Abstract
Objective
The study aims to determine the importance of global longitudinal strain echocardiography in diagnosing high-risk coronary artery disease in patients with chronic stable angina.
Methods
This study was a prospective observational study with a sample size of 101 patients aged above 18 years presenting with chronic stable angina to our hospital who were treadmill test positive. All the patients underwent two-dimensional speckle tracking echocardiography for measuring global longitudinal strain and an invasive coronary angiography. Treadmill test and global longitudinal strain were compared to see the sensitivity and specificity of both tests for diagnosing high-risk coronary artery disease. Receiver operating characteristic curve analysis was used to identify the ideal cutoff of global longitudinal strain for diagnosing high-risk coronary artery disease.
Results
In the total of 101 participants, global longitudinal strain was reduced significantly in participants with high-risk coronary artery disease than those without coronary artery disease [18.43 ± 1.97 vs. 15.78 ± 1.46, P < .001]. For treadmill test with Duke treadmill score cutoff as −3, it has a sensitivity of 78.9% and a specificity of 63.6% as compared to global longitudinal strain, which has a sensitivity of 71.9% and a specificity of 97.7%. Receiver operating characteristic curve analysis showed that the optimal cutoff for the identification of coronary artery disease for global longitudinal strain was −17.25% (sensitivity of 80.7% and specificity of 93.2%), confidence interval 0.76-0.89, area under curve = 0.895, P < .001.
Conclusion
The present study showed that resting global longitudinal strain is significantly reduced in patients with high-risk coronary artery disease, hence, when done in addition to stress testing in patients with chronic stable angina, it improves accuracy in diagnosing high-risk coronary artery disease.
Introduction
Worldwide, coronary artery disease (CAD) is the leading cause of death. Chronic stable angina (CSA), one of the initial signs of obstructive CAD, affects 50% of people and places a heavy burden on the medical system. 1
In detecting left ventricular (LV) dysfunction, strain echocardiography is more sensitive than left ventricular ejection fraction (LVEF). The subendocardial longitudinal muscle fibers are particularly susceptible to ischemia, making the evaluation of global longitudinal strain (GLS) at rest more effective than wall motion analysis in acute coronary syndrome (ACS). Speckle tracking is the method of choice for the assessment of LV strain and is particularly useful in settings when LVEF is normal or wall motion abnormalities are not visible.2-4
Left main coronary artery (LMCA) disease is a recognized poor prognostic factor in ischemic heart disease, and significant disease of this artery can lead to myocardial ischemia and death. 5 Triple vessel disease (TVD) is also a high-risk group, and thus urgent revascularization is frequently required to improve long-term prognosis in this subset of patients with symptoms.6-8 Strain is the percentage change in length or shortening brought on by cardiac contraction that occurs with each heartbeat (Figures 1 and 2).9-12
Strain is the Percentage Change in Length or Shortening Brought on by Cardiac Contraction that Occurs with Each Heartbeat.
Types of Left Ventricular (LV) Strain are Longitudinal, Circumferential, and Radial Strains.
Despite criticism for its relatively poor sensitivity and specificity, the exercise treadmill test (TMT) is advised as one of the first diagnostic procedures for patients with suspected CSA. 2 However, TMT is not appropriate for many patients and has limited sensitivity and specificity, particularly in women. Although they come at a higher cost, imaging tests, including nuclear imaging, computed tomography, and exercise or pharmacologic stress echocardiography, offer increased diagnostic value and accuracy, but they may not be easily accessible.
Global longitudinal strain obtained from speckle tracking is a reproducible, sensitive, and dependable indicator of global LV function that may be more predictive than EF. Speckle tracking techniques can evaluate typical ischemic subendocardial damage, that is, longitudinally oriented myocardial fibers that are found subendocardially, which is the region most vulnerable to ischemia. 3
This study is intended to determine the role of resting GLS imaging by speckle tracking in diagnosing high-risk CAD in patients presenting with CSA.
Methods
Our study is a prospective observational study in patients aged above 18 years presenting with CSA to Goa Medical College who were TMT positive.
Inclusion criteria: All patients studied were aged >18 years, had CSA and TMT positivity (Bruce protocol), had sinus rhythm without conduction abnormalities or ventricular premature complexes (VPCs), and had a normal LVEF > 55% with no regional wall motion abnormalities (RWMA) at rest.
