Stamatelopoulos Morphology of RR Interval Variation Atrioventricular Node Modification in Patients With Chronic Atrial Fibrillation: Role of

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Stamatelopoulos Morphology of RR Interval Variation Atrioventricular Node Modification in Patients With Chronic Atrial Fibrillation: Role of
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  StamatelopoulosStelios Rokas, Styliani Gaitanidou, Sofia Chatzidou, Costas Pamboucas, Dennis Achtipis and Stamatios Morphology of RR Interval VariationAtrioventricular Node Modification in Patients With Chronic Atrial Fibrillation: Role of  Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2001 American Heart Association, Inc. All rights reserved.is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/01.CIR.103.24.29422001;103:2942-2948 Circulation. http://circ.ahajournals.org/content/103/24/2942 Wide Web at: The online version of this article, along with updated information and services, is located on the World  http://circ.ahajournals.org//subscriptions/ is online at: Circulation Information about subscribing to Subscriptions:  http://www.lww.com/reprints Information about reprints can be found online at: Reprints:  document. and Rights Question and Answer Permissionsthe middle column of the Web page under Services. Further information about this process is available in thethe online version of the published article for which permission is being requested is located, click Request Permissions in can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once Circulation  Requests for permissions to reproduce figures, tables, or portions of articles srcinally published in Permissions:  by guest on December 3, 2013http://circ.ahajournals.org/ Downloaded from by guest on December 3, 2013http://circ.ahajournals.org/ Downloaded from   Atrioventricular Node Modification in Patients WithChronic Atrial Fibrillation Role of Morphology of RR Interval Variation Stelios Rokas, MD; Styliani Gaitanidou, MD; Sofia Chatzidou, MD; Costas Pamboucas, MD;Dennis Achtipis, MD; Stamatios Stamatelopoulos, MD  Background  —This study evaluates the role of RR interval distribution pattern as an outcome predictor of radiofrequency(RF) modification of atrioventricular (AV) node in chronic atrial fibrillation (AF) and attempts to elucidate the likelymechanism of rate control.  Methods and Results —Sixty-five patients with chronic AF underwent AV node modification. The RR interval distributionpattern was derived from 24-hour ECG recordings obtained before and after the procedure. The preablation pattern wasbimodal (B) in 36 patients (55%) and unimodal (U) in 29 patients (45%). After the modification procedure, the B patternshifted to U (78%) or became modified B (22%). The mean number of RF pulses delivered and the fluoroscopy timewere n  8  5 and 24  11 minutes, respectively, in patients with B pattern versus n  18  7 and 45  17 minutes inpatients with U pattern ( P  0.001 for both). The location of successful ablation was posteroseptal and lower midseptalin 26 patients (81%) with B pattern versus 2 (13%) with U pattern ( P  0.001). Mean and maximal ventricular rates andheart rate at peak exercise were reduced after the procedure in both groups ( P  0.001 for all). Long-term success rate,AV block incidence, and pacemaker implantation rate were 89%, 0%, and 8%, respectively, in patients with B patternversus 52% ( P  0.001), 21% ( P  0.006), and 48% ( P  0.001) in patients with U pattern. Conclusions —RF modification of the AV node is expected to be more effective, safe, and expeditious in patients withchronic AF and B RR interval distribution pattern. Posterior atrionodal input ablation may be the prevailing mechanismof rate control in these patients, whereas U-pattern patients may benefit from partial injury to the AV node.  ( Circulation .2001;103:2942-2948.)Key Words:  catheter ablation    atrioventricular node    fibrillation    intervals A trioventricular (AV) node modification has emerged asan effective means of rate control in symptomaticpatients with chronic atrial fibrillation (AF) and rapid ven-tricular response despite pharmacological therapy. 1–3 It hasbeen suggested that ablation of the “slow pathway” 1 or partialdamage of the compact AV node 2,3 might be the mechanismsthat explain the benefit of this method. Because all patients inthose studies had chronic AF, however, the underlyingelectrophysiological substrate of the AV node could not beevaluated by means of electrophysiological studies. Inchronic AF, evidence is arising from RR interval analysis thata bimodal RR interval distribution pattern may indicate thepresence of dual AV node physiology, whereas a unimodalpattern may be associated with orthodromic impulse propa-gation over the fast pathway alone. 