In patients with reperfused anterior AMI, a shorter DDT of the LAD flow detected within 24 hrs after coronary reperfusion and CFR less than 1.75 were feasible predictors of poor functional outcome. These parameters correlated with the quantitative results by HPDI with intravenous MCE. TTDE provides a simple and promising means of noninvasive assessment of myocardial viability in patients with reperfused anterior AMI.
Coronary Flow Pattern
Recent studies with intracoronary MCE have shown that about one fourth to one third of patients with AMI treated with primary PTCA have an inadequate tissue perfusion (no-reflow phenomenon) despite angiographically successful coronary recanalization . Characteristic coronary flow velocity pattern (systolic retrograde flow and rapid deceleration of diastolic flow) by using a Doppler guidewire is associated with the "no-reflow" phenomenon . This "no-reflow" phenomenon is thought to be the result of microvascular dysfunction.
In patients with MCE no reflow, the coronary microvasculature was profoundly damaged and it seemed that microvascular impedance increased and the intramyocardial blood pool decreased. The coronary microvasculature would be diffusely obstructed in patients with MCE no reflow. Early systolic retrograde flow (ESRF) has been reported to be observed frequently in patients with no reflow in case of AMI after successful recanalization and was explained by an occluded coronary microvasculature.
Kawamoto et al. showed that the degree of reduced systolic antegrade flow or the deceleration time of diastolic flow reflected the degree of microvasculature damage and was predictive of residual myocardial viability . They revealed that low average peak velocity and rapid DDT of coronary blood flow spectrum immediately after primary PTCA reflected a greater degree of microvascular damage in the risk area and analysis of coronary blood flow spectrum immediately after primary PTCA by use of a Doppler guidewire was useful in predicting recovery of regional LV function.
Recently, Wakatsuki et al. revealed that the coronary flow velocity pattern measured immediately after successful primary stenting is predictive of the recovery of regional and global LV function in patients with AMI . The changes of regional wall motion score (RWM) and EF were significantly greater in the non-ESRF group than it was in the ESRF group. These authors reported that ESRF is a parameter predicting poor functional recovery of LV wall motion. They explained that decreased extravascular pressure of the infarcted myocardium during systole might increase the apparent systolic flow, and increased vascular resistance might decrease the diastolic antegrade flow in mildly to moderately damaged myocardium.
In our study, there were 6 patients with early systolic retrograde flow. They had no myocardial perfusion in infarcted area by HPDI and revealed poor CFR. LV wall motion in all these patients did not recover at follow-up. The obstruction of the microvasculature with subsequent high impedance results in the inability to squeeze blood forward into the venous circulation during systole. It is consequently pushed back to the epicardial coronary artery to produce early systolic retrograde flow. The reduced intramyocardial blood pool, which fills rapidly during diastole, has been used to explain the rapid decline of diastolic velocity.
Recently, Lepper et al. reported that the coronary flow reserve immediately and 24 hr after PTCA for AMI relates to myocardial perfusion determined by MCE and LV function in four weeks . From our results, the patients with significantly altered coronary flow pattern, which showed rapid DDT, were found to have subsequent depression of LV function at follow up, confirming the prognostic importance of altered coronary blood flow patterns reported in previous studies [6, 7]. This study confirms recent reports on the difference in coronary blood flow pattern between patients with and without reperfusion determined by MCE.
There were no reports that were compared coronary blood flow velocity pattern and CFR by TTDE with intravenous MCE by using HPDI. Our study revealed that DDT at acute phase correlated with microvascular integrity by HPDI and with CFR after two weeks. The quantitative analysis by HPDI revealed the degree of microvascular dysfunction. HPDI is a feasible technique for the detection of a myocardial perfusion defect in patients with coronary artery disease after a venous injection of contrast agent. Previous works, however, used qualitative analysis of the HPDI . In the present study, we performed quantitative analysis of HPDI at rest and during hyperemia in patients with AMI.
We used Levovist, which is sensitive to microbubble destruction at diagnostic ultrasound frequencies . Several recent studies have demonstrated that the feasibility of applying this contrast agent to the assessment of myocardial perfusion by using HPDI .
In patients who had myocardial viability, the peak intensity of the risk area was 0.668 ± 0.178 dB at rest. In patients who had no myocardial viability in the risk area, the curves of intensity showed no increase and peak intensity was 0.248 ± 0.015 dB at rest. During ATP induced hyperemia, peak intensities were increased in the segments with preserved myocardial integrity. In the segments without preserved myocardial integrity, however, there was no change in peak intensities. We diagnosed quantitatively myocardial viability using by HPDI. HPDI is strictly dependent on microvascular integrity and PIR shows quantitatively the degree of microvascular damage. There were significant differences of LV function at follow-up between two groups. Our data may provide additional information from the point of coronary flow pattern.
Coronary Artery Flow Reserve
Our main findings were that the myocardial perfusion status assessed by HPDI at rest and during ATP stress corresponds closely to CFR and DDT of CF. CF at acute phase and CFR two weeks after AMI onset correspond to left ventricular remodelling at chronic phase.
A previous study showed that, in patients with myocardial infarction, CFR is inversely correlated with the extent of myocardial infarction and directly correlated with the improvement in wall motion contractility during the recovery period [4, 6]. A value above 1.75 is associated with an improved wall motion index. Reduction of MCE perfusion defects were associated with improvement of CFR, whereas persistent MCE perfusion defects were associated with unchanged depression of CFR, indicating a relation between microvascular integrity assessed by CFR and by intravenous MCE .
There were no reports that had been investigated the relationship between CFR and DDT of LAD. From our study, CFR correlated with DDT. CFR and DDT revealed the degree of microvascular damage in myocardium.
The patients with MCE no reflow, which had no viability in the infarcted area by HPDI, showed poor functional outcomes and left ventricular remodeling. The detection of viability with HPDI and CFR were useful for predicting of LV remodeling.
We compared the myocardial opacification obtained by HPDI with CFR and DDT of LAD in patients after PTCA for AMI. The machine settings used in this study relate to the best knowledge at the time of study initiation. Optimal echocardiographic machine settings for MCE are rapidly evolving and are dependent on the applied contrast agent. Thus, it is very challenging to set up and adhere to a study protocol in a field in which knowledge of how to use an evolving technology is improving very quickly.
The differences in the shell structure as well as gas compositions of different microbubbles are likely to influence their efficacy for myocardial perfusion assessment by HPDI. Unfortunately, real-time perfusion imaging is not available on the instrument used in this study. Using real-time assessment of perfusion defects, we can diagnose both wall motion and myocardial perfusion at the same time .
We could not perform MCE study immediately after the primary angioplasty. This analysis included only a limited number of patients.
Coronary flow reserve is related to the microcirculatory status, which will be either indirectly affected by epicardial coronary stenosis or directly affected by a previous myocardial infarction and other related factors.
The coronary flow pattern may be influenced by left ventricular pressure. But we didn't compare CFR and coronary flow pattern with the left ventricular pressure. Further study is needed to clarify this issue. Systolic reversal flow is a specific indication of the no reflow phenomenon, but it was sometimes difficult to record the complete Doppler spectral envelope throughout the entire cardiac cycle by TTDE because of the systolic heart motion.