|Year : 2019 | Volume
| Issue : 3 | Page : 126-130
Two-dimensional speckle tracking echocardiography as a predictor of significant coronary artery stenosis in female patients with effort angina who are treadmill test positive: An angiographic correlation
Suresh Madhavan MD, DM , Jayaprasad Narayanapillai MD, DM , Jose Sebastian Paikada MD, DM , K Jayaprakash, VL Jayaprakash MD, DM
Department of Cardiology, Government Medical College, Kottayam, Kerala, India
|Date of Web Publication||31-Jul-2019|
Dr. Suresh Madhavan
Department of Cardiology, Government Medical College, Kottayam - 686 008, Kerala
Source of Support: None, Conflict of Interest: None
Aim: This study aims to determine the diagnostic accuracy of two-dimensional speckle tracking echocardiography (2DSTE) in predicting the angiographic severity of coronary artery disease (CAD) in female patients with effort angina who are treadmill test (TMT) positive and for risk stratification, to decide on the need for invasive management. Materials and Methods: A total of 1000 female patients with effort angina who are TMT positive and are recommended for coronary angiogram based on standard treatment guidelines are subjected to 2DSTE and global longitudinal strain (GLS) score is obtained. Angiographic correlation was sought between lesion severity and GLS score. Results: The average age of patients included in the study is 55 years. Average Duke Score is −2. Average GLS score −15. 56% of patients had a significant coronary lesion of >70% in at least one of the coronary arteries. The optimum cutoff GLS score to predict significant coronary lesion is −17.5. Conclusion: GLS by 2DSTE correlates well with angiographic severity of CAD and can predict significant coronary lesion with a sensitivity of 94% and specificity of 76% in female patients with effort angina. Thus, GLS by 2DSTE can be used as a noninvasive screening test in predicting significant coronary artery stenosis and can complement TMT in risk stratification and in selecting patients for coronary angiogram.
Keywords: False-positive treadmill test, global longitudinal strain, speckle tracking echocardiography, stable coronary artery disease
|How to cite this article:|
Madhavan S, Narayanapillai J, Paikada JS, Jayaprakash K, Jayaprakash V. Two-dimensional speckle tracking echocardiography as a predictor of significant coronary artery stenosis in female patients with effort angina who are treadmill test positive: An angiographic correlation. J Clin Prev Cardiol 2019;8:126-30
|How to cite this URL:|
Madhavan S, Narayanapillai J, Paikada JS, Jayaprakash K, Jayaprakash V. Two-dimensional speckle tracking echocardiography as a predictor of significant coronary artery stenosis in female patients with effort angina who are treadmill test positive: An angiographic correlation. J Clin Prev Cardiol [serial online] 2019 [cited 2020 Mar 29];8:126-30. Available from: http://www.jcpconline.org/text.asp?2019/8/3/126/263834
| Introduction|| |
Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide. Exercise stress test or “treadmill test” (TMT) is the most common initial noninvasive test for evaluating myocardial ischemia. TMT in women has a relatively low diagnostic yield for CAD compared to men, especially when symptoms are atypical or nonspecific. TMT has been shown to correlate with underlying CAD. False-positive results can occur in female subsets. Women tend to have a greater release of catecholamines which may cause coronary vasospasm and augment exercise-induced ST-T changes.
Echocardiography is an important diagnostic tool in CAD. The left ventricular (LV) longitudinal mechanics at rest may be attenuated in patients with CAD and can be assessed with two-dimensional speckle tracking echocardiography (2DSTE). It is unknown whether myocardial strain analysis at rest in patients with effort angina predicts the presence of significant CAD.
Aims of the study were to determine the diagnostic accuracy (sensitivity and specificity) of 2DSTE in predicting the angiographic severity of CAD in female patients with effort angina who are TMT positive and to risk stratify TMT-positive female patients with effort angina based on global longitudinal strain (GLS) assessed by 2DSTE, to decide on the need for invasive management.
Prospective study was done from February 2015 to March 2018, at the Department of Cardiology, Government Medical College, Kottayam, Kerala, India. The study population included 1000 female patients with a positive exercise stress test. All these patients were either suspected or proven to have stable CAD but without a history of an acute coronary syndrome (ACS) who were referred for coronary angiography (CAG) after TMT.
