Modeling Patient-Specific Desaturation Patterns in Sleep Apnea.

OBJECTIVE: The physiological mechanisms involved in cardio-respiratory responses to sleep apnea events are not yet fully elucidated. A model-based approach is proposed to analyse the acute desaturation response to obstructive apneas. METHODS: An integrated model of cardio-respiratory interactions was proposed and parameters were identified, using an evolutionary algorithm, on a database composed of 107 obstructive apneas acquired from 10 patients (HYPNOS clinical study). Unsupervised clustering was applied to the identified parameters in order to characterize the phenotype of each response to obstructive apneas. RESULTS: A close match was observed between simulated oxygen saturation ( SaO2) and experimental SaO2 in all identifications (median RMSE = 1.3892 %). Two clusters of parameters, associated with different dynamics related to sleep apnea and periodic breathing were obtained. CONCLUSION AND SIGNIFICANCE: The proposed patient and event-specific model-based analysis provides understanding on specific desaturation patterns, consequent to apnea events, with potential applications for personalized diagnosis and treatment.

Kinesthetic stimulation for obstructive sleep apnea syndrome: An "on-off" proof of concept trial.

Obstructive sleep apnea (OSA) occurs when the upper airway narrows or collapses due to the loss of upper airway muscle activation at sleep onset. This study investigated the effectiveness of triggered kinesthetic stimulation in patients with OSA. This proof-of-concept, open-label, multicenter prospective study was conducted on 24 patients with severe OSA. During a one night evaluation, kinesthetic stimulation was intermittently delivered in 30 minute periods. The duration of apneas and hypopneas during Stim on and Stim off periods were compared. Five hospital-based university centers in France participated. Sleep studies were evaluated by a single scorer at a core laboratory (CHU Grenoble). Results show that during the Stim on phases, statistically significant decreases in durations of apneas and hypopneas were observed in 56% and 46% of patients, respectively. Overall, 75% of patients showed an improvement in apneas or hypopneas durations. The mean reduction in durations for patients with a significant decrease was 4.86 seconds for apneas and 6.00 seconds for hypopneas. This proof of concept study is the first to identify kinesthetic stimulation as a potentially effective therapy for OSA. These data justify evaluation in a controlled study.

Analysis of endocardial acceleration during intraoperative optimization of cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is the therapy of choice for selected patients suffering from drug-refractory congestive heart failure and presenting an interventricular desynchronization. CRT is delivered by an implantable biventricular pacemaker, which stimulates the right atrium and both ventricles at specific timings. The optimization and personalization of this therapy requires to quantify both the electrical and the mechanical cardiac functions during the intraoperative and postoperative phases. The objective of this paper is to evaluate the feasibility of the calculation of features extracted from endocardial acceleration (EA) signals and the potential utility of these features for the intraoperative optimization of CRT. Endocardial intraoperative data from one patient are analyzed for 33 different pacing configurations, including changes in the atrio-ventricular and inter-ventricular delays and different ventricular stimulation sites. The main EA features are extracted for each pacing configuration and analyzed so as to estimate the intra-configuration and inter-configuration variability. Results show the feasibility of the proposed approach and suggest the potential utility of EA for intraoperative monitoring of the cardiac function and defining optimal, adaptive pacing configurations.

Endocardial acceleration (sonR) vs. ultrasound-derived time intervals in recipients of cardiac resynchronization therapy systems.

AIMS: Optimization of cardiac resynchronization therapy (CRT) requires the gathering of cardiac functional information. An accurate timing of the phases of the cardiac cycle is key in the optimization process. METHODS AND RESULTS: We compared Doppler echocardiography to an automated system, based on the recording of sonR (formerly endocardial acceleration), in the detection of mitral and aortic valves closures and measurements of the duration of systole and diastole. We prospectively studied, under various conditions of cardiac stimulation, 75 recipients of CRT systems (69% men), whose mean age was 72 ± 9.2 years, left ventricular ejection fraction 35 ± 11%, baseline QRS duration 154 ± 29 ms, and New York Heart Association functional class 3.0 ± 0.7. We simultaneously recorded (i) sonR, detected by a non-invasive piezoelectric micro-accelerometer sensor clipped onto an electrode located in the parasternal region, (b) electrocardiogram, and (c) Doppler audio signals, using a multichannel data acquisition and analysis system. The correlation between timing of mitral and aortic valve closure by sonR vs. Doppler signals was examined by linear regression analysis. Correlation coefficients and the average absolute error were calculated. A concordance in the timing of the mitral (r = 0.86, error = 9.7 ms) and aortic (r = 0.93, error = 9.7 ms) valves closure was observed between the two methods in 94% of patients. Similarly, sonR and the Doppler-derived measurements of systolic (r = 0.85, error = 13.4 ms) and diastolic (r = 0.99, error = 12 ms) interval durations were concordant in 80% of patients. CONCLUSION: A high concordance was found between sonR and the cardiac ultrasound in the timings of aortic and mitral valve closures and in the estimation of systolic and diastolic intervals durations. These observations suggest that sonR could be used to monitor cardiac function and adaptively optimize CRT systems.

