Regional wall motion analysis by dobutamine stress echocardiography to distinguish between ischemic and nonischemic dilated cardiomyopathy

Cardiomyopathy

Regional wall motion analysis by dobutamine stress echocardiography to distinguish between ischemic and nonischemic dilated cardiomyopathy Carlo Vigna, MD, Aldo Russo, MD, Vincenzo De Rito, MD, Gian Piero Perna, MD, Marco Testa, MD, Antonella Lombardo, MD, a Pompeo Lanna, MD, Tommaso Langialonga, MD, Mauro Pellegrino Salvatori, MD, Raffaele Fanelli, MD, and Francesco Loperfido, MD a San Giovanni Rotondo and Rome, Italy To distinguish between ischemic and nonischemic dilated cardiomyopathy (DCM), we studied 43 patients with left ventricular dysfunction (15 ischemic and 28 nonischemic detected by coronary angiography) by dobutamine stress echocardiography. At rest, there were more normal segments (p<0.001) and a trend toward more akinetic segments (p, not significant) per ischemic than per nonischemic DCM patient. However, either at rest or with low-dose dobutamine, individual data largely overlapped. At peak dose, in ischemic DCM, regional contraction worsened in many normal or dyssynergic regions at rest (in the latter case after improvement with low-dose dobutamine); in contrast, in nonischemic DCM, further mild improvement was observed in a variable number of left ventricular areas. Thus with peak-dose dobutamine, more akinetic and less normal segments were present per ischemic than per nonischemic ~)CM patient (both, p < 0.001). A value of six or more akinetic segments was 80% sensitive and 96% specific for ischemic DCM. Our data show that analysis of regional contraction by dobutamine stress echocardiography can distinguish between ischemic and nonischemic DCM. (AM HEART J 1996; "!31:537-43.)

Differentiating between an ischemic and a nonischemic cause has important implications in dilated cardiomyopathy (DCM), 1, 2 but it may be difficult to distinguish between them clinically. An ischemic cause is probable in patients with a history of myo-

From the Department of Cardiology, "Casa Sonievo della Sofferenza" Hospital, Instituto Ricovero Cura Carattere Scientifico, San Giovanni Rotondo, and the ~Institute of Cardiology, Catholic University, Rome. Received for publication Feb. 22, 1995; accepted July 21, 1995. Reprint requests: Francesco Loperfido, MD, Istituto di Cardiologia, Universith Cattolica "Sacro Cuore," Policlinico A. Gemelli, Largo Gemelli 8, 00136 Rome, Italy. Copyright © 1996 by Mosby-Year Book, Inc. 0002-8703/96/$5.00 + 0 4/1/685~/0

cardial infarction (MI) or left ventricular (LV) aneurysm.3, 4 However, some patients with ischemic DCM have neither history nor electrocardiographic (ECG) evidence of MI, 5 never complain of chest pain, 6 and show diffuse, rather than regional, LV hypocontractility.3, 7 Conversely, many patients with idiopathic DCM report frequent episodes of chest pain s and have ECG evidence of MI.9 Several noninvasive techniques 1°14 have been used to distinguish between the two forms of DCM, but distinction has been limited because of controversial findings. To detect coronary artery disease in patients with DCM, dobutamine stress echocardiography 15-2° has recently been used by Sharp et al.,21 who found the change in global wall motion score index (WMSI) from low dose (LD) to peak dose (PD) dobutamine to be both sensitive and specific for this diagnosis. In their study, 21 most patients had ischemic DCM and a history of MI. To our knowledge, no study has focused on the contractile response to dobutamine in nonischemic DCM. The aims of our study were to characterize regional wall motion both at rest and during the infusion of dobutamine in ischemic and nonischemic DCM and to define the role of dobutamine stress echocardiography in differentiating between ischemic and nonischemic DCM in patients with severe LV dysfunction and dilation of unknown origin (all pretest clues as to an etiologic diagnosis were excluded). METHODS Study patients. Between January 1993 and April 1994,

all patients <70 years old with DCM and without history or ECG evidence of previous MI underwent dobutamine echocardiography and coronary angiography at our insti537

