The incremental diagnostic value of coronary flow reserve and left ventricular elastance during high-dose dipyridamole stress echocardiography in patients with normal wall motion at rest

Abstract

A “normal” dipyridamole stress echocardiogram by wall motion criteria identifies a subset of patients at low risk of experiencing hard events in the follow-up [1]. The sensitivity for identifying significant coronary artery disease (CAD) is suboptimal, and can be increased by adding coronary flow reserve (CFR) assessment by Doppler echocardiography [2] or myocardial contrast echo [3]. Another possible variable of incremental value over wall motion is the assessment of contractile reserve (CR) via the end-systolic pressure–volume relationship (PVR), which has been used with pacing [4], exercise [5] or dobutamine [6] — not yet with dipyridamole. We prospectively enrolled 111 patients (60men; age 68, SD 10 years) with normal baseline function who underwent dipyridamole (0.84 mg/ kg over 6 min) stress echocardiography with CFR evaluation of LAD by Doppler [7] and CR calculated as peak stress ESP (end-systolic pressure)/ ESV (end-systolic volume)− rest ESP/ESV [6]. All patients underwent quantitative coronary angiography performed independently of test results. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. All continuous data are reported as mean values ± standard deviation (SD). Known normal vs abnormal cutoff values of variation with stress (i.e., positive ESP/ESV index changes; CFR N 2) were tested as predictor of obstructive coronary disease in patients without inducible ischemia. Receiver operator characteristic curve analysis was used to determine potentially useful threshold values of ΔESP/ ESV derived predictors for identification of coronary artery disease in negative stress echo. Contingency tables were constructed to assess the sensitivity and specificity of the method. SPSS 13.0 (SPSS, Inc., Chicago, IL, USA) was used for the analysis. Stress echocardiogramwas positive for ischemia in 23 patients (21%). One or more significant coronary stenoses (≥50% luminal narrowing) were present in 51 patients (46%). Regional wall motion abnormalities (WMA) showed a sensitivity of 45% (95% CI 31% to 60%), which rose to 88% (95% CI 76% to 96%) with the combination of CFR positivity (LAD flow reserve≤ 2.0) and CR (b0.36 mmHg/mL/m) criteria (Fig. 1). Contractile reserve was negative (−3.6 SD 3 mmHg/mL/m) in patients with positive stress. In the subset with negative stress, contractile reserve was +3.5 SD 3 mmHg/mL/m in the 42 negative patients without, vs−1.4 SD 3.6 mmHg/mL/m in the 28 negative patients with ≥50% coronary stenosis diagnosis. With a receiver operating characteristic analysis, a ΔESP/ESV index b0.36 mmHg/mL/m from baseline to peak stress was the best value to identify angiographic evidence of significant (≥50%) coronary stenosis patient population (area under curve 0.9, 95% CI 0.84 to 0.96; Younden index= 1.73). This criterion showed good sensitivity (86%, 95% CI 74% to 94%) and specificity (87%, 95% CI 75% to 94%) for ≥50% coronary stenosis diagnosis. Specificity was 100% (95% CI 94% to 100%) with WMA and fell to 83% (95% CI 71% to 92%) with the combination of CFR and CR criteria. At individual patient analysis, all patients with wall motion abnormalities showed CAD, with high prevalence of CFR and CR impairment. In patients without wall motion abnormalities, CAD was more frequent in the presence of a depressed CR and/or CFR. The likelihood of underlying CAD was higher when both were altered (Fig. 2).