Effectiveness of Pulmonary Vein Isolation in Prevention of Atrial Fibrillation Following Heart Bypass Surgery
Effectiveness of Pulmonary Vein Isolation in Prevention of Atrial Fibrillation Following Heart Bypass Surgery
Atrial fibrillation (AF) is an irregular heart rhythm that occurs in 30% to 40% of patients
 following heart surgery. This irregular heart rhythm, although often self-limiting, can be
 cause for concern. AF is associated with a two-fold increase in patient complications and
 mortality after heart surgery. During AF, the heart muscle does not contract properly causing
 the blood flow through the heart to slow down potentially forming clots. A clot may then
 enter the blood stream and be carried to the brain, possibly causing a stroke. Patients in
 persistent AF require blood thinners to prevent strokes, and this carries its own bleeding
 risks especially in elderly patients.

 Patients in AF after heart surgery spend twice as many days in the intensive care unit and 3
 to 4 more days in the hospital, hence the impact on hospital resources is quite significant.
 Various medications are used to prevent AF after heart surgery but they are unable to
 completely prevent this complication and the medications have associated side effects. In an
 effort to optimize the care of heart surgery patients, strategies set on eliminating the
 onset of AF after surgery, as opposed to trying to control AF with less than effective
 medications, is a necessity.

 We are proposing a study to determine if isolating the misfiring areas that cause AF at the
 time of bypass surgery in high-risk patients will decrease the occurrence of AF following
 heart surgery. Consenting patients will be randomized to one of two groups. Group 1 will
 undergo bypass surgery plus the additional procedure of pulmonary vein isolation and Group 2
 will undergo bypass surgery only, without the additional procedure. Four staff cardiac
 surgeons at the London Health Sciences Centre will perform all surgeries. Patients will be
 seen postoperatively every six months and will be followed for a two-year period. The
 occurrence of AF will be recorded as well as other complications and lengths of hospital
 stay. We predict that the group with the additional pulmonary vein isolation procedure to
 prevent AF will have a much lower occurrence of this complication. If this is found to be
 beneficial, this will significantly decrease the complications and mortality associated with
 heart surgery. This will have a profound effect in the delivery of care to patients with
 coronary artery disease and other forms of heart disease.
Atrial fibrillation (AF) is a well recognized postoperative complication associated with
 cardiac surgery occurring in approximately 30% to 40% of patients. AF occurs most frequently
 within 24 to 72 hours after surgery. Even though postoperative AF is often a short-lived,
 self-limiting complication, it is associated with a two-fold increase in cardiovascular
 mortality and morbidity. Patients are often symptomatic due to irregular and/or rapid
 ventricular rates and complain of palpitations, anxiety, and diminished physical capacity.
 Postoperative AF is associated with increased incidence of other complications and increased
 hospital length of stay and overall costs. Patients may also develop congestive heart failure
 and hemodynamic instability as a result of this complication. As a result of stasis in the
 left atrium, the risk of thromboembolic complications is increased and the incidence of
 postoperative stroke is increased. Patients with persistent AF have a 13-fold higher hospital
 stroke rate than patients without persistent AF. Further morbidity is added in patients
 requiring anticoagulation if AF lasts greater than 48 hours. Elderly patients requiring
 anticoagulation have a significantly increased risk of hemorrhagic complications. The
 incidence of ventricular arrhythmias is also increased in patients in whom AF develops after
 cardiac operations.

 Postoperative AF has an immense impact on both the cardiac surgery patient and hospital
 resources. One study determined that patients developing AF after cardiac surgery spend about
 twice as many days in the Intensive Care Unit as patients without AF, and their hospital stay
 is extended by 3-4 days.Strategies aimed at preventing postoperative AF are necessary to
 optimize the postoperative care of patients undergoing open heart operations. A large number
 of clinical trials have evaluated the effectiveness of various pharmacologic modalities in
 decreasing rates of AF following cardiac surgery. A recent meta-analysis demonstrated that
 beta blockers, sotalol and amiodarone all reduce the risk of postoperative AF with no marked
 difference between them. However, neither agent completely eliminated the occurrence of
 postoperative AF. In the largest available beta blocker prevention trial, metoprolol
 decreased the prevalence of postoperative AF from 39% to 31%.

 The mechanism of AF following cardiac surgery is not well understood, but possible etiologies
 include rapid firing from an ectopic focus and multiple reentrant circuits within the atria
 to propagate this rhythm. It has been discovered that in chronic and paroxysmal AF, the
 pulmonary veins and the surrounding ostial areas frequently contain focal triggers or
 re-entrant circuits critical to the initiation of AF. In a study of 45 patients with frequent
 episodes of AF refractory to drug therapy, 94% of ectopic beats responsible for instigating
 AF were located in the pulmonary veins. Studies have shown that these foci are responsive to
 radiofrequency ablation. Although it has never been used in the prevention of postoperative
 AF, circumferential pulmonary vein ablation (CPVA) is a technique that has shown much success
 in the treatment of AF. In CPVA, radiofrequency lesions are created around the ostia of each
 pulmonary vein, with the aim to electrically isolate these veins from the left atrium. In one
 study, 26 patients with resistant AF were treated with CPVA and 64% had sinus rhythm
 restoration during ablation. In addition, 85% of patients were free of AF at 9 months, with
 62% no longer requiring antiarrhythmic drugs and 23% taking drugs that had been ineffective
 before ablation. Radiofrequency pulmonary vein isolation with electro-anatomic guidance is a
 safe and effective treatment of AF.