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tution. To be included, patients had (1) optimal echocardiographic images, allowing analysis of endocardial shortening and wall thickening along the entire LV perimeter; (2) echocardiographic LV end-diastolic internal dimension >6.0 cm; and (3) angiographic LV ejection fraction <0.40. Patients with regional dyssynergy at rest were included. Patients were excluded if any of the following were present: (1) congestive heart failure; (2) unstable angina pectoris; (3) LV aneurysm or large tissue scarring (defined by wall thickness <5 mm and increased wall acoustic reflectance); (4) atrial fibrillation or severe ventricular arrhythmias; or (5) any other contraindications to dobutamine infusion. 22 The study was approved by our Institutional Ethics Committee, and every patient provided written informed consent. The resulting group consisted of 43 patients, 31 men and 12 women, with ages ranging from 42 to 69 years (mean 60 +- 8). All patients underwent single-plane coronary angiography. Films were qualitatively read by an experienced observer unaware of clinical and dobutamine stress findings. Patients with >70% diameter stenosis in a major epicardial coronary artery or any major branch vessel constituted the ischemic DCM group. There were 15 patients, 3 with one-vessel, 5 with two-vessel, and 7 with three-vessel disease. No patient had significant disease of the left main coronary artery, 11 h a d disease of the left anterior descending artery, 13 of the circumflex artery, and 8 of the right coronary artery. The remaining 28 patients constituted the nonischemic DCM group. Of these, 27 patients had normal coronary arteries, and 1 had a 40% stenosis in a marginal branch. Dobutamine infusion protocol. After an overnight fast, patients were studied in the morning hours 24 to 72 hours before cardiac catheterization. ~-Blocker therapy (2 patients) was interrupted 48 hours before the test, whereas nitrate levels (12 patients) and calcium antagonist levels (6 patients) were not taken on the morning of the test. Treatment with digitalis glycosides, diuretics, or converting enzyme inhibitors was continued. After baseline echocardiographic images were recorded, dobutamine was infused intravenously by a pump beginning with a dose of 5 pg/kg/min and then increasing by 5 ~g/kg/min every 3 minutes up to a PD of 40 pg/kg/min. Blood pressure and ECG were recorded at the beginning of each stage. Two-dimensional echocardiogram was continuously monitored, and images were recorded on videotape at baseline and during the final minute of each stage. Dobutamine infusion was discontinued when any of the following end points was reached: (1) symptoms (chest pain or dyspnea) judged unacceptable; (2) >-20 mm Hg decline in systolic blood pressure with respect to baseline; (3) systolic blood pressure >220 mm Hg or diastolic blood pressure >110 mm Hg; (4) complex ventricular arrhythmias; (5) atrial fibrillation; (6) ->2 mm ST segment depression; (7) new dyssynergy in two or more contiguous LV segments; (8) achievement of 85% of the age-predicted maximal heart rate; and (9) maximal dose of 40 ~g/kg/min. In the case of discontinuation of dobutamine infusion, the maximal dosage of dobutamine was noted.

