INTRODUCTION

Dipyridamole stress echocardiography (DSE) is a first-line stress test for the diagnosis and/or prognosis of coronary artery disease, particularly in patients unable to exercise maximally. Although the sensitivity of DSE is lower in single-vessel disease, the diagnostic accuracy is similar to that of dobutamine stress echocardiography in protocols that include atropine or handgrip exercise in the final stage and employ a fast infusion rate. (1)

This type of stress also allows for the measurement of other parameters with a high degree of feasibility. These parameters include coronary flow reserve (CFR) in the left anterior descending (LAD) coronary artery and the assessment of myocardial deformation using speckle-tracking echocardiography. This is possible because the drug has vasodilator properties and produces lower increase in contractility and in heart rate (HR) compared to dobutamine, which makes it an ideal complement for the analysis of myocardial strain. It has been previously demonstrated that the information provided by these techniques increases the sensitivity of the test without significantly affecting its specificity and provides additional prognostic value. (2)

While myocardial strain quantification offers a more sensitive means of detecting early signs of myocardial dysfunction that may otherwise go undetected in subjective wall motion analysis, one of its limitations is its dependence on myocardial loading conditions. It has been suggested that measuring the pressure-strain loop is an effective method for estimating myocardial work (MW). This allows for a more comprehensive evaluation of myocardial function by considering the global myocardial work index (GWI), the global constructive work (GCW), the global wasted work (GWW), and the global work efficiency (GWE). The GWI is derived from the area of the pressure-strain loop. The GCW represents shortening of the myocardium during isovolumetric contraction and lengthening of the myocardium during isovolumetric relaxation. The GWW represents the amount of work that is not useful in this context (lengthening of the myocardium during systole or shortening during isovolumetric relaxation). Finally, the GWE is defined as the ratio between GCW and the sum of GCW and GWW. (3,4,5,6)

The aim of the present study was to evaluate the behavior of different MW parameters during an DSE study in a consecutive population of patients and the differences between those with and without ischemia.

METHODS

RESULTS

A total of 30 patients were consecutively included; mean age was 69.9 ± 10 years and 45% were men. One third had a history of coronary artery disease and the prevalence of cardiovascular risk factors was high. The main reason for performing DSE was to assess the preoperative risk of cardiac events before peripheral vascular intervention. These characteristics are summarized in Table 1.

Myocardial ischemia was evident in 8 patients (27%) according to the visual analysis of wall motion. These patients exhibited a trend toward higher prevalence of previous MI and cardiovascular risk factors. There were no differences in the baseline HR and blood pressure at rest and during pharmacologic stress. Left ventricular volumes had no differences in patients with and without ischemia but left ventricular ejection fraction (LVEF) and GLS were significantly lower in patients with dipyridamole-induced ischemia. The CFR in the LAD coronary artery was lower in patients with ischemia, and these patients had a trend toward lower contractile reserve. Table 2 summarizes the characteristics of the 2 groups.

When the different parameters of MW were analyzed, GWI and GCW decreased in both groups, although there was a tendency for a smaller decrease in patients without ischemia. In contrast, the GWW and GWE performed differently. In patients with ischemia, the GWW increased and the GWE decreased. In patients without ischemia, the GWW decreased while the GWE remained unchanged or significantly improved (Table 2, Figure 2 and 3).

DISCUSSION

Stress echocardiography is still a first-line test for the diagnosis and prognosis of coronary artery disease. About 20-30% of patients cannot exercise maximally and the use of high-dose dipyridamole administered over 4 minutes is an excellent option in this scenario. However, the main limitation of this approach is the subjectivity inherent in visual analysis of wall motion, particularly in less experienced operators. This is a relevant consideration given that the drug does not increase contractility and heart rate in a proportionate manner to that observed with dobutamine, and that a considerable proportion of patients are already receiving beta-blocker therapy.

