Acute myocardial infarction is a devastating condition carrying high incidence of morbidity and mortality despite considerable advances in lines of therapy over years . The resulting left ventricular (LV) dysfunction is definitely secondary to loss of myocardial muscle mass [1,2] but may have an additional component of LV dyssynchrony. All the efforts in the last decade focused mainly on decreasing infarction size through early reperfusion and adjunctive medical therapy [1–3]. Several studies could find some relation between LV dyssynchrony and acute myocardial infarction, however in these studies modest duration of time elapsed between the incidence of STEMI and imaging used [4–6]. In addition to date there is no evidence that early LV dyssynchrony can affect acutely the LV function. With the advances, ease and popularity in resynchronization therapy positive modification of dyssynchrony toward synchrony may be of value in the acute phase of STEMI. Gated SPECT was studied as a valuable tool to evaluate dyssynchrony in heart failure patients . Using technetium SestaMIBI offers the advantage of injecting the isotope on admission and acquiring the study after the revascularization without delay in the treatment offered for the patient [8–11].
2. Aim of work
Detection of LV dyssynchrony in Acute STEMI patients and its relation to LV dysfunction in these patients.
3. Patients and methods
Case control non randomized observational study. All patients signed written consent. The study was approved by the research council in Cairo University.
3.1. Inclusion criteria
Cases: Sixty acute STEMI patients admitted to the critical care department Cairo University were included in our study.
Control group: Sixty control subjects were chosen from the patients referred for diagnostic stress SestaMIBI MPI on elective bases. All controls had normal basic ECG, no history of coronary angiography or CABG, normal LV function and normal stress perfusion scans.
3.2. Exclusion criteria
Controls with abnormal ECG stress test and who developed significant symptoms or apparent structural abnormalities on perfusion scans (e.g. LV hypertrophy or dilatation) were excluded. STEMI Patients with a history or ECG evidence of old myocardial infarction, cardiomyopathy, left bundle branch block, patients who are not eligible for revascularization and refusal of myocardial perfusion imaging were excluded from the study.
STEMI diagnosis was based upon the European Society of Cardiology/ACCF/AHA/World Heart Federation Task Force for the Universal Definition of Myocardial Infarction which includes characteristic symptoms of myocardial ischemia associated with ST segment elevation and subsequent rise in serum biomarkers. New ST elevation at the J point in at least 2 contiguous leads of ≥2mm (0.2mV) in men or ≥1.5mm (0.15mV) in women in leads V2–V3 and/or of ≥1mm (0.1mV) in other contiguous chest leads or the limb leads .
All patients were subjected to:
- History taking and physical examination, Twelve lead ECG, Cardiac biomarkers including CPK, CK MB and Troponin T. Rest gated Technitium99m SestaMIBI Myocardial perfusion study was performed as follows; Patients were injected intravenously with 25mCi Technetium SestaMIBI on admission. After being subjected to primary PCI within 90min from admission, patients were transferred to the nuclear cardiology laboratory integrated in the critical care department and a rest ECG gated single photon emission computed tomography (SPECT) study was acquired. Acquisition of images done in the nuclear cardiology lab which is integrated in the critical care department Cairo University. Images were acquired in our dual head gamma camera (Symbia E, Siemens Medical Solutions USA, Inc., IL,USA) utilizing Cedars Sinai software, USA, 2009 (8 frames per cycle). Images were gated to the R wave of the ECG, and image acquisition was interrupted for one beat if the R–R interval varied by 15% of the preceding R–R interval.
First, Myocardial Perfusion images to calculate the myocardium at risk using the 20 segment scoring system. Second, LV functional parameters to derive the LVEDV, LVESV and LVEF. Third, Phase images where the expected LV dyssynchrony parameters were used, the latter included the histogram bandwidth, histogram standard deviation and entropy .
Gated SPECT MPI was obtained at rest with Tc99m SestaMIBI according to ESC guidelines . The step and shoot protocol was used, 180_ elliptical orbit with 32 projections. The patient was transferred after the primary percutaneous coronary intervention (PCI) procedure and stabilization within 6h of trace injection to the nuclear cardiology lab integrated into the critical care department, Cairo University. A dual-head detector Symbia E gamma camera (Siemens) with high resolution, low energy collimator was used. A window of 15% was centered on the 140keV gamma peak, and the ECG gating was done with 8 frames per R–R cycle.
Butterworth filtering followed by filtered back projection reconstruction performed on a 64×64 matrix. The images were reviewed and interpreted by 2 senior operators blinded to the ECG and PCI data and on separate occasion.
The LV volumes and EF were measured from the rest gated images based on the method described by Germano et al.  perfusion defects were interpreted and quantified using the 20 segment scoring system available in the Cedars Sinai QPS package 2009, to get the myocardium at risk for the acquired set of images.
Phase analysis of gated SPECT was done by the following 3 quantitative indexes obtained from the phase analysis of all patients:
- Histogram bandwidth: includes 95% of the elements of the phase distribution .
- Phase SD: is the SD of the phase distribution .
- Phase Entropy: is considered by some authors as a more appropriate dispersion measure than SD, which is expressed from 0% to 100%. In this modality perfect synchrony would be 0% of entropy being significant from 60% and corresponding to 100%, the theoretical maximum possible dyssynchrony .
