Study Population

Fifty-eight patients with previous MI and significant coronary stenosis (>50% diameter stenosis) detected by coronary angiography were initially included in the study. This was a prospective study with the inclusion of consecutive patients who fulfilled the following criteria: (1) previous first MI with ST-segment elevation ≥7 days before the study, (2) single-vessel coronary artery disease responsible for infarction, (3) echocardiographic identification of regional wall motion abnormalities corresponding to the site of infarction and coronary lesion, (4) optimal Doppler signal of diastolic coronary flow, and (5) scheduled percutaneous intervention of the infarct-related artery. Exclusion criteria were unstable angina or acute MI, multivessel coronary artery disease, occluded coronary artery, absence of regional wall motion abnormalities, atrial fibrillation, high-degree atrioventricular block, and severe chronic obstructive pulmonary disease.

Four patients had poor acoustic windows and suboptimal Doppler signals during the evaluation of coronary flow and were therefore excluded from further analysis. Four patients were lost to follow-up, and the final number of studied patients was 50 (41 men, nine women; mean age, 53 ± 8 years). The study protocol was approved by our institution’s medical ethics committee. All patients were informed about the procedure and provided consent.

Study Protocol

All patients underwent resting two-dimensional echocardiography and dipyridamole stress echocardiography (0.84 mg/kg in 6 minutes) with CFR evaluation of the infarct-related artery by transthoracic Doppler echocardiography 1 day before planned PCI, 24 hours after intervention with stent implantation, and 3 months after PCI. The intake of xanthine-containing foods or beverages was discontinued the day before the examination. At the time of testing, 23 patients (46%) were taking β-blockers, 12 (24%) were on long-acting nitrates, and all were on aspirin, clopidogrel, and statins.

Transthoracic stress echocardiography was performed using a commercially available digital ultrasound system (Acuson Sequoia C256; Siemens Medical Solutions USA, Inc., Mountain View, CA) with a 3V2C multifrequency transducer using second-harmonic technology. All standard echocardiographic views were obtained when possible. The volume of the left ventricle was measured from the dimension and area obtained from orthogonal apical views (four and two chamber) and then calculated using the modified Simpson’s method. A 17-segment model was used to determine systolic LV function. Segmental wall motion was graded as follows: 1 = normal, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic. The wall motion score index (WMSI) was obtained by dividing the sum of individual visualized segment scores by the number of visualized segments. Regional wall motion score in the infarct zone was calculated as the sum of the individual scores of the segments in infarct-related artery territory. Echocardiographic follow-up was obtained ≥3 months (average, 115 ± 9 days) after the revascularization procedure in all patients. Recovery of LV function was defined as a difference in WMSI before PCI and at follow-up of ≥0.20. Improvement in wall motion (ΔWMSI) was calculated as a difference between WMSI before angioplasty and WMSI at 3-month follow-up.

Two experienced observers, blinded to the coronary flow data, analyzed all studies separately. Interobserver agreement in our laboratory was 93% for the identification of ischemia and 96% for the identification of viable segments at follow-up, as shown in previous studies.

Transthoracic Doppler Echocardiographic Evaluation of CFR

Transthoracic Doppler echocardiography was performed using the same ultrasound unit. After standard examination, distal left anterior descending coronary artery or right coronary artery flow was evaluated using a 4-MHz transducer. In color Doppler flow mapping, the velocity range was set in the range of 16 to 24 cm/sec. For distal left anterior descending coronary artery examination, the acoustic window was around the midclavicular line in the fourth and fifth intercostal spaces in the left lateral decubitus position. For posterior descending coronary artery examination, the left ventricle was imaged in a standard apical two -chamber view. From this position, the transducer was slightly rotated anticlockwise and tilted anteriorly, until coronary blood flow in the posterior interventricular groove was identified by color Doppler. A sample volume (3–5 mm wide) was positioned on the color signal of the distal infarct-related artery. The spectral Doppler of the infarct-related artery flow showed a characteristic biphasic flow pattern with a larger diastolic component and a small systolic one. Flow velocity recordings were performed with the stable transducer position at rest and maximal hyperemia, which was induced by the administration of intravenous dipyridamole (0.84 mg/kg over 6 minutes). All studies were recorded on VHS videotapes, and stop frames and clips were digitally recorded and stored on magneto-optical disks for offline analysis. CFR was calculated as the ratio of hyperemic to basal peak diastolic flow velocities. At each time point, three optimal diastolic flow profiles were measured and the results averaged. DDT was measured from the peak diastolic velocity to the point of intercept of initial decay slope with baseline. Measurements of DDT were later repeated by independent observer. Interobserver agreement was 90%.

