Download The importance of exercise echocardiography for clinical decision

Systematic review
The importance of exercise echocardiography for clinical
decision making in primary mitral regurgitation
Caroline M. Van de Heyning, Julien Magne, Patrizio Lancellotti and
Luc A. Piérard
Primary mitral regurgitation is generally an insidious
disease with late onset of symptoms. Current European and
American guidelines recommend surgery in severe primary
mitral regurgitation when symptoms, overt left ventricular
dysfunction, pulmonary hypertension or atrial fibrillation,
occur. However, recent large studies reported an improved
outcome in asymptomatic patients with severe mitral
regurgitation referred for early mitral valve repair despite
the risk of operative mortality or mitral valve replacement.
Moreover, primary mitral regurgitation appears to have an
important dynamic character in up to one-third of patients.
This article provides an overview of the incremental
evidence of the ability of exercise echocardiography to
Introduction
Mitral regurgitation is the second most prevalent valvulopathy in Europe after aortic stenosis.1 Primary mitral
regurgitation has an organic cause such as rheumatic
disease, myxomatous degeneration or endocarditis. In
secondary mitral regurgitation, the mitral valve is structurally normal but dysfunctional due to ischaemic or
non-ischaemic cardiomyopathy. The disease course of
primary mitral regurgitation is usually insidious due to
progressive atrial and left ventricular remodelling which
compensates for the overload caused by the increasing
regurgitant volume.2 Although the late onset of symptoms often leads to late referral for surgery,3 the outcome
of medically treated asymptomatic severe primary mitral
regurgitation remains unclear. Enriquez-Sarano et al.4
reported a 5-year probability of 62 þ 8% for cardiac death,
heart failure or new atrial fibrillation in asymptomatic
patients with severe mitral regurgitation, whereas more
recently Kang et al.5 found a 7-year survival free of cardiac
death or heart failure of 85 þ 4% in asymptomatic mitral
regurgitation with a preserved left ventricular ejection
fraction (LVEF). The 2007 European Society of Cardiology (ESC) and 2008 American College of Cardiology
(ACC)/America Heart Association (AHA) guidelines
recommend surgery in severe primary mitral regurgitation with symptoms including LVEF of 60% or less, left
ventricular dilatation, atrial fibrillation and/or pulmonary
hypertension (PHT) (Table 1).6,7 Rosenhek et al.8
showed an excellent outcome in asymptomatic severe
mitral regurgitation with the ‘watchful waiting’ strategy
in accordance with these guidelines. Nevertheless,
numerous large studies have provided evidence for a
1558-2027 ß 2012 Italian Federation of Cardiology
assess the functional repercussions of mitral regurgitation
and the identification of high-risk patients who might
benefit from early referral for surgery.
J Cardiovasc Med 2012, 13:260–265
Keywords: exercise echocardiography, primary mitral regurgitation
University of Liege, University Hospital Sart Tilman, Liege, Belgium
Correspondence to Luc A. Piérard, MD, PhD, University Hospital Sart Tilman,
Liege 400, Belgium
Tel: +32 4 366 8870; fax: +32 4 366 7195; e-mail: [email protected]
Received 19 October 2011 Revised 8 November 2011
Accepted 29 November 2011
more favourable clinical course if patients are submitted
to surgery before left ventricular dysfunction or PHT has
developed.9–12 It is well established that mitral valve
repair yields a better prognosis than mitral valve replacement regarding operative mortality, postoperative LVEF
and prosthesis-related complications.2,3 Despite a low
operative mortality risk of 0.6% for asymptomatic
patients and increasing repairability rates,13 it should
be noted that there is a considerable variability in the
frequency of mitral valve repair between high and low
volume centres and surgeons.3,14 As a result, a heated
debate persists about the optimal timing for surgery.15–17
Moreover degenerative mitral regurgitation appears to be
a dynamic disease with significant progression of mitral
regurgitation during exercise in one-third of patients,
which is associated with a worse outcome.18,19 Risk
stratification to identify patients who could benefit from
early surgery appears to be crucial in the current management of primary mitral regurgitation. In this setting,
several recent articles have pointed out the emerging
role of exercise echocardiography.20–23 The most recent
guidelines of the European Association of Echocardiography (EAE)24 only recommend exercise echocardiography in primary mitral regurgitation when symptoms
are discordant with mitral regurgitation severity at rest.