Exclusion criteria: Patients with glomerular filtration rate (GFR) ≤ 60 or who have contraindications for coronary angiography (CAG), moderate-to-severe valvular disease, wall motion abnormalities at baseline, not achieving target heart rate (THR) on exercise TMT, left bundle branch block (LBBB) or baseline ST-T changes on electrocardiogram (ECG), suboptimal images on echo, high-grade atrioventricular (AV) block, hypertrophic cardiomyopathy (HCM), and pregnant patients.
All patients underwent 2D echocardiography with strain imaging to get the peak systolic GLS. Percutaneous CAG was performed in all 101 patients.
Exercise TMT was performed in all patients according to the Bruce protocol. Significant ST depression was defined as ≥1 mm of horizontal or down-sloping ST depression (J point + 80 ms) or ≥1 mm ST‑segment elevation in non-Q leads.
Duke treadmill score (DTS) was calculated for all patients.
DTS = Exercise time − (5 × ST deviation) − (4 × exercise angina).
Strain Echocardiography
The Vivid IQ (GE Vingmed; Horten, Norway) system was used to perform standard 2D echo examinations. Measurements of heart volumes, dimensions, and LVEF were part of the examination. Bull’s eye display was generated by an automated algorithm from the A4C, A3C, and A2C views using a 17-segment model.
For the global study of peak segmental longitudinal strain (PSLS) of the LV, we used a conventional S5-1 MHz transducer to produce 2D grayscale harmonic pictures. Every image was captured at 60-100 frames per second. Three cardiac cycles in a row were digitally stored. Aortic valve closure time was established in the apical three-chamber, two-chamber, and four-chamber views and used as reference values. We identified three endocardial locations in each apical view: one at the LV apex at the end-systolic phase and two basal LV points on either side of the mitral annulus. Next, using a speckle tracking technique, the program automatically identified the endocardial, myocardial, and epicardial layers. The tracking quality was verified, and the segmental PSLS in bull’s eye display was then produced by an automated method. The average of each of LV’s 17-segmental PSLSs was referred to as the global PSLS.
Coronary Angiography
An experienced interventional cardiologist evaluated the angiographic results in two orthogonal planes. Using the American Heart Association’s classification system for percentage of luminal diameter stenosis, the criterion of 70% stenosis for the three epicardial vessels and 50% for the LMCA was used to evaluate the number of affected vessels.
Angiographically, patients were grouped accordingly as follows: high-risk CAD was defined as LMCA luminal diameter stenosis ≥50%, TVD with luminal diameter stenosis ≥70%, or LM equivalent CAD was considered when a luminal diameter stenosis of ≥70% was present in the proximal LAD and proximal left circumflex (LCX) artery in the absence of LM CAD.7, 8 The remaining were grouped together as normal or low-risk CAD.
Statistical Analysis
Sample size (N) of 101 was calculated using the Cochran’s formula, using a prevalence of CAD being 7%. 16
Statistical analyses were done with IBM SPSS Statistics (IBM Corporation, Armonk, New York, USA). Categorical variables were summarized as frequencies and percentages, while continuous variables were expressed as mean, median, standard deviation, and quartiles. The chi-square test was used for comparisons between groups for categorical variables. For continuous variables, the Student’s t-test was used with P value <.05 to be considered significant. To identify ideal cutoffs, the receiver operating characteristic (ROC) curve was used, and the area under the curve (AUC) was measured for the accuracy of the test.
Results
A total of 101 participants were enrolled with a mean age of 56.56 ± 9.07 years, and 26% of them were female (Table 1). A total of 27 participants had normal coronaries, and 30 had low-risk CAD. Mean age was 56.56 ± 9.07 with 5 patients below 40 years of age, and 8 being >70 years. The most common risk factor was hypertension (HTN), which was present in 75% of the high-risk CAD patients, followed by diabetes mellitus (DM) in 59.1% of the high-risk CAD patients. In total, 19.8% of the patients were smokers. High-risk CAD was present in 44 of 101 participants (Table 2). Smokers had a higher incidence of high-risk CAD compared to non-smokers.
Association of Patient Characteristics with Low-/High-risk Coronary Artery Disease (CAD).
Angiographic Findings.
Longitudinal Strain and Coronary Artery Disease
High-risk CAD patients had significantly reduced GLS than those without CAD [15.78 ± 1.46 vs. 18.43 ± 1.97, P < .001]. Comparison of the TMT(DTS) between the two groups shows that TMT(DTS) is significantly lower in high-risk CAD (−4.64 ± 3.39 vs. −0.65 ± 3.81) group and is statistically significant with a P value of <.001 (Table 3).
