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    Vagal stimulation in heart failure

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    Heart failure (HF) is accompanied by an autonomic imbalance that is almost always characterized by both increased sympathetic activity and withdrawal of vagal activity. Experimentally, vagal stimulation has been shown to exert profound antiarrhythmic activity and to improve cardiac function and survival in HF models. A open-label pilot clinical study in 32 patients with chronic HF has shown safety and tolerability of chronic vagal stimulation associated with subjective (improved quality of life and 6-min walk test) and objective improvements (reduced left ventricular systolic volumes and improved left ventricular ejection fraction). Three larger clinical studies, including a phase III trial are currently ongoing and will evaluate the clinical role of this new approach

    Vagus nerve stimulation: A new approach to reduce heart failure

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    Autonomic imbalance with increased adrenergic and reduced parasympathetic activity is involved in the development and progress of heart failure (HF). Experimental data have demonstrated that stimulation of the vagus nerve is able to reverse ventricular remodeling of the failing heart. There is also evidence that increasing parasympathetic activity may stimulate the production of nitric oxide, and reduce the devastating inflammatory process involved in HF. Vagus nerve stimulation (VNS) has been successfully applied for many years to treat drug resistant epilepsy. The first study of right vagus stimulation in patients with advance HF has proven the feasibility and safety of this new approach. Long term follow-up of increased vagal tone over 12 months with a specially designed stimulating system (CardioFit, BioControl, Yehud, Israel) has demonstrated that symptoms of HF can be significantly diminished, left ventricular ejection fraction increased, and ventricular volumes reduced. These recently published data are very promising and may offer another approach for patients with advanced HF already treated with optimal medical therapy. A prospective randomized trial with a larger patient cohort is needed to confirm these beneficial results of VNS

    Vagus nerve stimulation: from pre-clinical to clinical application: challenges and future directions.

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    Vagus nerve stimulation was performed experimentally for the first time more than 150 years ago. In the 1980s and 1990s, vagus nerve stimulation was shown, both in the anesthetized and in the conscious animal, to exert marked antiarrhythmic effects, particularly during acute myocardial ischemia. There is a strong rationale for a beneficial effect of augmented vagal activity in the setting of chronic heart failure. Studies in experimental models of heart failure showed that chronic vagus nerve stimulation exerts beneficial effects on left ventricular function and on survival. Vagus nerve stimulation is approved in man for refractory epilepsy and depression. The first-in-man study performed in 32 patients with chronic heart failure suggests that vagus nerve stimulation was safe and well tolerated. Six months of open-label treatment was associated with significant improvements (P < 0.001) in NYHA class, quality of life, 6-min walk test, LV ejection fraction (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. Mechanisms of action may include the following: heart rate, anti-adrenergic, anti-apoptotic, and anti-inflammatory effects as well as an increase in nitric oxide. Controlled clinical trials will start soon to assess whether vagus nerve stimulation can indeed represent a new non-pharmacological approach for the treatment of symptomatic heart failure

    T-wave alternans in risk stratification of patients with nonischemic dilated cardiomyopathy: can it help to better select candidates for ICD implantation?

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    Background: Prophylactic implantable cardioverter-defibrillator (ICD) therapy reduces mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF), but the absolute risk reduction is relatively small. Thus, there is a strong need to identify reliable risk stratifiers, particularly among patients with nonischemic cardiomyopathy (NIDCM), in whom the search for risk predictors has been particularly frustrating. Objective: This study sought to review data regarding T-wave alternans (TWA) in patients with NIDCM and to discuss its potential role. Methods: We included in a meta-analysis clinical trials that enrolled ≥50 NICDM patients, had a follow-up of ≥1 year, and provided detailed data on NIDCM patients, in case of mixed population. Relative risks were derived from absolute numbers of events in abnormal (positive + indeterminate test whenever possible) TWA versus normal (negative) TWA group. Results: Eight studies with 1,456 patients (mean age 56 years, LVEF 30%, follow-up 25 months) were included. A negative TWA test occurred in 33%, and was indeterminate in 21% of the patients. The primary end point (VT+VF+sudden or all-cause death) occurred in 14.7% abnormal versus 3.8% normal TWA patients. The relative risk for the cumulative data was found to be 2.99 (95% confidence interval: 1.88 to 4.75). The negative predictive value was 96.2%. Conclusion: A normal TWA test identifies one-third of NIDCM patients who have a very good prognosis and are unlikely to significantly benefit from ICD therapy. A randomized clinical trial evaluating the utility of TWA in guiding therapy seems warranted, possibly a noninferiority trial of medical therapy only versus ICD in TWA-negative patients

    [Vagus nerve stimulation for the treatment of heart failure]

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    In the last two decades, the autonomic imbalance characterized by vagal withdrawal and sympathetic increase has been shown to play a major role in the progression and prognosis of heart failure. Therefore, modulation of the autonomic nervous system (neuromodulation) with the aim to restore autonomic balance is gaining increasing interest as a potential therapy for patients with heart failure. Recently, different non-pharmacological approaches to neuromodulation have been evaluated in phase II and III clinical trials. Electrical vagus nerve stimulation is the most studied. This technique showed excellent results in preclinical studies, but at present the clinical experience is limited to a few studies, the results of which are apparently conflicting.This review discusses the preclinical and clinical experience of vagal stimulation in heart failure, in order to help understand the complexity of the methodology and our still limited knowledge of the dose-response relationship, which make difficult to interpret and compare the results of studies conducted with different designs and evaluating different devices and stimulation protocols
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