Omega-3 Fatty Acids and the Risk of Ventricular Arrhythmias in HF
Background: Epidemiological studies support the protective effect of omega-3 fatty acids on sudden cardiac death. However, patients with structural heart disease and an implantable cardioverter defibrillator (ICD) showed no effect or even a proarrhythmic response to fish oil supplementation. Animal studies suggest different electrophysiologic effects of circulating and incorporated omega-3 fatty acids.
Methods: In 102 ICD patients in New York Health Association functional class II or III, the fatty acid composition of red blood cells was analyzed by gas chromatography. The omega-3 index was calculated from eicosapentaenoic acid and docosahexaenoic acid. Patients were followed for 1 year, and ventricular arrhythmias requiring antitachycardic therapy were analyzed. Twenty-five healthy subjects served as control.
Results: In ICD patients, the fatty acid profile was significantly altered and the baseline omega-3 index was significantly elevated, as compared to control subjects (5.12% ± 0.87% vs 4.24% ± 0.96%, P < .001). Kaplan-Meier estimates of probability of ventricular arrhythmias showed significant differences among quartiles of the omega-3 index. Twelve percent of patients in the lowest quartile had ventricular arrhythmias, as compared to 54% of patients in the highest quartile (P = .022). In a multivariate analysis, the omega-3 index was the only independent predictor for ventricular arrhythmias up to 9 months. At 12 months, a reduced ejection fraction was an additional risk predictor.
Conclusions: In heart failure patients, the red blood cell fatty acid profile is altered. Omega-3 fatty acids are elevated and predict the risk of ventricular arrhythmias.
Sudden cardiac death is estimated to account for approximately 50% of all deaths from cardiovascular cause. Because it is often the first manifestation of heart disease, identification of individuals who are at risk is a major challenge. Most sudden deaths are caused by ventricular arrhythmias in patients with structural heart disease and an impaired left ventricular function. Primary prevention trials have demonstrated a survival benefit in high-risk patients who receive an implantable cardioverter defibrillator (ICD), as compared to drug therapy.
Epidemiological studies support the protective effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on sudden cardiac death. Fish consumption was associated with a reduced risk of sudden cardiac death. In secondary prevention of myocardial infarction, n-3 PUFA supplementation reduced overall mortality and sudden cardiac death. On the contrary, in patients with angina pectoris, n-3 PUFA supplementation increased overall mortality and sudden cardiac death. Trials with ICD patients were conflicting because fish oil supplementation resulted in antiarrhythmic, proarrhythmic, or no response. A recent meta-analysis showed no significant benefits of n-3 PUFAs on cardiovascular events and mortality.
Animal studies suggest different electrophysiologic effects of circulating and incorporated n-3 PUFAs, possibly explaining these conflicting results. Incorporated dietary n-3 PUFAs shortened action potentials in isolated porcine ventricular myocytes. They promoted ventricular arrhythmias during acute regional myocardial ischemia in the absence of circulating n-3 PUFAs in isolated pig hearts. Short-term administration of n-3 PUFAs shortened action potentials in guinea pig and showed a dose-dependent response in adult rat ventricular myocytes. Membrane excitability, ventricular conduction, intracellular Ca handling, and sarcoplasmic reticulum function are only affected by circulating n-3 PUFAs.
We addressed the hypothesis that the level of incorporated n-3 PUFAs may predict the occurrence of ventricular arrhythmias. We performed a prospective cohort study in patients with structural heart disease and a previously implanted ICD.
Abstract and Introduction
Abstract
Background: Epidemiological studies support the protective effect of omega-3 fatty acids on sudden cardiac death. However, patients with structural heart disease and an implantable cardioverter defibrillator (ICD) showed no effect or even a proarrhythmic response to fish oil supplementation. Animal studies suggest different electrophysiologic effects of circulating and incorporated omega-3 fatty acids.
Methods: In 102 ICD patients in New York Health Association functional class II or III, the fatty acid composition of red blood cells was analyzed by gas chromatography. The omega-3 index was calculated from eicosapentaenoic acid and docosahexaenoic acid. Patients were followed for 1 year, and ventricular arrhythmias requiring antitachycardic therapy were analyzed. Twenty-five healthy subjects served as control.
Results: In ICD patients, the fatty acid profile was significantly altered and the baseline omega-3 index was significantly elevated, as compared to control subjects (5.12% ± 0.87% vs 4.24% ± 0.96%, P < .001). Kaplan-Meier estimates of probability of ventricular arrhythmias showed significant differences among quartiles of the omega-3 index. Twelve percent of patients in the lowest quartile had ventricular arrhythmias, as compared to 54% of patients in the highest quartile (P = .022). In a multivariate analysis, the omega-3 index was the only independent predictor for ventricular arrhythmias up to 9 months. At 12 months, a reduced ejection fraction was an additional risk predictor.
Conclusions: In heart failure patients, the red blood cell fatty acid profile is altered. Omega-3 fatty acids are elevated and predict the risk of ventricular arrhythmias.
Introduction
Sudden cardiac death is estimated to account for approximately 50% of all deaths from cardiovascular cause. Because it is often the first manifestation of heart disease, identification of individuals who are at risk is a major challenge. Most sudden deaths are caused by ventricular arrhythmias in patients with structural heart disease and an impaired left ventricular function. Primary prevention trials have demonstrated a survival benefit in high-risk patients who receive an implantable cardioverter defibrillator (ICD), as compared to drug therapy.
Epidemiological studies support the protective effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on sudden cardiac death. Fish consumption was associated with a reduced risk of sudden cardiac death. In secondary prevention of myocardial infarction, n-3 PUFA supplementation reduced overall mortality and sudden cardiac death. On the contrary, in patients with angina pectoris, n-3 PUFA supplementation increased overall mortality and sudden cardiac death. Trials with ICD patients were conflicting because fish oil supplementation resulted in antiarrhythmic, proarrhythmic, or no response. A recent meta-analysis showed no significant benefits of n-3 PUFAs on cardiovascular events and mortality.
Animal studies suggest different electrophysiologic effects of circulating and incorporated n-3 PUFAs, possibly explaining these conflicting results. Incorporated dietary n-3 PUFAs shortened action potentials in isolated porcine ventricular myocytes. They promoted ventricular arrhythmias during acute regional myocardial ischemia in the absence of circulating n-3 PUFAs in isolated pig hearts. Short-term administration of n-3 PUFAs shortened action potentials in guinea pig and showed a dose-dependent response in adult rat ventricular myocytes. Membrane excitability, ventricular conduction, intracellular Ca handling, and sarcoplasmic reticulum function are only affected by circulating n-3 PUFAs.
We addressed the hypothesis that the level of incorporated n-3 PUFAs may predict the occurrence of ventricular arrhythmias. We performed a prospective cohort study in patients with structural heart disease and a previously implanted ICD.