Characterizing Patients With POAF in Relation to Cardiac Surgery by wavECG and TTE

Atrial Fibrillation Clinical Trial

Official title:

Characterizing Patients With Post-operative Atrial Fibrillation in Relation to Cardiac Surgery by Signal Processed Surface Electrocardiogram (wavECG) and Transthoracic Echocardiography A LAACS-2 Sub-study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03962166
• Other study ID #: H-17033253-S1
• Status: Active, not recruiting
• Start date: October 7, 2019
• Est. completion date: December 31, 2026

Study information

• Verified date: January 2024
• Source: University Hospital Bispebjerg and Frederiksberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Post-operative atrial fibrillation (POAF) is frequently observed after open-heart surgery. Despite numerous attempts to predict POAF, it remains a challenge to correctly identify the patients at risk. New technologies are available but not yet in cooperated in clinical guidelines and prediction models. We aim at identifying patients at risk of AF occurrence/recurrence after open-heart surgery by use of signal processed surface ECG (wavECG).

The study is an explorative, prospective cohort study of 100 patients undergoing first-time elective open-heart surgery in the Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial (NCT03724318). Patients are examined by electrocardiogram (ECG), wavECG, transthoracic echocardiography and continuous heart rhythm monitoring. Primary endpoint is occurrence/recurrence of AF. Left ventricular diastolic dysfunction as evaluated by wavECG will be used to predict incidence of primary endpoint.

Description:

Introduction: Post-operative atrial fibrillation (POAF) is frequently observed after open-heart surgery,1-3 and atrial fibrillation (AF) is frequently complicated by stroke.4-6 During AF, the electrical activity is uncoordinated and the atrial contraction is reduced, increasing the risk of thrombi formation. Subsequently, the thrombi can enter the general circulation, reach the small intracerebral arteries and block blood flow resulting in ischaemic damage.5,7 Anti-coagulant medicines efficiently prevent ischaemic strokes,8 however many patients are asymptomatic or have vague symptoms why diagnosis can be difficult to obtain.5 Furthermore, AF that occurs secondarily to surgery is currently considered self-limiting and continuous anti-coagulation is not necessarily recommended.4,9 However, cumulating evidence suggest that secondary AF in patients with known heart disease increases the long-term risk of stroke and transitory ischaemic attack, recurrent AF and mortality.10-15 In patients undergoing coronary artery bypass grafting (CABG) new-onset AF is associated with increased long-term risk of stroke and mortality compared to patients without AF.14,15 Though there are well-established risk factors for AF, such as age, arterial hypertension, heart failure, myocardial infarction, heart valve disease and diabetes mellitus, the pathophysiology of AF is complex and not fully understood.6,16,17 Both structural remodelling of the atria and electrical pathways, as well as oxidative stress, calcium overload, myofibroblast activation, microRNAs and inflammation, are mentioned as possible factors involved in initiation and progression of AF.6,16-18 Attempts to create and improve risk stratification models for AF and stroke has previously been done, both in community based cohorts and patients undergoing cardiac surgery, e.g. CHA2DS2-VASC, FHS AF risk score, ARIC risk prediction tool, CHARGE-AF risk model, HAVOC score, SYNTAX score, POAF score and POAF prediction model.19-27 However, it remains challenging to accurately predict occurrence of AF both perioperatively and in the subsequent years.28,29

A recent systematic review and meta-analysis concluded that p-wave terminal force in lead V1 (PTFV1), p-wave duration and maximum p-wave area, are all correlated with stroke,30 and a recent review similarly suggest that short and prolonged p-wave and PTFV1 is correlated with AF.31 sp-ECG by Myovista (Southlake, Texas, USA) is a novel advanced ECG utilizing continues wavelet transform signal processing and can detect left ventricular diastolic dysfunction (LVDD) which is associated with AF and post-operative heart failure in other studies.17,32-35 LA strain and E/LA strain indices predicted new cardiovascular events including strokes, in a stroke population36 In patients undergoing catheter ablation for AF, LA strain can identify patients at risk of AF recurrence37,38 POAF has furthermore been predicted in a cohort of patients with severe aortic stenosis by LA strain indexes.39

Aim: We aim at characterizing patients with AF occurrence by novel, easy, and accessible methods such as electrocardiogram (ECG), signal processed surface ECG (Myovista, wavECG) and transthoracic echocardiography (TTE).

