(15-01-11) Preoperative Omega-3 PUFAs Decrease Early Atrial Fibrillation After Cardiac Surgery

In atrial fibrillation (AF), the most common type of arrhythmia, there are no
contractions of the atria, the upper chambers of the heart that receive blood
returning from the veins. As a consequence, blood that pools in the atria isn't
pumped completely into the ventricles, the heart's two lower chambers. Some
people who have AF feel no symptoms, but others experience chest pain, stroke
or heart failure, particularly when the heart rhythm is very rapid. The Figure
shows how a stroke can occur during atrial fibrillation. If a clot (thrombus)
forms in the left atrium, a piece of it can dislodge and travel to an artery in
the brain, blocking blood flow through the artery. The lack of blood flow to
the portion of the brain fed by the artery causes a stroke.

AF after cardiac surgery is associated with increased risk of death. Reasons
underlying an individual?s susceptibility to AF are unclear and the use of
antiarrhythmic agents has had mixed results. Some studies show cardiac
protection against AF by n-3 polyunsaturated fatty acids (PUFAs) during the
postoperative period, but others reported no effect or were inconclusive. A
recent study found no evidence for a beneficial effect of treatment with n-3
PUFA on the occurrence of AF in patients undergoing coronary artery bypass
grafting and/or valvular repair surgery. The controversial results are partly
related to the type of cardiac surgery performed, according to the authors of a
new study that evaluated the influence of preoperative PUFA therapy on AF after
cardiac surgery during hospitalization in the intensive care unit (early AF)
and the subsequent rehabilitation period (late AF).

This study included 530 participants recruited over 4 years, who were
undergoing cardiac surgery and had no history of AF or a pacemaker. The
patients (average age 66 yr, 69% male) were monitored for early and late AF
during their entire hospital stay. The investigators classified the occurrence
of AF, which they defined as lasting 15 minutes or longer, as ?early? if it
developed in the surgical department and ?late? if it happened during the
cardiac rehabilitation program. Considering all patients, the lengths of stay
in surgical and rehabilitation departments were 10 and 22 days, respectively.
The longest stays in both hospital units occurred in patients with
postoperative AF.

The cardiac surgeries included 278 (53%) coronary artery bypass grafts, 138
(26%) valve replacements, 80 (15%) combined procedures, and 6% other types.
Each participant underwent preoperative coronary angiography, transthoracic
echocardiography and (color-Doppler) ultrasound of the epiaortic vessels. The
latter assessment provides images of the parts of the aorta not covered by
transthoracic echocardiography. All preoperative medications, including PUFA,
were omitted on the day of the operation and restarted on the first
postoperative day. Patients were selected for PUFA treatment according to their
propensity score, a statistical risk model based on current medical conditions,
cardiac function, medications and type of operation being conducted. A total of
84 (16%) of the participants began preoperative n-3 LC-PUFA treatment at
admission (median duration of 5 days (range, 1?26 days) with 1000 mg/d in a
single gelatin capsule containing eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) as ethyl esters in the average ratio of EPA/DHA 0.9:
1.5.

The overall incidence of early AF among all participants was 45% (237 of 530
patients), with the highest occurrence among patients having combined cardiac
procedures (54%, or 43 of 80 patients). The lowest rate occurred among coronary
artery bypass graft patients (40%, or 111 of 278 patients). Early AF occurred
after a median of 2 days (range, 1?21) following surgery, and a recurrent AF
episode was registered in 21% of the affected individuals. Only 5% (112) of the
individuals with arrhythmia who were discharged to the rehabilitation program
had persistent AF. Late AF occurred in 15% (78) of the participants after a
median of 11 (range: 6?52) days from surgery, and 73% (57) of patients with
late AF had already experienced an episode of early AF.

Patients treated with long-chain omega-3 PUFAs (n-3 LC-PUFAs) prior to surgery
were 46% less likely to develop early AF (p = 0.025) compared with untreated
patients, but there was no association between n-3 LC-PUFA treatment and late
AF. Early AF occurred in 31% of the n-3 LC-PUFA-treated patients compared with
47% in those not receiving the n-3 LC-PUFAs (p = 0.006). Interestingly, the n-3
LC-PUFA-treated patients had a higher cardiovascular risk profile upon
enrollment, were an average of 6 years older and were significantly more likely
to have had a prior heart attack, percutaneous coronary intervention,
hypertension, diabetes, dyslipidemia, chronic obstructive pulmonary disease,
peripheral artery disease and poor ventricular function.

