Download Dobutamine-induced augmentation of left ventricular ejection

European Heart Journal (2001) 22, 849–856
doi:10.1053/euhj.2001.2654, available online at http://www.idealibrary.com on
Dobutamine-induced augmentation of left ventricular
ejection fraction predicts survival of heart failure
patients with severe non-ischaemic cardiomyopathy
T. M. Ramahi1, M. D. Longo2, A. R. Cadariu1, K. Rohlfs1, M. Slade1, S. Carolan1,
E. Vallejo1 and F. J. Th Wackers1
1
Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, U.S.A.; 2Division of Cardiology,
University of Turin, Molinette Hospital, Turin, Italy
Aims The prognosis of patients with severe non-ischaemic
dilated cardiomyopathy is variable. The predictive value of
currently utilized tests is suboptimal. The purpose of this
study was to determine the prognostic value of dobutamineinduced augmentation of left ventricular ejection fraction in
patients with non-ischaemic dilated cardiomyopathy.
Methods and Results Sixty-two patients with left ventricular ejection fraction c0·30 underwent exercise testing
with gas exchange analysis and assessment of left ventricular ejection fraction at rest and after a 10-min intravenous
infusion of dobutamine at 10 g . kg 1 min 1, using equilibrium radionuclide ventriculography. Age was 4811
years, 32% females, functional class 2·60·6, resting left
ventricular ejection fraction 0·200·06, and peak exercise
oxygen consumption (mVO2) 196 ml . kg 1 min 1.
Mean dobutamine-induced augmentation of left ventricular
ejection fraction (LVEF) was 0·090·06 (median 0·08,
range 0·03 to 0·26). Follow-up was 2515 months during which there were 12 deaths and five transplantations.
Patients were divided into two groups based on median
LVEF. The transplant-free survival was better in the
Introduction
The prognosis of patients with severe non-ischaemic
dilated cardiomyopathy is variable[1]. Accurate prediction of prognosis is important for guiding therapy and
determining the appropriate timing of cardiac transplantation[2]. Although a host of clinical, haemodynamic,
ventriculographic, and neurohormonal markers have
prognostic value in large groups of patients, only few
Manuscript submitted
15 February 2001.
26
November
2000,
and
accepted
Correspondence Tarik M. Ramahi, MD, 135 College Street, Suite
301, New Haven, CT 06510-2483, U.S.A.
0195-668X/01/100849+08 $35.00/0
group with higher LVEF (94% vs 64%, P<0·008). In
multivariate analysis incorporating age, gender, duration of
chronic heart failure, functional class, right and left ventricular ejection fraction, LVEF, left ventricular enddiastolic volume index, and mVO2, only LVEF was
predictive of 1-year, 3-year, and overall transplant-free survival (RR 0·09, 0·03, and 0·13; P 0·03, 0·09, and 0·08
respectively). The linear correlation between LVEF and
mVO2 (r=0·3) and between LVEF and left ventricular
ejection fraction (r=0·5) was weak.
Conclusion Dobutamine-induced augmentation of left
ventricular ejection fraction is a strong prognostic variable,
independent of exercise capacity and resting ventriculographic variables, in severe non-ischaemic systolic dysfunctional heart failure.
(Eur Heart J 2001; 22: 849–856, doi:10.1053/euhj.2001.2654)
2001 The European Society of Cardiology
Key Words: Heart failure, cardiomyopathy, inotropic
reserve, prognosis.
have achieved widespread clinical utility. Precise prediction of the prognosis of patients with severe left ventricular systolic dysfunction therefore remains a difficult
task[3–9]. Resting left ventricular ejection fraction has a
lower prognostic value in the severe systolic dysfunction
population[10], and resting haemodynamics are dependent on the adequacy of medical therapy[11,12].