This article will give an overview of the current utility of
exercise echocardiography in clinical decision making.
Exercise-induced haemodynamic changes in
primary mitral regurgitation
The dynamic character of secondary mitral regurgitation
and its implications are well established.25 Conversely,
DOI:10.2459/JCM.0b013e3283515c70
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Exercise echocardiography in primary MR Van de Heyning et al. 261
Surgical criteria for mitral valve repair in severe primary
mitral regurgitation
Table 1
Surgical criterion
Symptomatic severe MR
LVEF < 60%
End-systolic diameter > 45 mm
End-systolic diameter > 40 mm
SPAP > 50 mmHg at rest
SPAP > 60 mmHg at exercise
Atrial fibrillation
High probability mitral valve
repair, low comorbidity
Probability mitral valve repair
>90%, expert centre
2007 ESC
guidelines7
2008 ACC/AHA
guidelines6
Class I
Class I
Class I
Class I
Class I
Class IIa
Class IIa
Class IIb
Class
Class
Class
Class
I
IIa
IIa
IIa
Class IIa
ACC, American College of Cardiology; AHA, American Heart Association; ESC,
European Society of Cardiology; LVEF, left ventricular ejection fraction; MR, mitral
regurgitation; SPAP, systolic pulmonary arterial pressure.
few studies exist about exercise-induced changes in
primary mitral regurgitation. Stoddard et al.18 showed
that 32% of patients with mitral valve prolapse without
mitral regurgitation developed mitral regurgitation
during exercise. More recently and in line with these
data, Magne et al.19 found an increase in mitral regurgitation (regurgitant volume > 15 ml or effective regurgitant
orifice area > 10 mm2) in one-third of asymptomatic
patients with moderate-to-severe degenerative mitral
regurgitation. Interestingly, according to the effective
regurgitant orifice area, 32% of patients with moderate
mitral regurgitation at rest developed severe mitral regurgitation at exercise, whereas, respectively, 15 and 7% of
patients with severe and moderate mitral regurgitation
dropped one class. Both studies observed in these
patients an increased mitral valve annulus area which
could point at exercise-induced progressive ring dilatation with suboptimal leaflet coaptation as a possible
mechanism. The smaller cavity during exercise with
subsequent less tugging of the chordae and, thus, worsening mitral valve prolapse might be an additional factor
in degenerative mitral regurgitation.19 The rise in blood
pressure during exercise did not seem to play a major role
in increasing mitral regurgitation in the latter study.
Importantly, there was a strong correlation between
exercise-induced mitral regurgitation progression and
exercise PHT.
in symptomatic patients with less-than-severe mitral
regurgitation in order to assess the haemodynamic
consequences of mitral regurgitation. Continuous echocardiographic examination during semisupine ergometry
is preferred over postexercise echocardiography, as
measurements can differ significantly between peak
stress and the immediate postexercise period,22 specifically regarding the SPAP. After the patient is positioned
on the ergometer, a workload of 50 W is set. During the
test, the workload is increased with 25 W every 3 min in
young, otherwise healthy patients, but can be adjusted in
older individuals. Heart rate, blood pressure and symptoms should be noted at each level and during recovery,
as well as exercise duration (Fig. 1). Meanwhile, image
acquisition is performed with special attention to the
systolic left ventricular function, the evolution of mitral
regurgitation severity and the SPAP. Data from expert
echo laboratories show a high feasibility and reproducibility of mitral regurgitation quantification and a good
agreement between the flow convergence method and
the Doppler volumetric method both at rest and during
exercise,19,28 although this assessment might be challenging in less experienced hands.23 Exercise echocardiography is not recommended in severe mitral regurgitation
with symptoms or a LVEF less than 60% (indications for
surgery), severe hypertension, important arrhythmias,
systemic illness or the impossibility to perform an adequate exercise test.22
Assessment of functional repercussions of
mitral regurgitation
As in non-valvular cardiac abnormality,29 diastolic dysfunction appears to be a major determinant in reduced
functional capacity in primary mitral regurgitation,
Fig. 1
How to perform exercise echocardiography in
primary mitral regurgitation
First, the patients’ medical history and a directed physical
examination should be obtained to identify symptoms.
