Mechanical Left Ventricular Dyssynchrony in ACS
Mechanical Left Ventricular Dyssynchrony in ACS
The study included 227 patients admitted to the coronary care unit at Karolinska University Hospital, Huddinge, between August 2006 and January 2008, with a clinical diagnosis of ACS. The patients were consecutively included except for temporary interruptions of the study due to high work load at the coronary care unit. All patients underwent clinical assessment including clinical history, physical examination, standard 12-lead ECG, ECG-monitoring and serial measurement of biochemical cardiac markers up to 9–12 hours after admission. All other examinations as well as specific treatments of the patients were left to the discretion of the individual cardiologist. Clinical data were prospectively collected and entered into a database. An acute MI was defined according to current guidelines.
The primary endpoint was the composite of death from any cause, new MI, or rehospitalisation due to heart failure. Secondary endpoints were death from any cause, new MI and rehospitalisation due to heart failure as separate endpoints and the composite endpoint of death from any cause or rehospitalisation due to heart failure. All in-hospital events were registered in the study database. Only new MIs occurring more than 24 hours after admission were considered as events. Out of hospital, information about death and need for readmission because of MI or heart failure was obtained by merging the database with the Swedish population registry, which includes information of the vital status of all Swedish citizens, and the National Patient Registry, which includes diagnoses on all patients hospitalized in Sweden.
Before entering the study, all patients gave their written, informed consent. The study was conducted according to the principles of the Declaration of Helsinki and was approved by the local ethics committee.
All echocardiography data were collected at a (median(25th-75th percentile) time of 3(2–4)) days from admission according to the local standard clinical protocol at that time on Karolinska University Hospital by the cardiologist or sonographer on duty that day. The images, including 2D, TDI and spectral Doppler, were collected using a GE Vingmed vivid7 ultrasound machine with standard installed software.
The images were analyzed using a dedicated workstation (EchoPAC, GE Healthcare, Horten Norway) by a well-trained cardiologist (CW) blinded to baseline data and subsequent outcome.
Myocardial deformation can be calculated from the 2D images from the speckle tracking technique using reflector based identification of the individual reflection pattern of specific bright spots (speckles) in the myocardium and tracking these speckles from frame to frame. With this technique, we can calculate the percentage change in the systolic longitudinal shortening of the myocardium, i.e. longitudinal strain and furthermore the times to peak strain from onset of QRS on a segmental level of the LV. The intersegmental variation of time to peak longitudinal strain measure from speckle tracking has previously been used as a dyssynchrony parameter and has showed to predict outcome after ACS in a population selected for impaired systolic function. This parameter has also been shown to predict the incidence of ventricular arrhythmias which may suggest a prognostic value for CAD patients but has not specifically been tested in an ACS population. The time to peak strain information was exported from GE Echopac and imported to, and processed with GH-lab software (Figure 1) and presented as described below with -SD and –delta parameters. We also present Global Strain which is the average of the segmental peak systolic strain regardless of timing.
(Enlarge Image)
Figure 1.
Assessment of time-to-peak 2D strain. In the upper half of the figure we see the 2D strain curves for the six segments of the 4-chamber view with the corresponding ECG in the lower half of the figure, one line representing one segment. The left red marker indicates the R-wave from the ECG and the right marker shows the aortic valve closure and end of systole. Time to peak systolic strain is automatically generated for each of these segments and the segments in 2 and 3-chamber view. The Standard deviation of these 18 segments represents Time-to-peak Strain SD, and the difference between the shortest and the longest time Time-to-peak Strain Delta.
The degree of post systolic strain using post systolic index (PSI) also called post systolic shortening (PSS) has been shown to be highly correlated to both chronic and acute ischemia and also a predictor of recovery after NSTEMI but the prognostic value of PSI and it's intersegmental variation in ACS patients has not been determined. The Post systolic index (PSI) is given automatically in the workstation and is defined as ((peak strain-endsystolic strain)/Peak Strain)×100.
For both PSI and time to peak 2D-strain the intersegmental variation, standard deviation (SD) and the difference between the maximum and minimum (Delta) were used as measurements of LV dyssynchrony.
Measuring the time difference in peak systolic velocity in septum and lateral wall from TDI, often referred to as the septal-lateral delay, is both robust and feasible, and one of the most established methods. Also derived from TDI, the ratio between the sum of the isovolumetric relaxation and isovolumetric contraction times devided by contraction time, often referred to as the myocardial performance index (MPI) can be calculated, this index is similar to the Tei index, but the latter is not derived from TDI. MPI has shown to predict left ventricular dilatation and death after MI and also reflect the severity of ischemic heart disease. MPI has furthermore been shown to have a prognostic value after ACS in a subgroup of patients with preserved systolic function, in patients with ST-elevation myocardial infarction undergoing PCI and also in un unselected population. TDI is a robust measurement and has higher time resolution compared to 2D-imaging which makes it reasonable to assume that the intersegmental variation of MPI could be a suitable way to describe dyssynchrony of the LV. Whether this measurement can be useful as a prognostic marker has not been investigated.
