|Year : 2019 | Volume
| Issue : 2 | Page : 94-101
Three dimensional echocardiography in non ST elevation acute coronary syndrome in North India (3D-EINSTEIN) - A single centre prospective study
Dibbendhu Khanra1, SK Sinha2, Pradyot Tiwari3, MM Razi2, Puneet Aggrawal2, Shishir Soni1, CM Verma2, Ramesh Thakur2, Bhanu Duggal1
1 Department of Cardiology, All Institution of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Cardiology, LPS Institution of Cardiology, Kanpur, Uttar Pradesh, India
3 Department of Cardiology, Apex Heart Institute, Ahmedabad, Gujarat, India
|Date of Submission||25-Mar-2019|
|Date of Decision||02-Jul-2019|
|Date of Acceptance||24-Jul-2019|
|Date of Web Publication||19-Aug-2019|
Dr. Dibbendhu Khanra
Department of Cardiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand
Source of Support: None, Conflict of Interest: None
Background: In non ST elevated acute coronary syndrome (NSTEACS) significant coronary artery disease cannot be predicted by biological markers, electrocardiogram (ECG) or formal two dimensional echocardiography (2DE). Recent studies have demonstrated role of strain 2DE in determination of significant coronary artery disease but no studies on three dimensional echocardiography (3DE) is available in literature. Our objective was to evaluate role of 3DE in predicting SCAD among NSTEACS patients and compare 3DE viz-a-viz 2DE. Methods and Materials: Three dimensional echocardiography in non ST elevation acute coronary syndrome in North India (3D-EINSTEIN) study is a hospital based prospective study where 324 NSTEACS patients were evaluated by Troponin I levels, ECG, laboratory parameters. Global Registry of Acute Coronary Events (GRACE) risk score were calculated. 2DE and 3DE (4 beat full volume) loop were recorded in Philips iE33 xMATRIX, global ejection fraction (EF) and parametric images were analysed using QLAB9 3DQAdv software. Coronoary angiograms were undertaken and significant coronary artery disease was defined as luminal narrowing >70% in any epicardial coronary artery. Results: Unstable angina comprises only 15% of NSTEACS and clinical profile of them are similar to NSTEMI. Two third of NSTEACS patients had >70% stenosis in at least one coronary artery. 70% of them have single vessel disease (SVD). One third of NSTEACS patients had no significant ECG changes and 50% of them had lesions in left circumflex artery (LCX). Severe MR was present in 10% of total NSTEACS patients. Half of them had concomitant lesion in right coronary artery (RCA). Elevated Troponin I & 3DE changes are significantly more to be associated with significant coronary artery disease whereas ECG changes, 2DE changes & GRACE risk scores are not. Conclusion: In NSTEACS patients, 3DE is found to have more sensitivity and specificity than 2DE in predicting significant coronary artery disease and localising culprit arteries, which can be missed by 2DE in 23% cases. Large multi-centric studies exploring the role of 3DE in assessment of NSTEACS patients are needed.
Keywords: Angiography, echocardiography, non-ST elevated myocardial infarction
|How to cite this article:|
Khanra D, Sinha S K, Tiwari P, Razi M M, Aggrawal P, Soni S, Verma C M, Thakur R, Duggal B. Three dimensional echocardiography in non ST elevation acute coronary syndrome in North India (3D-EINSTEIN) - A single centre prospective study. J Pract Cardiovasc Sci 2019;5:94-101
|How to cite this URL:|
Khanra D, Sinha S K, Tiwari P, Razi M M, Aggrawal P, Soni S, Verma C M, Thakur R, Duggal B. Three dimensional echocardiography in non ST elevation acute coronary syndrome in North India (3D-EINSTEIN) - A single centre prospective study. J Pract Cardiovasc Sci [serial online] 2019 [cited 2020 Feb 22];5:94-101. Available from: http://www.j-pcs.org/text.asp?2019/5/2/94/264622
| Introduction|| |
Unlike ST elevated myocardial infarction (STEMI), diagnosis of non-ST elevated acute coronary syndrome A (NSTE-ACS) is difficult, as there are no classical electrocardiography (ECG) changes. Troponin may not be elevated always, and often, echocardiography does not show any regional wall motion abnormalities (RWMA). However, NSTE-ACS is diagnosed on the basis of chest pain and ECG changes, and can be classified as non-STEMI (NSTEMI) if troponin level is elevated and unstable angina (UA) if not. Coronary angiogram (CAG) in NSTE-ACS patients can range from normal coronaries to diffuse coronary artery diseases (CAD) including multivessel disease (MVD). Echocardiography can also range from normal to severe left ventricular (LV) dysfunction including significant mitral regurgitation (MR).
