PACE pace_3458 Dispatch: June 9, 2012 CE: AFL

Journal MSP No. No. of pages: 6 PE: Cynthia

12

3456789

101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

Persistent Atrial Fibrillation is Associated with Inabilityto Recover Atrial Contractility after MAZE IV Surgery inRheumatic DiseaseMATIAS TINETTI, M.D.,* RAMIRO COSTELLO, M.D.,* CESAR CARDENAS, M.D.,†ANTONIO PIAZZA, M.D.,† RICARDO IGLESIAS, M.D.,* and ADRIAN BARANCHUK, M.D.‡From the *Cardiology Division, and †Cardiovascular Surgery, Sanatorio de la Trinidad Mitre, Sanatorio de laTrinidad Palermo, Buenos Aires, Argentina; and ‡Heart Rhythm Service, Kingston General Hospital, Queen’sUniversity, Kingston, Ontario, Canada

Background: MAZE IV surgery is effective in restoring sinus rhythm (SR) and atrial contraction (AC)in patients with nonrheumatic persistent atrial fibrillation (AF). However, there is less information on itseffectiveness to restore AC in patients with rheumatic disease.

Aims: To assess the effectiveness of the MAZE IV surgery in restoring AC in patients with rheumaticdisease and long persistent AF.

Methods: Prospective, consecutive study in patients who underwent cardiovascular surgery and hadlong persistent AF in whom MAZE IV surgery was performed. The presence of AC was assessed by lateralmitral annulus tissue Doppler.

Results: A total of 75 patients were included. Mean age 60 years (±11.7); 27 men (36%). AF durationwas 63 months (±34.1). Primary indication for surgery: rheumatic mitral stenosis 67 patients and mitralinsufficiency eight patients. Mean left ventricular ejection fraction (LVEF) was 51.8% (±12.1) and meanleft atrial area was 37 cm2 (±10.3). After a mean follow-up of 28 months (±9.3), 69 patients remainedalive and 59 were in SR. AC was detected in 37.3% (Group A) and absent in 62.7% (Group B). The meandifference between groups was the high prevalence of AF longer than 5 years in group B (P = 0.000001).There were no differences related to left atrial size, LVEF, and age.

Conclusions: In patients with rheumatic disease, the absence of correlation between SR recovery andAC recovery post MAZE IV surgery is significant. A history of long persistent AF lasting more than 5 yearswas a strong predictor for the absence of AC. (PACE 2012; 00:1–6)

atrial fibrillation, MAZE surgery, rheumatic disease, atrial contractility

IntroductionAtrial fibrillation (AF) is the most common

cardiac arrhythmia and it is responsible for mor-tality and morbidity due to thromboembolism andheart failure.1,2 Stroke is one of its complicationsand unfortunately, optimal anticoagulation doesnot completely abolish the risk which persistsaccording to the patient’s associated risk factors.Anticoagulation remains a major problem due toassociated bleeding complications (annual risk of0.5–2.8%).3 Sometimes medical therapy is notenough to maintain sinus rhythm (SR) in the longterm and antiarrhythmic drugs often have seriousside effects including proarrhythmia.4

Address for reprints: Matias Tinetti, M.D., Departmentof Cardiology and Echocardiography, Sanatorio TrinidadPalermo, Buenos Aires, Argentina. Fax: 54941275564; e-mail:matiastinetti@hotmail.com

Received November 22, 2011; revised April 8, 2012; acceptedMay 19, 2012.

doi: 10.1111/j.1540-8159.2012.03458.x

Invasive interventions for the treatment ofAF have experienced significant improvementsin recent years. Cox-Maze surgery was the firstsuccessful surgical treatment for AF. It wasdeveloped by James Cox at Washington Universityin St. Louis two decades ago.5 The originaltechnique demonstrated high efficacy to restoreSR but its complexity was a major problem and itwas difficult for other groups to reproduce similarresults. Several modifications were introducedto the original technique during recent years,specifically the use of different energy sourceslike radiofrequency, microwave, cryoablation, andlaser to replace the classic “cut and sew.”6 Thesemodifications gave birth to the actual MAZE IVprocedure, which is easier to perform and hasacceptable results in terms of SR conversion ratein patients with concomitant cardiac diseases.7,8

The effectiveness of the surgery in restoringatrial contraction (AC) in patients with rheumaticcardiomyopathy, however, remains uncertain.