Both Septal to lateral delay and MPI are acquired in post processing recorded color-coded TDI images using the Q-analysis software in the EchoPAC. Septal-lateral delay is recorded from the four chamber projection as the time difference between peak systolic velocity in the basal segments of the septal and lateral myocardial walls. From the velocity curves and all three apical projections the regional time of the phases of the cardiac cycle where measured and the MPI was calculated, as showed in Figure 2. For each patient MPI was calculated for all six basal segments and SD and delta for MPI as described above.
(Enlarge Image)
Figure 2.
Illustrating how the different time intervals of the MPI are registered from TDI, velocities on the Y-axis and time on the X-axis and under the curve the corresponding ECG.
Ejection fraction was measured according to current EACV/ASE recommendations using the biplane Simpson method of discs from outlining the endocardial border in the apical 4-, and 2-chamber views.
Wall motion score index (WMSI) was derived by a visual assessment of the function of all 18 segments of the left ventricle where normokinetic segments got the value 1, hypokinetic segments 2, akinetic 3 and dyskinetic 4. Wall motion score index was calculated by dividing the sum by 18.
Continuous data are presented as medians with interquartile range (IQR) and categorical data are presented with frequencies and percentages. When analyzing differences between groups the Mann Whitney-test was used for continuous variables and Chi2-test for categorical variables. To compare the prognostic value regardless of chosen cut off-value, receiver operating characteristics (ROC) analyses expressing prognostic value as area under curve (AUC) with 95% confidence interval (CI)were used and the significance of this measurements are evaluated according to Hanley and McNeil. We also included (EF*Time-to-peak Strain SD) and (EF*PSI SD) to examine whether the combination of the two variables could give a larger AUC than when variables were used alone.
To examine whether measurements of dyssynchrony were independently associated with outcome, Cox-regression analyses were used in two models. In model 1 the analysis was made univariate and the parameters were entered one by one without adjustment for other variables. In model 2, adjustment was made for baseline characteristics well known to be associated with outcome (age, gender, diabetes, hypertension, previous heart failure, creatinine clearance and troponin level) and in this model, just as in model 1 the echocardiographic parameters was inserted one by one.
Methods
Study Population
The study included 227 patients admitted to the coronary care unit at Karolinska University Hospital, Huddinge, between August 2006 and January 2008, with a clinical diagnosis of ACS. The patients were consecutively included except for temporary interruptions of the study due to high work load at the coronary care unit. All patients underwent clinical assessment including clinical history, physical examination, standard 12-lead ECG, ECG-monitoring and serial measurement of biochemical cardiac markers up to 9–12 hours after admission. All other examinations as well as specific treatments of the patients were left to the discretion of the individual cardiologist. Clinical data were prospectively collected and entered into a database. An acute MI was defined according to current guidelines.
The primary endpoint was the composite of death from any cause, new MI, or rehospitalisation due to heart failure. Secondary endpoints were death from any cause, new MI and rehospitalisation due to heart failure as separate endpoints and the composite endpoint of death from any cause or rehospitalisation due to heart failure. All in-hospital events were registered in the study database. Only new MIs occurring more than 24 hours after admission were considered as events. Out of hospital, information about death and need for readmission because of MI or heart failure was obtained by merging the database with the Swedish population registry, which includes information of the vital status of all Swedish citizens, and the National Patient Registry, which includes diagnoses on all patients hospitalized in Sweden.
Before entering the study, all patients gave their written, informed consent. The study was conducted according to the principles of the Declaration of Helsinki and was approved by the local ethics committee.
Echocardiographic Acquisition, Analyses and LV Dyssynchrony Assessment
All echocardiography data were collected at a (median(25th-75th percentile) time of 3(2–4)) days from admission according to the local standard clinical protocol at that time on Karolinska University Hospital by the cardiologist or sonographer on duty that day. The images, including 2D, TDI and spectral Doppler, were collected using a GE Vingmed vivid7 ultrasound machine with standard installed software.
The images were analyzed using a dedicated workstation (EchoPAC, GE Healthcare, Horten Norway) by a well-trained cardiologist (CW) blinded to baseline data and subsequent outcome.
2D Strain
Myocardial deformation can be calculated from the 2D images from the speckle tracking technique using reflector based identification of the individual reflection pattern of specific bright spots (speckles) in the myocardium and tracking these speckles from frame to frame. With this technique, we can calculate the percentage change in the systolic longitudinal shortening of the myocardium, i.e. longitudinal strain and furthermore the times to peak strain from onset of QRS on a segmental level of the LV. The intersegmental variation of time to peak longitudinal strain measure from speckle tracking has previously been used as a dyssynchrony parameter and has showed to predict outcome after ACS in a population selected for impaired systolic function. This parameter has also been shown to predict the incidence of ventricular arrhythmias which may suggest a prognostic value for CAD patients but has not specifically been tested in an ACS population. The time to peak strain information was exported from GE Echopac and imported to, and processed with GH-lab software (Figure 1) and presented as described below with -SD and –delta parameters. We also present Global Strain which is the average of the segmental peak systolic strain regardless of timing.