But neither troponin values nor ECG changes alone can point toward significant CAD. Global registry of acute coronary syndrome risk score (GRACE RISK SCORE) aids in stratifying severity of NSTE-ACS which includes ECG changes, troponin levels, and other complications but surprisingly does not take echocardiography into consideration. Moreover, even GRACE RISK SCORE suggests the need of early intervention only but does not indicate the significant CAD (obstructive coronary artery disease) as such. Studies have been done to explore advanced two-dimensional echocardiography (2DE) parameters to assess obstructive coronary artery disease in NSTEMI, but role of three-dimensional echocardiography (3DE) has not been studied in the context of NSTE-ACS.
Our aims was to assess clinical, demographical, and angiographic profile of non-ST-elevation acute coronary syndromes (NSTEACS) patients and correlate it with ECG, 2DE, and 3DE and also compare 2DE viz-a-viz 3DE full-volume parametric imaging in assessment of NSTEACS.
| Materials and Methods|| |
In three dimensional echocardiography in non ST elevation acute coronary syndrome in North India (3D-EINSTEIN) study. All patients attending emergency department of LPS Institute of Cardiology, Kanpur with ACS from August 2016 to December 2017 were included. Newly diagnosed NSTEACS patients were included in the study on the basis of typical angina and ST/T changes in ECG with or without elevated troponin levels. Patients with STEMI, old myocardial infarctions, and previous revascularization were excluded. Assuming prevalence of 30%, precision of 5%, and population of 5000, sample size came down to be 300. Details of patient selection have been portrayed in [Figure 1]. A total of 324 patients were finally analyzed. Clearance from institutional ethics committee was taken. Written consent forms were obtained from all the patients.
Clinical profile including age in years, sex, and risk factors such as smoking or chewing tobacco, hypertension (HTN), diabetes mellitus (DM), known dyslipidemia, diagnosed as per Indian lipid guideline 2016, i.e., the presence of any one of the following in fasting or nonfasting lipid profile: (1) total cholesterol >200 mg/dl, (2) low-density lipoprotein >100 mg/dl, (3) triglyceride >150 mg/dl, (4) high-density lipoprotein <50 mg/dl (in females), <40 mg/dl (in males). Lipid profiles have not been drawn on patients with ACS at the time of diagnosis. Family history (FH) of premature heart attack was defined as having 1st-degree relative died due to heart attack in age <55 years in males and <65 years in females.
12-lead surface ECG was done at the time of admission and cases of STEMI were excluded from the study. Diagnosis of NSTEACS on ECG was made on the following basis as per AHA ACC 2014 NSTEMI guideline. Troponin I has been assayed by Alere™ TriageR Troponin I Test Device after 6 h of onset of chest pain and defined as positive when the level is >0.04 ng/dl as per manufacturer's instruction. Furthermore, quantitative values of troponin I level have been noted. NSTEACS with positive troponin level was diagnosed as NSTEMI and with negative values were diagnosed as UA. Routine hematological and biochemical parameters were studied.
Routine general and cardiovascular examinations were conducted. All the NSTEACS patients were treated with guideline-directed medical therapy. Complications such as heart blocks or tachyarrhythmias, LV failure (LVF), cardiogenic shock, azotemia, bleeding manifestations, or death were recorded and were managed accordingly.
Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine level as per Cockroft Gault formula, and azotemia was defined as eGFR <45 ml/h. Minor and major bleeding manifestations have been noted but not graded. Modifications of pharmacotherapies have been made accordingly. Bleeding complications after coronary interventions have not been analyzed in the present study. Patients who died during the hospital stay (i.e. within 7 days of admission) were noted and excluded from the statistical analysis. However, cause of death was recorded in those patients for descriptive analysis.
