Advertisement

2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures

Open ArchivePublished:June 30, 2014DOI:https://doi.org/10.1016/j.jtcvs.2014.06.036

      CTSNet classification

      Preamble

      Our mission was to develop evidence-based guidelines for the prevention and treatment of perioperative/postoperative atrial fibrillation and flutter (POAF) for thoracic surgical procedures. Sixteen experts were invited by the American Association for Thoracic Surgery (AATS) leadership: 7 cardiologists and electrophysiology specialists, 3 intensivists/anesthesiologists, 1 clinical pharmacist, joined by 5 thoracic and cardiac surgeons who represented AATS (see Online Data Supplement 1 for the list of members and Online Data Supplement 2 for the conflict of interest declaration online).

      Methods of Review

      Members were tasked with making recommendations based on a review of the literature, with grading the quality of the evidence supporting the recommendations, and with assessing the risk-benefit profile for each recommendation. The level of evidence was graded by the task force panel according to standards published by the Institute of Medicine (Table 1). For the development of the guidelines we followed the recommendations of The Institute of Medicine (IOM) 2011 Clinical Practice Guidelines We Can Trust: Standards for Developing Trustworthy Clinical Practice Guidelines; www.iom.edu/cpgstandards.
      Institute of Medicine
      Clinical Practice Guidelines We Can Trust.
      Efforts were made to minimize repetition of existing guidelines
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • Fernando H.C.
      • Jaklitsch M.T.
      • Walsh G.L.
      • Tisdale J.E.
      • Bridges C.D.
      • Mitchell J.D.
      • et al.
      The Society of Thoracic Surgeons practice guideline on the prophylaxis and management of atrial fibrillation associated with general thoracic surgery: executive summary.
      ; rather we focused on new information and advances in diagnosis and therapy, and present these current guidelines within the framework of the new IOM recommendations. In order to meet these standards, most societies (American Heart Association and AATS included) initiated the revision
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      of existing guidelines.
      Table 1Size of treatment effect and level of evidence for its impact
      Schema used to guide the grading of available published evidence and the expected effect of the interventions for their impact on patient outcomes (the arrow indicates the direction of increased effect size). COR, Class of recommendation.
      Task force subgroups were formed and tasked with preparing a summary of the available literature for each subtopic. Literature searches were conducted using PubMed, focused on articles published since 2000 except in rare circumstances. Both the summaries and original articles were made available to each task force member via a shared electronic folder. The subgroup summaries as well as the original literature were presented and discussed at 9 scheduled teleconferences. The conferences were recorded. Articles were selected for inclusion based on consensus opinion by task force members. Writing groups were formed to develop the draft guidelines for each subtopic, with 3 to 7 members and a leader for each group. Group recommendations were submitted before being presented for discussion and voting at a 1-day face-to-face conference.
      Members were specifically asked to assess the applicability of the available evidence to patients undergoing thoracic surgery. All recommendations were subjected to a vote. Acceptance for the final document required greater than 75% approval of each of the recommendations.
      A final draft was prepared by the chairman of the task force and made available in a written form to each member for final comments. Subsequently, the recommendations were posted for public comments for AATS members (via REDCap), and then peer reviewed by outside experts selected by the AATS Council.
      The following recommendations are based on the best available evidence from thoracic surgery. When evidence specific to thoracic surgery was not available, we extrapolated from the cardiac surgical literature. In the absence of direct evidence, we present the best expert opinion based on cardiology/cardiac electrophysiology experience and best practices.
      An executive summary was prepared for publication in a printed format; this more extensive guideline was prepared for online publication with additional comments, data, and a comprehensive list of references.

      AATS Member Survey

      Our survey of the AATS members (results presented in Online Data Supplement 3) indicated the need for a guideline update and identified opportunities for improvement in the areas of prevention, standards for postoperative electrocardiography (ECG) monitoring, and for the possible use of novel oral anticoagulants. When asked how the AATS could help members improve their practices; 29% of respondents recommended “initiating studies,” whereas 58% recommended that the AATS “issue guidelines” and promote uniform practices.

      Target Audience and the Patient Population

      These guidelines are intended for all noncardiac intrathoracic surgeries and esophagectomies, as well as for patients whose risk factors and comorbidities place them at intermediate to high risk for POAF, independent of the procedure. In assessing the patient's risk for POAF, it must be noted that the risks posed by the procedure and by patient factors/comorbidities will likely be additive, if not synergistic. Therefore, these factors should be evaluated in combination during the preoperative assessment.
      The target audience includes not only thoracic surgeons and anesthesiologists but all providers who participate in the care of thoracic surgical patients.
      The following novel information is included in this 2014 document: (1) standardized definitions for atrial fibrillation (AF) and (2) recommendations for: (a) ECG monitoring, (b) postdischarge management, (c) use of the new class of novel oral anticoagulants (NOAC); and (d) obtaining cardiology consultation. In addition, flow diagrams summarize the strategies for acute and chronic management. Specific drug recommendations and dosing tables are also included.

      Epidemiology of POAF, Its Impact on Outcomes, Cost, and Morbidity

      AF, the most common sustained arrhythmia after pulmonary and esophageal surgery, is a major, potentially preventable, adverse outcome. POAF peaks on postoperative days 2 to 4, and 90% to 98% of new-onset POAF resolves within 4 to 6 weeks. Postoperative atrial fibrillation has multiple negative implications. In the acute setting, the tachyarrhythmia can lead to hemodynamic instability, necessitating prompt intervention. A sustained increased heart rate can result in heart failure, a less common but clinically devastating situation, the incidence of which is not reported in the literature.
      The incidence of POAF varies widely based on the intensity of surgical stress (Table 2, A
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • De Decker K.
      • Jorens P.G.
      • Van Schil P.
      Cardiac complications after noncardiac thoracic surgery: an evidence-based current review.
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Park B.J.
      • Zhang H.
      • Rusch V.W.
      • Amar D.
      Video-assisted thoracic surgery does not reduce the incidence of postoperative atrial fibrillation after pulmonary lobectomy.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Ciszewski P.
      • Tyczka J.
      • Nadolski J.
      • Roszak M.
      • Dyszkiewicz W.
      Lower preoperative fluctuation of heart rate variability is an independent risk factor for postoperative atrial fibrillation in patients undergoing major pulmonary resection.
      • Krowka M.J.
      • Pairolero P.C.
      • Trastek V.F.
      • Payne W.S.
      • Bernatz P.E.
      Cardiac dysrhythmia following pneumonectomy. Clinical correlates and prognostic significance.
      • Hardy J.
      Risk factors for atrial fibrillation following extrapleural pneumonectomy, the effect of prophylactic beta blockade.
      • Lee G.
      • Wu H.
      • Kalman J.M.
      • Esmore D.
      • Williams T.
      • Snell G.
      • et al.
      Atrial fibrillation following lung transplantation: double but not single lung transplant is associated with long-term freedom from paroxysmal atrial fibrillation.
      • Henri C.
      • Giraldeau G.
      • Dorais M.
      • Cloutier A.-S.
      • Girard F.
      • Noiseux N.
      • et al.
      Atrial fibrillation after pulmonary transplantation: incidence, impact on mortality, treatment effectiveness, and risk factors.
      • Nielsen T.D.
      • Bahnson T.
      • Davis R.D.
      Atrial fibrillation after pulmonary transplant.
      • Tisdale J.E.
      • Wroblewski H.A.
      • Wall D.S.
      • Rieger K.M.
      • Hammoud Z.T.
      • Young J.V.
      • et al.
      A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy.
      ) and patient characteristics (Table 2, B
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Rao V.P.
      • Addae-Boateng E.
      • Barua A.
      • Martin-Ucar A.E.
      • Duffy J.P.
      Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation following oesophagectomy.
      • Ivanovic J.
      • Maziak D.E.
      • Ramzan S.
      • McGuire A.L.
      • Villeneuve P.J.
      • Gilbert S.
      • et al.
      Incidence, severity and perioperative risk factors for atrial fibrillation following pulmonary resection.
      • Polanczyk C.A.
      • Goldman L.
      Supraventricular arrhythmia in patients having noncardiac surgery: clinical correlates and effect on length of stay.
      ). Some of the risk factors for AF such as hypertension, obesity, and smoking, are modifiable, whereas others, such as older age, Caucasian ancestry, and male sex, are not.
      Table 2, aRisk stratification of thoracic surgical procedures for their risk of POAF
      Type of proceduresRisk of POAF by surgical procedures
      Low risk procedures (<5% incidence)Intermediate risk procedures (5%-15% incidence)High risk procedures (>15% incidence)
      Intrathoracic/airway procedures
       Minor proceduresFlexible bronchoscopy with and without biopsy

      Photodynamic therapy

      Tracheal stenting

      Placement of thoracostomy tube or PleurX catheter (CareFusion Corporation, San Diego, Calif)

      Pleuroscopy, pleurodesis, decortication
       Procedures with moderate stressTracheostomy

      Rigid bronchoscopy

      Mediastinoscopy

      Thoracoscopic wedge resection
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.


      Bronchoscopic laser surgery
      Thoracoscopic sympathectomy
       Major proceduresSegmentectomy
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      Resection of anterior mediastinal mass

      Thoracoscopic lobectomy

      Open thoracotomy for lobectomy
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • De Decker K.
      • Jorens P.G.
      • Van Schil P.
      Cardiac complications after noncardiac thoracic surgery: an evidence-based current review.
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Park B.J.
      • Zhang H.
      • Rusch V.W.
      • Amar D.
      Video-assisted thoracic surgery does not reduce the incidence of postoperative atrial fibrillation after pulmonary lobectomy.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Ciszewski P.
      • Tyczka J.
      • Nadolski J.
      • Roszak M.
      • Dyszkiewicz W.
      Lower preoperative fluctuation of heart rate variability is an independent risk factor for postoperative atrial fibrillation in patients undergoing major pulmonary resection.


      Tracheal resection and reconstruction/carinal resection

      Pneumonectomy
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • De Decker K.
      • Jorens P.G.
      • Van Schil P.
      Cardiac complications after noncardiac thoracic surgery: an evidence-based current review.
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Ciszewski P.
      • Tyczka J.
      • Nadolski J.
      • Roszak M.
      • Dyszkiewicz W.
      Lower preoperative fluctuation of heart rate variability is an independent risk factor for postoperative atrial fibrillation in patients undergoing major pulmonary resection.
      • Krowka M.J.
      • Pairolero P.C.
      • Trastek V.F.
      • Payne W.S.
      • Bernatz P.E.
      Cardiac dysrhythmia following pneumonectomy. Clinical correlates and prognostic significance.
      • Hardy J.
      Risk factors for atrial fibrillation following extrapleural pneumonectomy, the effect of prophylactic beta blockade.


      Pleurectomy
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.