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Dobutamine stress ECG. Continuous ECG monitoring was performed with a standard 12-lead system. Ischemic changes were defined as development of >-1 mm ST segment depression in a previously normal lead or >-2 mm ST segment depression in a lead with baseline ST segment abnormalities. Stress ECG changes in patients with left bundle branch block or receiving digitalis treatment were considered nondiagnostic. Dobutamine stress echocardiography. After the patient was placed in the left lateral position, two-dimensional echocardiograms were obtained with a Acuson 128 XP/5 system (MountainView, Calif.) providedwith a 2,0/2.5 MHz electronic sector transducer. Four views (parasternal long-axis, parasternal short-axis at the papillary muscle level, apical four-chamber, and two-chamber) were recorded at rest, at each stage of dobutamine infusion, and 5 minutes after termination of infusion. All studies were video-recorded and subsequently interpreted in a blinded manner by two investigators who had no knowledge of the clinical history and angiographic data. In the case of disagreement between the two observers, a third investigator reviewed the data, and a majority decision was achieved. LV and right ventricular end-diastolic diameters in the short-axis view23 were measured. LV ejection fraction was computed at baseline as the mean from the four-chamber and the two-chamber apical view values, by using the area-length method. The left ventricle was divided into 16 segments, according to the recommendations of the American Society of Echocardiography.24 For each segment, wall motion (systolic thickening and endocardial shortening) was qualitatively analyzed at rest, LD (10 ~g/kg/min), and PD dobutamine. In patients with left bundle branch block, showing at rest the characteristic abnormality of ventricular septal contraction, only systolic thickening was considered. To avoid the difficulty of distinguishing between different degrees of dyssynergy in the dilated hypocontractile left ventricle, LV segments were categorized according to the following 3-point scale: normal (or near normal), including mildly hypokinetic segments; severely hypokinetic; and akinetic or dyskinetic. In another group of 32 patients with coronary artery disease (512 segments), we previously tested this simplified classification, finding an intraobserver and interobserver variability of 2.6% and 3.6%, respectively. To provide an index of global LV function, a conventional WMSI also was derived, by using a standard 4-point scale (1 [normal or hyperkinetic], 2 [liypokinetic], 3 [akinetic], and 4 [dyskinetic]), adding the individual segment scores, and then dividing the resulting sum by the total number of segments. Sequential wall-motion response from rest to LD, and from LD to PD dobutamine in each LV segment was classified as (1) unchanged (normal LV segments were not considered); (2) improved (in severely hypokinetic or akinetic LV segments); (3) worsened (relative to normal or severely hypoldnetic LV segments); (4) biphasic (i.e., improvement at LD dobutamine followed by worsening at PD dobutamine relative to severely hypokinetic or akinetic LV segments). Statistics. Data are given as the mean value -- SD. Unpaired t and chi-square tests were used for comparisons of

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Table I. Clinical, electrocardiographic, a n d baseline

Ischemic DCM (n = 15)

Ischemic D C M Nonischemic D C M (n = 15) (n = 28) p Value

59 ± 8 20 (71%) 17 (61%) 11 (39%) 10 (36%) 3 (11%) 6 (21%) 9 (32%)

NS NS NS NS NS NS NS NS

0.29 ± 0.06 65.6 ± 4.5

NS NS

34.5 ± 5.8

NS

13 (46%)

NS

(n) NYHA, N e w York H e a r t Association; NS, not significant.

J~umerical a n d ordinal data, respectively. I n t r a g r o u p d a t a were analyzed by analysis of variance for r e p e a t e d measures, followed by the Bonferroni t test. Statistical significance was set at two-tailed p < 0.05.

RESULTS Clinical, ECG, and baseline echocardiographic data. Pertinent data in the two groups of patients are p r e s e n t e d i n T a b l e I. N o s i g n i f i c a n t d i f f e r e n c e s i n clinical, ECG, and baseline echocardiographic data were present between the two groups, although pat i e n t s w i t h i s c h e m i c D C M t e n d e d to h a v e a g r e a t e r prevalence of chest pain, and those with nonischemic D C M t e n d e d to h a v e a l a r g e r r i g h t v e n t r i c u l a r s i z e (p, N S ) .

Dobutamine infusion: general data and side effects ( T a b l e II). N o d i f f e r e n c e s i n m e a n i n f u s e d d o s e o f d o b u t a m i n e , a c h i e v e m e n t o f m a x i m a l d o s e o f dobu t a m i n e , a n d o f 85% o f m a x i m a l p r e d i c t e d h e a r t rate, in PD dobutamine heart rate, blood pressure, and rate-pressure product, or in incidence of chest pain and ventricular arrhythmias were observed bet w e e n t h e t w o g r o u p s . N o p a t i e n t c o m p l a i n e d o f severe side effects during the test. In particular, no pat i e n t h a d t h e t e s t i n t e r r u p t e d for s e v e r e c h e s t p a i n o r for d y s p n e a . O n e p a t i e n t i n e a c h g r o u p h a d a n ischemic ECG response. Hypotension and bradycardia occurred in one patient with nonischemic DCM, who rapidly recovered without treatment. Three patients in the nonischemic DCM group showed a run of three premature ventricular contractions at PD dobutamine.

