Preventing Atrial Fibrillation After Cardiac Surgery: What Matters Most

John H. Alexander, MD, MHS

Disclosures

J Am Coll Cardiol. 2021;77(1):68-70. 

Post-operative atrial fibrillation is one of the most common complications of cardiac surgery, occurring in 20% to 40% of patients. Its incidence varies on the basis of the definition of post-operative atrial fibrillation, the monitoring used to detect it, and the risk for atrial fibrillation in the population being studied. Post-operative atrial fibrillation is more common in older patients, patients with concomitant valvular heart disease, and, not surprisingly, patients with a history of atrial fibrillation. The cause of post-operative atrial fibrillation is multifactorial and related to both the underlying atrial substrate and the acute inflammation, oxidative stress, and sympathetic output associated with cardiac surgery.[1] Most post-operative atrial fibrillation is short lived and resolves, usually without intervention, in the days or weeks following cardiac surgery.[2] Post-operative atrial fibrillation is associated with longer hospital stays and higher health care costs, and, despite being short lived, is associated with worse long-term clinical outcomes including stroke, heart failure, recurrent hospitalization, and death.[3,4]

In this issue of the Journal, we learn of a simple, intraoperative intervention to prevent post-operative atrial fibrillation. Wang et al.[5] report the results of the CAP-AF (Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation) trial. CAP-AF was a single-center, randomized, controlled, clinical trial in 200 patients without a history of atrial fibrillation undergoing isolated, off-pump coronary artery bypass graft surgery. The intervention was intraoperative ablation of the 4 atrial ganglionic plexi via injection of calcium chloride (CaCl2), compared with a sham control of sodium chloride (NaCl). The primary outcome was the incidence of post-operative atrial fibrillation (≥30 s) on continuous telemetry monitoring through 7 days. Their main finding was that CaCl2 injection was effective and reduced the incidence of post-operative atrial fibrillation from 36% to 15% (hazard ratio: 0.37; 95% confidence interval: 0.21 to 0.64; p = 0.001). In this small study there was no effect of CaCl2 on the duration of hospitalization. There were transient arrhythmias, thought to be associated with injection technique, but no evidence of clinically significant adverse effects of CaCl2 injection. The study was too small and not designed to evaluate the effect of CaCl2 injection on clinical outcomes associated with post-operative atrial fibrillation.

Intraoperative CaCl2 atrial ganglionic ablation can now be added to the list of interventions that are effective in preventing post-operative atrial fibrillation in patients undergoing cardiac surgery. Other effective prophylactic options include beta-blockers, sotalol, amiodarone, magnesium, atrial pacing, and posterior pericardiotomy. In a recent meta-analysis, these interventions reduced post-operative atrial fibrillation by 45% to 66%, similar to the magnitude of reduction seen with CaCl2 ganglionic ablation in CAP-AF, and reduced length of hospital stay by roughly two-thirds of a day.[6] They also appear to have some effect on early post-operative stroke but do not reduce early mortality. Regrettably, none of these interventions have been adequately studied to determine if they affect the long-term adverse outcomes associated with post-operative atrial fibrillation. Despite their demonstrated effectiveness, prophylactic interventions are used in only a minority of patients undergoing cardiac surgery.[7]

These investigators should be congratulated for studying post-operative atrial fibrillation in cardiac surgery. Our therapeutic biases, and our clinical practice guidelines, lead us to assume that atrial fibrillation following cardiac surgery should be managed the same way as spontaneous atrial fibrillation.[8] Given the extreme and transient physiological perturbations associated with cardiac surgery, this may not be true.[9]

Despite the interesting and promising proof-of-concept results from CAP-AF, a number of important questions remain about the safety and efficacy of CaCl2 atrial ganglionic ablation to prevent post-operative atrial fibrillation in patients undergoing cardiac surgery. The CAP-AF trial was conducted at a single institution in China, and a 10-patient "run-in" was included for the surgical staff to become familiar with identifying the location of the atrial ganglionic plexi for injection. It is unknown how these results will generalize to other surgical practices and what the learning curve will be for other, less experienced surgeons unfamiliar with the atrial ganglionic plexi injection techniques. The trial included only relatively low-risk patients without a history of atrial fibrillation undergoing isolated coronary artery bypass graft surgery without cardiopulmonary bypass. It is unknown whether CaCl2 injection will also prevent post-operative atrial fibrillation in patients with a history of pre-existing atrial fibrillation. Atrial ganglionic ablation, with CaCl2 or other interventions, may be less effective in patients with more established atrial fibrillation.[10–12] It is also unknown whether CaCl2 injection will be effective and prevent post-operative atrial fibrillation in patients undergoing more extensive cardiac surgery, including valve replacement or repair, or in patients undergoing surgery with the support of cardiopulmonary bypass. Before the results of CAP-AF are incorporated into practice, these findings should be replicated, preferably in other settings and higher risk populations.

The most important limitation of CAP-AF, and almost all other studies on the prevention of post-operative atrial fibrillation, is their reliance on what is essentially a short-term electrocardiographic outcome. CAP-AF included 200 patients, randomized them to CaCl2 or NaCl, and followed them for 7 days for the occurrence of post-operative atrial fibrillation on telemetry. Presumably, the atrial ganglionic plexi are there for a reason. Are the effects of CaCl2 injection into the atrial ganglionic plexi temporary or permanent? Are there longer term adverse effects of CaCl2 injection? Although preventing post-operative atrial fibrillation is intuitively desirable and will likely reduce health care costs and shorten hospital stays, we do not know if it will improve the long-term clinical outcomes associated with post-operative atrial fibrillation. Given that post-operative atrial fibrillation is usually short lived and the associated adverse outcomes extend over years, it is a real and unanswered question as to whether the arrhythmia itself is the cause of the adverse outcomes or simply a marker of a higher risk population. Before perioperative CaCl2 injection is routinely adopted in surgical practice, larger, multicenter studies with longer term follow-up are needed to know whether CaCl2 ganglionic ablation has adverse effects and, more important, whether it improves what matters most to our patients.

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