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2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.

ABSTRACT: The objective of this study was to detect regional patterns of cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) using 11C-hydroxyephedrine (11C-HED) PET and determine the denervation rate over 2 y. METHODS:We obtained 62 cardiac 11C-HED PET scans in 39 patients (30 men and 9 women; mean age ± SD, 61.9 ± 5.9 y), including 23 patients with follow-up scans at 2 y. We derived 11C-HED retention indices (RIs; mL of blood/min/mL of tissue) reflecting nerve density and integrity for 480 left ventricular (LV) sectors. We compared IPD patients with 33 healthy controls using z score analysis; RI values ? 2.5 SDs were considered abnormal. We expressed global and regional LV denervation as the percentage extent of z score severity and severity-extent product (SEP) on 9-segment bullseye maps and decline in cardiac sympathetic innervation as the 2-y difference in SEP (diff-SEP). RESULTS:Baseline 11C-HED PET in the 39 IPD patients revealed an RI mean of 0.052 ± 0.022 mL of blood/min/mL of tissue. In comparison with data from normal controls, 12 patients had normal 11C-HED PET, 5 showed mild denervation (percentage extent < 30%), and 22 had moderate to severe denervation (percentage extent > 30%, z score ? 2.5 SD). In the 23 paired PET scans, worsening cardiac denervation (global diff-SEP > 9) occurred in 14 of 23 (60.9%) patients over 2 y, including percentage LV abnormality (59% increasing to 66%), z-severity (-2.4 down to -2.5), and SEP (-195 to -227) (P = 0.0062). We found a mean annual decline of 4.6% ± 5.6 (maximum, 13%) in 11C-HED retention from a baseline global RI mean of 0.0481 ± 0.0218 to 0.0432 ± 0.0220 (P = 0.0009). At baseline, 5 patients with normal uptake had no interval change; 3 with mild denervation developed interval decline in lateral and inferior segments (diff-SEP -82 to -99) compared with anterior and septal segments (-65 to -79), whereas the reverse pattern occurred in 15 patients with severe baseline denervation. CONCLUSION:Progressive decline in cardiac sympathetic neural integrity in IPD patients occurs at a modest rate over 2 y on 11C-HED scans with marked heterogeneity and a regional pattern of involvement and decline.

SUBMITTER: Wong KK

PROVIDER: S-EPMC5288743 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.

Wong Ka Kit KK Raffel David M DM Bohnen Nicolaas I NI Altinok Gulcin G Gilman Sid S Frey Kirk A KA

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20160818 2

The objective of this study was to detect regional patterns of cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) using <sup>11</sup>C-hydroxyephedrine (<sup>11</sup>C-HED) PET and determine the denervation rate over 2 y.<h4>Methods</h4>We obtained 62 cardiac <sup>11</sup>C-HED PET scans in 39 patients (30 men and 9 women; mean age ± SD, 61.9 ± 5.9 y), including 23 patients with follow-up scans at 2 y. We derived <sup>11</sup>C-HED retention indices (RIs; mL of blood/min/mL of ...[more]

PMID: 27539837

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Project description:PurposeTo determine whether cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) affects the left ventricle in a distinct regional pattern versus a more global pattern with use of carbon 11 (11C) meta-hydroxyephedrine (HED) positron emission tomography (PET).Materials and methodsThis prospective study was approved by the institutional review board and was compliant with HIPAA. Informed consent was obtained from all subjects. Cardiac PET was performed with 11C HED in 27 patients with IPD (20 men and seven women aged 50-74 years; mean age, 62 years±6 [standard deviation]). 11C HED retention indexes (RIs), which reflect nerve density and integrity, were determined. RIs for 33 healthy control subjects (15 men and 18 women aged 20-78 years; mean age, 47 years±17) were used as a control database. Patients with IPD were compared with control subjects by using z score analysis. Global and segmental measurements of sympathetic denervation were expressed as percentage extent, z score severity, and severity-extent product (SEP). Group comparisons were performed with the Student t test.ResultsThe mean 11C HED RI was 0.086 mL of blood per minute per milliliter tissue±0.015 for control subjects and 0.043 mL of blood per minute per milliliter tissue±0.016 for patients with IPD (P<0001). When compared with normative data from the control database, profound cardiac denervation (global extent>50%) was seen in most patients (19 of 27 patients, 70%). Four patients had normal 11C HED studies and four had mild denervation (global extent<25%). The mean global denervation extent was 62%±38, the mean severity z score was -2.7±1.2, and the mean SEP was -202±131 (range, -358 to 0). Segmental analysis revealed relative sparing of anterior and proximal septal segments (mean extent, 48%-51%; mean severity z score, -2.47 to -2.0; mean SEP, -167 to -139), with lateral and proximal inferior segments more severely affected (mean extent, 68%-73%; mean severity z score, -2.8 to -2.62; mean SEP, -271 to -230). Patients with normal findings or preserved denervation did not significantly differ in mean age (t=1.09) or disease duration (t=0.44) compared to patients with severe sympathetic denervation.ConclusionCardiac sympathetic denervation in IPD is extensive, with a segmental pattern that involves the proximal lateral left ventricular wall most severely, with relative sparing of the anterior and proximal septal walls.

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2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.

Publications

2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.

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