Global longitudinal strain (GLS) measured by 2-dimensional longitudinal speckle-tracking echocardiography may be a more sensitive measure of left ventricular (LV) mechanics than conventional LV ejection fraction (EF) to characterize adverse post–ST-segment elevation myocardial infarction (STEMI) remodeling. The aim of the present evaluation was to compare changes in LV GLS in patients with versus without diabetes after the first STEMI. Patients with first STEMI and diabetes (n = 143; age 64 ± 12 years; 68% men; 50% left anterior descending artery as culprit vessel) and 290 patients with first STEMI and without diabetes matched on age, gender, and infarct location were included. LV volumes and function and 2-dimensional LV GLS were measured after primary percutaneous coronary intervention (baseline) and at 6-month follow-up. At baseline, patients with and without diabetes had similar LVEF (46.8 ± 0.7% vs 48.0 ± 0.5%, p = 0.19) and infarct size (peak cardiac troponin T: 3.1 [1.2 to 6.5] vs 3.7 [1.3 to 7.3] μg/l, p = 0.10; peak creatine phosphokinase:1,120 [537 to 2,371] vs 1,291 [586 to 2,613] U/l, p = 0.17), whereas LV GLS was significantly more impaired in diabetic patients (−13.7 ± 0.3% vs −15.3 ± 0.2%, p <0.001). Although diabetic patients showed an improvement in LVEF over time similar to nondiabetic patients (52.0 ± 0.8% vs 53.1 ± 0.6%, p = 0.25), GLS remained more impaired at 6-month follow-up compared with nondiabetic patients (−15.8 ± 0.3% vs −17.3 ± 0.2%, p <0.001). After adjusting for clinical and echocardiographic characteristics, diabetes was independently associated with changes in GLS from baseline to 6-month follow-up (β 1.41, 95% confidence interval 0.85 to 1.96, p <0.001). In conclusion, after STEMI, diabetic patients show more impaired LV GLS at both baseline and follow-up compared with a matched group of patients without diabetes, despite having similar infarct size and LVEF at baseline and follow-up.
After ST-segment elevation myocardial infarction (STEMI), patients with diabetes mellitus have shown similar changes in left ventricular (LV) volumes and ejection fraction (EF) compared with patients without diabetes. However, the long-term prognosis of diabetics remains poor with an increased rate of heart failure and all-cause mortality. Despite showing a similar degree of LV remodeling after STEMI, one of the mechanisms that may explain why diabetic patients have a worse outcome compared with nondiabetic subjects may be related to the presence of more impaired LV mechanics, which are associated with an increased risk of heart failure. Previous studies in diabetic patients with normal LVEF have demonstrated the presence of subclinical LV dysfunction as assessed with 2-dimensional (2D) global longitudinal strain (GLS) speckle-tracking echocardiography. On the basis of these findings, it was hypothesized that LV GLS in diabetic patients after STEMI remains more impaired than in patients without diabetes, possibly explaining the increased risk for adverse events. The present evaluation aimed at (1) evaluating changes in LV GLS in a contemporary cohort of patients with STEMI with and without diabetes and (2) determining if diabetes alongside other relevant postinfarction parameters is independently associated with changes in GLS at 6-month follow-up.
Methods
Patients admitted with STEMI treated with primary percutaneous coronary intervention (PCI) at the Leiden University Medical Center were included in an ongoing registry (MISSION!). All patients were treated according to contemporary American College of Cardiology/American Heart Association and European Society of Cardiology guidelines. This included prompt initiation of optimal medical therapy and acquisition of 2D echocardiography within 48 hours of admission. Repeated clinical and echocardiographic evaluations are periodically performed during the first year after STEMI. Clinical and echocardiographic data are collected in the departmental Cardiology Information System (EPD-Vision; Leiden University Medical Center, Leiden, The Netherlands) and in the echocardiography database, respectively, and all data were retrospectively analyzed. For this retrospective analysis of clinically acquired data, the institutional review board waived the need of patient written informed consent.
