ROLE OF ASCORBIC ACID & STATIN IN REDUCTION OF THE INCIDENCE OF THE ATRIAL FIBRILLATION IN PATIENTS UNDER B-BLOCKER AND UNDERGOING CORONARY ARTERY BYPASS GRAFT OPERATION IN EARLY POST-OPERATIVE PERIOD

Mahmoud F. El-Safty and Hazem Gamal Bakr National Heart Institute, Cardiothoracic Surgery. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 10 July 2020 Final Accepted: 14 August 2020 Published: September 2020

548 fibrillation ranged between 17 and 40 percent (3). A higher frequency of postoperative atrial fibrillation is seen in patients undergoing combined CABG and valve surgery than in patients undergoing CABG alone (4). In most cases, 80 % of patients return to sinus rhythm within 1 to 3 days after initiation of digoxin or β-blocker therapy (1), but patients who experience postoperative atrial fibrillation have substantially higher monthly mortality rates (5). In most cases, atrial fibrillation after CABG is self-limited. The clear prophylactic efficacy of β-adrenergic blockers has been demonstrated in several randomised trials, and all patients without contraindications should receive β-blockers before and after cardiac surgery (4). β-blockers alone, however, are not adequate. Post-CABG atrial fibrillation prevention and antiarrhythmic medication administration can be ineffective and even dangerous, likely due to pro-arrhythmic and other side effects (6). The function of inflammation and oxidative stress in electrical remodelling is currently being studied. Therapeutic interventions targeting inflammation and oxidative stress may have beneficial effects on atrial electrical remodeling (7). Ascorbate can minimise electrical remodelling and the occurrence of postoperative atrial remodelling may be reduced. Because of fibrillation (8).

Aim of the work:
The goal of this research was to assess the effectiveness of β-blocker, statin, and ascorbic acid combination therapy in achieving further reduction of post-CABG atrial fibrillation compared to β-blocker therapy alone in the early post-operative period.  There is a high significant statistical difference among 3 groups as regard the intensive care unit stay as P value is <0.001.As intensive care unit stay is much lower in groups II & III than group I. More over, it is lower in group II than both groups I & III 1. With regard to the frequency of AF in gender, there is a substantial statistical difference between Group I. P value = 0.031 as it occurs more in males than in females.
2. There is a significant statistical difference among group I as regard the occurrence of AF in smokers. As it happens more in smoker patient P value = 0.041 3. There is a high significant statistical difference among group I as regard the occurrence of AF in patient with non significant ischemic mitral regurgitation .As it is more frequent with non significant ischemic mitral regurgitation P value = <0.001.
4. There is a high significant statistical difference among group I as regard need of inotropic support during 1st 24 hours after surgery. As inotropic support needed more with AF patient P value = <0.001.
5. There is a high significant statistical difference among group I as regard the need of ventilation more than 24 hours. AF patient needed to be ventilated more than patient without AF P value=<0.001.  1. There is a high significant statistical difference among group II as regard the occurrence of AF in patient with non significant ischemic mitral regurgitation .As it is more frequent with non significant ischemic mitral regurgitation P value = <0.001. 2. There is high significant statistical difference among group II as regard need of inotropic support during 1 st 24 hours after surgery. As inotropic support needed more with AF patient P value = 0.028. 3. There is a high significant statistical difference among group II as regard the need of ventilation more than 24 hours. AF patient needed to be ventilated more than patient without AF P value=<0.001.  1. There is a significant statistical difference among group III as regard the occurrence of AF in hypertensive patient. As it happens more in hypertensive patient P value = 0.025. 2. There is a significant statistical difference among groupIII as regard the occurrence of AF in smokers. As it happens more in smoker patient P value = 0.017. 3. There is a high significant statistical difference among group III as regard the occurrence of AF in patient with non significant ischemic mitral regurgitation .As it is more frequent with non significant ischemic mitral regurgitation P value = <0.001. 4. There is a high significant statistical difference among group III as regard the need of ventilation more than 24 hours. AF patient needed to be ventilated more than patient without AF P value=<0.001. 1. There is a high significant statistical difference among group III as regard the occurrence of AF & it's relation to mean age. As it happens more in older patient P value =< 0.001. 2. There is a significant statistical difference among group III as regard the occurrence of AF & it's relation to Mean aortic cross-clamp time .As it is more frequent with longer aortic cross-clamp time P value = 0.002. 3. There is a high significant statistical difference among group III as regard the occurrence of AF & it's relation to Mean pump perfusion time .As it is more frequent with longer pump perfusion time P value = <0.001. 4. There is a high significant statistical difference among group III as regard the occurrence of AF & it's relation to mean intensive care unit stay. As intensive care unit stay is longer with AF patient P value = <0.001.

