| | Relationship Between Systolic Pulsed Wave Tissue Doppler Parameters and Both Invasive and Noninvasive Reperfusion Criteria in Patients with Acute Anterior Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention published online 12 July 2007. BackgroundDespite normal flow in the infarct-related artery after primary percutaneous coronary intervention, patients may not achieve adequate perfusion at the tissue level. We examined the applicability of pulsed wave tissue Doppler (PTD) in detection of successful myocardial reperfusion. MethodsIn all, 24 patients with anterior infarction were enrolled. All patients underwent primary percutaneous coronary intervention. PTD was performed 2 days and 2 weeks after percutaneous coronary intervention, and recorded from 6 different locations at the mitral annular level. Peak systolic wave was determined and was related to various markers of reperfusion. ResultsSystolic PTD measurement in patients with myocardial blush grades 0 to 1 significantly deteriorated between second day and second week (6.5 ± 1.1-5.3 ± 1.1 for the anterior wall, and 6.2 ± 1.3-5.3 ± 1 for the anterior septum, P < .05 and P < .01, respectively). Systolic PTD parameters improved significantly in patients with myocardial blush grades 2 to 3 (6 ± 1.5-7.2 ± 2 for the anterior wall, and 5.4 ± 1.1-7.1 ± 1.6 for the anterior septum, P < .05 and P < .01, respectively). A significant relationship was observed between PTD and thrombolysis in myocardial infarction flow, S-T resolution, and creatine phosphokinase peaking. PTD recovery was highly sensitive and specific for the detection of left ventricular function recovery. ConclusionWe demonstrated a significant relationship between systolic PTD parameters and invasive and noninvasive markers of reperfusion. Larger studies are needed to confirm these results. The primary goal in the management of acute S-T segment elevation myocardial infarction (STEMI) is to institute reperfusion therapy as quickly as possible. Early reperfusion by thrombolytic agents has proven effective in reducing mortality, but better results including further reduction in mortality and recurrence of ischemia can be achieved with direct percutaneous coronary intervention (PCI).1 However, it is becoming increasingly clear that tissue perfusion, not just an open artery, is critical to myocardial salvage. Despite successful recanalization by either thrombolytic agents or PCI, a substantial number of patients still fail to obtain complete and sustained myocardial reperfusion at the tissue level, and remain at risk of developing large infarcts.2 Therefore, several markers of myocardial reperfusion have been developed, and the efficacy of these markers in the assessment of various modalities of reperfusion therapy has been established.3, 4, 5, 6, 7, 8 Doppler tissue imaging is a new modality developed in recent years that measures tissue velocity during cardiac cycle. It has been previously demonstrated that there is a significant relationship between successful reperfusion after thrombolysis in acute myocardial infarction (MI) as indicated by the conventional noninvasive reperfusion criteria and pulsed wave tissue Doppler (PTD) parameters.9 We aimed at assessing the relationship between PTD parameters and a number of invasive and noninvasive reperfusion criteria in patients undergoing primary PCI in the setting of acute MI, thus, evaluating a potentially new parameter for the detection of successful reperfusion at the tissue level. Methods  Study Population and Design The study group consisted of 24 consecutive patients, who had been hospitalized for acute anterior STEMI and treated with primary PCI between September 2003 and April 2004. Exclusion criteria were nonanterior infarctions, delayed presentation (>12 hours after the onset of symptoms), previous MI, or the presence of any cardiac or systemic condition that might complicate the evaluation of PTD data, such as valvular heart disease, cardiomyopathy, pericardial disease, and endocrine or rheumatologic diseases. Patients presenting with an electrocardiogram finding that might complicate the interpretation of the S-T segment, such as those with bundle branch block, pre-excitation, or complete atrioventricular block, were also excluded from the study. All patients gave informed consent to the study, and the study was approved by the local ethical committee. Procedures Coronary intervention Patients were treated according to the standard care for treatment of patients with acute STEMI. Before cardiac catheterization, all patients received 300 mg of oral acetylsalicylic acid and 300 mg of oral clopidogrel. After informed consent, patients were then subjected to a diagnostic coronary angiogram through the femoral approach. Coronary angioplasty and stenting were performed using standard techniques for the culprit lesion only, using bare metal stents in all included patients. The decision to use glycoprotein IIb/IIIa receptor inhibitors was according to the discretion of the treating physician. Coronary flow after revascularization was graded according to the thrombolysis in MI (TIMI) grading system. TIMI grade 3 