Detection of coronary artery disease in the presence of left ventricular hypertrophy

International

Journal

of

cardiology ELSEVIER

International Journal of Cardiology 57 (1996) 245-255

Detection of coronary artery disease in the presence of left ventricular hypertrophy Savvas T. Toumanidis*, Maria I. Pantelia, Chrysanthi 0. Trika, Nikolaos S. Saridakis, Stamatios F. Stamatelopoulos, Dimitrios A. Sideris, Spyridon D. Moulopoulos Department of Clinical Therapeutics, Alexandra Hospital, 80 Vas. Sojias-Lourou Avenue, 115-28 Athens, Greece Received 17 July 1996; accepted 11 September 1996

Abstract To evaluate the accuracy of exercise echocardiographyfor the recognition of coronary artery diseasein the presenceof left ventricular hypertrophy 70 patients were studied. Significant coronary artery diseasewas present in 25 patients and left ventricular hypertrophy had 29 patients. All patients underwent an exercise ECG and echocardiographictest during which tine-loop digitized echocardiographywas obtained.Wall motion was analyzed and a regional wall motion score index was calculated. The overall sensitivities of exercise ECG and echocardiographyfor detecting coronary artery diseasewere 60% and 64%, respectively, and the specificities were 49% and 78%, respectively. In patients with left ventricular hypertrophy the specificity of exercise echocardiography was higher (71%) compared to exercise ECG (21%) while in patients without hypertrophy the sensitivity was higher (70% vs. 40%, respectively). Of the 19 patients with a non-diagnostic stressECG, echocardiographycorrectly identified 100% of those with coronary artery diseasebut only 53% of those without disease.It is concluded that exercise digital echocardiographyrepresentsa good diagnostic alternative to the exercise ECG for identifying coronary artery diseasein the presenceof left ventricular hypertrophy and should be useful in patients with a non-diagnostic exercise ECG. Keywords: Coronary artery disease;Left ventricular hypertrophy; Exercise echocardiography;Exercise electrocardiography

1. Introduction Hypertensive patients with left ventricular hypertrophy represent a particularly high risk group for coronary artery disease events. The Framingham Study has demonstratedthat left ventricular hypertrophy is an independent risk factor for ischemic events [l]. Furthermore, there is evidence that left *Corresponding

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ventricular hypertrophy produces myocardial ischemia in the absenceof significant coronary artery disease, due to a reduced coronary flow reserve [2-41. Angina-like chest pain is a common finding in hypertensive patients with left ventricular hypertrophy [5]. Given that the probability of obstructive coronary artery diseasein this particular population is high, angina like symptomscould not be attributed solely to decreasedcoronary reserve. Non-invasive diagnostic tests for coronary artery disease, such as the exercise electrocardiogram (ECG) may be mis-

0 1996 Elsevier Science Ireland Ltd. All rights reserved

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leading due to the high incidence of false positive results [2]. Similarly, thallium-201 scintigraphy appears of limited value since it creates images mimicking myocardial infarction in the presence of left ventricular hypertrophy [2,6]. Exercise echocardiography has proved to be a valuable technique in the evaluation of patients with known or suspectedcoronary artery disease [7-91. Although the overall sensitivity for the detection of coronary artery diseasemay be high, the accuracy of the test in specific clinical situations has not been established. Questions remain regarding indications as well as applications in specific patient subgroups. The purpose of this study was to evaluate the diagnostic accuracy of exercise echocardiographyin order to detect significant coronary artery diseasein the presenceof left ventricular hypertrophy. 2. Methods 2.1. Study population

The study population consisted of 70 patients with no previous history of cardiovascular disease,other than hypertension. These patients were referred for evaluation of possible coronary artery disease.Clinical suspicion of coronary artery diseasewas basedon a history of chest discomfort, complaints considered to be anginal equivalents, an abnormal rest ECG or a stresstest suggesting myocardial ischemia. None of the patients had a previous history of myocardial infarction. Hypertension was defined as repeated blood pressure measurements >140/90 mmHg or >130 mmHg mean systolic blood pressure via a 24-h ambulatory blood pressure monitoring. All patients underwent a routine echocardiogrambefore cardiac catheterization. Satisfactory two-dimensional echocardiography was performed, using a 2.5MHz phased array transducer linked to an ultrasound system(Hewlett-Packard, Sonos 1000, model 77020A, Palo Alto, CA). No patient had valvular heart disease, asymmetric septal hypertrophy, congenital heart diseaseor cardiomyopathy. Two patients were excluded because of an unacceptable echocardiographic window. Measurementswere made, according to the recommendationsof the American Society of Echocardiography, on three to five consecutive car-

