Objective: In untreated Fabry patients without overt autonomic dysfunction and normal baroreflex sensitivity (BRS) at rest, BRS is impaired during orthostatic, sympathetic challenge but normalizes after enzyme-replacement therapy (ERT) (Hilz et al., J Hypertens 2010; 28:1438-1448). This study evaluated BRS during parasympathetic challenge with six cycles per minute metronomic deep breathing (MDB) in Fabry patients before and after ERT.
Methods: In 22 Fabry patients (28 ± 8 years), we monitored RR-intervals (RRIs), SBP, and respiratory frequency during spontaneous breathing (spont_breath) and MDB, before and after 18 (11 patients) or 23 months (11 patients) of biweekly ERT (1.0 mg/kg agalsidase beta). We determined spectral powers of mainly sympathetic low-frequency (0.04-0.15 Hz) RRI fluctuations, parasympathetic high-frequency (0.15-0.5 Hz) RRI fluctuations, sympathetically mediated low-frequency powers of SBP and high-frequency powers of SBP. We calculated BRS (ms/mmHg) during spont_breath and MDB as low-frequency-high-frequency alpha index (coherence >0.5). We compared parameters during spont_breath and MDB within and between patients before and after ERT and 15 age-matched (27 ± 5 years) healthy men (RANOVA and posthoc analysis; significance: P < 0.05).
Results: During spont_breath and MDB, parameters were similar between groups. Within the three groups, RRIs were lower, whereas RRI low-frequency powers and SBP low-frequency powers were higher during MDB than during spont_breath. BRS was similar during MBD and spont_breath in untreated patients (P > 0.05), but increased significantly with MDB in patients after ERT (P = 0.048) and in controls (P = 0.035).
Conclusion: In untreated Fabry patients, MDB uncovers impaired BRS. After 18 or 23 months of ERT, MDB-induced BRS increase is similar in Fabry patients and controls, demonstrating that ERT not only restores sympathetic but also parasympathetic baroreflex activation.