flow was considered one of the angiographic markers for successful reperfusion.5 Myocardial perfusion was described using the myocardial blush grades (MBG). To allow blush grading, the final angiographic run was long enough to see the venous phase of the contrast passage. The final angiographic runs were made both in the left lateral and right anterior oblique views, to prevent super-positioning of the noninfarcted myocardium. Patients with MBG 0 or 1 were studied as one group, and compared with patients with MBG 2 or 3, who were considered to be angiographically successfully reperfused.6 Cinefilms were reviewed with an angiographic projection system allowing frame-by-frame analysis, selection, and magnification of segments of interest. TIMI flow and MBG were visually assessed on the angiogram and described immediately after the primary coronary intervention by the performing cardiologist. Electrocardiographic analysis Serial S-T segment analysis on a 12-lead electrocardiogram recording just before and at the end of the coronary intervention was done by one observer blinded to clinical data. The sum of S-T segment elevations was measured manually 20 milliseconds after the end of the QRS complex from leads I, aVL, and V1 through V6. Adequate resolution of S-T segment elevation after successful recanalization was expressed as a percentage of the initial S-T segment elevation. S-T segment resolution 50% or less of the initial value (S-T ≤ 50%) was defined as a marker of impaired microvascular reperfusion. On the other hand, S-T segment resolution greater than 50% indicated good myocardial reperfusion.10 Biochemical markers Blood samples were collected from each patient just before coronary intervention, every 6 hours for 24 hours, then daily. Creatine phosphokinase (CK)-MB and total CK were used as biochemical markers of myocardial reperfusion. Serum CK peaking within the first 12 hours of coronary intervention was considered a noninvasive marker of reperfusion.7 Echocardiographic and PTD examination All patients in the study group underwent standard echocardiography and PTD examination within 2 days of the acute infarction, and 2 weeks later, using a system (Vivid Five, General Electric Vingmed, Horten, Norway) with a 2.5-MHz transducer. All examinations were done by one experienced echocardiographer, who was blinded to the results of the primary PCI. Left ventricular (LV) ejection fraction (EF) was estimated by the Simpson modified biplane method. LV functional recovery was defined as an increase of 5% or more of the calculated LV EF between the first and the second echocardiographic evaluation. For PTD examination, the mode was switched to tissue velocity imaging mode, allowing lowering of the velocity range to encode myocardial velocities. PTD samples were recorded from 6 different locations with the sample volume placed at the level of the mitral annulus (anterior, inferior, lateral, posterior, anterior septum, posterior septum), using the apical 2- and 4-chamber, and long-axis, views. At each point of examination, peak systolic wave (S) was estimated and was taken as a determinant of systolic function. Statistical Analysis All data analyses were performed with software (Statistical Package for Social Sciences SPSS for Windows 12.0, SPSS Inc, Chicago, IL). Continuous variables between groups were compared by the Student t test. The correlation between changes in systolic PTD parameters and global EF was calculated using Pearson’s correlation coefficient. Receiver operating characteristic curves were constructed to detect the best cut-off value for a change in mean S-wave velocity to detect LV functional recovery. The sensitivities, specificities, and positive and negative predictive values for the various markers of reperfusion in detecting LV functional recovery were calculated. A probability value less than .05 (2-tailed) was considered significant. Results are expressed as mean ± SD, unless otherwise specified. Results The baseline clinical characteristics of the studied patients are shown in Table 1; the angiographic findings are shown in Table 2. TIMI 3 flow was found in 17 (71%) of 24 patients with acute MI, and MBG 2 or 3 was found in 15 (63%). Fourteen patients (58%) had S-T segment resolution greater than 50%, whereas 18 (75%) had early peaking of CK levels within the first 12 hours. Twelve patients (50%) had LV functional recovery. | | |  | Characteristic | No. | |
|---|
| Age, y | 49 ±13 | | | Male, n (%) | 21(87.5) | | | Diabetes mellitus, n (%) | 4(16.7) | | | Hypertension, n (%) | 7(29.2) | | | Hypercholesterolemia, n (%) | 10(41.75) | | | Current smokers, n (%) | 18(75) | | | Family history, n (%) | 2(8.3) | | | Heart rate, beats/min | 85±20 | | | Systolic blood pressure, mm Hg | 122±32 | | | Modes of therapy⁎ | | | | Aspirin, n (%) | 24(100) | | | Clopidogrel, n (%) | 24(100) | | | IIb/IIIa Inhibitors, n (%) | 19(79.2) | | | Heparin, n (%) | 21(87.5) | | | LMWH, n (%) | 3(12.5) | | | ACE Inhibitors, n (%) | 24(100) | | | β-Blockers, n (%) | 23(95.8) | | | Statins, n (%) | 12(50) | | | | |
