Patients and study design
This is a CMR substudy of the prospectively conducted ISKE project (Imaging acute myocardial ischemia by body surface potential mapping) [
12]. In brief, from June 2003 to June 2005, patients admitted to the Coronary Care Unit of Helsinki University Hospital for suspected acute coronary syndrome were screened during office hours. Inclusion criteria were prolonged chest pain ≥20 min within 48 h of recruitment, associated with evidence of acute ischemia in the initial 12-lead electrocardiogram (ST-segment elevation, −depression, or T-wave inversion in ≥2 contiguous leads), or elevated cardiac enzymes (CK-MB mass > 7 μg/L or troponin T > 0.03 μg/L), or both [
12]. Patients with bundle branch block, atrial fibrillation, pacemaker, or need for ventilator support, were excluded. Also patients with contraindications for CMR, such as pacemakers, defibrillators or claustrophobia, were excluded.
In this CMR substudy, all eligible patients were diagnosed with acute spontaneous type 1 MI [
10], with elevated cardiac enzymes or scar at CMR, and underwent revascularization in the acute phase. Both patients with ST-elevation MI (STEMI) and non-ST elevation MI (NSTEMI) at presentation were included. All patients with prior MI, percutaneous coronary intervention (PCI), or coronary artery bypass craft (CABG), were excluded.
All patients were treated with successful PCI, CABG or thrombolysis in less than 3 days after the admission except for one patient treated successfully with CABG after 9 days during the same hospital stay, and received optimal secondary preventive medication for coronary artery disease.
All patients underwent two CMR examinations after MI to assess LV and infarct remodeling. The first CMR study occurred during the recovery phase 7–30 days after MI, and the second at the chronic infarct phase ≥6 months after MI. Revascularization was always performed before the first CMR.
CK-MB was measured according to routine clinical praxis: at arrival at the hospital, the following evening or morning, or both. The maximum value of these measurements, peak CK-MB, served as a measure of infarct size. In most patients, measurement of peak CK-MB occurred 12–24 h after the onset of chest pain.
CMR methods
CMR imaging was performed with a 1.5-T imager (Sonata, Siemens Medical Solutions) using body-array coil as a receiver. Breath-hold cine CMR was performed using retrospectively electrocardiographically gated segmented imaging with steady-state free-precession (SSFP). Cine CMR images were acquired in vertical, horizontal long-axis and short-axis planes covering the whole LV. Typical imaging parameters were TR/TE 3.0/1.51 ms, flip angle 52 degrees, 256 × 256 matrix and 240 × 340 mm field of view. Slice thickness was 6 mm. The temporal resolution was 42–47 ms.
Ten to fifteen minutes after intravenous injection of a contrast agent (gadodiamide, Omniscan TM, GE Healthcare, 0.2 mmol/kg), late gadolinium enhancement (LGE) images were acquired in the same views as for cine images, using inversion-recovery turbo fast-low angle shot (FLASH). Typical imaging parameters were TR/TE 8.6/4.3 ms, 256 × 256 matrix, slice thickness 8 mm and interslice gap 20%. Inversion times were optimized to null the signal intensity of normal myocardium (250–300 ms).
CMR analysis
CMR images were analyzed by two experienced observers blinded to clinical outcome. LV mass, end-diastolic (EDV) and end-systolic (ESV) volumes were evaluated by manually tracing the epicardial border (excluding epicardial fat) and endocardial borders (excluding papillary muscles) at end-diastole and -systole for short-axis slices. Volumetric indices were obtained by dividing values by body surface area.
LGE images were analyzed using the standard 17-segment model of the LV, leaving out the apex [
13]. Scar area was manually delineated, the method of which has recently shown the lowest overall variability for quantification of MI when analyzed by experienced observers [
14]. The global scar size was calculated by dividing the sum of segmental scar areas by the total area of all segments. Infarct transmurality was evaluated as the percentage area in each segment. Transmural MI was defined as ≥75% enhancement in at least one myocardial segment on recovery phase CMR [
15], irrespectively of STEMI/NSTEMI classification at presentation.
Repeatability of LGE analyses was also studied: 384 segments were analyzed for the presence of scar by two independent observers, and results were concordant for 366 (95%) of the segments (kappa = 0.86).
Segmental wall motion was visually estimated, blinded to LGE results. The degree of wall motion abnormality in each segment was scored as 0 (normokinesia), 1 (hypokinesia), 2 (akinesia) or 3 (dyskinesia). Wall motion abnormality index (WMAi) of the LV was then calculated as the sum of all segmental scores.
Follow-up
Follow-up data of major adverse cardiac events (MACEs) was post-hoc collected until the end of year 2012 based on local and national registries, including university and local hospital records, general practitioners’ records and the mortality information from the public organization Statistics Finland, without direct contact to patients. The survival time was calculated from the first CMR and only one event was tabulated per subject. A MACE was defined as cardiovascular death, aborted sudden death, heart failure hospitalization, or recurrent MI. Aborted sudden death was defined as documented resuscitation from cardiac arrest or appropriate implantable cardioverter defibrillator therapy, i.e. antitachycardia pacing or shock, for ventricular tachycardia or fibrillation.
Statistical analysis
Continuous variables are presented as median (interquartile range [IQR]) and categorical variables as frequency (%). Comparison between continuous variables was performed with Mann-Whitney U test. CMR variables were compared between recovery and chronic phase studies using related samples Wilcoxon signed rank test. Correlation between variables was calculated using Spearman’s method. Linear regression was performed to identify predictors of chronic phase ejection fraction (EF), reaching sufficient normality of residuals. In survival analysis, Cox regression analysis was performed to identify predictors of MACEs. A p-value of < 0.05 was considered statistically significant and all tests were 2-sided. Statistical analysis was performed on SPSS 21 statistical package (SPSS, Chigaco, IL).