Dobutamine stress echocardiography in the evaluation of hibernating myocardium

Author
Wilson S Colucci, MD
Section Editor
Warren J Manning, MD
Deputy Editor
Brian C Downey, MD, FACC
Disclosures: Wilson S Colucci, MD Consultant/Advisory Boards: Merck [Heart failure (Enalapril)]; Novartis [Heart
failure (Enalapril)]; Janssen [Heart failure]; Mast [Heart failure]. Equity Ownership/Stock Options: Cardioxyl [Heart
failure]. Warren J Manning, MDGrant/Research/Clinical Trial Support: Philips Medical Systems [Cardiac MR
(Imaging equipment)]. Equity Ownership/Stock Options: Pfizer (Pharmaceuticals). Equity Ownership/Stock Options
(Spouse): General Electric (Imaging equipment). Brian C Downey, MD, FACCEmployee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed
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All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Feb 2015. | This topic last updated: Jun 06, 2014.
INTRODUCTION Impaired left ventricular (LV) systolic function in patients with coronary heart
disease is often a partially reversible process (table 1). As an example, left ventricular function may
improve markedly, and even normalize, in subsets of patients following successful revascularization
(figure 1) [1-3].
Since many studies have established a relation between LV systolic function and cardiovascular
prognosis, it is reasonable to speculate that improved LV systolic function following
revascularization would be associated with a favorable effect on outcome. The superiority of
revascularization compared to medical management in selected patients with coronary disease and
LV dysfunction is compatible with this hypothesis [4,5]. The myocardium that recovers function after
revascularization has been called "hibernating." To the extent that improvement in regional or global
LV systolic function is a significant goal in such patients, the ability to accurately assess regional
myocardial viability in a dysfunctional territory prior to revascularization becomes an important
component of the decision making process (table 2 and algorithm 1 and algorithm 2).
(See "Diagnosis and management of ischemic cardiomyopathy", section on
'Revascularization' and "Clinical syndromes of stunned or hibernating myocardium".)
Dobutamine stress echocardiography has emerged as an important noninvasive clinical tool for the
detection of hibernating myocardium [6,7]. The role of dobutamine stress echocardiography in the
evaluation of myocardial viability in the setting of hibernation will be reviewed here. The use of other
modalities in conjunction with dobutamine stress, such as Doppler studies, the relative efficacy of
other imaging modalities (eg, radionuclide imaging, magnetic resonance imaging) for the detection
of hibernating myocardium, and protocols for dobutamine stress echocardiography are discussed
separately. (See "Evaluation of hibernating myocardium" and "Overview of stress
echocardiography", section on 'Dobutamine stress echocardiography'.)
DOBUTAMINE STRESS ECHOCARDIOGRAPHY Pharmacologic stress echocardiography
examines the "inotropic reserve" of dysfunctional but viable myocardium at rest by the

administration of an inotropic agent, with dobutaminebeing the most frequently used agent. Viable
myocardium shows improved global or regional contractile function (inotropic reserve), as assessed
by simultaneous transthoracic echocardiography, in response to inotrope administration [8]. The
prevalence of contractile reserve in patients with CHD and LV dysfunction is independent of the
angiographic extent and severity of coronary artery disease, and the improvement in contractility in
hypoperfused viable myocardium does not require an increase in regional myocardial perfusion
[9,10].
A contractile response to dobutamine appears to require that at least 50 percent of the myocytes in
a given segment are viable; the contractile response also correlates inversely with the extent of
interstitial fibrosis on myocardial biopsy [11]. In comparison, radionuclide myocardial perfusion
imaging identifies segments with fewer viable myocytes. In one series, for example, dobutamine
stress echocardiography and thallium imaging showed equivalent sensitivity among segments with
more than 75 percent viable myocytes (78 versus 87 percent) but dobutamine stress
echocardiography was much less sensitive among segments with 25 to 50 percent viable myocytes
(15 versus 82 percent) [12].
The predictive value of dobutamine stress echocardiography appears to be greatest when there is a
biphasic response: improvement at low dose and worsening at high-dose dobutamine [13,14]. The
initial improvement in wall motion reflects recruitment of contractile reserve during low-dose
dobutamine, and hence reflects viability [15]. In comparison, higher doses lead to subendocardial
ischemia and worsening of the wall motion abnormality, identifying stress-induced ischemia. Thus,
testing at various doses appears to be important for the optimal assessment of myocardial
hibernation by this technique.
The concurrent use of beta blockers at the time of the dobutamine stress echocardiogram can affect
the response to dobutamine and reduce the number of viable segments detected [16]. If a study
during beta blocker therapy shows only limited viability, it may be useful to repeat the test after the
dose has been reduced. (See "Overview of stress echocardiography", section on 'Dobutamine
stress echocardiography'.)
Improvement in LV function after CABG Dobutamine stress echocardiography can be used to
identify hibernating myocardium prior to coronary artery bypass graft (CABG) surgery. Several
studies have shown that it can be used to predict the likelihood of recovery after CABG [13,17,18]:
Among 18 patients with coronary disease and LV systolic dysfunction who underwent twodimensional echocardiography at rest and during dobutamine infusion, 61 percent of
dysfunctional segments with inotropic reserve showed improved regional systolic function after
CABG [17]. The positive and negative predictive accuracy of dobutamine infusion for
predicting functional improvement of dysfunctional segments after CABG was 91 and 82
percent, respectively.
Among 61 patients who underwent serial dobutamine stress echocardiography and
radionuclide ventriculography prior to CABG, a biphasic response (improvement at low dose
and worsening at high dose dobutamine) was highly predictive of recovery, especially in
segments with the most severe wall motion abnormalities at baseline [13]. Other patterns of
dobutamine responsiveness were predictors of non-recovery (figure 2).
In a series of 133 patients, those with the largest amount of dysfunctional but viable
myocardium, defined as 6 segments improving with low-dose dobutamine, had the greatest