| ⁎ Modes of therapy did not differ between first and second echocardiographic evaluation, except for heparins and IIb/IIIa inhibitors (only given in the acute phase). |
| | | | Characteristic | No. | |
|---|
| Pain to balloon, h | 5.6±2.4 | | | Diseased vessels | | | | One vessel, n (%) | 13(54.2) | | | Two vessels, n (%) | 4(16.7) | | | Three vessels, n (%) | 7(29.1) | | | TIMI flow | | | | TIMI 0, n (%) | 0(0) | | | TIMI 1, n (%) | 3(12.5) | | | TIMI 2, n (%) | 4(16.7) | | | TIMI 3, n (%) | 17(70.8) | | | MBG | | | | MBG 0, n (%) | 4(16.7) | | | MBG 1, n (%) | 5(20.8) | | | MBG 2, n (%) | 8(33.3) | | | MBG 3, n (%) | 7(29.2) | | | | |
Relationship Between PTD Parameters and Final TIMI Flow According to the TIMI flow after coronary intervention, patients were divided into those with TIMI 1 or 2 and those with TIMI 3 flow. Patients with TIMI 1 or 2 flow showed no statistically significant difference between the recorded systolic PTD parameters at the first and the second evaluation, with a trend toward deterioration in the posterior septum (6 ± 1.4-5.8 ± 0.9 cm/s), anterior septum (6.3 ± 1.3-5.9 ± 1.6 cm/s), and anterior wall (6.4 ± 1.4-5.9 ± 1.6 cm/s), and a trend toward improvement in the lateral wall (7.2 ± 1.2-7.3 ± 1.5 cm/s), inferior wall (6.4 ±1.5-7.3 ± 1.3 cm/s), and posterior wall (7.2 ± 1.9-7.4 ± 1.3 cm/s, P > .05 for all comparisons). On the other hand, patients with TIMI 3 flow demonstrated an improvement in systolic PTD parameters in all examined segments. This improvement was statistically significant in all examined walls except for the anterior wall (Table 3). Relationship Between PTD Parameters and MBG According to the postinterventional MBG, patients were divided into those with MBG 0 or 1 and those with MBG 2 or 3. Patients with MBG 0 or 1 demonstrated deterioration of systolic PTD parameters between the first and second evaluation in the anterior and posterior septum, anterior and lateral walls, with the deterioration being statistically significant in the anterior septum (6.2 ± 1.3-5.3 ± 1 cm/s, P < .01) and anterior wall (6.5 ± 1.1-5.3 ± 1.1 cm/s, P < .05). The posterior wall parameters, however, did not deteriorate, and the inferior wall parameters slightly improved (P > .05). Meanwhile, patients with MBG 2 or 3 displayed statistically significant improvement of systolic PTD parameters between the first and the second evaluation in all examined walls (Figure). Relationship Between PTD Parameters and Noninvasive Reperfusion Markers Patients with 50% or less S-T resolution demonstrated deterioration of systolic PTD parameters between the first and the second evaluation in the anterior and posterior septum, lateral and anterior walls, with the deterioration being statistically significant in the anterior wall only (5.8 ± 1.1-5 ± 0.9 cm/s, P < .05). Systolic PTD parameters of the inferior and posterior walls showed a trend toward improvement (6.2 ± 0.9-6.7 ± 0.9 and 6.4 ± 1.3-6.7 ± 1.4 cm/s, respectively, P > .05 for both). Similarly, patients with delayed CK peaking after 12 hours demonstrated significant deterioration in systolic PTD parameters in the anterior wall (7.5 ± 1.2-6.2 ± 1.3 cm/s, P < .01) and anterior septum (7.1 ± 1.2-6 ± 1.1 cm/s, P < .05), and a trend toward improvement in PTD parameters in the inferior, posterior, and lateral walls (P > .05). On the other hand, patients with greater than 50% S-T resolution and those with early CK peaking within 12 hours demonstrated a significant improvement in systolic PTD parameters in all walls (Table 4, Table 5). PTD Measurements and Global LV Function Between the first and the second echocardiographic evaluation, mean LV EF of the whole study population increased from 42.1 ± 6.5% to 44.3 ± 9.3% (P = .13). In patients with LV functional recovery (n = 12), mean S-wave velocity of the anterior wall increased from 5.8 ± 1.3 to 7.6 ± 2.0 cm/s, and mean S-wave velocity of the anterior septum from 5.1 ± 0.7 to 7.4 ± 1.7 cm/s (P = .006 and P = .003, respectively). Changes in mean S-wave velocity of the anterior wall and anterior septum significantly correlated with the change in global EF (r = 0.722 and 0.714 for the anterior wall and anterior septum, respectively, both P < .001). To detect the best cut-off value for a change in mean S-wave velocity to detect LV functional recovery, a receiver operating characteristic curve analysis was performed. For the anterior wall, the calculated area under the curve was 0.979, and an improvement of 0.23 cm/s had a sensitivity of 83% and a specificity of 100% in detecting LV functional recovery. For the anterior septum, the calculated area under the curve was 1.0, and an improvement of 0.17 cm/s had a sensitivity and specificity of 100% in detecting LV functional recovery. Detection of LV Functional Recovery The sensitivity, specificity, and positive and negative predictive values of individual markers of reperfusion compared with those of PTD improvement in detecting LV functional recovery are shown in Table 6. Based on the receiver operating characteristic curve analysis, PTD improvement was defined as any increase in the mean S-wave velocity in both the anterior wall and anterior septum between the first and the second evaluation. PTD improvement