Discussion:-
Coronary artery bypass graft surgery (CABG) is an successful treatment for ischemic heart disease, but the incidence of atrial fibrillation following CABG is known to be one of the main problems associated with unpleasant effects and mortality.

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Clinical studies have consistently shown that the combination of ascorbic acid and statins with b-blocker is better than b-blocker alone in reducing post-coronary artery bypass surgery risk and improving post-operative performance.
Our data shows that, when higher doses of statin combined with beta blockers atrial fibrillation incidence will be reduced postoperatively. Previously, Kourliouros et al had also found that higher dose statins were associated with greater reduction in postoperative AF (9).
Other studies have shown that when compared with on-pump surgery, the use of off-pump surgery did not substantially affect CRP and fibrinogen levels or the WBC count postoperatively (10).
Carnes and colleagues demonstrated a shortening of the atrial effective refractory period (ERP) with rapid atrial pacing. Treatment with ascorbate attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing. This is in keeping with the established link between ERP changes and early development of AF (11).
Shiroshita-Takeshita et al. compared the effect of vitamin C and E on atrial remodeling to that of simvastatin. Dogs were fitted with internal atrial pacing and were subjected to 1 week of atrial tachypacing (12).
Regarding the predictors of postoperative atrial Fibrillation, we examined age, hypertension, left ventricular ejection fraction, family history, history of smoking, history of diabetes mellitus gender, and left atrial diameter as risk factors of postoperative AF.
We also analyzed the relationship between postoperative AF and number of grafts, duration of aortic crossclamping, duration of cardiopulmonary bypass, operation performed (beating heart vs. not beating heart ), mild ischemic mitral regurgitation, Inotrop during first 24 hr after surgery & ventilation time more than 24 hours.
The most notable difference between the previous studies and the present investigation was that our study compared the effect of combination of both statin & ascorbic acid with b-blocker in three different groups, whereas, other studies compared the effect of combination of only ascorbic acid or statin respectively with b-blocker in 2 groups.
Another notable difference between the current and past study cohorts was that most of previous studies didn't exclude valvular operations, enlargement of left atrium, and other risk factor of atrial fibrillation which were excluded in our study to avoid any bias in the result of our study.
Our data shows that There is a high significant statistical difference among three groups as regard the occurrence of atrial fibrillation as P value is <0.001.
As AF is much lower in second group which is commenced on vitamin C plus b.blocker & third group which is commenced on statin plus b.blocker than first group which is commenced on b.blocker alone. Moreover, it is lower second group than first & third group These findings are close to those of Eslami et al, which showed that oral ascorbic acid is more efficient than betablockers alone in preventing atrial fibrillation after coronary artery bypass grafting when combined with betablockers (13).
Also similar to those of Mithani et al. which showed that among cardiac surgery patients treated with postoperative beta blockers& Statin treatment the incidence of postoperative AF is reduced (14).
There is a strong substantial statistical difference between both groups regarding the frequency of AF in patients with mild ischaemic mitral regurgitation, as it is more normal with non-significant ischaemic mitral regurgitation P value = < 0.001. Another noteworthy difference between the present and past cohorts of the study was.
Current data suggest that off-pump surgery does not reduce incidence of postoperative AF as compared with onpump surgery, this agree with the results in other studies, which is similar to Eslami et al (13).
In contrast, these results do not coincide with Buffolo et al (15) 555 Also, we found a high significant relationship between AF patients & need for ventilation more than 24 hours in all groups .As AF patient needed to be ventilated more than patient without AF P value=<0.001. This result met with Banach et al (16) Conclusion:-Postoperative Atrial Fibrillation is considered one of the most serious complications after CABG.
Our study showed that postoperative Atrial Fibrillation was less frequent in patients who treated with b.blocker combined with vitamin C & Statin than patients who treated with b.blocker alone (P value= <0.001) .
So, vitamin C & Statin in combination with Beta Blockers is more effective than Beta-Blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting in early post operative period.