Author + information
- Received April 27, 2005
- Revision received June 11, 2005
- Accepted July 6, 2005
- Published online November 1, 2005.
- Vicente Bodí, MD, FESC⁎,⁎ (, )
- Juan Sanchis, MD, FESC⁎,
- María P. López-Lereu, MD†,
- Antonio Losada, MD⁎,
- Julio Núñez, MD⁎,
- Mauricio Pellicer, MD⁎,
- Vicente Bertomeu, MD⁎,
- Francisco J. Chorro, MD, FESC⁎ and
- Àngel Llácer, MD, FESC⁎
- ↵⁎Reprint requests and correspondence:
Dr. Vicente Bodí, Cardiology Department, Hospital Clínico y Universitario de Valencia, Blasco Ibáñez 17, 46010, Valencia, Spain.
Objectives We sought to evaluate the usefulness of a comprehensive assessment of four cardiovascular magnetic resonance imaging (CMR)-derived myocardial viability indexes in the setting of myocardial stunning.
Background Cardiovascular magnetic resonance imaging allows the simultaneous assessment of several viability indexes.
Methods We studied 40 patients with a first ST-segment elevation myocardial infarction (MI) and an open infarct-related artery. At the first week, using CMR, wall motion (WM), and four viability indexes were determined: wall thickness, WM improvement with low-dose dobutamine, perfusion, and transmural extent of necrosis. We created a comprehensive score based on the presence and the relative power of these viability indexes for predicting normal WM at the sixth month.
Results Of 153 dysfunctional segments at the first week, 59 (39%) exhibited normal WM at the sixth month. According to the odds ratio of viability indexes for predicting normal WM, we developed a five-level predictive score. The proportions of segments showing normal WM at sixth month were as follows; Level 1 (0 indexes): 0 of 13 (0%); Level 2 (normal thickness and/or perfusion): 14 of 82 (17%); Level 3 (dobutamine response): 5 of 11 (45%); Level 4 (non-transmural necrosis): 20 of 26 (77%); Level 5 (non-transmural necrosis and dobutamine response): 20 of 21 (95%), p < 0.0001 for the trend. These proportions were similar in a matched prospective validation group comprising 16 patients (0%, 18%, 62%, 77%, and 90% for levels 1 to 5, respectively, p < 0.0001 for the trend).
Conclusions A comprehensive analysis of the four more widely used CMR-derived viability indexes is useful for predicting late systolic function after myocardial infarction.
The analysis of residual myocardial viability in the infarcted area is of paramount importance when defining the outcome and management of patients after myocardial infarction (MI) (1,2). It has been demonstrated that, separately, wall thickness, contractile reserve, perfusion, and transmural extent of necrosis are useful tools for predicting late systolic recovery (3–8). However, the relative value of these indexes is different, and an integrated analysis might allow a more accurate prediction. This type of comprehensive assessment has proved its utility in other clinical scenarios (9–11).
Cardiovascular magnetic resonance (CMR) imaging permits, in a single session, a simultaneous state-of-the-art analysis of these parameters (6,7,12). Focusing on a single variable may dismiss relevant information easily obtainable by a complete evaluation of the CMR study. We aimed to evaluate the usefulness of a comprehensive assessment of these four widely used viability indexes for predicting late systolic function after MI in the setting of myocardial stunning.
This study is a part of an ongoing protocol investigating several aspects of viability, perfusion, and remodeling after MI (3,6,13). We created a comprehensive score for predicting late systolic function by analyzing the results derived from the study group, which comprised the first 40 patients included in the study protocol. Afterwards, this score was tested in a matched prospective validation group, which comprised the next 16 patients included in this series. All 56 patients accomplished the inclusion criteria exposed in this report. The ethics committee of our institution approved the research protocol. Informed consent was obtained from all subjects.