occurred in all patients who recovered LV function, and did not occur in any patient who did not, yielding a sensitivity and specificity of 100% in detecting LV functional recovery after primary PCI. Discussion This study is probably the first to analyze the relationship between PTD parameters and both invasive and noninvasive markers of reperfusion in patients with STEMI undergoing primary PCI. The relationship between PTD parameters and noninvasive reperfusion criteria has been previously reported, but these were patients receiving thrombolytic therapy and, thus, invasive markers of reperfusion were not evaluated.9 The success of reperfusion in the patients enrolled in our study was examined by a variety of invasive and noninvasive markers. Of these, MBG and S-T segment resolution were specifically targeted, as these parameters also provide information about myocardial perfusion.11 We recorded systolic PTD parameters from 6 different locations at the level of the mitral annulus, evaluating the longitudinal shortening of the LV. As the LV contracts, shortening occurs along both the long and the short axes. Shortening across the LV long axis (movement of the atrioventricular plane) can be used in the evaluation of regional and global LV functions,12 and has been found to be more sensitive for ischemia.13 The reason for this might be that the longitudinal fibers, which operate in LV shortening along the long axis, are more dense in the subendocardial and subepicardial areas.14 Furthermore, the regional velocities recorded by PTD echocardiography reflect only the movement parallel to the local imaging plane. In addition, the velocities recorded parallel to the imaging plane of any region reflect not only the myocardial contraction and relaxation, but are affected by the rotation and motion of the contracting heart as well. Because the apex is relatively stable and the mitral annular motion is almost parallel to the imaging plane in apical views, the mitral annular motion recorded from the apical views was taken into consideration in the evaluation of regional LV function. Systolic PTD Parameters, TIMI Flow, and MBG As previously described, a substantial number of patients with TIMI 3 flow after primary PCI fail to obtain complete and sustained myocardial reperfusion and remain at risk of developing large infarcts.2 Today, angiographic definition of successful reperfusion includes both TIMI 3 flow and MBG 2 or 3.6 In our study, patients with MBG 2 or 3 demonstrated significant improvement of systolic PTD parameters in the infarct-related walls between the first and the second echocardiographic evaluation. Patients with MBG 2 or 3 have a smaller infarct size, attributed to the success of reperfusion at the myocardial level.6 Therefore, functional improvement of the infarct-related segments after a period of myocardial stunning is expected in these patients. On the other hand, patients with MBG 0 or 1 showed significant deterioration of systolic PTD parameters in the infarct-related walls. Because of the possible failure of myocardial reperfusion in these patients, they possibly demonstrate a larger infarct size with more deleterious infarct extension and infarct expansion,15 resulting in functional deterioration of systolic motion in the infarct-related segments. Patients with TIMI 3 flow demonstrated a similar trend, yet the differences between the first and the second reading were not statistically significant in some of the examined walls. This may be explained by the fact that patients with TIMI 3 flow do not necessarily demonstrate MBG 2 or 3, but may sometimes demonstrate lesser blush grades and, therefore, impaired myocardial reperfusion. Systolic PTD changes seem to be more closely related to myocardial reperfusion than to the infarct-related artery patency. A trend toward improvement of systolic PTD parameters in the noninfarct-related segments was also observed. Alam et al,12 in their study of PTD parameters 3 to 4 days after acute MI, demonstrated significant derangement of systolic PTD parameters in the noninfarct-related segments, as compared with control subjects. They speculated that this derangement might be the result of the interaction of the longitudinal fibers.12 In their study of PTD parameters in patients receiving thrombolytic therapy in the setting of acute MI, Iyisoy et al9 also observed a similar derangement in the noninfarct-related walls, which healed almost completely in all studied patients, including those with and without noninvasive evidence of successful reperfusion. They stated that, in the absence of visible wall-motion abnormalities, PTD recordings may reveal reduced functional PTD parameters, and that myocardial stunning can also develop in the presence of partial occlusion of the arterial lumen when the tissue oxygen requirements are increased temporarily. Therefore, because the noninfarcted regions are subjected to an additional workload during acute infarction, in the presence of a nonsignificant lesion in the arterial supply to these regions, myocardial stunning at the PTD sensitivity level might develop, and should then subside when the acute