GRACE risk score were calculated for all the patients with NSTEACS at the time of admission and stratified as high and low in >140 and <140, respectively. Complications arising out of interventions were recorded as part of this registry but were not analyzed as it is beyond the scope of the aims and objectives of the study.
During the hospital stay, within 24 h, 2DE assessments were done using S5 probe of PHILIPS xMATRIX iE33. Initial assessment of EF and RWMA were made by M mode and eye estimation using a 17 segment model encompassing short axis view at three levels, parasternal long axis, four chamber (4C), and two chamber (2C) view. Global function was estimated by EF measured by Simpson's method. Regional function was assessed by automated functional imaging where APLX, 4C, and 2C clips were sampled followed by tracing of endocardial border in zoom mode. Aortic valve closure was timed with end of T-wave in gated ECG tracing. Bull's eye and QUAD views were stored, and peak systolic strain was recorded and regional function abnormalities were noted. Severity of MR was assessed according to American Society of Echocardiography 2017 guideline on native valvular regurgitation.
3DE assessment was done in PHILIPS xMATRIX iE33 using X5-1 probe. A full-volume 4-beat apical 4C loop was taken with gated ECG. Using Image Loop, right and left cropping is done to get the ideal window and stored. The loop is analyzed by QLAB9 using 3DQAdv. End-diastolic and end-systolic image is isolated, and endocardial borders are traced after proper alignment followed by analyzing the segment which renders the volumetric data of LV with information regarding each 16 segments in different color-coded form. Regional function can be assessed in i-Slice view as well although frame rate is lower than 2DE. In report page, global EF is estimated using Simpson without any geometric assumption. LVEF in 3DQAdv has been correlated with cardiac magnetic resonance imaging with high level of accuracy. Regional function assessment was made by parametric imaging in Bull's eye form in 16 segment model. The patients who did not have echocardiographic assessments (2DE or 3DE or both) were excluded from the study.
Coronary angiography (CAG)
CAG were done in all the patients of NSTEACS patients within 1 week of admission in either PHILIPS Allura Xper FD20/10 or SIEMENS flat panel ARTIS ZEE cathlab. When azotemia was found, anticoagulation was modified accordingly, and serial measurements of eGFR were conducted and intervention if required was done only after serum creatinine levels are lower than 1.5 mg/dl. Either radial or femoral route had been employed. Patients with cardiogenic shock were posted for percutaneous coronary intervention (PCI) as early as possible considering the logistics of the institution.
Epi Info 126.96.36.199 software (Centers for Disease Control and Prevention) was used for descriptive and statistical analysis.
| Results|| |
Tobacco use was found to be the most common (84%) risk factor associated to NSTEACS. DM and HTN were present in 31% and 41% NSTEACS patients, respectively. Dyslipidemia and significant FH was present in 9% and 13% of NSTEACS patients, respectively. UA comprises only 15% of NSTEACS and reset were troponin I-positive NSTEMI. Two-third of NSTEACS patients (216/234) had >70% stenosis in at least one coronary artery. 70% of them (152/216) have single vessel disease (SVD). Distributions of coronary arterial involvements were depicted in [Figure 2]a. Twenty-four patients died within the hospital stay [Figure 2]b. Complications' profile of the NSTEACS patients are given in details in [Figure 2]c. Almost one-third (29%) of the NSTEACS patients were managed with optimal medical therapy (OMT). Among the rest, 42% were advised for PCI and 21% were advised for coronary artery bypass grafting (CABG) as per guideline [Figure 2]d. Among the cohort of NSTEACS patients, 70% (228/324) had GRACE risk score <140 [Figure 2]e.
