European Journal of Cardiovascular Medicine

Acute coronary syndrome (ACS) is a leading cause of morbidity and mortality globally, with India experiencing the highest burden. Isolated Left Circumflex (LCX) coronary artery disease is rare, occurring in a small percentage of patients undergoing coronary angiograms [1]. LCX stenosis may present with an ECG pattern similar to inferior myocardial infarction, akin to RCA occlusion. Patients with isolated LCX infarction show distinct myocardial damage patterns. Echocardiography is the most commonly used cardiac imaging technique, yet conventional echocardiography provides limited information on coronary artery disease (CAD) in suspected stable angina pectoris (SAP) cases [2]. Given that the myocardium at risk corresponds to the myocardium distal to the stenosis, and interventional therapy's effectiveness is greater in larger myocardial injuries, it is essential to correlate ECG and ECHO changes with coronary stenosis sites. Evaluating left ventricular function in isolated LCX disease, with or without myocardial infarction, is crucial [3].  For evaluating a myocardial function, echocardiography (including tissue Doppler imaging [TDI] and speckle tracking echocardiography [STE]), contrast-enhanced cardiac magnetic resonance (ceCMR), and single photon emission computed tomography (SPECT) are commonly used methods [4]. Echocardiography assesses left ventricular (LV) function and myocardial damage post-acute MI primarily by measuring ejection fraction (EF) and LV volume. However, these indices are global and load-dependent.  CeCMR is considered the gold standard for LV function assessment but is limited by its inability to be performed bedside, its time-consuming and costly nature, and its low temporal resolution [5]. SPECT exposes the patient to radiation. An emerging method, strain imaging based on STE, allows the assessment of both global and regional functions. STE provides an accurate analysis of LV function, as shown in previous studies [6]. Two-dimensional speckle tracking echocardiography (2D STE) is a cost-effective method offering better temporal and spatial resolution. It tracks grey-scale speckles along the LV wall, providing a comprehensive assessment of myocardial deformation, independent of the ultrasound beam's angle [7].  Three-dimensional STE (3D STE) is also in development, allowing strain measurement in all three directions, whereas 2D STE measures only two directions simultaneously [8]. However, 3D STE's temporal and spatial resolution needs improvement before it can be routinely used in clinical practice [8]. Due to the rarity of isolated LCX disease, limited studies are available. The clinical, electrocardiographic, echocardiographic, and angiographic features of isolated LCX disease are poorly characterized, and myocardial strain in such cases is underreported.  This study aims to examine the two-dimensional strain echocardiogram using speckle tracking in ACS patients with LCX disease and correlate these findings with angiographic profiles.

The present study was a cross-sectional analytical study, conducted in Mahatma Gandhi Medical College and Research Institute, Tertiary Care Hospital, Puducherry. The study was done for a period of one to one and a half years after getting clearance from the institutional ethical committee. All patients with Acute Coronary Syndrome (aged >18 years) requiring coronary angiography in the Department of Cardiology in MGMCRI were identified.

Inclusion criteria

Those patients with Acute Coronary Syndrome whose coronary angiogram showed isolated left circumflex coronary artery disease as the culprit vessel were included in our study.

Exclusion criteria

1. Multi-vessel disease with obstructive disease in the Left Anterior Descending (LAD) and Right Coronary Artery (RCA)
2. Prior angioplasty/ CABG
3. Patients with advanced heart failure
4. Chronic kidney disease
5. Patients with Dual Territory Myocardial Infarction (DTMI)-Anterior Wall Myocardial Infarction (AWMI) + Inferior Wall Myocardial Infarction (IWMI).

All Patients whose coronary angiogram showed isolated left circumflex coronary artery disease, receiving care in the Department of Cardiology, Mahatma Gandhi Medical College and Research Institute, Puducherry during the study period and satisfying the inclusion and exclusion criteria were selected.

In patients whose coronary angiogram showed isolated left coronary circumflex artery disease following parameters were studied

1. Electrocardiographic findings and their distribution and pattern in various leads.ST segment J point elevation >1mm and ST segment depression >1mm in two or more contiguous leads (V5, V6, I, aVL, and lead II, III, and aVF ) were considered as STEMI and NSTEMI in our study. T inversion and Q wave >1mm from the iso-electrical line of all leads were considered significant. 3) Conventional Echocardiographic analysis with respect to regional wall motion abnormalities, ejection fraction, and presence of MR
2. Speckle tracking Echocardiographic analysis
3. The distribution of LCX stenosis was stratified into 2 groups Central LCX stenosis which includes proximal LCX, OM branches, and Ramus, and Peripheral LCX stenosis which includes distal LCX and posterolateral branch (PLB).

Clinical presentation: The mode of clinical presentation of the study population was assessed with respect to presentation as effort angina, unstable angina, NSTEMI, and STEMI. Rhythm disturbance during acute presentation as STEMI was also assessed. Hemodynamic parameters were specifically looked for in patients presenting with STEMI.