      Volume reduction/bullectomy

      Bronchopleural fistula repair

      Clagett window

      Lung transplantation
      • Lee G.
      • Wu H.
      • Kalman J.M.
      • Esmore D.
      • Williams T.
      • Snell G.
      • et al.
      Atrial fibrillation following lung transplantation: double but not single lung transplant is associated with long-term freedom from paroxysmal atrial fibrillation.
      • Henri C.
      • Giraldeau G.
      • Dorais M.
      • Cloutier A.-S.
      • Girard F.
      • Noiseux N.
      • et al.
      Atrial fibrillation after pulmonary transplantation: incidence, impact on mortality, treatment effectiveness, and risk factors.
      • Nielsen T.D.
      • Bahnson T.
      • Davis R.D.
      Atrial fibrillation after pulmonary transplant.
      Esophageal proceduresEsophagoscopy/PEG/esophageal dilation and/or stentingLaparoscopic Nissen fundoplication/myotomy

      Zenker diverticulectomy
      Esophagectomy
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Tisdale J.E.
      • Wroblewski H.A.
      • Wall D.S.
      • Rieger K.M.
      • Hammoud Z.T.
      • Young J.V.
      • et al.
      A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy.
      Other proceduresPericardial window
      Thoracic surgical procedures were divided into low (<5%), moderate (5%-15%) and high (>15%) risk groups based on their expected incidence of POAF in order to facilitate the preoperative risk stratification of patients. POAF, Postoperative atrial fibrillation; PEG, percutaneous endoscopic gastrostomy.
      Table 2, bKnown patient risk factors for and comorbidities that increase the risk of POAF
      Risk factors and comorbiditiesThoracic surgery references
      Modifiable risk factors
       Hypertension
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Rao V.P.
      • Addae-Boateng E.
      • Barua A.
      • Martin-Ucar A.E.
      • Duffy J.P.
      Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation following oesophagectomy.
       MI
      • Ivanovic J.
      • Maziak D.E.
      • Ramzan S.
      • McGuire A.L.
      • Villeneuve P.J.
      • Gilbert S.
      • et al.
      Incidence, severity and perioperative risk factors for atrial fibrillation following pulmonary resection.
       VHD
       Heart failure
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Polanczyk C.A.
      • Goldman L.
      Supraventricular arrhythmia in patients having noncardiac surgery: clinical correlates and effect on length of stay.
       Obesity
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
       Obstructive sleep apnea
       Smoking
       Exercise
       Alcohol use
       Hyperthyroidism
       Increased pulse pressure
       Mitral regurgitation
       LVH
       Increased LV wall thickness
      Nonmodifiable risk factors
       Increasing age
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Ivanovic J.
      • Maziak D.E.
      • Ramzan S.
      • McGuire A.L.
      • Villeneuve P.J.
      • Gilbert S.
      • et al.
      Incidence, severity and perioperative risk factors for atrial fibrillation following pulmonary resection.
      • Polanczyk C.A.
      • Goldman L.
      Supraventricular arrhythmia in patients having noncardiac surgery: clinical correlates and effect on length of stay.
       African American (protective factor)
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
       Family history
       Genetic variants
       Male sex
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Passman R.S.
      • Gingold D.S.
      • Amar D.
      • Lloyd-Jones D.
      • Bennett C.L.
      • Zhang H.
      • et al.
      Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Polanczyk C.A.
      • Goldman L.
      Supraventricular arrhythmia in patients having noncardiac surgery: clinical correlates and effect on length of stay.
       History of arrythmias
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      Derived from the 2014 American Heart Association Atrial Fibrillation Guidelines and relevant literature for thoracic surgery. Patient risk factors and comorbidities that were shown to increase the risk of atrial fibrillation (AF) are listed. Much of this information was extracted from the general population, thoracic surgery–specific references are listed when available. These risk factors/comorbidities should be assessed in conjunction with the procedure-related risks of AF in order to determine the true risk of POAF. MI, Myocardial infarction; VHD, valvular heart disease; LV, left ventricle; LVH, left ventricular hypertrophy.
      Thromboembolic events such as stroke or acute limb ischemia are the most serious and feared consequences of AF. Studies have reported a wide range of the incidence of stroke related to POAF, although the risk for cardiac and thoracic surgery seems to be 50% to 200% higher than for general surgery.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Biancari F.
      • Mahar M.A.A.
      Meta-analysis of randomized trials on the efficacy of posterior pericardiotomy in preventing atrial fibrillation after coronary artery bypass surgery.
      The AFFIRM Investigators
      Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.
      Many studies show an increase in mortality in patients with POAF
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Henri C.
      • Giraldeau G.
      • Dorais M.
      • Cloutier A.-S.
      • Girard F.
      • Noiseux N.
      • et al.
      Atrial fibrillation after pulmonary transplantation: incidence, impact on mortality, treatment effectiveness, and risk factors.
      • Nielsen T.D.
      • Bahnson T.
      • Davis R.D.
      Atrial fibrillation after pulmonary transplant.
      • Bhave P.D.
      • Goldman L.E.
      • Vittinghoff E.
      • Maselli J.
      • Auerbach A.
      Incidence, predictors, and outcomes associated with postoperative atrial fibrillation after major noncardiac surgery.
      • Imperatori A.
      • Mariscalco G.
      • Riganti G.
      • Rotolo N.
      • Conti V.
      • Dominioni L.
      Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study.
      although some studies have not shown such an effect.
      • Hardy J.
      Risk factors for atrial fibrillation following extrapleural pneumonectomy, the effect of prophylactic beta blockade.
      • Cardinale D.
      • Martinoni A.
      • Cipolla C.M.
      • Civelli M.
      Atrial fibrillation after operation for lung cancer: clinical and prognostic significance.
      Given that patients with other significant comorbidities or who are undergoing more complex operations are more likely to experience POAF, it is unclear to what extent the arrhythmia itself contributes to mortality. It is feasible that the contribution of POAF to mortality is more significant for those patients with fewer other comorbidities, however this independent effect is more difficult to measure and has not been well reported in the literature.
      POAF is associated with longer intensive care unit and hospital stays, increased morbidity (including strokes/new central neurologic events) with incidence of 1.3%-1.7%
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Biancari F.
      • Mahar M.A.A.
      Meta-analysis of randomized trials on the efficacy of posterior pericardiotomy in preventing atrial fibrillation after coronary artery bypass surgery.
      The AFFIRM Investigators
      Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.
      ; and mortality (up to 5.6%-7.5%; RR 1.7-3.4
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Henri C.
      • Giraldeau G.
      • Dorais M.
      • Cloutier A.-S.
      • Girard F.
      • Noiseux N.
      • et al.
      Atrial fibrillation after pulmonary transplantation: incidence, impact on mortality, treatment effectiveness, and risk factors.
      • Nielsen T.D.
      • Bahnson T.
      • Davis R.D.
      Atrial fibrillation after pulmonary transplant.
      • Bhave P.D.
      • Goldman L.E.
      • Vittinghoff E.
      • Maselli J.
      • Auerbach A.
      Incidence, predictors, and outcomes associated with postoperative atrial fibrillation after major noncardiac surgery.
      • Imperatori A.
      • Mariscalco G.
      • Riganti G.
      • Rotolo N.
      • Conti V.
      • Dominioni L.
      Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study.
      ), as well as higher resource utilization.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Irshad K.
      • Feldman L.S.
      • Chu V.F.
      • Dorval J.-F.
      • Baslaim G.
      • Morin J.E.
      Causes of increased length of hospitalization on a general thoracic surgery service: a prospective observational study.
      Multiple studies have consistently demonstrated an increase in length of hospital stay in patients who develop POAF, generally by a mean of 2 to 4 days.
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      • Henri C.
      • Giraldeau G.
      • Dorais M.
      • Cloutier A.-S.
      • Girard F.
      • Noiseux N.
      • et al.
      Atrial fibrillation after pulmonary transplantation: incidence, impact on mortality, treatment effectiveness, and risk factors.
      • Nielsen T.D.
      • Bahnson T.
      • Davis R.D.
      Atrial fibrillation after pulmonary transplant.
      • Ivanovic J.
      • Maziak D.E.
      • Ramzan S.
      • McGuire A.L.
      • Villeneuve P.J.
      • Gilbert S.
      • et al.
      Incidence, severity and perioperative risk factors for atrial fibrillation following pulmonary resection.
      • Bhave P.D.
      • Goldman L.E.
      • Vittinghoff E.
      • Maselli J.
      • Auerbach A.
      Incidence, predictors, and outcomes associated with postoperative atrial fibrillation after major noncardiac surgery.
      • Imperatori A.
      • Mariscalco G.
      • Riganti G.
      • Rotolo N.
      • Conti V.
      • Dominioni L.
      Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study.
      An analysis of the Society of Thoracic Surgeons (STS) database by Onatis and colleagues
      • Onaitis M.
      • D'Amico T.
      • Zhao Y.
      • O'Brien S.
      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database.
      demonstrated that, in patients undergoing lobectomy or greater resection for lung cancer, the presence of POAF lengthened hospital stay by a median of 3 days. The cost of hospitalization is likewise increased for patients who develop POAF, with an increase reported in the literature anywhere from 30% to 68%.
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      • Roselli E.E.
      • Murthy S.C.
      • Rice T.W.
      • Houghtaling P.L.
      Atrial fibrillation complicating lung cancer resection.
      • Bhave P.D.
      • Goldman L.E.
      • Vittinghoff E.
      • Maselli J.
      • Auerbach A.
      Incidence, predictors, and outcomes associated with postoperative atrial fibrillation after major noncardiac surgery.
      To some extent, this increase reflects comorbid conditions that occur along with POAF, but POAF itself is associated with an increase in cost. Vaporciyan and colleagues
      • Vaporciyan A.A.
      • Correa A.M.
      • Rice D.C.
      • Roth J.A.
      • Smythe W.R.
      • Swisher S.G.
      • et al.
      Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients.
      found that for patients who developed POAF without any other complications, the cost of care increased by more than US$6000, representing a greater than 30% increase.

      The Possible Mechanisms of POAF After Thoracic Surgery

      The mechanisms that initiate and sustain AF, including POAF, are complex and require both a vulnerable atrial substrate
      • Akoum N.
      • Daccarett M.
      • McGann C.
      • Segerson N.
      • Vergara G.
      • Kuppahally S.
      • et al.
      Atrial fibrosis helps select the appropriate patient and strategy in catheter ablation of atrial fibrillation: a DE-MRI guided approach.
      and a trigger to initiate AF (Table 3). Today they remain incompletely understood. The role of triggers from the pulmonary veins and other atrial sites initiating AF
      • Haïssaguerre M.
      • Jaïs P.
      • Shah D.C.
      • Takahashi A.
      • Hocini M.
      • Quiniou G.
      • et al.
      Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins.
      is well appreciated. However, it remains to be understood why they occur and what exact mechanisms are essential for their propagation. The identified risk factors for the development of sustained POAF are mostly identical to those known to make the atrium vulnerable to development of AF in the nonsurgical setting. They include several risk factors that are associated with atrial fibrosis, such as increasing age, atrial dilatation, myocardial ischemia, volume overload, and a history of heart failure.
      • Amar D.
      • Roistacher N.
      • Burt M.
      • Reinsel R.A.
      • Ginsberg R.J.
      • Wilson R.S.
      Clinical and echocardiographic correlates of symptomatic tachydysrhythmias after noncardiac thoracic surgery.
      • Tisdale J.E.
      • Wroblewski H.A.
      • Kesler K.A.
      Prophylaxis of atrial fibrillation after noncardiac thoracic surgery.
      • Terzi A.
      • Furlan G.
      • Chiavacci P.
      • Dal Corso B.
      • Luzzani A.
      • Dalla Volta S.
      Prevention of atrial tachyarrhythmias after non-cardiac thoracic surgery by infusion of magnesium sulfate.
      They also include risk factors such as increased norepinephrine levels and increased vagal tone, both of which shorten atrial wavelength, the latter known to increase atrial vulnerability to AF.
      • Schotten U.
      • Verheule S.
      • Kirchhof P.
      • Goette A.
      Pathophysiological mechanisms of atrial fibrillation: a translational appraisal.
      Both adrenergic and vagal stimulation can promote triggers that initiate AF.
      • Fuster V.
      • Rydén L.E.
      • Cannom D.S.
      • Crijns H.J.
      • Curtis A.B.
      • Ellenbogen K.A.
      • et al.
      2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
      In addition, surgical procedures are associated with local or systemic inflammation (such as pericarditis), an important risk factor affecting the vulnerability of the atrial substrate to POAF.
      • Dixit S.
      Atrial fibrillation after major thoracic surgery: new insights into underlying mechanisms.
      The extent of pulmonary resection is another important risk factor for development of POAF.
      • De Decker K.
      • Jorens P.G.
      • Van Schil P.
      Cardiac complications after noncardiac thoracic surgery: an evidence-based current review.
      The development of POAF is likely to involve some or all of these mechanisms.
      Table 3Probable mechanisms contributing to POAF
      Clinically meaningful AF requires the presence of both a trigger and a vulnerable atrial substrate
      Atrial substrate changes that facilitate AF
       Sympathetic or parasympathetic stimulation
       Atrial dilation or acute atrial stretch
       Pericarditis
       Fibrosis
       Inhomogeneous dispersion of conduction abnormalities
       Short wavelength (conduction velocity × ERP)
       Other (like inflammation and oxidative stress)
      In addition, a driver(s) is thought to be needed to sustain AF in the vulnerable substrate
       Rapidly firing ectopic focus (atrial or other)
       Reentrant circuit(s) of short cycle length (ordered reentry)
       Potential role, if any, of multiple reentrant wavelets (random reentry)
      AF, Atrial fibrillation; ERP, effective refractory period.
      Insight into the mechanism of POAF can be gained by examining what prophylactic therapies decrease the rate of POAF occurrence after thoracic surgery. Higher norepinephrine levels were found in patients on preoperative β-blockers who had their β-blocker therapy interrupted than in patients not receiving a β-blocker at all. This was associated with a significantly higher incidence of POAF.
      • Tisdale J.E.
      • Wroblewski H.A.
      • Kesler K.A.
      Prophylaxis of atrial fibrillation after noncardiac thoracic surgery.
      • Merritt R.E.
      • Shrager J.B.
      Prophylaxis and management of atrial fibrillation after general thoracic surgery.
      Diltiazem therapy initiated in the early postoperative period has been found to significantly reduce the rate of POAF.
      • Amar D.
      • Roistacher N.
      • Rusch V.W.
      • Leung D.H.Y.
      • Ginsburg I.
      • Zhang H.
      • et al.
      Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery.
      This is believed to be related to its effects of decreasing pulmonary vascular resistance. It is known that pulmonary hypertension and dilatation of the right side of the heart are associated with an increased incidence of POAF.
      • Amar D.
      • Roistacher N.
      • Burt M.
      • Reinsel R.A.
      • Ginsberg R.J.
      • Wilson R.S.
      Clinical and echocardiographic correlates of symptomatic tachydysrhythmias after noncardiac thoracic surgery.
      There is also the possibility that as a systemic vasodilator, diltiazem could reduce preload and left atrial pressures.
      • Fuster V.
      • Rydén L.E.
      • Cannom D.S.
      • Crijns H.J.
      • Curtis A.B.
      • Ellenbogen K.A.
      • et al.
      2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
      The data on use of verapamil have been inconsistent with regard to decreasing the incidence of POAF.
      • Van Mieghem W.
      • Tits G.
      • Demuynck K.
      • Lacquet L.
      • Deneffe G.
      • Tjandra-Maga T.
      • et al.
      Verapamil as prophylactic treatment for atrial fibrillation after lung operations.
      Magnesium has been consistently shown to decrease the incidence of POAF after cardiac surgery, and the only prospective, randomized study on patients undergoing thoracic surgery also showed a significant decrease in the incidence of POAF.
      • Merritt R.E.
      • Shrager J.B.
      Prophylaxis and management of atrial fibrillation after general thoracic surgery.
      The reason for its effectiveness is uncertain.
      In the presence of a vulnerable substrate, additional electrophysiologic abnormalities (drivers) will sustain AF.