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disc cycles and averaged [lo]. Left ventricular hypertrophy was defined as a posterior wall thickness > 12 mm obtained by a two-dimensional guided M-mode tracing cut through the chordae tendineaeof the mitral valve apparatusin the standardparastemal long-axis image. The left ventricular mass was then calculated by the cube formula of Troy and associates [ 111: Left ventricular mass(g) = l.OS((Left ventricular internal diameter + ventricular septalthickness + posterior wall thickness)3 - (left ventricular internal diameter)3).

Left ventricular masswas indexed by body surface area using gender-specific normal limits from the Framingham Heart Study as follows: normal = < 150 g/m* for men and < 120 g/m2 for women [12]. The ejection fraction was calculated from the same Mmode tracings. The 29 patients with left ventricular hypertrophy were divided into two groups baaed on coronary arteriographic findings: Group LVH( + ) CAD(-) included 14 patients with pure left ventricular hypertrophy and normal coronary arteries; Group LVH( + ) CAD( + ) included 15 patients with left ventricular hypertrophy and significant obstructive lesions on epicardial coronary arteries. The above groups were studied concurrently with two other groups without left ventricular hypertrophy, consisted of 41 patients. The control group LVH(-) CAD(-) included 3 1 patients, who were demonstrated to have normal arterial pressure, without left ventricular hypertrophy and who underwent diagnostic cardiac catheterization for atypical chest pain and had normal coronary arteriographic and left ventriculographic findings. Group LVH(-) CAD( +) included 10 patients with pure significant coronary artery disease.The data in the control group LVH(-) CAD(-) served as the reference mean for comparison between normal subjects and patients with left ventricular hypertrophy and/or coronary artery disease.Coronary angiography was performed within 48 h after exercise electrocardiography and echo-

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cardiography. The study protocol was approved by the hospital ethics committee. Informed consent to participate in the study was obtained from all patients. 2.2. Exercise testing

Exercise testing was performed in the morning after overnight fasting, on a treadmill using the standard Bruce protocol. A 1Zlead ECG and blood pressuremeasurementswere obtained at baseline, at each minute of exercise and at 1, 3, and 5 min after exercise. Throughout the test, three electrocardiographic leads were simultaneously and continuously monitored during exercise and recovery. The location of the precordial electrodes was sometimes slightly modified to avoid interference with the optimal echocardiographicwindow. Exercise test end points were: development of fatigue, dyspnea or chest pain preventing further exercise, >3 consecutive premature ventricular contractions, > 10 mmHg decline in systolic blood pressure or systolic blood pressure >220 mmHg or diastolic blood pressure > 110 mmHg during exercise, development of horizontal or downsloping ST depression > 1 mm at 80 ms from the J-point in one precordial lead or in one peripheral lead with or without symptoms and attainment of >85% of the age-predicted maximal heart rate. All stressECGs were analyzed by a single blinded investigator who had no knowledge of the echocardiographic and angiographic data. The exercise ECG was defined as showing ischemia with the development of at least 1 mm or more of additional horizontal or downsloping ST-segmentdepressionat 80 ms after the J-point compared with the baseline values at rest. The electrocardiographic responsewas considered non-diagnosting in the presence of nonspecific ST-T changes at baseline or left bundle branch block. The mean ST depression at peak exercise was then calculated as the sum of the ST depression in all leads divided by the number of leads. 2.3. Exercise echocardiography

Prior to exercise, with patients in the left lateral decubitus position, images at rest were sequentially

