Effectiveness of Pulmonary Vein Isolation in Prevention of Atrial Fibrillation Following Heart Bypass Surgery
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): PVI with Medtronic's Cardioblate BP2 radiofrequency catheter
Intervention type(s): Device
Intervention description(s): Ablation of the right and left pulmonary veins
Other intervention name(s): Medtronic's Cardioblate BP2 radiofrequency catheter
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Effectiveness; Pulmonary Vein Isolation Procedure; Coronary Artery Bypass Surgery; Atrial Fibrillation