IACC Vol . 19. No . 4 March 15 . 1992'.955-50

765

Transesophageal Dipyridamole Echocardiography for Diagnosis of Coronary Artery Disease LUCIANO AGATI . M D. MARCO R ENZI . M D . SUSANNA SCIOMER . MD, DARIO C . VIZZA, MD, PAOLO VOCI, MD. MARIA PENCO . M D . FRANCESCO FEDELE, MD," ARMANDO DAGIANTI, MD, FESC Rome and 1.'Aquiln. Feisty

The mine of Iransthoraric dipyridamale echrrdiography has been eatenstvely documented . However, in some patients, because of a poor aemnie window, the rest transthnracic examination is not always feasible and the transesophagenl approach is more caauenienl. Therefore, srnsesophagea€ echocardiography with high dose dipyrldamole lop to 0 .84 mglkg body weight over 10 min) was performed In 32 patients in whom the transihoracie dipyridamok test either was eat feaslh!e In = 29) or yielded ambiguous results (a = 3) . The eransesophageal ectocardingraphie test results were considered abnormal when new dipyridamole4nduced regional wall motion abnormalities were observed . All 32 patients underwent eorotlry angrography; significant coronary artery disease was defined as ?70% amen diameter narrowing in at least one major vessel. All patients also performed a bicycle exercise test I day before transesophageal dipyridamele echocardiograms . Transesophageal stress studies were completed in all patients, with a maximal Imaging time (in tests with a legalise resuh) of

20 m4. No side effects or intolerance to drug or transducer was observed. The kit ventricle was always visualized in the faurchamber and transgaotrk short-mots views . High quality twodimensional eehocardapsphie Images weal obtained io all patients both at rest and at peak dipyridamek infmion and were digitally anayced In a mad-urea formal . Coronary angiagraphy showed weoiary artery abstraction In 24 patients: 6 had single-, 9 doable- and 9 triple-vessel disease . The trattsesophagv~ dipyridanlde tat shoved a specificity of 100% and an overall sensitivity of 92% . Thesensitivity of this test for single-, double- and triple-vessel disease was 67%, 100% and 100%, respectively. It is concluded that Iratsesophageal dipyridamote echocardiographic testing is a useful detector of myocardial ischenia in patients with coramuy, artery disease, parieularly in those in whom a transt oradc study either is not feasible or yields ambiguous results. (J Am Call Cordial 1992;19 :765-70)

The value of transrhoracic two-dimensionai echocardiography for detecting wall motion abnormalities during physical exercise . atria) pacing or pharrnacologic stress tests (with dipyridaw le, dobuhamine or adenosinel has been extensively documented (1-16) . With the introduction of digital cine loop technology, stress echocardiography has become a clinically useful method fur evaluating patients with known or suspected coronary artery disease 117-23) . However, because of a poor acoustic window the rest lransihuracic examination is not always feasible . Moreover . complete definition of endocardial and epicaadial sutures is sometimes difficult to obtain, particularly from the apical approach, which usually provides the highest quality view in patients with coronary artery disease- Superior image resolution can be obtained with use of tmnsesophageal echocardiography (24.25), and transesophageal stress echocardiog-

raphy was recently proposed (26-301 as a useful diagnostic method in patients with coronary artery disease . In this study . we sought to assess the feasibility, safety and diagnostic accuracy of transesophagoal dipyridamote echocardiography in patients in whom the transthoracic approach either was not feasible or yielded ambiguous results . The results of this new stress method were compared with those obtained v,i!h conventional bicycle vanocto testing .

From the Iksrtment of Cardiology- La Sapiens and Tao Veltelu . UnNeeohy of Rome, Rome . 11x19 and the 'Depnmmem of CardialogvUnivmhy d L'Aquila. L'Aquila. Italy. Menusedpl receiveciJuly 9. 1991 : revised omnuscript received September 20 .

1991 . accepted October 16 . 1991 .

