Eur J Echocardiography (2001) 2, 4045 doi:10.1053/euje.2000.0059, available online at http://www.idealibrary.

com on

Non-invasive Diagnostic and Prognostic Assessment of Single-vessel Coronary Artery Disease: Focus on Stress Echocardiography
R. Bigi*, L. Cortigiani and A. Desideri
Cardiovascular Research Foundation, S. Giacomo Hospital, Castelfranco Veneto, Italy

Aims: Revascularization procedures are increasingly applied in patients with single-vessel coronary artery disease in spite of the fact that a prognostic benet has been proved only for soft end-points. This review summarizes the results of stress echocardiography in the diagnostic and prognostic assessment of these patients. Methods and Results: The diagnostic and prognostic assessment of patients with single-vessel disease using stress (exercise, dobutamine, adenosine and dipyridamole) echocardiography are focused upon in the light of pathophysiological considerations and the results of clinical studies. Factors aecting test accuracy are individually addressed and comparisons made with dierent stress testing modalities, including exercise electrocardiography and nuclear techniques. Finally, therapeutic options are

discussed and the superior accuracy of the physiological assessment of coronary stenosis as compared to the simple anatomic evaluation emphasized. Conclusions: Patients with single-vessel disease represent an anatomically heterogeneous group. Although the suboptimal performance of any technique in their evaluation has to be acknowledged, stress echocardiography can eectively contribute to selection of the management strategy. (Eur J Echocardiography 2001; 2: 4045)  2001 The European Society of Cardiology Key Words: single-vessel disease; coronary artery disease; stress echocardiography.

Introduction
Single-vessel coronary artery disease (CAD) is a puzzling clinical setting from both the diagnostic and the prognostic point of view. It may present with variable functional expressions, but is generally associated with a favourable outcome[13]. Nevertheless, percutaneous transluminal coronary angioplasty (PTCA) is increasingly applied in these patients despite the fact that a prognostic benet has been proved only for soft endpoints, like recurrence of symptoms[4], and in spite of the superiority of physiological assessment of coronary stenosis compared to angiographic evaluation[5]. In the last few years echocardiographic imaging, combined with exercise or pharmacological stimuli, has been increasingly used for the diagnosis of CAD[6]. The aim of the present article is to summarize the results of this imaging technique in the diagnostic and prognostic assessment of single-vessel disease.
*Corresponding author: R. Bigi, Via Visoli 1, 23037 Tirano, Italy. 1525-2167/01/010040+06 $35.00/0

The Pathophysiological Rationale

Non-invasive stress tests are often performed not only to detect coronary stenosis, but also to determine the physiological importance of angiographically identied coronary lesions[7,8]. Baptista et al.[9] reported that the minimal lumen diameter was the best angiographic predictor of a positive dobutamine stress test. However, the results of functional testing are even better related to the physiological impairment in coronary ow reserve. Bartunek et al.[10] did not nd any relation between the qualitative descriptors of stenosis morphology and the degree of dobutamine-induced dyssynergy. On the other hand, Picano et al.[11] compared the results of dipyridamole stress echocardiography with the severity of CAD, as assessed by quantitative angiography, and the regional coronary reserve, as assessed by dynamic positron emission tomography. They found patients with positive stress echocardiography to have signicantly greater area reduction in stenotic vessel and signicantly lower maximal regional blood ow in stenotic vessel
 2001 The European Society of Cardiology

Assessment of Single-vessel Coronary Artery Disease Table 1. Factors inuencing the diagnostic sensitivity of stress echocardiography in single-vessel disease.
1. 2. 3. 4. 5. 6. 7. Type of stressor. Severity and location of stenosis. Eect of anti-ischaemic drugs. Lesion morphology. Test protocol. Collateral circulation. Status of distal myocardium.

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critical stenosis by vasodilators, which can lead to inappropriately negative results, particularly in the case of single-vessel disease.

