PUFAs and Left Ventricular Function in Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that n-3 PUFAs improve left ventricular systolic function in patients with stable chronic HF secondary to nonischemic dilated cardiomyopathy (NICM).

Detailed Description
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The results of the GISSI-HF trial indicate that in patients with chronic HF on evidence-based medical therapy and New York Heart Association (NYHA) functional class II-IV, long term treatment with n-3 PUFAs 1 g daily reduces mortality and hospitalizations for cardiovascular reasons. Several potential mechanisms may underlie the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) in HF patients, including, but not limited to, antiarrhythmic, and hemodynamic actions. The current investigation was therefore designed to test the hypothesis that treatment with n-3 PUFAs improves LV systolic function expressed as EF in patients with stable chronic HF secondary to a nonischemic dilated cardiomyopathy (NICM). Additionally, we sought to determine if n-3 PUFAs also exert positive effects on LV diastolic function assessed by echocardiography; functional capacity assessed by cardiopulmonary stress testing (CPET); and New York Heart Association (NYHA) functional class.

Official Title
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Effects of n-3 Polyunsaturated Fatty Acids (PUFAs) on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy

Conditions
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Dilated Cardiomyopathy, Heart Failure

Intervention / Treatment
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* Drug: n-3 PUFAs
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with a diagnosis of non ischemic cardiomyopathy (the absence of coronary artery disease,defined as the absence of stenosis > 50%, was confirmed by angiography performed at the time of the diagnostic workup of the cardiomyopathy) LV systolic dysfunction (defined as an EF < 45%) Stable clinical conditions with minimal or no symptoms for at least three month Evidence-based medical treatment at maximum tolerated target doses for at least six month Exclusion Criteria: presence of symptoms or evidence of CAD diagnosed through noninvasive tests; peripheral arterial disease; presence of congenital or primary valvular heart disease; persistent atrial fibrillation; inability to perform bicycle ergometry for noncardiac causes; moderately to severely reduced functional capacity; NYHA functional class IV; poor acoustic windows limiting the ability to assess echocardiographic measurements; chronic lung disease; advanced renal disease (eGFR < 30 mL/min/1.73 m2); advanced liver disease; any disease limiting life expectancy to one year or less; contraindications to study drugs; concomitant participation in other research studies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: n-3 PUFAs<br> | Drug: n-3 PUFAs<br>* 1.0 g gelatin capsules containing 850 to 882 mg of EPA and DHA ethyl esters in the average ratio EPA/DHA of 0.9:1.5 The treatment dose was five capsules daily for the first month followed by two capsules daily for the rest of the study.<br>* Other names: OMACOR, Pronova Biopharma, Lysaker, Norway;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1.0 g gelatin capsules containing olive oil. The treatment dose was five capsules daily for the first month followed by two capsules daily for the rest of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular (LV) Systolic Function Expressed as Left Ventricular Ejection Fraction (LVEF) Between Baseline and 12-month Follow-up | The primary end point of the study was the change in LV systolic function expressed as LVEF between baseline and 12-month follow-up. The following parameters were measured according to the professional standards defined by the American Society of Echocardiography and the European Association of Echocardiography | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LV Diastolic Function | Change in LV diastolic function assessed by echocardiography: mitral diastolic inflow velocities (peak velocity of early ventricular filling [E-wave], peak velocity of late ventricular filling [A-wave], E/A ratio, and E-wave deceleration time), diastolic function score (graded on a scale from 1 to 4) were used. | one year | 
| Functional Capacity (Change in Peak Oxygen Uptake, VO2) | Change in functional capacity expressed as a peak oxygen uptake (VO2), that was acquired breath-by-breath by pneumotachograph (with bidirectional differential pressure) during cardiopulmonary exercize testing. | one year | 
| Change in Mean New York Heart Association (NYHA) Functional Class Between Baseline and 12th Month Follow up. | NYHA class I: No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs, etc... NYHA class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. NYHA class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest NYHA class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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n-3 PUFAs, Heart Failure, Dilated cardiomyopathy, Ejection Fraction, Exercise Capacity