neither age nor disease duration.

Conclusion: The observed correlation between PET measurements and orthostatic hypotension suggest that cardiac postganglionic sympathetic denervation is a main causative factor of orthostatic hypotension in Parkinson syndromes.