© 2013, Wiley Periodicals, Inc. DOI: 10.1111/echo.12446
Echocardiography
Sequential Evaluation of Coronary Flow Patterns after Primary Angioplasty in Acute Anterior ST-Elevation Myocardial Infarction Predicts Recovery of Left Ventricular Systolic Function Dawod Sharif, M.D.,*,† Amal Sharif-Rasslan, Ph.D.,† Nabeel Makhoul, M.D.,* Arie Shefer, M.D.,* Amin Hassan, M.D.,* and Uri Rosenschein, M.D., F.A.C.C.* *Department of Cardiology, Bnai Zion Medical Center, Haifa, Israel; and †Technion – Israel Institute of Technology, Haifa, Israel
Background: Function of the microcirculation after primary percutaneous coronary intervention (PCI) is dynamic and contributes to unpredictability of recovery of left ventricular (LV) systolic function. Aim: This study was conducted to evaluate sequential Doppler velocity parameters of the left anterior descending coronary artery (LAD) in predicting recovery of global and regional LV systolic function. Methods: Thirty-five consecutive patients, 24 males, age 59 12 years, with acute anterior ST-elevation myocardial infarction (STEMI) who had primary PCI were studied. Thrombolysis in myocardial infarction (TIMI) and myocardial blush grades were evaluated. Transthoracic echocardiographic (TTE) studies, evaluation of left ventricular ejection fraction (LVEF), LAD territory wall-motion score index (WMSI), and sampling of LAD Doppler velocities up to 6 hours post-PCI, 48 hours postprocedure, and predischarge were performed. Results: Thrombolysis in myocardial infarction grade before PCI averaged 0.86 1.19 and post-PCI 2.89 0.32, P < 0.05. Myocardial blush grade before PCI was 0.41 0.98 and after PCI 2.22 0.93, P < 0.05. Diastolic velocity deceleration time (DDT) in the LAD early after PCI was less than 600 ms in 16 subjects. Immediately after PCI, in subjects with DDT > 600 ms, LVEF was 38.5 6% and predischarge 49.2 8.7%, P = 9.77 9 105 and LADWMSI decreased from 2 0.38 to 1.4 0.48, P = 0.000163. In subjects with DDT < 600 ms LAD-WMSI did not change significantly. Early and minimal LAD-DDT correlated with improvement in LV systolic function, r = 0.6, whereas post-PCI blush grade had lower correlation with LVEF, r = 0.39. Conclusions: Global and regional LV systolic function after PCI in acute anterior MI can be predicted by LAD-DDT better than by post-PCI myocardial blush. (Echocardiography 2014;31:644–653) Key words: angioplasty, myocardial infarction, microcirculation, coronary flow, left ventricular function
The treatment of choice in acute ST-elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PCI).1–4 The objective of primary PCI is to restore myocardial perfusion in the coronary bed distal to the occluded culprit artery. The thrombolysis in myocardial infarction (TIMI) classification5 and myocardial blush grades6–8 used to assess epicardial coronary artery flow and myocardial perfusion after primary PCI predict outcome. However, even with successful primary PCI and the high rate of patency of the culprit artery, left Address for correspondence and reprint requests: Dawod Sharif, M.D., Department of Cardiology, Bnai Zion Medical Center, 47 Golomb St, Haifa, Israel. Fax: 972-4-8359745; E-mail: [email protected]
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ventricular (LV) functional recovery is limited and not well predicted.9,10 Doppler sampling of coronary artery velocities by transthoracic echocardiography (TTE) is possible.11–15 It was shown that sequential sampling of left anterior descending coronary artery (LAD) velocities in patients with acute anterior STEMI is feasible and changes during the days after primary PCI.16 As coronary blood flow occurs mainly in diastole, and as the intra-myocardial capacitance vessels may be blocked after primary PCI; coronary diastolic deceleration time (DDT) may reflect the properties of the coronary microcirculation in a fashion similar to that of mitral deceleration time reflecting LV diastolic function. We reported recently that DDT after primary PCI may change favorably or may deteriorate
Coronary Heart Disease
reflecting improvement or worsening of the function of the microcirculation.17 Therefore, the purpose of this prospective study was to evaluate the significance of parameters derived from the LAD velocity profile as predictors of recovery of LV systolic function and comparison with TIMI and myocardial blush grades immediately after primary PCI. Methods: Population: Thirty-five consecutive patients with acute ST-elevation anterior myocardial infarction undergoing primary PCI were enrolled in the study. All fulfilled the following criteria: (1) first anterior wall ST segment elevation myocardial infarction (STEMI); (2) primary PCI within 12 hours of the onset of symptoms; (3) routine informed consent to perform primary PCI. Anterior STEMI was defined as continuous chest pain for at least 30 minutes and ST elevation of at least 2.0 mm in ≥2 contiguous precordial ECG leads. Exclusion criteria included one of the following clinical or angiographic findings: prior bypass surgery, previous anterior STEMI, significant left main artery disease, and failed primary PCI. Primary PCI: Primary PCI was performed in standard fashion. Patients were treated with an intravenous bolus injection of heparin (50–70 U/kg) to achieve coagulation time of ≥250 ms, oral clopidogrel (600 mg), and aspirin (300 mg) in the emergency department. The use of glycoprotein IIb, IIIa was left to the discretion of the attending physician. Coronary angiography and primary PCI were performed subsequently. Bare metal stents were deployed by high-pressure implantation techniques. Low-magnification angiogram at either the right 30° or 90° lateral projections with prolonged cine was performed to optimize myocardial blush grade documentation at the end of the intervention as previously described.6 After completion of primary PCI, patients were treated in the coronary care unit at the discretion of the attending physician. All patients were treated with clopidogrel and aspirin for 12 months after the procedure.
