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Credits: Rui Providência M.D. M.Sc.a,b, Sérgio Barra,b Luís Paivab
aCoimbra's Medical School, Coimbra, Portugal,
bCardiology Department, Coimbra's Hospital Centre and University,
Coimbra, Portugal
Corresponding Author: Rui Providência, M.D. M.Sc, Hospital Geral, Centro Hospitalar e Universitário de Coimbra, Quinta dos Vales, 3041-801 S.
Atrial fibrillation is the most frequent sustained arrhythmia and is an independent risk factor for stroke and death. In recent years, major echocardiographic advances have been made with the development of new techniques and applications that can be extremely useful for the management of these patients. This paper describes the role of echocardiography as a predictor of the incidence and progression of atrial fibrillation. A detailed description of the most relevant studies and recognition of unresolved questions regarding this subject are presented here. A special emphasis will be given on new techniques that allow the assessment of myocardial deformation and their possible role in the way we treat these patients.
Atrial fibrillation (AF) is the most frequent sustained
arrhythmia and is an independent risk factor for
stroke and death.1
In recent years, major advances
have been made in the field of echocardiography,
with the development of new techniques and applications.
Transthoracic Echocardiography (TTE) is an easily
accessible and non invasive technique. It presents
no radiation hazard and has very few contraindications,
which renders it ideal for the initial workup
of all patients presenting with AF.
In the following sections we will review most of the
current applications of echocardiography concerning the prediction of the incidence and progression
of AF and illustrate new findings and possible applications
for the near future. There are two main
parts in this article: the first, comprising sections 1
to 6, is about the natural course of atrial fibrillation
and describes echocardiographic parameters that
may predict its development and progression over
time, from paroxysmal to persistent, and eventually
permanent AF. The second part describes the predictors of AF relapse in procedures like cardioversion and radiofrequency ablation and the incidence
and relapse in cardiac surgery (other than ablation).
A brief summary of the different echocardiographic
parameters and the situations in which
they can be used is present on Tables I and II.
The Best Method for Measuring Left Atrial
Size
Left atrial (LA) dilation can be assessed using Mmode,
two or three dimensional (2D or 3D, respectively)
echocardiography.
It
is
known
that
LA
dilation
spatially occurs in an asymmetric way,
predominantly in the medial-lateral and superiorinferior
axes since enlargement in the anteropos-
terior axis may be limited by the thoracic cavity.
In face of this, and despite the fact that most classic
studies have used this parameter, diameter is
not an accurate way of assessing LA dimensions,
because it frequently underestimates LA size.
This is worrisome since underestimation is more
pronounced in patients with enlarged LA.
The measurement of LA area using planimetry in
apical four-chamber view can provide more consistent
information regarding size and be used
as part of the LA volume equation. Badano and
colleagues suggested that 2D LA area may be an
accurate method, however the available cut-off
criteria are inappropriate and need redefinition.2
LA biplane volume measurement using either the
area-length formula, or the modified Simpson's
rule, is currently recommended by the European
Society of Echocardiography (ESE) and American
Society Echocardiography (ASE) guidelines as the
preferred method, since it can more reliably reproduce
the atrial geometry (as it relies on fewer
geometric assumptions) and therefore has higher
accuracy and prognostic value.3,4
These biplane
methods have been successfully validated against
cine computed tomography and magnetic resonance
imaging.5-7
Table 1: Echocardiographic parameters that predict the Development or Progression of Atrial
Fibrillation
 AF – atrial fibrillation; LA – left atrial; PA-TDI – time interval from P wave on ECG lead II to A´on lateral atrial pulsed tissue Doppler imaging.