The aim of this study was to evaluate theeffectiveness of MAZE IV surgery to recover SRand left AC in patients with long persistent AFand rheumatic disease.

C©2012, The Authors. Journal compilation C©2012 Wiley Periodicals, Inc.

PACE, Vol. 00 2012 1

12

3456789

101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

TINETTI, ET AL.

MethodsStudy Design

Between September 2005 and July 2010,we performed a prospective cohort study of 75consecutive patients with rheumatic disease whohad long persistent AF requiring heart surgery incombination with a MAZE IV procedure.

We included patients with persistent AFlasting at least 1 year whom were treated undera rate control strategy, according to guidelines.9The presence of the arrhythmia was documentedthrough 12-lead electrocardiogram, 24-hour Holtermonitoring, and clinical records. Patients gavetheir written consent to undergo this therapeuticstrategy and to participate in the long-term follow-up of this study.

Surgical Procedure

After median sternotomy, the patient wasplaced on cardiopulmonary bypass (CPB) usingbicaval cannulation. The heart was arrestedusing blood cardioplegia. A left atriotomy wasperformed through the interatrial septum andthe left atrial appendage was excised. Then, wecontinued with the schematic diagram of atriallesions showed in Figure 1: encircling isolationof the pulmonary veins, connecting a lesion fromthe left atrial appendage to the left pulmonaryveins. A linear lesion was delivered connectingthe pulmonary veins and the atriotomy, and from

the latter to the mitral annulus at the level ofthe P2 and P3 scallops according to coronaryartery anatomy. In the right atrium (RA), lesionswere delivered only in the cavotricuspid isthmusto create an empiric bidirectional block of theisthmus. Atrial lesions were carried out with abipolar, saline-irrigated radiofrequency ablationdevice (Medtronic Cardioblate BP Surgical Ab-lation System R©, Minneapolis, MN, USA). Thesurgical hand piece incorporates two electrodeson separate arms of a hemostat instrument able todeliver bipolar radiofrequency energy using salineirrigation to allow better power delivery to thetissue. The device continuously monitors tissueimpedance, current, voltage delivered, and theduration of ablation in real time.

By continuously calculating impedancechanges, the tissue is ablated until there is aplateau in the impedance that is considered asthe point of transmurality. At that time, theobjective feedback of transmurality is providedby an audible signal. A technique for left atrialvolume reduction was included in five casespresenting with a giant left atrium (LA) > 60 cm2

area.

Follow-Up

Early postoperative care did not differ fromroutine open heart surgery. Atrial pacing at a rateof 90–100 beats per minute and an intravenous

Figure 1. Scheme of surgical technique and set of radiofrequency lesions used for the Maze IVsurgery (see explanation in the text).

2 2012 PACE, Vol. 00

12

3456789

101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

MAZE IV AND ATRIAL CONTRACTILITY

infusion of amiodarone 300 mg/day was initiatedin the operation room and for the first 48 hours.

Thereafter, in absence of contraindications,patients received 400 mg of oral amiodaronedaily for 4 months. Anticoagulation therapy wasstarted with warfarin and adjusted to achieve anINR between 2.5 and 3. Postoperative continuouselectrocardiographic monitoring was performed inthe coronary care unit and daily 12-lead surfaceelectrocardiograms were recorded during hospi-talization. Follow-up at 1, 3, 6, and 12 monthsQ1after surgery included 24-hour Holter monitoringand color-Doppler echocardiography in the samevisit.

Preoperative and postoperative echocardio-graphic measurements were compared including:diastolic left ventricular diameter, systolic leftventricular diameter, ejection fraction (EF), an-teroposterior, transverse and longitudinal diame-ter of the LA, and LA and RA areas. TransvalvularQ2mitral flow was also recorded. From the apicalfour-chamber view, a tissue Doppler imagingsample volume was placed at the lateral portion ofthe mitral annulus to record late diastolic velocity(Aa wave, atrial systole). The spectral Dopplersignal parameters were adjusted to obtain velocityscale limits between 15 and 20 cm/s by use ofthe lowest filter settings and the optimal gain toeliminate the spectral signal produced by bloodflow. The results were expressed in cm/s. If AFpersisted for over 3 months postoperatively, anexternal electrical cardioversion was performed.