      Recommendations and Reasoning

      Recommend the Use of the Following Definitions for the Diagnosis of POAF

      • Class I
      • 1.1.
        Electro-physiologic definition/diagnosis: ECG recordings (1 or more ECG leads) that demonstrate the presence of characteristic ECG features of AF lasting at least for 30 seconds or for the duration of the ECG recording (if shorter than 30 seconds)
        • January C.T.
        • Wann L.S.
        • Alpert J.S.
        • Calkins H.
        • Cleveland J.C.
        • Cigarroa J.E.
        • et al.
        2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
        • Anderson J.L.
        • Halperin J.L.
        • Albert N.M.
        • Bozkurt B.
        • Brindis R.G.
        • Curtis L.H.
        • et al.
        Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        (level of evidence LOE C). Clinical symptoms may include hypotension, dizziness, decreased urinary output, fatigue, and so on.
      • 1.2.
        Clinical definition/diagnosis: clinically significant POAF (Table 4) is AF in the (intra- and) postoperative setting that requires treatment with rate or rhythm control agents, or requires anticoagulation, and/or extends the duration of hospitalization (LOE C). Clinical symptoms may include hypotension, dizziness, decreased urinary output, fatigue, and so on.
        Table 4Recommended definitions for the diagnosis of POAF
        DefinitionsCOR
        Electrophysiologic definition/diagnosisECG recordings (1 or more ECG leads) with ECG features of AF lasting at least for 30 seconds or for the duration of the ECG recording (if <30 seconds) (LOE C)I
        Clinical definition/diagnosisClinically significant POAF: intra- and postoperative AF requiring treatment, or anticoagulation, and/or extending the duration of hospitalization (LOE C)I
        These measures should be included in the clinical documentation and reported in the clinical trials/studies. POAF, Postoperative atrial fibrillation; ECG, electrocardiography; COR, class of recommendation; LOE, level of evidence; AF, atrial fibrillation.
      We recommend that both electrophysiologically documented AF and clinically diagnosed AF be included in the clinical documentation and reported in the clinical trials/studies.

      Physiologic (ECG) Monitoring of Patients at Risk for POAF

      Recommendations for ECG monitoring of patients at risk for POAF are presented in Table 5.
      • Class I
      • 2.1.
        Patients should be monitored with continuous ECG telemetry postoperatively for 48 to 72 hours (or less if their hospitalization is shorter) if:
        • 2.1.1.
          They are undergoing procedures that pose intermediate (5%-15% expected incidence of AF) or high (>15%) risk for the development of postoperative AF or have significant additional risk factors (CHA2DS2-VASc ≥2) for stroke (LOE C).
        • 2.1.2.
          They have a history of preexisting or periodic recurrent AF before their surgery. These patients should also receive ECG monitoring in the immediate preoperative period if procedures (eg, epidural catheter or other regional anesthesia blocks) are performed (LOE C).
      • Class IIa
      • 2.2.
        Not using routine ECG telemetry is reasonable for patients who undergo low-risk (<5% expected incidence of AF) procedures, and have neither a previous history of AF nor significant risk for stroke (based on CHA2DS2-VASc score), and have no relevant comorbidities (such as heart failure or previous stroke) (LOE C).
        • Class I
        • 2.2.1.
          If patients exhibit clinical signs of possible AF while not monitored with telemetry, ECG recordings to diagnose POAF and ongoing telemetry to monitor the period of AF should be immediately implemented (LOE C).
      Table 5Recommendations for physiologic (ECG) monitoring
      Recommendations for monitoringCOR
      Patients should be monitored with continuous ECG telemetry postoperatively for 48-72 h (or less if their hospitalization is shorter) if:
      • they are undergoing procedures that pose high (>15% expected incidence of AF) or intermediate (5%-15%) risk for POAF or
      • they have significant additional risk factors (CHA2DS2-VASc >2) for stroke (LOE C)
      • they have a history of preexisting or periodic recurrent AF before their surgery
      • These patients should also receive ECG monitoring in the immediate preoperative period if procedures (epidural catheter, regional anesthesia blocks, and so forth) are performed (LOE C)
      I
      Not using routine ECG telemetry is reasonable for patients who
      • undergo low risk surgery (<5% expected incidence of AF) and
      • had no previous history of AF, or
      • have no significant risk for stroke and
      • have no relevant comorbidities (eg, heart failure or previous stroke) (LOE C)
      IIa
      • If patients exhibit clinical signs of possible AF while not monitored with ECG telemetry, ECG recordings to diagnose POAF and continuous telemetry to monitor the period of AF should be immediately implemented (LOE C)
      I
      ECG, Electrocardiography; COR, class of recommendation; AF, atrial fibrillation; POAF, postoperative atrial fibrillation; LOE, level of evidence.

      Rate Control and Antiarrhythmic Drugs, Mechanism of Action, Side Effects, and Limitations

      A detailed description of the drugs used for the management of rate (Table 6) or rhythm control (Table 7
      • Neumar R.W.
      • Otto C.W.
      • Link M.S.
      • Kronick S.L.
      • Shuster M.
      • Callaway C.W.
      • et al.
      Part 8: Adult advanced cardiovascular life support 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care.
      ), their mechanism of action, side effects, and limitations are discussed here. Dosing information is also presented in Table 6, Table 7.
      Table 6Commonly used rate control agents
      DrugRecommended dosesSignificant limitations and known side effects
      Diltiazem0.25 mg/kg IV loading dose over 2 min, then 5-15 mg/h IV continuous infusionHypotension

      Bradycardia

      Heart failure exacerbation
      Digoxin0.25 mg IV repeated every 2-4 h to a maximum dose of 1.5 mg over 24 hNausea, vomiting, anorexia

      Confusion

      AV block

      Ventricular arrhythmias

      Accumulates in acute kidney injury/chronic kidney disease
      Esmolol500 μg/kg IV bolus over 1 min, then 50-300 μg/kg/min IV continuous infusionBradycardia

      Hypotension

      Bronchospasm

      Heart failure exacerbation
      Metoprolol2.5-5.0 mg IV bolus over 2 min; maximum 3 dosesBradycardia

      Hypotension

      Bronchospasm

      Heart failure exacerbation
      Amiodarone150-300 mg IV over 1 h, followed by 10-50 mg/h IV continuous infusion over 24 hBradycardia

      QT interval prolongation

      Pulmonary toxicity has not been demonstrated at this dose
      Detailed information in section 3 and in references
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      ,
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      IV, Intravenous; AV, atrioventricular.
      Table 7Commonly used antiarrhythmic agents
      DrugRecommended dosesSignificant limitations and known side effectsRef
      ProcainamideConversion to sinus rhythm: 20-50 mg/min IV continuous infusion until AF terminated, hypotension occurs, or QRS duration prolonged by 50%, or cumulative total dose of 15 mg/kg reached

      Alternative dose: 100 mg IV every 5 min until AF terminated or other conditions as listed above are met

      If available orally, could be used for maintenance
      Hypotension

      QT interval prolongation

      Torsades de pointes

      Contraindicated in patients with heart failure with reduced left ventricular ejection fraction

      Contraindicated in patients with pretreatment QTc interval >470 ms (men) or 480 ms (women)
      • Neumar R.W.
      • Otto C.W.
      • Link M.S.
      • Kronick S.L.
      • Shuster M.
      • Callaway C.W.
      • et al.
      Part 8: Adult advanced cardiovascular life support 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care.
      FlecainideConversion to sinus rhythm: 200-300 mg single oral dose

      Maintenance of sinus rhythm: 50-150 orally once every 12 h
      Dizziness

      Blurred vision

      Sinus bradycardia

      AV block

      Contraindicated in patients with heart failure with reduced left ventricular ejection fraction

      Contraindicated in patients with coronary artery disease/structural heart disease
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      PropafenoneConversion to sinus rhythm: 450-600 mg single oral dose

      Maintenance of sinus rhythm: 150-300 mg orally every 8 h (immediate release); 225-425 mg orally every 12 h (extended release)
      Dizziness

      Blurred vision

      Sinus bradycardia

      AV block

      Contraindicated in patients with heart failure with reduced left ventricular ejection fraction

      Contraindicated in patients with coronary artery disease/structural heart disease
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      AmiodaroneProphylaxis: 300 mg IV bolus, then 600 mg orally twice daily for 3-5 d

      Treatment: 150 mg IV over 10 min; then 1 mg/min IV continuous infusion for 6 h; the 0.5 mg/min IV continuous infusion for 18 h or change to oral administration at 100-400 mg daily
      Bradycardia

      QT interval prolongation

      Pulmonary toxicity has not been demonstrated at this dose

      Bradycardia

      Hypotension

      QT interval prolongation

      Pulmonary toxicity has occurred at cumulative IV doses >2150 mg in patients undergoing pneumonectomy
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • Riber L.P.
      • Christensen T.D.
      • Jensen H.K.
      • Hoejsgaard A.
      • Pilegaard H.K.
      Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
      DofetilideNot ideal for conversion to sinus rhythm in the postoperative setting; may take 2-3 d to convert to normal sinus rhythm, which would require commitment to anticoagulation

