Improving Nocturnal Hypoxemic Burden with Transvenous Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
Authors: Oldenburg, Olaf; Costanzo, Maria Rosa; Germany, Robin; McKane, Scott; Meyer, Timothy E.; Fox, Henrik
Abstract
Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remede System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea-hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea-hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea-hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden.
t(1)-Noise eliminated dipolar heteronuclear multiple-quantum coherence solid-state NMR spectroscopy
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
Authors: Venkatesh, Amrit; Luan, Xuechen; Perras, Frederic A.; Hung, Ivan; Huang, Wenyu; Rossini, Aaron J.
Abstract
Heteronuclear correlation (HETCOR) spectroscopy is one of the key tools in the arsenal of the solid-state NMR spectroscopist to probe chemical and spatial proximities between two different nuclei and enhance spectral resolution. Dipolar heteronuclear multiple-quantum coherence (D-HMQC) is a powerful technique that can be potentially utilized to obtain(1)H detected 2D HETCOR solid-state NMR spectra of any NMR active nucleus. A long-standing problem in(1)H detected D-HMQC solid-state NMR experiments is the presence oft(1)-noise which reduces sensitivity and impedes spectral interpretation. In this contribution, we describe novel pulse sequences, termedt(1)-noise eliminated (TONE) D-HMQC, that minimizet(1)-noise and can provide higher sensitivity and resolution than conventional D-HMQC. Monte-Carlo and numerical simulations confirm thatt(1)-noise in conventional D-HMQC primarily occurs because random MAS frequency fluctuations cause variations in the NMR signal amplitude from scan to scan, leading to imperfect cancellation of uncorrelated signals by phase cycling. The TONE D-HMQC sequence uses(1)H pi-pulses to refocus the evolution of(1)H CSA across each SR421 recoupling block, improving the stability of the pulse sequence to random MAS frequency fluctuations. The(1)H refocusing pulses also restore the orthogonality of in-phase and anti-phase magnetization for all crystallite orientations at the end of each recoupling block, enabling the use of 90 degrees flip-back or LG spin-lock trim pulses to reduce the intensity of uncorrelated signals. We demonstrate the application of these methods to acquire(1)H detected 2D(1)H{Cl-35} and(1)H{C-13} HETCOR spectra of histidine center dot HCl center dot H2O with reducedt(1)-noise. To show generality, we also apply these methods to obtain 2D(1)H{O-17} spectra of 20%-O-17 fmoc-alanine and for the first time at natural abundance, 2D(1)H{Mg-25} HETCOR spectra of magnesium hydroxide. The TONE D-HMQC sequences are also used to probe(1)H-Mg-25 and(1)H-Al-27 proximities in Mg-Al layered double hydroxides and confirm the even mixing of Mg and Al in these materials.