|
Nevertheless biplane volume measurement is not always feasible, as the apical two-chamber view may not provide optimal LA border visualization. Russo et al have demonstrated that single-plane modified Simpson's method for measuring LA volume has a high correlation with LA volume assessed by three-dimensional echocardiography (r=0.93, p<0.001). Similar findings were reported for the biplane area length method (r=0.93, p<0.001). Nevertheless, single-plane volumes were significantly larger than biplane volumes with an overall mean difference of 1.9ml/m2. This difference, albeit small, resulted in a significant misclassification when using the ASE cut-offs.8 Similar findings were described by Badano and colleagues when comparing the single-plane area-length and biplane method of discs using 3D echocardiography as a reference standard.2 They demonstrated that left atrial diameters and area measurements were poor predictors of 3D LA volume. Using M-mode anteroposterior diameter or LA area resulted in misclassification of the degree of left atrial dilation in 57 to 70% of patients. A good correlation was between LA volumes assessed by 2D and 3D echo-cardiography. The biplane method seemed to be slightly more accurate than the single plane arealength method. Nevertheless, according to these authors, the additional accuracy obtained using a more technically demanding and time-consuming biplane method did not justify its usage.2
Table 2: Echocardiographic parameters that predict atrial fibrillation relapse after procedures  LA – left atrial; LV &nd' left ventricle; LAA – left atrial appendage; E - early transmitral flow velocity; A - late transmitral flow velocity; E' - early diastolic mitral annular velocity
|
Incidence of AF in the Dilated Left Atrium
According to data from the Framingham Heart
Study, during an 8-year follow-up of 1924 subjects,
a 5mm increment on LA size (diameter on
M-mode) was associated with a 39% increase in
the risk for subsequent development of AF.9
Psaty
and colleagues demonstrated in a cohort of 5201
elderly subjects that the risk of developing AF during
a
3
year
follow-up
period
was
increased
about
4
times in those with LA diameter over
5 cm.10
In patients admitted due to congestive heart failure,
LA
size
>
45mm
and
atrial
dissincrony
>
39ms
assessed
by
strain
were
independent
predictors
of
the
incidence of new-onset atrial fibrillation.11
Lin and colleagues have found that LA area independently
correlates with the incidence of paroxysmal
AF in patients with sick sinus syndrome:
each 1cm2 increase in LA area led to a 44% increase
in the incidence of AF.12
In a cohort of 1655 elderly patients followed during
an
average
of
3.97
years,
a
30%
increase
in
LA
volume
was associated with a 43% higher risk of
developing AF.13
In an elderly cohort of patients
with no history or evidence of prior atrial arrhythmias,
LA volume was an independent predictor
of first AF episode or atrial flutter during a mean
follow-up of 1.9±1.2 years.14
Progression of AF in the Dilated Left Atrium
LA enlargement was associated with progression
to chronic AF in patients with newly diagnosed AF
in the Canadian Registry of AF (CARAF).15
In a 14 years follow-up study, Kato et al have found
that aging (HR 1.27 per 10 years, 95%CI
1.06-1.47), a dilated left atrium (HR 1.39 per 10mm,
95%CI 1.11-1.69), myocardial infarction (HR 2.33,
95%CI 1.13-4.81) and valvular heart disease (HR
2.29, 95%CI 1.22-4.30) were independent predictors
of early progression of recurrent paroxysmal
AF to chronic AF.16
Kerr et al. have shown that left
atrial enlargement, diagnosis of cardiomyopathy,
significant aortic stenosis or mitral regurgitation,
age and heart rate were independent predictors of
progression of newly diagnosed AF to chronic AF
over an 11 year period.17
Pillariseti et al. have supported these findings
demonstrating that larger LA size (diameter ),
Valvular heart disease (moderate to severe mitral and aortic valve disease) and
cardiomyopathy (ischemic, non-ischemic or hypertrophic
obstructive cardiomyopathy) predicted
progression of paroxysmal AF to persistent or
permanent AF. A larger LA size and the presence
of valvular heart disease were also predictors of
progression to permanent AF.18
The role of cardio-
myopathy and valvular heart disease is thought to
be associated with the increase in LA stretch (see
below).