Female patients with effort angina who are TMT positive and awaiting angiogram were included in the study. Patients with previous ACS, LV dysfunction, poor acoustic window, significant valvular heart disease, previous heart surgery, atrial fibrillation, bundle branch block with QRS width >120 ms, wall motion abnormality, those with a history of chemotherapy or radiotherapy were excluded. Study tools included semi-structured pro forma, echocardiography machine equipped with 2D-Speckle tracking software, Philips Allura Xper FD C-arm machine for fluoroscopy to perform CAG.
Female patients with effort angina who were TMT positive and were recommended for CAG based on the standard treatment guidelines were selected and counseled regarding the 2DSTE before angiogram. Echocardiography was performed before CAG, using a Vivid E9 scanner (GE) with a phased-array transducer. Three consecutive cardiac cycles from the three standard apical planes (4-chamber, 2-chamber, and apical long-axis) obtained by conventional 2D grayscale echocardiography or a single-beat acquisition using 4D echo loops was digitally stored and later analyzed offline using Echo Pac version 7.0.0 (GE Vingmed Horten, Norway). GLS was measured by 2DSTE using a 17 LV segment model. For each segment, the peak negative systolic strain value (representing maximum segmental systolic shortening) peak positive early strain (representing maximum segmental systolic lengthening) duration of early systolic lengthening and postsystolic shortening was recorded by fully automatic software.
CAG was performed by the percutaneous radial or femoral approach. CAGs were obtained for each coronary vessel in ≥2 projections, and stenosis with ≥50% reduction of the arterial lumen area was considered significant as defined by coronary artery surgery study. The analysis of the CAG was performed visually by an experienced operator who was blinded to the results of the echocardiographic examinations.
Quantitative variables were expressed as mean and standard deviation. Qualitative variables were expressed as proportion. The comparison of quantitative variable between two groups was analyzed by independent sample t-test or Mann–Whitney U-test according to the nature of the data. Comparisons of quantitative variable among >2 groups were analyzed by ANOVA. Between groups comparisons of qualitative variables were analyzed by Chi-square test. For the diagnostic test evaluation sensitivity, specificity, positive predictive value, and negative predictive value were calculated. P < 0.05 was considered as statistically significant. Data analysis was performed using SPSS Statistics for Windows, Version 22.0 (SPSS Inc., IBM, Chicago, USA).
| Results|| |
A total of 1000 TMT-positive female patients were evaluated over a period of 3 years (February 2015–March 2018). Effort angina was the predominant symptom. About 70% of patients were in New York Heart Association class II. There were no regional wall motion abnormalities or LV dysfunction in any of the patients. The age of patients included in the study ranged from 38 to 72 years with the average being 55 years. The most common risk factor associated was hypertension [Figure 1]. Six hundred and seventy patients were hypertensive and 640 were diabetic. Dyslipidemia was observed in 460 patients. Of the 640 patients with diabetes, 510 (79%) had a significant coronary lesion. Of the 360 nondiabetic patients, only 60 (16%) had a significant coronary lesion. Of the 670 hypertensive patients, 370 (55%) had a significant coronary lesion. Of the 330 nonhypertensive patients, 200 (60%) had a significant coronary lesion. Six hundred patients had a creatinine clearance >90 ml/min and 20 patients had a creatinine clearance <30 ml/min.
2D-speckle tracking derived peak systolic GLS score of the patients ranged from −9 to −22, with average being –15.5 [Figure 2]. About 57% of patients had a significant coronary lesion of ≥50% severity in at least one of the coronary arteries. 43% of patients had minor CAD. Mean GLS score (taken as GLS cut off) for left main coronary artery (LMCA), multivessel disease and single-vessel disease were −10.6, −12.5, and −16, respectively [Figure 3]. This mean GLS score obtained was taken as the cutoff that may predict the disease of a particular vessel. Mean GLS cutoff score in patients with isolated involvement of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA) were −15, −16.4, and − 16.6, respectively [Figure 4]. Patients with a GLS >−18.85 had no significant coronary lesion and those with a GLS <−12.5 had multivessel disease. GLS ≥−17.5 could predict 94% of significant coronary lesion [Table 1] and [Table 2].
|Figure 3: (a) Global longitudinal score cutoff for different vessel involvement. (b) Global Longitudinal Score cut off for different vessel involvement|
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|Figure 4: Receiver operating characteristic curve for sensitivity and specificity|
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Sensitivity of GLS in predicting significant CAD in TMT positive female patients is 94% and specificity 76%. The positive predictive value is 84% and negative predictive value is 90%. The optimum cutoff value of GLS score to predict coronary lesion is −17.5 [Figure 4].
| Discussion|| |
Exercise stress test or TMT is one of the in-expensive investigations available for evaluating myocardial ischemia., TMT has a relatively low sensitivity (80%) and specificity (75%), especially in single- and double-vessel disease., It is important to discriminate whether an ischemic response in TMT is a false-positive result, to avoid unnecessary referrals for invasive CAG. A positive TMT is defined as ST-segment depression of 1 mm or greater of “J”-Point from the PQ junction with a relatively flat ST-segment slope (<0.7–1 mv/s), or 1 mm or more depression 80 ms after “J” point in three consecutive leads with a stable baseline.