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Table II. Stress test results and side effects

echocardiographic d a t a

Mean age (_+ SD) (yr) 62 ± 8 Male sex (n) 9 (60%) NYHA class II (n) 9 (60%) NYHA class III (n) 6 (40%) Angina (n) 8 (53%) Diabetes (n) 3 (20%) Hypertension (n) 2 (13%) Left bundle branch 4 (26%) block (n) LV ejection fraction 0.28 ± 0.07 LV end-diastolic 64.9 ± 3.9 diameter (ram) Right ventricular 32.1 _+6.1 end~diastolic diameter (ram) Mitral regm-gitation 5 (33%)

al.

Nonischemic DCM (n = 28) p Value

Dobutamine dose 28.7 ± 8.6 28.1 ± 8.1 achieved (pg/kg/min) Achievement of PD 9 (60%) 16 (57%) dobutamine (n) Achievement of 85% of 10 (67%) 18 (64%) maximal predicted HR (n) Peak dose HR 126 ± 24 129 -+ 21 (beats/min) Peak dose systolic BP 140 _+ 15 136 ± 18 (ram Hg) Peak dose HR-BP 17,912 _+3,383 17,805 ± 3,892 product (beats mm Hg x 10-2) Chest pain (n) 3 (20%) 4 (14%) Dyspnea (n) 2 (13%) 4 (14%) Ischemic ST segment 1 (7%) 1 (2%) changes (n) Severe ventricular 4 (27%) 7 (25%) arrhythmias (n)

NS NS NS NS NS NS NS NS NS NS

BP, Blood pressure; HR, h e a r t rate; NS, not significant.

Table III. G r a d i n g of LV segments per p a t i e n t at stress test Baseline

Ischemic DCM (n = 15) Normal seg4.0 _+ 1.1 ments (n) Severely hypoki7.5 -+ 2.7 netic segments

LD dobutamine

PD dobutamine

5.5 -+ 1.6"

3.7 ± 1.5t

6.6 -+ 2.3

4.7 ± 2.9"t

3.9 + 2.1

7.6 ± 3.7"t

4.8 ± 1.8"

6.3 ± 1.5"t5

8.4 -+ 2.2*§

7.3 ± 2.6"~§

2.8 ± 2.2

2.4 ± 1.9"t$

(n)

Akinetic seg4.5 ± 2.5 ments (n) Nonischemic DCM (n = 28) Normal seg2.1 _+ 1.15 ments (n) Severely hypoki- 10.8 _+2.85 netic segments (n)

Akinetic segments (n)

3.0 ± 2.4

Normal segments, Those with n e a r - n o r m a l contraction. *<0.05 vs baseline. ~<0.05 vs LD dobutamine. $<0.001 vs ischemic DCM. §<0.05 vs ischemic DCM.

Dobutamine stress echocardiography R e s t . A t r e s t , g l o b a l L V f u n c t i o n w a s s e v e r e l y decreased in both ischemic and nonischemic DCM g r o u p s ( e j e c t i o n f r a c t i o n , 0.32 _+ 0.11 a n d 0.30 _+ 0.12; W M S I , 2.3 _+ 0.3 a n d 2.2 _+ 0.2, r e s p e c t i v e l y ; p, NS). D a t a r e l a t i v e to g r a d i n g o f i n d i v i d u a l s e g m e n t s

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gigna et al.

LV s e g m e n t s

Rest

LD dobutarnine

Normal

~

Severely

i~3~'~8~~~ ~71~ /

hypokinetic

Akinetic

14 ~ ,

PD dobutamine

LD dobutamine

PD dobutamine

;~-55~

~

~

~

Rest

~

37

2~00~=4~

IschemicDCM

NonischemicDCM

Fig. 1. Grading of LV segments at dobutamine stress echocardiography. N u m b e r s in squares are LV segments with different classification at each stage. N u m b e r s over arrows indicate LV segments changing grade from rest to LD and PD dobutamine.