phase is over. Systolic PTD Parameters and Noninvasive Markers of Reperfusion Impaired S-T segment resolution in patients with TIMI 3 flow in the infarct-related artery most likely identifies patients with no myocardial reflow, which means that these patients have a higher risk for an adverse outcome.16 In this study, patients with greater than 50% S-T resolution demonstrated significant improvement of systolic PTD parameters in the infarct-related walls between the first and the second PTD evaluation, whereas those with 50% or less S-T resolution showed significant deterioration. Because of the failure of microvascular reperfusion in these patients, they possibly demonstrate a larger infarct size, resulting in functional deterioration of systolic motion in the infarct-related segments. Similarly, patients with an early CK peak showed significant improvement of systolic PTD parameters and those with a delayed CK peak showed significant deterioration in the infarct-related walls. Changes in PTD parameters could, therefore, be related to changes in CK peak levels, which are known to be related to the infarct-related coronary artery patency.7 Systolic PTD Changes in Acute MI, an Indicator of Myocardial Reperfusion? Although the actual objective of the different reperfusion modalities is the preservation of myocardial function through timely myocardial reperfusion, the evaluation of segmental myocardial performance by echocardiography did not play an integral part in estimating the success of myocardial reperfusion after acute MI. The relative subjectivity of the assessment of regional myocardial function by the conventional 2-dimensional echocardiography may explain this observation. With the development of Doppler tissue imaging, quantitative assessment of myocardial wall velocities represented a major advantage with a great potential in establishing the analysis of regional myocardial performance. After analysis of the collected data, it was evident that only systolic PTD changes in the infarct-related segments were closely related to the success of reperfusion as evidenced by the various markers used in this study. Therefore, changes in systolic PTD parameters in the anterior wall and anterior septum were used to categorize the studied patients according to the recorded values at two different settings. When compared with TIMI flow, MBG, S-T resolution, and early CK peaking, systolic PTD changes demonstrated the highest sensitivity and specificity in detecting global LV functional recovery. These results are encouraging and show that the use of PTD imaging for the detection of myocardial reperfusion after acute MI is clinically applicable and may be effective. This simple noninvasive tool could play an important role in detecting the success of microvascular reperfusion through the changes detected in regional myocardial function after acute MI. Study Limitations The most important limitation of this study is its small sample size. Larger studies may yield more striking results in view of the relationship detected despite the small number of patients enrolled. Another limitation of this study is that PTD data were obtained at two settings after primary PCI. Comparing PTD data before and after primary intervention was not performed and may yield interesting results, which may be readily available shortly after intervention, and should be an issue for future studies. Furthermore, it is not clear whether the drugs taken by the patient had any effects on PTD data, as there is little information about this in the literature. Shan et al17 observed a significant relationship between myocardial adrenergic receptor density and both systolic and diastolic PTD data, which might suggest that PTD data are affected by cardiac drugs with negative inotropic characters, such as beta blockers. In addition, nearly half of the studied patients had multivessel disease. The location, extent, and severity of the coronary lesions determine a wide variety of patterns in terms of regional myocardial function. Conclusion This study has demonstrated a significant relationship between systolic PTD parameters and both invasive and noninvasive markers of reperfusion in patients with acute STEMI undergoing primary PCI. Larger studies are needed to confirm the use of systolic PTD changes as a simple noninvasive marker of myocardial reperfusion in patients with acute infarction, with the advantage of being indicative of the actual myocardial performance at the same time. The authors acknowledge the valuable contribution of Dr Ahmed A. Khattab in the preparation and review of this manuscript. References 1. 1Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomized trials. Lancet. 2003;361:13–20.
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Cardiology Department, Ain Shams University Hospital, Cairo, Egypt.  Reprint requests: Mohamed Abdel-Wahab, MD, Cardiology Department, Ain Shams University Hospital, Abbassia, Cairo, Egypt.
PII: S0894-7317(07)00394-X doi:10.1016/j.echo.2007.05.032 © 2008 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved. | |
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