Using data from the Euro Heart Survey on AF, Vos
et al. have developed the HATCH score for the prediction
of AF progression. The multivariate logistic
regression included clinical factors only: heart
failure, age, previous ischemic attack or stroke,
chronic obstructive pulmonary disease and hy-
pertension. Still, patients with AF progression had
larger LA size (diameter ) and higher prevalence of
valvular disease.19
Recently, Suzuki and colleagues have found that
increased LA diameter is associated with a longer
period in AF (6.5% increase in the number
of days) and progression from paroxysmal to
persistent AF (HR 1.84) in hypertensive patients
from the Japanese Rhythm Management Trial II
( J.RHYTHM II).20
AF is self-regenerating and predisposes to the
progression of AF ("AF begets AF")21
due to electroanatomical
remodeling.
Accordingly,
AF
leads
to
left
atrial
dilation
which
subsequently
leads
to
more
AF
episodes
or
progression
to
persistent
and
permanent
forms.
Therefore,
left
atrial dilation is
a part of this vicious circle arising both as a cause
for and a consequence of AF. Besides left atrial
dilatation, the presence of pressure and volume
overload in the atria, resulting in cardiomyocite
elongation and increased atrial stretch, also seems
to have a preponderant role in atrial remodeling
and incidence and progression of AF.22
Mitral regurgitation,
arterial hypertension and diastolic
dysfunction are some of the factors that lead to
atrial stretching and cause structural remodeling.
The role of atrial stretch, occuring independently
of left atrial dilation needs to be further evaluated
and the echocardiographic deformation assessment
may have
an important role in this field.
Pulmonary vein dilation may be another possible
crosslink between LA enlargement and AF.23
Isolated
dilation of the pulmonary veins24
or alongside
with
left
atrial
dilation25
has been reported in
patients with AF. However, it is not totally clear
if pulmonary vein dilation precedes left atrial
dilation or arises as a cause of it.26
Unfortunately,
echocardiography is not as accurate as other
techniques (angiography, computed tomography
or magnetic resonance imaging) to assess these
structures.
The use of tissue Doppler imaging (TDI) allows
quantification of low-velocity, high-amplitude,
long-axis intrinsic myocardial velocities, and provides information regarding systole and diastole in
a load independent way.
A prolonged atrial conduction time measured
through signal averaged ECG has been previously
associated with history of AF27
and progression of
paroxysmal into permanent AF.28
A new transthoracic
echocardiographic
tool
has
been
recently
described,
the
PA-TDI,
which
measures
the
time
from
the
initiation
of
the
P
wave
on
the
ECG
in
lead
II
to
the
late
diastolic
mitral
annular
velocity
-
A'
wave
-
on
the
lateral
left
atrial
tissue
by
Doppler
tracing
and
reflects
the
total
atrial
conduction
time
(Figure
1).
A
prolonged
PA-TDI
seems
to
predict
a
new-onset
of AF,29
AF after acute myocardial infarction30
and recurrence of AF after radiofrequency catheter
ablation.31
This index has been proposed as an
early marker of paroxysmal AF32
and has also been
shown to be associated with echocardiographic
signs of diastolic dysfunction, valve incompetence
and LA dilation.33
Figure 1: Measurement of the atrial conduction time: PA-TDI is obtained using pulsed tissue doppler imaging with the sample placed in lateral border of the mitral annulus and measuring the time interval from the begining of the P wave (ECG lead II) to the late diastolic mitral annular velocity (A')
 É- early diastolic mitral annular velocity; S´- systolic
annular velocity.
|
LA mechanical function can be assessed with
pulsed wave Doppler measurement of transmitral
inflow patterns. The peak transmitral A wave velocity
is frequently used to provide information
regarding LA mechanical function but is absent
during AF. Other parameters of atrial function like
the velocity time integral of the A velocity and the
atrial fraction (ratio of the time velocity integral of the mitral A wave to that of the total diastolic transmitral
flow)
can
also
be
used,
but
only
in
patients
in sinus rhythm.34
Atrial ejection force, defined as
the force exerted by the LA to propel blood across
the mitral valve into the LV during atrial systole,
is another marker of atrial mechanical function.35
Since these markers are lacking in patients in AF,
they have limited interest in the assessment of
atrial mechanical function. Moreover, they are
highly dependent on loading conditions (LA and
LV pressures) and diastolic function.