were performed in all occasions from biplane apical views. Wall-motion score index of the LAD was calculated using the following formula: LAD WMSI ¼
R score of 9 segments 9
assigning a value of 1 for normal LV wall motion, 2 for hypokinesis, and 3 for akinesis applied for the LAD 9 LV myocardial segments. Velocity of the LAD and measurements: To obtain LAD flows, the color Doppler Nyquist limit was set at 17 cm/sec. From low parasternal short-axis view, search for diastolic color flow in the anterior interventricular groove followed by clockwise rotation was performed, whereas from apical foreshortened two-chamber views LAD diastolic flow was located in the interventricular groove and the counterclockwise rotation of the transducer was performed (Fig. 1). Parameters of LAD velocity patterns were averaged from 3 beats, all in sinus rhythm. Diastolic LAD deceleration time (DDT) was measured as the time from peak diastolic velocity to the intercept of tangent of the velocity envelope with baseline. As already mentioned, measurements were performed early (within 6 hours of primary PCI) and after 48 hours. These two measurements of DDT, their mean, and the minimum were evaluated. In addition, pressure half-time (P1/2T) (ms) was determined as theptime for peak ffiffiffi diastolic velocity to decrease to 1= 2 of its initial value. Moreover, search for LAD early systolic flow reversal with early systolic negative velocity (ESFR) was performed. Angiographic analysis: Coronary angiograms were reviewed by two experienced interventional cardiologists. TIMI and myocardial blush grades
Echocardiography: Siemens, Acuson Sequoia echocardiographic system (Siemens, Mountain View, CA, USA) equipped with 3.5–7 MHz transducers was used. All patients had complete Doppler echocardiographic studies, within the first 6 hours after primary PCI, 48 hours after primary PCI, and 5 days after primary PCI. Echocardiographic measurements: Measurements of left ventricular ejection fraction (LVEF)
Figure 1. Color and pulsed Doppler signals of left anterior descending coronary artery velocity.
