This study examined the prognostic value of novel diastolic indexes in ST-elevation acute myocardial infarction (AMI), derived from strain and strain rate analysis using 2-dimensional speckle tracking imaging. Echocardiograms were obtained within 48 hours of admission in 371 consecutive patients with first ST-elevation AMI (59.7 ± 11.6 years old). Indexes of diastolic function including mean strain rate during isovolumic relaxation (SR IVR ), mean early diastolic strain rate (SR E ) and mean diastolic strain at peak transmitral E wave (E) were obtained from 3 apical views. Mean early diastolic velocity from 4 basal segments by color-coded tissue Doppler imaging was measured. Indexes of diastolic filling including E/SR IVR , E/SR E , E/diastolic strain at E, and E/early diastolic velocity were calculated. The primary end point (composite of death, hospitalization for heart failure, repeat MI, and repeat revascularization) occurred in 84 patients (22.6%) during a mean follow-up of 17.3 ± 12.2 months. Mean SR IVR (p <0.001), multivessel disease (p <0.001), Thrombolysis In Myocardial Infarction grade 0 to 1 flow after percutaneous coronary intervention (p = 0.004), and left ventricular ejection fraction (p = 0.008) were independent predictors of the combined end point on Cox regression analysis. Mean SR IVR showed incremental prognostic value over baseline clinical and echocardiographic variables (global chi-square increase from 41.0 to 51.6, p <0.001). After dividing patient population based on median SR IVR , patients with SR IVR ≤0.24/second had significantly higher event rates than others (hazard ratio 2.74, 95% confidence interval 1.61 to 4.67, p <0.001). In conclusion, SR IVR was incremental to left ventricular ejection fraction, Thrombolysis In Myocardial Infarction grade 0 to 1 flow after percutaneous coronary intervention, and multivessel disease and superior to other diastolic indexes in predicting future cardiovascular events after AMI. SR IVR may be useful in identifying high-risk patients soon after AMI.
Several predictors of clinical outcome after acute myocardial infarction (AMI) have been described, including left ventricular (LV) systolic function and volume, infarct size and location, presence of mitral regurgitation, and ventricular arrhythmias. Predictive value of diastolic function, which often precedes the onset of systolic dysfunction in acute ischemia, has been variable. Currently used measurements of diastolic function obtained by conventional Doppler echocardiography are dependent on LV loading conditions that are subject to changes during the peri-infarction period. This may in part explain their variable predictive value when obtained instantaneously during the acute stages of AMI. Recently, new load-independent indexes of LV diastolic function derived by 2-dimensional strain and strain rate (SR) imaging techniques were introduced. In the present study, the long-term prognostic value of these novel diastolic indexes measured during ST-elevation AMI was evaluated.
Methods
Consecutive patients (n = 371) who presented with a first episode of ST-elevation AMI and underwent primary percutaneous coronary intervention were included. All patients underwent clinically indicated transthoracic echocardiography within 48 hours from admission for assessment of baseline LV filling patterns, volumes, and systolic function. Baseline clinical characteristics were obtained from the computerized hospital database.
Patients were followed using telephone interviews and reviews of computerized medical records. The primary end point was a composite of death from any cause, heart failure rehospitalization, repeat MI, and repeat revascularization. Repeat revascularization procedure of a lesion showing ≥50% stenosis, performed at any point after the primary revascularization, was driven by clinical symptoms at rest in conjunction with electrocardiographic evidence of ischemia or a positive stress test result.
Transthoracic echocardiography was performed with the subjects at rest in the left lateral decubitus position with a commercially available ultrasound transducer and equipment (M3S probe, Vivid 7, GE-Vingmed, Horten, Norway). All images were digitally stored for off-line analysis (EchoPac BT07.0.0, GE-Vingmed).
Complete 2-dimensional, color, pulse-wave, and continuous-wave Doppler images were acquired according to standard techniques. LV end-systolic volume index and end-diastolic volume index were calculated using the Simpson biplane method of disks and indexed to body surface area. LV ejection fraction was subsequently derived and expressed as a percentage. Global wall motion score index was calculated using a standard formula according to the American Heart Association and American Society of Echocardiography. Briefly, the left ventricle was divided into 16 segments and a semiquantitative scoring system (1 = normal, 2 = hypokinesia, 3 = akinesia, 4 = dyskinesia) was used to analyze each segment. Maximal left atrial volumes were calculated using the ellipsoid model as recommended by the American Society of Echocardiography and indexed to body surface area.