functional improvement in left ventricular ejection fraction after surgical revascularization and a
lower rate of cardiac events during a 20 month follow-up [18].
While a biphasic response to dobutamine is predictive of mechanical recovery after CABG, the
amount of dysfunctional but viable myocardium may be a better predictor of long term outcome.
This was suggested by a study of 95 patients in whom multiple indices of viability were measured
by dobutamine stress echocardiography prior to CABG [19]. After a five year follow up, the amount
of dysfunctional but viable myocardium, as assessed by wall motion score during low dose
dobutamine, was the most important independent predictor of survival (hazard ratio [HR] 6.7, 95%
CI 2.8 to 15.8). A biphasic response to dobutamine, while significant on multivariable analysis, was
less important.
The predictive value of dobutamine stress echocardiography is similar to that of positron emission
tomography (PET) scanning (figure 3) [20]. The accuracy is less, however, when there is a totally
occluded coronary artery [21]. (See"Evaluation of hibernating myocardium", section on 'Efficacy of
imaging tests'.)
Improvement in LV systolic function after percutaneous revascularization The accuracy
of dobutamine stress echocardiography for predicting recovery of LV function after percutaneous
revascularization in patients with stable coronary disease and LV dysfunction has also been
evaluated.
In a study of 20 patients undergoing dobutamine stress echocardiography, the accurate
prediction of recoverability of contractile function depended upon the type of wall motion
response observed during dobutamine [14].The greatest improvement in LV systolic function
was seen in patients with a biphasic response to dobutamine, with less improvement in
patients with either no change or sustained improvement after dobutamine.
The administration of nitroglycerin may improve the accuracy of dobutamine stress
echocardiography in detecting viable myocardium. In an animal model, nitroglycerin enhanced
the improvement with low dose dobutamine but did not prevent high dose dobutamine from
inducing ischemia in hibernating myocardium [22]. The clinical efficacy of nitroglycerindobutamine echocardiography was evaluated in a study of 32 patients in whom 309 of 512
myocardial segments were akinetic or dyskinetic [23]. In terms of improved contractility after
revascularization, nitroglycerin-dobutamine echocardiography had a lower sensitivity than restredistribution thallium and myocardial contrast echocardiography (63 versus 95 and 87
percent, respectively), but was the most specific (83 versus 37 and 48 percent). Nitroglycerin
alone increased regional thickening in 20 percent of viable akinetic segments, suggesting that
it may be a useful addition to dobutamine stimulation.
Improvement in survival after revascularization Patients with left ventricular systolic
dysfunction who demonstrate myocardial viability with dobutamine stress echocardiography have a
better outcome with revascularization than with medical therapy [15,24,25].
In a study of 318 patients with coronary heart disease and a left ventricular ejection fraction
35 percent, those with myocardial viability (as determined by dobutamine stress
echocardiography) had a lower mortality at 18 months when treated with coronary artery
bypass graft (CABG) surgery compared to those with viability who were treated medically or
those without viability who underwent CABG (6 versus 20 and 17 percent, respectively) [24].