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acquired in the parastemal long- and short-axis and apical 4- and 2-chamber views. Patients then performed the symptom-limited treadmill exercise described above. Immediately after cessation of peak exercise (completion within 60 s of exercise termination) and 3 min post exercise, the patients resumed the left lateral decubitus position and imaging was repeated in the four views described. The images were stored on videotapes and selected images at rest, peak and post exercise were digitized in an off-line analysis station and displayed on a fourquadrant screenusing a continuous tine-loop format (Cine’view Freeland System). Each view consisted of eight images, beginning at the R-wave, captured every 50 ms, and displayed as an eight-cell cineloop. The system continuously stores up cardiac heart beats in its digital memory and then allows the operator to choose the best four images at rest, peak and post exercise. These rest, peak and post exercise images are displayed in a quad-screenformat and are stored in a floppy disk. The software of the system enables rest and peak or post exercise images to be reviewed at the sametime. All exercise echocardiograms were interpreted by an experienced echocardiogapher who was unaware of the clinical history, the exercise ECG and the coronary angiographic results. Evaluation of wall motion abnormalities was based on the subjective impression of endocardial inward motion of each segmenttoward the center of the left ventricle and the presenceof systolic thickening of the myocardium. Resting and exercise echocardiograms were considered normal if all left ventricular segmentscontracted normally at rest and remained normal or became hyperdynamic with exercise. Exercise echocardiography was classified as abnormal or positive for myocardial ischemia if two or more contiguous segments within a region were graded as abnormal. More specifically, for those studies without wall motion abnormalities at rest, any wall motion abnormality during or after exercise-induced was considered positive. For those studies with wall motion abnormalities at rest, the study was considered positive if it showed either a higher grade wall motion abnormality in the abnormal segment at rest (i.e. from hypokinetic to akinetic) or new wall motion abnormality in a different segment.Wall motion was analyzed in 16

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myocardial segments using a qualitative scoring system. According to the recommendations of the American Society of Echocardiography, segmental wall motion was graded as: normal (score= l), hypokinetic (score= 2), akinetic (score= 3), or dyskinetic (score= 4) [ 131. Segments with suboptimal image quality were excluded from analysis (score=O). A global wall motion score index was derived at each stage by adding the scores assigned to each segment and dividing the final score by the number of segments visualized. To analyze the changesof wall motion during stress,a delta (A) wall motion score index was derived as peak index minus rest or post index and post minus rest index. The wall motion score index of a normal ventricle is 1.0, while progressively increasing scores indicate more severe or extensive dyssynergy.

2.4. Coronary angiography

Coronary arteriography was performed using the Judkins technique. Each study was reviewed by a blinded observer who had no knowledge of the patient’s clinical status. Determination of percent diameter stenosiswas by visual estimation in at least two orthogonal views. Significant coronary artery disease was defined as >50% reduction in luminal diameter of a major coronary artery or a major branch vessel, compared with a normal segment immediately proximal to the lesion. Multivessel coronary artery disease was defined as significant diseasein two or more coronary vessels.

2.5. Statistical analysis

Data are shown as mean?standard deviation. Significance was set at PcO.05 level. Numerical data from multiple groups were compared using the one-way analysis of variance with Duncan procedure. Frequency data were compared by chi-square analysis. Considering that coronary angiogram is the ‘gold standard’, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of exercise echocardiography were derived and compared with exercise electrocardiography according to the standard definitions.

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3. Results 3.1. Clinical features of the study population

The patient population was predominantly male (71%) with a mean age of 53.992 12.22 years. Fiftyfour per cent of the patient population had a history of arterial hypertension. Antihypertensive and antianginal medication was not discontinued at the time of the imaging studies. Fifty-six per cent of the patient population were on medication (nitrates and P-adrenergic blockers 35% and calcium-channel antagonists 33%). The clinical characteristics of the patients in each group are presentedin Table 1. 3.2. Coronary angiography

Significant coronary narrowing was present in 25 out of 70 (36%) patients. Single-vessel diseasewas present in nine (13%) patients while two-and threevessel diseasein eight (11.5%) patients, respectively (Table 1). 3.3. Exercise testing

Treadmill exercise test results are presented in Table 2. One-way analysis of variance revealed that the mean peak double product in group LVH( + ) CAD( + ) was significantly lower compared to all other groups. This is probably due to a significantly lower heart rate compared to the rest of the groups. The systolic blood pressure at peak exercise did not differ significantly between groups (P =NS). A comparison between groups showed that most of the patients (80%) in group LVH( + ) CAD( + ) were under P-blockers. This medication was taken by only five (16%) in group LVH(-) CAD(-), four (3 1%) in group LVH( + ) CAD(-), and three (30%) in group LVH(-) CAD( +), (P
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Table 1 Comparison of clinical features between groups with and without left ventricular hypertrophy Feature

LVH(-) CAD(-) Control

LVH( +) CAD-)

LVH(+) CAD(+)

LVH(-) CAD( + )