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were evaluated before and at the end of the intervention. Statistical Analysis: Statistical analyses were conducted using SPSS software version 13 (IBM, Petach-Tikva, Israel). All values were expressed as means and standard deviations. Intra- and inter-observer variability in DDT were evaluated as the mean standard deviation of the difference between the values of 15 measurements. Analysis of variance (ANOVA) with Bonferroni multiple comparison tests was used to assess the variability in DDT and P1/2T, considering P < 0.05 as statistically significant. Assessment of clinical utility of flow parameters was done by calculating sensitivity, specificity, positive, and negative predictive values as well as diagnostic accuracy. Correlation coefficients and their P-value were calculated to evaluate the relation of LAD flow parameters with LV systolic function parameters predischarge (5 days after PCI). Results: Study Populations Characteristics: The study population consisted of 35 patients, 24 males and 11 females, age 59 12.3 years, weight 79.8 14.6 kg, and height 169.4 3 cm. Coronary artery disease risk factors included arterial hypertension in 33%, hyperlipidemia 28%, cigarette smoking 28%, obesity 14%, family history 14%, and diabetes mellitus in 8%. No patients had severe LV hypertrophy. Patients were presented within 3.1 2.7 hours from the onset of chest pains. At presentation 75% of the patients were in Killip class I, 17% class II, and 8% class III. No patient was in cardiogenic shock. Pressors were not used
in these patients. Devices like intra-aortic balloon or impella were not used in any patient. Laboratory blood tests including troponin-I were taken routinely as usual. The average hospital stay was 5.5 0.4 days. All patients survived the hospital stay. Heart rate did not change significantly; on early evaluation 77 11, later 76 10, and before discharges 75 9 bpm, P = ns. Systolic blood pressure remained without significant change, on admission 128 8, later 126 7, and before discharge 129 8 mmHg, P = ns. Diastolic blood pressure did not change, on admission 75 6, later 77 5, and on discharge evaluation 77 7 mmHg, P = ns. Angioplasty: Evaluation of TIMI and myocardial blush grades were possible in 29 patients before primary PCI and in 27 after the procedure (Tables I and II). Before primary PCI, TIMI flow grades 0, 1, 2, and 3 were found in 17, 4, 3, and 5 patients, respectively, average 0.86 1.19. Before primary, PCI blush grades were 0, 1, 2, and 3 in 24, 1, 1, and 3 patients, respectively, average 0.41 0.98. After angioplasty, TIMI grades 0, 1, 2, and 3 were achieved in 0, 0, 3, and 24 patients, respectively, average 2.89 0.32, whereas post-PCI blush grades 0, 1, 2, and 3 were found in 1, 6, 6, and 14 patients, average 2.22 0.93, (Tables I and II). LV Function: At presentation, global systolic LV function, represented by LV ejection fraction, was moderately reduced, and increased 5 days after PCI (before discharge), by more than 5% in 18 patients, whereas regional LV systolic function assessed as
TABLE I Changes in TIMI Grades Pre- and Post-Angioplasty
TIMI pre-PCI TIMI post-PCI
0
1
2
3
N
Mean SD
P-Value (Pre/Post-PCI)
17 0
4 0
3 3
5 24
29 27
0.86 1.19 2.89 0.32
4.06 9 1010
PCI = primary angioplasty; N = number of patients.
TABLE II Changes in Myocardial Blush Grades Pre- and Post-Angioplasty
Blush pre-PCI Blush post-PCI
0
1
2
3
N
Mean SD
P-Value (Pre/Post-PCI)
24 1
1 6
1 6
3 14
29 27
0.41 0.98 2.22 0.93
3.27 9 109
PCI = primary angioplasty; N = number of patients.
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Coronary Heart Disease
(A)
(B)
(C) p=2.3×10-14
p=0.00048
EF- ejection fraction, LAD- left anterior descending coronary artery, LV- left ventricle, WMSI- wall motion score index, Early- within 6 hours after angioplasty, Late- 5 days after angioplasty.
Figure 2. Changes in LV functions
(A)
(B)
(C)
Figure 3. Three types of flow patterns through the left anterior descending coronary artery: A. prolonged diastolic deceleration time > 600 ms; B. brief diastolic deceleration time 600 ms and pressure half-time (P1/2T) >175 ms; (2) short DDT < 600 ms and P1/2T 600 (ms) 48 hours DDT > 600 (ms) Early P1/2T >175 ms 48 hours P1/2T >175 ms
Increase in LVEF > 10%
Sens. (%)
Spec. (%)
PPV (%)
NPV (%)
Dg. Ac (%)
Sens. (%)
Spec. (%)
PPV (%)
NPV (%)
Dg. Ac (%)
81 91
52 43
47 53
85 92
63 69
75 75
65 59
67 63
73 71
70 67
91 91
62 48
56 48
93 91
72 63
69 75
59 47
61 57
67 67
66 61
LVEF = left ventricular ejection fraction; DDT = diastolic deceleration time. Sens. = sensitivity; Spec = specificity; PPV = positive predictive values; NPV = negative predictive values; Dg. Ac diagnostic accuracy.
