Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment.

BACKGROUND: Sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) are associated with shorter survival in patients with heart failure. A novel treatment method for this patient group is unilateral phrenic nerve stimulation by the remede® system (Respicardia Inc., Minnetonka, MN, USA), a transvenously implantable neurostimulation device, which has recently been studied in a large randomized, controlled trial. Previous literature has shown efficacy and safety of the treatment with this first-generation device, but hardly any data are available on long-term clinical parameters, the remede® device's battery lifetime, device exchangeability, lead position stability, surgical accessibility, and manageability. METHODS: We performed remede® device replacements in consecutive patients for battery depletion, and documented clinical parameters, longevity, operation procedure, complications, and difficulties. RESULTS: All patients were on neurostimulation treatment by phrenic nerve neurostimulation when device replacement became necessary. Apnea-hypopnea index (from 45 ± 4/h to 9 ± 4/h), oxygen-desaturation index (from 35 ± 7/h to 7 ± 6/h), and time spent with oxygen saturation of <90% (T < 90% from 5 ± 7% to 0 ± 0%) were improved and improvements remained constant throughout the 4-year follow-up. Mean battery life was 4.2 ± 0.2 years and mean replacement procedure time was 25 ± 5.1 minutes. Apart from conventional X-ray documentation of stable lead positions in a long-term setting, no radiation or contrast dye usage was needed and no major complications occurred. In addition, clinical exercise capacity and sleepiness symptoms improved. CONCLUSIONS: Novel remede® device shows sustained therapy efficacy and safety in terms of stable lead positions over 4 years. Long-term phrenic nerve neurostimulation therapy for central SDB/CSR appears feasible in a clinical routine setting.

Electrical Myostimulation (EMS) Improves Glucose Metabolism and Oxygen Uptake in Type 2 Diabetes Mellitus Patients--Results from the EMS Study.

AIMS: In patients with type 2 diabetes mellitus (T2DM) exercise training is recommended to improve glycemic control. Electrical myostimulation (EMS) of skeletal muscles is a new method to increase exercise capacity in patients with chronic heart failure. The aim of this study was to investigate the effects of EMS in T2DM on glucose metabolism, body composition, and exercise performance using a newly designed stimulation suit that involves trunk, leg, and arm muscles. SUBJECTS AND METHODS: Fifteen individuals (nine males; 61.7±14.8 years old) were trained for 10 weeks twice weekly for 20 min with EMS. Effects on glucose, glycosylated hemoglobin (HbA(1c)), oxygen consumption, and body composition were evaluated. RESULTS: There was a significant increase of oxygen uptake at the aerobic threshold from 12.3±0.8 to 13.3±0.7 mL/kg/min (P=0.003) and of maximal work capacity from 96.9±6.4 to 101.4±7.9 W (P=0.046), with a concomitant trend for improved maximal oxygen uptake (from 14.5±0.9 to 14.7±0.9 mL/kg/min [P=0.059]). Fasting blood glucose level decreased from 164.0±12.5 to 133.4±9.9 mg/dL (P=0.001), and HbA(1c) level decreased from 7.7±0.3% to 7.2±0.3% (P=0.041), whereas mean total weight (from 101.5±4.0 to 103.1±4.3 kg) and proportion of body fat (from 38.8±3.2% to 40.3±3.4%) remained statistically unchanged. CONCLUSIONS: EMS can improve glucose metabolism and functional performance in T2DM patients. These data suggest that EMS might emerge as a novel additional therapeutic mode of exercise training and might help patients to overcome their sedentary lifestyle.

Electrical myostimulation improves left ventricular function and peak oxygen consumption in patients with chronic heart failure: results from the exEMS study comparing different stimulation strategies.

AIMS: Electromyostimulation (EMS) of thigh and gluteal muscles is a strategy to increase exercise capacity in patients with chronic heart failure (CHF). The aim of this non-randomised pilot study was to investigate the effects of different stimulation strategies in CHF patients using a newly developed stimulation suit also involving trunk and arm muscles [extended electromyostimulation (exEMS)] in comparison with EMS therapy limited to gluteal and leg muscles (limEMS). METHODS: 60 individuals joined the EMS training programme. Stable CHF patients (NYHA class II-III) received either exEMS (22 patients, 15 males, mean age 59.95 ± 13.16 years) or limEMS (12 patients, 9 males, 62.75 ± 8.77 years). 26 participants served as healthy control group (CG) receiving exEMS. Training was performed for 10 weeks twice weekly for 20 min, and the level of daily activity remained unchanged. Effects on exercise capacity, oxygen uptake, left ventricular function (EF) and biomarkers were evaluated. RESULTS: There was a significant increase of oxygen uptake at aerobic threshold in all groups (exEMS: 13.7 ± 3.9-17.6 ± 5.1 ml/kg/min (+28.46%, p < 0.001); limEMS 13.6 ± 3.0-16.0 ± 3.8 ml/kg/min (+17.6 %, p = 0.003); CG 15.0 ± 4.9-17.0 ± 6.4 ml/kg/min (+13.3%, p = 0.005). LVEF increased from 38.3 ± 8.4 to 43.4 ± 8.8% (+13.3%, p = 0.001) (limEMS 37.1 ± 3.0-39.5 ± 5.3% (+6.5%, p = 0.27); CG 53.9 ± 6.7-53.7 ± 3.9% (-0.4%, p = 0.18). In CHF patients changes in oxygen consumption and LVEF were higher in the exEMS group than in limEMS (not significant). Maximal workload improved in healthy controls (p = 0.002) but not in CHF patients. CONCLUSION: Extended EMS can improve oxygen uptake and EF in CHF. In patients with limited EMS and in control patients without heart failure but extended EMS, oxygen uptake can be improved but EF is unaltered. For all groups, NT proBNP is unaffected by EMS.