Add- for repdmx Luciano Atali . MD. 1 Cancdra di Ceudielogia. Petelinico Umbeno t. Universitd La Sepietua.00101 . Rome. Hall the Aneriwn Col leer of Cardiology

Methods Study patients, Thirty-two patients (22 men and 16 women . mean age 60 = 7 years) were ectolled in the study . Transtboracic echocardiography was not feasible because of chronic obstructive pulmonary disease in 20 patients, obesity in 5 and chest deformity in 4 . In the remaining three patients. transtboracic dipyridamole echocardiography yielded ambiguous results . Nine patients had had a previous myocardial infarction . Patients with rhythm disturbances, valcular heart disease, cardiomyopathy or vasospastic angina were excluded from the study. Coronary angiography, was performed in all patients to evaluate chest pain- An€ianginal medication (except sublingual nitrates) was discon0535-1097/9535.00

766

AGATr FT AL . TRANSESOPHACEAL DIPYRIDP.MOLE STRESS ECHOCARDIOGRAPHY

ED

JACC Vo! 19, No . a M,rci 15,1%2;765-M

Figure 1. Represenlalive teansesuphageal dipyridamole echocardiograms, transgastric short-axis vir, w, showing a positive resptmse in P patient with 95% stenosis of the left anterior descending coronary artery and 00% stenosis of the ten circumflex coronary artery. All segments contract normally in baseline candirioas (A). At peak dipyridamute infusion (H). The anterior septa) wall shows asynergy . ED = end-diastole; p5 = r •n d-svstole-

Es tined =4P, h bef rre exercise and dipyridamole stress lest, were performed. Informed wri[tcn consent was obtained from all patients. Bicycle exercise test. All patients performed a symptomlimited exercise test on a bicycle ergometer with stepwise increments of 20 W7min I day before transesophageal dipyridamole echocardiography . Exercise end points included attainment of the age-predicted target heart rate and development of marked ST segment depression, systolic hypotension (a decrease in systolic blood pressure of >10 runs s1g), shortness of breath, claudication or noncardiac symptoms requiring cessation of exercise . An ischemic electrocardiographic (ECG) change was defined as --1 .5 mm horizontal or downsloping ST segment depression 00 ms after the J point. Transesephageal dipyridamole echocardiography . Transesophageal echocardiographic monitoring was performed in combination with dipyridamole infusion . The drug was administered according to the following protocol 0 .56 mpEg body weight for 4 min, no dose far 4 min and, in patients with a negative low dose test result . 0 .28 me4tg for 2 min . The heart rate, blood pressure and 12-lead ECG were also continuously monitotsd during the procedure . Tlansesophageal echocardiographic images were repeatedly recorded an high fidelity videotape throughout the test until 10 min after the end of dipyridamole infusion . At the end of the test all patients received intravenous aminophylline (240 mgt to reverse the effects of dipyridamule . Patients were studied in the left decubilus position ; the pharyngeal region was anesthetized locally with lidocaine IXylocaine 107,, mall spray- . Before the examination, diazepam (S to 10 mg) and atropine sulfate (0 .25 to 0 .5 mg) were administered intravenously in each patient . Echocardiographic studies were performed with use of a HewlettPackard Scenes t000 and a 5-MHz single-plane phased-array

transesophageal probe. The left ventricle was visualized in a standardized tmnsgastric short-axis scan at various levels between the base and apex and in the four-chamber view with use of a previously described procedure (24,25). A slight to moderate extension of the probe tip was used to reduce the foreshortening of the left ventricle from the four-chamber view (25). During the test, the myocardial regions with abnormal wall motion were identified by rapidly moving the transducer through various positions . Image analysis. High quality frames were digitized offline (Micrasonics Prevue Ill) allowing for display of a continuous loop based on a sinr.(e cardiac cycle . Images were then displayed in a quad-screen formal with each echocardiographic view displayed as a pair, with the appropriate rest and peak dipyridamole images side by side . An example of a positive test result is shown in Figure 1 . Echocardiograms were analyzed independently from the floppy disks by two esperieneed observers without knowledge of the exercise EM test results or cardiac catheterization data. In case of disagreement, a third observer reviewed the study and his judgment was binding . According to a generally accepted qualitative analysis (1,2), the wall motion was graded as byperkinetic, normokinetic, hypokinetic, akinetic and dyskinetic on the basis of the subjective impression of the inward motion of the endocardial echo toward the center of the left ventricle and on the degree of thickening of the myocardium . A positive test result was based on detection of a worsening of contraction or new-onset asynergy . Presence ofregional asynergy an the baseline echocardiogram was not considered a criterion of a positive result . Segments ofthe left ventricle were assigned to regions of coronary perfusion (23-20) (Fig. 2). The right coronary artery tenitory included the proximal inferior septum and inferior wall . The lateral and posterior walls were assigned to



JACC Vol. 19. No. 4 Moos 15 . 1992 :765-70

RA

AGATI ET AL.

