Left Ventricular Scar in Atrial Fibrillation: Cause or Effect?∗

Journal of the American College of Cardiology
Ó 2013 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Left Ventricular Scar in
Atrial Fibrillation
Cause or Effect?*
Zhiyu Ling, MD, Harikrishna Tandri, MD
Baltimore, Maryland
Atrial fibrillation (AF) is the most common clinical
arrhythmia and is associated with increased risk for stroke,
heart failure, and all-cause mortality (1–3). The mortality
rate of patients with AF is about double that of patients in
normal sinus rhythm, and data from the Framingham Heart
Study show an AF-associated mortality risk even after
adjusting for preexisting cardiovascular conditions (3).
Although some of the mortality risk, such as stroke-related
death (4) and worsening heart failure, could be traced back
to AF, the fact remains that in most cases, AF is viewed
merely an association (5–8).
See page 2205
In this issue of the Journal, Neilan et al. (9) provide
intriguing data that attempt to connect the dots between AF
and all-cause mortality. In this study, pre-ablation late
gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) images of 664 consecutive patients with AF
were analyzed for the presence of left ventricular (LV)
fibrosis. None of the patients had a history of myocardial
infarction. In this otherwise low-risk cohort, 88 patients
(13%) had LV LGE on CMR. Furthermore, not only was
this unanticipated finding associated with increased
mortality, but the investigators also found a “dose effect”: the
larger the LGE, the worse the mortality.
Two obvious questions arise from this study: (1) What
comes first, AF or LV fibrosis? and (2) Are they independent
variables, or does one cause the other? Although no direct
evidence exists, circumstantial evidence suggests that AF
might be both the cause and subsequently the effect. AF has
been shown to affect LV systolic function by causing a raterelated cardiomyopathy. In animal models, AF results in
interstitial fibrosis with adverse LV remodeling (10). Although
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Division of Cardiology, Department of Medicine, The Johns Hopkins
Hospital, Baltimore, Maryland. Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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Vol. 62, No. 23, 2013
ISSN 0735-1097/$36.00
it is uncommon to find LV LGE in patients with paroxysmal
AF who are referred for catheter ablation, this statement is not
true especially in older patients with LV hypertrophy. Arterial
stiffness and LV diastolic dysfunction are often encountered
with older age and metabolic syndrome, which has been
associated with both AF and LV fibrosis. In a longitudinal
follow-up of older patients with pacemakers who had
LV diastolic dysfunction and fibrosis detected by echocardiographic acoustic densitometry, the incidence of new AF was
correlated with the severity of LV fibrosis, suggesting that
LV scar comes first (11). In contrast, using T1 mapping,
Ling et al. (12) showed diffuse LV myocardial fibrosis in
older patients with AF, suggesting abnormal LV remodeling
in AF. Focal LGE was also seen in 5 of 67 subjects (7%) in
this study.
Although mild interstitial fibrosis is common in older
subjects, the onset of AF might accelerate the remodeling
process, which may in turn perpetrate AF. This vicious cycle
eventually will culminate in atrial and ventricular dysfunction, with or without focal or macroscopic LGE (13). The
propensity to develop LGE might be multifactorial and
might depend upon coronary perfusion, hypertension, diabetes, renal failure, and, last but not least, genetic factors that
regulate injury and repair. Whatever the reason, the very
finding of LGE on CMR appears to be not trivial and has
important consequences. The presence of LV myocardial
fibrosis identified by LGE CMR imaging is an independent
predictor of adverse outcomes in various cardiomyopathies
In this study by Neilan et al. (9), patients with LGE were
on average older and more likely to have heart failure and
sleep apnea. Patients with LGE were also more likely to
have lower glomerular filtration rates, lower LV ejection
fractions, and increased LV mass and/or left atrial dimensions. Many of these comorbidities have been individually
linked to both AF and to myocardial fibrosis. Unrecognized
coronary disease was also prevalent in this cohort. Because of
the confounders, which are well known to promote and
maintain AF, and at the same time to cause adverse LV
remodeling, the causal link between AF and LV fibrosis is
difficult to ascertain.
Yet another interesting question this study raises is the
optimal imaging modality to image the left atrium before AF
ablation. Noninvasive cardiac imaging plays an important
role in pre-procedural planning and guidance of the procedures in many electrophysiology centers worldwide (16).
Multiple different techniques exist for anatomical imaging,
including angiography, computed tomography (CT), ultrasound, and CMR imaging. There are currently no guidelines, and the choice of imaging modality usually depends
on local expertise and available equipment. Both CT and
CMR imaging can provide accurate and detailed pulmonary
vein anatomy. LGE CMR imaging can provide additional
myocardial fibrosis information, but CMR has less availability,
lower spatial resolution, and standard contraindications.
Cardiac CT is widely available and may also provide additive
Ling and Tandri
LV Scar in Atrial Fibrillation: Cause or Effect?
information beyond pulmonary vein anatomy. But CT is
associated with radiation exposure and has less evidence for the
identification of myocardial fibrosis. Neilan et al. (9) provide
a valuable reference for choosing CMR as the preferred image
modality before catheter ablation in certain groups of patients
with AF, especially in those who are older, have heart failure
or sleep apnea, have lower glomerular filtration rates or LV
ejection fractions, and have increased LV mass or left atrial
dimensions. The finding of LGE in the left ventricle might
identify patients with occult coronary disease or cardiomyopathy or trigger aggressive risk factor management of modifiable
risks such as sleep apnea and hypertension. Whether this
strategy will better risk-stratify patients at risk for mortality
and thus change the observed outcomes needs to be tested
in prospective studies designed specifically to answer this
Patients who undergo pulmonary vein isolation are just
the tip of the AF iceberg, and those patients who are
screened and are thought not to be good candidates for
pulmonary vein isolation because of persistent AF with
severe comorbidities are very likely to harbor LV fibrosis.
The logical next step would be to investigate both the
prevalence of LV LGE and its association with cardiovascular mortality in this enriched group. Further studies are
needed to establish whether LGE is a major independent
predictive factor of cardiovascular mortality in patients with
Reprint requests and correspondence: Dr. Harikrishna Tandri,
Division of Cardiology, Department of Medicine, Johns Hopkins
Hospital, 600 N Wolfe Street, Carnegie 565D, Baltimore, Maryland 21287. E-mail: [email protected]
JACC Vol. 62, No. 23, 2013
December 10, 2013:2215–6
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Key Words: atrial fibrillation - cardiac magnetic resonance
late gadolinium enhancement.