This is the most frequently used index of left ventricular performance. However, it may not accurately reflect left ventricular contractility since it is heavily dependent on loading conditions 20 which is particularly important in patients with heart failure for the following reasons. First of all, mitral regurgitation is frequent in these patients, and can lead to overestimation of left ventricular contractility due to rise in ejection fraction caused by changes in loading conditions (higher preload, lower afterload) 21 Secondly, activation of neuroendocrine compensatory mechanisms may increase afterload, which in turn may subsequently decrease ejection fraction 22 Thirdly, left ventricular preload is dependant upon interventricular interaction which is exaggerated in cases of pulmonary hypertension 23 a frequent finding in DCM patients. Furthermore, dobutamine has variable influence on afterload, since it has been shown that it may decrease afterload by 10% in patients with mild heart failure, but may also increases afterload by 5% in patients with severe heart failure 24.

Despite all these potential drawbacks, the change in ejection fraction during stress has been shown to have crucial prognostic significance in patients with DCM. It is generally accepted that increase in ejection fraction by ≥ 5% or change from baseline ejection fraction by ≥ 20% during stress-echocardiography identifies patients with preserved left ventricular contractile reserve and better prognosis. Ejection fraction should be assessed by Simpson biplane formula.

Wall motion score index has been traditionally used in stress-echocardiography for the detection of coronary artery disease 25. Only two reports used this index of left ventricular contractility to assess prognosis and functional recovery of DCM patients 1015. Wall motion score index was assessed in a standard manner, by using 16 segment model of the left ventricle according to the recommendations given by American Society of Echocardiography 26. The major potential drawback for use of this index is semiquantitive assessment of wall motion, which is even more subjected to inter- and intraobserver variability in DCM patients due to preexisting wall motion abnormalities and substantial number of patients with left bundle branch. It has been suggested that dobutamine induced change in wall motion score index of ≥ 0.44 identifies patients who will do better during the follow-up.

This index is not sensitive to changes in afterload, and after optimization for preload accurately reflects contractile properties of the myocardium 27. Noninvasive calculation of cardiac power output is relatively complex and requires special instrumentation 11. The most practical formula to calculate cardiac power output in Watts was suggested by Cook and coworkers 28:

Cardiac power output = (cardiac output × mean arterial pressure) × 2.22 × 10 ^-3

where cardiac output is calculated by multiplying aortic velocity-time integral by aortic valve area, and mean arterial pressure is calculated in a standard manner.

The major problem with this index is that its calculation is time consuming, requires skilled echocardiographer, and is subjected to numerous sources of error. Furthermore, very few cardiologist are familiar with this index which precludes its wider use. Suggested cut-off point between patients with respect to prognosis is dobutamine induced change in cardiac power output of ≥ 1 W.

Most authors prefer low-dose dobutamine stress-echocardiography, probably because it is considered safe and is not time consuming. A report by Paelinck and coworkers has suggested that low-dose dobutamine can identify patients with atrial fibrillation induced dilated cardiomyopathy who will improve following restoration of sinus rhythm 29. These authors concluded that low-dose dobutamine may be used to identify patients with tachycardiomyopathy.

It has been shown, in a small number of patients, that changes in left ventricular wall motion score index and ejection fraction during low-dose dobutamine echocardiography are predictive of improvement of left ventricular systolic performance during medium term follow-up (Figure 1) 15. Since the degree of beta-receptor downregulation and desenzititation is a marker of progressive deterioration of left ventricular systolic function 30, the authors hypothetized that improvement in contractility during dobutamine infusion is greater in patients with preserved beta-receptor function who will subsequently show improvement in systolic performance.

These findings are further extended, so it has been shown that the presence of myocardial contractile reserve identifies patients who will respond favorably to beta-blocker therapy 31. Furthermore, Drozd and coworkers have demonstrated that the incidence of cardiac death or need for cardiac transplantation is lower in patients with preserved contractile reserve. In this paper, multivariate analysis identified left ventricular end-systolic volume of less than 150 ml after dobutamine infusion and no decrease of left ventricular end-diastolic volume after dobutamine infusion as significant predictors of combined end-point 32.

