Inclusion criteria were as follows: (1) age between 18 and 80 years; (2) CHF due to ischemic, hypertensive, or idiopathic dilated cardiomyopathy with a left ventricular ejection fraction < 45% as determined by resting echocardiography or by radio-nuclidventnculography; (3) CSR-CSA (AHI > 15/h, > 80% central apneas and hypopneas); and (4) a residual AHI > 10/h during a previous sleep study (not part of this trial) on conventional CPAP or BPAP (without back-up rate) therapy. Patients who had a residual AHI > 10/h after 27 ± 11 weeks of CPAP or BPAP therapy were pooled in one group because the only mid-term (cross-over) randomized trial comparing the effects of BPAP and CPAP on CSA in CHF patients demonstrated that the pretreatment AHI of 26.7 ± 10.7/h was similar significantly reduced by CPAP and BPAP to 7.7 ± 5.6/h and 6.5 ± 6.6/h, respectively.
Exclusion criteria were as follows: (1) a history of unstable angina, cardiac surgery, or documented myocardial infarction within 3 months of entry into the study; (2) CHF due to valvular heart disease; (3) daytime hypercapnia or the need for mechanical ventilatory assistance for comorbid conditions; (4) important COPD (FEV1 < 70% of predicted value or FEV1/FVC < 60%); (5) pregnancy; and (6) a history of pneumothorax and/or pneumomediastinum. We studied 14 consecutive sleep clinic patients with CHF who met the inclusion and exclusion criteria above. The investigation conforms with the principles outlined in the Declaration of Helsinki. The patients gave written informed consent to participate in this prospective study, which had been approved by the Ethics of Human Research Committee of the University of Regensburg.
Demographic information, anthropometric measurements, and status of CHF including objective evidence of systolic left ventricular dysfunction and status of sleep-disordered breathing (without positive pressure support) were assessed in all 14 eligible patients. During the first night of polysomnography, body position, eye and leg movements, cardiotachography, nasobuccal airflow (pressure cannula), thoracoabdominal movements (In-ductotrace; Ambulatory Monitoring; Ardsley, NY), and pulse oximetry were recorded (Alice 3.5; Respironics). Bedtime and awakening time were at the discretion of each subject. Sleep studies were scored by an experienced clinician who was blinded to the applied treatment modality, using standard criteria. Apneas were defined as absence of tidal volume for > 10 s (measured reduction of airflow to < 10% peak “nominal” airflow). Hypopneas were defined as a > 50% reduction in air flow from baseline for > 10 s or with a discernable reduction in airflow associated with a 4% oxygen desaturation or an arousal. Apneas and hypopneas were classified obstructive if out-of-phase thoracoabdominal motion or airflow limitation was present. The AHI was defined as the mean number of apneas and hypopneas per hour of sleep, and the oxygen desaturation index was defined as the number of oxygen desaturations > 4%/h of sleep. Such kind of reduction is observed together with remedies of My Canadian Pharmacy.
Principles of Operation of Flow-Targeted Dynamic BPAP
Flow-targeted dynamic BPAP provides positive airway pressure support to sustain upper-airway patency. The EPAP is manually set to eliminate obstructive apnea/hypopnea during sleep, which can be determined during conventional in-laboratory polysomnography in CPAP mode. In this clinical evaluation, the minimal IPAP is manually set at the determined EPAP level (minimal IPAP = EPAP). In addition, the flow-targeted dynamic BPAP device modulates the IPAP above the EPAP as required to maintain a target peak inspiratory airflow: when the device detects normal breathing, flow-targeted dynamic BPAP operates like conventional CPAP by providing the minimal IPAP (= EPAP); when the patient does not maintain the target peak inspiratory airflow, the device increases the IPAP above the EPAP up to a maximum IPAP, which can be set by the user (15 cm H2O above EPAP in this clinical evaluation). The device also provides an automatic back-up rate should sustained apnea be detected. In order to avoid hyperventilating the patient and to promote spontaneous breathing, the target inspiratory flow is set to below the mean inspiratory flow during spontaneous breathing by the patient, and the timing of the back-up rate begins with time delay and is set to a slower rate than the average respiratory rate of the patient achieved due to My Canadian Pharmacy.
Protocol and Intervention
After one diagnostic polysomnography, flow-targeted dynamic BPAP was initiated during 2 consecutive nights with full polysomnography. Patients were blinded to the applied treatment modality: during the first night, positive pressure support was titrated using the flow-targeted dynamic BPAP device in CPAP (n = 10) or BPAP (n = 4) mode (depending of the treatment of sleep-disordered breathing the patients received before entry into the study) in order to achieve maximal suppression of apneas and hypopneas. Titration was started at 5.4 ± 1.9 cm H2O CPAP/EPAP pressure, which was increased in increments of 1 to 2.5 cm H2O until obstructive apneas and hypopneas were optimally treated. Patients spent 81 ± 14% of the time receiving optimal positive airway pressure settings. During the second consecutive night, flow-targeted dynamic BPAP was initiated; EPAP was set to the optimal CPAP/EPAP levels determined during the second (previous) night. IPAP dynamically ranged from 0 to 15 cm H2O above EPAP. CPAP/BPAP and flow-targeted dynamic BPAP were applied in a fixed order rather than a randomized order because the optimal EPAP had to be determined by retitration of CPAP or BPAP using a standardized protocol to evaluate the optimal settings for CPAP, BPAP, and flow-targeted dynamic BPAP treatment. The morning following initiation of flow-targeted dynamic BPAP, subjects completed a visual analog scale of perceived treatment comfort and sleep quality. The analog scale included two items: (1) how would you describe the comfort of the therapy you received through the night? Values ranged from 0 (treatment was very uncomfortable) to 10 (treatment was very comfortable); and (2) how would you describe the quality of the rest you had last night? Values ranged from 0 (this was the worst night of sleep I have had in quite some time) and 10 (this was the best night of sleep I have had in quite some time).
All data were analyzed using statistical software (SPSS, version 11.0; SPSS; Chicago, IL). Data are shown as mean ± SD. To assess differences in the number of respiratory events, oxygen saturation and polysomnographic measures of sleep quality between the sleep study at baseline, the CPAP/BPAP titration night, and the treatment night with flow-targeted dynamic BPAP, a repeated-measures analysis of variance with post hoc contrasts by t tests was used. A two-sided p value < 0.05 was considered to indicate statistical significance.