Functional capacity classification suffers from interobserver variability and bias. Exercise capacity, precisely
determined by peak-exercise oxygen consumption
(mVO2), is a reproducible and widely used prognostic
test[13,14]. Exercise performance, however, is affected by
non-cardiac factors and reflects the limitation of a highly
integrated circuit involving the heart, lungs, vessels,
skeletal and respiratory muscles, and autonomic nervous
2001 The European Society of Cardiology
850
T. M. Ramahi et al.
system[15]. The same applies to the measurement of
ventricular function and haemodynamics during
exercise[16–18]. In view of the diminishing donor pool and
the significant improvement of some non-ischaemic dilated cardiomyopathy patients with medical therapy,
further refinement in the ability to predict the prognosis
of patients with severe left ventricular systolic dysfunction is desirable.
Several observations made over the past two decades
suggest a role for contractile reserve in predicting the
prognosis of patients with left ventricular systolic
dysfunction[19–21]. The human myocardium is a predominantly -adrenergic organ in which the receptor
density and sensitivity determine the response to adrenergic stimulation[22,23]. In patients with severe left ventricular systolic dysfunction, the responsiveness of the
-adrenergic receptors is diminished as a result of
decreased density of the 1 and sensitivity of the 2
receptors[24,25]. The extent of this ‘down-regulation’ and
the consequent decrease in responsiveness to adrenergic
agents are proportional to the extent of systolic
dysfunction[26–28]. The diminished contractile response
of myopathic hearts to inotropic agents is heterogeneous[20,21,28]. Its assessment might therefore reflect
the extent of -adrenergic receptor down-regulation and
provide a clinical tool for correlating the extent of
abnormality of the -adrenergic pathways to prognosis.
The purpose of this study was to evaluate the prognostic
value of the left ventricular inotropic response to intravenous dobutamine infusion in patients with severe
chronic non-ischaemic systolic dysfunction.
Methods
Patients
The study subjects were 62 consecutive ambulatory
patients with chronic heart failure, non-ischaemic dilated cardiomyopathy, and severe left ventricular systolic dysfunction (left ventricular ejection fraction c0·30)
referred to the Yale Heart Failure Clinic for consideration of cardiac transplantation. There were 42 males
and 20 females. Mean age was 4811 years, and mean
duration of chronic heart failure was 3·43·2 years.
After stabilization on optimal medical therapy, mean
functional class, assessed by the same physician, was
2·60·6. None were on intermittent or chronic intravenous inotropic infusion therapy. All patients were in
normal sinus rhythm except for one with chronic atrial
fibrillation. Coronary artery disease was excluded by
coronary angiography. Patients who could exercise
(n=52) underwent standard symptom-limited treadmill
exercise tolerance testing using the Naughton or modified Naughton protocols[29]. Continuous respiratory gas
exchange analysis was performed using a metabolic cart
(CPX/D System, Medical Graphics Corp., St. Paul,
MN, U.S.A.). Peak exercise oxygen consumption was
Eur Heart J, Vol. 22, issue 10, May 2001
defined as the average VO2 during the last minute
of exercise. Patient characteristics are summarized
in Table 1.
Radionuclide ventriculography
All study subjects underwent gated equilibrium radionuclide angiocardiography at rest and during the last
5 min of a 15-min peripheral intravenous infusion of
dobutamine (Dobutrex, Eli Lilly & Co., Indianapolis,
IN, U.S.A.) at 10 g . kg 1 min 1. Right and left
ventricular ejection fractions were measured after
modified in vivo red blood cell labelling (25–
30 mCi Technetium-99m pertechnetate) according to
standardized techniques[30]. Data were acquired in
electrocardiographic-synchronized frame mode (16
frames/RR cycle) in 6464 computer matrix. Left
ventricular ejection fraction was computed from the left
anterior oblique image using validated and standardized
software[31]. A varying left ventricular region of interest
and a cycle-dependent background region were used.