Contractile reserve has been shown to correlate well with peak oxygen consumption (Figure 2) 16. At multivariate analysis in this report, only percentage change in end-systolic volume index was significantly associated with occurrence of cardiac death or hospitalization for worsening heart failure. The area under receiver-operating characteristic curve was similar for percentage change in end-systolic volume index and peak oxygen consumption (0.86 ± 0.04 vs. 0.80 ± 0.06). Additionally, a report by Paraskevidis and coworkers suggested that low-dose dobutamine may further refine prognosis in patients with maximal oxygen consumption between 10 and 14 ml/kg/min 13. This finding may be used for prioritization of patients for cardiac transplantation.

Use of high-dose dobutamine is not associated with serious complications in DCM patients, and has an overall feasibility of 88.7%. The most common adverse event requiring discontinuation of dobutamine infusion is occurrence of complex ventricular arrhythmias, which was noted in 8% of patients (frequent multifocal ventricular extrasystoles in 6.4% and nonsustained ventricular tachycardia in 1.6%) 10. Although there are no data on the association of complex ventricular arrhythmias and serum potassium concentrations, it may be postulated that complex arrhythmias are more frequent in potassium depleted patients. Therefore, it appears prudent to check serum potassium level prior to high-dose dobutamine stress-echocardiography. Hypotension, defined as decrease in systolic blood pressure by more than 30 mmHg, is very rare in the absence of complex ventricular arrhythmias and, in authors experience, occurs in less than 1% of patients with angiographically documented idiopathic DCM. Potential advantage of high-dose, as compared to low-dose, dobutamine echocardiography is that it may evoke more complete contractile response.

Very intriguing finding is that early in the course of DCM, dobutamine induced change in left ventricular contractile response and geometry is able to predict late spontaneous recovery of left ventricular systolic performance 14. It is interesting that this study confirmed previous findings that increased left ventricular mass is associated with better outcome in DCM 33, and suggested that the presence of left ventricular hypertrophy implies the presence of myocardial contractile reserve.

The largest study that studied prognostic significance of high-dose dobutamine included 186 DCM patients. The major findings of this study are that dobutamine induced change in wall motion score index is able to identify patients at greater risk for cardiac death during the follow-up (Figure 3), and that change in wall motion score index carries superior prognostic information than change in ejection fraction 10 Additionally, it has been reported that dobutamine induced change in ejection fraction by ≥ 8%, assessed by radionuclide ventriculography, is prognostically superior to maximal oxygen consumption in patients with severe DCM 34.

Recent data by our group demonstrate that contractile reserve indices assessed by high-dose dobutamine correlate with myocardial histomorphometric features, suggesting that contractile reserve is strongly related to the degree of hystological disruption in DCM patients. Myocyte diameter and interstitial fibrosis showed strongest correlation with change in wall motion score index (r = -0.667, p < 0.001, and r = -0.567, p = 0.004, respectively), followed by change in ejection fraction (r = -0.603, p = 0.002, and r = -0.467, p = 0.021, respectively) 35.

It appears that dipyridamole may be used instead of dobutamine to evoke contractile response, since it is less arrythmogenic 36 better tolerated and yields similar prognostic information in patients with coronary artery disease 37. Ability of dipyridamole to recruit contractile reserve is mediated through increase in coronary blood flow and accumulation of endogenous adenosine 3839. Potential advantage of dipyridamole over dobutamine stress-echocardiography is that the former is not affected by the use beta-blocking agents which are frequently used in DCM patients. Only one study recently examined ability of dipyridamole to predict prognosis in DCM patients. The authors concluded that increase in wall motion score index ≥ 0.15 during dipyridamole stress identifies patients who are more likely to survive during the mean follow-up of more than three years 19. Reported overall feasibility of dipyridamole stress-echocardiography in this study was 99.2%, which is significantly higher than previously reported feasibility of dobutamine stress-echocardiography.

As previously said, there are no echocardiographic studies on exercise induced contractile response in DCM patients. However, Nagaoka and colleagues used radionuclide ventriculography to measure increase in ejection fraction during exercise in DCM patients with mild symptoms, and concluded that change in ejection fraction <4% identifies patients with worse prognosis 17. Additionally, it has been suggested that variables, such as cardiac power output, obtained by direct hemodynamic measurements during exercise may have important prognostic implications in patients with systolic dysfunction 12.