Statistical Analysis

The sample size was determined for the estimated change in CFR during angioplasty of 0.5. With a population standard deviation of 0.25, Δ of 0.40 (E/SD; E = 0.1), α error of 0.5, and 1 − β = 0.80 (80% power of the study), the calculated sample size was 50 patients. Quantitative variables are expressed as mean ± SD. Comparisons of quantitative variables were analyzed according to the two-tailed Student’s t test. Dichotomous variables were compared using χ ² statistics. Pearson’s correlation coefficients were calculated to describe the correlation between coronary flow variables and LV recovery. To determine the best cutoff value of DDT for predicting LV functional improvement on the basis of clinical relevance, the point of maximal specificity and best sensitivity was determined. Univariate analysis was used to evaluate the relation between various echocardiographic variables and improvement in the myocardial function in follow-up period. To select covariates independently associated with the improvement in myocardial function, significant univariate predictors were reassessed by multivariate logistic analysis, with values for inclusion and elimination set at P < .05. Sensitivity and specificity were calculated in the standard manner. P values < .05 were considered statistically significant.

CFR, DDT, and Myocardial Recovery

Before PCI, basal diastolic flow velocities were similar in the recovered and nonrecovered groups (23 ± 6 and 22 ± 4 cm/sec, respectively, P = NS), as well as CFR before PCI. CFR increased significantly 24 hours after PCI in groups I and II (from 1.52 ± 0.27 to 2.60 ± 0.70, P < .001, and from 1.56 ± 0.29 to 2.16 ± 0.34, P < .001, respectively). After PCI and at 3-month follow-up, CFR was significantly higher in group I than in group II, but there was substantial overlap between the groups ( Figure 1 ). CFR slightly but significantly ( P < .01) increased further at 3-month follow-up in group I, whereas in group II, it remained the same.

Changes in CFR and DDT over time. The difference in CFR between recovered and nonrecovered groups was significant 24 hours after PCI and after 3 months ( P < .001). The difference in DDT between the recovered and nonrecovered groups was significant both before and after angioplasty ( P < .001).

Compared with patients without improvements in LV function, patients with recovered LV function had longer DDTs before angioplasty (841 ± 286 vs 435 ± 80 msec, P < .001), 24 hours after PCI (885 ± 273 vs 567 ± 363 msec, P = .027), and at follow-up (970 ± 260 vs 445 ± 155 msec, P < .001) ( Figure 1 ). Characteristic flow patterns in both groups before PCI, at baseline, and during dipyridamole infusion are presented in Figure 2 . In addition, DDTs in patients with recovered LV function continued to increase at follow-up in comparison with values before PCI (970 ± 260 vs 841 ± 286 msec, P = .043). On the other hand, there was no significant change in DDTs over 3 months in patients without LV recovery.

Characteristic flow pattern before PCI in (A) a patient with recovered LV function at baseline and (B) during dipyridamole and (C) a patient without recovery at baseline and (D) during dipyridamole.

Univariate and multivariate predictors of myocardial recovery are presented in Table 3 . WMSI before PCI, end-diastolic and end-systolic volumes, and CFR 24 hours after PCI and DDT before PCI were univariate predictors of LV functional recovery ( Table 3 ). By multivariate analysis, DDT and regional wall motion score before PCI were independent predictors of LV recovery in the follow-up period ( P = .003 and P = .007, respectively; Table 3 ).

Table 3

Univariate and multivariate predictors of myocardial recovery

	Univariate analysis		Multivariate analysis
Variable	95% CI	P	95% CI	P
Regional WMS before PCI	10.47 to 12.95	<.001	−0.075 to −0.013	.007
Global WMSI before PCI	1.38 to 1.50	<.001
EDV	96.5 to 108.6	<.003
ESV	44.5 to 51.1	<.001
DDT before PCI	620 to 811	<.001	0.000 to 0.001	.003
CFR 24 h after PCI	2.26 to 2.65	.034
ΔCFR	0.75 to 1.12	.035

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