|Figure 2: (a) (A) Distribution of obstructive coronary artery disease in patients of non-ST-elevation acute coronary syndromes (n = 216/324), (B) distribution of single vessel disease in patients of obstructive coronary ar tery disease with non-ST-elevation acute coronary syndromes (n = 152/216), (C) involvement of coronary arteries in patients of single vessel disease with non-ST-elevation acute coronary syndromes (n = 152); (b) distribution of mode of death among patients of non-ST-elevation acute coronary syndromes (n = 24); (c) distribution of complications in patients of non-ST-elevation acute coronary syndromes (n = 348); (d) distribution of treatments advised in patients of non-ST-elevation acute coronary syndromes (n = 324); (e) distribution of coronary artery diseases among patients of non-ST-elevation acute coronary syndromes with respect to GRACE RISK SCORE.|
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One-third of NSTEACS patients had no significant ECG changes (72/324), and 50% of them (36/72) had lesions in left circumflex artery (LCX). Most common ST/T changes in ECG were confined to anterior chest leads (94/324), and 90% of them (84/94) had lesions in left anterior descending (LAD) artery [Table 1].
|Table 1: Distribution of electrocardiogram changes in different leads with respect to lesion in coronary artery in patients of non-ST elevated acute coronary syndrome with significant coronary artery disease (n=216) (including single vessel disease and multivessel disease)|
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2DE and 3DE were abnormal in 55% and 78% of NSTEACS patients with obstructive coronary artery disease, respectively, with 3DE having sensitivity and positive predictive value of 77% (54% for 2DE) and 73% (67% for 2DE), respectively [Figure 3]a, [Figure 3]b, [Figure 3]c. Severe MR was present in 10% of total NSTEACS patients. Half of them had concomitant lesion in the right coronary artery (RCA) [Figure 3]d.
|Figure 3: (a) Sensitivity and specificity of two-dimensional Echo in comparison to CAG, (b) sensitivity and specificity of three-dimensional Echo in comparison to CAG, (c) comparison between two-dimensional echocardiography versus three-dimensional echocardiography in localization of arterial territories in patients of non-ST-elevation acute coronary syndromes with obstructive coronary artery disease (n = 216 ), (d) (A) distribution of mitral regurgitation in patients of non-ST-elevation acute coronary syndromes (n = 324) and (B) its correlation with involvement of coronary arteries (n = 32, severe mitral regurgitation).|
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Elevated troponin I and 3DE changes are significantly more to be associated with obstructive coronary artery disease whereas ECG changes, 2DE changes, and GRACE risk scores are not [Table 2]. Higher age, DM, high GRACE risk score, and 3DE changes are significantly more associated with MVD whereas troponin I levels, ECG changes, and 2DE changes are not [Table 3]. ECG changes, MVD, and fall in 3DE global EF are significantly more associated with NSTEMI, whereas risk factors and 2DE changes are not [Supplementary Table 1]. Comparison between UA and NSTEMI is depicted in [Supplementary Table 2].
|Table 2: Comparison between patients of nonST elevated acute coronary syndrome patients with and without significant coronary artery disease (n=324)|
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|Table 3: Comparison between single vessel disease and multivessel disease patients of non-ST elevated acute coronary syndrome with significant coronary artery disease (n=216)|
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In NSTEACS patients, 3DE is found to have more sensitivity and specificity than 2DE in predicting obstructive coronary artery disease and localizing culprit arteries, which can be missed by 2DE in 23% cases. The subset of absent RWMA in 2DE but present in 3DE (n = 50) is significantly more associated with low GRACE risk score NSTEACS patients with SVD, easily amenable to PCI. The subset of absent RWMA in 3DE but present in 2DE (n = 10) is more to be found in the setting of thrombus or electrical abnormalities.
| Discussion|| |
Pathophysiology of NSTEMI is different than STEMI, so is the definitive management. The angiographic profile of NSTEMI varies from normal to MVD, and ECG changes, troponin I level, or 2DE features were often not conclusive to predict significant coronary artery disease (obstructive coronary artery disease). Composite GRACE risk score is therefore has been implicated as an important tool for assessing high-risk NSTE-ACS cases. Although the guidelines favor early PCI in NSTE-ACS patients with GRACE risk score >140, studies have demonstrated that very often, high GARCERS patients tend to have MVD and not suitable for PCI in urgent basis and especially when there are other complicating issues like cardiogenic shock or bleeding manifestations. There is also paucity of data or registry of NSTE-ACS in India unlike CREATE, Kerala-ACS registries for STEMI or Indian guidelines and consensus for management of STEMI.,, Interestingly, McManus et al. pointed to the recent decreases in the magnitude of STEMI, slight increases in the incidence rates of NSTEMI, and that holds true for India as well. In our study, however, of 1504 patients presenting with ACS, 504 were diagnosed as NSTE-ACS. The lower proportion of NSTE-ACS may be partly due to admission triage at Emergency Department and partly due to difficulty or delay in diagnosis of NSTE-ACS.