      Maintenance of sinus rhythm: calculated CrCl 20-40 mL/min: 125 μg orally once every 12 h

      Calculated CrCl 40-60 mL/min: 250 μg orally once every 12 h

      Calculated CrCl >60 mL/min: 500 μg orally every 12 h
      QT interval prolongation

      Torsades de pointes

      Risk of torsades de pointes is greater in patients with heart failure

      Dose adjustment is important in patients with acute kidney injury or chronic kidney disease

      Contraindicated in patients with calculated CrCl <20 mL/min

      Contraindicated in patients with pretreatment QTc interval >470 ms (men) or 480 ms (women)

      Monitor ECGs 2 h after doses, telemetry for at least 3 d
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      IbutilideConversion to sinus rhythm:

      Weight ≥60 kg: 1 mg IV administered over 10 min

      Weight <60 kg: 0.01 mg/kg IV administered over 10 min

      If the AF does not terminate within 10 min of completion of the first infusion, a second dose of equal strength may be administered IV over 10 min

      Not indicated for maintenance of sinus rhythm
      QT interval prolongation

      Torsades de pointes

      Risk of torsades de pointes greater in patients with heart failure

      Nonsustained ventricular tachycardia

      Sinus pauses after AF conversion

      Contraindicated in patients with pretreatment QTc interval >470 ms (men) or 480 ms (women)
      Corvert prescribing information 2006; Pfizer, Inc
      SotalolMaintenance of sinus rhythm: 40-160 mg orally every 12 h

      Dosing interval should be adjusted in patients with acute kidney injury or chronic kidney disease:

      If the calculated CrCl is 30-59 mL/min: administer every 24 h

      If the calculated CrCl is 10-29 mL/min: administer every 36-48 h
      Sinus bradycardia

      AV block

      QT interval prolongation

      Torsades de pointes

      Heart failure exacerbation

      Risk of torsades de pointes greater in patients with heart failure

      Bronchospasm

      Dose adjustment is important in patients with acute kidney injury or chronic kidney disease

      Use with extreme caution in patients with calculated CrCl <10 mL/min and in patients undergoing hemodialysis

      Contraindicated in patients with pretreatment QTc interval >470 ms (men) or 480 ms (women)
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • Calkins H.
      • Cleveland J.C.
      • Cigarroa J.E.
      • et al.
      2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      IV, Intravenous; AF, atrial fibrillation; AV, atrioventricular; CrCl, creatinine clearance; ECG, electrocardiography.

      Recommendation

      • Class IIa
      • 3.1.
        To optimize the efficacy and safety of amiodarone, it is reasonable to exercise caution when selecting its doses or intravenous versus oral route, because cases of acute respiratory distress syndrome (ARDS) have been reported following pneumonectomy with cumulative intravenous doses more than 2150 mg
        • Van Mieghem W.
        • Coolen L.
        • Malysse I.
        • Lacquet L.M.
        • Deneffe G.J.
        • Demedts M.G.
        Amiodarone and the development of ARDS after lung surgery.
        (LOE C).