We prospectively included 60 consecutive patients with a first ST-segment elevation MI treated with thrombolytic therapy within the first 6 h after the onset of chest pain. The inclusion criteria were: 1) stable clinical course without complications during the first six months; 2) single-vessel disease and a patent (Thrombolysis In Myocardial Infarction [TIMI] flow grade 3 and residual stenosis <50%) in the infarct-related artery (IRA) at the end of pre-discharge cardiac catheterization and at the sixth month; and 3) no contraindications to CMR. We excluded 20 patients because of multivessel disease (10 cases), TIMI flow grade <3 (2 cases), restenosis (5 cases), claustrophobia (2 cases), and re-infarction (1 case). Therefore, the final study group comprised 40 patients.
Cardiac catheterization was performed 4 ± 1 days after MI. A stent was placed in 33 patients (82%) in whom luminal narrowing in the IRA was >50%. At the end of the pre-discharge study, all patients showed TIMI flow grade 3 and residual stenosis <50%. Angiographic data were evaluated in a core laboratory (ICICOR, Valladolid, Spain). Cardiac catheterization was repeated 179 ± 8 days after MI, and TIMI flow grade 3 and residual stenosis <50% was confirmed in all cases.
We performed CMR (Sonata Magnetom, Siemens, Erlangen, Germany) at 7 ± 1 days (at least 48 h after cardiac catheterization) and 184 ± 11 days after MI according to our laboratory protocol (6). All images were acquired by a phased-array body surface coil during breath-holds and were electrocardiogram-triggered. Cine images (true fast imaging with steady-state precession [TrueFISP], repetition time/echo time: 3.2/1.6 ms; flip angle: 61°; matrix: 256 × 128; slice thickness: 6 mm; temporal resolution: 26 ms) were acquired in two-, three-, and four-chamber views and every 1 cm in short-axis views at rest and during intravenous infusion of low-dose (10 μg/kg/min) dobutamine.
After cine images, a minimum of three short-axis views (basal, midventricular, apical) and two long-axis views were performed for first-pass perfusion imaging (TrueFISP, inversion time: 110 ms, repetition time/echo time: 190/1 ms; flip angle: 49°; matrix: 128 × 72) after administering 0.1 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid (Magnograf, Juste S.A.Q.F., Madrid, Spain) at a flow rate of 3 ml/s, and acquiring images every other beat in all slices during a period of 90 to 120 s.
Late enhancement imaging was performed 10 min after contrast injection using a segmented inversion recovery TrueFISP sequence (repetition time/echo time: 2.5/1.1 ms; slice thickness: 6 mm; flip angle: 50°; matrix: 195 × 192) and nullifying myocardial signal.
Analysis of CMR data
An experienced observer who was blinded to all patient data analyzed CMR studies by using customized software (Syngo, Siemens, Erlangen, Germany). Segment location was defined in cine-image sequences applying the 16-segment model (14). The same projections used in cine images were recalled for analyzing perfusion (in first-pass perfusion imaging) and the transmural extent of necrosis (in late enhancement imaging). Wall motion (WM), abnormal if wall thickening at rest (end-systolic thickness − end-diastolic thickness) was ≤2 mm (6,7,15), was quantified in cine images.
Four viability indexes were evaluated: 1) end-diastolic thickness (abnormal if ≤5.5 mm) (6,15), and 2) WM during low-dose dobutamine (abnormal if ≤2 mm) (6,7) were quantified in cine images. 3) Abnormal perfusion was defined qualitatively as regions showing hypoenhancement (compared with non-infarcted segments at the same slice) at the end of the 90- to 120-s acquisition period in first-pass perfusion imaging (6,12,16,17). Perfusion defects were confirmed both in short- and long-axis views to avoid artifacts. Finally, 4) transmural extent of necrosis was defined as ≥ 50% in late enhancement imaging (6,7,12,18). In the CMR study performed at the sixth month, WM was re-evaluated. Normal systolic function at the sixth month was considered in the case of WM >2 mm.