The computer software automatically determines left
ventricular edges and background, but also allows for
operator interaction as may be necessary in patients with
intense radiotracer accumulation adjacent to the left
ventricle. Right ventricular ejection fraction was determined using the ECG-gated first pass method[32]. Left
and right ventricular ejection fractions were calculated
as end-diastolic counts minus end-systolic counts, divided by end-diastolic counts. Using this software the
lower limit of normal left ventricular ejection fraction is
0·50 and right ventricular ejection fraction 0·40. Left
ventricular end-diastolic volume was determined using
the Massardo count ratio method, by which normal
patients have a left ventricular end-diastolic volume
ranging from 100 to 150 ml[33]. It was indexed to the
body surface area.
Study end-points and data collection
The study end-point was prospectively defined as death
from any cause prior to cardiac transplantation. Study
subjects were followed at the clinic every 3–4 months.
Decision regarding candidacy for cardiac transplantation was made on the basis of clinical stability and
exercise limitation. Follow-up data were obtained for all
study subjects from clinic records and the computerized
database. Sudden death was defined as unexpected death
outside the hospital without preceding symptoms.
Statistical analysis
Data were expressed as meanstandard deviation.
Student’s t-test was used for comparison of continuous
variables, and Fisher’s exact probability test was used
for comparison of categorical variables. Probabilities of
Predicting survival of HF in severe non-ischaemic cardiomyopathy
Table 1
851
Baseline patient characteristics
Characteristic
Age
Sex (M/F)
Duration of HF† (years)
Functional class
I
II
III
IV
Medications
Loop diuretics
ACEI/ARB
Digoxin
Aldactone
Beta-blocker
Amiodarone
LVEF
LVEF
RVEF
LVEDVI (ml . m 2)
mVO2 (ml . kg 1 min 1)
All patients
n=62
Survivors*
n=45
Non-survivors
n=12
4811
32%
2·6
2·60·6
2
21
37
2
4811
33%
1·3
2·50·6
2
19
24
0
4511
42%
3·5
3·00·4
0
1
10
1
98%
95%
90%
19%
10%
5%
0·200·06
0·090·06
0·430·11
19759
196
98%
96%
87%
16%
11%
4%
0·200·05
0·090·06
0·450·10
19460
206
100%
100%
100%
42%
0
0
0·170·07
0·050·05
0·350·11
20660
172
P
0·01
ns
0·04
0·03
ns
ns
*Without transplantation.
†Median.
HF=heart failure; ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor
blocker; LVEF=left ventricular ejection fraction; LVEF=mean dobutamine-induced augmentation of left ventricular ejection fraction; RVEF=right ventricular ejection fraction; LVDVI=left
ventricular end-diastolic volume index; mVO2 =peak exercise oxygen consumption.
survival were determined using product-limit (Kaplan–
Meier) analysis. Cardiac transplantation was a censored
event. Log-rank analysis was used for comparison of
survival curves. Linear regression analysis was used to
examine the relationship between clinical and ventriculographic characteristics. Two-sided P value <0·05 was
considered statistically significant.
Univariate and multivariate analyses were performed to
determine which variables were predictive of death. The
following variables were included in the analysis: age,
gender, duration of chronic heart failure, functional class,
resting left and right ventricular ejection fractions, left
ventricular end-diastolic volume index, mVO2, and the
dobutamine-induced increase in left ventricular ejection
fraction (LVEF). Multivariate analysis was performed
using both logistic regression and Cox proportional hazards methods. In the latter, the best model was achieved
using a backward elimination procedure with a significance level of <0·05. Data were again censored for
patients alive at the end of the study and for patients who
had undergone cardiac transplantation during the study
period. All analyses were performed using PC-SAS 6.12
(SAS Institute Inc, Cary, NC, U.S.A.).