To address these limitations, the concurrent measurement of CFR in the LAD coronary artery and the analysis of myocardial deformation through two-dimensional strain have been proposed. The CFR allows for a comprehensive evaluation of the coronary vascular tree and numerous studies have demonstrated its significant prognostic value beyond the presence or absence of wall motion abnormalities. Therefore, its measurement is strongly recommended in all patients undergoing stress echocardiography. (10,11) Nevertheless, its implementation in routine clinical practice is limited due technical considerations, namely the necessity for an optimal configuration of imaging parameters, the fact that not all operators know how to use it, and economic reasons in our setting.

The quantification of myocardial deformation by analyzing GLS represents another valuable tool for enhancing the sensitivity of the test without significantly reducing its specificity. In this case, the slight increase in HR and contractility, which was previously regarded as a limitation of the method, is, in fact, an advantage. DSE is considered the ideal scenario for the use of two-dimensional strain. The analysis of the performance of subendocardial fibers, which are more sensitive to ischemia, allows for the detection of incipient abnormalities and helps in the interpretation of myocardial wall motion, as demonstrated in a study by Lowenstein et al. in which the inclusion of GLS increased the sensitivity of the test from 50% with visual analysis to 83.3% (p = 0.001). (2) The close relationship between the performance of CFR and GLS was demonstrated in a publication by Arbucci et al., in which both parameters were evaluated with DSE in a population of 179 patients. Both values showed a significant correlation, that was higher when the regional strain of the apical segments was considered. (12)

Myocardial work assessment has the advantage of incorporating loading conditions to conventional two-dimensional strain and the pressure-strain loop is proportional to myocardial oxygen uptake. (13) Its usefulness has been demonstrated in numerous clinical scenarios such as patients with arterial hypertension, valvular heart disease, coronary artery disease, heart failure and cancer, among others. (14,15,16) However, there is little evidence on its usefulness during stress echocardiography. Recently, Borrie et al. analyzed 60 patients who underwent exercise stress echocardiography. Of these patients, 30% exhibited evidence of ischemia, as indicated by wall motion abnormalities. With exercise, GWI increased and GWE remained unchanged in individuals without ischemia while in those with ischemia GWI remained unchanged (i.e., did not increase) and GWE showed a significant decrease (from 93% to 87%). This study determined that the best cut-off point for identifying patients with myocardial ischemia was a 25% increase in GWI, with a sensitivity of 90% and a specificity of 85%. (17) These findings suggest that this tool could have additional value in patients with a good ultrasound window. The study by Edwards et al. reaches similar conclusions. (18) One of the main limitations to the use of MW during exercise stress echocardiography is the quality of the ultrasound window and the elevated HR during exercise that hinders accurate analysis of myocardial wall motion during the cardiac cycle.

In a study using pharmacological stress echocardiography, Leitman et al. analyzed MW with the use of dobutamine in 119 patients without ischemia. Dobutamine stress echocardiography resulted in a decrease in all MW parameters despite improvement in GLS. The authors suggest that the dose of up to 40 mcg/kg/min until 85% of maximum heart rate is reached may have deleterious effects on contractility. (19) More recently, Liu et al. reported a study performed with adenosine in 78 patients with microvascular angina and evaluated the performance of MW according to the presence or absence of CFR. The main finding was that patients with microvascular disease (abnormal CFR) had increased GWW and decreased GWE, in addition to a trend towards a smaller increase in GWI and GCW. (20) Similar findings are reported in an abstract published by Lofrumento et al. in 50 patients with suspected macrovascular disease, where it is evident that the analysis of GWE and GWW has an additive role beyond GLS when implemented in a DSE. (21)

The results obtained in our study are in line with those studies evaluating MW with exercise and adenosine in terms of increased wasted work and decreased efficient work in patients with ischemia, which is related to the percentage of post-systolic strain. It should be noted that, in contrast to the effects observed during exercise, the use of vasodilators such as dipyridamole is expected to result in stable and potentially decreased blood pressure values. Consequently, it can be expected that the GWI and GCW will not increase or even decrease slightly during exercise.

CONCLUSIONS

The introduction of new quantitative analysis tools, such as MW, could assist in the interpretation of signs of myocardial ischemia in DSE. Further verification of these observations is required in larger patient cohorts with the inclusion of additional stressors such as exercise and dobutamine.

Conflicts of interest

None declared. (See authors' conflict of interests forms on the web).