Phrenic nerve stimulation in patients with central sleep apnea: a single­center experience from pilot and pivotal trials evaluating the remede System.

BACKGROUND: Patients with central sleep apnea (CSA) have recently been shown to have improved sleep metrics and quality of life (QoL) with phrenic nerve stimulation (PNS). AIMS: The aim of this study was to report the results of a partnership between cardiology, sleep medicine, and electrophysiology in a single clinical center as well as the enrollment, implantation, and follow­up experience demonstrating both the safety and efficacy of PNS. METHODS: This analysis included data from the pilot and pivotal trials investigating the effect of PNS using an implantable transvenous system in patients with CSA. We present our experience and data on the enrollment processes, implantation feasibility and safety, sleep indices, and QoL at 6 and 12 months of follow­up. RESULTS: Between June 2010 and May 2015, cardiology patients were prescreened and 588 of them were sent for in­home sleep test. Ninety­six patients were referred for polysomnographic studies, and 33 were enrolled and had an implant attempt, with 31 successfully receiving an implant. The apnea-hypopnea index was reduced in the pilot trial (mean [SD] of 48.7 [15.5] events/h to 22.5 [13.2] events/h; P <0.001) and in the pivotal trial (mean [SD] of 48.3 [18.8] events/h to 26.0 [21.9] events/h; P <0.001). Improvement in QoL was also observed. CONCLUSIONS: We showed that PNS improved sleep metrics and QoL in patients with CSA, which is a result of multiple factors, including a comprehensive coordination between cardiology, sleep medicine, and electrophysiology. This ensures appropriate patient identification leading to safe implantation and full patient compliance during follow­up visits.

Impact of an interatrial shunt device on survival and heart failure hospitalization in patients with preserved ejection fraction.

AIMS: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short-term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH). METHODS AND RESULTS: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta-analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post-IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta-analysis Global Group in Chronic Heart Failure score-predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD-treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan-Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload-corrected exercise pulmonary capillary wedge pressure at the 6 months post-IASD study were associated with HFH. CONCLUSIONS: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large-scale ongoing randomized studies are required to confirm the potential benefit of this therapy.

High-Throughput Preparation of Metal Oxide Nanocrystals by Cathodic Corrosion and Their Use as Active Photocatalysts.

Nanoparticle metal oxide photocatalysts are attractive because of their increased reactivity and ease of processing into versatile electrode formats; however, their preparation is cumbersome. We report on the rapid bulk synthesis of photocatalytic nanoparticles with homogeneous shape and size via the cathodic corrosion method, a simple electrochemical approach applied for the first time to the versatile preparation of complex metal oxides. Nanoparticles consisting of tungsten oxide (H2WO4) nanoplates, titanium oxide (TiO2) nanowires, and symmetric star-shaped bismuth vanadate (BiVO4) were prepared conveniently using tungsten, titanium, and vanadium wires as a starting material. Each of the particles were extremely rapid to produce, taking only 2-3 min to etch 2.5 mm of metal wire into a colloidal dispersion of photoactive materials. All crystalline H2WO4 and BiVO4 particles and amorphous TiO2 were photoelectrochemically active toward the water oxidation reaction. Additionally, the BiVO4 particles showed enhanced photocurrent in the visible region toward the oxidation of a sacrificial sulfite reagent. This synthetic method provides an inexpensive alternative to conventional fabrication techniques and is potentially applicable to a wide variety of metal oxides, making the rapid fabrication of active photocatalysts with controlled crystallinity more efficient.

InterAtrial Shunt Device (IASD®) implantation - a novel treatment method for heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a condition with complex pathophysiology and clinical profile. No treatment has been proven to reduce mortality or reduce morbidity in a meaningful way. In the era of percutaneous cardiac interventions, a novel method of reducing left atrial pressure by creating an iatrogenic interatrial shunt has been introduced. We present a report of implantation of InterAtrial Shunt Device (IASD®) in three consecutive patients.

One-Year Outcomes After Transcatheter Insertion of an Interatrial Shunt Device for the Management of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. METHODS AND RESULTS: Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II-IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. CONCLUSIONS: These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913613.

Transvenous stimulation of the phrenic nerve for the treatment of central sleep apnoea: 12 months' experience with the remede® System.

