Influence of Sacubitril/Valsartan on Autonomic Cardiac Nervous System in Heart Failure Patients: an Exploratory Study

Study Overview
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Brief Summary
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Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor with the ability to reduce myocardial hypertrophy, cardiac remodeling and cardiorenal fibrosis. The compound is also believed to have antiarrhythmic properties as it has been shown to significantly reduce ventricular arrhythmias in patients with implantable cardioverter defibrillators. Patients suffering from heart failure with reduced ejection fraction show impaired heart rate variability, knowing that in these patients such impairment is highly associated with an increased risk of sudden cardiac death. In its pivotal study, sacubitril/valsartan demonstrated a significant advantage over enalapril in terms of cardiovascular mortality and rehospitalization. Against this background, this study was designed to analyze the largely unknown electrophysiological effects of sacubitril/valsartan on the autonomic cardiac nervous system by determining heart rate variability.

Official Title
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Influence of Sacubitril/Valsartan on Autonomic Cardiac Nervous System in Heart Failure Patients: an Exploratory Study

Conditions
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Heart Failure Patients

Intervention / Treatment
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* Drug: sacubitril/ valsartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic severe heart failure with reduced ejection fraction (LVEF ≤40%,) Age > 20 years Consent capacity Sinus rhythm Suitable for a drug conversion from AT1/ACE inhibitors to sacubitril/ valsartan Exclusion Criteria: Age < 18 years Atrial fibrillation Pregnancy Lack of consent capacity Contraindications for a therapy with sacubitril/ valsartan

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Heart rate variability measurement is carried out by means of a 12-channel ECG for 30 minutes in supine position followed by 10 minutes in standing position. All parameters, including blood values and echocardiographic parameters are assessed before beginning of sacubitril/ valsartan therapy and 3 months after starting treatment.
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: sacubitril/ valsartan|Heart rate variability measurement is carried out by means of a 12-channel ECG for 30 minutes in supine position followed by 10 minutes in standing position. All parameters, including blood values and echocardiographic parameters are assessed before beginning of sacubitril/ valsartan therapy and 3 months after starting treatment|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in heart rate variability | Changes in heart rate variability after 3 months of treatment with sacubitril/ valsartan | 24 months | 
| Changes in left ventricular ejection fraction (%) | Changes in left ventricular ejection fraction (%) assessed by transthoracic echocardiogramChanges in echocardiographic parameters (left ventricular parameters) | 24 months | 
| Changes in mitral insufficiency grade | Changes in mitral insufficiency grade assessed by transthoracic echocardiogram | 24 months | 
| Changes in serum NT-proB-Type natriuretic peptide (ng/l) | Changes in laboratory parameters (serum NT-proB-Type natriuretic peptide (ng/l) | 24 months | 
| Changes in Serum creatinine level (mg/dl) | Changes in laboratory parameters (Serum creatinine level (mg/dl) | 24 months | 
| Changes in glomerular filtration rate (ml/min) | Changes in laboratory parameters (glomerular filtration rate ml/min) | 24 months | 
| Changes in serum potassium level (mmol/l) | Changes in laboratory parameters (glomerular filtration rate ml/min) | 24 months |