 Recently, Medtronic has developed the Cardioblate® BP and BP 2 Surgical Ablation System
 devices (Minneapolis, MN) to perform pulmonary vein isolation to treat AF. Vichol et al have
 demonstrated a mean ablation time of 15.2 seconds per lesion with the use of this device.

 It is clearly evident that postoperative AF increases morbidity, length of hospital stay, and
 costs associated with surgical coronary artery revascularization. The current prophylactic
 agents are not completely effective at eliminating the occurrence of postoperative AF. It has
 been shown that pulmonary vein isolation is an effective method of treating patients with
 chronic AF. We propose a study to determine if performing pulmonary vein isolation with the
 Cardioblate® BP 2 as an adjunct in those patients undergoing routine coronary artery bypass
 surgery, who are at increased risk of developing postoperative AF, will significantly reduce
 the occurrence of this complication.

 If pulmonary vein isolation is found to considerably decrease the incidence of postoperative
 AF, the associated morbidity will also be decreased. This will have a very profound effect in
 the delivery of care to patients with ischemic heart disease.

 Study Question/Purpose:

 In patients at an increased risk of developing postoperative atrial fibrillation following
 coronary artery bypass grafting, does pulmonary vein isolation with Cardioblate® BP 2 result
 in a decreased incidence of postoperative atrial fibrillation when compared to those patients
 that do not have this adjunct procedure?

 Hypothesis:

 Pulmonary vein isolation with Cardioblate® BP 2 will reduce the incidence of postoperative
 atrial fibrillation in patients undergoing coronary artery bypass grafting who are at an
 increased risk of developing postoperative atrial fibrillation.

 Sample Size A sample size of 79 patients per group was calculated to detect a reduction in
 incidence of postoperative atrial fibrillation from 40% to 20% using a two-sided α = 0.05 and
 a power of 80%.

 Blinding-The patients, outcome assessors, and data analysts will be blinded to which group
 the patients belong. Allocation concealment will be practiced and the randomization scheme
 will not be revealed. Due to the nature of the intervention, it is not possible to blind the
 surgeon performing the operation.

 Trial Implementation

 After randomization is complete, the baseline demographic characteristics of all patients
 will be recorded. Those patients randomized to the control group will undergo coronary bypass
 grafting with cardiopulmonary bypass. Those patients randomized to the experimental group
 will undergo coronary artery bypass grafting with cardiopulmonary bypass (CABG) and pulmonary
 vein isolation (PVI). Medtronic's Cardioblate® BP 2 will be used for the pulmonary vein
 isolation. The following will take place for each patient:

 1. Will be transferred to the Cardiac Surgery Recovery Unit following surgery

 2. Cardiac rhythm will be monitored with telemetry in the CSRU and on the floor until
 discharge home

 3. All arrhythmias will be documented with regards to onset, duration, and immediate
 management - will be recorded by research assistant

 4. All patients will be started on a beta blocker on POD #1 and will continue for minimum 2
 years if tolerable - will be discontinued if any adverse effect (i.e., heart block,
 decreased cardiac output, allergic reaction)

 5. All medications will be documented

 6. After discharge home, all complications and readmissions will be documented (i.e.,
 development of atrial fibrillation or other arrhythmia)

 7. Documentation of those patients requiring anticoagulation for persistent atrial
 fibrillation and duration and complications related to anticoagulation

 8. Follow-up of patients by surgeons, cardiologist and research assistant with ECG every 6
 months for 2 years - patients will be asked to fill out questionnaire at each visit that
 may elicit any symptoms related to arrhythmias Outcomes Statistical Analysis All
 outcomes will be analyzed by a biostatistician blinded to allocation groups using the
 intention to treat principle. The primary purpose of the data analyses is to determine
 whether pulmonary vein isolation reduces the incidence of postoperative atrial
 fibrillation in patients undergoing coronary artery bypass grafting who are at high risk
 of developing postoperative atrial fibrillation. The primary outcome will be compared
 between both groups with the Chi-square test. All patients will be accounted for and we
 will aim for 100% follow-up for all patients.
Inclusion Criteria:

 -  Adult patients (Age>=18) undergoing elective coronary artery bypass grafting with
 cardiopulmonary bypass by 4 surgeons at the London Health Sciences Centre

 -  Patients at high risk of developing postoperative atrial fibrillation--patients are
 required to meet one or more of the following criteria:

 -  Age >=65

 -  Ejection Fraction <50% or Left Ventricle Grade of 2-3

 -  Diabetes Mellitus (independent of type of management)

 Exclusion Criteria:

 -  Any documented prior history of atrial fibrillation (paroxysmal/chronic)

 -  Contraindication to Beta Blockers

 -  Severe COPD with intolerance to Beta Blockers

 -  Concomitant non-CABG procedure

 -  Enrollment in another RCT

 -  Inability to obtain informed consent

 -  Patients' inability to attend follow-up visits

 -  Grade IV left ventricle (EF <20%)

 -  Redo CABG procedure

 -  Off-pump coronary artery bypass surgery