Comparison of TMT and GLS in Patients with High-risk CAD Versus Low-risk or Normal.
Diagnostic Accuracy
For TMT, with a DTS cutoff of −3, it has a sensitivity of 78.9% and a specificity of 63.6%. Compared with GLS, which had a sensitivity of 71.9% and a specificity of 97.7%. TMT and GLS combined yielded the best overall diagnostic performance (Table 4).
Diagnostic Accuracy.
Receiver Operating Characteristic Curve Analysis
Receiver operating characteristic analysis for GLS identified an optimal cutoff value of −17.25% for the detection of high-risk CAD (sensitivity of 80.7% and specificity of 93.2%, AUC = 0.895, P < .001, confidence interval [CI] 0.76-0.89, Figure 3).
Discussion
Using CAG as the reference standard, GLS measured by speckle tracking at rest has excellent diagnostic accuracy for high-risk CAD in patients with CSA and normal EF. Using the automated function imaging (AFI) approach to measure longitudinal 2D strain, we discovered that patients with LM or TVD CAD had considerably worse systolic function (as measured by PSLS values) than patients with less severe or no CAD.
This study emphasizes the requirement to refine the existing diagnostic approach of using exercise TMT as the initial test in patients with CSA, who can exercise and have a readable ECG. Despite its limitations, TMT remains easily available, inexpensive, prognostically valuable, and recommended as a first-line investigation. 13 In our study, the diagnostic accuracy of TMT was modest at best, with a sensitivity of 78.9% and a specificity of 63.6%, similar to many previous studies across varying populations. 17 GLS offers a higher diagnostic accuracy for identifying high-risk CAD than TMT. Overall diagnostic accuracy was highest when TMT and GLS were combined. GLS has a sensitivity of 71.9% and a specificity of 97.7% in our study, which is comparable to the diagnostic accuracy of a number of other noninvasive imaging tools, like nuclear imaging and stress echo, and is available at a far lower cost.
Our study’s findings indicate that GLS imaging by speckle tracking, at rest, should be added for patients with CSA undergoing TMT to improve diagnostic accuracy.
To identify high-risk CAD, the cutoff for GLS was −17.25% (sensitivity of 80.7% and specificity of 93.2%). With increasing severity of CAD, the GLS values decreased, corroborating findings from previous studies evaluating longitudinal strain in patients with CSA, like Choi et al., who studied 96 patients and found that the optimal cutoff value GLS was −17.9%, for the detection of high-risk CAD. 15 Similarly, Bala et al. evaluated 150 patients with CSA with CAG and reported an optimal GLS cutoff of −17.75% for the detection of CAD. 18
A subtle GLS reduction in patients with LM or TVD CAD might provide an important diagnostic clue and a higher pretest probability for the presence of high-risk CAD. The feasibility of using GLS alone in situations when TMT is not possible or contraindicated needs further research.
Limitations
The sample size, being modest in a single-center study, means that the findings should be interpreted accordingly (N = 101). The apparent sensitivity of the study may have increased, as the selected subjects for coronary catheterization had a relatively higher probability of CAD. The applicability of these findings is limited to patients with normal systolic function at rest. The diagnostic accuracy of strain analysis depends on image quality, which excluded a number of participants from enrollment in the study.
Conclusion
In CSA patients with normal EF, resting 2D echocardiographic GLS provides excellent diagnostic accuracy for high-risk CAD. TMT alone has modest diagnostic value, and further research is needed to establish whether GLS alone can reliably diagnose CAD. Even when resting wall motion and LVEF are normal, the current study showed that individuals with severe CAD, especially LM or TVD, have considerably lower resting GLS. Therefore, in order to identify high-risk CAD early in patients with CSA, GLS measurement must be performed in addition to stress testing.
Key Messages
What is Already Known?
In patients with CSA, it is already known that exercise TMT can be used to diagnose high-risk CAD with modest sensitivity and specificity.
What this Study Adds?
In patients with CSA, GLS by two-dimensional speckle tracking echocardiography (2D-STE), along with exercise TMT, increases the accuracy of diagnosing high-risk CAD.
Footnotes
Declaration of Conflict of Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical Approval
This research was approved by the ethical committee of our institute (ref no. GMCIEC/2023/26).
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Patient Consent
Written consent was obtained from the patient for the conduct of the study.
