Atrial Overdrive Pacing In Obstructive Sleep Apnea Patients With Implanted Pacemaker

BackgroundThe prevalence of obstructive sleep apnea syndrome is up to 5% for adults in Western countries, with a similar proportion in adult Chinese urban population. But there are few data on the prevalence of sleep apnea in patients with bradyarrhythmias, although it was postulated that bradycardia may be one of the contributing factor to sleep apnea. In patients implanted with dual-chamber pacemakers for bradyarrhythmias, overdrive atrial pacing was reported to reduce the number of central and obstructive sleep apnea episodes by about 50% in a recent study by Garrigue et al.. Two key underlying mechanisms of the effect have been suggested: 1) Overdrive pacing can improve cardiac output as well as pulmonary congestion and thereby reduce hyperventilation and central apnea. 2) Overdrive pacing counteracts nocturnal hypervagotonia by influencing cardiac vagal or sympathetic afferent neurons, thus affecting ventilation and stabilizing respiration. However, these concepts have not been proven. Objectives1) To assess the prevalence of sleep apnea in patients with implanted permanent pacemaker (PPM) for bradyarrhythmias.2) To reproduce the findings in Garrigue's study and to further evaluate the overdrive pacing indications in the sleep apnea field.3) To investigate the possible underlying mechanisms of this novel therapy.MethodsPart I:A total of 108 patients with permanent pacemaker for bradyarrhythmias (88 menand 20 women; mean age, 68 years, age range, 38 to 81 years), and 105 of their gender-matched, age-matched, and comorbidity-matched community control subjects were asked to answer the questionnaire concerning snoring, daytime sleepiness and breathe apnea reported by their bed-partner. Those highly suspected of having sleep apnea (48 in PPM group and 43 in control subjects, respectively) were further tested by portable PSG for a whole night at home. The prevalence of sleep apnea, defined by an apnea-hypopnea index ^5/h, was estimated and compared. Part II and Part IV:Twelve patients with sleep apnea, who had received permanent atrial-synchronous ventricular pacemakers for sinus bradycardia were studied. All patients underwent three polysomnography evaluations on consecutive nights, the first night for base-line evaluation and then, in random order, one night in spontaneous rhythm and one night in dual-chamber pacing mode with atrial overdrive (15 beats per minute faster than the mean nocturnal sinus rate). The total episodes of obstructive or central sleep apnea or hypopnea were analyzed and compared. Data on sleep structure were also collected and compared. Urine was collected overnight and norepinephrine was measured by high-performance liquid chromatography and normalized to urinary creatinine. Blood samples were taken each morning directly after waking. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were determined by an electrochemoluniniscence immunoassay. Part III:Measurements of Po.i response to hypoxia and hypercapnia were performed in six male patients in a randomized crossover study in which devices were programmed for non-pacing, or for overdrive pacing at 15 beats per minute faster than the mean heart rate at base-line pacing. Results1) Prevalence of sleep apnea was 28.7% in the PPM group, which did not differ from that in control subjects (20%, P=0.14).2) In 12 patients with sleep apnea, the apnea-hypopnea index was 18 + 17 events per hour in spontaneous rhythm, with no significant difference from that in overdrive pacing (23+19, p=0.50). Overdrive pacing also did not change sleep fragmentation or sleep structure parameters.3) Nocturnal urine norepinephrine concentrations were 27 ± 17 nmol/mmol Crea during the non-pacing night and 29+14 nmol/mmol Crea during the overdrive pacing night (P=0.62), morning plasma ANP level and BNP level were 263.3 ± 107.2 pg/ml and 248.6+186.3 pg/ml right after the overdrive pacing nights, respectively, which were not different from that right after the non-pacing nights (254.6± 114.6 pg/ml and 234.5±232.4 pg/ml, respectively; P=0.58 and P=0.56, respectively).4) In 6 patients with sleep apnea, there were neither a significant difference of AP0.1/ASpC>2 between atrial overdrive pacing phase and non-pacing phase (—0.24±0.14cmH20/l% vs -0.26±0.18 cmH20/l%, P=0.83), nor a significant difference of AP0.1/APEtCO2 (0.34±0.26cmH20/mmHg vs 0.28±0.31 cmH20/mmHg, P=0.72).Conclusion1) Sleep apnea seems to be common in patients with implanted permanent pacemaker for bradycardias. Nevertheless, this study could not show sleep apnea to be more common in this specific population than in their gender-matched, age-matched, BMI-matched, and comorbidity-matched community control subjects. Therefore, this study did not support the postulation that bradycardias to be a contributor factor to sleep apnea.2) In sleep apnea patients with implanted permanent pacemaker for bradyarrhythmia, atrial overdrive pacing has no significant effect on obstructive sleep apnea nor on sympathetic activation or atrial and...