In a group of 15 patients (240 segments) not included in this study, we calculated intraobserver agreement with regard to the presence or not of the cut-off values applied. Intraobserver agreement on perfusion results was 94% (kappa = 0.86) versus 96% (kappa = 0.88) on late enhancement imaging and systolic function results (WM and wall thickness).
Continuous data were expressed as the mean ± standard deviation. Comparisons between groups were made using chi-square tests for discrete data. We analyzed separately the usefulness of the four viability indexes evaluated at the first week (1: wall thickness >5.5 mm; 2: WM during low-dose dobutamine >2 mm; 3: normal perfusion; 4: transmural extent of necrosis <50%) for predicting normal WM at the sixth month. We calculated sensitivity, specificity, and positive and negative predictive values of the four viability indexes evaluated.
A logistic regression model was applied including the four viability indexes to investigate the relative power of each variable for predicting late systolic function. According to the odds ratio magnitude, we constructed a five-level score. The percentage of segments with normal WM at the sixth month depending on the score level was determined. We used the chi-square test for trend for comparing percentages.
The utility of this score was tested in a matched prospective validation group that comprised the next 16 patients included in the ongoing study protocol (all of whom accomplished the inclusion criteria of the initial study group). Statistical significance was considered for p < 0.05. The SPSS statistical package (version 11.0, SPSS Inc., Chicago, Illinois) was used.
The baseline characteristics of the 40 patients included in the study group are shown in Table 1.According to the 16-segment model (14), the location of segments with transmural extent of necrosis in the entire segment group (126 of 640, 20%) was as follows: 66 (53%) in the anterior area, 13 (10%) in the lateral area, and 47 in the inferior area (37%). Of 126 segments with transmural extent of necrosis, 102 (81%) were dysfunctional at rest, whereas only 56 of 514 segments without transmural extent of necrosis (11%) were dysfunctional at rest (p < 0.0001).
Out of 640 segments evaluated, 158 (25%) were dysfunctional at the first week. Five segments were excluded because of unsatisfactory image quality in any of the variables evaluated. Therefore, we focused all our analyses on 153 dysfunctional segments: 83 (54%) in the anterior area, 9 (6%) in the lateral area, and 61 (40%) in the inferior area. Mean end-diastolic thickness in these segments was 8.5 ± 2.8 mm (range, 2.4 to 16.6 mm) and mean end-systolic thickness was 9.1 ± 2.9 mm (range, 2.4 to 16.9 mm). Of these 153 dysfunctional segments, 59 (39%) showed preserved WM at the sixth month.
Viability indexes and late systolic function
Of 153 dysfunctional segments at the first week, wall thickness >5.5 mm was present in 130 (85%), wall thickening during low-dose dobutamine >2 mm in 32 (21%), normal perfusion in 78 (51%), and transmural extent of necrosis <50% in 47 segments (31%). Segments with wall thickness >5.5 mm showed more frequently normal WM at the sixth month (56 of 130, 43%) than those with wall thickness ≤5.5 mm (3 of 23, 13%, p = 0.006).
Wall thickening during low-dose dobutamine >2 mm at the first week related to a higher proportion of segments with normal WM at the sixth month (25 of 32, 78% vs. 34 of 121, 28% in the case of absence of contractile reserve, p < 0.0001). Preserved perfusion at the first week related to more probable normal WM at the sixth month (47 of 78, 60% vs. 12 of 75, 16% in the case of abnormal perfusion, p < 0.0001). Segments with transmural extent of necrosis <50% more frequently showed normal WM at the sixth month (40 of 47, 85%) than those with transmural extent of necrosis ≥50% (19 of 106, 18%, p < 0.0001).
