Author + information
- †Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- ‡Section of Cardiology, Department of Medicine, University of Illinois at Chicago
- §Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina
- ↵∗Reprint requests and correspondence:
Dr. Raymond Y. Kwong, Brigham and Women’s Hospital, Cardiovascular Division, Department of Medicine, 75 Francis Street, Boston, Massachusetts 02115.
Catheter ablation has become an established therapeutic option in symptomatic patients with atrial fibrillation (1); however, long-term procedural success has been disappointing because of arrhythmia recurrence in up to 25% of patients at 1 year and 40% at 5 years (1). The need for repeat ablations remains a major problem. Moreover, the procedure is associated with a nontrivial risk of serious complications. Thus, understanding the factors that determine arrhythmia recurrence is critical to clinical decision making. Common variables predictive of atrial fibrillation recurrence after ablation include the presence of nonparoxysmal atrial fibrillation, left ventricular systolic dysfunction, heart failure, structural/valvular heart disease, left atrial enlargement, hypertension, and duration of atrial fibrillation (2). However, these associations are generally weak and not universally observed. Therefore, currently there is no accepted way to individualize the risk of recurrence.
Cardiac magnetic resonance (CMR) can be used to provide pre-procedural anatomic information, particularly regarding the location of the pulmonary veins. This typically involves gated post-contrast acquisition of a 3-dimensional volume set that encompasses the left atrium and pulmonary veins, with subsequent integration into the electroanatomic mapping system used during the procedure. However, CMR is also capable of providing a wealth of other information about the heart that may be informative in these patients. This includes assessment of atrial and ventricular scar, chamber function, and presence of thrombus (3–6).
Late gadolinium enhancement (LGE) with CMR has emerged as the gold standard technique for imaging of myocardial scar and focal fibrosis (7). The basic principle is inversion-recovery imaging after a 5- to 10-min delay after intravenous administration of gadolinium contrast. With appropriate settings, normal myocardium appears nulled or black, whereas regions of scar or focal fibrosis appear bright (enhanced). The mechanism underlying LGE is likely based on the inability of gadolinium chelates to cross intact cell membranes. In regions of scar or focal fibrosis, the interstitial space is expanded, which leads to increased gadolinium concentrations, shortened T1 relaxation times, and consequent signal enhancement.
The presence and extent of ventricular LGE have been shown to be significant adverse predictors of events in numerous conditions, including ischemic and nonischemic cardiomyopathies, diabetes mellitus, valvular heart disease, hypertrophic cardiomyopathy, myocarditis, amyloidosis, and sarcoidosis. The presence of unrecognized myocardial infarction by LGE is a strong predictor of death in symptomatic and asymptomatic people, including in a large population-based study of older people (8). The mechanism for these adverse associations may involve regions of LGE that act as a substrate for ventricular arrhythmias. Recently, Neilan et al. (4) showed the prognostic value of myocardial LGE in predicting all-cause mortality in 664 patients without known prior myocardial infarction who were referred for atrial fibrillation ablation and followed up for a median of 42 months. They found regions of left ventricular LGE in 13% of their patients. Both the presence and extent of LGE were associated with mortality. The mortality rate was 8.1% per patient-year in those with LGE compared with 2.3% in patients without LGE.
It is on this background that the question of the impact of left ventricular LGE on atrial arrhythmia recurrence arises. In this issue of iJACC, Suksaranjit et al. (9) performed contrast-enhanced 3-dimensional angiography, as well as ventricular and left atrial LGE imaging, before atrial fibrillation ablation in 778 patients. The primary endpoint was atrial arrhythmia recurrence, assessed by 8-day Holter monitoring at 3, 6, and 12 months and yearly thereafter. In addition, symptom-guided Holter monitoring and 12-lead electrocardiograms were also used at the physicians’ discretion. Atrial arrhythmia recurrence was defined as any sustained atrial arrhythmia that lasted >30 s without antiarrhythmic drugs. After a median follow-up of 52 months, 40% of patients had atrial arrhythmia recurrence. Left ventricular LGE was detected in 6.5% of their patients. The recurrence rate was 69% in patients with left ventricular LGE compared with 38% in those without LGE. In their final multivariable model, only left ventricular and left atrial LGE were independent predictors of atrial arrhythmia recurrence.