TMT in women has a relatively low diagnostic yield for CAD compared with men, especially when symptoms are atypical or nonspecific. TMT has been reported to have sensitivity of 70% and specificity of 61% for the detection of CAD in women.,, The relative lack of evidence regarding the diagnostic accuracy of TMT in females is challenging. TMT in women has questionable reliability both with a cardiologist and the primary care physician.
Women tend to have a greater release of catecholamines during exercise, which could potentiate coronary vasospasm and augment the incidence of abnormal exercise results. False-positive results have been reported to be more common during menstruation and preovulation. CAG is used to establish the presence or absence of coronary artery stenosis due to CAD.,, In a review of nine studies correlating exercise-induced ST-segment changes with angiographic findings in female patients, the prevalence of CAD ranged from 18% to 40%. The Duke Treadmill Score is a point system to predict 5-year mortality based on treadmill electrocardiography (ECG) stress testing in patients without known CAD. The exercise time is based on using the standard Bruce protocol.
The subendocardium is the area of LV most vulnerable to the effects of hypoperfusion and ischemia. LV longitudinal mechanics at rest may, therefore, be attenuated in patients with CAD. Ischemic myocardium with reduced active force will lengthen when LV pressure rises during early systole before onset of systolic shortening. Because strain and strain rates are homogeneously distributed across the myocardium; the detection of even subtle changes in either measure suggests myocardial dysfunction.
Strain is a measure of tissue deformation, and strain rate is deformation rate. As the ventricle contracts, muscle shortens in the longitudinal and circumferential dimensions (a negative strain) and thickens or lengthens in the radial direction (a positive strain). Strain rate measures the time course of deformation and is the primary parameter of deformation. STE is a new technique based on tracking the movement of natural acoustic markers (speckles) present on standard grey scale images. A speckle is a unique acoustic pattern resulting from the interaction of ultrasound energy with tissue. Speckle is caused by scattering, reflection, and interference of ultrasound beam with myocardial tissue. Strain can measure myocardial deformation; an intrinsic mechanical property of the myocardium. The assessment of strain reflects myocardial systolic function more directly than conventional cavity based echocardiographic parameters. Strain and strain rate parameters are relatively independent of wall tethering and loading conditions. In healthy individuals, average peak systolic LV longitudinal strain assessed by speckle tracking technique is in the range of −18–−20. The ischemic myocardium is characterized by reduced regional systolic longitudinal strain.
In patient with CAD, the presence of coronary artery occlusions might be identified by STE. Myocardial strain shows regional postischemic dysfunction in systole and diastole and may become a useful diagnostic tool in patients presenting with chest pain with a normal ECG. Jamal et al. in their study showed that strain rate and strain can better assess segmental dysfunction severity than myocardial velocities alone after an acute myocardial infarction. Choi et al. reported that a midsegmental and basal segmental peak longitudinal strain cutoff value of –17.9% was capable of discriminating severe 3 vessel disease or LMCA disease from diseases with less severity with a sensitivity of 78.9% and specificity of 79.3%.
STE also offers the unique opportunity to assess torsional deformation of the LV. Indeed, LV contraction not only generates shortening and thickening but also torsion due to the orientation of LV muscle fibers varying across the LV wall-from a right-hand helix in the subendocardium, through circumferential fibers in the midwall, to a left hand helix in the subepicardium. The shortening of obliquely oriented LV fibers generates a wringing motion responsible for LV torsion. During the cardiac cycle, a systolic twist and an early diastolic untwist are generated by opposite basal and apical rotations. When viewed from the apex during systole, the apex rotates counterclockwise relative to the base. Torsion, or twist, plays an important role in ejection and the storage of potential energy at end systole, the release of this energy as elastic recoil during early diastole assists ventricular suction. Torsion has been studied in clinical and experimental studies, and it is well established that LV rotation is sensitive to changes in LV function. It is, therefore, of obvious clinical interest to assess LV torsion noninvasively. Until recently, tagged cardiovascular magnetic resonance (CMR) was the only method capable of assessing LV torsion noninvasively. It is also not surprising that it is currently considered as the reference. With the advent of STE, LV torsional deformation can also be looked at with echocardiography, thus permitting a broader use of this new functional approach. The TMQ (Qlab, Philips, Massachusetts, USA) allows for the assessment of LV torsion and untwisting in subendocardium, midwall, and subepicardial layers. Estimates of LV torsion and LV twisting velocities measured by STE in patients with or without cardiomyopathy are well correlated to those measured by tagged CMR.