TRANSESOPHAIEAL DIPYOIDAMOI.E srRESS ECHOCARDIOGRAPHY

LA LV LV

Diagrams illustrating the relation of two-dimenennxl transesophageal echocardiographic short- and long-axis views and coronary artery perfusion. LA = left atrium : LAD = left descending coronary artery ; LCX -- left eircumacx coronary artery : LV = left ventricle ; RA = right atrium : RCA = right coronary artery : RV = right ventricle . Figure 2.

the circumflex coronary artery . The left anterior descending coronary artery region included the anterior septum, apex and anterior wall . In patients with normal watt motion at rest, multivcssel disease was defined as present when two or more coronary perfusion beds showed abnormal wall motion and reduced myocardial thickening. In patients with previous myocardial infarction and regional asynergy on the baseline echocardiogram, two- or three-vessel disease was diagnosed if abnormal wall motion or thickening was identified in one or two vascular beds other titan the area of infarction . Coronary cipeangiography . Selective percutaneous coronary arteriography was performed in multiple projections, including craniocaudal views- within 2 weeks of stress testing. Coronary cineangiograms, recorded on 35-mm film, were reviewed on a Vanguard projector. Significant coronary artery disease was defined as z7O% reduction in lumen diameter of a major epicardial coronary artery or one of its major branches in each of two orthogonal projections . stall analysts- Sensitivity, specificity and predictive values were calculated by standard methods . The results of transesophageal stress echocardiography and exercise testing were compared with use of Fisher's exact test . Results were considered significant at p < 0 .05 .

767

result was positive or negative was unanimous for '0 of 32 transcsophagcal tests : the 2 remaining studies yielded a split decision . Coronary angio¢raphy (Table 1) . At coronary anuiograohy, 8 patients had nonsignificant and 24 had significant obstruction of at least one major epicardiai coronary artery ; of the 24 pa0eots, 6 had single-vessel . 9 had double-vessel and 9 had triple-vessel disease . Bicycle exercise test (Table 1) . A bicycle test was pertvrmed by all patients . The bicycle ergometer test was considered diagnostic of ischemia in 15 of the 24 patients with coronary artery disease and in I of the 8 patients without significant coronary lesions . Thus, the sensitivity for detection of coronary artery disease was 63% and the specificity was 88% (Table 2) . The positive predictive value of the exercise test was 94% . Transesophageal dipyridamote echocardiography, (Table 1) . During the test, 12 of the 24 patients with coronary artery disease had both angina and ?1 .5 mm of ST segment depression on the ECG . Transient wall motion abnormalities were observed in 14 patients with coronary artery disease after low dose dipyridamole infusion . The remaining 18 patients underwent high dose dipyridamole infusion ; 8 of these patients had a positive test result. Dipyridamoleinduced wall motion abnormalities included segmental bypokinesia in 6 patients and regional akinesia in 16. All eight subjects with normal coronary angiograms showed a normal contraction pattern during the test. Thus, the overall sensitivity of dipyridamole transesophageal echocardiography for the detection of coronary artery disease was 92% and the specificity was 100% (Table 2), with a positive predictive value of 100% . Sensitivity for single-, double- and triplevessel disc se was 67% (four of six patients)- 100%A (nine of nine) and 100% (nine of nine), respectively . Multiple wall motion abnormalities suggestive of multivessel disease were detected in 14 (77%) of these patients . All patients with a previous myocardial infarction, regional asynergy on rest echocardiogram and multivessel disease were correctly identified . Seven patients had dipyridamole-induced wag motion abnormalities in the absence of chest pain or ST segment depression during exercise . None had an abnormal result on exercise electrocardiography with a normal result on transesophageal dipyridamole echocardiography . The two patients with a false negative transesophageal stress test had single-vessel disease and a negative exercise test resent .

