**6. Non-pharmacologic strategies for the prevention of POAF in cardiac surgery**

### **6.1 Pacing**

The use of right atrial, left atrial, bi-atrial and pacing of the Bachman's bundle all have been evaluated in their merit in reducing post-operative supraventricular arrhythmias. The mechanism of atrial fibrillation is in part believed to be related to changes in the substrate on a temporary basis which causes lengthening of the P-R interval thereby allowing re-entrant POAF (Fan et al., 2003). There is evidence that bi-atrial pacing is beneficial especially in the age group over 70 (Gerstenfeld et al., 2001). While bi-atrial pacing has demonstrated some success it is noted the right atrial pacing alone is less favorable (Chung et al., 1996). Pacing thresholds and stability of the pacing wire has become problematic and alternate sources of pacing locations have been sought out (Goette et al., 2002). Bachman's bundle, a thick fibrous strip of muscle at the roof of both atria that crosses the intra-atrial septum has been demonstrated to have low pacing thresholds for at least five days post-operatively. This site may reduce intra-atrial conduction times thus reducing POAF (Goette et al., 2002).

TZD patients received amiodarone. Despite this, the study was unable to show a significant reduction in POAF. This may have been due to a lack of power due to small sample size, dilution of effect from concomitant beta-blocker and/or amiodarone use, or increased fluid retention associated with TZD use. In this same analysis, statins did demonstrate a significant reduction in POAF (28% versus 37%, p<0.05). This suggests that the most likely reason TZDs were of no benefit is due to their risk of fluid accumulation thereby attenuating any anti-inflammatory effect (Lertsburapa K, 2008). At this time, TZDs can not be recommended as an option for POAF prophylaxis, either alone or in combination with beta-

The rationale behind the use of triiodothyronine (T3) for POAF prophylaxis lies in the observation that CPB results in a euthyroid sick or low T3 state (Klemperer et al., 1996). The mechanism by which T3 may prevent POAF is unknown (Reichert & Verzino, 2001). Interestingly, it has been shown that POAF is more common in patients with subclinical hypothyroidism when compared to those with normal thyroid function, after adjustments for other variables (Park et al., 2009). One demonstrated that intravenous administration of T3 starting at the time of cross clamp removal significantly decreases the incidence of POAF when compared to placebo (24% versus 46%, p=0.009) (Klemperer et al., 1996). All patients had a left ventricular ejection fraction of less than 40%. While T3 administration was associated with significantly higher postoperative cardiac indices and lower systemic vascular resistance, there was no significant difference in LOS (Klemperer et al., 1995). The authors previously reported data from this same study but included those patients with a history of preoperative atrial fibrillation (Klemperer et al., 1995). In this earlier study, there were no significant differences in the incidence of SVT between the two treatment groups. The authors do not report postoperative beta-blocker use but suggest that because the study population was more ill (ejection fraction <40%), beta-blockade may not be as effective and add-on therapy would be warranted. None of the guidelines currently recommend the use of T3 due to low quality of evidence (Bradley et al., 2005). Until more data becomes available

supporting its for POAF prophylaxis, it should not be routinely utilized.

**6. Non-pharmacologic strategies for the prevention of POAF in cardiac** 

may reduce intra-atrial conduction times thus reducing POAF (Goette et al., 2002).

The use of right atrial, left atrial, bi-atrial and pacing of the Bachman's bundle all have been evaluated in their merit in reducing post-operative supraventricular arrhythmias. The mechanism of atrial fibrillation is in part believed to be related to changes in the substrate on a temporary basis which causes lengthening of the P-R interval thereby allowing re-entrant POAF (Fan et al., 2003). There is evidence that bi-atrial pacing is beneficial especially in the age group over 70 (Gerstenfeld et al., 2001). While bi-atrial pacing has demonstrated some success it is noted the right atrial pacing alone is less favorable (Chung et al., 1996). Pacing thresholds and stability of the pacing wire has become problematic and alternate sources of pacing locations have been sought out (Goette et al., 2002). Bachman's bundle, a thick fibrous strip of muscle at the roof of both atria that crosses the intra-atrial septum has been demonstrated to have low pacing thresholds for at least five days post-operatively. This site

blockers.