Subclinical impairment of the LV has been demonstrated by 2DSTE in the setting of many disorders, including hypertension, diabetes mellitus, atrial fibrillation, and heart failure, with preserved ejection fraction. Smaller previous studies have also demonstrated impaired peak longitudinal strain in patients with CAD.
The myocardial fibers most susceptible to ischemia are the longitudinally orientated fibers that are located subendocardially. Measurements of longitudinal motion and deformation are therefore the most sensitive markers of CAD. It was previously demonstrated that color tissue Doppler imaging (TDI) velocities are sensitive markers of longitudinal dysfunction caused by CAD and that these TDI velocities can improve the diagnostics of CAD. However, local myocardial velocities obtained by TDI have the disadvantage of being influenced by heart movement and tethering to adjacent segments, which makes 2D strain echocardiography (2DSE) more suitable for diagnosing impaired segmental longitudinal mechanics caused by CAD. Furthermore, in previous studies, GLS had a higher area under the curve for diagnosing CAD compared with TDI velocities.
Despite preserved LV ejection fraction (LVEF), the longitudinal systolic function of the LV in terms of GLS proved to be impaired among patients with CAD. Previous studies have demonstrated a similarly early impairment of the longitudinal systolic function in patients with CAD and preserved regional wall motion in addition to a normal LVEF. However, the previous studies on the predictive power of 2DSE have included patients with various types of CAD ranging from patients admitted with ACS to patients without chest pain but in high risk of CAD determined from their Duke clinical score. None of the previous studies have included an exercise test in the diagnostic workup. This makes our population more homogeneous, less confounded by difference in phenotype, and mimics the challenging clinical setting better.
In addition, 2DSE seemed to be able to rule out or identify patients at high risk, determined by the presence of left main stenosis or multivessel disease. Revascularization in these high-risk patients has been proven to improve prognosis. GLS declined incrementally with increasing severity of CAD defined by increasing number of stenotic coronary vessels. Therefore, the risk of multivessel disease increases with decreasing GLS. The basal myocardial segments seem more affected by proximal coronary stenosis, which are known to be the most dangerous.
According to our data, family history of premature CAD was present in 90 patients. About 57% of patients had a significant lesion of >70% in at least one of the coronary arteries. Hence, the prevalence of significant CAD in our study is 57%. Out of 640 patients with diabetes, significant coronary lesion was present in 510 patients. Out of the 360 nondiabetic patients, 60 were having a significant coronary lesion. Out of 670 hypertensive patients, 370 were having significant coronary lesion. 200 out of 330 nonhypertensive patients were having a significant coronary lesion. The average Duke TMT score of the patients was −2 and ranged from 4 to −13. The GLS score of the patients ranged from −9 to −22 with average being −15.
A cutoff GLS score of − 17.5 had a sensitivity of 94% and specificity of 76% in predicting significant CAD in TMT-positive female patients. The positive predictive value was 84% and negative predictive value was 90%. P < 0.001 is considered statistically significant. This is in concordance with a previous study conducted by Singh et al. Patients with a GLS more than −18.85 had no significant coronary lesion and those with a GLS <−12.5 had multivessel disease. Compared to Duke Score, GLS score showed a better correlation with a significant coronary lesion. About 34% of patients with significant CAD had multivessel disease and single-vessel disease was noted in 56% of patients. The GLS cutoff for predicting significant LMCA disease was −10.6 and this is in concordance with a previous study which was conducted by Choi et al.
About 33% of patients had an estimated glomerular filtration rate <90 ml/min and showed a higher cutoff for predicting significant CAD. This can be explained by the fact that chronic kidney disease alone can impair the GLS. Among patients with single-vessel disease LAD was involved in 40% of patients and GLS cutoff was −15. In 36% of patients with single-vessel disease, RCA was involved and the GLS cutoff was −16.6. In 24% of patients with single-vessel disease, LCX was involved and the GLS cutoff was −16. The higher GLS cutoff among LAD patients may be explained by the fact that LAD supplies more myocardium.
| Conclusions|| |
GLS by 2DSTE correlates well with angiographic severity of CAD and can predict significant coronary lesion with a sensitivity of 94% and specificity of 76% in female patients with effort angina. The optimum cutoff value of GLS score to predict significant coronary lesion in this study is −17.5. GLS by 2DSTE can be used as a noninvasive screening test in predicting significant coronary artery stenosis and can complement TMT in risk stratification and in selecting patients for CAG.
