https://doi.org/10.1007/s00392-025-02625-4
1Kardiologische Praxis Spreebogen Berlin, Deutschland; 2Deutsches Herzzentrum der Charite (DHZC) Berlin, Deutschland; 3Charité - Universitätsmedizin Berlin CC11: Med. Klinik m.S. Kardiologie Berlin, Deutschland; 4Charité - Universitätsmedizin Berlin Medizinische Klinik m. S. Kardiologie, Kompetenznetz Herzinsuffizienz Berlin, Deutschland; 5Charité - Universitätsmedizin Berlin CC11: Med. Klinik m. S. Kardiologie und Angiologie Berlin, Deutschland
Background:
Previous studies suggest that n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against arrhythmia and sudden death. However, their role in the prevention of atrial fibrillation (AF) remains controversial. Recent trials indicate that high dose n-3 PUFA supplementation is associated with increased AF risk. Arachidonic acid (AA), EPA and DHA are used as alternative substrates by cytochrome P450 (CYP) enzymes that convert the respective parental n-6 and n-3 PUFAs into different sets of bioactive lipid mediators. CYP epoxygenases produce epoxyeicosatrienoic acids (EETs) from AA, epoxyeicosatetraenoic acids (EEQs) from EPA, and epoxydocosapentaenoic acids (EDPs) from DHA. In particular, the omega-3 epoxides (17,18-EEQ, 19,20-EDP) are increasingly recognized to serve as important mediators of the vasculo- and cardioprotective effects attributed to dietary n-3 PUFAs.
Purpose:
This prospective observational study aims to determine the correlation between AF and plasma levels of EETs, EEQs and EDPs as well as the impact of omega-3-index and PUFA metabolism on AF in patients with severe chronic heart failure (HF).
Methods:
We enrolled 60 patients (50 men; 83.3%) at a mean age of 64.1 ± 11.1 years with severely reduced left ventricular ejection fraction (LVEF) and guideline-based indication for an implantable cardioverter-defibrillator (ICD) implantation. All patients were included in the Biotronik Home Monitoring® system and episodes were analyzed on a daily basis. The cause of HF was coronary artery disease (CAD) in 42 (70.0%) cases, dilatative cardiomyopathy in 17 (28.3%) of the cases and valvular heart disease in 1 (1.7%) case. Twenty-three (38.3 %) patients were diagnosed with atrial fibrillation (AF), of which 16 (26.7%) had paroxysmal, and 7 (11.7%) persistent AF. Quality of life was determined using a validated questionnaire (KCCQ). Echocardiography was analyzed at baseline with a mean LVEF of 31.2 ± 6.4%. Blood samples were collected at baseline, at 12 months follow-up and in case of new onset of AF or progression from paroxysmal to persistent AF. Red blood cells were used for determining the individual fatty acid profiles and calculating the omega-3 index. Plasma samples served to measure the CYP-eicosanoid levels.
Results:
During the follow-up (13.8 ± 7.2% months), first occurrence of AF was documented in 3 of 37 patients without a history of AF. In patients with a history of paroxysmal AF (n = 16), atrial fibrillation episodes occurred during the follow-up in 50% (n = 8), with progression to persistent AF in 3 patients. While the fatty acid profile and the omega-3-index showed no difference between patients with and without the occurrence of AF during the follow-up, there were significant changes in the endogenous eicosanoid profile. Compared to patients without AF occurrence in the course of the study, patients with AF occurrence showed on univariate analysis significant lower plasma values of epoxyeicosanoids. Moreover, low levels of 17,18-EEQ (OR 0.001; p<0.05), 7,8-EDP (OR 0.034; p<0.05), 10,11-EDP (OR 0.086; p< 0.05) and 13,14-EDP (OR 0.000; p < 0.05) were identified as independent predictor of AF occurrence on multivariate analysis.
Conclusion:
Our results show that various epoxyeicosanoids forms, in particular those derived from EPA and DHA, are associated with a significant lower incidence of AF in patients with chronic heart failure.