The slope of the pressure-volume relation at end-systole, termed Emax by Suga and Sagawa,1 has been considered for the assessment of contractile performance in view of its sensitivity to inotropic changes and relative independence from ventricular load. Because the determination of Emax requires obtaining pressure/volume curves at different loads, attempts have been made to identify a simplified index in humans.2 The variation between rest and peak stress end-systolic pressure-volume relation (ESPVR; the Suga index) is easily obtained during routine stress echocardiography and has been established as a reasonably load-independent index of myocardial contractile performance3–11 that allows a more accurate prognostic stratification than ejection fraction in patients without inducible wall motion abnormalities.12–15

However, like most indexes, the ESPVR does not take into account the diastolic dimensions of the left ventricle. Suga et al.16 reported the size dependence of Emax in experimental conditions and it has since been emphasized that left ventricular (LV) function indexes in humans should be normalized17,18 to enable comparisons of contractile function among patients. The present study was designed to relate the ESPVR index obtained during stress echocardiography at rest and the ΔESPVR (the difference between peak and rest ESPVR) to LV end-diastolic volume (LVEDV) in both normal controls and in patients.

From January 2003, 1142 patients underwent stress echocardiography in quality-controlled stress echo laboratories.9,11,12,14,19–23 The study complied with the Declaration of Helsinki. Informed consent was obtained from all patients (or their guardians) before testing, and the study protocol was approved by the institutional ethics committee. Stress echo data were collected and analyzed by stress echocardiographers not involved in patient care. Exclusion criteria were significant congenital heart disease, unsatisfactory imaging of the left ventricle at rest or during stress, atrial fibrillation, or positive stress echocardiography. From the initial population of 1142 patients, 118 were excluded for stress echo positivity, 11 for congenital heart disease, 18 for atrial fibrillation, and 41 for unsatisfactory echo imaging. Thus, the study population included 891 patients, 593 (67%) men, 298 (33%) women; the mean age was 63 ± 12 years and mean ejection fraction was 47% ± 12%, with negative stress echo by wall motion criteria. Data were prospectively acquired and retrospectively analyzed. Patients were categorized ex-post as: normal, n = 91; idiopathic dilated cardiomyopathy, n = 222; known coronary artery disease, n = 331 (dilated ischemic cardiomyopathy, n = 102; not dilated, n = 229); diagnostic tests, n = 162, and hypertensive, n = 85.

The normal group was composed of participants with normal LV function in baseline conditions and at peak stress and were not receiving therapy at the time of testing. Diagnostic tests consisted of stress tests in patients with a low pretest probability of coronary artery disease, electrocardiogram (ECG) abnormalities at rest or exercise electrocardiography, and no LV dilation. Diagnosis of coronary artery disease was based upon history of myocardial infarction or coronary revascularization and/or the presence of ≥ 1 angiographically documented coronary stenosis > 50%.

The stressor used (exercise, dipyridamole, dobutamine) was chosen on the basis of specific contraindications, local facilities and physician preferences. Dobutamine was the preferred stressor for viability assessment.24

Two-dimensional echocardiography and 12-lead electrocardiographic monitoring were performed in combination with semisupine bicycle exercise, or high-dose (up to 40μg/kg/min) dobutamine, or high-dose dipyridamole (84mg/kg/min, over 6min), according to protocols suggested by the European Association of Echocardiography24 guidelines. During the procedure, blood pressure and ECG were recorded each minute. Echocardiographic images were semiquantitatively assessed using a 17-segment, 4-point scale model of the left ventricle.24 A wall motion score index was derived by dividing the sum of individual segment scores by the number of interpretable segments. The LV ejection fraction (LVEF) was assessed using the biplane Simpson method.25 Ischemia was defined as stress-induced new and/or worsening of a pre-existing wall motion abnormality, or biphasic response (ie, low-dose improvement followed by high-dose deterioration). By selection, all patients had negative stress echo by wall motion criteria. Improvement of the wall motion score index between resting and peak of stress indicated myocardial viability.26

The LV end-systolic volume (LVESV) and the LVEDV are obtained from apical 4-chamber and 2-chamber view using the biplane Simpson method.12,19,25 The LVESV and the LVEDV are assessed at rest and at peak stress and normalized by dividing it by body surface area. Only representative cycles with optimal endocardial visualization are measured and the average of 3 measurements are taken. The endocardial border is traced, excluding the papillary muscles. The frame with the smallest LV cavity is considered to be the end-systolic frame and the frame captured at the R wave of the ECG is considered to be the end-diastolic frame. The LV end-systolic pressure (mmHg) is obtained as LV end-systolic pressure = 0.9 × systolic blood pressure (mmHg), a noninvasive estimate of end-systolic pressure that accurately predicts pressure-volume loop measurements of end-systolic pressure.27

The ESPVR (mmHg/mL/m2) is obtained as the ratio of the end-systolic pressure to the LVESV indexed for body surface area. The ESPVR is determined at rest and at peak stress. The ΔESPVR is calculated as the variation between rest and peak stress ESPVR. The rest ESPVR, the peak stress ESPVR and the ΔESPVR are built offline.11,12,19

All studies were performed by an experienced cardiologist with documented experience in stress echocardiography and who passed the quality-control procedures of stress echocardiography reading according to the criteria adopted in the Echo Persantine International Cooperative and in the Echo Dobutamine International Cooperative multicenter studies.26 By selection, 2-dimensional measurements of LV volumes were feasible in all patients. By selection, no test was interrupted because of limiting side effects and no test was positive for regional wall motion abnormalities. Moderate mitral regurgitations were included: 89 (40%) of the 222 patients with idiopathic dilated cardiomyopathy, 47 (46%) of the 102 patients with ischemic dilated cardiomyopathy, and 6 (3%) of the 229 patients with ischemic heart disease had moderate mitral regurgitation. The 331 dilated heart patients with or without moderate mitral regurgitation had similar resting LVEF (28% ± 7% vs 29% ± 9%, P = ns) and ΔESPVR (0.92 ± 2mmHg/mL/m2 vs 0.87 ± 1.6mmHg/mL/m2, P = ns).