Methods: Explorative, prospective cohort study of adult patients undergoing first-time elective open-heart surgery at Department of Cardiothoracic Surgery at Copenhagen University Hospital, Rigshospitalet. One hundred consecutive patients enrolled in the Left Atrial Appendage Closure by Surgery-2 (LAACS-2) trial (NCT03724318) fulfilling the inclusion/exclusion criteria are included in the current study.

The study is approved by the Regional Committee on Health Research Ethics and all procedures followed are in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration. All patients have signed informed consent prior to study enrolment.

Study timeline: One day prior to surgery; patient charts are reviewed, and ECG, wavECG and TTE are obtained. Anaesthesiologists will report AF occurred during intra-operative cardiac monitoring. Post-surgery cardiac rhythm monitoring is applied for at least 48 hours. At discharge patient charts and monitoring are reviewed for any occurrence of new-onset AF. Three months after surgery, patient charts are reviewed, and patients are invited for a single visit at Department of Cardiology at Frederiksberg hospital, where a control ECG, wavECG and TTE are performed. Deviation of the examination programme is accepted, i.e. patients can decline parts of the pre- or post-surgery examinations and remain in the study for follow-up.

Statistics: Precise sample size calculations are not applicable in this explorative study with LVDD in sp-ECG as primary end-point. One previous study has been performed where wavECG identified patients with LVDD in a population (n=188) referred for computed tomography coronary angiography.32 LA strain measured by TTE predicted POAF in 26 of 60 patients undergoing open-heart surgery for severe aortic stenosis.39 P-wave indices from pre-operative ECGs have predicted POAF in a population of 105 cardiac surgery patients.40 The study will include 100 consecutive patients undergoing open-heart surgery. Expected distribution of patients are n=10 for pre-surgery AF (corresponding to the incidence in the background population 1%6), POAF n= 35-50 (corresponding to the incidence in previous cardiac surgery populations; 35-50%1-3), and non-AF n=40-55 (remaining population). Follow-up will be three months.

Parametric statistics is used as normal distribution is expected (e.g. two-sample unpaired Student's t-test) and data is presented with mean ± standard deviation. All tests are two-sided and a P-value < 0.05 is considered statistically significant. IBM SPSS version 22 will be used for statistical analyses.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 353
• Est. completion date: December 31, 2026
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years

• First time open-heart surgery

• Coronary artery bypass grafting and/or valve surgery

• Signed informed consent

Exclusion Criteria:

• Planned closure of the left atrial appendage

• Planned ablation for atrial fibrillation during surgery

• Ongoing inflammation or infection (including endocarditis)

• Connective tissue disease

• Ongoing cancer (not control)

• Pregnancy

• Follow-up not possible

Related Conditions & MeSH terms

• Atrial Fibrillation
• Left Ventricular Diastolic Dysfunction
• Ventricular Dysfunction, Left

Locations

Country	Name	City	State
Denmark	Cardiology department Y, Bispebjerg-Frederiksberg Hospital	Frederiksberg

Sponsors (2)

Lead Sponsor	Collaborator
Helena DOMINGUEZ	Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (40)

Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2005 Jul 20;2005(3):CD001927. doi: 10.1002/1465185 — View Citation

Ahlsson A, Fengsrud E, Bodin L, Englund A. Postoperative atrial fibrillation in patients undergoing aortocoronary bypass surgery carries an eightfold risk of future atrial fibrillation and a doubled cardiovascular mortality. Eur J Cardiothorac Surg. 2010 — View Citation