Rest

PD Dobutamine ooe

O00

[]

•

?

Aklnetic LV segments perpatient '

_

O0

•

[]

[]

00000

[]

QO

I

00 lll~l

llLI

3

III

"

2_ i. _ i o1_

ill

000

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]

Nonischemic

DCM

l = ~

•

~lllll

QO

~11111

Ischemic

DCM

Nonischemic

DCM

Ischemic

DCM

Fig. 2. Number of akinetic LV segments per patient at rest and with PD dobutamine. All three patients with ]schemic DCM and fewer than six akinetic segments with PD dobutamine had single-vessel coronary artery disease. are shown in Fig. 1. D a t a relative to the m e a n n u m ber of s e g m e n t s with different grading per p a t i e n t are shown in Table III a n d Fig. 2. T h e e x t e n t of regional d y s s y n e r g y was significant in m o s t p a t i e n t s w i t h e i t h e r ischemic or nonischemic DCM. T h e r e were m o r e n o r m a l s e g m e n t s (4.0 _+ 1.1) and a t r e n d t o w a r d m o r e akinetic segments (4.5 +_ 2.5) per pat i e n t w i t h ischemic DCM t h a n per p a t i e n t with nonischemic DCM (2.1 _+ 1.1 [p < 0.001] a n d 3.0 ± 2.4 [p, NS], respectively). Although LV hypocontractility t e n d e d to be more h o m o g e n e o u s l y distributed in p a t i e n t s w i t h nonischemic DCM, large overlaps of individual d a t a were observed at baseline b e t w e e n the two groups, as evident in Fig. 2. L D d o b u t a m i n e . At LD dobutamine, the W M S I

d e c r e a s e d to 1.9 + 0.3 in e i t h e r group (p < 0.05 vs baseline). W i t h respect to baseline, t h e r e was a n increase in n o r m a l segments (p < 0.05) a n d a decrease in akinetic segments, e i t h e r per ischemic DCM or per nonischemic DCM p a t i e n t (p < 0.05; Fig. i a n d Table III). Also t h e r e was a decrease in severely hypokinetic s e g m e n t s per patient, which was however, significant w i t h respect to baseline only in the nonischemic DCM group (p < 0.05). P D d o b u t a m i n e . At PD dobutamine, the WMSI decreased f u r t h e r to 1.7 +_ 0.3 in the nonischemic DCM group (p < 0.05 vs LD dobutamine) b u t ret u r n e d to baseline (2.3 ± 0.3) in the ischemic DCM group (p < 0.001 b e t w e e n the two groups). However, large overlaps of the individual W M S I values were

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Table IV. Patterns of contractile response at stress test Pattern of contractile response

Unmodified(n) I m p r o v e m e n t (n)

W o r s e n i n g (n)

B i p h a s i c (n)

Ischemic DCM (n = 240)

Nonischemic DCM (11= 448)

128 (53.3%) 71 severelyhypokinetic 57 akinetic 37 (15.4%)* 35 severelyhypokinetic 2 akinetic 32 (13.3%) 12 normal 20 severelyhypokinetic 25 (10.4%) 17 severelyhypokinetic 8 akinetic

260 (58.0%) 195 severelyhypokinetic 65 akinetic 166 (37.0%)t 146 severelyhypokinetic 20 akinetic 2 (0.4%) 2 severelyhypokinetie 0

p Value

NS <0.001 <0.001 <0.001

n, Number of segments. "18 normal LV segments improving at stress test are not included. t20 normal LV segments improving at stress test are not included.