(Enlarge Image)
Figure 1.
Assessment of time-to-peak 2D strain. In the upper half of the figure we see the 2D strain curves for the six segments of the 4-chamber view with the corresponding ECG in the lower half of the figure, one line representing one segment. The left red marker indicates the R-wave from the ECG and the right marker shows the aortic valve closure and end of systole. Time to peak systolic strain is automatically generated for each of these segments and the segments in 2 and 3-chamber view. The Standard deviation of these 18 segments represents Time-to-peak Strain SD, and the difference between the shortest and the longest time Time-to-peak Strain Delta.
The degree of post systolic strain using post systolic index (PSI) also called post systolic shortening (PSS) has been shown to be highly correlated to both chronic and acute ischemia and also a predictor of recovery after NSTEMI but the prognostic value of PSI and it's intersegmental variation in ACS patients has not been determined. The Post systolic index (PSI) is given automatically in the workstation and is defined as ((peak strain-endsystolic strain)/Peak Strain)×100.
For both PSI and time to peak 2D-strain the intersegmental variation, standard deviation (SD) and the difference between the maximum and minimum (Delta) were used as measurements of LV dyssynchrony.
Tissue Doppler Imaging
Measuring the time difference in peak systolic velocity in septum and lateral wall from TDI, often referred to as the septal-lateral delay, is both robust and feasible, and one of the most established methods. Also derived from TDI, the ratio between the sum of the isovolumetric relaxation and isovolumetric contraction times devided by contraction time, often referred to as the myocardial performance index (MPI) can be calculated, this index is similar to the Tei index, but the latter is not derived from TDI. MPI has shown to predict left ventricular dilatation and death after MI and also reflect the severity of ischemic heart disease. MPI has furthermore been shown to have a prognostic value after ACS in a subgroup of patients with preserved systolic function, in patients with ST-elevation myocardial infarction undergoing PCI and also in un unselected population. TDI is a robust measurement and has higher time resolution compared to 2D-imaging which makes it reasonable to assume that the intersegmental variation of MPI could be a suitable way to describe dyssynchrony of the LV. Whether this measurement can be useful as a prognostic marker has not been investigated.
Both Septal to lateral delay and MPI are acquired in post processing recorded color-coded TDI images using the Q-analysis software in the EchoPAC. Septal-lateral delay is recorded from the four chamber projection as the time difference between peak systolic velocity in the basal segments of the septal and lateral myocardial walls. From the velocity curves and all three apical projections the regional time of the phases of the cardiac cycle where measured and the MPI was calculated, as showed in Figure 2. For each patient MPI was calculated for all six basal segments and SD and delta for MPI as described above.
(Enlarge Image)
Figure 2.
Illustrating how the different time intervals of the MPI are registered from TDI, velocities on the Y-axis and time on the X-axis and under the curve the corresponding ECG.
Ejection Fraction
Ejection fraction was measured according to current EACV/ASE recommendations using the biplane Simpson method of discs from outlining the endocardial border in the apical 4-, and 2-chamber views.
Wall Motion Score Index
Wall motion score index (WMSI) was derived by a visual assessment of the function of all 18 segments of the left ventricle where normokinetic segments got the value 1, hypokinetic segments 2, akinetic 3 and dyskinetic 4. Wall motion score index was calculated by dividing the sum by 18.
Statistical Analysis
Continuous data are presented as medians with interquartile range (IQR) and categorical data are presented with frequencies and percentages. When analyzing differences between groups the Mann Whitney-test was used for continuous variables and Chi2-test for categorical variables. To compare the prognostic value regardless of chosen cut off-value, receiver operating characteristics (ROC) analyses expressing prognostic value as area under curve (AUC) with 95% confidence interval (CI)were used and the significance of this measurements are evaluated according to Hanley and McNeil. We also included (EF*Time-to-peak Strain SD) and (EF*PSI SD) to examine whether the combination of the two variables could give a larger AUC than when variables were used alone.
To examine whether measurements of dyssynchrony were independently associated with outcome, Cox-regression analyses were used in two models. In model 1 the analysis was made univariate and the parameters were entered one by one without adjustment for other variables. In model 2, adjustment was made for baseline characteristics well known to be associated with outcome (age, gender, diabetes, hypertension, previous heart failure, creatinine clearance and troponin level) and in this model, just as in model 1 the echocardiographic parameters was inserted one by one.
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