What is the possible mechanism linking left ventricular LGE with atrial arrhythmia recurrence? The authors suggest that the presence of ventricular fibrosis alters the diastolic filling properties of the left ventricle, resulting in a less compliant chamber and consequent elevation of left ventricular end-diastolic and left atrial pressures, which leads to atrial stretch and remodeling. Left atrial volume was not presented in the paper, but 2-dimensional left atrial “area” was found to be significantly larger in patients with left ventricular LGE and associated with atrial arrhythmia recurrence in unadjusted analysis. The authors do not provide functional data regarding left ventricular diastolic filling properties. However, a recent study by Dodson et al. (5) shed some light on this by assessing left atrial passive function with CMR in 346 patients before atrial fibrillation ablation. Maximum left atrial volumes (VOLmax) and volumes before atrial contraction (VOLbac) were measured. Left atrial passive function was calculated as: (VOLmax − VOLbac) / VOLmax × 100. After adjustment for age, sex, and known clinical characteristics associated with atrial fibrillation recurrence (hypertension, diabetes mellitus, VOLmax, nonparoxysmal atrial fibrillation, left ventricular ejection fraction, history of prior ablation), left atrial passive function remained a strong predictor of atrial fibrillation recurrence. Left atrial passive function occurs in early diastole and represents the conduit phase of left atrial function as blood is transferred from the pulmonary veins into the left ventricle (10). In patients with impaired left ventricular relaxation, filling pressures increase and left atrial passive function declines. However, assessment of left atrial passive function requires the presence of sinus rhythm, and it was not clear what proportion of patients in the study by Suksaranjit et al. (9) were in atrial fibrillation at the time of imaging.
Interestingly, Suksaranjit et al. (9) state that they used a single-shot, free-breathing technique for left ventricular LGE image acquisition and interpretation. This results in decreased spatial resolution and greater partial volume effects and may have impacted their ability to visualize small areas of left ventricular LGE (11). This may explain in part the lower prevalence of left ventricular LGE in this study compared with similar populations examined by Dodson et al. (5) and Neilan et al. (4).
The authors also measured left atrial LGE, and their group has published several papers using this technique, including a recent multicenter study suggesting an association with arrhythmia recurrence (6). It is notable that both left ventricular and left atrial LGE were independently associated with atrial arrhythmia recurrence in the current study, which indicates that atrial remodeling and LGE are not purely secondary to ventricular LGE. However, at present, LGE imaging of the thin-walled atrium in patients with frequently irregular heartbeats is challenging to perform. In contrast, ventricular LGE imaging is easy to do and universally available. Data from the current study and the work of Neilan et al. suggest that this provides additional useful prognostic information and should be considered in patients undergoing CMR before atrial fibrillation ablation.
Another interesting question raised by this work relates to the origin of the underlying ventricular LGE. The authors analyzed the pattern of LGE and found that almost one-half of the cases were subendocardial or transmural in location and therefore likely caused by underlying myocardial infarction. This presumably relates to either underlying coronary artery disease or embolic phenomenon. It would therefore be of interest to know what proportion of patients in the current study had a known history of coronary artery disease (patients with known prior myocardial infarction were excluded). The cause of LGE in the remainder of cases was not clear in this study, except for 2 patients with hypertrophic cardiomyopathy.
The authors of the current study are to be commended for adding to a growing body of data showing the utility of CMR in assessing patients with atrial fibrillation before ablation. Similar to computed tomography, CMR provides anatomic data helpful for procedure planning. However, CMR has several advantages over computed tomography. This includes detailed tissue characterization of the myocardium, which, as shown by this study, provides additive prognostic information. Within the same procedure, CMR also provides high-resolution functional assessment of ventricular and atrial function. In addition, left atrial tissue characterization with LGE imaging potentially provides direct information regarding the underlying substrate for atrial fibrillation and is an area of active research. Finally, emerging techniques (such as 4-dimensional flow) that provide detailed blood flow patterns within the left atrium may give further mechanistic insights in the future. We agree with the authors that when available, CMR should be considered before atrial fibrillation ablation.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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