Second, a rest echocardiography should be performed
according to the guidelines26,27 to identify and localize
the valvular lesion and to quantify mitral regurgitation
severity, LVEF, left ventricular dimensions (especially
the left ventricular end-systolic diameter) and the systolic
pulmonary arterial pressure (SPAP). Subsequently,
exercise echocardiography is recommended in asymptomatic patients with severe mitral regurgitation or
Setting semisupine ergometer in exercise echocardiography.
Echocardiographic images are acquired at rest, during several steps of
exercise and during recovery. Meanwhile, continuous 12-lead ECG
recording is performed and blood pressure and symptoms are noted at
each step.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
262 Journal of Cardiovascular Medicine 2012, Vol 13 No 4
regardless of compensatory left atrial dilatation.30,31
Moreover, resting left ventricular filling pressures may
predict exercise PHT32 which is correlated with a
decreased exercise capacity.33 To a lesser extent,
reduction of exercise tolerance is associated with a lower
exercise cardiac output,31 caused by the inability of the
left ventricle to maintain a large forward stroke volume.
Exercise forward stroke volume in mitral regurgitation
is determined by two opposing mechanisms, namely
contractile reserve and eventually increasing mitral regurgitation.23 The presence of contractile reserve itself is
associated with a significantly better functional capacity
in comparison with lack of contractile reserve.34
Fig. 2
Due to the slow disease progression, the patient may be
unaware of their adaptation of daily activities and will
often deny symptoms. It is well recognized that there is a
primary role for exercise testing to unmask these ‘asymptomatic’ patients.35
Current EAE guidelines advocate exercise echocardiography when symptoms are discrepant with mitral regurgitation severity at rest.24,26 These recommendations are
based on a small study by Tischler et al.36 which found
that exertional dyspnoea in mild rheumatic valve disease
is frequently explained by an increase in mitral regurgitation combined with exercise PHT. This observation
was recently confirmed by a study in 78 asymptomatic
patients with moderate-to-severe degenerative mitral
regurgitation in which patients with exercise-induced
increase in mitral regurgitation had higher SPAP, more
frequent exercise PHT and presented more often
dyspnoea during exercise33 (Fig. 2). In brief, there is
incremental evidence that exercise echocardiography is
an interesting tool for the objective evaluation of the
functional repercussions of mitral regurgitation.
Identification of high-risk patients
There is not yet a consensus about the optimal timing for
surgery in asymptomatic patients with severe mitral
regurgitation and preserved left ventricular systolic function. Although a LVEF less than 60% is highly predictive for postoperative left ventricular deterioration,9 a
decreased LVEF is only a late marker of left ventricular
dysfunction in significant primary mitral regurgitation.
Indeed, in these patients, the LVEF remains generally
normal or supranormal due to the increased preload and
the alternative low impedance pathway provided by the
regurgitant orifice.37,38 Detection of subclinical systolic
left ventricular dysfunction in patients with severe mitral
regurgitation is, therefore, mandatory to avoid postoperative overt left ventricular impairment. In recent years,
exercise echocardiography has become an important tool
for this purpose.39 The absence of contractile reserve,
initially defined as less than 4% increase in the LVEF
at exercise, predicts a worse postoperative LVEF and
event-free survival in minimally symptomatic severe
mitral regurgitation patients submitted to surgery.34,40
Example of an exercise echocardiogram in a 78-year-old male patient
with severe primary mitral regurgitation and a normal ejection fraction of
67%. The first column represents images at rest of, respectively, the
colour flow mapping of the mitral regurgitation, the velocity–time
integral of the regurgitant jet and the transtricuspid gradient (both
measured by continuous Doppler). The second column depicts the
same images during exercise and shows a slight increase in the
effective regurgitant orifice (from 40 to 46 mm2) and the regurgitant
volume (from 63 to 72 ml) with concomitant increase of the systolic
pulmonary arterial pressure (increase of the transtricuspid gradient from
55 to 74 mmHg).