findings of others,6,16 however, their measurements were repeated much later. In addition, invasive coronary Doppler studies31–33 as well as noninvasive studies16,28,34–38 reported previously are consistent with our findings. Thus, our study differs from others by earlier and serially performing the measurements of LAD velocity parameters during the first 48 hours after primary PCI. This time period is of critical importance for achieving adequate coronary and myocardial flow to achieve recovery LV function. In fact, to achieve recovery of LV function, early and more frequent sampling of LAD velocities after primary PCI may be valuable to promptly detect and correct coronary flow abnormalities. Limitations: The number of patients included in this study is rather small; however, statistically significant findings were achieved. A larger study may add more information regarding the effects of fre-
quent confounders. In addition, studies with more frequent sampling of LAD blood velocities after primary PCI to investigate if an added benefit can be achieved from earlier detection of coronary flow abnormalities. In summary, repeated evaluation of LAD velocity patterns after primary PCI in acute anterior STEMI is feasible and predicts recovery of LV systolic function better than immediate myocardial flow and blush grades after primary PCI. Future studies to investigate treatment strategies are indicated to improve outcome. References 1. Grines CL, Brown KF, Marco J, et al: A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction: The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993;328:673–679. 2. Zijlstra F, de Boer MJ, Hoorntje JC, et al: A comparison of immediate angioplasty with intravenous streptokinase in
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acute myocardial infarction. N Engl J Med 1993;38:680– 684. GUSTO IIb Investigators: A clinical trial comparing primary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336: 1621–1628. De Luca G, van’t Hof AW, de Boer MJ, et al: Time to treatment significantly affects the extent of ST-segement resolution and myocardial blush in patients with acute myocardial infarction treated by primary angioplasty. Eur Heart J 2004;25:1009–1013. Chesebro JH, Knatteud G, Roberts R, et al: Thrombolysis in myocardial infarction (TIMI) trial phase I: A comparison between intravenous tissue plasminogen activator and streptokinase. Circulation 1987;76:142–154. van’t Hof AW, Liem A, Suryapranata H, et al: Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: Myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation 1998;97: 2302–2306. Gibson CM, Cannon CP, Murphy SA, et al: Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000;101:125–130. Stone GW, Peterson MA, Lansky AJ, et al: Impact of normalized myocardial perfusion after successful angioplasty in acute myocardial infarction. J Am Coll Cardiol 2002;39:591–597. Stone GW, Grines CL, Rothbaum D, et al, PAMI Trial Investigators: Analysis of the relative costs and effectiveness of primary angioplasty versus tissue-type plasminogen activator: The Primary Angioplasty in Myocardial Infarction (PAMI) trial. J Am Coll Cardiol 1997;29:901– 907. Zijlstra F, Beukema WP, van’t Hof AW, et al: Randomized comparison of primary coronary angioplasty with thrombolytic therapy in low risk patients with acute myocardial infarction. J Am Coll Cardiol 1997;29:908–912. Voci P, Testa G, Plaustro G: Imaging of the distal left anterior descending coronary artery by transthoracic color-Doppler echocardiography. Am J Cardiol 1998;81: 74G–78G. Caiati C, Montaldo C, Zedda N, et al: New noninvasive method for coronary flow reserve assessment: Contrastenhanced transthoracic second harmonic echo Doppler. Circulation 1999;99:771–778. Hildick-Smith D, Shapiro LM: Coronary flow reserve improves after aortic valve replacement for aortic stenosis: An adenosine transthoracic-echocardiography study. J Am Coll Cardiol 2000;36:1889–1896. Higashiue S, Watanabe H, Yoki Y, et al: Simple detection of severe coronary stenosis using transthoracic Doppler echocardiography at rest. Am J Cardiol 2001;87:1064– 1068. Pizzuto F, Voci P, Mariano E, et al: Assessment of flow velocity reserve by transthoracic Doppler echocardiography and venous adenosine infusion before and after left anterior descending coronary artery stenting. J Am Coll Cardiol 2001;38:155–162. Hozumi T, Knazaki Y, Ueda Y, et al: Coronary flow velocity analysis during short term follow up after coronary reperfusion: Use of transthoracic Doppler echocardiography to predict regional wall motion recovery in patients with acute myocardial infarction. Heart 2003;89:1163– 1168. Sharif D, Rofe G, Sharif-Rasslan A, et al: Analysis of serial coronary artery flow patterns early after primary angioplasty: New insights into the dynamics of the microcirculation. Isr Med Assoc J 2008;10:440–444. Shah A, Wagner GS, Granger CB, et al: Prognostic implications of TIMI flow grade in the infarct related artery
