Philippe Bordier

Sleep apnea: A new indication for cardiac pacing?

In the general adult population, prevalence of sleep apnea syndrome reaches 4% in men and 2% in women. Continuous positive airway pressure is the most efficient treatment. At the present time, although severe atrial bradycardias could occur during sleep apnea episodes, cardiac pacing has not been demonstrated as an efficient treatment for those bradycardias. Treating sleep apnea generally reduces the number of bradyarrhythmias. However, recent studies reported a beneficial effect of atrial pacing on the sleep apnea burden. The mechanisms rely on two phenomena: first to counteract nocturnal hypervagotonia, and second to treat heart failure. By increasing the heart rate, cardiac output improves, which mitigates pulmonary subedema. Consequently, stimulation of the pulmonary afferent vagal fibers is diminished, which reduces central sleep apnea incidence. During nocturnal hypervagotonia, snoring and obstructive apnea episodes are increased, mainly due to an excessive muscular relaxation of the upper airway area inducing cyclical substantial decreases in the airway caliper. In patients with a low heart rate, atrial pacing can counteract hypervagotonia by enhancing the sympathetic tone and modifying the degree of vigilance. Accordingly, in the near future, sleep apnea treatment might potentially rely on atrial pacing in bradycardic patients with hypervagotonia (with or without heart failure). The role of the physician would then be not only to diagnose sleep apnea, but also to identify potential responders to cardiac pacing. (PACE 2004; 27:204–211)

Causes of Syncope in Patients with Alzheimer’s Disease Treated with Donepezil

IntroductionTreatment of Alzheimer’s disease (AD) with cholinesterase inhibitors carries a theoretical risk of precipitating bradycardia. Though syncope occurs in patients with AD, its aetiology is unclear. The aim of this study was to determine the causes of syncope in patients with AD who were treated with donepezil and hospitalised for evaluation of syncope.MethodsWe studied 16 consecutive patients (12 women, 4 men) with AD aged 80 ± 4 years who were hospitalised for evaluation of syncope. All patients underwent staged evaluation, ranging from physical examination to electrophysiological testing.ResultsThe mean dose of donepezil administered was 7.8 mg/day, and the mean duration of donepezil treatment at the time of syncope was 12 ± 8 months. A cause of syncope was identified in 69% of patients. Carotid sinus syndrome was observed in three patients, complete atrioventricular block in two patients, sinus node dysfunction in two patients, severe orthostatic hypotension in two patients and paroxysmal atrial fibrillation in one patient. A brain tumour was discovered in one patient. No cause of syncope was found in 31% of patients despite comprehensive investigation. Repetition of the investigations after discontinuation of donepezil was noncontributory.ConclusionIn patients with AD treated with donepezil, a noninvasive evaluation identified a probable cause of syncope in over two-thirds of patients. Cardiovascular abnormalities were predominant. Noninvasive evaluation is recommended before discontinuing treatment with cholinesterase inhibitors in patients with AD and unexplained syncope.

Cardiovascular effects and risk of syncope related to donepezil in patients with Alzheimer's disease.

AbstractBackground: When otherwise unexplained, syncope in patients with Alzheimer’s disease may be attributed to bradycardia caused by cholinesterase inhibitors. We studied prospectively the clinical events and cardiovascular changes occurring during treatment with donepezil in patients with Alzheimer’s disease. Methods: Consecutive patients presenting with mild-to-moderate Alzheimer’s disease were included in the study. Their clinical characteristics, blood pressure, heart rate and electrocardiogram were recorded before (baseline) and during treatment with donepezil. The drug was administered at a dosage of 5 mg/day for 1 month and 10 mg/day for the following 7 months, as tolerated. We compared the baseline observations with those made at 1, 2 and 8 months of donepezil treatment. We also examined the effects of negatively chronotropic or dromotropic drugs concomitantly administered with donepezil. Results: Thirty patients were included in the study, of whom 43% were taking negatively chronotropic or dromotropic drugs. The first month of therapy (donepezil 5 mg/day) was completed by 26 patients. During the 7-month high-dosage phase (10 mg/day), four patients dropped out of the study; thus, 22 patients completed the full 8 months of the study.The mean heart rate was 66 ± 8 beats/min at baseline in the overall study population. This decreased significantly to 62 ± 9, 61 ± 7 and 62 ± 8 beats/min at the 1, 2 and 8 month timepoints, respectively (all p = 0.002 vs baseline). Among patients not receiving negatively chronotropic or dromotropic drugs, heart rate decreased significantly over the course of the study (from 67 ± 8 beats/min at baseline to 62 ± 8 beats/min at 1 month, 62 ± 7 beats/min at 2 months and 62 ± 8 beats/min at 8 months [all p = 0.005 vs baseline]). There was no significant change in heart rate in patients who were receiving negatively chronotropic or dromotropic drugs.The PR interval increased over the course of the study in all patient groups, but these changes were only statistically significant in the group of patients who were not taking negatively chronotropic or dromotropic drugs (155 ± 23ms at baseline vs 158 ± 21, 160 ± 22 and 163 ± 24ms at the 1, 2 and 8 month timepoints; all p = 0.02 vs baseline).One patient developed syncope due to orthostatic hypotension; there were no cases of bradycardia-induced syncope. Gastrointestinal manifestations were reported in ten of the study patients. Abdominal pain and vomiting were the reasons for study termination in five of the eight patients who did not complete the trial. Conclusion: A donepezil-induced decrease in heart rate and increase in PR interval were observed only in patients with Alzheimer’s disease who were not treated with negatively chronotropic or dromotropic drugs. These changes were not associated with bradycardia-induced syncope.

