INTRODUCTION
Dobutamine stress echocardiography (DSE) is well-established for identifying inducible ischemia and increasingly used for the detection of myocardial viability. Ischemia is defined as a regional reduction of myocardial thickening or abnormal wall motion.[1,2] Myocardial viability can be determined using the DSE protocol when either an improvement in resting wall motion or a biphasic response is observed.[3] A biphasic response is characterized by dyssynergic myocardium at baseline that recovers contraction at a low dose of dobutamine but deteriorates at a higher dose because of reduced coronary flow reserve.[4,5] Visual assessment of the left ventricular (LV) wall motion is a method for interpreting rest and stress echocardiography.[6,7] However, it is a subjective method, limited by the operators experience in image acquisition and interpretation. Moreover, the detection of wall motion during DSE seems to be even more challenging in the presence of preexisting wall motion abnormalities and during induced tachycardia.[1] Contrarily, deformation analysis based on speckle-tracking echocardiography provides quantitative data describing the contractile function of each ventricular segment. Correlations between visual wall-motion score and longitudinal global and regional strain in patients with myocardial infarction, noncoronary chest pain, and dilated cardiomyopathy were reported.[8] Despite theoretical advantages, little is known about longitudinal strain values typical for normokinetic, hypokinetic, and akinetic LV segments measured at basal and peak stages of DSE and the changes of deformation parameters in segments with improved in comparison to segments with impaired contractility observed during DSE.[8]
The aim of this study was to compare values of longitudinal strain among LV segments with normokinetic, hypokinetic, and akinetic as stratified by experienced investigators during baseline and peak stage of diagnostic and viability study of DSE and to compare the changes of deformation between segments with impaired or improved with preserved contractility observed during DSE.
METHODS
This study included 112 patients referred for DSE to the echocardiography laboratory of National Cardiovascular Center Harapan Kita from February 2021 to July 2022. The data were taken from EchoPAC software GE workstation echocardiography laboratory. The indication of DSE was either for diagnostic or viability study.
The patient underwents a standard DSE protocol for the diagnostic study. Incremental dobutamine infusion rates 10, 20, 30, and 40 μg/kg/min for 3 min each. Electrocardiogram (ECG) was monitored continuously and blood pressure was measured at each stage. Criteria for terminating the test were achievement of target heart rate of (220-age) ×0.85 bpm, development or deterioration of wall motion abnormalities, angina, ischemic ECG changes, systolic blood pressure increase to >240 mmHg or decrease to <100 mmHg, and severe ventricular or supraventricular arrhythmias. While for the viability study, low-dose dobutamine infusion was used with incremental dose with maximal rate 20 μg/kg/min.[9]
Transthoracic echocardiography was performed with subjects in the left lateral decubitus position using the GE Vivid E95. Wall motion was assessed by Echocardiography Consultant at National Cardiovascular Center Harapan Kita, using 16 myocardial segment model classified for each segment as normokinetic, hypokinetic, and akinetic. Loops from standard echocardiographic views (three apical view and LV short-axis view at mid-level) were digitally stored at baseline and peak stage of DSE for further analysis. The calculation of parameters of longitudinal deformation was done off line using EchoPac workstation (GE ultrasound) using the automated function imaging method [Figure 1].
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Figure 1: Calculation of longitudinal strain using AFI. (a) Longitudinal strain showing normal strain. (b) Longitudinal strain showing decreased strain. AFI = Automated function imaging
Statistical analysis was performed using IBM-SPSS, version 23 (SPSS Inc, Chicago, IL, USA). Continuous variables were expressed as means and standard deviations in normal distribution data, or, in the setting of nonnormal distribution, as median and interquartile range. Mean values were compared with ANOVA tests and medians were compared with Wilcoxon’s test. The Mann–Whitney test was used for the comparison of deformation changes during DSE. The 2 × 2 tables were used for sensitivity and specificity analysis.
RESULTS
A total of 129 patients performing DSE from February 2021 to July 2022, 17 patients were excluded due to inadequate tracked segments analysis. The final study population was 112 patients that [Table 1] consist of 58 patients referred for diagnostic study and 54 patients referred for viability study. No contrast echo was used.
Table 1: Clinical characteristic and echocardiography parameter of the study population
A total of 3584 myocardial segments were analyzed on the rest and peak stress level (1792 segments for each level). The value of longitudinal strain decreased from normokinetic, through hypokinetic to akinetic segments during both at baseline (−16.33 ± 6.26 in normokinetic, −13.05 ± 6.44 in hypokinetic, and − 8.46 ± 5.69 in akinetic during baseline) and peak stages (−15.37 ± 6.89 in normokinetic, −11.37 ± 5.11 in hypokinetic, and −7.37 ± 3.92 in akinetic segments) [Figure 2].
Figure 2: Comparison of longitudinal strain with visually assessed contractility
In the diagnostic study, the longitudinal strain of segments with visually impaired contractility and segments without impaired contractility were analyzed. At peak dose, in segments with visually observed impaired contractility, the median longitudinal strain was significantly lower than in segments without impaired contractility. The absolute reduction of longitudinal strain between both groups was also observed. In segments with impaired contractility, the changes in the median longitudinal strain were significantly higher than in segments without impaired contractility [Table 2].
Table 2: Comparison of longitudinal strain in segments with and without contractility worsening in the diagnostic study
In the viability study, the longitudinal strain of segments with visually improved contractility and segments without improved contractility were analyzed. At peak dose, in segments with visually observed improved contractility, the median longitudinal strain was significantly higher than in segments without improved contractility. The absolute reduction of longitudinal strain between both groups was also observed. In segments with improved contractility, the changes of median longitudinal strain were significantly higher than in segments without impaired contractility [Table 3].