Use of a new cardiac pacing mode designed to eliminate unnecessary ventricular pacing.

AIMS: To examine the performance of AAIsafeR2, a new pacing mode to minimize the cumulative proportion of ventricular pacing in patients who do not need regular ventricular support. METHODS AND RESULTS: The safety of AAIsafeR2 was examined in 123 recipients (73 +/- 12 years old, 51% men) of dual chamber pacemakers implanted for sinus node dysfunction, paroxysmal AV block or the bradycardia-tachycardia syndrome. Data were collected from pacemaker diagnostics, and the first 43 patients underwent 24-h Holter recordings before being discharged from the hospital with AAIsafeR2 activated. No adverse event related to AAIsafeR2 was observed. All ventricular pauses detected on Holter tapes triggered immediate back-up ventricular pacing. Appropriate switches to DDD occurred in 97 of 123 patients. In 69 of 123 devices (56%) switches to DDD were non-sustained, and the average % ventricular pacing in this group was 0.2+/-0.5%. CONCLUSION: AAIsafeR2 mode seems to be safe and reliable in patients with infrequent slowing or pauses in ventricular activity, while maintaining ventricular pacing below 1%.

A new dual-chamber pacing mode to minimize ventricular pacing.

Despite the low long-term incidence of high-degree atrioventricular (AV) block and the known negative effects of ventricular pacing, programming of the AAI mode in patients with sinus node dysfunction (SND) remains exceptional. A new pacing mode was, therefore, designed to combine the advantages of AAI with the safety of DDD pacing. AAIsafeR behaves like the AAI mode in absence of AV block. First- and second-degree AV blocks are tolerated up to a predetermined, programmable limit, and conversion to DDD takes place in case of high-degree AV block. From DDD, the device may switch back to AAI, provided AV conduction has returned. The safety of AAIsafeR was examined in 43 recipients (70 +/- 12-year old, 24 men) of dual chamber pacemakers implanted for SND or paroxysmal AV block. All patients underwent 24-hour ambulatory electrocardiographic recordings before hospital discharge and at 1 month of follow-up with the AAIsafeR mode activated. No AAIsafeR-related adverse event was observed. At 1 month, the device was functioning in AAIsafeR in 28 patients (65%), and the mean rate of ventricular pacing was 0.2%+/- 0.4%. Appropriate switches to DDD occurred in 15 patients (35%) for frequent, unexpected AV block. AAIsafeR mode was safe and preserved ventricular function during paroxysmal AV block, while maintaining a very low rate of ventricular pacing. The performance of this new pacing mode in the prevention of atrial fibrillation will be examined in a large, controlled study.

Comparison of the cardiopulmonary response to exercise in recipients of dual sensor DDDR pacemakers Versus a Healthy control group.

The authors previously have shown in healthy subjects that age related loss of muscular strength did not alter the chronotropic response during treadmill exercise, whether with sudden onset of effort, as in the chronotropic assessment exercise protocol (CAEP) or more gradual effort as in the Harbor exercise protocol. This study was performed to verify that in patients suffering from chronotropic insufficiency, and in absence of other effort-limiting disorders, "physiologic" pacing enables a cardiorespiratory response comparable to that of age-matched healthy subjects. Furthermore, the aim of the study was to confirm that the response of a new dual sensor-based pacing system was properly adapted to the metabolic demand, whether during CAEP or during Harbor test, by subjecting patients to both protocols. All study participants were able to undergo treadmill exercise testing, had normal cardiopulmonary function tests at rest, and no cardiac, muscular, or pulmonary disease. A healthy group (control) included 16 subjects (mean age 70.4 +/- 3.9 years), and the test group (pacemaker [PM] included 9 subjects (mean age 67.1 +/- 10.8 years) permanently paced for isolated chronotropic insufficiency with a dual sensor pacing system. All subjects underwent CAEP and Harbor tests with measurements of gas exchange, 24 hours apart, in randomized order. All subjects reached an appropriate level of exercise, as expressed by mean lactate plasma concentrations, which were slightly higher in the control than the PM group during CAEP (4.9 +/- 1.9 vs 3.7 +/- 1.9 mmol/L, NS) and Harbor (5.3 +/- 1.9 vs. 3.8 +/- 1.8 mmol/L, P < 0.05) tests. No statistical difference was observed in VO2 and VE at peak exercise between the two groups during either test. In the PM group, heart rate at peak exercise and metabolic reserve slope were higher during the CAEP than the Harbor protocol. These two measurements were significantly lower than in the control group. The PM group also had lower plasma lactate concentrations and dyspnea/fatigue scores. The Harbor test seems less suitable than the CAEP test to study the chronotropic response of pacemakers with dual sensors during exercise. A high performance of the new dual sensor-based pulse generator was confirmed in this physically fit patient population, whose peak heart rate was considerably higher than in other similar studies.