The fundamental principle of stress echocardiography is that left ventricular (LV) abnormalities are usually not apparent in the early stages disease because of the heart’s functional reserve. In the routine interpretation of stress echocardiography, a search for abnormal regional wall motion is complemented by an assessment of the global response to exercise. The normal LV response to exercise involves an increment of ejection fraction (EF) and reductions of ventricular volumes, and this information has been used in interpretation from the earliest days of two-dimensional stress echocardiography. Indeed, extensive (usually left main or multivessel) ischemia can cause LV dilatation and reduction of EF.

Loss of LV contractile reserve is a more subtle abnormal global LV response, indicating failure of these parameters to improve with exercise rather than to worsen. Typically, this response is defined as a failure to improve EF by >5%, but in addition to assessment of these findings with EF or LV volumes, they have also been defined on the basis of annular excursion, including tissue Doppler. The phenomenon of functional reserve is not limited to systole: the diastolic equivalent of contractile reserve is diastolic reserve. Common causes of impaired contractile reserve include the performance of submaximal exercise and increased ventricular afterload (poorly controlled systemic hypertension or pulmonary hypertension). However, the findings may signify the presence of pathology, including primary myocardial disease, or the beginnings of decompensation from regurgitant valve lesions. The possibility of an association between a lack of contractile reserve and overt coronary artery disease has been discounted on the basis that the changes are global rather than regional. What has not been clear is whether the findings might originate from diffuse coronary artery disease.

In this issue of the journal, Nasis et al . provide strong evidence that the changes are likely to reflect subclinical myocardial disease rather than coronary disease. In this observational study, 1,134 consecutive patients undergoing treadmill echocardiography underwent invasive angiography or coronary computed tomography. Exclusion of patients with obstructive coronary disease, a hypertensive response, a submaximal heart rate, resting LV impairment, and valvular disease led to a final study group of 332 patients, 110 of whom demonstrated abnormal LV contractile reserve, defined by failure to increase EF by >5% with stress. In addition to this response, occurring in the absence of changes on the “coronary lumenogram,” patients with and without these responses demonstrated no differences in coronary microvascular function, as evidenced by myocardial blush grade or Thrombolysis In Myocardial Infarction frame count. These findings allay concerns that the observation of impaired contractile reserve may be a sign of subclinical coronary artery disease.

Instead, impaired contractile reserve appears to be a marker of subclinical LV dysfunction. The subgroup of patients without contractile reserve were older, more likely to be female, limited by dyspnea, and more often associated with hypertension, diabetes mellitus, and slightly greater body mass index. These patients also had reduced resting diastolic tissue velocity with increased atrial volumes. Their higher heart rate responses may reflect abnormal sympathetic activation, as proposed by the authors, or may simply reflect lesser levels of physical fitness and the need for greater heart rate to compensate for relatively lower stroke volume.

Two aspects of this observation are of particular interest. First, this response is clearly afterload dependent. The authors removed patients with hypertensive responses to exercise, but as their definition of this entity was a systolic blood pressure >210 mm Hg in men and >190 mm Hg in women, these exclusions represent the most extreme manifestation of this problem. Indeed, despite the exclusion of overt hypertensive responses to exercise, arterial elastance was more abnormal in patients lacking contractile reserve. This balance between peak systolic pressure and end-systolic volume has been the source of an often neglected body of work in the stress echocardiography literature, with some studies showing events to be associated with failure to increase the ratio between blood pressure and end-systolic volumes.

Second, the findings of this study align the contractile reserve response with other markers of subclinical (mainly longitudinal) myocardial dysfunction, such as diastolic dysfunction and abnormal global longitudinal strain. In the current environment of seeking an earlier diagnosis of heart failure, the recognition of myocardial disease (inferring stage B heart failure) is important in patients with heart failure risk factors (stage A heart failure), because this reclassification has treatment implications. Unfortunately, the ability of echocardiography to recognize wall motion abnormalities and scar has made stage B heart failure more readily identified in ischemic rather than nonischemic heart disease. Recent work has demonstrated that impaired exercise capacity (which can be looked upon as a surrogate for a subsequent adverse outcome) may also be identified in patients at risk for nonischemic cardiomyopathy with not only LV hypertrophy but also resting diastolic dysfunction and abnormal global longitudinal strain. In the context of the report by Nasis et al ., this list might also include patients with abnormal contractile reserve. As with heart failure with preserved EF, this group with subclinical LV dysfunction is likely to be heterogeneous, with subgroups caused by abnormal relaxation, fibrosis, volume overload, and pulmonary vascular changes. At present, we do not know the optimal test for the recognition of subclinical LV dysfunction, nor do we know whether a single “optimal” test can be realized.

Despite these interesting and positive observations, there are some reservations regarding the use of this parameter in individuals rather than across populations. An obvious disadvantage to contractile reserve is that the measurement of volumes and EF after stress can be technically challenging. More important, although LV EF corresponds on average to reference markers for the severity of LV dysfunction, the ability to recognize change is compromised by the test-retest variation of these parameters. It is important to realize that this is not well reflected by measures of inter- and intraobserver variation, which address variability in repeated measurements of the same image clip. For two-dimensional echocardiography, this test-retest variation is in the vicinity of 10%, although this can clearly be improved in the setting of clinical studies, contrast echocardiography, and the use of three-dimensional imaging. Thus, although the use of contractile reserve seems promising for making treatment decisions across populations, its use in individual treatment decisions should be nuanced with the degree of impairment and the clinical setting.

The publication by Nasis et al . is a pragmatic clinical study whose results could be applied in a couple of ways. For patients undergoing exercise echocardiography, lack of contractile reserve should not be considered a marker of coronary disease, just as failure to augment regional function is no longer considered a marker of ischemia. When this response is identified, myocardial disease should be considered, although because of the inherent inaccuracy of this parameter within individuals, caution should be applied to making a diagnosis on the basis of this evaluation alone. Instead, verification of this diagnosis should be based on the evaluation of markers of myocardial disease, including tissue Doppler and strain. Nonetheless, better awareness of the implications of this abnormal response may facilitate the recognition and treatment of stage B heart failure.