Significance of syncope in patients with Alzheimer's disease treated with cholinesterase inhibitors

We describe three cases of patients with Alzheimers disease who presented with cardiac syncope soon after initiation of a cholinesterase inhibitor therapy (donepezil). Bradyarrhythmia was documented in two patients, considered probable in one, and was presumed related to the cholinergic therapy. Pacemaker implantation seemed justified rather than donepezil cessation. More over, it permitted an increase in donepezil dosage.

Nocturnal oxygen therapy in patients with chronic heart failure and sleep apnea: a systematic review

Chronic heart failure (CHF) is a public health problem which affects >2% of the adult population, with high morbidity, mortality, and financial cost. Sleep apnea, prevalent in >50% of patients with CHF, can aggravate vital prognosis due to worsening of heart failure. It is considered that a decrease in the apnea-hypopnea load may improve outcomes for those patients. Nocturnal non invasive ventilation can be proposed to treat sleep apnea in this situation, there being few alternatives. The present review concerns the use of nocturnal oxygen therapy (NOT) in patients suffering from both CHF and sleep apnea. The interest of NOT in this situation lies in its ability to reduce the central apnea-hypopnea index and to improve nocturnal oximetry disorders related to sleep apnea. Impact on cardiac contractility, patient tolerance, side effects, and costs of NOT are also approached as well as the underlying mechanisms of NOT. In addition, the results of the SERVE-HF trial have shown an increased death rate in patients with CHF and central sleep apnea and who were treated with adaptive servo-ventilation versus control patients. This may lead to renewed interest in NOT in those patients.

Flecainide-induced Increase in QRS Duration and Proarrhythmia during Exercise

SummaryIn patients taking flecainide, exercise-induced arrhythmias are believed to be related to QRS widening at rest and during exercise. Our aim was to determine, retrospectively, predictive factors of flecainide-induced (a) QRS widening at rest and during exercise, and (b) proarrhythmia (PA) during exercise. Flecainide was administered to 119 patients for atrial and/or ventricular arrhythmias who performed a maximal treadmill test. A total of 63 patients had a normal heart (defined by the absence of structural heart disease and an ejection fraction ≥ 55% by echocardiography and/or cardiac catheterisation), 26 had coronaropathy, 18 valvulopathy and 3 had both, and 7 had dilated and 2 hypertrophic cardiomyopathy. The mean dosage of flecainide was 190 or 200 ± 10 mg/day. Previous myocardial infarction (MI) was a predictive variable of flecainide-induced QRS widening at rest (p = 0.04). During exercise, the risk factors of QRS widening were previous MI (p = 0.008), angina without previous MI (p = 0.009), structural heart disease (p = 0.001) and a bundle branch block at rest (p = 0.01). PA on exercise occurred in 7 patients. Structural heart disease (p = 0.04) and an impaired left ventricular ejection fraction (LVEF) [p = 0.02] were predictive variables of PA. All patients with left ventricular dysfunction and PA had a QRS widening with flecainide at rest ≥ 25%. The risk factors of QRS widening at rest and during exercise with flecainide were distinct from those of PA on exercise. In patients with an impaired LVEF, a flecainide-induced QRS widening of 25% at rest was the threshold value beyond which there was a high risk of PA during exercise. This study was retrospective and not a double-blind trial, therefore the results need to be corroborated in a prospectively designed trial.

Effect of atrioventricular synchronous pacing on cardiac output determined by CO2 rebreathing at constant submaximal exercise

This study compared cardiac output assessed by a noninvasive CO2 rebreathing method at identical submaximal exercise and heart rate response in patients undergoing DDD or VVI pacing. Our results did not show any hemodynamic superiority of AV synchronous pacing.