      Reasoning

      • 3.2.
        Rate control agents: their mechanisms of action and side effects
        • 3.2.1. β-Blockers
          β-Blockers are Vaughan Williams class II antiarrhythmic agents that inhibit sympathetic nervous system activity and slow the rate of phase IV repolarization, thus slowing the discharge from the sinus node.
          • Camm J.
          Antiarrhythmic drugs for the maintenance of sinus rhythm: risks and benefits.
          This antiadrenergic activity inhibits the renin-angiotensin-aldosterone system, inhibits apoptosis, and reduces hyperphosphorylation of calcium-releasing channels.
          • Dorian P.
          Antiarrhythmic action of beta-blockers: potential mechanisms.
          Metoprolol and atenolol are relatively selective β-1 receptor antagonists (primarily affecting cardiac tissue) and in moderate doses have less effect on the β-2 receptors in smooth muscle cells in the vasculature and bronchial tree. Propranolol and esmolol are nonselective, and carvedilol is nonselective and possesses α-receptor blocking activity.
        • Intravenous administration of metoprolol, propranolol, and esmolol reduces ventricular response in patients with AF within 5 minutes of administration,
          • Fuster V.
          • Rydén L.E.
          • Cannom D.S.
          • Crijns H.J.
          • Curtis A.B.
          • Ellenbogen K.A.
          • et al.
          American College of Cardiology/American Heart Association Task Force on Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, Heart Rhythm Society, ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
          and both intravenous and oral regimens attain resting and exercise rate control, variably defined, in 68% to 75% of patients.
          • Van Gelder I.C.
          • Groenveld H.F.
          • Crijns H.J.G.M.
          • Tuininga Y.S.
          • Tijssen J.G.P.
          • Alings A.M.
          • et al.
          RACE II Investigators
          Lenient versus strict rate control in patients with atrial fibrillation.
          • Olshansky B.
          • Rosenfeld L.E.
          • Warner A.L.
          • Solomon A.J.
          • O’Neill G.
          • Sharma A.
          • et al.
          AFFIRM Investigators
          The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation.
          • Farshi R.
          • Kistner D.
          • Sarma J.S.
          • Longmate J.A.
          • Singh B.N.
          Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of 5 drug regimens.
          • Abrams J.
          • Allen J.
          • Allin D.
          • Anderson J.
          • Anderson S.
          • Blanski L.
          • et al.
          Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: a multicenter double-blind clinical trial.
          Rate-lowering efficacy varies with acuity and cardiac function and is enhanced with digoxin.
          • Olshansky B.
          • Rosenfeld L.E.
          • Warner A.L.
          • Solomon A.J.
          • O’Neill G.
          • Sharma A.
          • et al.
          AFFIRM Investigators
          The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation.
          • Farshi R.
          • Kistner D.
          • Sarma J.S.
          • Longmate J.A.
          • Singh B.N.
          Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of 5 drug regimens.
        • The major adverse effects of β-blockers are bronchospasm in patients with asthma, particularly if the asthma is not well controlled; worsening of symptoms in patients with severe peripheral arterial disease; hypotension; and worsening of heart failure symptoms in patients with decompensated heart failure with reduced ejection fraction. Intravenous β-blockers should not be used in patients with suspected accessory conduction pathways.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Fuster V.
          • Rydén L.E.
          • Cannom D.S.
          • Crijns H.J.
          • Curtis A.B.
          • Ellenbogen K.A.
          • et al.
          American College of Cardiology/American Heart Association Task Force on Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, Heart Rhythm Society, ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
          Profound bradycardia can result from acute concomitant administration of β-blockers and diltiazem or verapamil.
        • 3.2.2. Diltiazem
          Diltiazem is a nondihydropyridine calcium channel antagonist and class IV Vaughan Williams agent. Diltiazem inhibits L-type calcium channels in vascular and conduction tissue, and especially in nodal tissue.
          • Echizen H.
          • Eichelbaum M.
          Clinical pharmacokinetics of verapamil, nifedipine and diltiazem.
          In addition, diltiazem affects the transient outward and ultrarapid delayed rectifier potassium currents in atrial myocytes. Intravenous diltiazem administered as a bolus and continuous infusion can control ventricular response in 70% to 90% of patients with the recent-onset of AF. The onset of action of diltiazem is 2 to 7 minutes.
          • Fuster V.
          • Rydén L.E.
          • Cannom D.S.
          • Crijns H.J.
          • Curtis A.B.
          • Ellenbogen K.A.
          • et al.
          American College of Cardiology/American Heart Association Task Force on Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, Heart Rhythm Society, ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
          • Siu C.-W.
          • Lau C.-P.
          • Lee W.-L.
          • Lam K.-F.
          • Tse H.-F.
          Intravenous diltiazem is superior to intravenous amiodarone or digoxin for achieving ventricular rate control in patients with acute uncomplicated atrial fibrillation.
          • Delle Karth G.
          • Geppert A.
          • Neunteufl T.
          • Priglinger U.
          • Haumer M.
          • Gschwandtner M.
          • et al.
          Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias.
        • Oral treatment with diltiazem in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial was efficacious in controlling rest and exercise heart rate in approximately 60% of patients, and in 66% and 79% of patients, respectively, when combined with digoxin.
          • Olshansky B.
          • Rosenfeld L.E.
          • Warner A.L.
          • Solomon A.J.
          • O’Neill G.
          • Sharma A.
          • et al.
          AFFIRM Investigators
          The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation.
        • Diltiazem can worsen heart failure in patients with reduced ejection fraction, and can cause important gastrointestinal adverse effects including ileus. Diltiazem must be used cautiously, especially acutely, in patients concomitantly receiving β-blockers, and is contraindicated in patients with an accessory pathway.
          • Fuster V.
          • Rydén L.E.
          • Cannom D.S.
          • Crijns H.J.
          • Curtis A.B.
          • Ellenbogen K.A.
          • et al.
          American College of Cardiology/American Heart Association Task Force on Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, Heart Rhythm Society, ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
        • 3.2.3. Digoxin
          Digoxin inhibits sodium potassium adenosine triphosphatase (ATPase), thereby increasing intracellular sodium concentration leading to increased intracellular calcium concentrations. In addition, digoxin administration is associated with an increase in baroreceptor sensitivity disproportionate to hemodynamic improvement, and imparts vagomimetic (parasympathetic) effects. The vagomimetic effects of digoxin occur at low serum concentrations and contribute to decreasing sinus and atrioventricular (AV) nodal conduction. At higher serum concentrations, the parasympathetic effects actually shorten the refractory period of nonnodal specialized conduction tissue.
          • Gheorghiade M.
          • Adams K.F.
          • Colucci W.S.
          Digoxin in the management of cardiovascular disorders.
        • The onset of action of digoxin after intravenous administration of 0.5 to 0.75 mg bolus doses is 30 minutes to 2 hours.
          • Jordaens L.
          • Trouerbach J.
          • Calle P.
          • Tavernier R.
          • Derycke E.
          • Vertongen P.
          • et al.
          Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo.
          Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group.
          With additional intravenous bolus doses of 0.25 mg every 2 to 6 hours after the first dose, up to a total dose within 24 hours of 1.25 to 1.5 mg, 75% of patients with AF can achieve rate control at rest.
          • Siu C.-W.
          • Lau C.-P.
          • Lee W.-L.
          • Lam K.-F.
          • Tse H.-F.
          Intravenous diltiazem is superior to intravenous amiodarone or digoxin for achieving ventricular rate control in patients with acute uncomplicated atrial fibrillation.
          • Delle Karth G.
          • Geppert A.
          • Neunteufl T.
          • Priglinger U.
          • Haumer M.
          • Gschwandtner M.
          • et al.
          Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias.
          Exercise rate control is achieved much less frequently, except when digoxin is administered concomitantly with a β-blocker or calcium channel blocker.
          • Olshansky B.
          • Rosenfeld L.E.
          • Warner A.L.
          • Solomon A.J.
          • O’Neill G.
          • Sharma A.
          • et al.
          AFFIRM Investigators
          The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation.
        • Digoxin should not be administered to patients with suspected accessory pathways or obstructive hypertrophic cardiomyopathy. The potential for digoxin toxicity, including accelerated junctional rhythm, accelerated ventricular escape rhythms (sometimes heralded by regularization of the longest R-R intervals), nausea, and visual symptoms is increased in the presence of hypokalemia, hypomagnesemia, hypercalcemia, and concomitant therapy with amiodarone, dronedarone or verapamil.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Fuster V.
          • Rydén L.E.
          • Cannom D.S.
          • Crijns H.J.
          • Curtis A.B.
          • Ellenbogen K.A.
          • et al.
          American College of Cardiology/American Heart Association Task Force on Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, Heart Rhythm Society, ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
          Propensity matched comparisons in the AFFIRM trial do not suggest an increase in mortality associated with chronic digoxin use.
          • Gheorghiade M.
          • Fonarow G.C.
          • Van Veldhuisen D.J.
          • Cleland J.G.F.
          • Butler J.
          • Epstein A.E.
          • et al.
          Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial.
        • 3.2.4. Amiodarone
          Amiodarone is a Vaughan Williams class III agent that inhibits inward potassium current, prolonging the action potential. However, amiodarone also has properties that could place it in the other 3 Vaughan Williams classes. It has antisympathetic and calcium-blocking activity that leads to important effects on the sinoatrial (SA) and AV nodes, and the drug also has sodium channel–inhibiting properties that increases the threshold for depolarization.
          • Balser J.R.
          The rational use of intravenous amiodarone in the perioperative period.
          • Sanoski C.A.
          Antiarrhythmic agents.
        • Intravenous amiodarone, administered as a bolus and continuous infusion, has an effect on heart rate within 4 hours that is similar to intravenous diltiazem and intravenous digoxin, and improves ventricular rate in 74% of patients with AF by 24 hours.
          • Delle Karth G.
          • Geppert A.
          • Neunteufl T.
          • Priglinger U.
          • Haumer M.
          • Gschwandtner M.
          • et al.
          Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias.
          Oral amiodarone can require days for effective rate control to occur. Chronic oral amiodarone therapy for rate control can have effects similar to those of digoxin.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Tse H.F.
          • Lam Y.M.
          • Lau C.P.
          • Cheung B.M.
          • Kumana C.R.
          Comparison of digoxin versus low-dose amiodarone for ventricular rate control in patients with chronic atrial fibrillation.
        • Amiodarone is highly lipophilic, and intravenous administration may exert effects that are different from those following oral administration. Intravenous amiodarone can be associated with AV block, vasodilation, and hypotension. Intravenous amiodarone should not be used in patients who have a suspected accessory pathway.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          Pulmonary toxicity associated with high-dose intravenous amiodarone is discussed in section 3.5.1.
        • Chronic administration of oral amiodarone can be associated with pulmonary, hepatic, thyroid, neurologic, cutaneous, and ocular toxicities.
          • Fuster V.
          • Rydén L.E.
          • Cannom D.S.
          • Crijns H.J.
          • Curtis A.B.
          • Ellenbogen K.A.
          • et al.
          American College of Cardiology/American Heart Association Task Force on Practice Guidelines, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, Heart Rhythm Society, ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
          Amiodarone inhibits the metabolism of warfarin and inhibits elimination of the new oral anticoagulants. Amiodarone administration can restore sinus rhythm so patients who receive it after 24 to 48 hours of AF require anticoagulation.
      • 3.3.
        Antiarrhythmic medications (mechanisms of action, side effects)
        • 3.3.1.
          Amiodarone (see section 3.2.4)
        • 3.3.2.
          Flecainide
        • Flecainide is a Vaughan Williams class IC antiarrhythmic agent that is a potent inhibitor of fast sodium conduction.
          • Camm J.
          Antiarrhythmic drugs for the maintenance of sinus rhythm: risks and benefits.
          Consequently, flecainide decreases the maximum upstroke velocity and amplitude of atrial, ventricular, and Purkinje fiber action potentials.
          • Roden D.M.
          • Wood A.
          • Wilkinson G.R.
          • Woosley R.L.
          Disposition kinetics of encainide and metabolites.
          Flecainide may also inhibit IKr current, and prolongs the duration of atrial and ventricular action potential. In patients without structural heart disease, oral flecainide is relatively well tolerated; adverse effects include dizziness (15%-20%) and visual abnormalities, including blurred vision and difficulty in focusing (up to 15%), which can usually occur during dose uptitration.
          • Tamargo J.
          • Capucci A.
          • Mabo P.
          Safety of flecainide.
          However, in patients with structural heart disease, flecainide is associated with more severe adverse effects. Flecainide is associated with ventricular proarrhythmia in this population; this proarrhythmia is not torsades de pointes (TdP), but rather monomorphic ventricular tachycardia. This proarrhythmia was the likely cause of death associated with flecainide (and encainide) in the Cardiac Arrhythmia Suppression Trial (CAST),
          • Echt D.S.
          • Liebson P.R.
          • Mitchell L.B.
          • Peters R.W.
          • Obias-Manno D.
          • Barker A.H.
          • et al.
          Mortality and morbidity in patients receiving encainide, flecainide, or placebo.
          in which patients with a history of myocardial infarction and symptomatic or asymptomatic ventricular ectopy (≥6 ventricular premature depolarizations VPDs per hour) were randomized to receive flecainide, another Vaughan Williams class IC agent encainide, or placebo for VPD suppression. Patients randomized to receive therapy with flecainide or encainide had an increased risk of total mortality and an increased risk of nonfatal cardiac arrest and death from arrhythmia. The risk of proarrhythmia associated with Vaughan Williams class IC antiarrhythmic agents seems to be highest in patients with ventricular conduction delays (QRS duration >120 milliseconds), structural heart disease, ventricular scar tissue, or left ventricular (LV) dysfunction.
          • Naccarelli G.V.
          • Wolbrette D.L.
          • Luck J.C.
          Proarrhythmia.
          Consequently, flecainide should be avoided in these patients.
        • In addition to the risk of proarrhythmia, flecainide has potent negative inotropic activity, and has been associated with worsening heart failure in patients with coronary artery disease or preexisting heart failure (New York Heart Association NYHA class II to IV and/or LV ejection fraction <30%).
          • Tamargo J.
          • Capucci A.
          • Mabo P.
          Safety of flecainide.
          Therefore, flecainide is contraindicated in patients with heart failure and reduced ejection fraction.
        • Intravenous flecainide is not available in the United States, but is available in other countries. In addition to the potential for ventricular proarrhythmia in patients with structural heart disease and worsening of heart failure in patients with LV dysfunction, intravenous flecainide may be associated with hypotension.
        • 3.3.3. Magnesium
          Magnesium administered intravenously is often referred to as a physiologic calcium channel blocker, due to its antagonism of L- and T-type calcium channels.
          • Wu J.Y.
          • Lipsius S.L.
          Effects of extracellular Mg2+ on T- and L-type Ca2+ currents in single atrial myocytes.
          Intravenous magnesium diminishes atrial automaticity
          • Iseri L.T.
          • Allen B.J.
          • Ginkel M.L.
          • Brodsky M.A.
          Ionic biology and ionic medicine in cardiac arrhythmias with particular reference to magnesium.
          ) and inhibits AV node conduction.
          • Rasmussen H.S.
          • Larsen O.G.
          • Meier K.
          • Larsen J.
          Hemodynamic effects of intravenously administered magnesium on patients with ischemic heart disease.
          Intravenous magnesium is well tolerated; sinus bradycardia or AV block have been reported with an incidence of approximately 3%.
          • Ho K.M.
          • Sheridan D.J.
          • Paterson T.
          Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis.
          Intravenous magnesium may also cause hypotension (approximate incidence 4%).
          • Ho K.M.
          • Sheridan D.J.
          • Paterson T.
          Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis.
          Transient adverse effects including flushing, tingling, and dizziness may occur in up to 17% of patients.
          • Ho K.M.
          • Sheridan D.J.
          • Paterson T.
          Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis.
        • 3.3.4. Dofetilide
          Dofetilide is a Vaughan Williams class III antiarrhythmic agent that inhibits IKr current,
          • Carmeliet E.
          Voltage- and time-dependent block of the delayed K+ current in cardiac myocytes by dofetilide.
          and prolongs atrial and ventricular action potential duration.
          • Mounsey J.P.
          • DiMarco J.P.
          Cardiovascular drugs. Dofetilide.
          Although dofetilide has been shown to be effective for converting nonsurgical AF to sinus rhythm
          • Singh S.
          • Zoble R.G.
          • Yellen L.
          • Brodsky M.A.
          • Feld G.K.
          Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study.
          and for maintenance of sinus rhythm in patients with nonoperative AF,
          • Pedersen O.D.
          • Bagger H.
          • Keller N.
          • Marchant B.
          • Køber L.
          • Torp-Pedersen C.
          Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy.
          it has not been studied specifically for prevention or management of AF after noncardiac thoracic surgery. As a result of its propensity to inhibit IKr and prolong ventricular repolarization, dofetilide may cause TdP, with an incidence of approximately 1% in patients with normal LV function.
          • Mounsey J.P.
          • DiMarco J.P.
          Cardiovascular drugs. Dofetilide.
          However, the incidence increases to 3.3% in patients with heart failure with reduced LV ejection fraction.
          • Torp-Pedersen C.
          • Møller M.
          Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigators of Arrhythmia and Mortality on Dofetilide Study Group.
          To minimize the risk of TdP, dofetilide doses must be appropriately adjusted for kidney disease.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
        • 3.3.5. Dronedarone
          Dronedarone is a Vaughan Williams class III antiarrhythmic agent that was developed as a potentially safer congener of amiodarone. Dronedarone is similar to amiodarone in that it inhibits multiple ion currents, including fast Na+ current, IKr, acetylcholine-activated K+ current, and L-type calcium current.
          • Adlan A.M.
          • Lip G.Y.
          Benefit-risk assessment of dronedarone in the treatment of atrial fibrillation.
          Dronedarone is also a noncompetitive β-adrenergic inhibitor. Unlike amiodarone, however, which possesses 2 iodine atoms that compose 37% of its molecular weight, dronedarone's structure does not include iodine atoms. In addition, the half-life of dronedarone (13 to 31 hours) is much shorter than that of amiodarone (10 to 40 days).
          • Adlan A.M.
          • Lip G.Y.
          Benefit-risk assessment of dronedarone in the treatment of atrial fibrillation.
          Dronedarone's primary adverse effects include gastrointestinal distress (16%), dizziness (9%), and bradycardia (3%).
          • Adlan A.M.
          • Lip G.Y.
          Benefit-risk assessment of dronedarone in the treatment of atrial fibrillation.
          Dronedarone was associated with an increased incidence of mortality in a randomized, double-blind, placebo-controlled study.
          • Køber L.
          • Torp-Pedersen C.
          • McMurray J.J.V.
          • Gøtzsche O.
          • Lévy S.
          • Crijns H.
          • et al.
          Dronedarone Study Group
          Increased mortality after dronedarone therapy for severe heart failure.
          and therefore is contraindicated in patients with NYHA class III to IV heart failure, and in those patients with unstable NYHA class II heart failure.
        • Dronedarone has been shown to be effective for maintenance of sinus rhythm in patients with nonsurgical paroxysmal AF. Dronedarone is contraindicated in patients with permanent AF, due to increased mortality associated with dronedarone in that patient population.
          • Connolly S.J.
          • Camm A.J.
          • Halperin J.L.
          • Joyner C.
          • Alings M.
          • Amerena J.
          • et al.
          PALLAS Investigators
          Dronedarone in high-risk permanent atrial fibrillation.
          The efficacy of dronedarone for maintenance of sinus rhythm in patients with nonsurgical AF has not been investigated.
