A Pharmaco-surgical Approach to Reduce Postoperative Atrial Fibrillation After Cardiac Surgery

Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery with an estimated incidence around 35%. It has been found to be an independent predictor of 30-day and 6-month mortality, stroke, renal failure, respiratory failure, and need for permanent pacemaker among others. Previous studies including meta-analyses demonstrate a protective benefit of prophylactic amiodarone to decrease the risk of POAF. However, this has not been widely adopted, and recent society guidelines only give prophylactic amiodarone a Class IIA recommendation, citing risk of amiodarone-related toxicity and hypotension as reasons for the Class IIA recommendation. A meta-analysis comparing cumulative doses of amiodarone found that moderate to higher doses of amiodarone have a marginally increased benefit in reducing the incidence of postoperative atrial fibrillation over lower doses; however, the study did not assess risk of complications stratified by cumulative doses, which has been previously described. Finally, a recent meta-analysis showed that a posterior pericardiotomy was highly effective at reducing postoperative atrial fibrillation. Consequently, the investigators' institution has adopted a pharmaco-surgical approach (prophylactic amiodarone and posterior pericardiotomy) in an effort to reduce postoperative atrial fibrillation after coronary artery bypass cardiac surgery for all patients who meet inclusion/exclusion criteria.

Study Overview

• Status: Active, not recruiting
• Conditions: Atrial Fibrillation New Onset
• Intervention / Treatment: Other: Prophylactic amiodarone and posterior pericardiotomy

• Study Type: Observational
• Enrollment (Anticipated): 242

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population includes all patients undergoing coronary artery bypass cardiac surgery at the Massachusetts General Hospital who meets the above criteria.

Description

Inclusion Criteria:

• Preoperative normal sinus rhythm
• Procedures:
• CABG
• CABG + concomitant valve or aortic replacement/repair

Exclusion Criteria:

• Emergent operation

Procedures:

• MAZE or PVI performed
• Isolated valve replacement or repair
• Isolated aortic procedures
• Heart transplant
• Lung transplant Pre-existing atrial arrhythmias Pre-operative amiodarone use Contraindications to amiodarone use
• PR interval > 240 ms
• 2nd or 3rd degree heart block
• QTc > 550ms
• 2nd or 3rd degree heart block
• Liver impairment (INR > 1.7, AST/ALT > 2x normal)
• Uncontrolled hypothyroidism/hyperthyroidism
• Interstitial lung disease
• Allergy to amiodarone

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pharmaco-Surgical Arm	Other: Prophylactic amiodarone and posterior pericardiotomy; Patients after the implementation of the protocol receive postoperative prophylactic amiodarone and a posterior pericardiotomy. The amiodarone regimen consists of amiodarone 1mg/min x 10 hours (600 mg total) via central line upon arrival to the intensive care unit followed by 400 mg PO BID on postoperative days 1 and 2 followed by 200 mg PO BID on postoperative days 3 and 4 or until discharge, whichever occurs first. The posterior pericardiotomy occurs during the cardiac procedure.
Standard of Care Arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative atrial fibrillation	At least 1 minute duration detected by continuous telemetry or 12-lead electrocardiogram.	Prior to patient discharge or within 30 days after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initiation of systemic anticoagulation	New indication of systemic anticoagulation for stroke prophylaxis due to atrial fibrillation	Either in-hospital or within 30 days of procedure
Readmission	Rates of hospital readmission will be estimated for patients in each of the study intervention groups. Readmissions will be counted in this calculation if patients are admitted to the hospital. Emergency room visits without admission and outpatient visits will not count toward this calculation of readmission rates.	Within 30 days of procedure
Symptomatic bradycardia	Symptomatic bradycardia (HR < 55 bpm) requiring intervention	Either in-hospital or within 30 days of procedure
Number of patients with Amiodarone-related pulmonary toxicity	Clinical diagnosis of amiodarone-related pulmonary toxicity that uses a combination of x-ray findings consistent with known amiodarone-related pulmonary toxicity and clinical findings including shortness of breath, non-productive cough, and other diagnoses have been excluded.	Either in-hospital or within 30 days of procedure
Operative mortality	Operative mortality as defined by either in-hospital death or death within 30 days of discharge.	Either in-hospital death or death within 30 days of discharge
Stroke	Characterized by deficits lasting > 24 hours and/or imaging findings of infarction	Either in-hospital or within 30 days of procedure
Transient ischemic attack	Characterized by examination findings lasting < 24 hours without associated imaging findings	Either in-hospital or within 30 days of procedure
Persistence of atrial fibrillation at discharge	Atrial fibrillation as diagnosed by final ECG	At postoperative surgical visit (around 4-6 weeks)
Postoperative hospital length of stay	The postoperative length of stay will be calculated starting from the end of the procedure to time of discharge	Up to 90 days
Postoperative pleural effusions requiring intervention	Postoperative pleural effusions requiring interventions including thoracostomy drainage or surgical drainage	Either in-hospital or within 30 days of procedure

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Asishana A Osho, MD, MPH, Massachusetts General Hospital

Publications and helpful links

General Publications

• Arsenault KA, Yusuf AM, Crystal E, Healey JS, Morillo CA, Nair GM, Whitlock RP. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD003611. doi: 10.1002/14651858.CD003611.pub3.
• Greenberg JW, Lancaster TS, Schuessler RB, Melby SJ. Postoperative atrial fibrillation following cardiac surgery: a persistent complication. Eur J Cardiothorac Surg. 2017 Oct 1;52(4):665-672. doi: 10.1093/ejcts/ezx039.
• Chatterjee S, Sardar P, Mukherjee D, Lichstein E, Aikat S. Timing and route of amiodarone for prevention of postoperative atrial fibrillation after cardiac surgery: a network regression meta-analysis. Pacing Clin Electrophysiol. 2013 Aug;36(8):1017-23. doi: 10.1111/pace.12140. Epub 2013 Apr 29.
• Buckley MS, Nolan PE Jr, Slack MK, Tisdale JE, Hilleman DE, Copeland JG. Amiodarone prophylaxis for atrial fibrillation after cardiac surgery: meta-analysis of dose response and timing of initiation. Pharmacotherapy. 2007 Mar;27(3):360-8. doi: 10.1592/phco.27.3.360.
• Colunga Biancatelli RM, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of Amiodarone. J Geriatr Cardiol. 2019 Jul;16(7):552-566. doi: 10.11909/j.issn.1671-5411.2019.07.004.
• Orr CF, Ahlskog JE. Frequency, characteristics, and risk factors for amiodarone neurotoxicity. Arch Neurol. 2009 Jul;66(7):865-9. doi: 10.1001/archneurol.2009.96.
• Wolkove N, Baltzan M. Amiodarone pulmonary toxicity. Can Respir J. 2009 Mar-Apr;16(2):43-8. doi: 10.1155/2009/282540.
• Gaudino M, Sanna T, Ballman KV, Robinson NB, Hameed I, Audisio K, Rahouma M, Di Franco A, Soletti GJ, Lau C, Rong LQ, Massetti M, Gillinov M, Ad N, Voisine P, DiMaio JM, Chikwe J, Fremes SE, Crea F, Puskas JD, Girardi L; PALACS Investigators. Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery: an adaptive, single-centre, single-blind, randomised, controlled trial. Lancet. 2021 Dec 4;398(10316):2075-2083. doi: 10.1016/S0140-6736(21)02490-9. Epub 2021 Nov 14.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: February 28, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Postoperative atrial fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Amiodarone
• Other Study ID Numbers: 2004P001528

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No