Alternatively, contractile reserve can be assessed by
two-dimensional speckle-tracking whereby less than
1.9% increase in global longitudinal strain (GLS) at peak
exercise predicts postoperative left ventricular deterioration in asymptomatic patients41 (Fig. 3). Recent data from
our echocardiography laboratory show that evaluation of
contractile reserve by GLS is more accurate than by
ejection fraction in predicting adverse outcome (accepted
abstract ESC Congress 2011). Contractile reserve can also
be appreciated by pharmacological stress testing, its only
indication in primary mitral regurgitation.24
Apart from revealing early left ventricular dysfunction,
exercise echocardiography is also useful for identification
of several risk factors which yield a poor outcome. First, it
has been shown that decreased exercise capacity itself,
marked by a reduced peak oxygen consumption during
cardiopulmonary exercise testing31 or a diminished
duration at exercise tolerance test,42 is predictive for
mortality and the development of symptoms or other
criteria for surgery in asymptomatic mitral regurgitation.
Second, both exercise PHT (>60 mmHg)33 and exerciseinduced increase in mitral regurgitation severity19 have
recently been shown to be strongly correlated with a
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Exercise echocardiography in primary MR Van de Heyning et al. 263
Fig. 3
Absence of contractile reserve in a patient with severe primary mitral regurgitation. The upper panel represents two-dimensional strain calculations at
rest for the patient also used for Fig. 2. The lower figure shows the two-dimensional strain values during exercise. Despite an increase in mitral
regurgitation and ejection fraction, there was almost no increase in global longitudinal strain (23.7% at rest versus 24.0% during exercise), indicating
subclinical left ventricular dysfunction.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
264 Journal of Cardiovascular Medicine 2012, Vol 13 No 4
decreased symptom-free survival. On the basis of these
data, the 2010 EAE recommendations26 state that the
absence of contractile reserve, a limited exercise capacity,
the presence of exercise PHT or an exercise-induced
increase in mitral regurgitation severity may identify
high-risk patients who might benefit from early surgery.
At least a closer follow-up should be provided in these
high-risk patients, as in patients who almost fulfil the
surgical criteria. The 2008 ACC/AHA guidelines6 already
adopted exercise PHT more than 60 mmHg as a class IIa
indication for surgery. However, it should be noted that
over one-third of normal individuals older than 60 years
present PHT of at least 60 mmHg at peak exercise,43 and
that exercise PHT can be predicted by age and rest
echocardiographic parameters.32
Conclusion
In patients with primary mitral regurgitation, current
guidelines support the use of exercise echocardiography
in patients with discordant symptoms, to evaluate the
functional repercussion of mitral regurgitation in an
objective manner. Like secondary mitral regurgitation,
primary mitral regurgitation appears to be a dynamic
condition which is incompletely characterized at rest.
Recent studies show that limited exercise capacity and
exercise-induced mitral regurgitation progression or exercise PHT are correlated with the development of symptoms. Furthermore, there is growing evidence that
exercise echocardiography should be performed on a
regular basis in asymptomatic patients with severe mitral
regurgitation to detect absence of contractile reserve
which points at subclinical left ventricular dysfunction.
Implementation of exercise echocardiography in asymptomatic severe primary mitral regurgitation permits a
more precise identification of patients who require a
closer follow-up and who might benefit from early referral
for surgery. Watchful waiting seems more appropriate in
patients without the above-mentioned risk factors or
when mitral valve repair is unlikely.
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