23

The Role of MRI-Detected Left Atrial Delayed Enhancement inSelecting the Right Patient and Choosing the Optimal Strategy

for Catheter Ablation of Atrial FibrillationDIPEN SHAH, M.D.

From the Electrophysiology Unit, Cardiology Service, Hopitaux Universitaires de Geneve, Geneva, Switzerland

Editorial Comment

The last 10 years have witnessed a frenetic growth in thepopularity of catheter ablation of atrial fibrillation (AF). Stan-dardized endpoints, low complication rates, improved toolsfor the ablating electrophysiologist, and greater awarenessamong the referring community may largely be responsible.Nevertheless, our understanding of the underlying mecha-nisms of AF is still limited, particularly in the clinical setting.It is abundantly clear that the 50 year old with paroxysmalrecurrent short-lasting lone AF is a different pathophysio-logical entity compared with the 75-year-old patient withmitral valve pathology and left atrial (LA) dilatation andlong-standing persistent AF, yet it is unclear whether (andwhich) different ablation strategies should be used and whatprobability of successful maintenance of sinus rhythm thesedifferent patients should expect.

The study1 from the University of Utah Health ScienceCenter published in this issue of the Journal is among thelatest in a series from this group describing the magneticresonance imaging (MRI) evaluation of LA changes in AFand their relevance to catheter ablation. MRI not only bringsvery important attributes to the electrophysiologist’s table in-cluding unrivalled soft tissue imaging and rapidly improvingresolution, but also the ability to provide histopathology-likeinsights into tissue changes. First described in the evalu-ation of infarcted ventricular tissue, delayed enhancement(DE) MR images after intravenous injection of a gadolin-ium compound highlight irreversibly ischemic necrotic tissuewith remarkable correlation to triphenyl-tetrazolium chloride(TTC)-injected dog ventricle slices. From that first step to theevaluation of DE of the approximately six-times thinner LAwall has taken time and considerable innovation. The Utahgroup has developed their own DE MRI acquisition and pro-cessing protocol with the aim of detecting and quantifyingfibrosis in the LA. The bare bones of their protocol include thefollowing: a 1.5-Tesla MRI scanner was used with a specificpulse sequence to obtain a scan 15 minutes after a gadolin-ium contrast injection; navigator gating during free breath-ing was used (data acquisition was active only if the respi-ration dependent superoinferior LA displacement was less

J Cardiovasc Electrophysiol, Vol. 22, pp. 23-24, January 2011.

No disclosures.

Address for correspondence: Dipen Shah, M.D., Medecin adjoint agrege,Electrophysiology Unit, Cardiology Service, Hopitaux Universitaires deGeneve, Rue Gabriel Perret Gentil 4, CH 1211 Geneve 14, Switzerland.Fax: +41 (0) 22-3727229; E-mail: dipen.shah@hcuge.ch

doi: 10.1111/j.1540-8167.2010.01904.x

than 1.5 mm) as was ECG gating in order to acquire imagesduring the diastolic phase of the LA cycle; voxel size (a mea-sure of 3D spatial resolution) was 1.25 × 1.25 × 1.25 mm,very similar to the thickness of many areas of the LA wall;and signals from fat and water were suppressed. Depend-ing upon the underlying rhythm and the subject’s respiratorypattern, the scan took 5–10 minutes. The quantification of en-hancement performed thereafter required considerable man-ual interaction—both segmentation of the LA and tracing theepicardial and endocardial LA borders were manually per-formed on image slices. The percentage of LA wall enhance-ment was quantified with a threshold based algorithm. Thisalgorithm selects a threshold enhancement signal intensitybetween 2% and 40% of the maximum intensity within theLA wall as “normal.” The abnormal enhancement thresholdwas selected as 2 to 4 standard deviations above the mean of“normal.” The specific threshold was operator determined—on a slice-by-slice basis, compared to the original slice for“appropriateness” and adjusted accordingly. The percentageof enhanced pixels within the LA wall volume was calculatedas the enhancement parameter. Despite the above subjectiv-ity, this group has reported good inter- and intraobserveragreement in estimating LA wall DE.2

In this nonprospective and apparently unblinded study,Akoum et al.1 acquired DE MRI images of the left atriumboth before and after catheter ablation of AF in an effort tounderstand the significance of the observed changes. Theyfound that preablation DE defined 4 stages of the extent of LAwall DE in patients with AF at baseline, which correlated withsinus rhythm maintenance after catheter ablation. Extensiveenhancement correlated with low rates of sinus rhythm andthe absence of enhancement with high success rates. It is alittle surprising that no clinical parameter (age, hypertension,diabetes, coronary artery disease, congestive heart failure,and LV ejection fraction or the type of AF) correlated withthe preablation extent of DE.

