Patients with typical chest pain were admitted to the chest pain unit (CPU) at Coburg hospital, Germany between February 2019 and August 2020. Three hundred ten patients with stable and unstable angina (TIMI risk score 0-1) were screened. Among them 108 individuals matched the inclusion criteria and gave their written consent to be enrolled in this study (Figure 1). All included subjects were older than 18 years and suited for stress testing. Coronary angiography was performed within 48 hours from admission to the chest pain unit. For the purposes of this analysis, we characterized significant coronary stenosis as ≥ 70% luminal obstruction. Although less severe stenosis might be associated with risk for cardiovascular events, we elected to use a widely accepted standard for defining angiographic significance. Exclusion criteria were elevated troponin level, ST-segment elevation or depression as well as dynamic ECG-changes during admission at CPU, history of coronary artery disease or acute myocardial infarction, coronary artery bypass grafting, chronic total coronary occlusion, significant valvular heart disease, end stage renal failure, or refusal to give the written consent.
After enrollment, Dobutamine stress echocardiography was conducted before invasive assessment with coronary angiography.
Echocardiography
Examinations were performed with a digital ultrasonic device system (Vivid 9, GE Vingmed Ultrasound, Horten, Norway). In harmonic mode 2.0/4.3 MHz with maximal frame per second (FPS) count available at necessary sector width. Range of FPS was from 64 to 112 with mean value 83.
Conventional echocardiography study was done including 2D based M-mode measures of cardiac chambers and Ejection Fraction (EF%), pulsed and continuous wave Doppler studies, Color Doppler study, calculation of ejection fraction by Simpson`s method and analysis of wall motion abnormalities.
Dobutamine Echocardiography
DSE was performed using a standard staged protocol. Dobutamine was infused through a peripheral infusion line intravenously with a mechanical pump starting at dose of 10 mg/kg/min. The dose was increased at 3-min intervals to 20, 30, and 40 mg/kg/min with intravenous atropine up to 2 mg given, if necessary, to augment the heart rate response. Blood pressure and electrocardiogram were monitored continuously. Criteria for terminating the test were achieving a target heart rate response of 85% of the age-predicted maximum, development of wall motion abnormality, angina pectoris, severe ischemic electrocardiographic changes, systolic blood pressure >240 mm Hg, abnormal blood pressure reaction during stress, or significant arrhythmia.
Images were obtained by two experienced echocardiographers with patients in the lateral decubitus position. Standard 2D grayscale images of three standard apical views (four-chamber, two-chamber, and apical long-axis) and parasternal long-axis and parasternal short-axis views at the level of mitral valve, papillary muscles, and apex were acquired at rest, at a dobutamine dose of 20 mg/kg/min, at peak stress, and at recovery 1 min after stress. Per protocol, a cine image of one representative cardiac cycle per stage and view was digitally stored for later offline analysis. To optimize speckle-tracking at high heart rate, images were individually optimized for left ventricular analysis, and the frame rate was increased to achieve at target of 60 to 90 frames/sec without compromising endocardial border detection. Wall motion was analyzed visually by two experienced echocardiographers blinded to the results of other investigations. The operators repeated the evaluation of wall motion abnormalities of 20 random studies at the end of enrollment to assess intra- and interobserver variation.
Quantification of strain measurements
Echocardiographic images were obtained prior to coronary angiography. Three uninterrupted cardiac cycles were applied for each of three standard apical (two-, three-, and four-chamber) views and were kept for off-line longitudinal strain analysis, using EchoPAC software (GE Ultrasound). For assessment of longitudinal strain, we recorded standard 2D ultrasound images with a frame rate between 60 and 90 frames per second (fps) from the standard views. The endocardium was manually marked out from selected cineloops of apical view images. A further manual adjustment of the region of interest was applied after visual evaluation. The Full image was excluded if > 2 segments were poorly tracked. Speckle tracking was carried out on all three apical views of rest images and negative global systolic longitudinal strain was estimated. The average of GLS in apical 4, 3, and 2 chamber imaged was used for our analysis.
Statistical Analysis
All statistical analyses were performed using SPSS 21.0 (SPSS Inc, Chicago, Illinois). Continuous variables are expressed as mean ± standard deviation and categorical variables are expressed as counts and %. Diagnostic measures including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The receiver operating characteristic (ROC) curve analyses were performed to compare the diagnostic performance of myocardial strain at rest and under stress. Pearson’s correlation was used to assess the strength of association among variables. Inter- and intra-observer reproducibility values were evaluated through the intra-class correlation coefficient (ICC). For all analyses, p < 0.05 was considered to be statistically significant.