**surgery 6.1 Pacing** 

**5.3 Triiodothyronine** 

In a meta-analysis of 10 clinical trials it was demonstrated that atrial pacing at the right atrium, left atrium or Bachman's bundle produced a decrease in atrial fibrillation (Fan et al., 2003). These 10 studies are limited by multiple pacing protocols, including using complex algorithms, fixed pacing and flexible algorithms. Eight of these studies demonstrated that bi-atrial pacing reduced the odds of POAF by 54% (OR=0.46; 95% CI 0.3-0.71). There was a significant lack of use of beta-adrenergic blocking drugs used in the post-operative phase in the meta-analysis at 56%. In a small group of patients (n=80) who underwent valvular surgery it was found that bi-atrial synchronous pacing for 72 hours decreased atrial fibrillation from 45% in the control group to 20% in the paced group (p=0.02) (Debrunner et al., 2004). It is noted that only 30% of this small group were exposed to pre-operative betaadrenergic blockade, and post-operative use was not collected.

Pacing of the atria is not without risk. In a randomized trial of 100 patients it was found that atrial fibrillation occurred in 27.5% of the paced patients and 28.6% of the control group (Chung, 2003). There was an increase in atrial ectopy (10 fold increase) in the group of patients whom developed atrial fibrillation (Chung, 2003). It was hypothesized that inconsistent pacing in the atria, under sensing and intermittent loss of capture were factors in the increase in ectopy (Chung, 2003). A sub-analysis of patients paced at a lower rate (80 bpm) and use of an algorithm that maintained the atrial rate 50 ms above the intrinsic rate, demonstrated no difference in atrial fibrillation rates (Chung, 2003).

The most recent 2010 European AF guidelines recommend that biatrial pacing should be considered for prophylaxis (Class 2B recommendation based on Level A evidence) (ESC, 2010). Earlier publication in 2006 by EACTS for the guidelines for POAF after cardiothoracic surgery in 2006 (Grade A recommendation based on Level 1B studies) and in 2005 by the American College of Chest Physicians (ACCP) (Strength: B, Evidence: good, Net Benefit: small/weak) both similarly recommend biatrial pacing for prophylaxis (Dunning et al., 2006; Maisel & Epstein, 2005). (Table 1) Specifically, the 2005 ACCP guideline specifically recommends not using unilateral pacing of the right or left atrium. (Strength: I, Evidence: fair, Net Benefit: small/weak) (Maisel & Epstein, 2005). Furthermore, the 2006 EACTS guidelines recommend that temporary pacing should be used in high risk patients receiving beta-blockers and amiodarone for prophylaxis as protection from complications of bradycardia (Grade A recommendation based of Level 1B studies). The CCS guideline also recommends considering atrial pacing with or without a ventricular lead in patients with symptomatic bradycardia (Class 2A recommendation based on Level A evidence) and those patients who are not on a beta-blocker before surgery (Class 2A recommendation based on Level B evidence) (Mitchell et al., 2005a; Kerr & Roy, 2004). Last, the CCS guidelines strongly recommend placing temporary ventricular epicardial pacing electrode wires at the time of surgery to allow for backup pacing as necessary (Class 1 recommendation based on Level C evidence) (Mitchell et al., 2005a; Kerr & Roy, 2004).

### **6.2 Posterior pericardiotomy**

The pathophysiology of posterior pericardiotomy is based upon adequate drainage of the pericardial space thereby reducing pericardial effusion (Biancari, 2010). Only the earlier European guidelines do include posterior pericardiotomy as a non-pharmacologic option for the prevention of POAF (Grade B recommendation based on Level 1B studies) (Dunning et al., 2006). A recent meta-analysis evaluating 763 patients found that patients who had a posterior pericardiotomy significantly reduced POAF (10.8% versus 28.1%, p=0.003; OR. 0.33, 95% CI 0.16–0.69) and early (6.9% versus 46.2% p<.0001) or late (0% versus 11.3%,

Strategies for the Prevention of Postoperative Atrial Fibrillation in Cardiac Surgery 225

identified that hypothermia decreases sympathetic activation which lowers plasma norepinephrine levels and neuropeptide Y levels (Adams et al., 2000). A study randomized

The surgical maze procedure, or Cox-maze procedure, uses surgical incisions in the atria to form scar tissue to interrupt possible macroreentrant circuits (Cox et al., 1991). Alternative energy sources including radiofrequency or cryothermia have been incorporated to create lesions blocking atrial conduction without surgical incision into the atria. These procedures can be effective in restoring sinus rhythm, however when it is combined with other open heart operations to treat chronic AF, operative morbidity is consistently increased (Banach, et al., 2010). It is usually only performed on patients needing open-heart surgery for other issues, such as valve replacement or repair or CABG. The Canadian and most recent European guidelines both mention surgical ablation, however it should only be considered in patients with symptomatic AF already undergoing cardiac surgery (Kerr & Roy, 2004; ESC, 2010). The Canadian guidelines additionally mention that it should be considered in patients with previous AF who are undergoing mitral valve surgery, who may be at higher