The 3-month postablation extent of LA DE provided in-teresting insights. Peri-PV circumferential DE was observedonly in a minority of patients and, along with the overallextent of LA wall DE, correlated with high rates of sinusrhythm maintenance in the largest group of patients, thosewith intermediate grades of baseline DE. LA volume andage were less important but significant parameters predictingarrhythmia recurrence.

While DE represents irreversibly fibrotic tissue in thepostinfarct setting as validated by experimental studies ininfarct models, the significance of LA wall DE is unclear.Although there is enough evidence to support the existenceof significant fibrosis in the atrial wall in patients with AF,there is little or none to support the extrapolation that LAwall DE preablation in AF patients represents structural

24 Journal of Cardiovascular Electrophysiology Vol. 22, No. 1, January 2011

remodeling related fibrosis. Similarly, the underlying tissuebasis of the DE observed postablation has not been estab-lished but may be a combination of preablation pathologycombined with ablation-induced modifications.

In this study, Akoum et al. used the same protocol toquantify the extent of DE at baseline and postablation. How-ever, their study does not clarify how postablation scarringrelated enhancement was distinguished from preablation en-hancement, although a subjectively higher intensity of en-hancement is asserted. It is likely therefore that essentiallya summated overall enhancement (combining baseline andpostablation changes) was measured postablation. Becauseno qualitative assessment of the distribution of peri-PV en-hancement at baseline was provided it is possible that nonencirclement by DE still correlates with complete PVI (asacknowledged by the authors) and in addition when postab-lation scans reveal contiguous enhancement encircling thePV, it remains unclear what part of it represents preablationenhancement.

The authors indicate that all patients received a similarlesion set although data on RF delivery time and distributionhave not been provided. This may well represent a significantweakness: a different ablation strategy may conceivably bemore effective in certain subgroups. It is well accepted thatPV isolation alone is associated with high recurrence ratesin long-standing persistent AF, and in single center studies,the addition of linear lesions and the targeting of fractionatedelectrograms have both improved sinus rhythm maintenancerates. However, the authors’ ablation strategies ignore therole of the coronary sinus, superior vena cava, of the an-terior LA, and perhaps even the RA. Although this studydoes not provide electrophysiologic correlations, a previousstudy from this group2 was able to show a correlation oflow bipolar voltage areas with DE. Therefore, it is entirelyconceivable that the patients with the most extensive DE hadthe largest low voltage areas and therefore received less ab-lation (because of fewer or lower voltage EGM targets) witha possible impact on sinus rhythm maintenance.

The study design also does not account for the dynamicsof the evolution of tissue changes that may have occurredafter the 3-month scan, but during the overall follow-up pe-riod of 283 days (during which arrhythmia recurrences wereassessed).

Interestingly, the authors report that patients with fewerPVs encircled by DE also manifested a lower burden of over-

all LA DE at 3 months. Is this a reflection of tissue composi-tion/thickness and/or operator experience, and variations incontact? It must be noted that there is no proof of a direct cor-relation between the quality (temporal stability, completion,and continuity) of PVI lesions and that of lesions elsewherein the LA. In the light of this, it is difficult to agree with theauthors that patients with advanced remodeling (indicatedin this study by baseline DE extent) necessarily require ad-ditional substrate modification because their own findingsindicate that PV encirclement by DE is only infrequentlyachieved; thus, the full potential of a strategy of PV isola-tion/encirclement is probably underestimated. Evidently, amore uniform distribution of patients with different degreesof enhancement would also improve the reliability of thisstudy. The other unknown variable in this MR assessment isthe degree of transmural versus nontransmural enhancement,because it is very probable that the imaging technology usedlacks the necessary resolution. One suspects that electricalconduction would correlate with the extent of transmuralrather than nontransmural enhancement and intuitively, withrhythm outcome.

Because of the preceding concerns, the present study’sdirect clinical applicability is limited. Clearly this study,in line with this group’s preceding publications, should beconsidered hypothesis generating, but an adequately pow-ered and structured prospective study is required to test thehypothesis that extensive LA DE preablation is a markerof poor rhythm outcome. Such a study would presupposea uniformly designed and uniformly implemented abla-tion strategy, whereas another prospective study evaluatingthe choice of an optimal strategy should implement differ-ent ablation strategies in DE extent stratified preablationgroups.

References

1. Akoum N, Daccarett M, McGann C, Segerson N, Vergara G, KuppahallyS, Badger T, Burgon N, Haslam T, Kholmovski E, MacLeod R, Mar-rouche N: Atrial fibrosis helps select the appropriate patient and strategyin catheter ablation of atrial fibrillation: A DE-MRI guided approach. JCardiovasc Electrophysiol 2011;22:16-22.

2. Oakes RS, Badger TJ, Kholmovski EG, Akoum N, Burgon NS, Fish EN,Blauer JJE, Rao SN, DiBella VR, Segerson NM, Daccarett M, Wind-felder J, McGann CJ, Parker D, MacLeod RS, Marrouche N: Detec-tion and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrilla-tion. Circulation 2009;119:1758-1767.