P-value

Number of patients (%) Male (n, %) Mean age (years) History of Ht (n,%) Medications (n,%) B-Blockers Nitrates Calcium antagonists LBBB (n,%) CAD @I,%) l-vessel Z-vessel 3-vessel

:31(44%) 21 (68%) ,$I* 142.3.4 ‘7 (23%) ‘7 (23%) .5 (16%) 4 (13%) .5 (16%) .3 (10%)

14 (20%) 6 (43%) 58210’ 12 (86%) 6 (43%) 4 (31%) 1 (8%) 5 (39%) 5 (36%)

15 (22%) 14 (93%) 6125’ 14 (93%) 14 (93%) 12 (80%) 12 (80%) 9 (60%) 0 (0%)

10 (14%) 9 (90%) 6029’ 5 (50%) 8 (80%) 3 (30%) I (70%) 4 (40%) 2 (20%)

co.01 co.05
0 (0%) 0 (0%) 0 (0%)

0 (0%) 0 (0%) 0 (0%)

3 (20%) 6 (40%) 6 (40%)

6 (60%) 2 (20%) 2 (20%)


CAD, coronary artery disease;Ht, arterial hypertension; LBBB, left bundle branch block; LVH, left ventricular hypertrophy; n, number; + , with; -, without. Superscript number(s)denote the serial number of the group(s) with a significant difference (P
CAD( + ) group, P
predictive value of 73%, a negative predictive value of 50% and a diagnostic accuracy of 48%. The percentages for patients without left ventricular hypertrophy were 61%, 40%, 50%, 86% and 50% respectively (Table 3). Five patients (7%) with coronary artery disease experienced chest pain during exercise test. In the control group the mean exercise time was significantly longer comparedto LVH( + ) CAD( + ) group, although differences between the other three groups

Table 2 One-way analysis of variance of exercise electrocardiographicresults among the four patient groups

Resting HR SBP DBP Peak HR SBP DBP RPP Exercise time (mm) Mean ST (mm) Angina (n, %)

LVH (-) CAD (-)

LVH(+)CAD-)

LVH(+)CAD(+)

LVH (-) CAD ( + )

1129 123t9= 79”6

78211’ 139215’ 8329

65?12’ 136214’ 84512

71+17 132?21 7728

1622 153,4 1792 17 8858 29?43 8.2+2.g3 0.3+0.9 0 (0%)

151211’ 191222 93*& 29+43 6.822.8 0.4kO.9 0 (0%)

122?16’.*.4 180?27 93t94

143-c27’.3 181212 83t8’.’ 26Z53 6.622.8 0.721.0 2 (20%)

22-51.2.4 5.5k1.8’ 0.9? 1.2 3 (20%)

DBP, diastolic blood pressure (rmnHg); HR, heart rate (beats/mm); mean ST, mean ST depressionat peak exercise; RPP, ratexpressure product (beats/minXmmHgX 10’); SBP, systolic blood pressure(mmHg). Other abbreviations as in Table 1.

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Table 3 Comparison of exercise electrocardiography and exercise echocardiographyfor the prediction of coronary artery disease Patients with LVH (n=29) StressECG Stressecho Patientswithout LVH (n =41) StressECG Stressecho Patients with NnDSE (n = 19) Stressecho Overall (n = 70) StressECG Stressecho

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

DA (%)

73 60

21 71

73 69

50 67

48 66

40 70

61 81

50 54

86 89

50 78

100

53

36

100

63

60 64

49 78

65 62

79 80

53 73

DA, diagnostic accuracy; NnDSE, non diagnostic stressECG, NPV, negative predictive value; PPV, positive predictive value; StressECG, exercise electrocardiography; stressecho, exercise echocardiography.Other abbreviations as in Table 1.

were not significant. The mean ST depression at peak exercise did not differ significantly between groups (P=NS, Table 2). 3.4. Echocardiography