Results
Ventriculographic findings
Mean resting left ventricular ejection fraction was
0·200·06 (median 0·19, range 0·05 to 0·30) and mean
dobutamine-induced increase of left ventricular ejection
fraction (LVEF) was 0·090·06 (median 0·08, range
0·03 to 0·26). The distribution of LVEF is shown in
Fig. 1. The linear correlation between LVEF and left
ventricular ejection fraction (r=0·5, P<0·0001), and
between LVEF and mVO2 (r=0·3, P=0·03) was weak
(Fig. 2). The linear correlation between LVEF and
other variables was also weak: right ventricular ejection
fraction (r=0·3, P 0·04), left ventricular end-diastolic
volume index (r= 0·3, P=0·05), and duration of heart
failure (r= 0·03, P=0·01).
Survival and predictors of death
Mean follow-up was 2515 months, during which there
were 12 deaths and five transplantations. No patients
were lost to follow-up. Patients were divided into two
groups based on median LVEF. The transplant-free
survival was better in the group with higher LVEF at
1 year (97% vs 74% P=0·02), 2 years (97% vs 64%,
P=0·002), and at 3 years (97% vs 56%, P<0·001) (Fig. 3
and Table 2). Patients with higher inotropic response
had shorter duration of heart failure, better functional
capacity, higher left and right ventricular ejection fractions, and smaller left ventricular size. There was no
significant difference between the two groups with
regard to mVO2 (Table 2).
Both LVEF and right ventricular ejection fraction
were higher in the surviving group, but there was no
Eur Heart J, Vol. 22, issue 10, May 2001
852
T. M. Ramahi et al.
30
0·30
(a)
r = 0·5
25
0·25
20
∆LVEF
0·20
0·15
15
10
0·10
5
0·05
0
0·00
–5
0
5
10
15
20
LVEF
–0·05
(b)
Figure 1 Distribution of LVEF for 62 patients with
non-ischaemic dilated cardiomyopathy.
Discussion
This study shows that dobutamine-induced increase in
left ventricular ejection fraction is a strong independent
Eur Heart J, Vol. 22, issue 10, May 2001
30
35
30
Number of patients
r = 0·3
25
20
∆LVEF
significant difference in left ventricular ejection fraction,
left ventricular end-diastolic volume index, and mVO2
between non-transplanted survivors and non-survivors
(Table 1). The difference in LVEF between survivors
and non-survivors was most pronounced in the group
of patients with left ventricular ejection fraction lower
than the median (LVEF 0·070·04 vs 0·030·02
P=0·008). By univariate analysis, the following variables were correlated to mortality at 1 year, 3 years, and
for the entire study duration: LVEF, functional class,
right ventricular ejection fraction, and left ventricular
ejection fraction (Table 3).
In the logistic regression multivariate analysis model,
only LVEF was predictive of both 1 and 3-year
transplant-free survival (RR=0·09, 95% CI=0·01–0·79,
P=0·03, and RR=0·03, 95% CI=0·002–0·42, P=0·009,
respectively) (Table 3A). Using Cox proportional
hazards analysis, the following four variables were
related to mortality: LVEF, functional class, right
ventricular ejection fraction, and left ventricular ejection
fraction. In the backward elimination model only
LVEF was an independent predictor of overall
transplant-free survival (RR=0·13, 95% CI=0·03–0·058,
P=0·008) (Table 3B).
Of the 12 patients who died prior to transplantation,
six patients died suddenly and six died of progressive
heart failure. The latter group tended to have lower
LVEF (0·030·02 vs 0·080·06, P=0·08) with both
left ventricular ejection fraction and LVEF below the
median.
25
15
10
5
0
–5
5
10
15
20
mVO2
25
30
35
Figure 2 Correlation between LVEF and left ventricular ejection fraction, and between LVEF and mVO2.
predictor of survival of patients with severe nonischaemic left ventricular systolic dysfunction. Patients
with LVEF >0·08 had excellent 1-year and overall
survival probabilities. The prognostic value of LVEF is
independent of left ventricular ejection fraction and
mVO2, the two most commonly utilized predictors of
mortality. It was apparent at 1 year, and as such it
provides additional prognostic information that might
help determine the appropriate time of listing for cardiac
transplantation, especially in patients with severely
depressed left ventricular ejection fraction.