The results of dobutamine stress echocardiography can also predict long-term outcome
[15,25]. In a study of 87 patients with heart failure due to an ischemic cardiomyopathy who
were followed for 40 months, cardiac mortality in patients with at least 5 (out of 12) segments
showing myocardial viability who underwent CABG was 3 percent, with associated
improvement in functional class and left ventricular ejection fraction [25]. In contrast, cardiac
mortality was 31, 50, and 44 percent in those with myocardial viability in at least 5 segments
who were treated medically and in those with less than 5 segments showing myocardial
viability who underwent revascularization or medical therapy, respectively.
Similar mortality benefits have been reported with all of the major imaging techniques for the
detection of myocardial viability. In a meta-analysis of 24 viability studies (with viability determined
by dobutamine echocardiography, thallium perfusion imaging, or positron emission tomography
(PET) scanning) involving 3088 patients with coronary artery disease and left ventricular
dysfunction, myocardial viability was present in 42 percent [26]. The patients with myocardial
viability had an 80 percent reduction in annual mortality with revascularization (3.2 versus 16
percent with medical therapy). In contrast, there was no difference in annual mortality with
revascularization in patients without myocardial viability (annual mortality 7.7 versus 6.2 percent
with medical therapy).
A similar difference in mortality was noted in another review in which annual mortality was reduced
after revascularization only in patients with myocardial viability (7 versus 20 percent with medical
therapy) [27]. (See"Diagnosis and management of ischemic cardiomyopathy", section on
'Revascularization'.)
Use after MI Dobutamine stress echocardiography is also useful for establishing the presence of
hibernating myocardium due to a residual stenosis following a myocardial infarction (MI). In one
series of 232 patients undergoing a dobutamine-atropine stress echocardiography within one week
after MI, the presence of either an ischemic or a biphasic response in two or more contiguous
infarction zones was both sensitive (82 percent) and specific (80 percent) for a residual stenosis
and had a predictive accuracy of 82 percent [28]. Sensitivity was greatest when a biphasic response
was observed. In another study sustained improvement with high dose dobutamine was the most
specific predictor (100 percent) for the absence of significant residual stenosis [29].
Dobutamine stress echocardiography is also of use for predicting recovery and the extent of
irreversibly damaged myocardium after direct angioplasty in patients with an acute MI [30]. Its
predictive value for improvement is higher for hypokinetic than akinetic segments. Recovery of rest
regional LV contraction usually occurs quickly after revascularization, although one-quarter of
patients require up to six weeks [31]. Patients who recover rest function after angioplasty show the
most marked improvement with dobutamine; however, some improvement may be seen in those
without recovery of rest function, particularly when there was evidence of ischemia before
revascularization.
Although dobutamine stress echocardiography is useful for predicting recovery, dysfunctional but
viable segments may show less improvement in basal contractility after revascularization than
predicted. As an example, one study performed dobutamine stress echocardiography more than
three months after CABG [32]. Most infarct zones which showed contractile reserve before surgery
but which failed to recover after surgery had the same or greater contractile reserve with

dobutamine; some contractile reserve was present even in those infarct zones that showed no
reserve preoperatively [32].
Use in LV dysfunction after MI Dobutamine stress echocardiography after a myocardial
infarction (MI) can identify residual, ischemic viable myocardium which can act as a substrate for
further events.
In one study of 138 patients with left ventricular (LV) dysfunction following MI, the presence
of myocardial viability was the only independent predictor of recurrent ischemic events (20
versus 7 percent without viable myocardium) [33]. However, viability in the absence of
underlying ischemia may be protective in patients with global LV dysfunction after MI in whom
the recovery of LV function can offset the risk of ischemia.
In another study evaluating 314 patients with moderate to severe resting LV dysfunction after
an MI, the presence and extent of viability was associated with a lower mortality at 9 months
(1.9 versus 5.5 percent for no viability) [34]. In patients with a greater number of segments
showing improvement, there was a larger impact of viability on survival. In contrast, the
presence of inducible ischemia was the best predictor of cardiac death.
Use in the elderly Dobutamine stress echocardiography can be used safely in elderly patients to
evaluate chest pain. In 550 octogenarians evaluated for chest pain, DSE was safe, predicted the
risk of cardiac events over the subsequent two years, and identified a subset at high risk of a
cardiac event [35].
Comparison with perfusion imaging Direct comparisons between nuclear imaging techniques
and dobutaminestress echocardiography are limited. However, when used for the assessment of
myocardial viability and hibernating myocardium, dobutamine stress echocardiography has both a
high negative predictive value as well as a high positive predictive value (figure 4). (See "Evaluation
of hibernating myocardium", section on 'Pooled analysis of rMPI and DE studies'.)
Comparison with CMR Late gadolinium enhancement cardiovascular magnetic resonance
imaging (CMR) can accurately discriminate nonviable from viable myocardial segments. However,
the accuracy of low-dose dobutamineCMR and low-dose dobutamine echocardiography is not
known as they have not been directly compared. However, in a comparative study using high-dose
dobutamine stress echocardiography and dobutamine CMR, CMR had a higher sensitivity and
specificity for detection of viable segments. This was primarily related to nonvisualization of
segments on surface echocardiography. Comparison of late gadolinium enhancement CMR versus
low dose dobutamine stress CMR suggests that low dose dobutamine CMR is superior, primarily
related to improved accuracy for patients with intermediate late gadolinium enhancement pattern.
(See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Myocardial
viability'.)
Role in idiopathic dilated cardiomyopathy Dobutamine stress echocardiography is useful for
establishing the prognosis of patients with an idiopathic dilated cardiomyopathy, as an improvement
in left ventricular contractility (ejection fraction or wall motion score) predicts a lower incidence of
cardiac death or need for transplantation [36,37].
In one of the largest prospective studies, dobutamine stress echocardiography was performed using
high-dose dobutamine (up to 40 g/kg per min) in 184 patients with a left ventricular ejection
fraction less than 30 percent [36]. After a 15 month follow-up, patients with a large inotropic