For the prevention of postoperative atrial fibrillation in patients undergoing cardiac surgery, pharmacologic prophylaxis with beta-blockers and amiodarone are widely utilized. Evidence based guidelines also support the use of sotalol, magnesium, and atrial pacing. While these agents reduce the incidence of POAF, they do not eliminate it. Thus, there is a need for additional effective therapies. Other strategies that may be beneficial for prophylaxis include dofetilide, renin-angiotensin-aldosterone-system modulators, statins, corticosteroids, omega-3 fatty acids, ascorbic acid, N-acetylcysteine, sodium nitroprusside, levosimendan or intraoperative maze procedure in symptomatic AF patients undergoing cardiac surgery. For most of these strategies, there is a need for additional large scale, adequately powered, clinical studies to determine the benefit before they can be considered for routine use. Identification of high risk patients undergoing cardiac surgery and use of appropriate pharmacologic and non-pharmacologic therapies may further reduce the incidence of POAF and lead to improvements in the overall morbidity and burden to the

Acikel, S.; Bozbas, H.; Gultekin, B.; Aydinalp, A.; Saritas, B.; Bal, U.; Yildirir, A.;

Muderrisoglu, H.; Sezgin, A. & Ozin, B. (2008). Comparison of efficacy of

 C) and found no difference in the incidence of POAF between the groups, thus did not validate this pathophysiologic basis of POAF (Adams et al., 2000). The study was completed without benefit of knowledge regarding use of beta blockers or other adjunct measures to prevent POAF which could influence the outcome of that study.. It should be noted that POAF is still common in beating heart surgery with normothermia, therefore negating the

C) and moderate hypothermia

patients into two groups including mild hypothermia (34

use of hypothermia as a valid tool in prevention of POAF.

**6.6 Maze procedure during open-heart surgery** 

risk of POAF (Kerr & Roy, 2004)

**7. Conclusion** 

health care system.

**8. References** 

(28

p=0.0001) pleural effusion (Biancari & Mahar, 2010). The authors noted several limitations to the studies favoring pericardiotomy, including no data regarding hemodynamic instability, re-operation for bleeding and use of drugs for prevention of POAF (Biancari & Mahar, 2010). Posterior pericardiotomy however is not risk free. Potential risks include cardiac herniation as well as compromise of grafts protruding thought the pericardiotomy (Biancari & Mahar, 2010).

### **6.3 Coronary bypass surgery without the use of cardiopulmonary bypass ("Off-pump" CABG)**

The introduction of cardiac surgery without the use of cardiopulmonary bypass, also referred to as "off-pump", has been hypothesized to lower the incidence of POAF. The multiple mechanisms hypothesized to cause POAF may all be avoided when coronary bypass surgery is completed without the use of the cardiopulmonary bypass circuit. Salamon et al evaluated a series of over 2500 patients with 252 undergoing "off-pump" coronary bypass surgery (Salamon et al., 2003). Patient on cardiopulmonary bypass had higher rates of atrial fibrillation and concluded that avoiding cardiopulmonary bypass did not aid in the reduction of AF. Another retrospective analysis by Enc and colleagues in 670 patients undergoing conventional compared to "off-pump" coronary bypass surgery, found a lower, but non-significant reduction in POAF respectively (16.1% versus 14.6%) (Enc et al., 2004).

Elimination of the use of cardiopulmonary bypass in cardiac surgery has shown inconsistent results from meta-analyses and studies. Only the European EACTS 2006 guidelines supports its use as a non-pharmacologic option are the 2006 EACTS guidelines and include earlier metaanalysis that show conflicting results (Dunning et al., 2006). Focus for the prevention of POAF in cardiac surgery patients should focus on the use more standard prophylactic regimens including beta-blockers, rather than explicit avoidance of cardiopulmonary bypass.

### **6.4 Pericardial fat pad**

Two other novel non-pharmacologic options that have been studied include preservation of pericardial fat pad and regulation of body temperature during cardiac surgery which targets disruption of AV node and inflammation, respectively. The anterior fat pad is commonly disrupted to provide clear field of view while applying the cross clamp during cardiac surgery. The anterior fat pad is known to possess parasympathetic ganglia as well as vagal pathways (Singh et al., 1996). The fat pads located at the superior vena cava-atrial junction contain post ganglionic fibers that lead to the sino-atrial node (Carlson et al., 1992). The fat pads located at the pulmonary vein-left atrium contain post ganglionic fibers that innervate the atrio-ventricular node (Quan et al., 2001). These fat pads are analogous to dog physiology and has been determined that ablation of these fibers in dogs reduces susceptibility of POAF. In a study of 55 patients where the fat pad was preserved, a significant reduction of POAF was observed (Cummings et al., 2004). A significant limitation of this research includes a small sample size and not accounting for the use of beta-adrenergic blocking drugs. Secondarily the rate of atrial fibrillation in "off-pump" cardiac surgery remains a significant problem despite no manipulation of the epicardial fat pads (Salamon et al., 2003).