Demographic parameters and risk factors
In our study cohort, 324 NSTEACS patients were followed up and 70% of patients were found to be male. Sharma et al. reposted male preponderance (79%) among the NSTE-ACS patients. The mean age of presentation was 54 years in our study. The mean age of presentation was 54.71 ± 19.90 years among NSTE-ACS patients in the study by Sharma et al. About 84% patients of NSTEA-ACS in our study were using tobacco in some form, which goes with the trend of high tobacco usage of Kanpur. HTN and DM were present in 40% and 30%, respectively. In the study by Sharma et al., smoking was present in 49.3%, HTN in 40.2%, and diabetes in 37%. In our study, using tobacco has been found to significantly more in the NSTE-ACS patients with obstructive coronary artery disease. A higher mean age and having DM were significantly associated with having MVD. Higher mean age, male sex, nicotine use, having DM or HTN were noted significantly more in patients with high GRACE risk score (>140). There were no significant differences of risk factors among patients with NSTEMI and UA.
In our study, UA was present in only 15% of NSTE-ACS cohort. In a South Indian study of ACS patients, incidence of UA was more than NSTEMI (25% vs. 11%). In our group of cohort, we believe that a quantitative assay of troponin I may be responsible for early detection of NSTEMI.
Among the patients of NSTE-ACS, in almost one-third, no significant ECG abnormalities were found. Among the patients with no ECG changes, most commonly lesions were found in LCX (50%). Among the rest of patients, ECG changes were found most commonly in anterior leads and 90% of them having lesion in LAD. This observation is similar to the findings of the study reported by Sanaani et al. However, ECG changes, although elevate GRACE risk score in patients presenting with NSTE-ACS, it does not have any significant correlation with the presence or absence of obstructive coronary artery disease or MVD in our study.
Obstructive coronary artery disease (>70% luminal narrowing in any coronary artery and >50% narrowing of LMCA) was found in one-third of our NSTE-ACS patients. 70% of them were found to have SVD, potentially amenable to PCI. Most common involved coronary artery was found to be LAD followed by RCA and LCX similar to the finding of Liu et al.
Complications and death
In our study, 4.76% NSTE-ACS patients died during hospitalization (i.e. within 7 days) most commonly due to cardiogenic shock. A total of 7.9% patients died in hospital in the study of Sharma et al. Bleeding manifestations were found in 7% patients in our study. No other study recorded bleeding manifestations in the setting of NSTE-ACS. In our study, azotemia was noted in 8% of NSTE-ACS patients. Liu and Huang noted a significantly higher percentage of NSTEMI patients had end-stage renal diseases in comparison to STEMI. Cardiogenic shock was present in 7.5% patients in our study which is higher than the finding of Sharma et al. (2.9%). LVF and cardiac arrest was present in 7.5% and 6.5% patients, respectively, in our study. 21 patients had cardiac arrest in our study due to arrhythmia (including bradyarrhythmia or tachyarrhythmia), and these events were significantly correlated with obstructive coronary artery disease and MVD. Ventricular tachycardia (VT) and complete heart block (CHB) were found in equal number of patients, and AF was found in one patient only. In the study by Liu and Huang, rhythm abnormalities constitute atrial fibrillation (4.7%), bundle branch block (3.1%), frequent PVCs (1.6%), and asystole (1.6%). Intuitively, all the aforesaid complications were found to be significantly more among the patients with obstructive coronary artery disease in our study. Cardiac complications were significantly more in patients with MVD, but noncardiac complications, namely bleeding manifestations and azotemia were not significantly different. Cardiac as well as noncardiac complications were significantly more in NSTE-ACS patients with high GRACE risk score.
Among the cohort of NSTEACS patients, one-third were advised for OMT. For the rest of the patients, two-third were eligible for PCI owing to more number of SVD and simple CAD and one third were advised for CABG. However, percentage of patients who underwent PCI were significantly more than patients who underwent PCI were significantly more than patients who underwent CABG (69% vs. 43%) in the present study. No other Indian studies assessed the management strategy of NSTE-ACS patients.