Spectral Doppler velocities were measured from the apical 4-chamber view using a 2-mm sample volume. Transmitral early (E wave) and late (A wave) diastolic velocities, and E-wave deceleration time were measured at mitral leaflet tips.
Mitral regurgitation severity was determined semiquantitatively from color Doppler images obtained from conventional parasternal long-axis and apical views using the regurgitant jet area to left atrial area ratio as previously published.
Color-coded tissue Doppler images of the left ventricle obtained in apical 2- and 4-chamber views were acquired at highest frame rates possible (>100 frames/s) during end-expiration and stored for off-line analysis. Peak early diastolic myocardial velocities (Em) were measured in 4 basal LV segments (septal, lateral, inferior, and anterior) with tissue Doppler imaging (TDI) and averaged to calculate the mean early diastolic myocardial velocities (TDI Em ). Two-dimensional images of the LV apical 4-, 2-, and 3-chamber views were obtained using the highest possible frame rates. During 2-dimensional speckle-tracking analysis, the endocardial border was manually traced and region-of-interest width adjusted to include the entire myocardium. The software package then automatically tracked and accepted segments of good tracking quality and rejected poorly tracked segments and allowed an observer to manually override its decisions based on visual assessments of tracking quality. Individual global longitudinal strain and SR curves were obtained automatically from the 3 apical views. Peak global SR during the isovolumic relaxation period and during early diastole were measured and averaged from the 3 apical views. Time from R wave of the QRS complex to peak transmitral E wave was used to identify early diastolic strain.
In summary, the following indexes of LV diastolic function were obtained from the color-coded TDI and 2-dimensional speckle tracking: (1) mean TDI Em , (2) early diastolic strain (DS E ), (3) early diastolic SR (SR E ), and (4) SR during the isovolumic relaxation period (SR IVR ). Similarly, the following indexes of LV filling pressures were manually calculated: (1) ratio of peak transmitral E wave to mean Em (E/TDI Em ), (2) ratio of peak transmitral E wave to early diastolic strain (E/DS E ), (3) ratio of peak transmitral E wave to early diastolic strain rate (E/SR E ), and (4) ratio of peak transmitral E wave to strain rate during the isovolumic relaxation period (E/SR IVR ).
All echocardiographic measurements were performed by 2 experienced observers from the same center and blinded to all clinical data. To determine intra- and interobserver variabilities, all color-coded TDI and 2-dimensional speckle-tracking measurements were repeated in 30 randomly selected subjects ≥4 weeks apart by the same observer on the same echocardiographic images and by a second independent observer.
Continuous variables are presented as mean ±SD unless otherwise stated. Categorical data are summarized as frequencies and percentages. Chi-square test with Yates correction was used to compare categorical variables. Student’s t test and Mann-Whitney U test were used to compare 2 groups of unpaired data of Gaussian and non-Gaussian distribution, respectively. Pearson correlation was employed to examine the linear association between continuous variables. Kaplan-Meier survival curves were compared by log-rank test. For identification of independent predictors for the combined primary end point, a multivariate Cox regression analysis was used with significant univariate predictors entered as covariates using the stepwise-enter method. To avoid colinearity between univariate predictors, a correlation coefficient cutoff <0.70 was set. A 2-tailed p value <0.05 was considered statistically significant. The incremental value of novel diastolic indexes over baseline clinical and echocardiographic variables was assessed by calculating the global chi-square test. Intraobserver and interobserver agreements for color-coded TDI and 2-dimensional speckle-tracking measurements were evaluated by calculating intraclass correlation coefficients, with good correlation being defined as an intraclass correlation coefficient >0.8. All statistical analyses were performed using SPSS 16 for Windows (SPSS, Inc., Chicago, Illinois).
Results
The study cohort consisted of 288 men (77.6%) and 83 women (22.4%) with a mean age of 59.7 ± 11.6 years. Mean duration of follow-up was 17.3 ± 12.2 months. No patients were lost to follow-up. The combined clinical end point occurred in 84 patients (22.6%), including 26 deaths (7%), 5 (1.3%) cases of recurrent MI, 48 (12.9%) cases of repeated revascularization, and 5 (1.3%) admissions for heart failure.