Although the patients were enrolled consecutively, selection bias may have occurred. Only patients without prior history of heart disease, patients with a normal LVEF, and patients with a normal resting ECG were enrolled. Hence, the patients enrolled in the present study may have a relatively low risk of CAD. Despite this limitation, 2DSTE performed at rest was found to be an independent predictor of CAD, and 2DSTE would probably be an even stronger predictor in patients with a higher risk of CAD. Other limitations were lack of intracoronary imaging modalities and fractional flow reserve. Radial and circumferential strains were not measured. Torsion and twist mechanics were also not studied.
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| References|| |
Writing Group Members, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, et al.
Heart disease and stroke statistics-2010 update: A report from the American Heart Association. Circulation 2010;121:e46-215.
Celermajer DS, Chow CK, Marijon E, Anstey NM, Woo KS. Cardiovascular disease in the developing world: Prevalences, patterns, and the potential of early disease detection. J Am Coll Cardiol 2012;60:1207-16.
Froelicher VF Jr., Yanowitz FG, Thompson AJ, Lancaster MC. The correlation of coronary angiography and the electrocardiographic response to maximal treadmill testing in 76 asymptomatic men. Circulation 1973;48:597-604.
Bruce RA, DeRouen TA, Hossack KF, Blake B, Verona RN. Value of maximal exercise tests in risk assessment of primary coronary heart disease events in men. Am J Cardiol 1980;46:371-8.
Junker J, Meyer A, Flake D. Is exercise testing helpful for detecting heart disease in women? J Fam Pract 2004;53:308-31.
Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999;83:660-6.
Dere, Burnard, David. Diagnostic accuracy of TMT in clinical subsets of women. Circulation 1982;65:1465-72.
Glaser, Clark. Interpretation of exercise test results in women. Pract Cardiol 1998;14:85-95.
Sketch MH, Mohiuddin SM, Lynch JD, Zencka AE, Runco V. Significant sex differences in the correlation of electrocardiographic exercise testing and coronary arteriograms. Am J Cardiol 1975;36:169-73.
Morise AP, Haddad WJ, Beckner D. Development and validation of a clinical score to estimate the probability of coronary artery disease in men and women presenting with suspected coronary disease. Am J Med 1997;102:350-6.
Ismail M, Andrabi SM, Rashid A, Jan A, Ashraf M, Kumar R. Coronary artery profile on coronary angiography in TMT positive female patients. J Evol Med Dent Sci 2015;4:16510-12.
Liang HY, Cauduro S, Pellikka P, Wang J, Urheim S, Yang EH, et al.
Usefulness of two-dimensional speckle strain for evaluation of left ventricular diastolic deformation in patients with coronary artery disease. Am J Cardiol 2006;98:1581-6.
Nucifora G, Schuijf JD, Delgado V, Bertini M, Scholte AJ, Ng AC, et al.
Incremental value of subclinical left ventricular systolic dysfunction for the identification of patients with obstructive coronary artery disease. Am Heart J 2010;159:148-57.
Williams RI, Payne N, Phillips T, D'hooge J, Fraser AG. Strain rate imaging after dynamic stress provides objective evidence of persistent regional myocardial dysfunction in ischaemic myocardium: Regional stunning identified? Heart 2005;91:152-60.
Jamal F, Kukulski T, Sutherland GR, Weidemann F, D'hooge J, Bijnens B, et al.
Can changes in systolic longitudinal deformation quantify regional myocardial function after an acute infarction? An ultrasonic strain rate and strain study. J Am Soc Echocardiogr 2002;15:723-30.
Choi JO, Cho SW, Song YB, Cho SJ, Song BG, Lee SC, et al.
Longitudinal 2D strain at rest predicts the presence of left main and three vessel coronary artery disease in patients without regional wall motion abnormality. Eur J Echocardiogr 2009;10:695-701.
Singh J, Kannan A, Saleh A, Abidov A. Diagnostic accuracy of 2D-speckle tracking echocardiography for detection of obstructive coronary artery disease. J Am Coll Cardiol 2013;61 Suppl 10:E1008.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]