[Electromyostimulation (EMS) in cardiac patients. Will EMS training be helpful in secondary prevention?]. / Elektromyostimulation (EMS) bei kardiologischen Patienten. Wird das EMS-Training bedeutsam für die Sekundärprävention?

BACKGROUND: Current guidelines concerning the treatment of patients with chronic congestive heart failure (CHF) include ergospirometry-directed dynamic exercises on a daily basis. Several prospective, randomized trials have confirmed its positive influence on clinical symptoms and prognosis of the disease. Patients with stable coronary artery disease (CAD) can benefit from a 27% reduction of mortality, as shown in meta-analyses of several studies. By contrast, patients with CHF have traditionally been discouraged from physical activities, which may have had detrimental consequences. They became even less able to participate in daily activities that in turn hastened the disease-driven atrophies of skeletal muscles. On the other hand, well-adjusted endurance training at 50-70% of maximum oxygen uptake was shown to improve overall fitness. In a recent metaanalysis, the mortality of patients with CHF was reduced by 35% by sports, and the rate of hospitalizations dropped by 28%. It is a well-perceived clinical problem that successful treatment is not possible without intensive guidance and a close therapeutic relationship. Being left in their routine situation and circumstances, the majority of patients cannot cope with the day-to-day challenge of an independent, active lifestyle. Among the primary reasons not to sustain physical activity are mental, psychological or social barriers. PATIENTS AND METHODS: The authors have begun, in a cohort of patients with CHF, a prospective pilot study to investigate the impact of, and attitude to, electromyostimulation (EMS). Unique features of this treatment include its passive nature that remains independent of mental attitude. RESULTS: An up to 96% increase of peak oxygen uptake at the anaerobic threshold could be shown (pre- vs. posttraining phase, VO(2at) 19.39 [+/- 5.3] ml/kg vs. 24.25 [+/- 6.34] ml/kg). The diastolic blood pressure decreased significantly. A 14% gain in muscle volume was observed, while overall body weight remained unchanged. All patients kept up the training until the conclusion of the study and found their overall fitness to be considerably improved. CONCLUSION: The results may indicate the enormous potential of EMS for the treatment of patients within the cardiologic arena, especially those with CHF.

Myocardial perfusion after one year of spinal cord stimulation in patients with refractory angina.

AIM: Spinal cord stimulation (SCS) is recommended for patients with coronary artery disease (CAD) and refractory angina. We used positron emission tomography (PET) to investigate the long-term effect of SCS on regional myocardial perfusion in patients suffering from angina pectoris refractory to medical treatment and without option for coronary intervention. PATIENTS, METHODS: We analyzed data of 44 patients with stable CAD (91% three vessel disease). At baseline, we determined coronary flow reserve (CFR) using 13N-ammonia-PET and myocardial viability with 18F-FDG. SCS was performed for one year (Medtronic Itrell III or Synergy, Düsseldorf, Germany). During follow-up, no cardiac interventions were necessary and no myocardial infarctions occurred. At one year follow-up, CFR was measured again. RESULTS: In the majority of patients (77%), SCS led to an improvement of clinical symptoms. CFR did not change significantly during follow-up. Subjective improvement did not correlate with an increase of CFR. CONCLUSIONS: Despite its clinical effect, SCS does not have a direct impact on CFR in patients with stable CAD. According to our results, the pain relief is not due to an improvement of the myocardial blood supply.

Management of angina pectoris: the role of spinal cord stimulation.