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compared with continuous 12-lead ST-segment resolution analysis: Reexamining the “gold standard” for myocardial reperfusion assessment. J Am Coll Cardiol 2000;35:666–672. Van’t Hof AW, Leim A, de Boer MJ, et al: Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Lancet 1997;350:615–619. Claeys MJ, Bosmans J, Veenstra L, et al: Determinants and prognostic implications of persistent ST-segment elevation after primary angioplasty for acute myocardial infarction. Circulation 1999;99:1972–1979. The TIMI Study Group: The thrombolysis in myocardial infarction (TIMI) trial: Phase 1 findings. N Engl J Med 1985;312:932–936. Gibson CM, Cannon CP, Daley WL, et al: TIMI frame count: A quantitative method of assessing coronary artery flow. Circulation 1996;93:879–888. Gibson CM, Murphy SA, Rizzo MJ, et al: Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Circulation 1999;99:1945– 1950. Gibson MC, de Lemos JA, Murphy SA, et al: Combination therapy with abxiximab reduces angiographically evident thrombus in acute myocardial infarction. A TIMI 14 substudy. Circulation 2001;103:2550–2554. de Lemos JA, Braunwald E: ST-segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol 2001;38:1283–1294. € rge H, Neumann T, Behrends M, et al: Perfusion-conDo traction mismatch with coronary microvascular obstruction: Role of inflammation. Am J Physiol 2000;279: H2587–H2592. Kawamoto T, Yoshida K, Akasaka T, et al: Can coronary blood flow velocity pattern after primary percutaneous transluminal coronary angioplasty predict recovery of regional left ventricular function in patients with acute myocardial infarction? Circulation 1999;100: 339–345. Yamamuro A, Akasaka T, Tamita K, et al: Coronary flow velocity pattern immediately after percutaneous coronary intervention as a predictor of complications and in-hospital survival after acute myocardial infarction. Circulation 2002;106:3051–3056. Sezer M, Oflaz H, Goren T, et al: Intracoronary streptokinase after primary percutaneous intervention. N Engl J Med 2007;356:1823–1834. Lepper W, Sieswerda GT, Franke A, et al: Repeated assessment of coronary flow velocity pattern in patients with first acute myocardial infarction. J Am Coll Cardiol 2002;39:1283–1289. Ali A, Cox D, Dib N, et al, AIMI Investigators: Rheolytic thrombectomy with percutaneous intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study. J Am Coll Cardiol 2006;48:244–252. Lefevre T, Garcia E, Reimers B, et al., X AMINE ST Investigators: X-sizer for thrombectomy in acute myocardial infarction improves ST-segment resolution: Results of the X-sizer in AMI for negligible embolization and optimal ST resolution (X AMINE ST) trial. J Am Coll Cardiol 2005;46:246–252. Akasaka T, Yoshida K, Kawamoto T, et al: Relation of phasic coronary flow velocity characteristics with TIMI perfusion grade and myocardial recovery after primary percutaneous transluminal coronary angioplasty and rescue stenting. Circulation 2000;101:2361– 2367. Iwakura K, Ito H, Kawano S, et al: Assessing myocardial perfusion with the transthoracic Doppler technique in patients with reperfused anterior myocardial infarction: Comparison with angiographic, enzymatic
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and electrocardiographic indices. Eur Heart J 2004;25: 1526–1533. 35. Okamura A, Ito H, Iwakura K, et al: Usefulness of a new grading system based on coronary flow velocity pattern in predicting outcome in patients with acute myocardial infarction having percutaneous coronary intervention. Am J Cardiol 2005;96:927–932. 36. Katayama M, Yamamuro A, Ueda Y, et al: Coronary flow velocity pattern assessed noninvasively by transthoracic color Doppler echocardiography serves as a predictor of adverse cardiac events and left ventricular remodeling in patients with acute myocardial infarction. J Am Soc Echocardiogr 2006;19:335–340.
37. Hoffmann R, Haager P, Lepper W, et al: Relation of coronary flow pattern to myocardial blush grade in patients with first acute myocardial infarction. Heart 2003;89:1147–1451. 38. Takeuchi M, Miyazaki C, Yoshitani H, et al: Assessment of coronary flow velocity with transthoracic Doppler ehocardiography during dobutamine stress echocardiography. J Am Coll Cardiol 2001;38:117–123. 39. Baykan M, Baykan EC, Turan S, et al: Assessment of left ventricular function and Tei index by tissue Doppler imaging in patients with slow coronary flow. Echocardiography 2009;26:1167–1172.