Alonso A, Krijthe BP, Aspelund T, Stepas KA, Pencina MJ, Moser CB, Sinner MF, Sotoodehnia N, Fontes JD, Janssens AC, Kronmal RA, Magnani JW, Witteman JC, Chamberlain AM, Lubitz SA, Schnabel RB, Agarwal SK, McManus DD, Ellinor PT, Larson MG, Burke GL, Laun — View Citation

Asanin MR, Vasiljevic ZM, Matic MD, Mrdovic IB, Perunicic JP, Matic DP, Vujisic-Tesic BD, Stankovic SD, Matic DM, Ostojic MC. The long-term risk of stroke in patients with acute myocardial infarction complicated with new-onset atrial fibrillation. Clin Ca — View Citation

Bessissow A, Khan J, Devereaux PJ, Alvarez-Garcia J, Alonso-Coello P. Postoperative atrial fibrillation in non-cardiac and cardiac surgery: an overview. J Thromb Haemost. 2015 Jun;13 Suppl 1:S304-12. doi: 10.1111/jth.12974. Erratum In: J Thromb Haemost. 2 — View Citation

Bishara R, Telman G, Bahouth F, Lessick J, Aronson D. Transient atrial fibrillation and risk of stroke after acute myocardial infarction. Thromb Haemost. 2011 Nov;106(5):877-84. doi: 10.1160/TH11-05-0343. Epub 2011 Aug 25. — View Citation

Brecher O, Gulati H, Roistacher N, Zhang H, Shi W, Thaler HT, Amar D. Preoperative Echocardiographic Indices of Diastolic Dysfunction and Brain Natriuretic Peptide in Predicting Postoperative Atrial Fibrillation After Noncardiac Surgery. Anesth Analg. 201 — View Citation

Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, L — View Citation

Chamberlain AM, Agarwal SK, Folsom AR, Soliman EZ, Chambless LE, Crow R, Ambrose M, Alonso A. A clinical risk score for atrial fibrillation in a biracial prospective cohort (from the Atherosclerosis Risk in Communities [ARIC] study). Am J Cardiol. 2011 Ja — View Citation

Dawson AG, Asopa S, Dunning J. Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion? Interact Cardiovasc Thorac Surg. 2010 Feb;10(2):306-11. doi: 10.1510/icvts.2009.227991. Epub 2009 Nov 26. — View Citation

Frendl G, Sodickson AC, Chung MK, Waldo AL, Gersh BJ, Tisdale JE, Calkins H, Aranki S, Kaneko T, Cassivi S, Smith SC Jr, Darbar D, Wee JO, Waddell TK, Amar D, Adler D; American Association for Thoracic Surgery. 2014 AATS guidelines for the prevention and — View Citation

Gecmen C, Babur Guler G, Erdogan E, Hatipoglu S, Guler E, Yilmaz F, Unkun T, Cap M, Bengi Bakal R, Bayram T, Deniz Acar R, Candan O, Ozdemir N. SYNTAX score predicts postoperative atrial fibrillation in patients undergoing on-pump isolated coronary artery — View Citation

German DM, Kabir MM, Dewland TA, Henrikson CA, Tereshchenko LG. Atrial Fibrillation Predictors: Importance of the Electrocardiogram. Ann Noninvasive Electrocardiol. 2016 Jan;21(1):20-9. doi: 10.1111/anec.12321. Epub 2015 Nov 2. — View Citation

Gu J, Andreasen JJ, Melgaard J, Lundbye-Christensen S, Hansen J, Schmidt EB, Thorsteinsson K, Graff C. Preoperative Electrocardiogram Score for Predicting New-Onset Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery. J Cardiothorac V — View Citation

He J, Tse G, Korantzopoulos P, Letsas KP, Ali-Hasan-Al-Saegh S, Kamel H, Li G, Lip GYH, Liu T. P-Wave Indices and Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis. Stroke. 2017 Aug;48(8):2066-2072. doi: 10.1161/STROKEAHA.117.017293. Epub 201 — View Citation