Progress in prevention as well as drug and interventional therapy has improved the prognosis of patients with cardiovascular disorders. Many patients at risk have advanced coronary artery disease (CAD), have had multiple coronary interventions, and present with significant co-morbidity. Despite adequate risk factor modulation and often several revascularization procedures, some of these patients still have refractory angina pectoris. Apart from advanced CAD and insufficient collateralization, the cause is often endothelial dysfunction. For this situation, one treatment option is neuromodulation. Controlled studies suggest that, in patients with chronic refractory angina pectoris, spinal cord stimulation (SCS) provides a relief from symptoms equivalent to that provided by surgical therapy, but with fewer complications and lower rehospitalization rates. SCS may result in significant long-term pain relief with improved quality of life. In patients with refractory angina undergoing SCS, some studies have shown not only a symptomatic improvement, but also a decrease in myocardial ischemia and an increase in coronary blood flow. Discussion is ongoing as to whether this is a direct effect on parasympathetic vascodilation or merely a secondary phenomenon resulting from increased physical activity following an improvement in clinical symptoms. Results from nuclear medical studies have sparked discussion about improved endothelial function and increased collateralization. SCS is a safe treatment option for patients with refractory angina pectoris, and its long-term effects are evident. It is a procedure without significant complications that is easy to tolerate. SCS does not interact with pacemakers, provided that strict bipolar right-ventricular sensing is used. Use in patients with implanted cardioverter defibrillators is under discussion. Individual testing is mandatory in order to assess optimal safety in each patient.

Myocardial sympathetic innervation in patients with symptomatic coronary artery disease: follow-up after 1 year with neurostimulation.

UNLABELLED: In both diabetic and nondiabetic patients, there is a loose correlation between coronary flow reserve (CFR) and sympathetic innervation in viable myocardial segments. The loose correlation implies that sympathetic innervation may be preserved even with major impairment of myocardial blood supply. In some patients, denervation is due to repetitive episodes of ischemia in areas with severely reduced CFR. We investigated the long-term effect of reduced CFR on myocardial sympathetic innervation in diabetic and nondiabetic patients with spinal cord stimulation. METHODS: We analyzed 23 patients (10 diabetic and 13 nondiabetic) with coronary artery disease and without known cardiac autonomic neuropathy. At baseline, we determined quantitative myocardial blood flow using (13)N-ammonia PET, myocardial viability using (18)F-FDG PET, and cardiac innervation using (11)C-hydroxyephedrine (HED) PET. At the 1-y follow-up we measured CFR and (11)C-HED retention. During follow-up, no cardiac intervention was performed and no myocardial infarction occurred. In all patients, spinal cord stimulation was performed for relief of angina. RESULTS: There was no significant difference in segmental (11)C-HED retention between baseline and follow-up in the whole patient group. In diabetic patients, as well as in segments with severely reduced CFR (<1.5), (11)C-HED retention showed a small but significant decrease (P<0.05). Linear regression of segmental (11)C-HED retention between baseline and follow-up was high (r(2)=0.81), confirming good reproducibility of the investigation on the one hand and little change in regional sympathetic innervation on the other hand. CONCLUSION: In patients with stable chronic coronary artery disease, sympathetic innervation of the myocardium is almost unchanged in both diabetic and nondiabetic patients in a 1-y follow-up. In myocardial segments with severely altered blood supply, a small but significant decrease in (11)C-HED retention most probably reflects ischemic neuronal damage. The prognostic relevance of sympathetic denervation in viable myocardium still has to be determined.

Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study.

OBJECTIVES: The purpose of this study was to investigate the efficacy safety of the novel cryoballoon device (Arctic Front, Cryocath, Quebec, Canada). BACKGROUND: Antral pulmonary vein (PV) ablation with radiofrequency energy is widely used as a strategy for catheter ablation of paroxysmal atrial fibrillation (PAF). A novel double lumen cryoballoon catheter was designed for circumferential pulmonary vein isolation (PVI) with the cryoablation technique. METHODS: We consecutively enrolled 346 patients with symptomatic, drug refractory paroxysmal (n = 293) or persistent (n = 53) atrial fibrillation (AF). In all patients, PVI of all targeted PVs was the therapeutic aim. The primary end points of this nonrandomized study were: 1) acute isolation rate of targeted PV; and 2) first electrocardiogram-documented recurrence of AF. The secondary end point was occurrence of PV stenosis or atrio-esophageal fistula. RESULTS: The 1,360 of 1,403 PVs (97%) were targeted with balloons or balloons in combination with the use of Freezor Max (Cryocath). We found that ablation with the cryoballoon resulted in maintenance of sinus rhythm in 74% of patients with PAF and 42% of patients with persistent AF. No PV narrowing occurred. The most frequent complication was right phrenic nerve palsy observed during cryoballoon ablation at the right superior PV. CONCLUSIONS: Pulmonary vein isolation with a new cryoballoon technique is feasible. Sinus rhythm can be maintained in the majority of patients with PAF by circumferential PVI using a cryoballoon ablation system. Cryoablation was less effective in patients with persistent AF than in patients with PAF.