Non-invasive functional quantification of LA deformation
properties
provides
functional
information
that is independent of cardiac rotational motion
and
from
tethering
of
contiguous
segments
of
the
heart. The rhythm, sinus or AF, during strain
imaging does not seem to affect the analysis of
LA strain or strain rate. Tissue Doppler velocities
measure global tissue motion, whereas strain and
strain rate respectively represent the extent and
rate of regional deformation that the tissue experiences.
Regional left atrial function assessed by tissue Doppler
velocity
and
strain
imaging
is
markedly
compromised
in patients with AF.36
Wang et al. compared52
patients
with
AF
for
less
than
1
year
with27
matched
normal
control
subjects
and
found
that
LA
early
diastolic strain rate was lower in the AF
group.37
Di Salvo et al. have also described compromised
atrial
myocardial
properties
assessed
by
tissue
Doppler
myocardial
velocity,
strain
rate
and
strain
in AF patients when compared to normal
subjects.38
Schneider et al described differences in the left
atrial deformation properties assessed by TDI in
patients before undergoing catheter ablation of
AF. Both paroxysmal and persistent AF patients
had compromised deformation of the LA, but persistent
AF patients presented even lower values
.39
Changes were also found in the left atrial appendage
(LAA)
pulsed
wave
TDI
with
reduction
of
late
systolic
wave
(upward)
and
late
diastolic
wave
(downward)
and disappearance of initial upward
velocity wave during early ventricular diastole.40
Angle-dependence, signal artifacts, suboptimal
reproducibility and lack of information about the
atrial roof and other atrial regions are some of the
limitations that have been pointed out to Dopplerderived strain. To overcome these limitations,
the use of speckle tracking has been proposed. It
is not derived from Doppler but rather from 2D
echocardiography. It is angle-independent and
allows the measurement of global as well as regional
atrial strain.41
LA enlargement and fibrosis cause disruption
of normal electric conduction and establish reentry
circuits
that
lead
to
increased
susceptibility
and
predisposition to maintenance of AF.42
The
extent of this histologically determined remodelling
process
has
been
shown
to
correlate
with
the
persistence
of AF.43
Oakes and colleagues have
described a method using delayed-enhancement
MRI (DE-MRI) to assess what is presumed to be
LA wall fibrosis.54
Kuppahally and colleagues
have demonstrated that LA wall fibrosis assessed
by DE-MRI is inversely related to strain and
strain rate derived from vector velocity imaging
echocardiography45
mostly in patients with persistent
AF. Patients with persistent AF had significantly
more
DE
(marker
of
fibrosis)
alongside
with
decreased strain and strain rate compared
to those with paroxysmal AF, supporting the
concept that there is a progressive remodelling
process once AF develops.46
LA relaxation and
lengthening during ventricular systole (markers
of LA compliance) are translated by a positive
strain and strain rate that seem to be impaired in
AF due to fibrosis.