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Echocardiography
Sequential Evaluation of Coronary Flow Patterns after Primary Angioplasty in Acute Anterior ST-Elevation Myocardial Infarction Predicts Recovery of Left Ventricular Systolic Function Dawod Sharif, M.D.,*,† Amal Sharif-Rasslan, Ph.D.,† Nabeel Makhoul, M.D.,* Arie Shefer, M.D.,* Amin Hassan, M.D.,* and Uri Rosenschein, M.D., F.A.C.C.* *Department of Cardiology, Bnai Zion Medical Center, Haifa, Israel; and †Technion – Israel Institute of Technology, Haifa, Israel
Background: Function of the microcirculation after primary percutaneous coronary intervention (PCI) is dynamic and contributes to unpredictability of recovery of left ventricular (LV) systolic function. Aim: This study was conducted to evaluate sequential Doppler velocity parameters of the left anterior descending coronary artery (LAD) in predicting recovery of global and regional LV systolic function. Methods: Thirty-five consecutive patients, 24 males, age 59 12 years, with acute anterior ST-elevation myocardial infarction (STEMI) who had primary PCI were studied. Thrombolysis in myocardial infarction (TIMI) and myocardial blush grades were evaluated. Transthoracic echocardiographic (TTE) studies, evaluation of left ventricular ejection fraction (LVEF), LAD territory wall-motion score index (WMSI), and sampling of LAD Doppler velocities up to 6 hours post-PCI, 48 hours postprocedure, and predischarge were performed. Results: Thrombolysis in myocardial infarction grade before PCI averaged 0.86 1.19 and post-PCI 2.89 0.32, P < 0.05. Myocardial blush grade before PCI was 0.41 0.98 and after PCI 2.22 0.93, P < 0.05. Diastolic velocity deceleration time (DDT) in the LAD early after PCI was less than 600 ms in 16 subjects. Immediately after PCI, in subjects with DDT > 600 ms, LVEF was 38.5 6% and predischarge 49.2 8.7%, P = 9.77 9 105 and LADWMSI decreased from 2 0.38 to 1.4 0.48, P = 0.000163. In subjects with DDT < 600 ms LAD-WMSI did not change significantly. Early and minimal LAD-DDT correlated with improvement in LV systolic function, r = 0.6, whereas post-PCI blush grade had lower correlation with LVEF, r = 0.39. Conclusions: Global and regional LV systolic function after PCI in acute anterior MI can be predicted by LAD-DDT better than by post-PCI myocardial blush. (Echocardiography 2014;31:644–653) Key words: angioplasty, myocardial infarction, microcirculation, coronary flow, left ventricular function
The treatment of choice in acute ST-elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PCI).1–4 The objective of primary PCI is to restore myocardial perfusion in the coronary bed distal to the occluded culprit artery. The thrombolysis in myocardial infarction (TIMI) classification5 and myocardial blush grades6–8 used to assess epicardial coronary artery flow and myocardial perfusion after primary PCI predict outcome. However, even with successful primary PCI and the high rate of patency of the culprit artery, left Address for correspondence and reprint requests: Dawod Sharif, M.D., Department of Cardiology, Bnai Zion Medical Center, 47 Golomb St, Haifa, Israel. Fax: 972-4-8359745; E-mail: [email protected]
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ventricular (LV) functional recovery is limited and not well predicted.9,10 Doppler sampling of coronary artery velocities by transthoracic echocardiography (TTE) is possible.11–15 It was shown that sequential sampling of left anterior descending coronary artery (LAD) velocities in patients with acute anterior STEMI is feasible and changes during the days after primary PCI.16 As coronary blood flow occurs mainly in diastole, and as the intra-myocardial capacitance vessels may be blocked after primary PCI; coronary diastolic deceleration time (DDT) may reflect the properties of the coronary microcirculation in a fashion similar to that of mitral deceleration time reflecting LV diastolic function. We reported recently that DDT after primary PCI may change favorably or may deteriorate
Coronary Heart Disease
reflecting improvement or worsening of the function of the microcirculation.17 Therefore, the purpose of this prospective study was to evaluate the significance of parameters derived from the LAD velocity profile as predictors of recovery of LV systolic function and comparison with TIMI and myocardial blush grades immediately after primary PCI. Methods: Population: Thirty-five consecutive patients with acute ST-elevation anterior myocardial infarction undergoing primary PCI were enrolled in the study. All fulfilled the following criteria: (1) first anterior wall ST segment elevation myocardial infarction (STEMI); (2) primary PCI within 12 hours of the onset of symptoms; (3) routine informed consent to perform primary PCI. Anterior STEMI was defined as continuous chest pain for at least 30 minutes and ST elevation of at least 2.0 mm in ≥2 contiguous precordial ECG leads. Exclusion criteria included one of the following clinical or angiographic findings: prior bypass surgery, previous anterior STEMI, significant left main artery disease, and failed primary PCI. Primary PCI: Primary PCI was performed in standard fashion. Patients were treated with an intravenous bolus injection of heparin (50–70 U/kg) to achieve coagulation time of ≥250 ms, oral clopidogrel (600 mg), and aspirin (300 mg) in the emergency department. The use of glycoprotein IIb, IIIa was left to the discretion of the attending physician. Coronary angiography and primary PCI were performed subsequently. Bare metal stents were deployed by high-pressure implantation techniques. Low-magnification angiogram at either the right 30° or 90° lateral projections with prolonged cine was performed to optimize myocardial blush grade documentation at the end of the intervention as previously described.6 After completion of primary PCI, patients were treated in the coronary care unit at the discretion of the attending physician. All patients were treated with clopidogrel and aspirin for 12 months after the procedure.