In 60 randomly selected patients, there was excellent interobserver agreement with the Bland Altman method with mean ± standard deviation for LVEDV at rest (2.3 ± 18mL; 95% confidence interval [95%CI], −38 mL to 34 mL) and at peak stress (5.8 ± 16mL; 95%CI, −38mL to 26mL), LVESV at rest (3.6 ± 23mL; 95%CI, −48 to 41mL) and at peak stress (0.3 ± 13mL; 95%CI, −27 to 27mL). Variability was lower for LVEDV and LVESV both for pharmacological and exercise echo at low heart rates (< 100 bpm) at peak stress.

Left ventricular volumes and stress-related variables are presented separately for exercise, dipyridamole and dobutamine stress echo in Table 1, Table 2, and Table 3. At rest, an inverse relation was observed for normal participants and each group of patients between the ESPVR and the end-diastolic volume (ie, the larger the LV cavity, the smaller the ESPVR) (Figure 1). The slope of the ESPVR/LVEDV index (a marker of the size dependence of the end-systolic pressure/volume ratio) was significantly different between dilated ischemic cardiomyopathy, dilated idiopathic cardiomyopathy, and other groups, as the slope was steeper in patients without dilated left ventricle (Figure 1, upper panels). At a given end-diastolic volume, the mean end-systolic pressure/volume ratio was higher in the nondilated patient groups than in the dilated ischemic cardiomyopathy and dilated idiopathic cardiomyopathy groups (Figure 1, lower panels).

Figure 1.

Relationships between ESPVRi and the LVEDVi at rest. The relationships between the LVEDVi and the ESPVRi are presented separately for the patients scheduled for EX (red symbols), DIP (blue symbols) and DOB (green symbols). For each group of patients, linear regression values are represented. CAD, coronary artery disease; DC, dilated ischemic cardiomyopathy; DCM, idiopathic dilated cardiomyopathy; DIP, dipyridamole stress echo; DOB, dobutamine stress echo; ESPVRi, end-systolic pressure-volume relation index; EX, exercise stress echo; HYP, hypertensive participants; LVEDVi, left ventricular end-diastolic volume index; NL, normal participants; Test, diagnostic test patients.

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In the overall population, an inverse relationship between ESPVR and LVEDV was present at rest (r2 = 0.69, P < .001) and peak stress (r2 = 0.56, P < .001), but was absent if only the ΔESPVR was considered (r2 = 0.13). The ΔESPVR value was highest for normal or near-normal or hypertensive individuals and was lowest for ischemic or nonischemic dilated cardiomyopathy patients. Absolute values of ΔESPVR were higher for exercise and dobutamine than for dipyridamole. At peak stress, as at baseline, an inverse relation was observed for normal individuals and each group of patients between the ESPVR and the end-diastolic volume (ie, the larger the LV cavity, the smaller the end-systolic pressure/volume ratio) both for the exercise stress, dipyridamole stress, and dobutamine stress groups.

The end-diastolic volume dependence of the ESPVR disappeared and/or significantly decreased vs rest when we considered the ΔESPVR (Table 4). The relationships between the LVEDV and the ΔESPVR are presented separately for the exercise, dipyridamole, and dobutamine stress echo groups (Figure 2, color symbols), and for normal participants and patients inside the stress group (Figure 2, upper and lower panels).

Figure 2.

Relationships between ΔESPVRi and the LVEDVi. For each group of patients, linear regression values are represented. The relationships between the LVEDVi and the ΔESPVRi are presented separately for the patients who underwent EX (red symbols), DIP (blue symbols) and DOB (green symbols). ΔESPVRi, end-systolic pressure-volume relation index changes with stress; CAD, coronary artery disease; DC, dilated ischemic cardiomyopathy; DCM, idiopathic dilated cardiomyopathy; DIP, dipyridamole stress echo; DOB, dobutamine stress echo; EX, exercise stress echo; HYP, hypertensives; LVEDVi, left ventricular end-diastolic volume index at rest; NL, normals; Test, diagnostic test patients.

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The end-systolic pressure /end-systolic volume index ratio (the Suga index) at increasing heart rates is easily obtained during routine stress echocardiography and has been established as a reasonably load-independent index of myocardial contractile performance.3–11 However, like most indexes, this ratio does not take into account the diastolic dimensions of the left ventricle.

These data emphasize the size independence of the ΔESPVR and its consequences for a comparative assessment of a large number of patients with different diseases. The LVEDV does not affect rest-stress changes in ESPVR in either normal or abnormal left ventricles during physical or pharmacological stress.

None declared.