4,5 Therefore, we con-ducted a study to evaluate the possible role of the RR intervaldistribution pattern in the outcome of patients with chronicAF and rapid ventricular response who undergo radiofre-quency (RF) modification of AV node conduction. Methods Symptomatic patients with chronic AF and uncontrolled ventricularrates who were referred for RF modification of AV node conductionwere eligible to enter the study protocol provided that (1) allantiarrhythmic (AA) drugs, including amiodarone, has been provedineffective in converting AF to sinus rhythm or in controllingventricular rate; (2) electrical cardioversion had failed to restoresinus rhythm; and (3) the patients agreed to discontinue all the AAagents before the RF modification procedure for a period   5half-lives. Amiodarone was discontinued   2 months before thepatients entered the study. The following were criteria for exclusionfrom the study: (1) during the period of discontinuation of the AAtreatment, the presence of (a) symptomatic bradyarrhythmia or pause  1.5 seconds, (b) arrhythmia-related symptoms during the 24-hourambulatory ECG recording irrelevant to ventricular rate augmenta-tion  100 bpm during the recording, or (c) severe symptoms at rest(eg, congestive heart failure) caused by tachyarrhythmia; (2) leftventricular function severely impaired (ejection fraction   0.40),angina pectoris, or recent myocardial infarction; and (3) abnormalthyroid function or severe systematic illness. In accordance with theHelsinki agreement, the study was subject to the local ethicalcommittee, and all patients had given informed written consent. Received November 1, 2000; revision received March 19, 2001; accepted March 29, 2001.From the Interventional Cardiology Unit, Department of Clinical Therapeutics, Alexandra Hospital, Athens University Medical School, Athens, Greece.Correspondence to Dr Stelios Rokas, 41 Alkmanos St, Athens 115 28, Greece. E-mail katsioli@otenet.gr© 2001 American Heart Association, Inc. Circulation  is available at http://www.circulationaha.org  2942  by guest on December 3, 2013http://circ.ahajournals.org/ Downloaded from   Distribution Pattern of RR Intervals The day before the RF modification procedure, a 24-hour ambulatoryECG recording was obtained from all patients under conditions of usual daily activities and while the patients were on no AAtreatment. The data were recorded on tape. These analog data werestored in a computer, and the method of heart rate–stratifiedhistogram was used for analysis of the distribution pattern of all24-hour RR intervals during AF. 6 The RR interval distributionpattern may be unimodal, bimodal, or multimodal. Bimodality isdefined as the existence of 2 RR populations separated distinctly bya visually estimated intersection point, the value of which must bethe same in   2 consecutive heart rate measurements. We havepreviously described the technique of analysis elsewhere. 7 RF Modification Protocol All RF modification procedures were performed by the sameoperator, who was unaware of the patients’ RR interval distributionpattern. Induction of permanent AV block was not our intention inany case. Three quadripolar electrode catheters were introducedpercutaneously and positioned in the right ventricular apex, Hisbundle region, and coronary sinus (CS). CS venography was per-formed with a multipurpose catheter to define the CS ostium. Thesites of the His bundle catheter and the CS ostium were identifiedand recorded on cine film in the 30° right anterior oblique and 45°left anterior oblique projections before the delivery of RF energy.The ablation area from the His bundle region to the CS ostium wasdivided into 6 anatomic target regions (A 2  to P 1 ). Current generatedby a 500-kHz RF energy source (Osypka 300S) was deliveredbetween the distal 4-mm tip of a deflectable 7F catheter (EPTSteerocath-T, EP Technologies) and a left subscapular chest wallpatch (7.25  1.5 in).The same protocol of RF energy delivery was strictly followed ineach patient, as follows: The ablation catheter was initially posi-tioned in the most posterior region of the ablation area (P 1 ), adjacentto the CS ostium. If the ablation attempts at this site were unsuc-cessful, the ablation catheter was gradually advanced anteriorly,toward sites P 2 , M 1 , M 2 , and A 1 . At each of those 5 sites, up to 5 RFpulses were delivered in a position slightly different from theprevious one. If after the delivery of RF energy at a specific targetregion, transient reduction, either little or significant, of the ventric-ular rate occurred, 3 more RF pulses were delivered at this site beforethe catheter was moved to the next site. Power, impedance, andtemperature were measured, displayed, and stored via an interface byuse of a microprocessor. RF pulses were applied at a maximum of 50 TABLE 1. Baseline Clinical Characteristics of the 65 Patients Divided IntoBimodal and Unimodal Pattern-Groups CharacteristicsBimodal Pattern(n  36)Unimodal Pattern(n  29)  P   All Patients(n  65) Age, y 64  8.9 62  6.7 NS 63  8.1Range 40–75 52–73 40–75Male sex, n (%) 22 (61) 18 (62) NS 40 (61)Duration of symptoms, y 3.8  2.6 4.3  2.8 NS 4.1  2.9Type