Assessment of myocardial reinnervation in cardiac transplants by positron emission tomography: functional significance tested by heart rate variability.

While it is known that scintigraphically measured uptake of [C-11] hydroxyephedrine (HED) correlates well with the catecholamine uptake and storage in the nerve terminals of the myocardium, the functional significance of this morphologic marker remains unclear. It had been shown that normal, innervated myocardium exhibits pronounced heart rate variability (HRV). In this study, parallel to the scintigraphic determination of regional HED uptake, the functional sympathetic innervation of the left ventricle was measured by spectral analysis of HRV. Prior to PET scanning, changes in the low frequency HRV after tilt were determined as validated marker of sympathetic function in 12 patients with cardiac transplants (mean time after transplantation 4.7 years). Dynamic PET data acquisition allowed the definition of a retention index as regional marker for sympathetic nerve terminals. Intensity as well as regional extent of this marker were then compared to the results of HRV studies. Two groups were defined based on the scintigraphic findings: 8 of 12 patients displayed regionally increased HED retention (11.5 +/- 3.1%/min.) in the anteroseptal region of the left ventricle, while 4 patients showed little HED uptake (4.3 +/- 0.5%/min.). Uptake values tended to increase for longer times after surgery. Average HRV in the first group (7.57 +/- 7.47 ms2/Hz) was significantly higher (p < 0.05) compared to the low HED uptake group (1.17 +/- 1.08 ms2/Hz). HRV was lower than normal values even in the first group. These independent electrophysiological measurements prove the significance of HED retention for the functional characterization of reinnervation in cardiac transplants.