Statistical Analysis

Data were prospectively obtained and wereanalyzed using χ2 test or Fisher test for categoricalvariables and t-test or Mann-Whitney-Wilcoxontest for continuous variables. A Kaplan-Meiercurve was obtained using SPSS-13.0 statisticalanalysis software. Descriptive statistics are pre-Q3sented as means and standard deviation forcontinuous data and relative frequencies forcategorical variables.

ResultsClinical characteristics of the study popu-

lation are depicted in Table I. A total of 75patients were analyzed. Mean age was 60 years(±11.7); 27 men (36%). Mean AF duration was63 months (±34.1). Primary indications for surgerywere: rheumatic mitral stenosis (89%) and mitralregurgitation in (11%). Mean EF was 51.8%(±12.1) and mean left atrial area was 37 cm2

(±10.3). Biological valves were used in 47 patients(62%). The mean CPB time was 131 minutes (±25).Mean time to perform MAZE IV procedure was 14(± 3.2) minutes.

Table I.

Baseline Characteristics (N = 75)

Male gender 36%

Age 60 years ± 11.7AF duration 63 months ± 34.1Time of AF evolution >5 years 48%Hypertension 81%Diabetes 30%Smoke 11%Dyslipemia 51%Prior stroke 7.5%Mitral stenosis 89%Mitral regurgitation 11%Previous cardiac surgery 8%Left atrial area (cm2) 37 ± 10.3Left ejection fraction 51.8% ± 12.1DDVI (mm) 50.6On pump time (minutes) 131 ± 41.1Time to perform MAZE (minutes) 14 ± 2.8

All patients were admitted to the coronarycare unit immediately after surgery with anepicardial pacemaker. Only one patient requireda permanent pacemaker immediately after surgerydue to complete atrioventricular block. Onepatient required immediate reoperation due tomediastinal bleeding with normal evolution afterthe second procedure. Elective electrical car-dioversion was performed in 12 patients duringfollow-up due to AF recurrence (five patients)or failure of restoration of SR (seven patients).All patients in SR received amiodarone for 4months after the procedure. No discontinuationof drugs due to adverse event was recorded.No cardioembolic events occurred during thefollow-up.

After a mean follow-up of 28 months (±9.3),69 patients remained alive. Two patients diedduring in-hospital stay, one patient died due tocardiovascular complications, and three patientsdied due to noncardiovascular causes.

SR rate during the follow-up was 46% at 1month, 71% at 3 months, 86% at 6 months, and86% at 12 months. AC rate was 24% at 1 month,47% at 3 months, 54% at 6 months, and 54% at12 months (Fig. 2). The value of a’ wave on tissueDoppler indicating left AC was 9.6 (± 1.8) cm/sand was stable all along the follow-up. Q4

SR rate was 86% (59 patients) and ACwas detected in 37% (22 patients) using mitralannulus tissue Doppler (Group A). Despite SRrestoration, 62.7% (37 patients) did not recover AC(Group B). The mean difference between groups

PACE, Vol. 00 2012 3

12

3456789

101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

TINETTI, ET AL.

Figure 2. Recovery of sinus rhythm and atrial contraction during the follow-up.

was long-lasting AF duration more than 5 years(P = 0.00001). There were no significant differ-ences in age, left atrial area, and EF in patients inSR with AC compared to subjects in SR withoutAC (Table II).