Severity and Location of CAD

The diagnostic accuracy of dobutamine stress echocardiography depends strongly on the number of diseased coronary arteries[21], with a mean sensitivity of 74% for single-vessel as compared to 86% for doublevessel and 92% for triple-vessel disease. Nevertheless, the degree of dierence is smaller as compared with exercise electrocardiography, in which sensitivity for singlevessel disease ranges from 25 to 60%[22]. Moreover, even though coronary angiography is generally considered the gold standard for assessing the diagnostic accuracy of non-invasive tests, visual assessment of stenosis is limited by substantial interobserver variability[23], particularly in the case of intermediate lesions (lumen reduction of 5070%), where stress echocardiography can contribute to identify the physiological signicance of coronary narrowings[24]. The stenosis location also aects the accuracy of stress echocardiography. Mean sensitivity and specicity for individual vessels reported in eight studies[2532] were as follows: left anterior descending coronary artery 69% and 91%, circumex coronary artery 43% and 92%, right coronary artery 69% and 88%, respectively.

area, thus providing evidence of both anatomical and functional correlates of the stenotic lesion. More recently, Danzi et al.[12] reported that stenotic ow reserve, assessed by intracoronary Doppler, is the variable that best describes the functional signicance of an isolated lesion of the left anterior descending coronary artery. Even in the case of moderate coronary stenosis, a detailed physiological assessment by means of myocardial fractional ow reserve correlates closely with the results of non-invasive stress tests[13]. All these results are in keeping with previous reports on exercise ECG[14] and nuclear techniques[1517] and conrm the close correlation between the physiological signicance of coronary lesions and the non-invasive assessment of myocardial ischaemia.

Diagnostic Assessment
Many studies have addressed the issue of the diagnosis of single-vessel disease by exercise ECG with or without radionuclide ventriculography, but almost general agreement exists on the insucient sensitivity of ECG signal[18] and the poor reproducibility and specicity of radionuclide ventriculography[19]. Studies comparing stress echocardiography and perfusion scintigraphy for assessing single-vessel CAD have been reviewed recently by Geleijnse et al.[20]. Irrespective of the stressor used, perfusion scintigraphy proved to be the more sensitive test (78% vs. 67% with exercise; 78% vs. 69% with dobutamine; 76% vs. 61% with dipyridamole and 81% vs. 51% with adenosine), with a marginally superior specicity using the echocardiographic technique. The accuracy of stress echocardiography for detecting single-vessel CAD is aected by several factors (Table 1), the majority of which are discussed below.

Anti-ischaemic Drugs
Anti-ischaemic drugs decrease the sensitivity of both physical and pharmacological stressors[29,33]. The sensitivity of dipyridamole stress seems to be more inuenced in both echocardiographic[3335] and nuclear[36] studies as compared to dobutamine stress. In a placebo-controlled, cross-over study[33], 91% of 57 patients with signicant (>70% diameter stenosis) CAD undergoing dipyridamole stress echocardiography developed ischaemia o therapy, whilst only 65% of them did so on therapy (P<001). The eect was most marked for the combination of beta-blockers and nifedipine. The eect of beta-blockade on dobutamine stress echocardiography has been a matter of debate. In experimental single-vessel disease in an animal model, betablockers attenuated the ability of dobutamine stress to detect a signicant coronary lesion[37,38]. This has been attributed to the reduced increase in heart rate and left ventricular pressure, improvement of regional coronary ow per heart beat and attenuation of regional ischaemic lactate production[38]. Surprisingly, no eect of beta-blockers on the accuracy of dobutamine stress was reported in some clinical studies[3941], whilst a correlation of this therapy with false negative results was reported by others[42]. A possible explanation of this discrepancy is that more symptomatic CAD, which is therefore more severe and more likely to precipitate
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Type of Stressor
Dobutamine and exercise show a superior sensitivity (69% and 67%, respectively) compared to dipyridamole and adenosine (61% and 52%, respectively) in detecting single-vessel CAD, whilst specicity is similar for all stressors[20]. The background to these ndings may be the dependence on inducing coronary steal to assess

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R. Bigi et al. whether pharmacological stress echocardiography could contribute to risk stratication in this clinical setting, Cortigiani et al.[58] analysed data from 754 single-vessel disease patients. On multivariate analysis, positive stress echo was the only independent predictor of death and myocardial infarction (odds ratio=29) in medically treated patients. Moreover, a signicantly higher 4-year event-free survival was found in invasively versus medically treated patients with a positive (P=0012) but not with a negative (P=0853) stress result, thus emphasizing the superior benet from an ischemia-guided therapeutic strategy. Detection of myocardial viability after acute uncomplicated infarction with low dose dobutamine has been shown to predict unstable angina[59]. Moreover, we recently demonstrated that ischaemia in dys-synergic but viable segments can predict cardiac events[60]. The clinical impact of these data in the subset of patients with single-vessel disease is still unknown.

