Performance of conventional and enhanced adaptive servoventilation (ASV) in heart failure patients with central sleep apnea who have adapted to conventional ASV.

PURPOSE: Adaptive servo-ventilation (ASV) is a positive pressure ventilator support system to normalize ventilation in patients with Cheyne-Stokes respiration (CSR). The latest generation enhanced ASV device (PaceWave; ResMed) has a new feature--auto-adjustment of EPAP. This study tested the hypothesis that enhanced ASV with auto-adjustment of EPAP (PaceWave) is non-inferior to conventional ASV (AutoSetCS). METHODS: This prospective, randomized, crossover, single-center study enrolled adult patients with stable heart failure (HF) and moderate-to-severe sleep-disordered breathing (SDB) who had been receiving conventional ASV therapy for at least 4 weeks. Patients received conventional ASV for one night and enhanced ASV on another night. Support settings for the two ASV devices were similar, with fixed expiratory positive airway pressure (EPAP) set to between 4 and 10 cm H2O and variable EPAP set to between 4 and 15 cm H2O. Full polysomnography was performed during ASV therapy on both nights. Endpoints were the number of nocturnal respiratory events and oxygen desaturations, and changes in blood pressure (BP). RESULTS: Levels of EPAP were comparable during the use of enhanced and conventional ASV, but minimum and maximum inspiratory pressure support values were significantly higher with the PaceWave device. All measures of apnea and hypopnea, and oxygen saturation, were significantly improved during ASV therapy with either device. There were no significant changes in BP or heart rate. CONCLUSIONS: Enhanced ASV is non-inferior to ASV with fixed EPAP in patients with chronic HF and CSR, with a trend towards better control of respiratory events.

Obstructive sleep apnoea: longer respiratory event lengths in patients with heart failure.

This study investigated the effect of heart failure on respiratory patterns in patients with obstructive sleep apnoea (OSA). 39 patients with established OSA (apnoea/hypopnoea index (AHI) >10 events·h(-1)) and either with heart failure (New York Heart Association (NYHA) class II and III, left ventricular-ejection fraction (LVEF) ≤40%; n=26, age mean ± SD 67 ± 9 years) or without heart failure (LVEF ≥50%, N-terminal pro-brain naturic peptide <400 pg·mL(-1); n=13, age 73 ± 6 years) underwent simultaneous right- and left-heart catheterisation within 12 h of cardiorespiratory polygraphy recording. Respiratory patterns of OSA were significantly longer in OSA patients with heart failure versus without heart failure, including mean ± SD cycle length (46.0 ± 10.0 versus 37.8 ± 10.6 s; p=0.024), ventilation length (25.4 ± 6.3 versus 21.3 ± 7.1 s; p=0.044), apnoea length (20.5 ± 4.9 versus 16.5 ± 3.9 s; p=0.013), time-to-peak ventilation (10.6 ± 3.0 versus 8.3 ± 2.5 sc; p=0.021) and circulatory delay (28.5 ± 7.5 versus 22.6 ± 3.7 s; p=0.005). Positive and robust correlations were found between some of these parameters and the degree of congestion in heart failure: cycle length (r=0.53; p=0.006), ventilation length (r=0.55; p=0.004) and time-to-peak ventilation (r=0.47; p=0.015) all increased with a rise in pulmonary capillary wedge pressure. Respiratory patterns in OSA appear to be dependent on cardiac function, with an increase in event lengths as cardiac function decreases. In patients with heart failure, some of these events correlate with the degree of pulmonary congestion.

Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes.

BACKGROUND: Intron gains reportedly are very rare during evolution of vertebrates, and the mechanisms underlying their creation are largely unknown. Previous investigations have shown that, during metazoan radiation, the exon-intron patterns of serpin superfamily genes were subject to massive changes, in contrast to many other genes. RESULTS: Here we investigated intron dynamics in the serpin superfamily in lineages pre- and postdating the split of vertebrates. Multiple intron gains were detected in a group of ray-finned fishes, once the canonical groups of vertebrate serpins had been established. In two genes, co-occurrence of non-standard introns was observed, implying that intron gains in vertebrates may even happen concomitantly or in a rapidly consecutive manner. DNA breakage/repair processes associated with genome compaction are introduced as a novel factor potentially favoring intron gain, since all non-canonical introns were found in a lineage of ray-finned fishes that experienced genomic downsizing. CONCLUSION: Multiple intron acquisitions were identified in serpin genes of a lineage of ray-finned fishes, but not in any other vertebrates, suggesting that insertion rates for introns may be episodically increased. The co-occurrence of non-standard introns within the same gene discloses the possibility that introns may be gained simultaneously. The sequences flanking the intron insertion points correspond to the proto-splice site consensus sequence MAG upward arrowN, previously proposed to serve as intron insertion site. The association of intron gains in the serpin superfamily with a group of fishes that underwent genome compaction may indicate that DNA breakage/repair processes might foster intron birth.