DiscussionAF is the most common clinical arrhythmia

and one of the main therapeutic goals is to preventcardioembolism. Rhythm control strategies areintended to reduce the risk of stroke with thepossibility of avoiding long-term anticoagulationtherapy. Other potential benefits of rhythmcontrol strategies include less risk of developingtachycardiomyopathy and improving exercisecapacity.10,11 However, the ability to maintain SRis often poor with antiarrhythmic drugs, whichmay also have serious adverse events; in addition,AF recurrence is frequent.12

The association between AF and mitral valvedisease is well established and is present in almost60% of cases that need surgical correction. Mitralvalve surgery per se, only resolves about 20% ofAF-associated cases.13

There is a strong association between mi-tral rheumatic disease and AF. This type ofcardiomyopathy is still a major health problemin underdeveloped countries.14 AF is usually alate complication of this disease, probably dueto persistent inflammatory activity in the atrialmyocardium that occurs even years after theacute phase. Severe mitral valve stenosis alsocontributes as an anatomical substrate for AFdevelopment.15 Maintenance of SR is particularly

difficult in this population.16 Maze surgery is aneffective option for the treatment of AF in patientsneeding cardiovascular surgery.17

Table II.

Patients with and without Atrial Contraction (AC)

AC No AC(Group A) (Group B)

Variable (n = 22) (n = 37) P Value

Male gender 14 (58%) 10 (42%) 0.007Age 61 ± 9 59 ± 11 0.36Patients with AF

duration >5 years3 (14%) 27 (73%) 0.00001

Hypertension 17(77%) 30(81%) 0.72Diabetes 6 9 0.80Prior stroke 2 2 0.58Mitral stenosis 18 (81%) 34 (92%) 0.24Mitral regurgitation 4 (9%) 3 (8%) 0.24Congestive heart

failure5 (22%) 9 (24%) 0.88

Left atrial area (cm2) 36 ± 8 37 ± 7 0.4Left ventricular

ejection fraction(%)

52 ± 5 50 ± 1 0.73

DDVI (mm) 49 ± 2 51 ± 35 0.20Mechanical

prosthetic valveimplantation

9 (41%) 14 (38%) 0.81

4 2012 PACE, Vol. 00

12

3456789

101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

MAZE IV AND ATRIAL CONTRACTILITY

Our results showed that after a mean follow-up of 28 ± 9.3 months; 86% of patients remainedin SR despite having several comorbidities suchas advanced age, hypertension, impaired leftventricular ejection fraction (LVEF) and advancedNew York Heart Association functional class.These results are concordant with prior reports.18

Other studies that also included patients withstructural heart disease have reported SR recoveryin 81–95% of patients after a follow-up of 5years; however, these studies do not mentionthe status of the atrial mechanical function.19

There are several conditions like age, left atrialsize, AF duration, LVEF that can affect SRconversion rates. From this perspective, the rateof left AC recovery was acceptable but less thanSR recovery.20 Prior studies using transthoracicechocardiography techniques showed left AC in60–70% of patients at 1-year follow-up aftersurgery.21

The vast majority of publications about Mazesurgery come from studies that included patientswith low prevalence of structural heart disease,similar proportion of cases of persistent AFand paroxysmal AF, and in most cases patientsunderwent only a MAZE procedure (with noconcomitant heart surgery). The excellent long-term outcomes and the absence of ischemic neu-rological events during the follow-up, regardlessof the efficiency to restore AC, may be explainedin part by the clinical characteristics of thesepopulations.22

Historically, long persistent AF and left atrialsize were variables that had a negative impacton restoration of SR.23 Impairment in AC was afrequent finding in the original studies; however,its incidence was reported as less than 10% inthe last years, as a result of modifications tothe original technique.24 Our population differsfrom the traditional reported series. Despite SRrecovery, we found that long persistent AF andrheumatic disease are important variables inrestoring AC in patients in SR. AF duration longerthan 5 years was highly specific and sensitive topredict failure in the recovery of AC. Left atrialsize did not show differences between patientsthat recover AC and patients that did not (P =0.11).

It is well known that long persistent AF has astrong relationship with electrical and anatomicalatrial remodeling.25 Structural changes in atrialarchitecture could explain the low rates of AC in

patients with AF longer than 5 years despite SRconversion.