Diabetes status was assessed during the presentation of index infarction by the treating physician and defined as known history of diabetes treated with diet or insulin and/or oral glucose-lowering agents. Patients with new-onset diabetes diagnosed at the index admission were not included. Furthermore, only patients in whom echocardiography was available at baseline and 6-month follow-up were included. Subsequently, a control group including patients without diabetes was selected from the MISSION! registry. Patients were eligible as controls if they were admitted with a first STEMI treated with primary PCI and if echocardiography was available at baseline and 6-month follow-up. Nondiabetic patients were matched to the diabetic group according to age, gender, and left anterior descending coronary artery as culprit vessel in a 2:1 ratio.
Images were obtained with patients at rest in the left lateral decubitus position using a commercially available ultrasound system (Vivid 7 and E9; General Electric-Vingmed, Horten, Norway). Data acquisition was performed with a 3.5-MHz or M5S transducer in the parasternal and apical views. Standard M-mode and 2D, color, pulsed wave and continuous wave Doppler images were acquired and saved in cineloop format. Echocardiographic data analysis was performed offline (EchoPac 112.0.1; GE Medical Systems, Horten, Norway).
From the parasternal long-axis view, LV dimensions were measured, and LV mass was calculated and indexed to body surface area. Using the biplane Simpson method, LV end-diastolic and end-systolic volumes and LVEF were measured in the apical 4- and 2-chamber views. To calculate wall motion score index (WMSI), the LV was divided into 16 segments, as previously described. Mitral regurgitation severity was graded according to present guidelines. LV diastolic parameters included peak early (E) and late (A) diastolic velocities and E-wave deceleration time measured on pulsed wave Doppler recordings of the transmitral flow. E′ was measured with tissue Doppler imaging at the septal and lateral side of the mitral annulus in the apical 4-chamber view, and E/septal E′ ratio and E/lateral E′ ratio, respectively, were calculated. Finally, according to the biplane Simpson technique, maximal left atrial volume was measured in the apical 4- and 2-chamber views and indexed to the body surface area.
To quantify LV GLS, 2D speckle-tracking analyses were performed offline on standard routine grayscale images of apical 4-, 2-chamber, and long-axis views as previously described. Images were acquired with a frame rate ≥40 frames/sec for a reliable analysis. LV GLS was provided by the software as the average of the peak systolic longitudinal strain of the 3 apical views, displayed in a 17-segment “bull’s eye” plot. GLS measurement was feasible at baseline and 6-month follow-up in 98% of patients. Intraobserver and interobserver variabilities for LV GLS analysis in our laboratory have been reported (−0.09 ± 2.2% and −0.20 ± 1.1%, respectively). For LV circumferential strain, 2D speckle-tracking analyses were performed on the LV short-axis midventricular view at the papillary muscle level, as previously described. LV circumferential strain was calculated as the average of the peak systolic circumferential strain of the short-axis midventricular view. At baseline and 6-month follow-up, LV circumferential strain measurement was feasible in 84% and 89% of patients, respectively. Intraobserver and interobserver variabilities for LV circumferential strain analysis in our laboratory have been reported in previous studies (1.2 ± 1.0% and 2.3 ± 2.4%, respectively).
Continuous data are reported as mean ± SD or SE and median with interquartile range, as appropriate, and categorical data as frequencies and percentages. To obtain a Gaussian distribution, peak troponin T, peak creatine phosphokinase, and estimated glomerular filtration rate levels were log transformed. In statistical tests that required normality (or symmetry), these transformed data were used. Thereafter, data were back-transformed to the original data scales and expressed as median with interquartile range. Differences in baseline clinical parameters between patients with and without diabetes were analyzed using the Student t test and chi-square test. Using linear mixed model analyses, differences in echocardiographic variables were assessed between patients with and without diabetes from baseline to 6-month follow-up, including changes from baseline to 6-month follow-up within each group and differences between groups at each time point. Finally, unadjusted and adjusted linear mixed modeling was used to test the association between diabetes and changes in GLS. Covariates (baseline clinical characteristics and changes in echocardiographic parameters) with a p value <0.10 at the univariate level were included in a linear mixed regression model including diabetes and changes in GLS. Peak creatine phosphokinase and peak cardiac troponin levels were not included in the same model to avoid multicollinearity. Likewise, changes in LV end-diastolic volume, LV end-systolic volume, LVEF, WMSI, and circumferential strain and changes in diastolic function parameters (E/A ratio, deceleration time, E/septal E′ ratio, and E/lateral E′ ratio) were not included in the same model. Moreover, age, gender, and left anterior descending coronary artery as culprit vessel were not included in the multivariate model because patients were matched for these variables. All statistical tests were 2 sided, and a p value <0.05 was considered to be statistically significant. All statistical analyses were performed using SPSS software version 20.0 (SPSS Inc., Chicago, Illinois).