response to dobutamine (defined as a change in wall motion score index 0.44) had a significantly
better survival (94 versus 69 percent for a small or no response to dobutamine). A large change in
wall motion score index was an independent predictor of outcome on multivariate analysis.
(See"Predictors of survival in heart failure due to systolic dysfunction".)
ENOXIMONE STRESS ECHOCARDIOGRAPHY Dobutamine stress echocardiography is widely
used to assess myocardial viability, but the inotropic response to adrenergic stimulation may be
attenuated in patients receiving a beta blocker. In addition, dobutamine may sometimes induce
ischemia in patients with a critical coronary stenosis, which might mask hibernation by preventing
the improvement in wall motion.
An alternative approach is the use of a phosphodiesterase inhibitor such as enoximone
or milrinone, drugs which have been used for inotropic support in the treatment of heart failure.
These drugs are relatively unaffected by concurrent use of a beta blocker. (See "Overview of the
therapy of heart failure due to systolic dysfunction".)
The possible role of enoximone stress echocardiography was evaluated in one study of 45 patients
with chronic coronary artery disease and left ventricular dysfunction who underwent
echocardiography with both dobutamine and enoximone [38]. Both increased heart rate, but
enoximone did not cause a change in systolic blood pressure. Concordant results were seen in 85
percent of affected segments, but enoximone had a higher sensitivity (88 versus 79 percent for
dobutamine) and negative predictive value (90 versus 84 percent) in predicting functional recovery
after revascularization. Specificity and positive predictive value were similar between enoximone
and dobutamine.
While enoximone is not approved for use in the United States, the pharmacology of milrinone is
very similar, and this agent could be considered for use as a pharmacologic stress agent in selected
patients on beta blockers. Given the limited data, however, we feel that further investigations are
required to validate this approach.
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SUMMARY
Dobutamine stress echocardiography is an important noninvasive clinical tool for the
detection of viable "hibernating" myocardium, or myocardium that recovers systolic function
after revascularization. Viable myocardium shows improved global (ejection fraction) or

regional contractile function (inotropic reserve) in response to inotrope administration.

(See 'Dobutamine stress echocardiography' above.)
When performed on patients with ischemic heart disease and left ventricular
dysfunction, dobutamine stress echocardiography predicts the likelihood of left ventricular
functional recovery following both surgical and percutaneous revascularization. In addition, in
patients with left ventricular dysfunction post-myocardial infarction who have not undergone
revascularization, dobutamine stress echocardiography is useful for establishing the presence
of hibernating myocardium due to a residual stenosis. (See 'Improvement in LV function after
CABG'above and 'Improvement in LV systolic function after percutaneous
revascularization' above and 'Use after MI'above.)
Patients with left ventricular dysfunction who demonstrate myocardial viability
with dobutamine stress echocardiography have a better survival with revascularization than
with medical therapy. (See 'Improvement in survival after revascularization' above.)
Direct comparisons between radionuclide imaging and cardiovascular magnetic resonance
imaging techniques anddobutamine stress echocardiography in the same patients are limited.
(See 'Comparison with perfusion imaging'above and "Evaluation of hibernating myocardium",
section on 'Pooled analysis of rMPI and DE studies'.)
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