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

Study Questions:

Does n-3 polyunsaturated fatty acid (PUFA) therapy impact left ventricular (LV) function or functional capacity in mild chronic nonischemic heart failure (HF)?

Methods:

Patients (n = 133) ages 18-75 years with nonischemic HF (LV ejection fraction [LVEF] ≤45%) with minimal or no HF symptoms for ≥3 months underwent double-blind randomization to PUFA (five 1 g capsules daily for 1 month, then two capsules daily thereafter) or matching placebo. Patients underwent blinded echocardiography, cardiopulmonary stress testing, and laboratory assessment (including measurement of inflammatory markers) before and 12 months after therapy. The primary outcome of interest was change in LVEF. The secondary endpoint included changes in functional capacity (peak oxygen consumption [pVO2] on stress testing) and inflammatory markers.

Results:

Mean ± standard deviation patient age was 63 ± 10 years and 9.8% were women. Baseline LVEF was 37 ± 6% and mean pVO2 was 19 ± 4 ml/kg/min (mean 70 ± 11% predicted pVO2). After 12 months of therapy, LVEF increased by 10.4 ± 9.5% (within group, p < 0.001) in the PUFA group (n = 67), and this difference was significantly different from placebo (n = 66) (between group, p < 0.001). Exercise capacity also increased 6.2% (p < 0.001) within the PUFA group and was significantly improved compared with placebo (p < 0.001). There was a concomitant improvement in New York Heart Association (NYHA) class with PUFA therapy. Serum inflammatory cytokines (interleukin [IL]-6, IL-1, and tumor necrosis factor-alpha) were significantly lower following PUFA compared with control.

Conclusions:

In chronic mild nonischemic HF, PUFA improved function and patient functional capacity.

Perspective:

This is a small, but provocative study of PUFA therapy in mild HF. The group overall was very low risk at baseline based on high pVO2 and systolic blood pressure and low NYHA class. The main take-home points are as follows: 1) The improvements in EF following PUFA were very striking, especially in a group on good background HF therapy with a relatively high utilization of cardiac resynchronization therapy given baseline risk profile. 2) A decline in maximum heart rate may have impacted pVO2 results in the placebo group, and it is unknown if a <1 MET improvement in functional capacity in the PUFA group is clinically relevant. 3) All outcomes in the placebo group seemed to worsen at follow-up, but no baseline differences were noted between placebo and PUFA groups. Thus, given the above results with high potential for clinical impact, a larger independent study to confirm PUFA’s impact on HF outcome is warranted.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, Lipid Metabolism, Nonstatins, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Follow-Up Studies, Oxygen Consumption, Ventricular Function, Left, Fatty Acids, Omega-3, Heart Failure, Blood Pressure, New York, Heart Rate, Cardiomyopathy, Dilated, Cardiac Resynchronization Therapy, Echocardiography


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