Results
Of 2,443 patients with first STEMI treated with primary PCI, 263 (11%) were diabetic and 2,180 (89%) were nondiabetic. In diabetics, echocardiography was available at baseline and 6-month follow-up for 154 patients (59%). Of the nondiabetic patients, 1,569 patients (72%) were eligible as the potential control group. On the basis of age, gender, and left anterior descending coronary artery as culprit vessel, the 154 patients with diabetes were matched in a 1:2 ratio with 308 patients without diabetes. A further 11 diabetic and 18 nondiabetic patients were excluded owing to the presence of a pacing device at the baseline and/or 6-month echocardiogram. Therefore, the final patient population comprised 143 diabetic and 290 nondiabetic patients.
Most diabetic patients had type 2 diabetes (77%). Antidiabetic treatment at admission consisted of diet only (13%), oral glucose-lowering agents (75%; including metformin, sulfonylureas, glitazones, and dipeptidyl peptidase-4 inhibitors), and insulin (27%). At admission, the mean hemoglobin A 1c level was 58 ± 19 mmol/mol (or 7.4 ± 1.8%), and the mean nonfasting glucose level was 11.6 ± 4.3 mmol/l. Table 1 summarizes the baseline characteristics of patients with and without diabetes. Patients with diabetes presented more often with cardiovascular risk factors compared with nondiabetic patients, including hypercholesterolemia and hypertension. The groups were comparable for other variables.
| Variable | Diabetes Mellitus | P ∗ | |
|---|---|---|---|
| Yes n=143 | No n=290 | ||
| Clinical characteristics | |||
| Age (years) | 64 ± 12 | 63 ± 12 | 0.55 |
| Men | 97 (68%) | 201 (69%) | 0.76 |
| Killip class ≥2 | 8 (6%) | 11 (4%) | 0.39 |
| Current smoker | 38 (27%) | 130 (45%) | <0.001 |
| Family history of CAD | 65 (46%) | 132 (46%) | 0.99 |
| Hypercholesterolemia † | 58 (41%) | 46 (16%) | <0.001 |
| Hypertension ‡ | 77 (54%) | 105 (36%) | <0.001 |
| Coronary angiography | |||
| LAD as culprit vessel | 72 (50%) | 150 (52%) | 0.79 |
| Multivessel coronary disease | 81 (57%) | 153 (53%) | 0.45 |
| TIMI 2 – 3 flow | 143 (100%) | 286 (99%) | 0.16 |
| Laboratory tests | |||
| Peak CPK level (U/L) | 1,120 (537-2,371) | 1,291 (586-2,613) | 0.17 |
| Peak cTnT level (μg/L) | 3.1 (1.2-6.5) | 3.7 (1.3-7.3) | 0.10 |
| eGFR level (mL/min/1.73 m 2 ) | 97 (71-125) | 91 (70-112) | 0.26 |
| Medication at discharge | |||
| ACE-inhibitors/ARBs | 139 (97%) | 286 (99%) | 0.30 |
| Antiplatelets | 143 (100%) | 290 (100%) | 1.00 |
| Beta-blockers | 139 (97%) | 274 (95%) | 0.21 |
| Statins | 143 (100%) | 286 (99%) | 0.16 |
∗ p-values are provided for the comparisons between patients with and without diabetes.
† Total cholesterol ≥ 190 mg/dl or previous pharmacological treatment.
‡ Blood pressure ≥ 140/90 mm Hg or previous pharmacological treatment.