The time of early AF occurrence and the recurrence rate were not influenced by
treatment; however, there was a lower persistence of arrhythmia at the time of
discharge in the PUFA-treated group. Preoperative PUFA therapy was associated
with decreased levels of postoperative C-reactive protein (CRP, a protein in
the blood that is elevated in response to inflammation); 3.8 ? 2.9 vs 5.1 ? 4.0
mg/L, p = 0.025). Study participants treated with both n-3 LC-PUFAs and a
statin did not differ in their reduced risk of early AF compared with statin
treatment alone, but the few patients taking only n-3 LC-PUFAs had only a
quarter of the risk of early AF compared with statin-only patients.

Early AF patients had increased levels of white blood cells after surgery
compared with patients who did not develop AF. High white blood cell counts
usually indicate disease or infection. The use of beta-blockers did not
influence the prevalence of early AF, whereas preoperative PUFA significantly
reduced it (p = 0.006). Withdrawal of participants from ?-blocker and
angiotensin-converting enzyme (ACE) inhibitor treatments was associated with
early AF development (p = 0.047 and p = 0.039, respectively). Conversely,
preoperative statins slightly reduced AF occurrence (p = 0.052).

Late AF occurred more frequently in older males with left atrial enlargement
and a higher degree of pericardial effusion. Postoperative statins and ?-
blockers were both associated with a reduction in late AF (P = 0.003 and P =
0.046, respectively). Length of hospital stay for patients with early AF was
significantly shorter than for late AF patients (10 vs. 24 days).

The underlying mechanisms for the effects of PUFAs on reducing the chance of
early AF may be related to their anti-inflammatory properties. The role of
inflammation in the pathology of postoperative AF is known from previous
studies on the inhibition of arachidonic acid conversion to prostaglandin E2
and leukotriene B4, both of which are mediators of inflammation, and to
decreased synthesis of these inflammatory agents in monocytes when n-3 LC-PUFAs
are present. The reduction in early postoperative AF, but not late AF, in this
study was characterized by higher inflammatory measures and higher white blood
cell counts after surgery. Participants with preoperative PUFA therapy had
decreased CRP levels compared with those without PUFA therapy. The authors
speculated that the anti-inflammatory effect of the n-3 LC-PUFAs would be a
valid mechanism only in the early postoperative phase, as preoperative PUFA
therapy was not associated with a reduction in late AF. On the other hand,
pericardial effusion, a measure of persisting post-operative inflammatory
status, was an independent predictor of late AF (Table 1).

A second possible antiarrhythmic effect of n-3 LC-PUFAs involves the autonomic
nervous system's sympathetic activation following coronary surgery. The
sympathetic nervous system functions to mobilize the body's resources under
stress. Cardiac surgery trauma triggers release of catecholamines, which are
key in the development of AF. Elevated norepinephrine, a stress hormone that
increases heart rate, suggests that sympathetic activation may be important in
the pathogenesis of atrial fibrillation, and n-3 LC-PUFAs can reduce plasma
norepinephrine concentrations.

This study showed that administration of n-3 LC-PUFAs prior to several types
of cardiac surgery was associated with a significant reduction in the
development of early, but not late, AF following surgery. This difference may
be related to the anti-inflammatory and autonomic nervous system inhibitory
properties of n-3 LC-PUFAs, both of which act in the earliest days after
cardiac surgery. The study is limited by the lack of a placebo control group
and its non-randomized assignment of patients to the n-3 LC-PUFA treatment.

Source:
Mariscalco G, Sarzi Braga S, Banach M, Borsani P, Bruno VD, Napoleone M,
Vitale C, Piffaretti G, Pedretti RF, Sala A. Preoperative n-3 polyunsaturated
fatty acids are associated with a decrease in the incidence of early atrial
fibrillation following cardiac surgery. Angiology 2010;61:643?650.[PubMed]

News

---

In evidenza

"L'informazione presente nel sito serve a migliorare, e non a sostituire, il rapporto medico-paziente."

Per coloro che hanno problemi di salute si consiglia di consultare sempre il proprio medico curante.