Results

Discussion

Feasibility and safety of transesophageal dipyridamole echocardiography . The transesophageal stress study was completed in all patients with a maximal imaging time of 20 vain in tests with a negative result . Neither side effects nor intolerance to drug or transducer was observed . High quality images were obtained in all patients both at rest and at peak dipyridamote infusion ; the success rate in recording adequate images was 1005e. Interpretation of whether a test

Recently, dipyridamole echocardiography was proposed as a method not dependent on exercise for the diagnosis of coronary artery disease (7-12) . High dose dipyridamole echocardiography has a reported sensitivity of 70% to 80% and a very high specificity (8-12) . In addition, dipyridamale echocardiography has provided a useful method for the detection of residual myocardial ischemia in patients with previous myocardial infarction (31) and for the early assess-



768

JACC Vol . 19, No .4 March 15, 1992:765-70

AGATI ET AL . TRANSESDPHAGEAL DIPVRID .AMOLE STRESS ECHOC.AREOCRAPHY

Table l. Clinical, AOgiographic, Bicycle Ergumetry and Echncardiographic Data in 32 Palieuts Traacesophageal Dipyridamole Echocardiography Pt N.

A.gelyOr

I 2

51101 69101

u o

3

54F

4

61195

G'ader

Coronary AO-

Prkor Ml Silt

slcna¢,19r1

WMA Site

Exercise

Peak

Basal

LCa

RCA

Tceling

ECG

o

0

o

+

0

0

0

0 0

0 0

o 0

a 0

o

0

0

a

0

0

0

0

0

0

0

o o

e

0

0

0

LAD

5

677

0

0

a

0 n

0 7

6171

0

0

o

0

0

0

51 ;

a

0

0

0

0

0 0

a

6s1F

n o

0

o

0

0

0

0

9

65SF

10

41JM

0 0

0 0

0

AS . AP

I

6

90

o

o

0

0

0

.0

0

o

a

o

90

0

U

+

11

55101

12

SLIP

so

0

0

0

0

0

AS ,A

13

it/F

0

0

95

0

-

0

IS,I

14 IS

69(01 65161

0

90 95180'

0 0

o P .L

I' IS

0

0 85

16

53161

90

0

55

0

AS

A,IS

17

44!95

0

0

PL

67101

n0

75 100

0

18

95 0

+

As,AAP

1, 5

19

5256:

E0

80

0

+

0

0

AS .A

20

55101

0

0

90

90380`

0

0

0

P,L .IS

21

671M

A

100

0

100

0

+

1

22

69191

0

95

90

65101

0 70

IS

AS,A

62IF

00 80

0

24

I 0

0 0

0

23

0 95

AS.A.AP 0 0

AS .P .L

25

521M

0

91,

75

75

0

AS ,P

26

65191

70

95

is

AS

27

S61M

A

5 90

70

8o

+

ASS

A,I5,1

28

69101

€

101

90

100

0

I .P,L

AS,A .L

29

651F

0

80

70

95

I

+

0

AS.P.L

30

521M

75

75

+

1

0

A.AS,P

11 32

68151 621M

0 I

;11

1.

95

+

IS

AS,A

0

95

60

a0

+

I

AS,A,AP

'Valves represent Ino female ; I = inferior, IS =

Inuns (it, record is r mferm

septum ; L

=

95 +

r the more distil lesion! . A = anterior, AP - apex: AS latest ; LAB =ten anterior de cendin0 eor0rmry artery;

- anterior LCa - ten

1,15

AS

acptun . ECU = eleclrocarEioBmm ; F = ci,endcr comnmy mrery ; M = male ;

MI = myocardial infarction ; P = posteovr ; Pt = patient ; RCA = right coronary artery; WMA = wall motion abnormatilfes; 0 - negaase m absent: + = positive .

meat of coronary reserve after coronary angioplasty (32) . However, in a small group of pa-dens transthoracic echocardiugraphy may be of inadequate quality because of obesity, chronic obstructive pulmonary disease or chest deformity . Particularly in these patients, traasesophageal echocardiography may provide an alternative imaging modalityComparison with previous studies . Previous studies have demonstrated that trasescphageal echocardiography is a sensitive method for the intmnperative detection of ischemia-induced segmental wall motion abnormalities (26,27) . Using transesophageal echocardiography in combination with simultaneous atria) pacing, Lambertz et al . (28) reported very high sensitivity and specificity (93%n and 100%, respectively) in detecting significant coronary artery disease . The sensitivity of this technique for single-, double- and triple-vessel disease was 85%, 100% and I0090, respectively .

