PUFAs and Left Ventricular Function in Heart Failure

Phase 3

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
n-3 PUFAs	n-3 PUFAs	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change in Left Ventricular (LV) Systolic Function Expressed as Left Ventricular Ejection Fraction (LVEF) Between Baseline and 12-month Follow-up	one year	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

Secondary Outcome Measures

Name	Time	Method
LV Diastolic Function	one year	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.
Functional Capacity (Change in Peak Oxygen Uptake, VO2)	one year	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.
Change in Mean New York Heart Association (NYHA) Functional Class Between Baseline and 12th Month Follow up.	one year	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.