### **6.5 Regulation of body temperature during surgery**

The other novel non-pharmacologic strategy is to regulate body temperature to limit systemic effects of the inflammatory cascade during cardiac surgery. Adams and colleagues identified that hypothermia decreases sympathetic activation which lowers plasma norepinephrine levels and neuropeptide Y levels (Adams et al., 2000). A study randomized patients into two groups including mild hypothermia (34 C) and moderate hypothermia (28 C) and found no difference in the incidence of POAF between the groups, thus did not validate this pathophysiologic basis of POAF (Adams et al., 2000). The study was completed without benefit of knowledge regarding use of beta blockers or other adjunct measures to prevent POAF which could influence the outcome of that study.. It should be noted that POAF is still common in beating heart surgery with normothermia, therefore negating the use of hypothermia as a valid tool in prevention of POAF.

### **6.6 Maze procedure during open-heart surgery**

The surgical maze procedure, or Cox-maze procedure, uses surgical incisions in the atria to form scar tissue to interrupt possible macroreentrant circuits (Cox et al., 1991). Alternative energy sources including radiofrequency or cryothermia have been incorporated to create lesions blocking atrial conduction without surgical incision into the atria. These procedures can be effective in restoring sinus rhythm, however when it is combined with other open heart operations to treat chronic AF, operative morbidity is consistently increased (Banach, et al., 2010). It is usually only performed on patients needing open-heart surgery for other issues, such as valve replacement or repair or CABG. The Canadian and most recent European guidelines both mention surgical ablation, however it should only be considered in patients with symptomatic AF already undergoing cardiac surgery (Kerr & Roy, 2004; ESC, 2010). The Canadian guidelines additionally mention that it should be considered in patients with previous AF who are undergoing mitral valve surgery, who may be at higher risk of POAF (Kerr & Roy, 2004)

### **7. Conclusion**

224 Special Topics in Cardiac Surgery

p=0.0001) pleural effusion (Biancari & Mahar, 2010). The authors noted several limitations to the studies favoring pericardiotomy, including no data regarding hemodynamic instability, re-operation for bleeding and use of drugs for prevention of POAF (Biancari & Mahar, 2010). Posterior pericardiotomy however is not risk free. Potential risks include cardiac herniation as well as compromise of grafts protruding thought the pericardiotomy (Biancari

The introduction of cardiac surgery without the use of cardiopulmonary bypass, also referred to as "off-pump", has been hypothesized to lower the incidence of POAF. The multiple mechanisms hypothesized to cause POAF may all be avoided when coronary bypass surgery is completed without the use of the cardiopulmonary bypass circuit. Salamon et al evaluated a series of over 2500 patients with 252 undergoing "off-pump" coronary bypass surgery (Salamon et al., 2003). Patient on cardiopulmonary bypass had higher rates of atrial fibrillation and concluded that avoiding cardiopulmonary bypass did not aid in the reduction of AF. Another retrospective analysis by Enc and colleagues in 670 patients undergoing conventional compared to "off-pump" coronary bypass surgery, found a lower, but non-significant

Elimination of the use of cardiopulmonary bypass in cardiac surgery has shown inconsistent results from meta-analyses and studies. Only the European EACTS 2006 guidelines supports its use as a non-pharmacologic option are the 2006 EACTS guidelines and include earlier metaanalysis that show conflicting results (Dunning et al., 2006). Focus for the prevention of POAF in cardiac surgery patients should focus on the use more standard prophylactic regimens