Sensitivity, specificity, and positive and negative predictive values of these four viability indexes for predicting normal WM at the sixth month are displayed in Table 2.A combined analysis of dobutamine response and transmural extent of necrosis was performed (Table 3).Depending on the transmural extent of necrosis, segments were categorized in three groups: 0% to 25% (n = 37 segments), 26% to 75% (n = 42 segments), and 76% to 100% (n = 74 segments). The percentages of segments with normal wall thickening at the sixth month in these three groups were 92%, 38%, and 12%, respectively (p < 0.0001 for the trend). Sensitivity, specificity, and positive and negative predictive values of response to dobutamine for predicting normal WM at the sixth month in these three groups are displayed in Table 3.
Comprehensive assessment of viability indexes
A multivariate analysis for predicting normal WM at the sixth month was performed, including all viability indexes as independent variables. According to the odds ratio obtained (wall thickness = 2.3, 95% confidence interval [CI] 0.5 to 9.4, p = 0.2; perfusion = 2.6, 95% CI 1.01 to 6.9, p = 0.05; response to dobutamine = 4.4, 95% CI 1.4 to 13.5, p = 0.009; non-transmural necrosis = 13, 95% CI 4.6 to 36.7, p < 0.0001) we created a five-level comprehensive score depending on the indexes present (indexes with low value: wall thickness and perfusion; intermediate value: response to dobutamine; and high value: non-transmural necrosis).
The percentage of dysfunctional segments with normal WM at the sixth month increased gradually: level 1 (no index present): 0 of 13 (0%); level 2 (wall thickness and/or perfusion normal; response to dobutamine absent and non-transmural necrosis absent): 14 of 82 (17%); level 3 (response to dobutamine present; wall thickness and/or perfusion normal or not; non-transmural necrosis absent): 5 of 11 (45%); level 4 (non-transmural necrosis present; wall thickness and/or perfusion normal or not; response to dobutamine absent): 20 of 26 (77%); and level 5 (response to dobutamine present and non-transmural necrosis present; wall thickness and/or perfusion normal or not): 20 of 21 (95%), p < 0.0001 for the trend (Fig. 1).
No significant difference in baseline characteristics was observed between the study group and the validation group (Table 1). Of 256 segments, 73 were dysfunctional at the first week (28%). Of these, 31 (42%) showed preserved WM at the sixth month. The percentage of segments with normal WM at the sixth month increased gradually: Level 1: 0 of 4 (0%); Level 2: 7 of 38 (18%); Level 3: 5 of 8 (62%); Level 4: 10 of 13 (77%); and Level 5: 9 of 10 (90%), p < 0.0001 for the trend. When the score was included in the multivariate analysis along with the four viability indexes, the only independent variable selected for predicting normal WM at the sixth month was the score: odds ratio = 3.9, 95% CI 2.1 to 7 for each additional level (p < 0.0001).
The use of CMR allows the simultaneous assessment of wall thickness, response to dobutamine, perfusion, and transmural extent of necrosis. The main finding of this work is that a comprehensive and integrated analysis of these indexes early after MI is helpful for predicting late systolic function.
Viability indexes and late systolic function
Within the last decade, it has been clearly established that systolic dysfunction is not always a definitive status after MI (1–8); in the presence of residual viable myocardium and an adequate myocardial perfusion, contractility may normalize—this process being related to a remarkable prognostic benefit (1,2).
Great efforts have been carried out to detect the presence of residual viability in the infarcted area. Using different techniques, researchers have observed that preserved wall thickness (19), improvement with dobutamine (20,21), normal perfusion (3–5), and non-transmural necrosis (6,7) relate (when analyzed individually) to a higher probability of systolic recovery. The use of CMR has emerged as a reliable tool for evaluating post-infarction patients (12). Moreover, it allows, in the same session, a simultaneous assessment of those indexes mentioned previously without the limitations imposed by radiation or the echocardiographic window (Fig. 2).
To avoid confusing factors (previous MI, multivessel disease, or residual lesion in the IRA, which could alter the interpretation of viability indexes) and to assure an adequate epicardial perfusion (which permitted myocardial recovery in the case of residual viability), we included a homogeneous study group composed of patients with a first MI, single-vessel disease, and TIMI flow grade 3 both at the first week and at the sixth month after MI.