The success rate in obtaining diagnostic images during atrial pacing was 100%. Using the transesuphageal approach during high dose dipyridamole infusion, Biagini et al. (29) demonstmted that it is possible with [his technique to derive useful information on the results of aortocorunary bypass surgery even in the early postoperative hours . Transesophagent dipyridamole eehocnrdlography . The present study shows that traosesophageal dipyridamole echocardiography is a safe, feasible and accurate provocative test, with very high specificity and sensitivity for the detection of coronary artery disease . The success rate in obtaining two-dimensional echocardiograms of diagnostic quality from the transcsophegeal approach is very high, as previously reported in a study using simultaneous atria) pacing (2B). However, Iransesophageal atrial pacing may produce chest discomfort secondary to .ssophageal stimulation (28,3D), a side effect that is not encountered with



JACC Vul. 19 . Na.4 Mamh 15 . 1992.765-70

or

Table 2. Results

ACATI ET At .. TRANSESOPHAGEALDIPYRIDAMOLESTRESS ECHOCARDIOGRAPHY

Bicycle Ergometry and Transesophageal

769

observed in this study . Moreover, even though the combi-

Dipyridamole Echocardiography in 24 Patients With and 8

nation of four-chamber and short-axis views allows for the

Without Coronary APel y Disease

visualization of most of the myocardium supplied by all three

'rest HralI

CAD

N. CAD

m jor coronary arteries, in some patients the apex remains a

Hicycle crgomclry

15

I

relatively obscured area (25-27) . However, our false nega-

9

7

Positive

tive studies occurred in patients with single-vessel disease

Negative

Sensitivity - 63% ; specificity - 88'%

and with negative exercise stress test results . Thus, as previously demonstrated (7,23). in some cases angiographi-

Echocardiography

cally documented coronary obstructions may not induce

Positive

22

0 8

Negative

wall motion abnormalities during stress testing. Conclusions. Transesophageal echocardiogaphic detec-

Sensitivity - 9279' : specificity - 100%

tion of wall motion abnormalities during high dose dipyrid-p < 0 .01 ; CAD = coronary artery disease . Echocardlograahy - loon amole infusion is a safe, feasible and accurate procedure, esophageal dipyridamole echmardiography . with very high specificity and sensitivity for the detection of angiogaphically assessed coronary artery disease . Because

of

transesophageal

the tansesophageal echocardiographic stress test was per-

dipyridamole echocardiography with respect to single-,

formed only in patients in whom transthoracic dipyridamole

double- or triple-vessel disease was similar to that observed

testing proved inadequate for analysis or yielded ambiguous

with use of atrial pacing (28) and was slightly higher than that

results, the clinical impact

previously reported for transthoracic dipyridamole echocar-

echocardiography cannot be ascertained from this study.

diography (8-12) . The high signal to noise ratio and the lack

Further studies on a larger cohort of patients are needed to

of interference by the respiratory cycle are the major advan-

directly compare transesophageal with transthoracic stress

tages of this technique . The entire endocardial and epicardial

echocardiography in patients with suspected coronary artery

pharmacologic testing . The sensitivity

contours

of the

left ventricle are visualized in most patients .

of

this new method of stress

disease.