of heart disease, n (%)None 12 (33) 9 (31) NS 21 (32)Coronary artery disease 5 (14) 2 (7) NS 7 (11)Dilated cardiomyopathy 5 (14) 5 (7) NS 10 (15) Valvular 4 (11) 3 (10) NS 7 (11)Hypertensive 10 (28) 10 (34) NS 20 (31)Left ventricular ejection fraction, % 54  5.7 56  5.1 NS 55  5.3Data are mean  SD or number (%) of patients. TABLE 2. Ablation Results ResultsBimodal Pattern(n  36)Unimodal Pattern(n  29)  P   All Patients(n  65)Short-termSuccess 34 (94) 17 (59) 0.002 51 (78)Failure 2 (6) 7 (24) 0.031 9 (14)Inadvertent AV block 0 (0) 5 (17) 0.014 5 (8)Intentional AV block 2 (6) 7 (24) 0.031 9 (14)Early eventsRecurrence 2 (6) 2 (12) NS 4 (8)Sudden death 1 (3) 0 (0) NS 1 (2)Syncope 0 (0) 1 (6) NS 1 (2)Long-termSuccess 32 (89) 15 (52)   0.001 47 (72)Inadvertent AV block 0 (0) 6 (21) 0.006 6 (9)Intentional AV block 3 (8) 8 (27) 0.019 11 (17)Permanent pacemaker 3 (8) 14 (48)   0.001 17 (26) Values are number (%) of patients. Rokas et al RR Interval Variation and Rate Control in AF  2943  by guest on December 3, 2013http://circ.ahajournals.org/ Downloaded from   W for 40 seconds to obtain a maximum distal tip temperature of 70°C. RF energy delivery was discontinued immediately in the caseof impedance rise, catheter displacement, abrupt increase in RRinterval, or occurrence of AV conduction block. The ablativeprocedure was considered successful when mean ventricular rate hadbeen reduced by  20% and without exceeding the value of 130 bpmafter administration of isoproterenol (2   g/min). When this end pointwas not reached, the procedure was considered to have failed. Measurement of Ventricular Rate and Follow-Up Measurements of ventricular rate derived (1) from the whole 24-hourECG recording in which the mean, maximal, and minimum heartrates were calculated or (2) from symptom-limited exercise treadmilltesting at peak exercise. In all cases, these rates were measured in theabsence of AA drug therapy both before and after the modificationprocedure.After the procedure, the patients were admitted to the coronarycare unit for 24 hours. Seven days after the procedure, a 24-hourambulatory ECG recording was obtained under conditions of usualdaily activities and was repeated after 3, 12, and 24 months duringthe follow-up period. An exercise stress test was carried out 3months after the procedure. The follow-up period was not less than8 months for any of the patients, and 60% of them were followed upfor  2 years. Statistical Analysis Data are presented as mean  SD. Continuous and categorical vari-ables were compared by Student’s  t   test and    2 test, respectively.Comparisons between the 2 groups, for various periods of follow-up,were made by 1-way ANOVA with Bonferroni transformation.Significance was set at  P  0.05. Results During the period between June 1996 and November 1999,65 of 133 patients with AF who underwent RF modificationfulfilled the inclusion criteria for participation in this study.Forty patients were men and 25 were women, with a meanage of 63  8 years (range 40 to 75 years). The mean durationof symptoms was 4.1  2.9 years (range 3 months to 19 years).Before the ablation procedure, a mean of 3.7  1.6 AA drugshad been ineffective in converting AF to sinus rhythm orcontrolling ventricular rate. All patients had a left ventricularejection fraction   0.50, except 13 patients whose left ven-tricular ejection fractions ranged from 0.40 to 0.49. Theanalysis of all 24-hour RR intervals showed that 36 patients(55%) had a bimodal pattern of RR interval distribution, and29 patients (45%) presented a unimodal pattern. The baselinecharacteristics of the study population are summarized inTable 1. Ablation Results The ablation results are shown in Table 2. During the earlyfollow-up period (within 3 months after the procedure), 2patients from each group relapsed to rapid ventricular rates.Of those, 1 patient from each group responded adequately toa combination of AA medications (propranolol 40 mg BIDand amiodarone 200 mg BID), whereas the other 2 patients (1from each group) underwent AV junction ablation withsubsequent pacemaker insertion. One patient with bimodalpattern died of sudden death on day 45 after the procedure.The autopsy findings were consistent with acute myocardialinfarction. One patient with unimodal pattern experienced 2episodes of near syncope 3 months after the procedure. TheECG revealed intermittent complete heart block.In successful cases, the number of RF pulses ranged from1 to 22 (mean 8.6  5.3) in patients with bimodal pattern andfrom 9 to 33 (mean 18.3  7.8) in patients with unimodalpattern ( P  0.001), and the mean duration of fluoroscopy was24.2  11.7 minutes (range 6 to 57 minutes) and 45  17.8minutes (range 19 to 86 minutes), respectively ( P  0.001).The location of successful ablation was posteroseptal andlower midseptal (P 1 –M 1 ) in 26 patients (81%) with bimodalpattern versus 2 patients (13%) with unimodal pattern( P  0.001) and upper midseptal and anteroseptal (M 2 –A 1 ) in6 patients (19%) versus 13 patients (87%), respectively( P  0.001). The location of the target region where RFenergy delivery resulted in high-degree AV block was mid-septal in 3 and anteroseptal in another 3 patients. Ventricular Rate Control The mean and maximal ventricular rates derived from 24-hour ambulatory ECG recordings before the RF modificationprocedure and during the follow-up period in the 32 patientswith bimodal pattern and in the 15 patients with unimodalpattern who had a successful outcome are shown in Figure 1.The baseline ventricular rate at peak exercise was 190  26bpm in patients with bimodal pattern and 182  19 bpm inpatients with unimodal pattern ( P  NS). Three months afterthe procedure, the respective values were 150  13 and142  12 bpm ( P  0.058). The exercise duration was in-creased from 4.7  1.9 to 7.6  1.7 minutes in patients withbimodal pattern ( P  0.001) and from 5.1  2.4 to 7.4  1.7minutes in patients with unimodal pattern ( P  0.001). Allpatients who underwent successful RF modification remainedasymptomatic or minimally symptomatic, with no need forrate-limiting medications. Figure 1.  A, Reduction in mean ventricular rate remained with-out statistically significant changes throughout follow-up periodin both groups. B, Changes in maximal ventricular rate.* P  0.001, † P  0.01, ‡ P  0.05, § P  0.001. Symbols *, †, and ‡indicate statistically significant differences between maximalventricular rate at 7 days and respective rates at 3, 12, and 24months in each group. §Statistically significant difference inmaximal ventricular rate between 2 groups at 12 months.  2944 Circulation  June 19, 2001  by guest on December 3, 2013http://circ.ahajournals.org/ Downloaded from   Patterns of Response to the Ablative Procedure The distribution pattern of RR intervals was assessed at 7days and at 3 months after the RF modification procedure inall patients who had a successful outcome. In 25 of the 32patients (78%) with bimodal pattern, ablation resulted inelimination of the histogram lying to the left of the intersec-tion point, which represents the RR population with short RRintervals. In other words, the bimodal pattern shifted to aunimodal one (Figure 2). In the remaining 7 patients (22%),ablation resulted in displacement of the intersection point tothe right (Figure 3). In all patients with a unimodal preabla-tion pattern, this pattern remained unimodal after the success-ful procedure. In the 2 patients with bimodal preablationpattern who relapsed to rapid ventricular rates after 12 and 35days, a 24-hour ambulatory ECG recording was obtainedimmediately after the recurrence. It is remarkable that in bothpatients, the first 24-hour ECG recording obtained 7 daysafter the procedure (that is, before recurrence) exhibited aunimodal pattern, whereas the recording obtained after therecurrence displayed a bimodal pattern identical to the prea-blation pattern (Figure 4). Discussion Previous studies reported that adequate slowing of the ventric-ular rate can be achieved by posteroseptal RF ablation in  70%of patients with chronic AF. 1,2 The ablation results cannot bepredicted, however, and  25% of the patients receive a perma-nent pacemaker because of inadvertent AV block. 3,8 The resultsof our study are comparable to those reported in the aforemen-tioned studies. Indeed, in all 65 patients studied, the overalllong-term success rate was 72%, and 26% of them received apermanent pacemaker. When the preablation RR interval distri-bution pattern is taken into consideration, however, the results of the AV node modification demonstrate several statisticallysignificant differences. In patients presenting a bimodal preab-lation pattern, the short-term success rate of AV node modifica-tion reaches a value of 94%, with no occurrence of proceduralAV block. Conversely, only half of the patients with a unimodalpattern had a successful outcome, whereas the other half re-ceived a permanent pacemaker because of inadvertent AV block or failure of the procedure. It is also remarkable that in patientspresenting a bimodal pattern, successful AV node modificationwas achieved with smaller numbers of ablative attempts and Figure 2.  Top, Typical bimodal preablationpattern of RR interval distribution. RR histo-gram is made up of 7616 RR intervals(NRR) obtained over a 24-hour period ataverage heart rate of 80 to 90 bpm. All RRintervals below intersection of 2 RR popula-tions are identified as short intervals, andvalues above this point are long intervals.Intersection point (551 ms) is indicated byarrow. Bottom, After successful ablation,distribution pattern shifted to unimodal withsubstantial increase of number of RR inter-vals (27 200) at same heart rate. Populationof RR intervals below value of intersectionpoint (551 ms) has been markedlydecreased. Rokas et al RR Interval Variation and Rate Control in AF  2945  by guest on December 3, 2013http://circ.ahajournals.org/ Downloaded from 
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