observed between the two groups. With respect to LD dobutamine, normal segments further increased in the nonischemic DCM group but decreased in the ischemic DCM group (both, p < 0.05; Fig. 1 and Table III). Akinetic segments per patient were more in the latter group (p < 0.001) (Fig. 2). At PD dobutamine, extensive regional dyssynergy (->6 akinetic segments per patient) was 80% sensirive and 96% specific for predicting associated coro~aary artery disease. All three patients with this parameter falsely negative had one-vessel coronary ar1;erydisease (one a stenosis of a large diagonal branch and two a stenosis of circumflex artery). Thus at PD dobutamine in patients with coronary artery disease, new or renewed dyssynergy was observed. On the contrary, in patients with nonischemic DCM, the improvement in regional wall motion extended also to some segments still akinetic at LD dobutamine. S e q u e n t i a l p a t t e r n o f contractile r e s p o n s e to L D a n d P D d o b u t a m i n e (Table IV). In 12 of the 15

patients with ischemic DCM, dobutamine-induced dyssynergy (isolated or preceded by improvement at LD dobutamine) developed in at least one segment during the test. More LV segments improved at increasing doses of dobutamine in the nonischemic DCM group t h a n in the ischemic DCM group. DISCUSSION

We showed t h a t in patients with LV dysfunction of unknown origin, an ischemic etiology is suggested by regional dyssynergy induced by PD dobutamine infusion. Such dyssynergy may occur in either normal or dyssynergic regions at rest (in the latter case, after improvement at LD dobutamine). In a carefully selected patient population, we confirmed t h a t dobutamine stress echocardiography can distinguish

between the two forms of DCM, but the analysis of global function (WMSI) was not so accurate as previously reported. 21 We also observed that in nonischemic DCM, the contractile response to dobutamine is characterized not by global hyperkinesia 21 but by slow and mild contractile recruitment, often restricted to a portion of the left ventricle. Other techniques. Thallium-201 scintigraphy, performed at rest, 1°, 25 after exercise, 26 and after infusion of dipyridamole, 11 has been used for differentiating between ischemic and nonischemic DCM. In most scintigraphic studies, however, the cause of DCM could frequently be presumed from clinical and ECG indicators alone. Either fixed 1°, 25, 2~ or reversible 11 perfusion defects have been found to be indicative ofischemic DCM. However, these findings have not been confirmed, 12, 27 and major diagnostic limitations have been found in the presence of left bundle branch block. ~2 More sophisticated techniques, such as positron emission tomography14 and transthoracic high-frequency coronary echocardiography, 13 have been investigated, but their use is limited by high costs and low availability. Rest dyssynergy. Rest dyssynergy may be a clue to ischemic LV dysfunction, as it is present not only in patients developing LV dilation after one or more episodes ofMI 3 but also in those with coronary artery disease and no previous MI. 3, 4 However, true aneurysms and large areas of scarring may also develop after myocarditis,2s, 29 and mild to moderate regional dyssynergy is common in primary DCM 4, 21 likely because of microcirculatory involvement and myocardial hypoperfusion.3°, 31 In our study, the baseline hypocontractility tended to be less homogeneous in patients with ischemic DCM t h a n in those with nonischemic DCM. However, large overlaps in the