Rheumatic disease remains a public healthproblem in developing countries. It is a chronicinflammatory process that affects cardiac valves,endocardium, and myocardium.26 We found that62% of rheumatic patients in SR do not haveleft AC. The real impact of this finding remainsunknown. It is likely that patients in SR withoutAC represent a group who are at a higher riskof stroke when compared to patients in SR withnormal left AC. The usual anatomical location forthrombus formation in nonrheumatic AF patientsis the left appendage (90%). This condition can besolved by eliminating the appendage with surgery,but in rheumatic patients, 50% of the thrombusformation is located out of the appendage, usuallyin the posterior atrial wall.27 This could be one ofthe reasons why AC recovery is more important inrheumatic patients than in nonrheumatic patients.There are no prior studies with long-term follow-up in patients with rheumatic disease in SRbut without AC that allow us to understand thereal risk of stroke and how safety is to stopanticoagulation therapy in this scenario.

MAZE IV in rheumatic disease is an effectiveoption to restore SR but still carries low rates ofAC recovery. Longer follow-up studies with largernumber of patients may be needed to completelyanswer this question.

LimitationsSome limitations of this study need to be

acknowledged. First, the sample size of patientswith rheumatic disease is small. The lack of aconnection between AC and left atrial size inpatients with rheumatic disease may be affected bythe low number of patients included. Second, themonitoring of AF recurrence during the follow-upwas based on symptoms and Holter recordings, soprobably asymptomatic episodes of AF may havebeen lost and the true recurrence rate of AF aftersurgery was underestimated.

ConclusionsDespite conversion to SR after surgery; atrial

contractility following Maze surgery remainsimpaired in patients with rheumatic disease andlong persistent AF. This information may be usefulin deciding on a long-term anticoagulation strategyafter surgery.

References1. Le Heuzey JY, Paziaud O, Piot O, et al. Cost of care distribution

in atrial fibrillation patients: The COCAF study. Am Heart J 2004;147:121–126.Q5

2. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed

atrial fibrillation in adults: National implications for rhythmmanagement and stroke prevention: The AnTicoagulation and RiskFactors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285:2370–2375.

PACE, Vol. 00 2012 5

12

3456789

101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

TINETTI, ET AL.

3. Fihn SD. Aiming for safe anticoagulation. N Engl J Med 1995;333:54–55.

4. Corley SD, Epstein AE, DiMarco F, et al. Relationships betweensinus rhythm, treatment and survival in the Atrial FibrillationFollow up Investigation of Rhythm Management (AFFIRM) study.Circulation 2004; 109:1509–1513.

5. Cox JL, Schuessler RB, D’Agostino HJ, Stone C, Chang BC, Cain ME,et al. The surgical treatment for atrial fibrillation. III. Developmentof a definitive surgical procedure. J Thorac Cardiovasc Surg 1991;101:569–583.

6. Lall SC, Melby SJ, Voeller RK, Zierer A, Bailey MS, Guthrie TJ, et al.The effect of ablation technology on surgical outcomes after the Cox-Maze procedure: A propensity analysis. J Thorac Cardiovasc Surg2007; 133:389–396.

7. De Lima GG, Kalil RAK, Leiria TLL, et al. Randomized study ofsurgery for patients with permanent atrial fibrillation as a result ofmitral valve disease. Ann Thorac Surg 2004; 77:2089–2095.

8. Raanani E, Albage A, David TE, Yau TM, Armstrong S. The efficacyof the Cox/Maze procedure combined with mitral valve surgery:A matched control study. Eur J Cardiothorac Surg 2001; 19:438–442.

9. Fuster V, Ryden LE, Cannom DS, Crijin HJ, Curtis AB, ZamoranoJL, et al. ACC/AHA/ESC 2006 guidelines for the managementof patients with atrial fibrillation: A report of American CollegeCardiology/American Heart Association Task Force on PracticeGuidelines and the European Society of Cardiology Committeefor Practice Guidelines (Writing Committee to revise the 2001Guidelines for the Management of Patients with Atrial Fibrillation).Circulation 2006; 114:e257–e354.

10. Daoud EG, Weiss R, Bahu M, et al. Effect of an irregular ventricularrhythm on cardiac output. Am J Cardiol 1996; 78:1433–1436.

11. Shinbane JS, Word MA, Jensen DN, Ellenbogen KA, Fitzpatrick AP,Scheinmann MM. Tachicardia induced cardiomyopathy: A reviewof animal models and clinical studies. J Am Coll Cardiol 1997;29:709–715.