Using CMR, we confirmed that all four indexes analyzed were useful for predicting systolic recovery of dysfunctional segments. Several issues should be pointed out. First, the sensitivity and specificity of these variables for identifying recovery of WM was different (Table 2). In addition, the odds ratio and 95% CIs displayed different predictive values. Second, wall thickness was a sensitive but not specific index. This lack of specificity was probably due to the high prevalence of segments with a thickness greater than the pre-established and widely used (6,15) cut-off value (5.5 mm).
Third, the response to dobutamine was highly specific but not sensitive for predicting late systolic recovery (sensitivity <50% for all transmural extent of necrosis levels). This low sensitivity was probably due to the small number of responders segments soon after MI (Table 3). Similar to previous studies (21,22) that analyzed patients with chronic ischemic disease before revascularization (hibernation), response to dobutamine was very low (5%) in cases with transmural extent of necrosis >75%. However, in segments with transmural extent of necrosis between 0% and 75%, we detected contractile reserve less frequently than these studies (21,22). A stunning phenomenon in early phases may explain this observation; in fact, in our group we have reported that the percentage of segments with contractile reserve increased from 21% at the first week to as much as 40% at the sixth month after MI (13).
Fourth, normal perfusion retained higher sensitivity but less specificity than dobutamine and transmural extent of necrosis. The coexistence of preserved microvasculature in necrotic areas (especially in patients like ours, all of them having TIMI flow grade 3) and the presence of segments with a transitory microvascular dysfunction early after MI (3–6,16) could lower the specificity of this variable. Finally, as recently suggested, transmural extent of necrosis appeared as a reliable variable for predicting late systolic function (6,7,12). The simplicity and strength of this index are spreading its use in daily practice.
As commented on previously, each CMR-derived viability index exhibited some peculiarities for predicting systolic recovery. Therefore, focusing on a single parameter may dismiss relevant information that could be easily available with a complete evaluation of the data contained in the CMR study. An integrated analysis seems recommendable for a best understanding of the possibilities of systolic recovery. This type of comprehensive assessment has been shown to be useful in works investigating other topics and using CMR (9–11).
Applying a comprehensive score based on the power of each variable in the multivariate analysis, we observed a gradual increase in the rate of segments showing preserved late systolic function. In the case of transmural necrosis the rate was 0% when all other indexes were negative, 17% when only low-powered indexes were positive (wall thickness and/or perfusion), and 45% when response to dobutamine was detected. In the case of non-transmural necrosis, the rate was 77% in absence and 95% in presence of response to dobutamine. The validation of these data in a matched prospective group strengthens the robustness of the score. Although quantification of transmural extent of necrosis may be enough for daily practice viability studies, our results suggest that a complete assessment is helpful to achieve a more accurate and “comprehensive” prediction.
The results obtained can only be generalized to patients with characteristics similar to our own. Further studies including a larger number of patients are necessary to confirm our results on a patients basis and to evaluate the clinical implications of these findings.
Cardiovascular magnetic resonance allows a complete analysis of myocardial viability by means of a simultaneous study of wall thickness, response to dobutamine, perfusion and transmural extent of necrosis. Our work clarifies the relative merits of each variable early after MI: the predictive value is low in the case of wall thickness and perfusion, intermediate in the case of response to dobutamine and high in the case of transmural extent of necrosis. A comprehensive assessment of all four indexes is helpful and provides a better understanding for predicting late systolic recovery rather than a separate analysis of each parameter.
Supported by the Spanish Ministry of Health (RECAVA-FIS and PI030013 grants).
- Abbreviations and Acronyms
- cardiovascular magnetic resonance imaging
- infarct-related artery
- myocardial infarction
- Thrombolysis In Myocardial Infarction
- true fast imaging with steady state precession
- wall motion
- Received April 27, 2005.
- Revision received June 11, 2005.
- Accepted July 6, 2005.
- American College of Cardiology Foundation
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