Healey JS, Crystal E, Lamy A, Teoh K, Semelhago L, Hohnloser SH, Cybulsky I, Abouzahr L, Sawchuck C, Carroll S, Morillo C, Kleine P, Chu V, Lonn E, Connolly SJ. Left Atrial Appendage Occlusion Study (LAAOS): results of a randomized controlled pilot study — View Citation

Horwich P, Buth KJ, Legare JF. New onset postoperative atrial fibrillation is associated with a long-term risk for stroke and death following cardiac surgery. J Card Surg. 2013 Jan;28(1):8-13. doi: 10.1111/jocs.12033. Epub 2012 Nov 27. — View Citation

Hsu PC, Lee WH, Chu CY, Lee HH, Lee CS, Yen HW, Lin TH, Voon WC, Lai WT, Sheu SH, Su HM. Prognostic role of left atrial strain and its combination index with transmitral E-wave velocity in patients with atrial fibrillation. Sci Rep. 2016 Feb 1;6:17318. do — View Citation

Jalife J, Kaur K. Atrial remodeling, fibrosis, and atrial fibrillation. Trends Cardiovasc Med. 2015 Aug;25(6):475-84. doi: 10.1016/j.tcm.2014.12.015. Epub 2014 Dec 31. — View Citation

January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the manageme — View Citation

Kaw R, Hernandez AV, Masood I, Gillinov AM, Saliba W, Blackstone EH. Short- and long-term mortality associated with new-onset atrial fibrillation after coronary artery bypass grafting: a systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2011 — View Citation

Khaji A, Kowey PR. Update on atrial fibrillation. Trends Cardiovasc Med. 2017 Jan;27(1):14-25. doi: 10.1016/j.tcm.2016.06.007. Epub 2016 Jun 22. — View Citation

Kourliouros A, Camm AJ. Does inflammation influence atrial fibrillation recurrence following catheter ablation? Europace. 2009 Feb;11(2):135-7. doi: 10.1093/europace/eun386. No abstract available. — View Citation

Kwong C, Ling AY, Crawford MH, Zhao SX, Shah NH. A Clinical Score for Predicting Atrial Fibrillation in Patients with Cryptogenic Stroke or Transient Ischemic Attack. Cardiology. 2017;138(3):133-140. doi: 10.1159/000476030. Epub 2017 Jun 28. — View Citation

Lee SH, Kang DR, Uhm JS, Shim J, Sung JH, Kim JY, Pak HN, Lee MH, Joung B. New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary artery bypass graft. Am Heart J. 2014 Apr;167(4):593-600.e1. doi: 10.1016/j.ahj. — View Citation

Lip GYH, Nielsen PB, Skjoth F, Lane DA, Rasmussen LH, Larsen TB. The value of the European society of cardiology guidelines for refining stroke risk stratification in patients with atrial fibrillation categorized as low risk using the anticoagulation and — View Citation

Ma XX, Zhang YL, Hu B, Zhu MR, Jiang WJ, Wang M, Zheng DY, Xue XP. The usefulness of global left atrial strain for predicting atrial fibrillation recurrence after catheter ablation in patients with persistent and paroxysmal atrial fibrillation. Arch Cardi — View Citation

Mariscalco G, Biancari F, Zanobini M, Cottini M, Piffaretti G, Saccocci M, Banach M, Beghi C, Angelini GD. Bedside tool for predicting the risk of postoperative atrial fibrillation after cardiac surgery: the POAF score. J Am Heart Assoc. 2014 Mar 24;3(2): — View Citation

Materazzo C, Piotti P, Mantovani C, Miceli R, Villani F. Atrial fibrillation after non-cardiac surgery: P-wave characteristics and Holter monitoring in risk assessment. Eur J Cardiothorac Surg. 2007 May;31(5):812-6. doi: 10.1016/j.ejcts.2007.02.007. Epub — View Citation

