Patients and protocol
We retrospectively studied patients who were initially included in the viability-guided angioplasty after acute myocardial infarction-trial (VIAMI-trial; NCT00149591: http://www.clinicaltrials.gov). The VIAMI-trial was a prospective, multicenter, randomized controlled clinical trial [19, 20]. Between April 2001 and January 2006, 291 patients were enrolled from 11 participating Dutch hospitals. Patients admitted to any of the participating centers with a (sub)acute myocardial infarction, who were not treated by primary or rescue angioplasty, and who were stable during the first 48 hours after the acute event, were screened for the study. Stable patients revealed no signs of ongoing ischemia based on electrocardiographic characteristics or persistent chest discomfort.
Patients less than 80 years of age were considered suitable for the study when they met the criteria for definite myocardial infarction: a significant rise in creatine kinase-MB levels (twice the upper limit of normal), 1 mm ST segment elevation in two or more standard leads or 2 mm ST segment elevation in two contiguous chest leads, and/or the development of Q waves.
Patients underwent LDDE for the detection of viability within 72 hours after AMI. Patients with viability in the infarct area were randomized to an invasive or a conservative treatment strategy. The invasive strategy patients underwent in-hospital coronary angiography with the intention to perform PCI with stenting of the IRA. In the conservative group, an ischemia-guided approach was adopted with stress testing before hospital discharge. After a positive test for ischemia, coronary angiography was strongly recommended.
Patients were followed up for 3 years, with the intension to perform an echocardiogram after 3, 6, and 12 months. Eventually, 224 patients had an evaluable baseline and follow-up echocardiogram.
In this echocardiographic substudy, patients were divided into three new groups to investigate the influence of revascularization and viability on LV remodeling. These groups were based on their initial randomization, LDDE response, and revascularization status. Ninety four patients were classified as viable and were revascularized before their follow-up echocardiogram (group 1). Seventy one patients were also viable, but medically treated without revascularization (group 2). Fifty nine patients were classified as non-viable (group 3).
Ethical approval and consent
The VIAMI-trial was approved by the Clinical Research Ethical Committee of the VU University Medical Center (ref: 1999/123). The local research ethics committee of each participating hospital approved for local feasibility (see Additional file 1). All eligible patients provided written informed consent. The study complied with the Declaration of Helsinki.
The baseline, LDDE, and follow-up echocardiograms were performed with a Hewlett-Packard Sonos 5500 imaging system (2.5 and 3.5 MHz transducers; Hewlett-Packard Inc., Andover, MA, USA). All patients were imaged while taking their prescribed medication. Beta-blockers were withdrawn 24 hours before the LDDE. At baseline and at follow-up, a complete cross sectional ultrasound examination was performed according to the guidelines of the American Society of Echocardiography under resting conditions .
To perform the LDDE, dobutamine was administrated intravenously at doses of 5, 10, and 15 μg/kg/min, for 5 minutes at each dose. When a 10% increase in heart rate was not achieved with 15 μg/kg/min, a 5-minute infusion with 20 μg/kg/min could be used as the final stage of the procedure [22–24]. Patients were continuously monitored by a 12-lead electrocardiogram, and blood pressure was recorded at the end of each stage. The criteria for stopping dobutamine infusion were as follows: hypotension decrease in systolic or diastolic blood pressure of more than 30 mmHg; hypertension (systolic blood pressure above 220 mmHg, diastolic pressure above 130 mmHg); intolerable angina; supraventricular tachycardia; ventricular tachycardia, significant ST segment depression or elevation (more than 2 mm); significant ischemia on the echocardiogram (more than 1 segment). All patients reached the 10% increase in heart rate. Patients with significant ischemia were excluded from the study because coronary angiography was mandatory.
All echocardiographic images were sent to the core-lab (VU University Medical Center) and analyzed by two experienced observers. A third observer was used in case of disagreement to reach consensus.
Baseline and follow-up
Five standard views were obtained: the parasternal long-axis and short-axis view (mid-ventricular view) and the apical two-, three- and four-chamber view. A 16-segment model was used in which the apex is divided into four segments. Segmental wall motion and thickening was scored according to a 4-point scale: 1 = normal, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic. Wall motion score index was calculated by summing the scores for each segment and dividing by the number of segments analyzed. LV volumes and EF were measured by use of the modified Simpson’s rule algorithm from orthogonal apical long-axis projections (four- and two-chamber view) as recommended by the American Society of Echocardiography [21
]. Tracing of the endocardial borders was performed on a digitized frame. The mean values of at least three measurements of the technically best cardiac cycles were taken from each examination. EF was calculated as:
A relative increase of LV ejection fraction >10% at follow-up was defined as a significant LV improvement .
Low-dose dobutamine echocardiogram
Viability was defined as the improvement of wall motion abnormalities in two or more segments of the infarct zone. Changes from hypokinesia to normokinesia and from dyskinesia or akinesia to hypo- or normokinesia are considered an improvement in wall motion abnormality. Dyskinesia changing to akinesia was not considered as an improvement.
Baseline descriptive data are presented as mean ± SD. Differences in clinical and echocardiographic variables were assessed by unpaired Student’s t test. Differences between proportions were assessed by chi-square analysis; a Fisher’s exact test was used when appropriate. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) and EF at baseline and at follow-up were compared for mean values and changes over time, using one-way repeated measures analysis of variance, with time being the within-subject variable. Variables that were significantly different between patients with and without LVEF improvement (relative increase of >10%) were submitted for univariate regression analysis. Variables that showed a significant correlation with LVEF improvement were included in the multivariate stepwise logistic regression model to determine the independent correlates. A probability value of P < 0.05 was considered significant. All analyses were performed with the use of SPSS software, version 16.0 (SPSS, Inc., Chicago, IL, USA).