Higher response to dobutamine identifies healthier
patients, characterized by better functional capacity,
shorter duration of chronic heart failure, higher left
and right ventricular ejection fractions, and smaller
Predicting survival of HF in severe non-ischaemic cardiomyopathy
1·0
∆LVEF ≥ 0·08
0·9
0·8
Surviving
0·7
0·6
∆LVEF < 0·08
0·5
0·4
0·3
0·2
0·1
0
5
10
15
20
Interval
25
30
35
Figure 3 Cumulative transplant-free survival based on
LVEF. Group 1, LVEF d0·08, n=34; group 2,
LVEF <0·08, n=28; P<0·008.
ventricles (Table 2). Non-survivors had significantly
lower inotropic reserve (Table 1), particularly in the
group of patients with left ventricular ejection fraction
below the median value (LVEF 0·030·02 vs
0·070·04, P=0·008). Furthermore, patients who died
suddenly tended to have higher inotropic reserve
(LVEF 0·080·06 vs 0·030·02, P=0·08), whereas all
853
patients who died of progressive heart failure had low
left ventricular ejection fraction and low LVEF. This
suggests that low inotropic reserve might be a strong
predictor of death from progressive pump failure especially in patients with very low left ventricular ejection
fraction.
The absence of strong linear correlation between
LVEF and resting left ventricular ejection fraction and
between LVEF and mVO2 supports an independent
and additive prognostic role for inotropic reserve. The
lack of a strong correlation with exercise capacity is
probably due to the non-cardiac limitations to maximal
exercise. Adrenergic inotropic reserve, as defined in this
study, is a measure of myocardial contractile response to
circulating catecholamines, which in some ways simulates the effect of exercise on cardiac function. It might
bridge the prognostic discrepancy between resting left
ventricular ejection fraction and mVO2, two weakly
inter-correlated prognostic tests. The addition of
LVEF to a prognostic model incorporating left ventricular ejection fraction and mVO2 might therefore
further refine the ability to predict the survival of severe
non-ischaemic dilated cardiomyopathy patients.
Previous studies
The results of this study are in agreement with earlier
studies that suggested a prognostic role for the increase
in peak ventricular power and peak positive left ventricular dp/dt in response to dobutamine infusion[20,21].
Table 2 Baseline clinical and ventriculographic characteristics of patients with low
vs high response to dobutamine
Number
Age (years)
Females
Functional class*
Duration of CHF† (years)
LVEF
LVEF
RVEF
LVEDVI (ml . m 2)
mVO2 (ml . kg 1 . min 1)
Medications
Loop diuretics
ACEI/ARB
Digoxin
Aldactone
Beta-blocker
Amiodarone
Survival
1 year
2 year
3 year
LVEF <0·08
LVEF d0·08
28
4811
21%
2·90·5
3·5
0·180·06
0·040·03
0·360·11
21551
186
34
4811
41%
2·40·6
1·3
0·210·05
0·120·05
0·480·09
18261
206
0·04
<0·001
<0·001
0·03
ns
100%
93%
93%
25%
11%
4%
97%
97%
88%
15%
9%
6%
ns
ns
ns
ns
ns
ns
74%
64%
56%
97%
97%
97%
0·02
0·002
<0·001
P value
ns
ns
<0·001
*NYHA classification.
†Median.
For explanation of abbreviations see Table 1.