The gated SPECT acquisition followed the method described by Germano et al. . The criteria for dyssynchrony has been described by Chen et al.  and we used the methodology described by Boogers et al.  for phase analysis and distribution using the Cedars Sinai QGS software. In brief, three-dimensional count distributions were extracted from each of the LV short-axis data set, submitted to Fourier phase analysis, and that generated a three-dimensional phase distribution (0–360°) over the whole R–R interval and represented on a histogram.
All controls were subjected to:
- Two days stress and rest imaging according to imaging guidelines [17,13] using the same acquisition technique and tools described earlier. Patients were exercised according to Bruce protocol to reach age predicted target heart rate. Only patients who reached 100% of the target heart rate were included in the study. All exercised patients were injected intravenously at the peak of exercise with Tc99m SestaMIBI (hexakis-isobutyl-isonitrile) (monrol weight based dose and imaged 30–45min later. Rest gated SPECT studies were acquired on separate day. Data from rest studies were used in comparisons for the control against the studied group. Only patients with essentially normal perfusion and functional scans were included.
3.3. Statistical methods
Numerical variables were described as mean±SD. Categorical variables were described as percentages. Comparisons were done using Student “t” test for numerical variables and Chi square test for categorical variables. Correlations were plotted and r values (correlation coefficients) were stated. p value was considered significant if ≤0.05. Statistics were calculated using SPSS 17 package.
4.1. Study group demographic data
A total number of 60 patients with acute STEMI were included in our study, including 54 males (90%) and 6 females (10%) with a mean age (54.8±10.38years) range from 29 to 74years. Besides 60 controls the mean age (50.7+20.3years) ranges from 26–69years.
4.1.1. Risk factors for coronary artery disease
Smoking was the most prevalent risk factor for coronary artery disease among our patients (Table 1).
4.2. Electrocardiographic data
Electrocardiograms were analyzed to locate site of acute myocardial infarction. Thirty patients had acute anterior STEMI and 30 had acute inferior STEMI (see Tables 2 and 3).
4.3. Scintigraphic data
4.3.1. Acute myocardial perfusion imaging
Most of patients showed a large area of myocardium at risk with a mean of 43.1±20.5% of the myocardium on semi quantitative analysis.
4.3.2. Gated SPECT data
Acute STEMI cases showed increased LV volumes and impaired mean LVEF with significantly higher values of phase parameters Table 4.
There ranges of different phase parameters values are listed in Tables 5 and 6.
There was a significant reverse correlation between phase parameters values and the LV ejection fraction in the studied patients. Histogram entropy was the most correlated value (Figs. 1 and 2, Table 7).
The reverse correlations between different phase parameters and the LVEF were valid in control cases as well as demonstrated in Figs. 3 and 4, and Table 8.
Several imaging tools have been used to study LV dyssynchrony, of them new nuclear cardiology technique that used ECG gated SPECT study phase image had good repeatability, reproducibility and predictive value [14,18–20].
Increased bandwidth, standard deviation and entropy had been studied by several investigators especially in heart failure patients [7,14,21,20,22–24]. These parameters improved after cardiac resynchronization therapy.
We used Tc99m SestaMIBI gated SPECT phase imaging to study the effect of LV dyssynchrony in acute STEMI, this was achieved through injecting the tracer on patient admission and the performing of the image acquisition after primary PCI within the first 6h in the acute setting and compared these results to healthy controls referred for stress myocardial perfusion imaging. The minimal distribution of technetium from the cardiomyocytes allows imaging within 6h of injection. The acquired image represents the defect at the time of injection “frozen image” or the myocardium at risk. In addition there is no delay in revascularization procedure (see Fig. 6b).
Several studies on STEMI patients emphasized on the presence of LV dyssynchrony several days after the infarction. Different tools were used including echocardiography and magnetic resonance imaging [4,20,6] however all the imaging studies were performed after the infarction in the first few days which may not reflect the initial actual degree of LV dysfunction (see Figs. 7a and 7b).
The main findings of this study are that LV dyssynchrony occurs during acute STEMI even in the absence of LBBB and its severity is inversely related to LV systolic dysfunction as measured by LVEF. This study does not answer the question of whether the dyssynchrony is the cause or the result of LV dysfunction but it is conceivable that it contributed to the dysfunction. Improvement of LVEF days after acute MI is likely related to relief of stunning and possibly also to improvement of dyssynchrony. Recent studies suggest that dyssynchrony is related to ischemia when assessed by PET imaging .
We found in our study a significant increase in bandwidth duration, standard deviation and entropy in cases when compared to controls. In addition there was significant drop in LV systolic function in these patients. LV dysfunction in acute STEMI was demonstrated in a previous study in our center, however the software used at that time couldn't demonstrate the phase imaging parameters mentioned [26,27].
The degree of bandwidth, standard deviation and entropy showed a highly significant reverse correlation with the gated LV ejection fraction which points toward the negative impact of acute LV dyssynchrony on LVEF. Further studies are needed to evaluate the impact of revascularization on this phenomenon.
LV dyssynchrony may be acquired acutely very early in STEMI and may have a negative impact on LV ejection fraction.
Conflict of interest
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