Evidence suggests that LA diameter assessed
through echocardiography is inversely related
to the success of cardioversion (CV).47-59
Subjects
with enlarged LA are more prone to present AF
recurrences after CV.48, 50, 51
An increase in LA
area has also been associated with AF relapse after
successful CV.48, 52, 53
According to Marchese
et al. the same can be observed with the indexed
LA volume, where each ml/m2 increase independently
associates with a 21% increase in the
risk of AF recurrence (OR 1.21 p<0.001). The area
under receiver operating characteristic (ROC) curve regarding indexed LA volume as predictor
of AF recurrence was 0.85, which was far superior
to the one obtained for LA diameter (AUC 0.59;
p<0.001).53
Systolic pulmonary venous flow is a marker of
atrial compliance and reservoir function. Low values
before
or
early
after
CV
seem
to
predict
relapse
at
6 and 12 months.54, 55
Preserved LAA peak emptying velocity (high values)49, 56
has been associated with restoration and
maintenance of sinus rhythm in subjects underdoing
electrical CV.47, 56, 57
In a study by Okçün et al a LAA ejection fraction
<30% was the only independent predictor of relapse
of AF
at 6 months after CV.54
Higher values of LA inferior wall peak systolic
strain rate and LA septal peak systolic strain assessed
through colour Doppler myocardial imaging
before
electrical
CV
have
also
been
associated
with
a greater likelihood of maintaining patients
in sinus rhythm. In multivariate analysis, traditional
parameters like atrial appendage flow
velocity (Figure 2) had no additional predictive
value when added to those two parameters (both
p<0.0001).38
Wang T et al. have shown that a lower
early diastolic strain rate and larger LA transverse
diameter were independent predictors of failure
of both CV and maintenance of sinus rhythm at 4
weeks.37
Figure 2: Measuring of left atrial appendage flow velocities: placing the pulsed wave Doppler sample 1 cm from the entry of the LAA into the body of the LA. Emptying (Emp – positive defletion, towards the probe) and filling (Fill – negative deflection, away from the probe) velocities should be estimated from an average of five well-defined waves
|
Shin and colleagues have reported that LA volume
measured through echocardiography was a strong
independent predictor of AF recurrence after catheter
ablation.58
An increased ratio of early transmitral flow velocity
(E)
to
early
diastolic
mitral
annular
velocity
(E’)
(over
11.2)
has
been
associated
with
AF
recurrence
after
catheter ablation.59
Schneider et al. described significantly different
atrial myocardial properties (LA strain and strain
rate assessed by TDI) after catheter ablation of AF
in patients with persistent AF when compared to
healthy controls. Using data from the echocardiographic
assessment after ablation, septal systolic
strain rate (p<0.0001) and inferior systolic strain
(p<0.0001) were the best predictors on logistic regression
analysis for sinus rhythm maintenance.
These authors have shown that there are specific
parts of the cardiac cycle and segments of the LA
wall that can provide more relevant information
for this endpoint. Additionally, in patients who
maintained sinus rhythm in the 3 months period
following ablation, an improvement in deformation
properties of the LA and decrease in LA size
was also found in contrast to patients with recurrent
AF
(p=0.001).39
Hammerstingl el al. have used speckle tracking for
the measurement of LA strain and strain rate (Figure
3) and found that global LA strain and strain
rate displayed better results than regional LA
function analysis (despite the fact that LA-septal
wall strain was an independent predictor for AF
recurrence after ablation).60
Moreover, average
systolic strain was the only independent predictor
of AF relapse after catheter ablation on multivariate
analysis.
Other
independent
predictors
on
univariate
analysis,
as
LA
volume
index,
did
not
add
predictive
value
to this variable.61
Some limitations should be mentioned regarding
speckle tracking: it strictly depends on the frame
rate, image quality (with potential errors in epicardial/endocardial
border tracing if suboptimal)
and the need for an appropriate learning curve to
achieve adequate experience in using the analysis
software. Moreover, the currently available software
is
not
dedicated
to
LA
analysis,
as
it
has
been
originally
developed
for left ventricle
study.41
Figure 3: Left atrial deformation assessment using speckle tracking derived longitudinal strain. Six segments identified by different colours (red, blue, pink, green, light blue and yellow) are seen in the apical 4 chamber view image (A.). The corresponding segment strain and its variation during the cardiac cycle can be seen in the corresponding curves to the left (B.) and colour graph beneath the echocardiogram image (C.). The curves show a predominant positive strain (reflecting stretching). Different strain values can be observed in the different regions. The scale shows that positive strain in A. and C. is represented by the blue colour scale and negative strain by the red colour scale
 AVC – aortic valve closure.