        • 3.3.6. Ibutilide
          Ibutilide is a Vaughan Williams class III antiarrhythmic agent that exerts its antiarrhythmic activity via activation of slow inward sodium current
          • Lee K.S.
          Ibutilide, a new compound with potent class III antiarrhythmic activity, activates a slow inward Na+ current in guinea pig ventricular cells.
          and inhibition of IKr.
          • Yang T.
          • Snyders D.J.
          • Roden D.M.
          Ibutilide, a methanesulfonanilide antiarrhythmic, is a potent blocker of the rapidly activating delayed rectifier K+ current (IKr) in AT-1 cells. Concentration-, time-, voltage-, and use-dependent effects.
          Ibutilide is effective for conversion of atrial flutter and fibrillation to sinus rhythm.
          • Stambler B.S.
          • Wood M.A.
          • Ellenbogen K.A.
          • Perry K.T.
          • Wakefield L.K.
          • VanderLugt J.T.
          Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators.
          Ibutilide is not available in an oral dosage form, and therefore is not used for maintenance of sinus rhythm. Ibutilide has been shown to be effective for conversion to sinus rhythm of AF occurring after coronary artery bypass graft surgery.
          • VanderLugt J.T.
          • Mattioni T.
          • Denker S.
          • Torchiana D.
          • Ahern T.
          • Wakefield L.K.
          • et al.
          Efficacy and safety of ibutilide fumarate for the conversion of atrial arrhythmias after cardiac surgery.
          The efficacy of ibutilide for conversion to sinus rhythm of AF after noncardiac surgery has not been investigated.
        • The primary adverse effect associated with ibutilide is TdP, which occurs in 1% to 3% of patients. The incidence of TdP is 2- to 3-fold higher in patients with heart failure as a result of reduced ejection fraction, which is a known risk factor for TdP. Ibutilide may also cause nonsustained monomorphic ventricular tachycardia in up to 8% of patients.
        • 3.3.7. Procainamide
          Procainamide is a Vaughan Williams class IA antiarrhythmic agent that exerts its antiarrhythmic effects through inhibition of fast sodium current as well as inhibition of IKr. In addition, a primary metabolite of procainamide, N-acetylprocainamide, inhibits IKr current and contributes to the overall antiarrhythmic activity of procainamide. Procainamide is effective for conversion of nonoperative AF to sinus rhythm.
          • Slavik R.S.
          • Tisdale J.E.
          • Borzak S.
          Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.
          The efficacy of procainamide for conversion to sinus rhythm of AF after noncardiac thoracic surgery has not been investigated. Procainamide is no longer available in an oral dosage form, and therefore is no longer indicated for maintenance of sinus rhythm in patients with nonsurgical AF.
        • The primary adverse effects associated with intravenous procainamide are hypotension, QT interval prolongation and TdP, and lengthening of the QRS complex.
        • 3.3.8. Propafenone
          Propafenone is a Vaughan Williams class IC antiarrhythmic agent that is a potent inhibitor of sodium conductance.
          • Seipel L.
          • Breithardt G.
          Propafenone–a new antiarrhythmic drug.
          Propafenone may also inhibit the transient outward potassium current (Ito) and the ultrarapid delayed rectifier potassium (Ikur) current in atrial myocytes.
          • Seki A.
          • Hagiwara N.
          • Kasanuki H.
          Effects of propafenone on K currents in human atrial myocytes.
          Propafenone is effective for maintenance of sinus rhythm in patients with nonoperative AF.
          • Pritchett E.L.
          • McCarthy E.A.
          • Wilkinson W.E.
          Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy.
          In addition, single-oral dose propafenone is effective for conversion of nonsurgical AF to sinus rhythm.
          • Boriani G.
          • Biffi M.
          • Capucci A.
          • Botto G.L.
          • Broffoni T.
          • Rubino I.
          • et al.
          Oral propafenone to convert recent-onset atrial fibrillation in patients with and without underlying heart disease. A randomized, controlled trial.
          The efficacy of propafenone for prophylaxis or management of AF after noncardiac thoracic surgery has not been investigated.
        • Oral propafenone is well tolerated overall. Adverse effects include dizziness and blurred vision. However, propafenone possesses negative inotropic activity, and is contraindicated in patients with heart failure due to reduced ejection fraction.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          In addition, propafenone is contraindicated in patients with coronary artery disease or a history of myocardial infarction. Although propafenone was not studied in the CAST trial, the effects of flecainide and encainide in that study are believe to be to the result of potent sodium channel inhibition, and contraindications in patients with structural heart disease have been applied to propafenone.
        • 3.3.9. Sotalol
          Sotalol is an adrenergic β-receptor blocking agent
          • Singh B.N.
          • Nademanee K.
          Sotalol: a beta blocker with unique antiarrhythmic properties.
          that also prolongs atrial and ventricular action potential duration via inhibition of IKr.
          • Carmeliet E.
          Electrophysiologic and voltage clamp analysis of the effects of sotalol on isolated cardiac muscle and Purkinje fibers.
          Sotalol is effective for reducing the incidence of recurrent AF in patients with paroxysmal AF
          • Benditt D.G.
          • Williams J.H.
          • Jin J.
          • Deering T.F.
          • Zucker R.
          • Browne K.
          • et al.
          Maintenance of sinus rhythm with oral d,l-sotalol therapy in patients with symptomatic atrial fibrillation and/or atrial flutter. d,l-Sotalol Atrial Fibrillation/Flutter Study Group.
          and after conversion to sinus rhythm.
          • Lafuente-Lafuente C.
          • Mouly S.
          • Longas-Tejero M.A.
          • Bergmann J.F.
          Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation.
          Sotalol has not been shown to be effective for conversion of AF to sinus rhythm. Sotalol has been used to reduce the risk of AF after coronary artery bypass graft (CABG) surgery.
          • Auer J.
          • Weber T.
          • Berent R.
          • Puschmann R.
          • Hartl P.
          • Ng C.-K.
          • et al.
          Study of prevention of postoperative atrial fibrillation. A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial.
          However, the efficacy of sotalol for prophylaxis of AF after noncardiac thoracic surgery has not been investigated.
        • 3.3.10. Quinidine
          Quinidine is a Vaughan Williams class IA antiarrhythmic agent that inhibits sodium conduction
          • Nattel S.
          • Quantz M.A.
          Pharmacological response of quinidine induced early afterdepolarisations in canine cardiac Purkinje fibres: insights into underlying ionic mechanisms.
          as well as conductance of a variety of potassium currents, including IKr, IKI, and Ito.
          • Nenov N.I.
          • Crumb W.J.
          • Pigott J.D.
          • Harrison L.H.
          • Clarkson C.W.
          Quinidine interactions with human atrial potassium channels: developmental aspects.
          The use of oral quinidine for management of AF has largely been discontinued, because of evidence that quinidine may increase mortality.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Lafuente-Lafuente C.
          • Mouly S.
          • Longás-Tejero M.A.
          • Mahé I.
          • Bergmann J.-F.
          Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials.
          Quinidine may prolong the QT interval and cause TdP. The efficacy of quinidine for prevention or management of AF after noncardiac thoracic surgery has not been evaluated.
      • 3.4.
        Serum drug concentration monitoring
        • 3.4.1.
          Digoxin
          Serum drug concentration monitoring may be warranted only if toxicity is of concern.
        • Digoxin has a narrow therapeutic index, meaning that serum concentrations required for efficacy are similar to those that may cause toxicity. When used for heart failure, the desired therapeutic range is 0.5 to 0.9 ng/mL.
          • Yancy C.W.
          • Jessup M.
          • Bozkurt B.
          • Butler J.
          • Casey D.E.
          • Drazner M.H.
          • et al.
          2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
          The optimal therapeutic range for digoxin for the management of AF has not been established. The incidence of adverse effects associated with digoxin increases with serum concentrations greater than 2 ng/mL.
          • Smith T.W.
          • Haber E.
          Digoxin intoxication: the relationship of clinical presentation to serum digoxin concentration.
        • During the management of AF after noncardiac thoracic surgery, monitoring of serum digoxin concentrations for assessment of efficacy is not necessary, as a strong relationship between rate control efficacy and serum digoxin concentration has not been established. Determination of serum digoxin concentration may be warranted if patients exhibit symptoms of digoxin toxicity, including nausea, vomiting, anorexia, or ventricular arrhythmias. If a serum concentration is believed to be necessary, the blood sample should be obtained at least 12 hours, and preferably 24 hours, after the previous digoxin dose, as a result of the prolonged tissue distribution phase
          • Burton M.E.
          Applied Pharmacokinetics & Pharmacodynamics.
          (pp410-439); if the blood sample is obtained less than 12 hours after the dose, the serum concentration may be falsely increased, as a result of incomplete distribution of digoxin from serum to tissue.
        • To reduce the risk of digoxin toxicity in patients receiving the drug for AF after noncardiac thoracic surgery, serum digoxin concentration monitoring may be warranted if digoxin therapy must be continued for longer than 1 week, for those patients who remain in AF after hospital discharge. For patients with normal kidney function, the half-life of digoxin is approximately 36 hours; therefore, steady state serum concentrations require approximately 1 week. Routine determination of a steady state serum digoxin concentration after 1 week of therapy is not required in all patients. However, determination of a serum digoxin concentration after 1 week of therapy may be warranted in patients with chronic kidney disease or acute kidney injury, or in patients who are treated concomitantly with a drug that inhibits digoxin elimination, such as amiodarone, dronedarone, propafenone, quinidine, and verapamil.
          • Burton M.E.
          Applied Pharmacokinetics & Pharmacodynamics.
          (pp410-439)
        • 3.4.2.
          Procainamide: serum drug concentration monitoring is not warranted
        • The suggested therapeutic range for procainamide efficacy is 4 to 10 mg/L.
          • Burton M.E.
          Applied Pharmacokinetics & Pharmacodynamics.
          (pp440-462) However, this therapeutic range was determined using suppression of ventricular premature depolarizations and prevention of episodes of ventricular tachycardia. Serum procainamide concentrations have not been correlated with efficacy in AF, and therefore, desired serum procainamide concentrations for efficacy in AF are unknown. Serum concentration monitoring for intravenous procainamide for management of AF after noncardiac thoracic surgery is not warranted. The risk of adverse effects associated with intravenous procainamide can be minimized by terminating the loading dose of 20 to 50 mg/min continuous infusion if hypotension occurs, QRS duration is prolonged by 50%, or a cumulative intravenous dose of 17 mg/kg has been administered.
          • Neumar R.W.
          • Otto C.W.
          • Link M.S.
          • Kronick S.L.
          • Shuster M.
          • Callaway C.W.
          • et al.
          Part 8: Adult advanced cardiovascular life support 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care.
        • 3.4.3.
          Amiodarone: serum drug concentration monitoring is not warranted
        • Serum amiodarone concentration monitoring has been performed during therapy for ventricular arrhythmias. However, a relationship between serum amiodarone concentrations and efficacy for prevention or management of AF has not been established. Similarly, a relationship between serum amiodarone concentrations and most of the adverse effects of amiodarone, particularly those that occur during short-term therapy, has not been established. Therefore, monitoring of serum amiodarone concentrations during prophylaxis or management of AF after noncardiac thoracic surgery is not warranted. However, to minimize the risk of pulmonary toxicity, it is recommended to keep total cumulative intravenous amiodarone doses to less than 2150 mg.
        • 3.4.4.
          Flecainide: serum drug concentration monitoring is not warranted
        • The therapeutic range for serum flecainide concentrations is often cited as 0.3 to 2.5 mg/L.
          • Burton M.E.
          Applied Pharmacokinetics & Pharmacodynamics.
          (pp440-462) However, this therapeutic range was developed using suppression of ventricular premature depolarizations as an end point, rather than efficacy for the management of AF. A relationship between serum flecainide concentrations and efficacy for prophylaxis or management of AF, particularly that occurring after noncardiac thoracic surgery, has not been established. Serum flecainide concentration monitoring for prophylaxis or treatment of AF after noncardiac thoracic surgery is not warranted.
      • 3.5.
        Key limitations of drugs
        • 3.5.1.
          Pulmonary toxicity
        • A primary concern regarding the administration of intravenous amiodarone following lung resection is pulmonary toxicity, specifically ARDS. This concern was prominently identified by Van Mieghem and colleagues,
          • Van Mieghem W.
          • Coolen L.
          • Malysse I.
          • Lacquet L.M.
          • Deneffe G.J.
          • Demedts M.G.
          Amiodarone and the development of ARDS after lung surgery.
          who initiated a study to determine the comparative effectiveness of amiodarone, verapamil, or placebo for prevention of AF after pulmonary resection. The study was terminated prematurely due a high incidence of ARDS in amiodarone-treated patients, specifically in patients who had undergone pneumonectomy. At the time of discontinuation of the amiodarone arm, the drug had been administered to 32 patients, of whom 21 had undergone lobectomy and 11 had undergone pneumonectomy. No patients who underwent lobectomy developed amiodarone-associated ARDS. In contrast, 3 of 11 patients (27%) in the amiodarone group who underwent pneumonectomy developed ARDS. The investigators recommended avoiding amiodarone administration for patients undergoing pulmonary resection.
        • Other investigators have administered intravenous amiodarone to patients undergoing lung surgery without adverse effects. In a prospective, randomized, unblinded amiodarone prophylaxis,
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection.
          the incidence of ARDS among the 65 amiodarone-treated patients (of whom 40 underwent lobectomy, 8 underwent bilobectomy, and 17 underwent pneumonectomy) was 0%. Barbetakis and colleagues
          • Barbetakis N.
          • Vassiliadis M.
          Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery?.
          administered intravenous amiodarone to 43 patients for treatment of AF after lung resection. No patients developed ARDS; 21 of these patients underwent pneumonectomy. Riber and colleagues
          • Riber L.P.
          • Christensen T.D.
          • Jensen H.K.
          • Hoejsgaard A.
          • Pilegaard H.K.
          Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
          conducted a randomized, prospective, double-blind, placebo-controlled study of amiodarone for prevention of AF after lung resection. Only 2 patients of the 122 who received amiodarone underwent pneumonectomy; the remainder underwent right-side lobectomy or bilobectomy. No patients in this study developed ARDS or any pulmonary toxicity.
        • One potential difference in patients undergoing pneumonectomy in the Van Miegham study
          • Van Mieghem W.
          • Coolen L.
          • Malysse I.
          • Lacquet L.M.
          • Deneffe G.J.
          • Demedts M.G.
          Amiodarone and the development of ARDS after lung surgery.
          compared with these more recent trials
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection.
          • Barbetakis N.
          • Vassiliadis M.
          Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery?.
          • Riber L.P.
          • Christensen T.D.
          • Jensen H.K.
          • Hoejsgaard A.
          • Pilegaard H.K.
          Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
          include the cumulative intravenous amiodarone dose administered. In the Van Mieghem study, intravenous amiodarone was administered as a bolus of 150 mg over 2 minutes, followed by a continuous infusion of 1200 mg over 24 hours for 3 consecutive days, for a possible cumulative intravenous amiodarone dose of 3750 mg. The 3 patients who developed amiodarone-induced ARDS received cumulative intravenous amiodarone doses of 2150, 3750, and 3350 mg before discontinuation of therapy. In the more recent studies, patients received a cumulative intravenous amiodarone dose of 1050 mg, after which oral amiodarone was initiated,
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection.
          or a loading dose of 300 mg intravenous amiodarone before switching to oral amiodarone.
          • Riber L.P.
          • Christensen T.D.
          • Jensen H.K.
          • Hoejsgaard A.
          • Pilegaard H.K.
          Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
          In the Barbetakis study,
          • Barbetakis N.
          • Vassiliadis M.
          Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery?.
          intravenous amiodarone was administered as a loading dose of 5 mg/kg over 5 minutes, followed by 15 mg/kg for an undefined time period. In addition, in the Van Miegham study, the 3 patients who developed amiodarone-associated ARDS underwent right-sided pneumonectomy, which is associated with a higher risk of postoperative ARDS than other types of lung surgery.
        • Overall, administration of amiodarone at the dose shown to be effective by Riber and colelagues
          • Riber L.P.
          • Christensen T.D.
          • Jensen H.K.
          • Hoejsgaard A.
          • Pilegaard H.K.
          Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
          (300 mg intravenous loading dose followed by 600 mg orally twice daily for 5 days) seems to be safe and effective for prevention of AF after pulmonary resection.
        • 3.5.2.
          QT interval prolongation/torsades de pointes
        • Several of the drugs that may be used for prophylaxis or management of postoperative AF may cause QT interval prolongation, and therefore pose a risk for the life-threatening polymorphic ventricular arrhythmia known as TdP.
          • Tisdale J.E.
          Ventricular arrhythmias.
          Drugs that prolong the QT interval are generally those that inhibit IKr, and include amiodarone, procainamide, dofetilide, dronedarone, ibutilide, sotalol, and quinidine. A Bazett-corrected QT (QTc) interval greater than 500 ms markedly increases the risk for drug-induced TdP.
          • Trinkley K.E.
          • Page R.L.
          • Lien H.
          • Yamanouye K.
          • Tisdale J.E.
          QT interval prolongation and the risk of torsades de pointes: essentials for clinicians.
          Patients receiving a drug that prolongs the QTc interval should have the QTc interval measured from a rhythm strip or 12-lead ECG at least once daily during therapy. In addition, because the occurrence of TdP is highly dependent on the presence of other risk factors (female sex, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, heart failure, increased serum drug concentrations),
          • Tisdale J.E.
          Ventricular arrhythmias.
          • Trinkley K.E.
          • Page R.L.
          • Lien H.
          • Yamanouye K.
          • Tisdale J.E.
          QT interval prolongation and the risk of torsades de pointes: essentials for clinicians.
          modifiable risk factors should be corrected. Serum potassium, magnesium, and calcium concentrations should be maintained in the normal range. Drug interactions leading to increased concentrations of a QT interval–prolonging drug should be avoided. Doses of renally eliminated QT interval–prolonging drugs (dofetilide, procainamide, sotalol) should be appropriately adjusted for declining kidney function. In addition, concomitant therapy with other QT interval-prolonging drugs, particularly noncardiovascular QT interval-prolonging drugs (fluoroquinolone and macrolide antibiotics, azole antifungal agents, antidepressants, antipsychotics, many others)
          • Tisdale J.E.
          Ventricular arrhythmias.
          should be avoided or performed cautiously.
        • 3.5.3.
          Hypotension
        • Several drugs administered intravenously for prophylaxis or management of postoperative AF may cause hypotension, including diltiazem, esmolol, metoprolol, procainamide, and amiodarone. Drug-associated hypotension is more likely to occur when patients are volume depleted, which is often the case after thoracic surgery. In the population with AF after coronary artery bypass graft, hypotension associated with intravenous diltiazem was more likely when the pretreatment systolic blood pressure was less than 115 mm Hg.
          • Tisdale J.E.
          • Padhi I.D.
          • Goldberg A.D.
          • Silverman N.A.
          • Webb C.R.
          • Higgins R.S.
          • et al.
          A randomized, double-blind comparison of intravenous diltiazem and digoxin for atrial fibrillation after coronary artery bypass surgery.
        • 3.5.4.
          Bradycardia
        • Drugs used for ventricular rate control can also result in bradycardia through inhibition of sinus node function or AV nodal conduction. These drugs include amiodarone, propafenone, flecainide, esmolol, metoprolol, sotalol, and diltiazem.
          • Tisdale J.E.
          Ventricular arrhythmias.
          The risk is higher when combinations of sinus node or AV node-inhibiting drugs are used.
        • 3.5.5.
          Exacerbation of heart failure with reduced LV ejection fraction
        • Several drugs used for prophylaxis or treatment of postoperative AF possess negative inotropic activity and are contraindicated in patients with heart failure with reduced LV ejection fraction. These drugs include diltiazem, procainamide, propafenone, and flecainide.