AIMS: Patients with central sleep apnoea (CSA) often have poor quality of life and are at increased risk of morbidity and mortality. This study sought to evaluate the 12-month clinical outcomes of patients with CSA treated with unilateral transvenous phrenic nerve stimulation in the prospective, multicentre, non-randomized remede® System pilot study. METHODS AND RESULTS: Forty-seven patients with CSA were treated with the remede® System (Respicardia Inc., Minnetonka, MN, USA) for a minimum of 3 months. Sleep-disordered breathing parameters were evaluated by polysomnography (PSG) at 3, 6, and 12-month follow-up. Sleep symptoms and quality of life were also evaluated. Forty-one patients completed all follow-up PSGs and were included in the analysis. At 12 months, there was sustained improvement compared with baseline in the apnoea-hypopnoea index (49.9 ± 15.1 vs. 27.5 ± 18.3 events/h, P < 0.001) and central apnoea index (28.2 ± 15.0 vs. 6.0 ± 9.2 events/h, P < 0.001). Sustained improvement in the oxygen desaturation index (46.1 ± 19.1 vs. 26.9 ± 18.0 events/h, P < 0.001), rapid eye movement sleep (11.4 ± 6.1% vs. 17.1 ± 8.0%, P < 0.001), and sleep efficiency (69.3 ± 16.9% vs. 75.6 ± 17.1%, P = 0.024) were also observed. There were also continued favourable effects on sleepiness and quality of life. Three deaths unrelated to remede® System therapy and five serious adverse events occurred over 12 months of follow-up. CONCLUSION: The present study demonstrates that in patients with CSA, unilateral transvenous phrenic nerve stimulation is associated with sustained improvement in key sleep parameters, sleep symptoms, and quality of life over 12 months of follow-up.

Phrenic nerve stimulation for the treatment of central sleep apnea.

OBJECTIVES: The aim of this study was to evaluate chronic, transvenous, unilateral phrenic nerve stimulation to treat central sleep apnea (CSA) in a prospective, multicenter, nonrandomized study. BACKGROUND: CSA occurs predominantly in patients with heart failure and increases the risk for morbidity and mortality. Established therapies for CSA are lacking, and those available are limited by poor patient adherence. METHODS: Fifty-seven patients with CSA underwent baseline polysomnography followed by transvenous phrenic nerve stimulation system implantation and follow-up. Feasibility was assessed by implantation success rate and therapy delivery. Safety was evaluated by monitoring of device- and procedure-related adverse events. Efficacy was evaluated by changes in the apnea-hypopnea index at 3 months. Quality of life at 6 months was evaluated using a sleepiness questionnaire, patient global assessment, and, in patients with heart failure at baseline, the Minnesota Living With Heart Failure Questionnaire. RESULTS: The study met its primary end point, demonstrating a 55% reduction in apnea-hypopnea index from baseline to 3 months (49.5 ± 14.6 episodes/h vs. 22.4 ± 13.6 episodes/h of sleep; p < 0.0001; 95% confidence interval for change: -32.3 to -21.9). Central apnea index, oxygenation, and arousals significantly improved. Favorable effects on quality of life and sleepiness were noted. In patients with heart failure, the Minnesota Living With Heart Failure Questionnaire score significantly improved. Device- or procedure-related serious adverse events occurred in 26% of patients through 6 months post therapy initiation, predominantly due to lead repositioning early in the study. Therapy was well tolerated. Efficacy was maintained at 6 months. CONCLUSIONS: Transvenous, unilateral phrenic nerve stimulation appears safe and effective for treating CSA. These findings should be confirmed in a prospective, randomized, controlled trial. (Chronic Evaluation of Respicardia Therapy; NCT01124370).

Coronary collateral circulation is less developed when ischaemic heart disease coexists with diabetes.

BACKGROUND: The extent of myocardial ischaemia and the magnitude of systolic function impairment following myocardial infarction (MI) depend to a large degree on the performance of coronary collateral circulation. Endothelial function is altered in several disorders, including diabetes. An impaired development of coronary collateral circulation may be a factor responsible for post-MI complications in patients with diabetes. AIM: To compare the degree of coronary collateral circulation development between patients with advanced ischaemic heart disease (IHD), with or without diabetes. METHODS: The study group consisted of 70 consecutive patients with diabetes who underwent coronary angiography between September 1998 and December 1999 and had total occlusion of at least one of the main coronary vessels. The control group consisted of 70 age-, gender, and MI history-matched non-diabetic patients. Coronary collateral circulation was assessed using the collateral score (CS). RESULTS: Patients with diabetes had less developed coronary collateral circulation than the patients without diabetes which was reflected by a significantly lower CS value - 1.47+/-1.56 vs 2.03+/-1.81; p < 0.05. No significant relationship was found between CS and age, gender, body mass index, history of MI or the presence of IHD risk factors. There was a significant association between the number of vessels with lesions and CS: r=0.40, p=0.0006 in the control group and r=0.42, p=0.0003 in patients with diabetes. The CS values in patients with single-, two- or three-vessel disease were 1.27+/-1.34, 2.38+/-1.85 and 2.98+/-2.07 in the control group, and 0.70+/-0.90, 1.10+/-1.30 and 2.23+/-1.76 in patients with diabetes, respectively. A multivariate analysis revealed that the presence of diabetes (t=-3.04, p=0.003) and the number of affected vessels (t=5.23, p=0.0001) were independently related to the CS values. CONCLUSIONS: Patients with IHD and diabetes have less developed coronary collateral circulation than IHD patients without diabetes, regardless of the extent of coronary lesions. Patients with diabetes who undergo coronary angiography, have more advanced coronary atherosclerotic lesions than patients without diabetes.