GRACE risk score
Among the cohort of NSTE-ACS patients, 70% had GRACE risk score <140, and PCI for SVD was advised significantly more in this age group in comparison to rest 30% patients with GRACE risk score >140 who were significantly more advised for CABG due to concomitant MVD. Hence, higher GRACE risk score not only indicates high-risk NSTE-ACS but also indicates PCI-unamenable MVD. However, in the bivariate analysis, composite GRACE risk score was not significantly different among NSTE-ACS patients with and without obstructive coronary artery disease.
Troponin levels were significantly higher in NSTE-ACSA patients with obstructive coronary artery disease (n = 216). However, ECG changes 2DE or GARCE risk scores were similar among NSTEACS patients with or without obstructive coronary artery disease. Similarly, troponin levels or ECG changes or 2DE abnormalities were not significantly different in pts with MVD form SVD. However, GRACE risk score >140 was significantly more associated with the presence of MVD.
UA was present only in 15% of NSTE-ACS pts and ECG abnormities; MVD and mean GRACE risk score were significantly lower among them when compared to NSTEMI despite a similar demographic profile. Obstructive coronary artery disease was present in 32 pts which were not significantly different among NSTEMI pts. However, MVD was significantly more associated in NSTEMI than UA.
RWMA was noted among 118 pts in 2DE whereas among 168 pts in 3DE. Falsely absent RWMA in 2DE can be identified by 3DE, especially in low GRACE SVD pts. In NSTE-ACS patients, 3DE had been found to be an easy, rapid, and valuable tool in predicting obstructive coronary artery disease and localizing culprit arteries, which was being missed by 2DE in 23% cases. NSTE-ACS patients with absent RWMA in 2DE but RWMA present in 3DE consist of 50 pts (23%). 40% of them had hypokinesia in lateral wall. Moreover, troponin I level was significantly lower; ECG changes were significantly absent and SVD was present significantly more with an overall significantly lower GRACE risk score. Abnormalities in 3DE were significantly more in NSTE-ACS patients with the presence of obstructive coronary artery disease. When 3DE was compared to 2DE in predicting obstructive coronary artery disease, 3DE had a significantly higher sensitivity, PPV, and positive likelihood ratio. After despite extensive literature review, we could not find any material which formally assessed 3DE in assessment of NSTEACS. Although no composite risk scores for ACS (including GRACE) do not include 2DE parameters into consideration while assessing risk of mortality/severity of disease, inclusion of 3DE changes could be an important supplementation in risk assessment.
Despite the limitations of the study such as nonperformance of stress testing (in asymptomatic patients on OMT), SYNTAX scoring, and FFR, this is the first study from North India not only exploring the clinical and angiographic profile of NSTE-ACS but also correlating them with Troponin I, ECG changes, GRACE risk score, 2D, and 3DE.
| Conclusion|| |
Unlike Indian data and registries of STEMI, there is no robust data on NSTE-ACS. Echocardiography parameters are never part of risk stratification of NSTE-ACS patients. The echocardiogrpahic abnormalities in NSTEACS are not always present in conventional imaging but strain echocardiography and myocardial contrast echocardiography can be useful in detecting subtle ishaemic changes. However, they are still out of reach for practical application as they are cumbersome and time-consuming and need a good interpreter. 3DE is emerging in India, and being utilized in dys-synchrony management, and structural interventions. Role of 3DE in NSTE-EACS has not been studied much. 3DE can clinch echo abnormalities early the course of ACS. However, low frame rates may compromise RWMA analysis in 3DE and thus has to be relied on parametric imaging, which often may be operator dependent and not well standardized. However, 3DE is a more sensitive and specific tool with respect to 2DE in predicting significant coronary artery disease and localizing culprit arteries, which were missed by 2DE in 23% cases in our NSTEACS cohort. Large multicentric studies exploring the role of 3DE in assessment of NSTEACS patients are needed.
Institutional Ethics Committee of GSVM Medical College, Kanpur, issued ethical clearance in a meeting held on 24.7.2016.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]