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individual data were observed. Thus only the response by dyssynergic areas to dobutamine was helpful in distinguishing between the two forms of DCM. We did not specifically examine whether dobutamine stress echocardiography can separate truly necrotic from hibernating myocardium, m, 20, 32, 33 Dobutamine-induced dyssynergy. In our study, neither hemodynamic nor ECG data were useful in differentiating between ischemic and nonischemic DCM. The response to LD dobutamine was similar in the two groups, because contraction improved in most hypokinetic areas of the myocardium. However, in ischemic DCM, this improvement also extended to some akinetic segments that m a y have been hibernating myocardium, whereas other segments remained dyssynergic. At PD dobutamine in nonischemic DCM, the contraction improved further in most hypokinetic and akinetic areas of the myocardium. In contrast, in ischemic DCM, the contraction worsened in some regions that were either normal or dyssynergic at baseline but improved at LD dobutamine (hibernating myocardium?). Thus with PD dobutamine, either large (>-6 akinetic segments), new, or renewed areas of dyssynergy predicted very accurately significant coronary artery disease associated with LV dysfunction. WMSI was also found to be different in the two groups at PD dobutamine, as recently detected by Sharp et al., 21 but the individual values largely overlapped, thereby limiting its diagnostic importance. In our opinion, the use of global function scores to distinguish between ischemic and nonischemic DCM may also be influenced by the difficulties encountered in attributing scores on a standard 4-point scale to diffusely hypocontractile ventricles. The results of our study are in part different from those of Sharp et al. 21 In fact, their patients with nonischemic DCM showed a mild decrease in wallmotion score from LD to PD dobutamine, whereas those with ischemic DCM showed a variable response, with a tendency, however, toward increase. Differences i n study populations and dobutamine infusion protocols (over the dose of 10 pg/kg/min, there were increases of 5 and 10 ]~g/kg/min in our and Sharp's study, respectively) may in part explain these different results. However, our data are in complete agreement with recent data by Afridi et al., 34 who described a biphasic response to dobuta~nine in hibernating dyssynergic myocardium. In agreement with Sharp et al., 21 the small number of our patients with false-negative ischemic DCM at PD dobutamine had limited coronary artery d i s ease. 21 In such patients, the cause of the LV dysfunction frequently remained unclear even after an-

American Heart Journal

giography, because both ischemic and nonischemic factors may contribute. Extensive collateral vessels or the failure to produce a sufficient amount of stress to induce ischemia also may reduce the sensitivity of dobutamine stress testing for ischemic DCM. 21 In patients with nonischemic DCM, no hyperkinetic reaction to dobutamine was observed, in contrast with previous conjecture. 21 Rather the contractile recruitment was slow, slight, and sometimes restricted to a portion of the left ventricle. However, higher doses of dobutamine may cause global LV function to deteriorate in some patients with nonischemic DCM, probably because of an advanced degree ofmyopathic disease or a reduced coronary flow reserve. 21 Study limitations. Our study has several limitations. The number of patients was small. No LV angiographic analyses were compared to baseline echocardiographic findings. Moreover, we did not perform side-by-side comparisons on the digitized quad-screen format. An echocardiographic interpretation performed solely from videotape, as in our study, may be limited in noting subtle responses to dobutamine in patients with diffuse or severe wallmotion abnormalities. The criteria to separate ischemic and nonischemic DCM derived in this study have not yet been validated prospectively. In thinking about the response of the myocardium to dobutamine in a patient with nonischemic DCM, one would hypothesize that the more fibrotic the myocardium, the less improvement in wall motion would occur with dobutamine. Thus the longer the duration of the nonischemic DCM, the less likely one might expect the myocardial segments would be to demonstrate the behavior described. It is then possible that the duration of DCM, which could not be determined with precision in o u r two subsets of patients, somewhat influenced our findings. It has been reported that patients with ischemic DCM more commonly have preserved right ventricular function and size compared with those with nonischemic DCM. In our study, the two groups of patients did not have significantly different right ventricular size on the resting echocardiogram. However, the response of the right ventricle to dobutamine was not analyzed. There was some overlap in data between ischemic and nonischemic DCM. Therefore, for the individual patient, dobutamine stress echocardiography may not always be able to differentiate ischemic and nonischemic DCM. Moreover, the association of DCM and coronary artery disease does not imply in all patients (especially in one-vessel disease) that the DCM is ischemic in origin. For example, survivors of idiopathic DCM with viral disease or alcoholism m a y develop coronary ar-

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tery disease over a time. Possibly confirming this hypothesis, our patients with one-vessel disease frequently did not develop significant worsening of segments with PD dobutamine. Practical implications. Differentiating between ischemic from nonischemic DCM is very difficult in the absence of a history of MI, typical and frequent episodes of angina, and objective ECG or scintigraphic signs of ischemia. Analysis of inducible dyssynergy at dobutamine stress echocardiography may complement clinical findings and, therefore, reduce the need for invasive procedures.

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17.

18.

19.

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