Table 1 presents baseline clinical characteristics of all patients and of those patients with and without clinical events. Multivessel coronary artery disease was noted in 44.8% of all patients and reperfusion by percutaneous coronary intervention was achieved in 99.5%. Patients with clinical events were more likely to be older (p = 0.040), have a larger number of stenosed coronary arteries (p <0.001), and lower Thrombolysis In Myocardial Infarction flow grade after primary percutaneous coronary intervention (p = 0.033).
| Variable | Total Population (n = 371) | Combined End Point | p Value | |
|---|---|---|---|---|
| Yes (n = 84) | No (n = 287) | |||
| Age (years) | 59.7 ± 11.6 | 62.0 ± 12.1 | 59.0 ± 11.4 | 0.040 |
| Men/women | 288/83 | 68/16 | 220/67 | 0.406 |
| Diabetes mellitus | 26 (7%) | 7 (8.3%) | 19 (6.6%) | 0.589 |
| Hypertension | 108 (30%) | 30 (36%) | 80 (28%) | 0.166 |
| Hypercholesterolemia (total cholesterol >5.0 mmol/L) | 73 (20%) | 19 (22%) | 56 (20%) | 0.894 |
| Smoker | 194 (52%) | 47 (56%) | 147 (51%) | 0.445 |
| Family history of premature coronary artery disease (male first-degree relative <55 years old, female first-degree relative <65 years old) | 150 (40%) | 29 (35%) | 121 (42%) | 0.210 |
| Anterior wall acute myocardial infarction | 178 (48%) | 39 (46%) | 140 (49%) | 0.704 |
| Peak troponin T level (μg/L) | 7.1 ± 6.2 | 8.4 ± 8.6 | 6.7 ± 5.2 | 0.306 |
| Number of narrowed coronary arteries | <0.001 | |||
| 1 | 205 (55%) | 27 (32%) | 179 (62%) | |
| 2 | 116 (31%) | 30 (36%) | 85 (30%) | |
| 3 | 50 (14%) | 27 (33%) | 23 (8.0%) | |
| Thrombolysis In Myocardial Infarction grade flow after percutaneous coronary intervention | 0.033 | |||
| 3 | 345 (94%) | 75 (89%) | 273 (95%) | |
| 2 | 18 (4.9%) | 6 (7.3%) | 12 (4.2%) | |
| 1 | 3 (0.8%) | 1 (1.2%) | 2 (0.7%) | |
| 0 | 2 (0.5%) | 2 (2.4%) | 0 (0.0%) | |
| Treatment | ||||
| β blockers | 34 (92%) | 79 (94%) | 262 (91%) | 0.395 |
| Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers | 366 (99%) | 84 (100%) | 282 (98%) | 0.263 |
| Statins | 367 (99%) | 84 (100%) | 283 (99%) | 0.317 |
| Antiplatelet agents | 372 (100%) | 84 (100%) | 287 (100%) | |
Echocardiograms were obtained in all patients within 48 hours from their index admission. Table 2 lists baseline echocardiographic parameters. Mean 2-dimensional speckle tracking and color-coded TDI frame rates were 73.8 ± 15.4 and 159.0 ± 17.8 frames/s, respectively. The overall feasibilities for SR IVR , DS E , SR E , and mean TDI Em measurements were 83.3%, 98.7%, 99.2% and 93.3%, respectively. Of diastolic function indexes, patients with clinical events had significantly lower mean TDI Em (p = 0.003) and SR IVR (p <0.001). Similarly, of the LV filling pressure indexes, patients with clinical events had significantly higher E/TDI Em (p = 0.003) and E/SR IVR (p <0.001). There were no significant differences in SR E , E/SR E , DS E , and E/DS E between patients with and without clinical events.