were performed in all occasions from biplane apical views. Wall-motion score index of the LAD was calculated using the following formula: LAD WMSI ¼
R score of 9 segments 9
assigning a value of 1 for normal LV wall motion, 2 for hypokinesis, and 3 for akinesis applied for the LAD 9 LV myocardial segments. Velocity of the LAD and measurements: To obtain LAD flows, the color Doppler Nyquist limit was set at 17 cm/sec. From low parasternal short-axis view, search for diastolic color flow in the anterior interventricular groove followed by clockwise rotation was performed, whereas from apical foreshortened two-chamber views LAD diastolic flow was located in the interventricular groove and the counterclockwise rotation of the transducer was performed (Fig. 1). Parameters of LAD velocity patterns were averaged from 3 beats, all in sinus rhythm. Diastolic LAD deceleration time (DDT) was measured as the time from peak diastolic velocity to the intercept of tangent of the velocity envelope with baseline. As already mentioned, measurements were performed early (within 6 hours of primary PCI) and after 48 hours. These two measurements of DDT, their mean, and the minimum were evaluated. In addition, pressure half-time (P1/2T) (ms) was determined as theptime for peak ffiffiffi diastolic velocity to decrease to 1= 2 of its initial value. Moreover, search for LAD early systolic flow reversal with early systolic negative velocity (ESFR) was performed. Angiographic analysis: Coronary angiograms were reviewed by two experienced interventional cardiologists. TIMI and myocardial blush grades
Echocardiography: Siemens, Acuson Sequoia echocardiographic system (Siemens, Mountain View, CA, USA) equipped with 3.5–7 MHz transducers was used. All patients had complete Doppler echocardiographic studies, within the first 6 hours after primary PCI, 48 hours after primary PCI, and 5 days after primary PCI. Echocardiographic measurements: Measurements of left ventricular ejection fraction (LVEF)
Figure 1. Color and pulsed Doppler signals of left anterior descending coronary artery velocity.
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were evaluated before and at the end of the intervention. Statistical Analysis: Statistical analyses were conducted using SPSS software version 13 (IBM, Petach-Tikva, Israel). All values were expressed as means and standard deviations. Intra- and inter-observer variability in DDT were evaluated as the mean standard deviation of the difference between the values of 15 measurements. Analysis of variance (ANOVA) with Bonferroni multiple comparison tests was used to assess the variability in DDT and P1/2T, considering P < 0.05 as statistically significant. Assessment of clinical utility of flow parameters was done by calculating sensitivity, specificity, positive, and negative predictive values as well as diagnostic accuracy. Correlation coefficients and their P-value were calculated to evaluate the relation of LAD flow parameters with LV systolic function parameters predischarge (5 days after PCI). Results: Study Populations Characteristics: The study population consisted of 35 patients, 24 males and 11 females, age 59 12.3 years, weight 79.8 14.6 kg, and height 169.4 3 cm. Coronary artery disease risk factors included arterial hypertension in 33%, hyperlipidemia 28%, cigarette smoking 28%, obesity 14%, family history 14%, and diabetes mellitus in 8%. No patients had severe LV hypertrophy. Patients were presented within 3.1 2.7 hours from the onset of chest pains. At presentation 75% of the patients were in Killip class I, 17% class II, and 8% class III. No patient was in cardiogenic shock. Pressors were not used
in these patients. Devices like intra-aortic balloon or impella were not used in any patient. Laboratory blood tests including troponin-I were taken routinely as usual. The average hospital stay was 5.5 0.4 days. All patients survived the hospital stay. Heart rate did not change significantly; on early evaluation 77 11, later 76 10, and before discharges 75 9 bpm, P = ns. Systolic blood pressure remained without significant change, on admission 128 8, later 126 7, and before discharge 129 8 mmHg, P = ns. Diastolic blood pressure did not change, on admission 75 6, later 77 5, and on discharge evaluation 77 7 mmHg, P = ns. Angioplasty: Evaluation of TIMI and myocardial blush grades were possible in 29 patients before primary PCI and in 27 after the procedure (Tables I and II). Before primary PCI, TIMI flow grades 0, 1, 2, and 3 were found in 17, 4, 3, and 5 patients, respectively, average 0.86 1.19. Before primary, PCI blush grades were 0, 1, 2, and 3 in 24, 1, 1, and 3 patients, respectively, average 0.41 0.98. After angioplasty, TIMI grades 0, 1, 2, and 3 were achieved in 0, 0, 3, and 24 patients, respectively, average 2.89 0.32, whereas post-PCI blush grades 0, 1, 2, and 3 were found in 1, 6, 6, and 14 patients, average 2.22 0.93, (Tables I and II). LV Function: At presentation, global systolic LV function, represented by LV ejection fraction, was moderately reduced, and increased 5 days after PCI (before discharge), by more than 5% in 18 patients, whereas regional LV systolic function assessed as
TABLE I Changes in TIMI Grades Pre- and Post-Angioplasty
TIMI pre-PCI TIMI post-PCI
0
1
2
3
N
Mean SD
P-Value (Pre/Post-PCI)
17 0
4 0
3 3
5 24
29 27
0.86 1.19 2.89 0.32
4.06 9 1010
PCI = primary angioplasty; N = number of patients.
TABLE II Changes in Myocardial Blush Grades Pre- and Post-Angioplasty
Blush pre-PCI Blush post-PCI
0
1
2
3
N
Mean SD
P-Value (Pre/Post-PCI)
24 1
1 6
1 6
3 14
29 27
0.41 0.98 2.22 0.93
3.27 9 109
PCI = primary angioplasty; N = number of patients.
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(A)
(B)
(C) p=2.3×10-14
p=0.00048
EF- ejection fraction, LAD- left anterior descending coronary artery, LV- left ventricle, WMSI- wall motion score index, Early- within 6 hours after angioplasty, Late- 5 days after angioplasty.
Figure 2. Changes in LV functions
(A)
(B)
(C)
Figure 3. Three types of flow patterns through the left anterior descending coronary artery: A. prolonged diastolic deceleration time > 600 ms; B. brief diastolic deceleration time 600 ms and pressure half-time (P1/2T) >175 ms; (2) short DDT < 600 ms and P1/2T 600 (ms) 48 hours DDT > 600 (ms) Early P1/2T >175 ms 48 hours P1/2T >175 ms
Increase in LVEF > 10%
Sens. (%)
Spec. (%)
PPV (%)
NPV (%)
Dg. Ac (%)
Sens. (%)
Spec. (%)
PPV (%)
NPV (%)
Dg. Ac (%)
81 91
52 43
47 53
85 92
63 69
75 75
65 59
67 63
73 71
70 67
91 91
62 48
56 48
93 91
72 63
69 75
59 47
61 57
67 67
66 61
LVEF = left ventricular ejection fraction; DDT = diastolic deceleration time. Sens. = sensitivity; Spec = specificity; PPV = positive predictive values; NPV = negative predictive values; Dg. Ac diagnostic accuracy.
findings of others,6,16 however, their measurements were repeated much later. In addition, invasive coronary Doppler studies31–33 as well as noninvasive studies16,28,34–38 reported previously are consistent with our findings. Thus, our study differs from others by earlier and serially performing the measurements of LAD velocity parameters during the first 48 hours after primary PCI. This time period is of critical importance for achieving adequate coronary and myocardial flow to achieve recovery LV function. In fact, to achieve recovery of LV function, early and more frequent sampling of LAD velocities after primary PCI may be valuable to promptly detect and correct coronary flow abnormalities. Limitations: The number of patients included in this study is rather small; however, statistically significant findings were achieved. A larger study may add more information regarding the effects of fre-
quent confounders. In addition, studies with more frequent sampling of LAD blood velocities after primary PCI to investigate if an added benefit can be achieved from earlier detection of coronary flow abnormalities. In summary, repeated evaluation of LAD velocity patterns after primary PCI in acute anterior STEMI is feasible and predicts recovery of LV systolic function better than immediate myocardial flow and blush grades after primary PCI. Future studies to investigate treatment strategies are indicated to improve outcome. References 1. Grines CL, Brown KF, Marco J, et al: A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction: The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993;328:673–679. 2. Zijlstra F, de Boer MJ, Hoorntje JC, et al: A comparison of immediate angioplasty with intravenous streptokinase in
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