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Exercise Training in Chronic Heart Failure: Beneficial Effects on Cardiac ¹¹C-Hydroxyephedrine PET, Autonomic Nervous Control, and Ventricular Repolarization

¹ Department of Medicine, Turku University Central Hospital, Turku, Finland
² Turku PET Centre, Turku, Finland
³ Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
⁴ Department of Pediatrics, Turku University Central Hospital, Turku, Finland
⁵ Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Abnormalities of autonomic nervous function are associated with a poor prognosis of patients with chronic heart failure (CHF). We studied the effects of a 6-mo exercise training program on Q–T interval dispersion, heart rate and blood pressure variability, baroreflex sensitivity, myocardial blood flow (MBF), and presynaptic sympathetic innervation in 13 patients with New York Heart Association class II–III heart failure. Methods: MBF was measured with the H₂¹⁵O and C¹⁵O technique. Cardiac presynaptic innervation was studied by ¹¹C-hydroxyephedrine (HED) retention assessed with PET. Heart rate and blood pressure variability and baroreflex sensitivity were tested with the phenylephrine method. All studies were performed before and after a 6-mo exercise training program. The exercise capacity was determined by spiroergometry, and Q–T dispersion was measured from a standard 12-lead electrocardiogram. Results: Q–T dispersion was reduced after the training period (mean ± SEM, from 52 ± 5 to 36 ± 5 ms [P = 0.01]). Global ¹¹C-HED retention improved from 0.228 ± 0.099 to 0.263 ± 0.066 s^-1 (P < 0.05). Global MBF was not affected by training, but MBF increased in areas of low initial perfusion in patients with coronary artery disease (from 0.382 ± 0.062 to 0.562 ± 0.083 mL/g/min [P < 0.005]). The high-frequency spectrum and total R-R interval variability increased (from 4.53 ± 0.30 to 5.02 ± 0.36 ms² [P < 0.05] and from 3.60 ± 0.34 to 4.31 ± 0.37 ms² [P < 0.005], respectively). Both changes correlated significantly with the observed change in ¹¹C-HED retention. There was a significant reduction of total and a near-significant reduction of low-frequency (LF) systolic blood-pressure (SBP) variability (from 4.89 ± 1.03 to 3.18 ± 0.48 [P < 0.05] and from 2.79 ± 0.38 to 1.76 ± 0.24 [P = 0.059], respectively). The decrease in LF SBP variability correlated inversely with the enhancement of ¹¹C-HED retention (r = -0.66; P < 0.05). Baroreflex sensitivity increased from 5.83 ± 0.82 to 10.15 ± 1.66 ms/mm Hg (P < 0.05). Conclusion: Exercise training induces beneficial changes in functional and imaging measures of cardiovascular autonomic nervous control. These observations point to a training-induced shift toward normalization of the compensatory autonomic nervous imbalance in CHF.

Key Words: chronic heart failure • exercise training • hydroxyephedrine • autonomic nervous function • myocardial blood flow

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