The echocardiographic characteristics of the four groups are presented in Table 4. Patients with pure left ventricular hypertrophy (group LVH( + ) CAD(-)) appeared with a significantly larger left ventricular end-diastolic dimension compared to all groups. The end-systolic dimension did not differ significantly between groups. The ejection fraction did not vary significantly between groups. Mean left ventricular mass indices were significantly higher in LVH( + ) CAD(-) and LVH( + ) CAD( + ) groups compared to LVH(-) CAD( -) and LVH(-) CAD( + ) groups. Exercise echocardiography was interpreted as positive in six (19%) of group LVH(-) CAD(-),

four (29%) of group LVH( +) CAD(-), 11 (73%) of group LVH( + ) CAD( + ) and seven (70%) of group LVH( -) CAD( + ) (P < 0.000). The overall sensitivity was 64%, the specificity 78%, the positive predictive value 62%, the negative predictive value 80% and the diagnostic accuracy 73% (Table 3). Sensitivity was similar whether or not patients were on P-blockers (67% vs. 60%, respectively). One-way analysis of variance showed that the mean wall motion index score at rest did not differ significantly between groups (Table 5). At peak exercise, the mean wall motion index score was found significantly higher in groups with coronary artery disease compared to the control group (1.2320.16 group LVH( +) CAD(+) and 1.19kO.19 group LVH(-) CAD(+) vs. 1.05+0.12 group LVH(-) CAD(-)) and in patients with combined left ventricular hypertrophy and coronary artery disease (group LVH( + ) CAD( + )) than those with pure left ventricular hypertrophy (1.09+0.12 for group

Table 4 Differences in echocardiographiccharacteristicsbetween groups

LVEDDlBSA LVESDIBSA IVSEDTlBSA LVPWEDTIBSA LV MASSIBSA EF (W)

LVH (-) CAD (-)

LVH ( + ) CAD (-)

LVH(+)CAD(+)

LVH(-)CAD(+)

2.7kO.3’ 1.620.2 0.6?0.12.3.4 0.41r0.12’” 103+20*,3,4 7026

3.0t0.21.3*4 1.820.3 0.7t0.1’ 0.6?0.1’.4 178Z36’.4 72klO

2.7?0.22 1.620.3 0.8-+0.1’.4 0.6k0.1’.4 184Z201.4 68?12

2.7kO.4’ 1.6kO.3 o.7zo.1’.3 0.520.1 2.3 121+-22’***’ 7127

BSA, body surfacearea (m’); EF, ejection fraction; IVSEDT, interventricular septumend-diastolic thickness (cm); LVEDD, left ventricular end-diastolic dimension (cm); LVESD, left ventricular end-systolic dimension (cm); LV MASS, left ventricular mass (g/m’); LVPWEDT, left ventricular posterior wall end-diastolic thickness (cm). Other abbreviations as in Table 1.

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Table 5 One-way analysis of variance of the wall motion index score among the four patient groups

Rest Peak Post APeak-rest APeak-post APost-rest

LVH (-) CAD (-)

LVH ( + ) CAD (-)

LVH(+)CAD(+)

LVH (-) CAD ( + )

1.05~0.14 1.05’o.123.4 1.05~o.133 0.00f0.063.4 0.00k0.084 0.00+-0.063

1.10t0.15 1.09ko.123 1.09+o.143 0.01ko.073~4 -o.02-co.124 0.0320.13

1.13k0.16 1.23t0.16’.* 1.21~o.15”2’4 o.10~o.15’~2 0.0220.15 0.09?0.17’

1.08ZO.10 1.19?0.19’ 1.09+o.123 0.11~0.21’~* 0.1o-to.22’.* O.O1tO.ll

A, Difference. Other abbreviations as in Table 1.

LVH( + ) CAD(-)). At post exercise, the patients of group LVH( + ) CAD( + ) maintained a significantly higher score (1.2120.15) than patients of LVH(-) CAD(-) 1.0520.13, LVH( +) CAD(-) 1.09f0.14 and LVH(-) CAD( +) 1.09+0.12, P
Among the 47 patients with a negative or nondiagnostic exercise electrocardiography, echocardiography identified 6 out of 10 patients with coronary artery disease (60% sensitivity) and 27 patients without the disease (73% specificity). The positive predictive value of a positive exercise echocardiogramin a patient with a negative or nondiagnostic stressECG was 38%. The stressECG was positive in 23 patients; 10 of them had a positive echocardiogram (sensitivity 67%, specificity 100%). Among patients with a positive stress ECG and a normal echocardiogram,coronary artery diseasewas present in five. The negative predictive value of exercise echocardiographyin patients with a positive stressECG was 62%. In 19 patients the stress ECG result was nondiagnostic. In this particular group of patients the

exercise echocardiography diagnosed correctly 4 patients with coronary artery disease (sensitivity 100%) but only eight out of the 15 patients without disease (specificity 53%, diagnostic accuracy 63%, Table 3).