Table 3: Comparison of longitudinal strain in segments with and without contractility improvement in viability study
In the diagnostic study, the sensitivity and specificity of visual assessment for the absolute decrease of >2%, longitudinal strain were 77% and 32%, respectively. While in the viability study, the sensitivity and specificity of visual assessment for the absolute decrease of ≥2% longitudinal strain was 82% and 37%, respectively.
DISCUSSION
At present, visual assessment of myocardial thickening by an experienced observer remains a gold standard during stress echocardiography. Deformation analysis based on speckle-tracking echocardiography provides quantitative data describing the contractile function of each ventricular segment. This objective and noninvasive approach offers an advantage over the visual assessment of regional systolic function.[8,10]
This study found that the average longitudinal strain of normokinetic segments at rest was lower than that observed in healthy individuals. It can be explained by the fact that our group represented patients with cardiovascular disease and cardiovascular risk factors. We observed that the visual assessment of normokinetic, hypokinetic, and akinetic segments was associated with further reduction of the longitudinal strain value during DSE. Wierzbowska-Drabik et al.[8] also reported that longitudinal strain value significantly decreased further from normokinetic, hypokinetic, and akinetic. Longitudinal strain analysis has advantages for the quantitative assessment of myocardial function at rest and during stress echocardiography. Despite growing acceptance for their use in evaluating global longitudinal strain (GLS), the application of segmental deformation is still waiting for deepened validation.[11-15]
In the diagnostic study, at peak dobutamine dose, segments with impaired contractility had lower longitudinal strain than those without impaired contractility. Further, the absolute reduction of longitudinal strain at peak dobutamine dose relative to baseline was more apparent in segments with impaired contractility than those without impairment. Similar findings were also reported by Wierzbowska-Drabik et al.[8]
In the viability study, at peak dose, segments with improved contractility had higher longitudinal strain than segments without improved contractility. The absolute increase of longitudinal strain at peak dobutamine dose relative to baseline was more apparent in segments with improved contractility than those without improvement. According to our knowledge, there are still limited data about regional longitudinal strain changes value viability study.
Limited studies evaluate the association between regional longitudinal strain changes during DSE and visual kinetic assessment. Some studies about longitudinal strain mostly focused on GLS rather than segmental longitudinal strain. In the study by Joyce et al.,[16] 105 patients after ST-elevation myocardial infarction (STEMI), the GLS was worsened from 16.8% ±0.5% at rest to 12.6% ±0.5% at peak dose of DSE in a subgroup with coronary stenosis. In the subgroup without stenosis, the GLS worsened from 16.6% ±0.4% to 14.3% ±0.3%. The changes of ≥1.9% showed 87% sensitivity for the detection of coronary artery disease (CAD).[16] Another study reported prolonged poststress impairment of GLS in diabetic patients without significant coronary artery stenoses, which may reflect abnormal myocardial mechanics.[17] Among the few published studies, Hwang et al. proposed a cutoff value for absolute GLS of <19% at the recovery stage of DSE for the detection of significant CAD.[18]
The study focused on segmental deformation by Wierzbowska-Drabik et al.[8] found that the absolute value of segmental longitudinal deformation <23% at peak DSE stage and drop of Systolic Longitudinal Strain (SLS) >2% have sensitivity 90% and 76%, respectively, for the detection of visually impaired contractility.[8] At the same time, other viability studies for longitudinal strain found that postdobutamine longitudinal strain was significantly high in a viable group.[4] Ismail and Nammas et al.[5] evaluated viability assessment in 60 patients at least 4 weeks after a STEMI. They found that dobutamine-induced strain and strain rate were considerably higher in viable segments than in nonviable segments. A cutoff value of strain rate ranging from −0.5 to −1.7s−1 was identified for segment viability.[4,5]
In our study, we found for the diagnostic study, the sensitivity of visual assessment for the absolute decrease of >2% longitudinal strain was 77%. While in the viability study, the sensitivity of visual assessment for the absolute decrease of ≥2% and longitudinal strain was 82%. The sensitivity was higher in the viability study than in the diagnostic study. This result is probably in accordance with theory that a frame rate of 50–80 frames/s is an optimal condition for speckle tracking in the resting heartbeat at about 70 beats/min. In a stressed myocardium, the heart rate increase, and the mechanical events become shorter. The acquisition frame rate should thus be increased. Acquiring the left ventricle myocardium at higher heart rates may need higher frame rates. It will be challenging and probably decrease the sensitivity of diagnostic studies compared to viability studies.[19,20]
Compare to widely studied GLS, the clinical potential of regional deformation analysis is still not fully discovered. GLS measurements at rest have modest diagnostic accuracy for predicting CAD among patients with chest pain.[21] There are only sparse data indicating the potential better accuracy of peak GLS over GLS at rest. Finally, in a meta-analysis, the regional longitudinal strain showed greater potential in detecting CAD, although heterogeneity of regional data remains a challenge.[8] Therefore, proving the added value of strain parameters for DSE interpretation would require a dedicated large-sized study, which has not been conducted to date.[8]
The limitations of our study were the frame rate not adjustable to heart rate at peak dose DSE that probably decrease the sensitivity, no contrast echo was used to increase visual sensitivity as it is not yet available in our country, but we have used harmonic imaging for better evaluation of contractility, and there were no data of coronary angiography as the gold standard.
CONCLUSIONS
There is an association between strain analysis and visual assessment of wall motion contractility, during the DSE.
Ethical clearance
This study was approved by Institutional Ethics Committee of National Cardiovascular Center Harapan Kita. Approval No : UM.01.05/2.2.2/8/2022.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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