Eur Heart J, Vol. 22, issue 10, May 2001
854
T. M. Ramahi et al.
Table 3A
Univariate and multivariate predictors of death by logistic regression
1 year
RR*
Univariate
LVEF
FC
RVEF
LVEF
LVEDVI
mVO2
Duration of CHF
Gender
Age
Multivariate
LVEF
0·09
11·1
0·11
0·87
1·00
0·89
1·00
1·5
1·0
3 years
CI†
P
RR*
CI†
P
(0·01–0·79)
(1·25–97·8)
(0·01–0·92)
(0·75–1·01)
(0·99–1·02)
(0·75–1·06)
(0·98–1·02)
(0·28–8·2)
(0·90–1·02)
0·03
0·03
0·04
0·06
ns
0·19
ns
ns
ns
0·56
11·5
0·07
0·87
1·0
0·90
1·0
0·5
0·96
(0·01–0·46)
(1·5–91·5)
(0·01–0·54)
(0·76–0·99)
(1·00–1·02)
(0·77–1·04)
(1·0–1·03)
(0·13–1·9)
(0·91–1·02)
0·008
0·02
0·01
0·04
ns
0·16
ns
ns
ns
0·03
0·03
(0·002–0·4)
0·009
0·09 (0·01–0·79)
*Relative risk.
†95% confidence interval.
For explanation of abbreviations see Table 1.
Table 3B Predictors of death by proportional hazards
regression
LVEF‡
FC
RVEF
LVEF
LVEDVI
mVO2
Duration of CHF
Gender
Age
RR*
CI†
P
0·13
5·7
0·15
0·88
1·0
0·89
1·0
0·6
0·98
(0·03–0·58)
(1·5–21·9)
(0·03–0·70)
(0·79–0·99)
(0·99–1·01)
(0·79–1·02)
(0·99–1·02)
(0·18–1·98)
(0·93–1·03)
0·008
0·01
0·02
0·03
ns
0·08
ns
ns
ns
*Adjusted relative risk.
†95% confidence interval.
‡The only independent predictor in best model.
For explanation of abbreviations see Table 1.
They are also consistent with those of a recent echocardiographic study that suggested a prognostic role for a
dobutamine-induced decrease in the left ventricular end
systolic volume index in non-ischaemic dilated cardiomyopathy patients[34]. Neither this study nor previous
studies measured true myocardial contractile reserve, an
entity that is difficult to define. Instead, they measured
the contractile response to the stimulation of the myocardial adrenergic receptors, a parameter that should
perhaps be more precisely defined as adrenergic
inotropic reserve. It provides valuable prognostic information even if it were not a true measure of myocardial
contractile reserve. Unlike earlier studies, this study
examined a well-defined cohort with chronic stable heart
failure and severe left ventricular systolic dysfunction in
the absence of coronary artery disease. Previous studies
examined patients with acute and chronic heart failure
of ischaemic and non-ischaemic causes, utilizing intracoronary dobutamine infusion and invasively obtained
measures of contractile response[20,21]. Although intracoronary infusion of dobutamine is a more precise
Eur Heart J, Vol. 22, issue 10, May 2001
method for the assessment of inotropic reserve (it minimizes peripheral effects of dobutamine on cardiac loading), intravenous dobutamine infusion is less invasive,
safer, and clinically practicable. The dose of dobutamine
used in this study was chosen based on previous experience. It was intended to maximize the inotropic response
while minimizing the chronotropic response, the risk of
arrhythmia, and the peripheral effects of dobutamine.
Infusion duration of 10 min prior to repeat imaging
allows for the attainment of steady state. Unlike previous studies, the use of gated equilibrium radionuclide
ventriculography provides a consistent and reproducible
measurement of the left ventricular ejection fraction.
Finally, this is the first study to examine transplant-free
survival as the endpoint.
Exercise capacity
In contrast to previous studies, mVO2 was not an
independent predictor of death in this cohort. This may
be due in part to non-cardiac limitations to exercise.
Another reason is the use of mVO2 as a criterion for
selecting patients for cardiac transplantation, an event
that was censored in the survival analysis, thereby
removing patients with low mVO2. Although the study
subjects had severe left ventricular systolic dysfunction
(mean left ventricular ejection fraction=0·20) and a first
year mortality of 14%, their mean mVO2, obtained with
treadmill exercise, was higher than that reported for
comparable patients in other series. This is a consistent
finding for optimally treated patients in our laboratory.
