A Pilot Feasibility Study in Recovered Heart Failure

Study Overview
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Brief Summary
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One third of patients diagnosed with heart failure demonstrate left ventricular reverse remodelling and recovery of cardiac function following a period of medical therapy. These patients have an excellent long-term prognosis. Whether they need to remain on long-term medical therapy is not clear. The investigators will investigate the safety of therapy withdrawal in patients with a previous diagnosis of heart failure and recovered cardiac function, in a randomised controlled trial.

Detailed Description
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Patients with a previous diagnosis of heart failure, who have recovered cardiac function, without symptoms, normal serum biomarker concentrations and who are currently still taking heart failure medications, will be recruited. Participants will be randomised to withdrawal of therapy and control arms and will undergo imaging investigations and cardiopulmonary exercise tests at baseline along with serum biomarker tests. Those participants randomised to withdrawal of therapy will have a gradual, supervised reduction of medications. If, at anytime, there are signs of recurring heart failure, medications will be restarted. Participants in the control arm will continue their medical therapy as usual. Participants will be followed up with further biomarker testing, cardiopulmonary exercise testing and imaging investigations at 6 months. The primary end-point will be a relapse in heart failure, defined by adverse remodelling, increase in left ventricular size, rise in serum biomarkers or clinical evidence of heart failure as judged by the clinical team.

Official Title
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A Pilot Feasibility Study in Recovered Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Withdrawal of therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have an index diagnosis of heart failure confirmed by 2 independent operators based on clinical details. Be currently taking at least 1 of the following medications loop diuretic, betablocker, angiotension converting enzyme inhibitor/angiotensin receptor blocker and mineralocorticoid receptor antagonist. Have demonstrated evidence of left ventricular reverse remodelling following the initial diagnosis with subsequent improvement in ejection fraction to >50% and normalisation of left ventricular (LV) volumes. Have no symptoms of heart failure (NYHA Class 1). Low plasma NTproBNP. Exclusion Criteria: Uncontrolled hypertension. More than moderate valvular disease. Estimated glomerular filtration rate <30mls/min. Atrial/supraventricular/ventricular arrhythmia requiring beta-blockade. Pregnancy. Unstable angina. Age <16 years

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 85 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Withdrawal of therapy<br>Gradual, supervised withdrawal of medical therapy over 4-16 weeks | Drug: Withdrawal of therapy<br>* Withdrawal of heart failure therapies (angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists and loop diuretics)<br>|
| No Intervention: Control<br>Continuation of usually prescribed pharmacological therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart failure relapse | Defined by one of the following: 1) A reduction in left ventricular ejection fraction; 2) An increase in left ventricular size; 3) An increase in serum biomarker concentration from baseline; 4) Clinical evidence of heart failure | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiopulmonary exercise testing with peak oxygen consumption | Change in peak oxygen consumption between baseline and follow-up test | 6 months | 
| Quality of life | Patient questionnaires - Kansas City Cardiomyopathy Questionnaire and Heart Failure Symptom Questionnaire (symptom scores are calculated on the basis of the participants' answers to the questionnaires) | 6 months | 
| Major adverse cardiovascular events (MACE) - safety end-point | MACE - unplanned cardiovascular (CV) hospitalisation, CV mortality and major adverse CV events (non-fatal myocardial infarction and non-fatal cerebrovascular accident) | 6 months | 
| Percentage of participants with new and sustained arrhythmias | New and sustained arrhythmias diagnosed during follow-up | 6 months | 
| Increase in left atrial volume as measured on cardiovascular magnetic resonance (CMR) | Increase in left atrial volume as measured on CMR (in millilitres) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recovery