| Variable | Total Population (n = 371) | Combined End Point | p Value | |
|---|---|---|---|---|
| Yes (n = 84) | No (n = 287) | |||
| 2-dimensional echocardiography | ||||
| Left ventricular ejection fraction (%) | 45.2 ± 8.0 | 42.4 ± 9.6 | 46.0 ± 7.3 | 0.002 |
| Left ventricular end-systolic volume index (ml/m 2 ) | 29.0 ± 10.2 | 31.8 ± 12.4 | 28.2 ± 9.4 | 0.045 |
| Left ventricular end-diastolic volume index (ml/m 2 ) | 52.7 ± 15.3 | 58.4 ± 20.5 | 52.2 ± 14.7 | 0.094 |
| Left atrial volume index (ml/m 2 ) | 16.8 ± 6.1 | 16.7 ± 5.9 | 16.8 ± 6.2 | 0.927 |
| Wall motion score index | 1.49 ± 0.26 | 1.51 ± 0.29 | 1.48 ± 0.26 | 0.531 |
| Color Doppler data | ||||
| Mitral regurgitation grade ≥2 | 28 (7.5%) | 11 (13.1%) | 17 (5.9%) | 0.029 |
| Left ventricular filling | ||||
| Mitral early/late diastolic velocities | 0.96 ± 0.34 | 1.07 ± 0.38 | 0.95 ± 0.33 | 0.773 |
| Deceleration time (ms) | 208.1 ± 72.6 | 190.0 ± 64.5 | 209.8 ± 73.2 | 0.147 |
| Peak transmitral E wave/mean early diastolic myocardial velocity | 12.5 ± 5.30 | 14.4 ± 6.9 | 12.0 ± 4.6 | 0.003 |
| Peak transmitral E wave/mean strain rate during isovolumic relaxation period | 410.4 ± 505.8 | 481.4 ± 458.8 | 391.2 ± 517.1 | <0.001 |
| Peak transmitral E wave/mean early diastolic strain rate | 91.0 ± 35.6 | 97.1 ± 43.2 | 89.3 ± 33.0 | 0.132 |
| Peak transmitral E wave/mean early diastolic strain | 8.51 ± 4.96 | 9.1 ± 4.9 | 8.3 ± 4.9 | 0.146 |
| Diastolic function | ||||
| Mean early diastolic myocardial velocity (cm/s) | 5.83 ± 2.04 | 5.21 ± 1.96 | 6.00 ± 2.04 | 0.003 |
| Mean strain rate during isovolumic relaxation period (s −1 ) | 0.29 ± 0.19 | 0.21 ± 0.12 | 0.31 ± 0.21 | <0.001 |
| Mean early diastolic strain rate (s −1 ) | 0.80 ± 0.34 | 0.77 ± 0.30 | 0.81 ± 0.35 | 0.303 |
| Mean early diastolic strain (%) | 8.68 ± 2.66 | 8.27 ± 2.70 | 8.80 ± 2.65 | 0.112 |
Table 3 lists significant univariate predictors for the combined clinical end point. On multivariate analysis, only multivessel disease (p <0.001), LV ejection fraction (p = 0.008), Thrombolysis In Myocardial Infarction grade 0 to 1 flow after primary percutaneous coronary intervention (p = 0.004), and mean SR IVR (p <0.001) were independent predictors of clinical events after AMI. In addition, mean SR IVR added incremental value to the prognostic stratification achieved with a model consisting of baseline clinical and echocardiographic data, including age, number of the stenosed vessels, Thrombolysis In Myocardial Infarction flow, mitral regurgitation, LV ejection fraction, end-systolic volume index, E/TDI Em , and E/SR IVR (global chi-square increase from 41.0 to 51.6, p <0.001; Figure 1 ).
| Variable | Univariate Analysis | Multivariate Analysis | ||
|---|---|---|---|---|
| HR (95% CI) | p Value | HR (95% CI) | p Value | |
| Age | 1.02 (1.00–1.04) | 0.028 | ||
| Multivessel disease ⁎ | 3.0 (1.89–4.77) | <0.001 | 3.46 (2.00–5.99) | <0.001 |
| Thrombolysis In Myocardial Infarction grade 0–1 flow after percutaneous coronary intervention † | 1.84 (0.85–4.00) | 0.004 | 5.86 (1.75–19.60) | 0.004 |
| Left ventricular ejection fraction | 0.95 (0.92–0.97) | <0.001 | 0.96 (0.93–0.99) | 0.008 |
| Left ventricular end-systolic volume index | 1.03 (1.01–1.05) | 0.013 | ||
| Mitral regurgitation grade ≥2 | 2.38 (1.26–4.49) | 0.008 | ||
| Peak transmitral E wave/mean early diastolic myocardial velocity | 1.07 (1.03–1.11) | <0.001 | ||
| Mean early diastolic myocardial velocity | 0.84 (0.74–0.95) | 0.005 | ||
| Mean strain rate during isovolumic relaxation period | 0.04 (0.01–0.22) | <0.001 | 0.04 (0.01–0.21) | <0.001 |
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