Melduni RM, Schaff HV, Lee HC, Gersh BJ, Noseworthy PA, Bailey KR, Ammash NM, Cha SS, Fatema K, Wysokinski WE, Seward JB, Packer DL, Rihal CS, Asirvatham SJ. Impact of Left Atrial Appendage Closure During Cardiac Surgery on the Occurrence of Early Postope — View Citation

Parwani AS, Morris DA, Blaschke F, Huemer M, Pieske B, Haverkamp W, Boldt LH. Left atrial strain predicts recurrence of atrial arrhythmias after catheter ablation of persistent atrial fibrillation. Open Heart. 2017 Apr 28;4(1):e000572. doi: 10.1136/openhr — View Citation

Pernigo M, Canneto B, Betta D, Molinari G, Ribichini F, Zannini G, Vassanelli C, Rossi A. Dyspnea following thoracostomy closure after right pneumonectomy: An uncommon echocardiographic diagnosis and therapeutic approach. Echocardiography. 2017 May;34(5): — View Citation

Pillarisetti J, Patel A, Bommana S, Guda R, Falbe J, Zorn GT, Muehlebach G, Vacek J, Sue Min Lai, Lakkireddy D. Atrial fibrillation following open heart surgery: long-term incidence and prognosis. J Interv Card Electrophysiol. 2014 Jan;39(1):69-75. doi: 1 — View Citation

Schnabel RB, Sullivan LM, Levy D, Pencina MJ, Massaro JM, D'Agostino RB Sr, Newton-Cheh C, Yamamoto JF, Magnani JW, Tadros TM, Kannel WB, Wang TJ, Ellinor PT, Wolf PA, Vasan RS, Benjamin EJ. Development of a risk score for atrial fibrillation (Framingham — View Citation

Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD, Newton-Cheh C, Lubitz SA, Magnani JW, Ellinor PT, Seshadri S, Wolf PA, Vasan RS, Benjamin EJ, Levy D. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in — View Citation

Sellers D, Srinivas C, Djaiani G. Cardiovascular complications after non-cardiac surgery. Anaesthesia. 2018 Jan;73 Suppl 1:34-42. doi: 10.1111/anae.14138. — View Citation

Sengupta PP, Kulkarni H, Narula J. Prediction of Abnormal Myocardial Relaxation From Signal Processed Surface ECG. J Am Coll Cardiol. 2018 Apr 17;71(15):1650-1660. doi: 10.1016/j.jacc.2018.02.024. — View Citation

Siu CW, Jim MH, Ho HH, Miu R, Lee SW, Lau CP, Tse HF. Transient atrial fibrillation complicating acute inferior myocardial infarction: implications for future risk of ischemic stroke. Chest. 2007 Jul;132(1):44-9. doi: 10.1378/chest.06-2733. Epub 2007 Mar — View Citation

Szymanski C, Magne J, Fournier A, Rusinaru D, Touati G, Tribouilloy C. Usefulness of preoperative atrial fibrillation to predict outcome and left ventricular dysfunction after valve repair for mitral valve prolapse. Am J Cardiol. 2015 May 15;115(10):1448- — View Citation

Zusman O, Amit G, Gilutz H, Zahger D. The significance of new onset atrial fibrillation complicating acute myocardial infarction. Clin Res Cardiol. 2012 Jan;101(1):17-22. doi: 10.1007/s00392-011-0357-5. Epub 2011 Sep 11. — View Citation

* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Left atrial dysfunction	Evaluated by speckle-tracking and strain analysis (transthoracic echocardiography)	Two years post surgery
Other	Left ventricular diastolic dysfunction	Evaluated by wavECG	Two years post surgery
Primary	Atrial fibrillation	Occurence/recurrence of atrial fibrillation	before discharge within two weeks after surgery