4. Discussion

Exercise echocardiography appears to have high sensitivity and specificity in detecting coronary artery disease [7-91. The goal of this study was not to verify these findings, but to determine its diagnostic value in patients with left ventricular hypertrophy and suspected coronary artery disease. Exercise electrocardiography has limited sensitivity and specificity in this particular group. This is even more limited in several patient groups (e.g., patients with left bundle branch block, left ventricular hypertrophy, nonspecific repolarization abnormalities on the resting ECG, prior myocardial infarction, women, etc.) [14-161. Since hypertension is a major risk factor for the development of coronary artery disease, the reliability of exercise electrocardiography for the evaluation of chest pain in patients with left ventricular hypertrophy is an important clinical problem. The low specificity of the exercise ECG, due to the ST segment depression in the presence of left ventricular hypertrophy without angiographically detected coronary artery disease, dramatically lowers the diagnostic accuracy of this test [17,18]. Unfortunately, alternative stressing procedures, such as exercise radionuclide angiography, thallium-201 stress imaging and positron emission tomography were found to be inadequate screening tests for coronary artery disease because of the

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frequent occurrence of false-positive responses [6,16,19]. Previous experimental and clinical studies have shown that left ventricular hypertrophy, irrespective of pathogenetic mechanism, presents depressedcoronary flow reserve despite normal epicardial coronary arteries [20-221. This patbophysiologic mechanism could be an explanation for the ST segment depression and thallium-201 defects during the dipyridamole stresstest in the absenceof obstructive coronary artery disease [4,23]. This pattern of findings resembles patients with microvascular disease such as in Syndrome X and diabetesmellitus. In the present study, the patients with pure left ventricular hypertrophy during the exercise test, were similar to normal group regarding the wall motion index score. This did not differ significantly from the normal group at any stageof the exercisewhile it was shown to be significantly lower than in the LVH( +) CAD( +) group at peak and post exercise (Table 5). Our findings are consistent with previous studies showing that patients’ with pure left ventricular hypertrophy do not develop a regional dyssynergy of contraction although they present dipyridamole induced chest pain and/or ST segmentdepression[24]. On face value these findings appearto be a paradox since the mechanical properties of the left ventricle are more sensitive to ischemia and appear earlier than the electrocardiographic changes or the chest pain. A possible explanation is that regional wall motion abnormalities develop when ischemia involves the left ventricle transmurally, as it occurs in coronary artery disease. In left ventricular hypertrophy, as in any ‘small vessel’ disease, ischemia evolves in a horizontal (circumferential) direction, large enough to induce ST segment depression or chest pain but not so deep to provoke wall motion abnormalities [24,25]. In our study, there was no statistically significant linear relation between indexed left ventricular massand wall motion index score. Similarly, Houghton et al. did not find any correlation between coronary flow reserve and left ventricular hypertrophy, suggesting that the relation is more complex [4]. The behavior of the wall motion index score was proven to be a good arithmetic predictor of coronary artery disease in the presence of left ventricular hypertrophy. Although left ventricular hypertrophy

alone seemsto be insufficient to produce significant regional wall motion abnormalities, the combination with coronary artery disease results in significantly higher score. This score, in LVH( +) CAD( +) group, appearsnot only at peak exercise but also at the 3 min post exercise. One must assumethat the combination of the reduced coronary flow reserve produced by left ventricular hypertrophy with ischemia due to the coronary artery diseaseleads to an excessive ischemic burden on the left ventricle. Thus, the left ventricle is unable to recover in this short period of time as it happens in patients with pure coronary artery disease(Table 5). This behavior of the score at peak and post exercise differentiates patients with combined coronary artery diseasewith left ventricular hypertrophy from pure left ventricular hypertrophy or coronary artery disease.The patients with pure coronary artery disease at peak exercise showed a similar increase of the wall motion index score as patients of group LVH( + ) CAD( + ), but the score fell significantly to rest value at the post exercise period. In patients with pure left ventricular hypertrophy the wall motion index score behaved quite similarly as in the control group. The mean ST depression,as arithmetic predictor of coronary artery disease in exercise electrocardiography, failed to distinguish the differences between groups (Table 2). In the present study the exercise echocardiography proved to be superior to exercise electrocardiography in detecting coronary artery diseasein the presence of left ventricular hypertrophy. In patients with left ventricular hypertrophy the specificity (71%) and diagnostic accuracy (66%) were higher compared to exercise electrocardiography (21% and 48%, respectively). Even in patients without left ventricular hypertrophy the sensitivity (70%) and the diagnostic accuracy (78%) were shown to be higher with exercise echocardiography. Picano et al. reported a 67% sensitivity and 92% specificity in hypertensive patients with dipyridamole-echocardiography although only 16 of the 63 hypertensive patients had echocardiographic evidence of left ventricular hypertrophy [23]. Similarly, Marwick et al. by treadmill exercise testing and Senior et al. by dobutamine stress detected a higher specificity and diagnostic accuracy of exercise echocardiography compared to electrocardiography in patients with known left ventricular hypertrophy [26,27]. The main disadvan-

