Changes in the T-wave Alternans in Patients With Heart Failure Treated Wih Sacubitril-Valsartan

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to know if the Sacubitril-Valsartan treatment improves the T-wave alternans in those patients that begin its treatment, which would indirectly show a lower risk of malignant ventricular arrythmias.

Detailed Description
-----------------
Sacubitril-Valsartan has shown to reduce sudden death in its principal clinical trial, PARADIGM-HF. A T wave alternans (TWA) is an electrophysiological phenomenon that acts as an independent predictor of sudden death and ventricular arrhythmias in postinfarct myocardial. TWA is measured by using a special software and electrodes during a treadmill test, that analyse small changes in the microvolt of the T wave consecutive with a complex algorithm in three dimensions. The TWA could be negative (normal), positive (pathological) or indeterminate. If a TWA is pathological it reflects an electric instability in depolarization. Our hypothesis is that the treatment with Sacubitril-Valsartan in heart failure patients with reduced ejection fraction, could improved the TWA.

Official Title
-----------------
Changes in the T-wave Alternans in Patients With Heart Failure Treated Wih Sacubitril-Valsartan

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Drug: Sacubitril-Valsartan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults from 18 to 80 years old. Patients with grade II heart failure according to the New York Heart Association (NYHA). Left systolic disfunction: left ventricle ejection fraction<40% NT-proBNP > 600 pg/ml (or > 100 pg/ml in the case the patients has been hospitalised during the last year. Treated with ACE or ARA II+betablocker at stable doses during the prior 4 weeks to the beginning of the study. Exclusion Criteria: Previously treated with Sacubitril-Valsartan. Allergy or intolerance to ARA II. Systolic blood pressure < 100 mmHG at inclusion. Glomerular Filtration <35 ml / min / 1.73 m2 of body surface. Level of potassium > 5,4 mEq/l. Impossibility to walk on a treadmill. Record of recovered sudden death or documented ventricular tachycardia. Carrier of an automatic implantable defibrillator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sacubitril-Valsartan cohort<br>Patients with left systolic disfunction (left ventricle ejection fraction<40%) heart failure and diagnosed with grade II heart failure that have been treated with an ACE or ARA II+betablocker at stable doses during the last 4 weeks and after being evaluated by the cardiologist start Sacubitril-Valsartan treatment. | Drug: Sacubitril-Valsartan<br>* After signing the Informed Consent, in the shortest possible time, the study investigator will carry out an ergometric test for the T-wave alternans (TWA) while still taking the basal medication. The patient will also sign the prototype Informed Consent for carrying out a stress test on a treadmill. It will also be carried out a basal life quality questionnaire, an analytical determination and a colour doppler echocardiography.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analyze the changes in the T-wave alternans | Comparison of the results in the same patient just before the beginning of the Sacubitril-Valsartan pharmacological treatment versus 6 months after its beginning, in patients with grade II heart failure and left systolic disfunction (left ventricle ejection fraction<40%). | Up to 6 months after the beginning of the Sacubitril-Valsartan treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the results in the life quality questionnaire. | Comparison of the life quality questionnaires results before and after the Sacubitril-Valsartan treatment. | Up to 6 months after the beginning of the Sacubitril-Valsartan treatment | 
| Study the levels of the n-terminal type B natriuretic propeptide | Comparison of the n-terminal type B natriuretic propeptide levels before and after the Sacubitril-Valsartan treatment. | Up to 6 months after the beginning of the Sacubitril-Valsartan treatment | 
| Evaluate the echocardiographic results | The echocardiographic results will be assessed by a combination of the measurement of the parameters: left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end systolic volume (LVESV) and left ventricle diastolic function, that will be compared before and after the Sacubitril-Valsartan treatment to evaluate its effect in patients with heart failure. | Up to 6 months after the beginning of the Sacubitril-Valsartan treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart Failure, Sacubitril-Valsartan, T-wave changes alternans