ischaemia, is more frequently on treatment. On the other hand, non-beta-blocker antianginal therapy showed only a modest eect[43]. However, additional atropine co-administration can eectively counterbalance the limiting eect of both beta-blocker and non-betablocker therapy on diagnostic sensitivity of dobutamine stress[28,43,44]. The inuence of drugs on the ischaemic response at stress echo can be also used to control anti-ischaemic drug eects[45]. This can be of interest in patients with single-vessel disease who most benet from appropriate medical treatment.

Lesion Morphology
The accuracy of stress echocardiography generally parallels the severity of CAD[46]. However, the importance of plaque morphology has also been emphasized by recent studies[4749]. Complex lesions (angiographic characteristics suggestive of thrombi and/or ulcer) were associated with higher sensitivity (85% vs. 53% in simple lesions, P<0001) using dipyridamole[4748]. This result was not conrmed in a later study with dobutamine[50]. The pathophysiological background for the better correlation of dipyridamole echo and stenosis morphology could be related to the more extensive endothelial involvement in the case of complex stenosis[48].

Therapeutic Options
Historical data of the CASS Study show that medically treated patients with single-vessel disease had a 10-year survival rate not statistically dierent than those undergoing surgery[63]. These ndings have been conrmed by the Duke Data Bank Registry[64]. The ACME study[4] randomized 328 patients with a positive exercise ECG, 166 to PTCA and 162 to medical treatment. Five-year results revealed that more patients were angina-free and drug-free with PTCA than with medical treatment. However, the number of events and hospitalizations in the two groups was similar. Even in patients with proximal left anterior descending coronary artery involvement, no dierences were found in terms of incidence of infarction and death between medically treated and revascularized patients in the MASS Study[65]. Moreover, broad basis clinical practice failed to demonstrate a reduction of subsequent myocardial infarction or death even with use of coronary stenting[66]. Stress echocardiography has been demonstrated to be a reliable method to detect relevant restenosis after PTCA, and helps to select patients who may benet from repeated angiography[6769].

Miscellaneous Factors
Conditions reducing compensatory microvascular dilatation (such as left ventricular hypertrophy, arterial hypertension or increased low-density-lipoprotein cholesterol) and left anterior descending location of coronary stenosis may inate the sensitivity of stress echocardiography. Increasing stenosis severity has a similar eect, whilst milder stenosis, even limiting peak hyperaemic ow, may produce little or no ischaemia[51]. Similarly, the presence of collaterals and submaximal tests may underscore sensitivity, particularly in the case of moderate stenosis. Finally, resting echocardiographic aspects related to the pathophysiological status of the myocardium may decrease (scar) or increase (viable) diagnostic sensitivity.

Prognostic Assessment
Patients with single CAD and positive stress tests are frequently revascularized. Consequently, the prognostic value of any stress testing modality is dicult to assess. Although exercise-dependent techniques convey prognostic information in patients with multivessel disease, a similar evidence in patients with single-vessel disease was not denitely proved[24,25,5262]. Moreover, single-vessel disease population was not separately analysed in a consistent proportion of studies. In order to verify
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Conclusions
The practice of performing coronary revascularization purely on the basis of the anatomic data, with no knowledge of their functional correlates, is a frequent but inadequate therapeutic option. Patients with singlevessel disease are an anatomically heterogeneous group as regards location and severity of stenosis, plaque morphology, collateral circulation and presence of viable or infarcted myocardium. This hetereogenity explains the diculties in demonstrating the superiority of an ischaemia-guided strategy as compared to a direct

Assessment of Single-vessel Coronary Artery Disease referral to revascularization. Indeed, the suboptimal performance of any technique in the evaluation of single-vessel disease has to be acknowledged: 7580% for perfusion imaging and 6570% for stress echocardiography. In particular, the pharmacological stressor (adenosine) or the anatomical location of the disease (circumex coronary artery) can negatively aect the performance of stress echocardiography (52% and 43%, respectively). Nevertheless, this technique provides a panoramic view on the main markers of risk (i.e. resting function, viability and ischaemia) and, therefore, may be of help in selecting the management strategy for the individual patient.

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