Median time between PCI and baseline echocardiography was 24 (interquartile range 17 to 41) hours. Table 2 illustrates the echocardiographic parameters at baseline and 6-month follow-up in patients with and without diabetes. LV volumes were similar in patients with and without diabetes at baseline and 6-month follow-up. Although both baseline LVEF and WMSI were comparable between patient groups, LV GLS at baseline was more impaired in diabetic patients than in those without diabetes ( Figure 1 ). Over time, both groups demonstrated an improvement in LV function from baseline to 6-month follow-up. Despite similar LVEF in patients with and without diabetes at 6-month follow-up, 6-month GLS values remained more impaired in diabetic patients compared with those without diabetes ( Figure 1 ).
| Variable | Diabetes Mellitus n=143 | No Diabetes Mellitus n=290 | ||||
|---|---|---|---|---|---|---|
| Baseline | 6 months | P within group ∗ | Baseline | 6 months | P within group ∗ | |
| Left ventricular end-systolic volume (mL) | 53.8 ± 1.7 | 55.0 ± 2.1 | 0.50 | 52.3 ± 1.2 | 51.2 ± 1.5 | 0.33 |
| Left ventricular end-diastolic volume (mL) | 100.4 ± 2.6 | 110.6 ± 3.1 | <0.001 | 100.0 ± 1.8 | 106.7 ± 2.1 | <0.001 |
| Left ventricular ejection fraction (%) | 46.8 ± 0.7 | 52.0 ± 0.8 | <0.001 | 48.0 ± 0.5 | 53.1 ± 0.6 | <0.001 |
| Wall motion score index | 1.46 ± 0.03 | 1.35 ± 0.03 † | <0.001 | 1.42 ± 0.02 | 1.28 ± 0.02 † | <0.001 |
| Global longitudinal strain (%) | -13.7 ± 0.3 † | -15.8 ± 0.3 † | <0.001 | -15.3 ± 0.2 † | -17.3 ± 0.2 † | <0.001 |
| Circumferential strain (%) | -10.3 ± 0.4 † | -12.1 ± 0.4 | <0.001 | -11.5 ± 0.3 † | -12.6 ± -0.3 | 0.001 |
| Left atrial indexed volume (mL/m 2 ) | 19.5 ± 0.7 | 22.1 ± 0.7 | <0.001 | 19.8 ± 0.5 | 21.4 ± 0.5 | 0.001 |
| E/A ratio | 0.94 ± 0.04 | 0.97 ± 0.03 | 0.41 | 0.95 ± 0.03 | 0.92 ± 0.02 | 0.15 |
| Deceleration time (ms) | 207.5 ± 6.2 | 229.4 ± 6.4 | 0.008 | 212.8 ± 4.4 | 243.5 ± 4.5 | <0.001 |
| E/septal E′ ratio | 14.3 ± 0.4 † | 15.1 ± 0.8 † | 0.27 | 13.0 ± 0.3 † | 13.0 ± 0.5 † | 1.00 |
| E/lateral E′ ratio | 13.3 ± 0.9 | 11.7 ± 0.5 † | 0.01 | 12.6 ± 0.6 | 10.4 ± 0.3 † | 0.001 |
| Mitral regurgitation grade | 0.52 ± 0.06 | 0.57 ± 0.06 | 0.43 | 0.47 ± 0.04 | 0.50 ± 0.04 | 0.47 |
| Left ventricular mass (g/m 2 ) | 110.9 ± 2.6 † | 105.5 ± 2.4 | 0.04 | 103.5 ± 1.8 † | 102.1 ± 1.7 | 0.34 |
∗ p-values within groups are provided for the differences from baseline to 6 months follow-up within each group.
† p <0.05 for the comparison between patients with and without diabetes at that particular time point.
Unadjusted models showed that diabetes was significantly associated with changes in LV GLS (β 1.54, 95% confidence interval 0.87 to 2.20, p <0.001). Other significant unadjusted correlates of changes in GLS are reported in Table 3 . The final adjusted model included diabetes, Killip class ≥II, hypertension, peak cardiac troponin level, statin usage at discharge, changes in LV end-diastolic volume, E/septal E′ ratio, mitral regurgitation grade, and LV mass. In this model, diabetes emerged as an independent determinant of changes in LV GLS (β 1.41, 95% confidence interval 0.85 to 1.96, p <0.001; Table 3 ).