12. The AFFIRM Investigators. A comparison of rate control and rhythmcontrol in patients with atrial fibrillation. N Engl J Med 2002;347:1825–1833.

13. Lim E, Barlow CW, Hosseinpour AR, Wisbey C, Wilson K, PridgeonW, et al. Influence of atrial fibrillation on outcome following mitralvalve repair. Circulation 2001; 104:I59–63.

14. Bocchi EA, Guimaraes G, Tarasoutshi F, Spina G, Mangini S, BacalF. Cardiomyopathy, adult valve disease and heart failure in SouthAmerica. Heart 2009; 95:181–189.

15. Guillherme L, Kalil J. Rheumatic fever : From sore throat

to autoimmune heart lesions. Int Arch Allergy Inmunol 2004;134:56–64.

16. Skoularigis J, Rothlisberger C, Skudicky D, Essop MR, Wisenbaug T,Sareli P. Effectiveness of amiodarone and electrical cardioversionfor chronic rheumatic atrial fibrillation after mitral valve surgery.Am J Cardiol 1993; 72:423–427.

17. Bando K, Kobayashi J, Kosakai Y, Hirata M, Sasako Y, Hitamura S,et al. Impact of Cox Maze procedure on outcomes in patients withatrial fibrillation and mitral valve disease. J Thorac Cardiovasc Surg2002; 124:575–583.

18. Prasad M, Maniar H, Camillo C, Boineau P, Sundt T, Damiano R. TheCox Maze III procedure for atrial fibrillation: Long term efficacy inpatients undergoing lone versus concomitant procedures. J ThoracCardiovasc Surg 2003; 126:1822–1827.

19. Bando K, Kobayashi J, Kosakai Y, Hirata M, Sasako Y, Hitamura S,et al. Impact of Cox Maze procedure on outcomes in patients withatrial fibrillation and mitral valve disease. J Thorac Cardiovasc Surg2002; 124:575–583.

20. Albirini A, Scaglia GM, Murray, et al. Left and right atrialtransport function after the Maze procedure for atrial fibrillation: Anechocardiography Doppler follow up study. J Am Soc Echocardiogr1997; 10:37–45.

21. Yuda S, Nakatani S, Isobe F, Kosakai Y, Miyatake K. Comparativeefficacy of the Maze procedure for restoration of atrial contractionin patients with and without giant left atrium associated with mitralvalve disease. J Am Coll Cardiol 1998; 31:1097–1102.

22. Cox JL, Niv A, Palazzo T. Impact of the Maze procedure on thestroke rate in patients with atrial fibrillation. J Thorac CardiovascSurg 1999; 118:833–840.

23. Gillinov M, Sirak J, Blackstone E, McCarthy P, Rajeswaran J, NataleA, et al. The Cox Maze procedure in mitral valve disesase. Predictorsof recurrent atrial fibrillation. J Thorac Cardiovasc Surg 2005;130:1653–1660.

24. Cox JL, Scheussler RB, Lappas DG, Boineau JP. An 8.5 year clinicalexperience with surgery for atrial fibrillation. Ann Surg 1996;224:267–275.

25. Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begetsatrial fibrillation. A study in awake chronically instrumented goats.Circulation 1995; 92:1954–1968.

26. Guilherme L, Cunha-Neto E, Coelho V, Snitcowsky R, Pillegi F,Kalil J. Human infiltrating T cell clones from rheumatic heartdisease patients recognize both streptococcal and cardiac proteins.Circulation 1995; 92:415–420.

27. Jordan RA, Schiefly CH, Edwards JE. Mural thrombosis and arterialembolism in mitral stenosis. Circulation 1951; 3:363. Q6

6 2012 PACE, Vol. 00

Queries

Q1 Author: Please define INR.

Q2 Author: Please check the sentence “Preoperative and . . .” for the intended meaning.

Q3 Author: Please provide product details (manufacturer and location) for SPSS 13.0.

Q4 Author: Please check the sentence “The value of . . .” for the intended meaning.

Q5 Author: Please list all the authors if seven or fewer in all et al. type references.

Q6 Author: Please provide first and last pages for Ref. 27, if it is not a one-page article.

7