S.T. Toumanidis et al. / International

tage of the exercise electrocardiography was the number of patients with a non-diagnostic test due to the presence of non-specific ST-T changes or left bundle branch block. The superiority of the exercise echocardiographyin this particular group (sensitivity of lOO%, specificity of 53% and diagnostic accuracy of 63%), was established while the exercise electrocardiography was non-diagnostic (Table 3). Ryan et al. in a heterogenouspopulation of 309 patients with known or suspectedcoronary artery diseasereported that of the 104 patients with a non-diagnostic ECG, echocardiography correctly identified 95% of those with coronary artery disease and 75% of those without disease [28]. Similar results have been reported previously, although in a much smaller series [8]. If the two techniques were combined our results indicate that diagnostic accuracy will be increased.

5. Clinical implications The results of the present study suggest that exercise digital echocardiography is a feasible, safe and accuratenoninvasive technique for the detection of coronary artery disease in the presence of left ventricular hypertrophy. In the subgroup of patients with a non-diagnostic exercise ECG, due to the presenceof non-specific ST-T abnormalities or to the left bundle branch block, exercise echocardiography shows an extremely high sensitivity. Therefore, its use as a screening test in those patients with an inconclusive exercise ECG is fully justified.

6. Limitations There are some limitations of our study. The small number of patients is certainly a major limitation of this study. Another limitation is the lack of a more quantitative approach,both for the echocardiographic and angiographic data. A detailed quantitative evaluation of regional wall motion may have enhanced the detection of subtle wall motion changes. At present, visual semiquantitative assessmentof wall motion remains the simplest and the most accurate diagnostic method.

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Reported criteria for defining an abnormal stress echocardiogram are varied. Most investigators consider a response to exercise to be normal if wall motion improves or does not worsen [29]; others classify a segmentas abnormal if it does not become hypercontractile with exercise [8]. In some studies, a positive stress echocardiogram refers to a test that has either a resting or stresswall motion abnormality. A consensusregarding the finer points of diagnosing ischemia by stress echocardiography has not been reached. In this study echocardiography was performed at rest and immediately after treadmill exercise in all patients. Thus wall motion abnormalities must persist into early recovery to be reliably detected and accuracy critically dependenton rapid acquisition of postexerciseviews. Recent data suggestthat bicycle exercise echocardiography, which permits imaging during exercise, may have slightly higher sensitivity for the detection of coronary artery diseasecompared to echocardiographyperformed after treadmill exercise [28]. It should be emphasizedthat most of the patients do not reach their target heart rate by bicycle as would be expected with treadmill exercise.When higher workload is attained, it is probable that rapid recovery would be less likely. However, the optimal modality of stressto combine with echocardiography has not been established. Finally, left ventricular hypertrophy was diagnosed exclusively on the basis of left ventricular mass calculations with sex-specific limits after correction for body surface area. The upper limits of normal left ventricular mass were adopted from the Framingham Heart Study. In the literature, different sets of criteria were used [12,30]. Ideally, outcomeguided left ventricular hypertrophy criteria are best suited for clinical application, but such criteria are not yet available.

7. Conclusions Echocardiographic determined left ventricular hypertrophy has been recognized as an important marker of cardiovascular morbidity and mortality. The exercise ECG test is the most widely used clinical tool for the diagnosis of coronary artery

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disease. In the presence of left ventricular hypertrophy, the exercise ECG was found to be inadequate screening test for coronary artery diseasebecauseof the frequent occurrence of false-positive responses. Our results suggestthat exercise echocardiographyis a feasible, safe and accurate noninvasive technique for the detection of coronary artery disease in the presenceof left ventricular hypertrophy. Especially, in patients with a non-diagnostic exercise ECG the diagnostic yield of exercise echocardiography permits a more accurate separation of patients with and without disease.

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