      Prevention Strategies and Their Efficacy

      Recent evidence suggest that some prevention strategies (avoiding β blockade withdrawal for those chronically on those medications, correction of serum magnesium when abnormal) may be effective for all patients for reducing the incidence of POAF. By surveying the AATS membership, we also found that many of these strategies are currently underused (Figure 1).
      Figure thumbnail gr1
      Figure 1Prevention strategies and their efficacy for postoperative atrial fibrillation (POAF). LOE, Level of evidence; PVI, pulmonary vein isolation; i.v., intravenous; LVEF, left ventricular ejection fraction; AF, atrial fibrillation.

      Recommendations

      • 4.1.
        Recommended prevention strategies for all patients
        • Class I
        • 4.1.1.
          Patients taking β-blockers before thoracic surgery should continue them in the postoperative period to avoid β-blockade withdrawal.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Anderson J.L.
          • Halperin J.L.
          • Albert N.M.
          • Bozkurt B.
          • Brindis R.G.
          • Curtis L.H.
          • et al.
          Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
          • Nattel S.
          • Rangno R.E.
          • Van Loon G.
          Mechanism of propranolol withdrawal phenomena.
          • Jakobsen C.-J.
          • Bille S.
          • Ahlburg P.
          • Rybro L.
          • Hjortholm K.
          • Bay Andresen E.
          Perioperative metoprolol reduces the frequency of atrial fibrillation after thoracotomy for lung resection.
          • Bayliff C.D.
          • Massel D.R.
          • Inculet R.I.
          • Malthaner R.A.
          • Quinton S.D.
          • Powell F.S.
          • et al.
          Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery.
          • Burgess D.C.
          • Kilborn M.J.
          • Keech A.C.
          Interventions for prevention of post-operative atrial fibrillation and its complications after cardiac surgery: a meta-analysis.
          • Rena O.
          • Papalia E.
          • Oliaro A.
          • Casadio C.
          • Ruffini E.
          • Filosso P.L.
          • et al.
          Supraventricular arrhythmias after resection surgery of the lung.
          (LOE A).
        • Class IIb
        • 4.1.2.
          Intravenous magnesium supplementation may be considered to prevent postoperative AF when serum magnesium level is low or it is suspected that total body magnesium is depleted.
          • Terzi A.
          • Furlan G.
          • Chiavacci P.
          • Dal Corso B.
          • Luzzani A.
          • Dalla Volta S.
          Prevention of atrial tachyarrhythmias after non-cardiac thoracic surgery by infusion of magnesium sulfate.
          • Anderson J.L.
          • Halperin J.L.
          • Albert N.M.
          • Bozkurt B.
          • Brindis R.G.
          • Curtis L.H.
          • et al.
          Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
          • Rostron A.
          • Sanni A.
          • Dunning J.
          Does magnesium prophylaxis reduce the incidence of atrial fibrillation following coronary bypass surgery?.
          (LOE C).
        • Class III
        • 4.1.3.
          Digoxin should not be used for prophylaxis against AF.
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Anderson J.L.
          • Halperin J.L.
          • Albert N.M.
          • Bozkurt B.
          • Brindis R.G.
          • Curtis L.H.
          • et al.
          Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
          • Ritchie A.J.
          • Tolan M.
          • Whiteside M.
          • McGuigan J.A.
          • Gibbons J.R.
          Prophylactic digitalization fails to control dysrhythmia in thoracic esophageal operations.
          • Kaiser A.
          • Zünd G.
          • Weder W.
          • Largiadèr F.
          Preventive digitalis therapy in open thoracotomy.
          • Amar D.
          • Roistacher N.
          • Burt M.E.
          • Rusch V.W.
          • Bains M.S.
          • Leung D.H.
          • et al.
          Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy.
          (LOE A).
        • 4.1.4.
          Catheter or surgical pulmonary vein isolation (at the time of surgery) is not recommended for prevention of POAF for patients who have no previous history of AF
          • See V.Y.
          • Roberts-Thomson K.C.
          • Stevenson W.G.
          • Camp P.C.
          • Koplan B.A.
          Atrial arrhythmias after lung transplantation: epidemiology, mechanisms at electrophysiology study, and outcomes.
          (LOE C).
        • 4.1.5.
          Complete or partial pulmonary vein isolation at the time of (even bilateral) lung surgery should not be considered for prevention of POAF, as it is unlikely to be effective
          • See V.Y.
          • Roberts-Thomson K.C.
          • Stevenson W.G.
          • Camp P.C.
          • Koplan B.A.
          Atrial arrhythmias after lung transplantation: epidemiology, mechanisms at electrophysiology study, and outcomes.
          • Mason D.P.
          • Marsh D.H.
          • Alster J.M.
          • Murthy S.C.
          • McNeill A.M.
          • Budev M.M.
          • et al.
          Atrial fibrillation after lung transplantation: timing, risk factors, and treatment.
          • Dizon J.M.
          • Chen K.
          • Bacchetta M.
          • Argenziano M.
          • Mancini D.
          • Biviano A.
          • et al.
          A comparison of atrial arrhythmias after heart or double-lung transplantation at a single center: insights into the mechanism of post-operative atrial fibrillation.
          (LOE B).
        • For those patients at increased risk for the development of POAF, preventive administration of medications (diltiazem or amiodarone) may be reasonable. However, these strategies may not be useful for all thoracic surgical patients.
      • 4.2.
        Recommended prevention strategies for intermediate to high-risk patients
        • Class IIa
        • 4.2.1.
          It is reasonable to administer diltiazem to those patients with preserved cardiac function who are not taking β-blockers preoperatively in order to prevent POAF
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Amar D.
          • Roistacher N.
          • Rusch V.W.
          • Leung D.H.Y.
          • Ginsburg I.
          • Zhang H.
          • et al.
          Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery.
          • Khalil M.A.
          • Al-Agaty A.E.
          • Ali W.G.
          • Abdel Azeem M.S.
          A comparative study between amiodarone and magnesium sulfate as antiarrhythmic agents for prophylaxis against atrial fibrillation following lobectomy.
          (LOE B).
        • 4.2.2.
          It is reasonable to consider the postoperative administration of amiodarone to reduce the incidence of POAF for intermediate and high risk patients undergoing pulmonary resection
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy.
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection.
          • Barbetakis N.
          • Vassiliadis M.
          Is amiodarone a safe antiarrhythmic to use in supraventricular tachyarrhythmias after lung cancer surgery?.
          • Riber L.P.
          • Christensen T.D.
          • Jensen H.K.
          • Hoejsgaard A.
          • Pilegaard H.K.
          Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
          • Khalil M.A.
          • Al-Agaty A.E.
          • Ali W.G.
          • Abdel Azeem M.S.
          A comparative study between amiodarone and magnesium sulfate as antiarrhythmic agents for prophylaxis against atrial fibrillation following lobectomy.
          (LOE A).
        • Class IIb
        • 4.2.3.
          Postoperative administration of intravenous amiodarone may be considered to prevent POAF in patients undergoing esophagectomy
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy.
          • Riber L.P.
          • Christensen T.D.
          • Jensen H.K.
          • Hoejsgaard A.
          • Pilegaard H.K.
          Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
          • Khalil M.A.
          • Al-Agaty A.E.
          • Ali W.G.
          • Abdel Azeem M.S.
          A comparative study between amiodarone and magnesium sulfate as antiarrhythmic agents for prophylaxis against atrial fibrillation following lobectomy.
          • Lanza L.A.
          • Visbal A.I.
          • DeValeria P.A.
          • Zinsmeister A.R.
          • Diehl N.N.
          • Trastek V.F.
          Low-dose oral amiodarone prophylaxis reduces atrial fibrillation after pulmonary resection.
          (LOE B).
        • 4.2.4.
          Atorvastatin may be considered to prevent POAF for statin-naive patients scheduled for intermediate- and high-risk thoracic surgical procedures
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Amar D.
          • Zhang H.
          • Heerdt P.M.
          • Park B.
          • Fleisher M.
          • Thaler H.T.
          Statin use is associated with a reduction in atrial fibrillation after noncardiac thoracic surgery independent of C-reactive protein.
          • Fauchier L.
          • Pierre B.
          • de Labriolle A.
          • Grimard C.
          • Zannad N.
          • Babuty D.
          Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials.
          • Chopra V.
          • Wesorick D.H.
          • Sussman J.B.
          • Greene T.
          • Rogers M.
          • Froehlich J.B.
          • et al.
          Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis.
          (LOE C).
      • 4.3.
        Recommended prevention strategies for the highest-risk patients
        • Class IIb
        • 4.3.1.
          Left atrial appendage excision may be considered at the time of extensive left lung surgery for patients with preexisting AF who are considered too high a risk for anticoagulation in the perioperative period
          • January C.T.
          • Wann L.S.
          • Alpert J.S.
          • Calkins H.
          • Cleveland J.C.
          • Cigarroa J.E.
          • et al.
          2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
          • Anderson J.L.
          • Halperin J.L.
          • Albert N.M.
          • Bozkurt B.
          • Brindis R.G.
          • Curtis L.H.
          • et al.
          Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
          • Johnson W.D.
          • Ganjoo A.K.
          • Stone C.D.
          • Srivyas R.C.
          • Howard M.
          The left atrial appendage: our most lethal human attachment! Surgical implications.
          (LOE C).