|
In patients treated with the Cox maze IV procedure
an enlarged left atrial diameter was a risk
factor for AF relapse at medium (12 months)62
and
long-term (38 months)63
follow-up. Chen et al. described
a
preoperative
left
atrial
area
cuttof
point,56.25cm2,
with
50.5%
sensitivity
and
86.2%
specificity
for
predicting
conversion
to
sinus
rhythm
after
surgery.63
Furthermore, in patients undergoing
mitral valve surgery plus radiofrequency ablation
maze operation a 6 cm cutoff value of preoperative
left atrial diameter was predictive of persistent
atrial
fibrillation
at
6
months
(100%
sensitivity
and
73.6% specificity).64
The role of left atrial diameter as a predictor of
long-term sinus rhythm maintenance in patients
undergoing open-heart procedures and concomitantly
with a radiofrequency modified maze procedure
has been demonstrated by other
authors.65,66
Finally, in a recent review of 12 papers67
concerning
the impact of left atrial size on maze surgery
in terms of recurrence of AF the following cutoff
points were found: left atrial volume index > 135
ml/m2 had 100% specificity68
and left atrial diameter
> 60mm a 100% sensitivity for procedure failure;
conversely
a
left
atrial
diameter
<
48.3mm
conferred
100% sensitivity for sinus conversion.
According to Gibson et al, the transmitral early (E)
to late (A) diastolic filling velocity ratio and the early
diastolic myocardial velocity (E´) predicted AF
after isolated CABG on univariate analysis. However,
no echocardiographic parameters remained
significant on multivariate analysis.69
In 205 patients underdoing cardiac surgery, an
indexed LA volume > 32ml/m2 increased the risk
of postoperative AF around five fold, independently
of
age
and
clinical
risk
factors
(adjusted
HR
4.84
95%CI 1.93-12.17, p=0.001). The area under
the ROC-curve for indexed LA volume was 0.729
(p<0.0001).70
The development of a score using echocardiographic
parameters, alongside with other data, in
order to predict recurrences after cardioversion
might help us redefine treatment decisions for patients
with
AF.
It
could
be
an
effective
and
accurate
method
of
deciding
between
further
cardioversions
or
a
rate
control
strategy.
The
same
might
apply
to
AF
catheter ablation.
The debate remains open regarding the best way
(more accurate, reproducible and easy to use) for
LA volume assessment.2,8
Morevoer, there seems
to be a need to redefine reference values for singleplane
LA volume and LA area measurement, and
to establish new cut-off values for category classification
.
The best way of assessing LA deformation also
needs to be clarified. Further investigations are
needed to define which is the best technique (Doppler
derived,
speckle
tracking
or
vector
velocity
imaging)
or
method
(strain,
strain
rate
or
both),
whereto place the sample for data measurement (regional
vs. global deformation; if regional, which wall
provides the best information) and the best portion
of the cardiac cycle to retrieve
information.
Also, more studies will be necessary to reproduce
findings correlating LA deformation and MRI
delayed-enhancement, namely with other techniques
(speckle tracking and Doppler derived
strain and strain rate).
The use of 2D and Doppler echocardiography
for anatomic and functional study should be the
starting point of evaluation in all patients with AF
in order to diagnose concomitant cardiac disease
(myocardial, pericardial, valvular or congenital
heart disease, LV systolic or diastolic compromise)
predisposing to AF. Furthermore, this technique
would be extremely helpful in guiding treatment
decisions and providing prognostic information.
Conversely, transesophageal echocardiography
is an invasive and poorly tolerated technique that
should be reserved for other specific clinical settings.
Left atrial and left atrial appendage deformation
assessment is a field of very active research that
warrants further validation before potential implementation
in clinical practice.
No disclosures relevant to this article were made by the authors.
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