Two other novel non-pharmacologic options that have been studied include preservation of pericardial fat pad and regulation of body temperature during cardiac surgery which targets disruption of AV node and inflammation, respectively. The anterior fat pad is commonly disrupted to provide clear field of view while applying the cross clamp during cardiac surgery. The anterior fat pad is known to possess parasympathetic ganglia as well as vagal pathways (Singh et al., 1996). The fat pads located at the superior vena cava-atrial junction contain post ganglionic fibers that lead to the sino-atrial node (Carlson et al., 1992). The fat pads located at the pulmonary vein-left atrium contain post ganglionic fibers that innervate the atrio-ventricular node (Quan et al., 2001). These fat pads are analogous to dog physiology and has been determined that ablation of these fibers in dogs reduces susceptibility of POAF. In a study of 55 patients where the fat pad was preserved, a significant reduction of POAF was observed (Cummings et al., 2004). A significant limitation of this research includes a small sample size and not accounting for the use of beta-adrenergic blocking drugs. Secondarily the rate of atrial fibrillation in "off-pump" cardiac surgery remains a significant problem despite no manipulation of the epicardial fat

The other novel non-pharmacologic strategy is to regulate body temperature to limit systemic effects of the inflammatory cascade during cardiac surgery. Adams and colleagues

including beta-blockers, rather than explicit avoidance of cardiopulmonary bypass.

**6.3 Coronary bypass surgery without the use of cardiopulmonary bypass** 

reduction in POAF respectively (16.1% versus 14.6%) (Enc et al., 2004).

& Mahar, 2010).

**("Off-pump" CABG)** 

**6.4 Pericardial fat pad** 

pads (Salamon et al., 2003).

**6.5 Regulation of body temperature during surgery** 

For the prevention of postoperative atrial fibrillation in patients undergoing cardiac surgery, pharmacologic prophylaxis with beta-blockers and amiodarone are widely utilized. Evidence based guidelines also support the use of sotalol, magnesium, and atrial pacing. While these agents reduce the incidence of POAF, they do not eliminate it. Thus, there is a need for additional effective therapies. Other strategies that may be beneficial for prophylaxis include dofetilide, renin-angiotensin-aldosterone-system modulators, statins, corticosteroids, omega-3 fatty acids, ascorbic acid, N-acetylcysteine, sodium nitroprusside, levosimendan or intraoperative maze procedure in symptomatic AF patients undergoing cardiac surgery. For most of these strategies, there is a need for additional large scale, adequately powered, clinical studies to determine the benefit before they can be considered for routine use. Identification of high risk patients undergoing cardiac surgery and use of appropriate pharmacologic and non-pharmacologic therapies may further reduce the incidence of POAF and lead to improvements in the overall morbidity and burden to the health care system.

### **8. References**

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**1. Introduction** 

and treat them appropriately.

precordial leads are all unipolar and include V1-V6.

**2. Normal physiology** 

heart. (1)

**10** 

*USA* 

**Post Operative Arrhythmias** 

Rama Dilip Gajulapalli and Florian Rader

Heart rhythm disturbances are being increasingly recognized during the postoperative period. While many are transient and short lived without altering the recovery phase after cardiac or non-cardiac surgery, they do have the potential to pose a threat to patient's health, prolong hospital stay, and in a minority of patients may even cause death. Continuous monitoring is becoming the standard of care after surgery and therefore rhythm disturbances are being more frequently diagnosed during the postoperative recovery period. While cardiology consultation may be required, surgeons and anesthesiologists are often the first responders and are expected to be able to recognize the rhythm disturbance

Normal sinus rhythm is when the heart beats in an orderly predetermined sequence. The atria contract initially in response to the firing of an impulse by the Sino-Atrial (SA) node located at the junction of the superior vena cava and the right atrium. The SA node contains specialized tissue with 'pacemaker cells', which can initiate repetitive rhythmic action potentials. These potentials then travel via internodal atrial pathways to the AtrioVentricular (AV) node located at the right posterior portion of the interatrial septum. The AV node slows conduction into the bundle of HIS which then leads to its right and left branches. The left bundle branch further divides into anterior and posterior fascicles. The final pathway of conduction is the Purkinje system, which consists of a network of fibers that transmit the electrical impulse to the myocardium near the apex of the

The Electrocardiogram (ECG) is a reliable and practical way to document the underlying cardiac rhythm. It essentially consists of a recording obtained by 12 surface leads which trace the electrical activity of the heart from different directions. The 12 leads include 6 limb and 6 precordial leads. The limb leads include 3 bipolar leads (I, II, III) meaning they have 2 electrodes of opposite polarity. The other limb leads are aVR, aVL, aVF which are the unipolar leads meaning they have only one electrode connecting to a central terminal. The

The limb leads are the frontal plane leads representing electrical current along the coronal plane of the heart, i.e. right/left and superior/inferior. The precordial leads represent the horizontal plane of the heart measuring transverse currents, i.e. right/left and anterior/posterior. Lead I traces currents from right shoulder to left shoulder, lead II from

*Case Western Reserve University* 