      Reasoning

      • 4.4.
        Prevention of postoperative AF
      • AF, the most common sustained arrhythmia after pulmonary and esophageal surgery, is associated with longer intensive care unit and hospital stays, increased morbidity and mortality, and higher utilization of health care resources.
        • Roselli E.E.
        • Murthy S.C.
        • Rice T.W.
        • Houghtaling P.L.
        Atrial fibrillation complicating lung cancer resection.
        • Irshad K.
        • Feldman L.S.
        • Chu V.F.
        • Dorval J.-F.
        • Baslaim G.
        • Morin J.E.
        Causes of increased length of hospitalization on a general thoracic surgery service: a prospective observational study.
        POAF also represents a major potentially preventable adverse outcome. Several randomized controlled studies and meta-analyses have examined the efficacy of a variety of agents including antiarrhythmics, β-blockers, and novel agents such as magnesium and statins to prevent the development of POAF in patients undergoing thoracic surgery. However, it should be appreciated that there is a dearth of data indicating that prophylactic therapy for AF improves outcomes after thoracic surgery (eg, stroke) and reduces length of hospital stay, and many of the recommendations are extrapolated from the cardiac surgery arena.
      • The recommendation to avoid withdrawal of β-blockers in all patients undergoing thoracic surgery is mainly derived from the cardiac surgery literature. Nattel and colleagues
        • Nattel S.
        • Rangno R.E.
        • Van Loon G.
        Mechanism of propranolol withdrawal phenomena.
        showed that abrupt propranolol withdrawal was associated with increased sensitivity to isoproterenol, and a large meta-analysis of randomized studies confirmed that acute withdrawal of β-blockers before cardiac surgery increases the risk of developing POAF.
        • Burgess D.C.
        • Kilborn M.J.
        • Keech A.C.
        Interventions for prevention of post-operative atrial fibrillation and its complications after cardiac surgery: a meta-analysis.
        There are only limited data supporting the role of prophylactic β-blockers in patients undergoing thoracic surgery.
        • Hardy J.
        Risk factors for atrial fibrillation following extrapleural pneumonectomy, the effect of prophylactic beta blockade.
        • Jakobsen C.-J.
        • Bille S.
        • Ahlburg P.
        • Rybro L.
        • Hjortholm K.
        • Bay Andresen E.
        Perioperative metoprolol reduces the frequency of atrial fibrillation after thoracotomy for lung resection.
        • Bayliff C.D.
        • Massel D.R.
        • Inculet R.I.
        • Malthaner R.A.
        • Quinton S.D.
        • Powell F.S.
        • et al.
        Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery.
        Although two of these randomized studies showed a reduction in POAF, there was a high incidence of hypotension and bradycardia that limited the use of β-blockers in the perioperative setting.
        • Devereaux P.J.
        • Yang H.
        • Yusuf S.
        • Guyatt G.
        • Leslie K.
        • et al.
        POISE Study Group
        Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.
        There remains controversy in the recent literature as to whether to initiate perioperative β-blockers in patients who are not already taking them. At recommended doses aimed at achieving a target heart rate, β-blockers may cause significant postoperative hypotension and stroke-related mortality.
        • Devereaux P.J.
        • Yang H.
        • Yusuf S.
        • Guyatt G.
        • Leslie K.
        • et al.
        POISE Study Group
        Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.
        In randomized controlled trials, diltiazem has not been associated with perioperative hypotension. The ability of diltiazem to reduce AF after thoracic surgery is moderate.
        • Akoum N.
        • Daccarett M.
        • McGann C.
        • Segerson N.
        • Vergara G.
        • Kuppahally S.
        • et al.
        Atrial fibrosis helps select the appropriate patient and strategy in catheter ablation of atrial fibrillation: a DE-MRI guided approach.
      • To date, the best evidence for efficacy of AF prevention in general thoracic surgery patients has been with amiodarone. An important issue with any prevention efforts is the acceptance of a recommended medication by the responsible surgical team, particularly with a drug like amiodarone that has potential for side effects. The antiarrhythmic mechanism of amiodarone combines varying degrees of class III antiarrhythmic activity, β-blockade, and calcium channel antagonism. Slower postoperative heart rates with short-term use and greater than moderate efficacy in reducing AF may result in wider physician acceptance of amiodarone, although concerns regarding rare reports of pulmonary toxicity with right lung resection or lung transplantation may moderate its use (discussed in more detail in section 3).
      • 4.5.
        Pharmacologic therapies to prevent POAF
        • 4.5.1.
          Amiodarone
        • Efficacy of amiodarone: Tisdale and colleagues
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection.
          showed that amiodarone 1.05 g given by continuous intravenous infusion over the first 24 hours after pulmonary resection and then 400 mg orally twice daily for up to 6 days, reduced the rate of POAF requiring treatment, 9 of 65 (14%) in comparison with 21 of 65 (32%), in an untreated control group. In a similar study, the same investigators
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy.
          showed that continuous infusion of amiodarone 43.75 mg/h for 96 hours (total dose 4200 mg) was associated with a lower POAF rate of 6 of 40 (15%) in patients undergoing esophagectomy compared with 16 of 40 (40%) in an untreated control group. The largest trial to date by Riber and colleagues
          • Riber L.P.
          • Christensen T.D.
          • Jensen H.K.
          • Hoejsgaard A.
          • Pilegaard H.K.
          Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer.
          used a randomized, double-blind, placebo-controlled design of amiodarone given by loading 300 mg intravenously immediately when stable after surgery followed by 600 mg orally twice daily for up to 5 days. They showed that amiodarone-treated patients had a rate of POAF (lasting >5 min) of 9% (11 of 122), compared with placebo controls who had a rate of 32% (38 of 120). A final study of patients undergoing pulmonary resection randomized 2 groups of patients in a prospective, double-blind design to either amiodarone (postoperative intravenous loading 5 mg/kg, then 15 mg/kg for 48 hours intravenous infusion) or magnesium sulfate (preoperative loading of 80 mg/kg and then 8 mg/kg/h for 48 hours intravenous infusion after surgery).
          • Khalil M.A.
          • Al-Agaty A.E.
          • Ali W.G.
          • Abdel Azeem M.S.
          A comparative study between amiodarone and magnesium sulfate as antiarrhythmic agents for prophylaxis against atrial fibrillation following lobectomy.
          This study showed that the incidence of POAF (lasting >30 seconds) was 10% (21 of 219) with amiodarone and 13% (27 of 219) with magnesium. None of these studies reported any serious adverse effects caused by amiodarone except occasional bradycardia.
        • Safety of amiodarone: In the nonsurgical population, it is commonly accepted that amiodarone-related pulmonary toxicity does not occur with short-term (<1 month) exposure. Concerns about amiodarone-related perioperative pulmonary toxicity were raised 2 decades ago in a small randomized study that was interrupted early because 3 right-sided pneumonectomy patients of a total of 11 patients who received amiodarone for prevention of POAF developed ARDS, whereas none of the 21 patients undergoing lobectomy and exposed to amiodarone developed this complication.
          • Van Mieghem W.
          • Coolen L.
          • Malysse I.
          • Lacquet L.M.
          • Deneffe G.J.
          • Demedts M.G.
          Amiodarone and the development of ARDS after lung surgery.
          The investigators acknowledged that right-sided pneumonectomy in itself was a well-established risk for ARDS, but nevertheless cautioned on the use of amiodarone for AF prevention after pulmonary resection. Since then, several observational and more recent prospective randomized trials failed to find a link between use of amiodarone for AF prevention and ARDS immediately after pulmonary resection.
          • Tisdale J.E.
          • Wroblewski H.A.
          • Wall D.S.
          • Rieger K.M.
          • Hammoud Z.T.
          • Young J.V.
          • et al.
          A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy.