Author + information
- Received December 27, 2008
- Revision received February 26, 2009
- Accepted March 9, 2009
- Published online September 1, 2009.
- Gastón A. Rodriguez-Granillo, MD, PhD⁎,§,⁎ (, )
- Miguel A. Rosales, MD⁎,
- Santiago Baum, MD†,
- Paola Rennes, MD†,
- Carlos Rodriguez-Pagani, MD†,
- Valeria Curotto, MD†,
- Carlos Fernandez-Pereira, MD‡,
- Claudio Llaurado, BSc‡,
- Gustavo Risau, MD‡,
- Elina Degrossi, MD⁎,
- Hernán C. Doval, MD, PhD† and
- Alfredo E. Rodriguez, MD, PhD⁎,‡
Reprint requests and correspondence:
Dr. Gastón A. Rodriguez-Granillo, Department of Cardiovascular Imaging, Otamendi Hospital, Azcuenaga 870 (C1115AAB), Buenos Aires, Argentina
Objectives We sought to explore the relationship between established parameters of reperfusion and the extent of myocardial damage measured by the delayed enhancement (DE) of iodinated contrast by multidetector computed tomography (MDCT) immediately after primary percutaneous coronary intervention (PCI).
Background Early detection of myocardial viability should be valuable for risk stratification of patients with reperfused acute myocardial infarction (AMI).
Methods Consecutive patients without a history of previous AMI who underwent primary PCI for an ST-segment elevation AMI were examined by DE-MDCT without an additional contrast injection immediately after completion of PCI. No medication was administrated to lower the heart rate. Dose modulation lead to an approximate mean radiation dose of 5.5 mSv.
Results Thirty patients constituted the study population. Mean age was 61.4 ± 15.6 years, 24 (80%) were men, and 4 (13%) were diabetic. Although post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved in all patients, DE was detected in 14 (47%) patients. Age, sex, hypertension, diabetes, smoking history, serum creatinine levels, and pain duration were not associated with the presence of DE. Door-to-balloon time (DE 70.3 ± 33.6 min vs. non-DE 98.3 ± 70.7 min, p = 0.19) and lesion crossing time (DE 18.6 ± 11.4 min vs. non-DE 16.4 ± 9.6 min, p = 0.58) did not differ between groups. The TIMI myocardial perfusion grade (0 to 1 vs. 2 to 3) after stent implantation and electrocardiogram ST-segment resolution (<50% or ≥50%) were associated with the presence of DE (p = 0.001 and p = 0.02, respectively). Pre-discharge left ventricular ejection fraction was lower in DE than in non-DE patients (44.6 ± 12.4% vs. 54.1 ± 10.3%, respectively, p = 0.05). Hospitalization days (DE 5.6 ± 3.8 vs. non-DE 4.8 ± 1.0, p = 0.41) and 6-month cardiac events (DE 3 of 14 vs. non-DE 1 of 16, p = 0.22) did not differ between groups.
Conclusions Early detection of myocardial viability immediately after primary PCI by the use of DE-MDCT is related to clinical and angiographic parameters of myocardial reperfusion.
With the advent of primary percutaneous coronary intervention (PCI), the prognosis of patients with acute myocardial infarction (AMI) has improved significantly (1). However, clinical outcomes are not only associated with the final angiographic flow in the epicardial artery but also with flow in the myocardium (2–5). Accurate and early distinction between viable and nonviable myocardium would represent a valuable instrument for risk stratification of reperfused AMI patients by providing the clinician the ability to discriminate between stunned and irreversibly damaged myocardium.
The rapidly evolving field of multidetector computed tomography (MDCT) coronary angiography has lead investigators to explore noncoronary applications of the technique. Recently, the authors of several studies (9–14) established that the identification of myocardium delayed enhancement (DE) of iodinated contrast by MDCT (DE-MDCT) is a direct marker of the presence, extent, and morphology of irreversible damage of the myocardium. The physiopathological mechanism is similar to the gadolinium in cardiac magnetic resonance imaging. Because 75% of myocardial mass is intracellular, rupture of the sarcolemmal membrane and subsequent entrance of contrast material enables an increase in the volume of distribution as the result of a combination of delayed wash-in and wash-out kinetics of nonviable tissue (9–13).
The absence of hyperenhancement in DE-MDCT has been related to viable myocardium assessed by low-dose dobutamine echocardiography (15). Nevertheless, the association between clinical and angiographic parameters of reperfusion and myocardium viability evaluated by DE-MDCT remains unknown. We therefore sought to explore the relationship between established parameters of reperfusion and the presence and extent of myocardial damage measured by DE-MDCT immediately after primary PCI.
Consecutive patients without a history of previous myocardial infarction (MI) who underwent primary PCI for a ST-segment elevation myocardial infarction (STEMI) were examined with DE-MDCT without additional iodine injection immediately after completion of PCI. Exclusion criteria included a history of previous MI, hemodynamic instability, and the presence of a pacemaker or implantable devices.
Patients were included if they were >18 years of age with the first MI presenting within 12 h of their symptom onset. We defined STEMI as ST-segment elevation of at least 1 mm in ≥2 contiguous leads with associated chest pain persisting >30 min. Pre-infarction angina was defined as recent onset discomfort or chest pain during the previous 7 days. The degree of ST-segment reduction after PCI was considered as a dichotomic (<50% vs. ≥50%) variable. The peak creatine kinase value was evaluated in every patient. In-hospital morbidity was evaluated as electrical (ventricular tachycardia, ventricular fibrillation) and mechanical (acute ventricular septal defect, acute mitral insufficiency, and rupture of the ventricular free wall) complications and worst Killip-Kimbal class achieved during hospitalization. In case more than 1 complication was present, the highest ranked was computed. Pre-discharge and 6-month left ventricular ejection fraction (LVEF) were measured by electrocardiogram (ECG)-gated radionuclide ventriculography. The incidence of major cardiac and cerebrovascular events defined as the composite of death, nonfatal AMI, stroke, and clinically driven target vessel revascularization within 6 months was recorded.
Angiography: analysis and definitions
All patients received aspirin and load dose of 600-mg clopidogrel. Administration of glycoprotein IIb/IIIa receptor antagonists (tirofiban) was administrated at discretion of the treating physician, and infusion was started before PCI. Invasive coronary angiography was performed by the use of meglumine sodium diatrizoate (Mallinckrodt, St. Louis, Missouri). The culprit coronary artery was defined by use of the ECG and the angiographic result. Post-procedural suboptimal coronary flow was defined as final Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2 and normal flow as TIMI flow grade 3 in the infarct-related artery. The crossing time was defined as the time elapsed between the first contrast injection in the infarct related artery and the first dilation of the culprit lesion. The final TIMI flow grade and the TIMI myocardial perfusion grade (TMPG) were determined by an independent observer who was unaware of the CT results to assess epicardial and microvascular coronary blood flow in the culprit artery after PCI, respectively.
Ten seconds of cine filming were required to allow some filling of the venous system to evaluate the washout phase of contrast dye. In brief, and as previously described, in TMPG 0 there is minimal or no myocardial blush; in TMPG 1 dye stains the myocardium and persists on the next injection; in TMPG 2 dye enters the myocardium but washes out slowly so that dye is strongly persistent at the end of the injection; and in TMPG 3 there is normal entrance and exit of dye in the myocardium (16). A TIMI coronary flow grade 3 in the treated vessel with a residual stenosis <30% was considered successful PCI. Total iodine volume and time lasting from the last coronary injection to the CT scan were measured.
DE-MDCT acquisition and analysis
Scans were performed by the use of a 64-channel MDCT scanner (Brilliance 64, Philips Healthcare, Cleveland, Ohio) without the administration of medication to lower the patient's heart rate. Scan parameters were a collimation of 64 × 0.625 mm, rotation time 0.42 s, tube voltage 120 kV, and tube current of 500 to 600 mAs corresponding to an approximate mean radiation dose of 5.5 mSv. A dose modulation protocol was applied to reduce the radiation dose during systole (17). An ECG was recorded simultaneous to the CT scan to enable retrospective gating of the image data. A dedicated cardiac gating algorithm was used that identified the same physiological phases of the cardiac cycle while taking into account the nonlinear changes in the individual cardiac states with the heart rate variations during the CT acquisition (18). A cardiac adaptive multisegment reconstruction technique was used that combined data from consecutive cardiac cycles, thus significantly improving temporal resolution between 53 and 210 ms (19).
All patients underwent 64-slice CT immediately after primary PCI. In our institution, the CT scanner is next to the catheterization laboratory. All scans were acquired without contrast medium injection within a time frame of 40 min from the last angiogram. In all patients, images were reconstructed at 75% of the cardiac phase by the use of axial planes, multiplanar reconstructions, and maximum intensity projections at 1-mm slice thickness. Short axis (from base to apex), 2-, 3-, and 4-chamber views were obtained initially by the use of 5-mm slice-reformatted images. The presence of iodine-DE was evaluated by 2 experienced observers. The number or segments with DE was assessed by the American Heart Association 17-segment model (20), and the percent of segments involved was determined. The infarct mass was calculated as follows: hyperenhancement mass (g) = ΣHyperenhanced area × slice thickness × 1.06.
All analyses were performed by the use of dedicated software (Comprehensive Cardiac Analysis, Version 3.5, Philips Healthcare, Cleveland, Ohio) on a CT workstation (Extended Brilliance Workspace, Philips Healthcare). The extent of DE was considered transmural if ≥50% of the thickness was involved and subendocardial if <50% was hyperenhanced (Fig. 1). The primary objective of the study was to explore the relationship between established parameters of myocardial reperfusion (ECG ST-segment resolution and TMPG) and the presence and extent of myocardial damage measured by DE-MDCT immediately after primary PCI. The study was approved by our institution′s ethics committee, and all the patients enrolled gave their written informed consent.
Discrete variables are presented as counts and percentages. Continuous variables are presented as mean ± SD or median (25th, 75th percentile) as indicated. Comparisons among groups were performed with independent Student t tests, chi-square tests, the Fisher exact tests, and Mann-Whitney U tests, as indicated. We explored correlations between the peak creatine kinase and the infarcted mass, the percent of the left ventricle (LV) involved, and the number of segments with DE, using Spearman correlation coefficients. A 2-sided p value of <0.05 indicated statistical significance. Statistical analyses were performed with SPSS version 13.0 (SPSS Inc., Chicago, Illinois).
Thirty patients constituted the study population. The mean age was 61.4 ± 15.6 years, 24 (80%) were men, and 4 (13.3%) were diabetic. Eighteen (60%) patients had pre-infarction angina. The culprit lesion was the right coronary artery in 15 (50%) patients, the left circumflex in 5 (16.7%), and the left anterior descending in 10 (33.3%) patients. The baseline TIMI flow grade was 0 in 22 (73%) patients, 1 in 4 (13%) patients, and 2 (13%) in 4 patients. All patients underwent stent placement in the infarct related artery. Final TIMI flow grade 3 with residual stenosis <30% was achieved in all cases. Mean door-to-balloon time (DTB) was 85.2 ± 57.4 min and the mean crossing time was 17.4 ± 10.3 min. Mean contrast volume administration was 219.2 ± 68.7 ml.
The median time elapsed between last contrast injection and CT scan was 16 min (interquartile range 12.5 to 20.25 min), within a time frame of 40 min. The mean heart rate during the scan was 80.3 ± 16.5 beats/min, and the mean scan time was 9.5 ± 1.2 s. Image quality of all scans was deemed sufficient. Delayed enhancement was detected in 14 (47%) patients; in 11 (79%) patients the extension was transmural and in 3 (21%) subendocardial. A total of 510 segments were evaluated, and DE was detected in 61 segments (12.1%).
Age, sex, hypertension, diabetes, smoking history, serum creatinine levels, and pain duration were not associated with the presence of DE (Table 1). Hypercholesterolemia was inversely associated with the presence of DE. The DTB time (DE 70.3 ± 33.6 min vs. non-DE 98.3 ± 70.7 min, p = 0.19) and lesion crossing time (DE 18.6 ± 11.4 min vs. non-DE 16.4 ± 9.6 min, p = 0.58) did not differ between groups.
Comparative data between groups regarding parameters of reperfusion and clinical outcomes are reported in Table 2. The TMPG (0 to 1 vs. 2 to 3) after stent implantation and ST-segment resolution (<50% or ≥50%) was associated with the presence of DE (p = 0.001 and p = 0.02, respectively). Peak creatine kinase levels were significantly greater in patients with DE than in those with viable myocardium (1,531 [interquartile range 442 to 2,177] U/l vs. 461 [interquartile range 253 to 1,114] U/l, p = 0.03).
Pre-infarction angina was not associated with the extension of necrosis (Table 3). Patients with ST-segment resolution <50% and patients with poor flow at the microvascular level had larger extension of markers of necrosis (Table 3, Fig. 2). Regarding the MI territory, anterior wall AMIs had significantly larger markers of necrosis (Table 3). There was a significant positive correlation between the peak creatine kinase and the infarcted mass (r = 0.54, p = 0.002), the percent LV involved (r = 0.56, p = 0.001), and the number of segments with DE (r = 0.57, p < 0.001) (Fig. 3).
Pre-discharge LVEF was lower in DE vs. non-DE patients (44.6 ± 12.4% vs. 54.1 ± 10.3%, p = 0.05). Hospitalization (DE 5.6 ± 3.8 days vs. non-DE 4.8 ± 1.0 days, p = 0.41) did not differ between groups. Patients without DE had no in-hospital complications (Table 2), whereas 6 (43%) of 14 DE patients had complications (p = 0.005).
Clinical outcome and functional recovery
At 6-month follow-up, no patient had died, and there were no significant differences in major cardiac and cerebrovascular events (DE 3 of 14 [21%] vs. non-DE 1 of 16 [6%], p = 0.22). Both at baseline and follow-up, LVEF was significantly greater in patients with viable myocardium (Table 4). At 6-month follow-up, the LVEF increased from 50.5 ± 11.4% to 55.7 ± 13.7% (p = 0.009), representing a relative increment of 14.2% (interquartile range 3.0% to 19.8%). Nevertheless, the absolute and relative differences in LVEF between DE and non-DE patients did not differ significantly.
From the subset of patients with 6-month 99mTc-sestamibi gated SPECT (n = 22), 374 segments (American Heart Association 17-segment model) were evaluated, and 41 segments showed DE (11.0%), whereas 333 segments were viable. Functional recovery was detected in 10 (24%) of 41 DE segments, whereas 329 (99%) of 333 viable segments had normal wall motion at follow-up (p < 0.001).
The main finding of our study was that clinical and angiographic parameters of reperfusion were related to the presence of DE detected by DE-MDCT. Our findings can be summarized as follows: 1) The performance of DE-MDCT immediately after primary PCI was fast and feasible, with a median delay between procedures of 16 min and a mean scan duration of 9.5 s. 2) Despite the fact that recommended DTB time targets were accomplished and although TIMI flow grade 3 was achieved after successful primary PCI, DE was present in 47% of the patients. 3) Both ST-segment resolution and TMPG, parameters that reflect the functional status of the myocardium at risk and the patency of coronary arteries at the microvascular level, respectively, were highly related to the presence of DE. 4) Despite the 6-month outcome, which did not differ between groups, patients with myocardium DE showed larger enzyme release, lower pre-discharge LVEF, and a greater rate of in-hospital morbidity.
The widely available use of primary PCI has significantly improved the clinical outcome of STEMI patients. Nevertheless, prognosis of these patients seems to be related not only to the epicardial flow obtained after revascularization but to the microvascular flow achieved as well (6,7). A number of tools exist that provide insight regarding the restoration of perfusion in an acute setting, namely the ECG ST-segment resolution and the TMPG. These parameters are readily available and provide independent prognostic information after an AMI (4,7,8). However, the ejection fraction, a strong predictor of death after MI (21), depends on the load and might be normal in patients with akinetic areas with hyperkinetic remote myocardium.
The use of DE-MDCT offers clinicians the unique ability to identify the extent, localization, and morphology of irreversibly damaged myocardium immediately after primary PCI. More importantly, it can be achieved in a few seconds, without further contrast administration, and by the use of a low radiation dose. The capability of DE-MDCT to provide an early discrimination between viable (Fig. 4) and nonviable myocardium renders the technique a potential additional tool for risk stratification of reperfused AMI patients. Detection of nonviable myocardium may have an important influence on long-term ventricular geometry and function (22). Furthermore, it might prevent risks related to eventual further revascularization procedures when the potential benefit to be obtained is uncertain.
A previous seminal report has explored the agreement between DE-MDCT performed immediately after angiography in an AMI setting and low-dose dobutamine echocardiography (15). To our knowledge, our study is the first study to explore the relationship between established parameters of reperfusion and the presence of myocardial damage measured by DE-MDCT without further iodine injection immediately after primary PCI.
In line with previous reports demonstrating that clinical outcomes are not only associated with final angiographic flow in the epicardial artery but also with angiographic flow in the myocardium (2–5), in the present study, all patients with impaired flow at the microvascular level (TMPG 0 to 1) showed DE in the infarct-related artery territory, whereas only 27% of patients with normal or near-normal microvascular flow (TMPG 2 to 3) showed DE. In parallel, 86% of patients with poor (<50%) ECG ST-segment resolution showed DE areas, whereas hyperenhancement was seen in only 35% of patients with >50% ECG ST-segment resolution.
Patient demographics were not related to the presence of DE. However, hypercholesterolemia appeared to act as a protective factor, although our data do not support a beneficial effect of statins. Pre-infarction angina, which has been recognized as a protective factor against death and heart failure (23) attributed by different authors to a higher likelihood of presenting multiple vessel disease, preconditioning, and/or extensive collateral development (24,25), was not associated to the presence of DE.
Patients with inferior wall AMI were more likely to have viable myocardium. Of note, 64% of patients with anterior AMI showed DE myocardium, whereas 69% of patients with inferior AMI had viable myocardium. In addition, inferior wall AMIs showed significantly smaller infarct extension. These findings are in line with a seminal report that demonstrated significantly lower peak enzyme levels and lower rates of in-hospital mortality, congestive heart failure, and conduction defects in patients with inferior wall AMI compared with anterior wall AMI (26).
Overall, our findings indicate that in the setting of STEMI, patients with myocardium DE at noncontrast multidetector CT performed immediately after primary PCI are more likely to have failed reperfusion at the microvascular level, whereas viable myocardium identified as the absence of DE was associated to normal microvascular flow and ECG ST-segment resolution. Although 6-month outcome was similar, patients with myocardium DE showed larger enzyme release, worse pre-discharge LVEF, and a greater rate of in-hospital complications compared with patients without DE.
In our institution, the catheterization laboratory is next to the CT room, which allowed a median delay of 16 min between the last contrast injection and the CT scan. We acknowledge that this time frame is unlikely to be achieved in most hospitals; however, myocardium DE can be identified as late as 40 min after contrast injection (12). The present study included a relatively small population. Studies with larger populations and long-term follow-up might address the clinical impact of these findings and whether the early identification of myocardial viability by means of DE-MDCT has an additive prognostic value on top of the established parameters of reperfusion.
It is worth mentioning that the radiation dose in this study might be further reduced using lower kv at the expense of increased image noise (15,27). Finally, the lack of additional contrast administration might have influenced the accurate discrimination between transmural and subendocardial infarcts.
In the setting of STEMI, the absence of myocardium DE at noncontrast multidetector CT performed immediately after primary PCI was associated to normal microvascular flow and ECG ST-segment resolution.
Dr. Rodriguez-Granillo has received a research grant from Philips Healthcare.
- Abbreviations and Acronyms
- acute myocardial infarction
- delayed enhancement
- door-to-balloon time
- left ventricle
- left ventricular ejection fraction
- multidetector computed tomography
- percutaneous coronary intervention
- ST-elevation acute myocardial infarction
- Thrombolysis In Myocardial Infarction
- Thrombolysis In Myocardial Infarction myocardial perfusion grade
- Received December 27, 2008.
- Revision received February 26, 2009.
- Accepted March 9, 2009.
- American College of Cardiology Foundation
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