Use of Beta-agonists in Stable Severe Congestive Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Salbutamol is effective in the treatment of severe heart failure due to ischemic and non- ischemic cardiomyopathy.

Conditions
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Ischemic Cardiomyopathy, Non-ischemic Cardiomyopathy, Heart Failure

Intervention / Treatment
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* Drug: Salbutamol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory Patients with a diagnosis of ischemic and non-ischemic cardiomyopathy with a measured EF <35%, class III as defined by the NYHA with ICD and who receive optimal pharmacological therapy. Exclusion Criteria: Heart Failure class I, II, IV atrial fibrillation any significant valvular disease chronic obstructive pulmonary disease who treated with inhaled β2 agonist significant kidney disease with eGFR <30% severe uncontrolled electrolyte abnormalities prior allergic reaction to Salbutamol Pregnancy and nursing women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Salbutamol<br>The patients in the study groups will receive the selective β2 agonist, Salbutamol, in addition to their ongoing optimal heart failure therapy. | Drug: Salbutamol<br>* The initial dose will be 0.5mg bid, with acceleration of the dose every two weeks by 1mg, up to a maximal dose of 2mg bid or an increase in heart rate by 50% above the baseline heart rate, as long as it remains <100 bpm<br>|
| No Intervention: control<br>The patients in the control group will continue with their regular optimal medical therapy without any intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma level of N-terminal pro-BNP at twelve weeks relative to baseline pro-BNP. |  | 12 weeks from baseline pro-BNP assessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse cardiovascular event: Death, ICD discharge, significant ventricular arrhythmias and hospitalization due to heart failure exacerbation | Record events of death, ICD discharge and hospitalization due to heart failure exacerbation. Interrogate ICD memory for significant ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) that did not cause ICD discharge. | 12 weeks after baseline assessment | 
| NYHA class changes | We will assess NYHA functional class at baseline and after 12 weeks from the beginning of study medication. | 12 weeks after baseline assessment | 
| Echocardiography parameters changes | END-SYSTOLIC DIAMETER: _ _ _ MM END-DIASTOLIC DIAMETER: _ _ _ MM LVEF (SIMPSON'S) : _____% Left atrial diameter: ____MM Left atrial area:______cm2 dP/dT: ___32/∆t (mm Hg/msec) E/A: ___ E': ___ cm/s E/E': _____ E wave deceleration time:_____msec Isovolumic relaxation time (IVRT):_____msec Dimensionless myocardial performance index (MPI) (n<0.4) : MPI=(TST-ET)/ET TST- total systolic time -from the end of mitral inflow A wave to the beginning of mitral inflow E wave ET - ejection time - time from the beginning to the end of left ventricular outflow tract Doppler envelope | 12 weeks after baseline assessment | 
| Minnesota Living with Heart Failure Questionnaire changes | repeat Minnesota Living with Heart Failure Questionnaire assessment | 12 weeks after baseline assessment | 
| Non-ventricular arrhythmias and electrolytes disturbances | Plain ECG will be performed at the specified time intervals to detect asymptomatic non-ventricular arrhythmias (atrial fibrillation, atrial flutter, atrial premature beats, etc.) The venous blood will be drawn at the specified time intervals to follow closely after potassium levels (for timely detection of salbutamol induced hypokalemia and to correct accordingly), as well to monitor sodium levels as a prognostic and clinical marker of heart failure exacerbation | baseline, 1 week, 4 weeks, 8 weeks and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart failure stage 3, beta 2 agonist, N-terminal pro-brain natriuretic peptide, ejection fraction <35%