Beta-blocker therapy
Only six of the study subjects were on beta-blocker
therapy at the start of the study. They were equally
distributed, 11% of the low augmentation group and 9%
Predicting survival of HF in severe non-ischaemic cardiomyopathy
of the high augmentation group (Tables 1 and 2). As
such, use of beta-blockade at baseline cannot be considered a confounder since it applied to the two groups
equally. Although it might theoretically complicate the
interpretation of the results, exclusion of these six
patients from the analysis provides similar results. These
patients might have had a blunted LVEF response to
dobutamine (median LVEF=7, lower than that of the
entire cohort), yet none of them died during follow-up.
This probably diminished the predictive value of
LVEF noted in this study.
Half of the study subjects were started on betablockers during the follow-up period. The criteria used
for initiation of beta-blockers were purely clinical,
based on stability, functional class, and tolerability.
As expected, patients with milder disease were more
frequently treated with beta-blockers. These patients
tended to have a higher baseline left ventricular ejection
fraction, right ventricular ejection fraction, mVO2, and
lower functional class. As shown in this study, these
healthier patients also tend to have higher baseline
LVEF (Table 2). This explains why use of betablockers tended to be higher in the high augmentation
group (58%, n=34 vs 39%, n=28, P=0·20). Since these
healthier patients have better survival and since betablocker therapy improves survival, it is not therefore
surprising that surviving patients had higher use of
beta-blockers (60%, n=45 vs 25%, n=12, P=0·07). This
raises the question of whether there is an interaction
between higher augmentation and use of beta-blockers.
Namely whether higher augmentation also predicts the
tolerability and survival benefit of beta-blockers. Due to
the relatively small sample size, it would be difficult to
control for this possible modifying effect of beta-blocker
therapy. Nevertheless, whether use of beta-blockers is a
modifier, it still does not detract from the ability of
baseline dobutamine-induced augmentation of left ventricular ejection fraction to predict the probability of
death, regardless of what therapy is used thereafter. The
increasing treatment of chronic heart failure patients
with beta-blockers, however, might diminish the prognostic role of inotropic reserve assessment. For betablocker treated patients, assessment of inotropic reserve
with phosphodiesterase inhibitors might provide additional prognostic information.
Patients with ischaemic cardiomyopathy
This study aimed to examine the prognostic value of
adrenergic inotropic reserve. The exclusion of patients
with coronary artery disease eliminated the complicating
effect of myocardial ischaemia and prior infarction. The
concept probably applies to patients with ischaemic
cardiomyopathy. The issue would be complicated, however, by the presence and extent of coronary artery
disease and old myocardial infarction. The viable dysfunctional myocardium has the same down-regulation
of adrenergic receptors and variably diminished inotropic reserve. The response of the entire ventricle to
855
adrenergic agents, however, depends on the extent of
infarcted myocardium and the presence of haemodynamically important coronary artery disease. If there is
extensive ischaemic burden, adrenergic stimulation
might increase oxygen demand and worsen ischaemia.
This might blunt the contractile response or even
diminish the ejection fraction, rendering the assessment
of inotropic reserve imprecise. It might still, nevertheless, be of prognostic value, reflecting the ischaemic and
infarct burdens in addition to inotropic reserve[19,35,36].
Conclusions
In severe non-ischaemic dilated cardiomyopathy,
dobutamine-induced augmentation of left ventricular
ejection fraction is a strong predictor of mortality,
independent of left and right ventricular ejection fractions and exercise capacity. Its prognostic value is
strongest in the very low left ventricular ejection fraction
population and is apparent at 1 year. It might therefore
be helpful in determining the appropriate timing of
listing for cardiac transplantation.
References
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[2] Keogh AM, Freund J, Baron DW, Hickie JB. Timing of
cardiac transplantation in idiopathic dilated cardiomyopathy.
Am J Cardiol 1988; 61: 418–22.
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