Therefore, the evaluation of wall motion abnormalities can be based not only on the subjective impression of the inward

w e thank Crimea Maett r« reviewing tie mamrrrript .

motion of the endocardial border toward the center of the left ventricle, but also on the degree of myocardial thicken . ing, Biplane and omniplane transesophageal transducers may further increase the diagnostic accuracy

of

this new

method of stress echocardiography (33,34). Transesophageal dipyridamole echocardiography showed the highest sensitivity in detecting disease in patients with high risk coronary anatomy (Table 1). This finding confirms

(8-12) on dipyridamole testing response is more likely to be positive

previous data

indicating that

the test

in patients with

n,ultivessel than in those with single-vessel disease . The sensitivity

of

the transesophageal approach in detecting

patients with single-vessel disease is slightly higher than that previously reported for the transthoracic approach

(8-12).

The superior image resolution should explain this difference . As expected, the sensitivity of Lransesopbageal dipyridamole echocardiography was higher than that

ECG

and the dipyridamole

ECU tests

of

the bicycle

(Table 2) . This finding

is consistent with previous experimental and clinical evidence (27,35) that regional wall motion abnormalities precede ECG changes. Pain and ECG changes are in fact late . inconstant and nonspecific markers of myocardial ischemia (4,8) . Limitations

of the

study. The main disadvantage of trans-

esophageal stress echocardiography is that it requires passage of a large probe into the esophagus and stomach, with

all the

precautions and complications inherent to this prod

dure in patients who are awake. The dif iculty f in obtaining simultaneous optimal imaging of all regions of the left ventricle may explain some

of

the false negative results

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AGATI ET AL, TRANSESOPHAOEAL DIPYRIDAMOLE STRESS ECHOCARDIOGRAPHY

I1 . L bovitz At . on AC. Chairman BR. Doppler and two-dimensional echocardiographic assessment of left ventricular function before and after Pears dipyrdamole stress testing for detection of coronary aver' disease. Am J Cardiol 1988;621180-5. 12 . Agali L, Arala l., Pcraldo N fa C. ei al . Usefulness of the dipyridamoleDoppler lest far diagnosis of coronary artery disease . Am J Cardtul 1990 :65 :829-34 . 13 . Fang AY. Gallagher Kb. Rude AJ- The phy,icilark basis as comed with dipyrdamole stress inter-ions in the aascavnenl of critica17 onary slenawc Circulation 1987 :76941-51 . 14 . Berlhe C . Pierzrd LA, Iliernnax M, et al PrMiming the cater , mid location of coronary anery disease in acute myocardial hi-ii- by echocardiography donor dnhntamine inlminn . Am J Card, .[ 1986;58: 1167-72 . 15 . Mannerin8 D, Cripps T, L-h G, t al . The Aabatamine stress test az an aaemative m execise testing after acute myocardial infarction . Br Heart J 198859:521-6. 16 . Trakhtenbroit AD, Charif J, Kleiman NS . ct al . Intravenous adenonlne echocardiography, a now pharmacologic stress test : preliminary results and comparison with simultaneous thallium scinligrnphy labstrl . J Am Call Cirmol 1990 15234A . I7 . Ryan T . VaseyCG. Preset CF . 0 Dannell IA. Feigenbaum H, Armstrong WP. Exercise echocardiography : detection of coronary artery disease in patients with normal lent ventricular wall mottun at rest . J Am Coll Cordial 1986 ;11 :99:-9. I8 . Armstrong WF. Excreke echocardiography : ready . 'r:Tog unit albie . J Am Cull Cardtul 1988 :11 :1359-61 . 19 . Braderich T . Sawadu S . Armstrong WF, et al . Improvement in rest and exercise-induced wall motion abnormalities after coronary angioplasty : echocardiographic study. J Am Coll Cardiol 1990 :15 :591-9. 20 . I ..bovtle AJ . Exercise echocardogrphy after coronary angioplasty : expanding applications, J Am Call Cordial 199015 :600-I . 21 . Sheikh KH, Benglson JR, Helmy S, et at . Relaron of nuanlitalive nary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography . J Am Coll Cardiol 1990;15:1043-51 . 22 . Obeonan A . Fan P-H. Nanda NC . e1 al . Reproducibility of two . dimensional exercise echocardiography . 1 Am Coll Cordial 1989:14: 923-8 . 23 . Agati L, Arata L, Luongo R, et a1- Assessment or seventy of coronary narrowiegs by quantitative exercise echocardiography and comparison with quantitative arteriogmphy . Am 1 Cordial 1991 ;67 :1201-7.

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