Conventional Echocardiographic analysis: The ECHO machine used for the analysis was VIVID GE E95 with 2D and 4D adult probes. Baseline LV systolic function was assessed by modified Simpson’s method in all study patients. LV dysfunction was characterized as mild if the LV ejection fraction was between 46 – 55%. Moderate LV dysfunction was defined as LV ejection fraction between 30 – 45%. Severe LV dysfunction was defined as LV EF less than 30%. Normal LV function was defined as LV EF above 55%. All the patients enrolled underwent color flow imaging for the presence of mitral regurgitation. Mitral regurgitation was graded as mild, moderate, and severe as per AHA guidelines. Regional wall motion abnormality was assessed for patients presented with documented STEMI.

Speckle tracking echocardiographic analysis: Speckle tracking was evaluated by a non-invasive recording of recording three consecutive end-expiratory cardiac cycles using a high frame rate (80–100 frames/s) and harmonic imaging was acquired in the apical four-, two-chamber views as well as long axis views for quantification of peak systolic strain by automated function imaging speckle tracking analysis. GLPSS for the complete LV will be provided by the software using a 17-segment model in a bull's eye plot calculated as the average of a longitudinal peak systolic strain of each view and the mean of the three views the normal value of longitudinal peak systolic strain is -20%.

Angiographic analysis: The diagnostic coronary angiograms of the patients enrolled were collected and assessed. The location and severity of stenosis in LCX were studied in detail in multiple angiographic views. The frequency of stenosis in LCX was analyzed. Significant stenosis was defined as stenosis more than or equal to 70% in LAD, LCX, and RCA. Significant stenosis in LMCA was defined as stenosis severity more than or equal to 50%. The presence of non-significant stenosis in RCA and LAD (stenosis severity less than 50%) was studied. non-significant stenosis in LMCA was defined as stenosis severity of less than 30%. The dominance of the coronary artery was assessed. For the sake of analysis, LCX was divided into proximal and distal segments. The portion of LCX above the origin of OM1 was considered proximal. The distal segment was defined as the portion of LCX below the origin of OM1. The presence of stenosis in OMs was specifically looked for inpatients presented with high lateral MI. Collateral circulation was also assessed in patients showing total or near total occlusion of LCX.

Risk factor analysis: Patients enrolled in the study were evaluated for major risk factors for CAD, including hypertension, diabetes mellitus, family history of coronary artery disease, smoking, and hypercholesterolemia. The average number of risk factors per patient was recorded. The presence (single or multiple) or absence of risk factors, along with the specific nature of each risk factor, was analyzed concerning the outcome of LCX disease.

Statistical analysis: The data was entered into Microsoft Excel and analyzed using standard statistical software (SPSS version 21). Qualitative variables were presented as frequencies and percentages, while quantitative variables were expressed as mean & SD or median & IQR. Appropriate statistical tests (e.g., independent t-test, chi-square test) were applied based on the data's nature and distribution. A p-value of less than 0.05 was considered statistically significant. Correlation analysis was conducted to assess the relationship between the site of stenosis (central vs. peripheral) and electrocardiographic patterns/speckle tracking echocardiographic findings.

A total of forty-two patients meeting the inclusion and exclusion criteria were analyzed. Data were collected on age, gender, risk factors, and indications for coronary angiogram, along with abnormal ECG findings in relation to the distribution of LCX stenosis. In this study a total of 35(83.3%) cases were males and the remaining 7(16.7%) were females. The male-to-female ratio was 5:1.

Prevalence of Risk Factors: The prevalence of risk factors among ACS cases was categorized. In the study population, 16.7% were female and 83.3% were male, indicating a predominance of males with isolated LCX disease. Additionally, 54.8% were smokers, 47.6% had systemic hypertension, 42.9% had diabetes mellitus, 40.5% had a family history of CAD, and 35.7% had hypercholesterolemia (Figure 1).

Figure 1: Distribution of risk factors in cases of the study

Electrocardiographic changes in isolated LCX Stenosis: Among the included cases of ACS, there were STEMI cases(n=17) of 40.5%. NSTEMI cases (n=20) of 47.6% and unstable angina cases(n=5) of 11.9%. Out of 40.5% of STEMI cases, High lateral wall MI was noticed in 5.8% of cases (Table 1).

Table 1: Distribution of ACS in the cases of the study

ECG changes were observed in all 42 cases, and they were analyzed based on the presence of Q wave, ST -T changes like ST elevation or depression or flattening, presence or absence of T wave inversion Among 42 ACS cases, the presence of Q wave was noted in 7 cases (16.7%). Among 71.4% of cases with ST changes, ST elevation(n=17) was noted in 40.5% of cases, ST depression(n=12) in 28.6% of cases, and flattened ST changes(n=3) were noted in 7.1% of cases. T wave inversion was noticed in 19 cases (45.2%).

Table 2: Distribution of LV Dysfunction

Table 2 represents the Left ventricular functions in the cases of the study.  On echocardiographic evaluation, there was evidence of a minimum ejection fraction of 40% and a maximum EF of 65% with the mean value of 54.09 ± 7.03%. 17 cases presented with normal LV function (40.5%), 20 cases with mild LV dysfunction (47.6%), 5 cases with moderate LV dysfunction (11.9%), and none of them had severe LV dysfunction.

On the Echocardiogram evaluation of 42 ACS cases (Table 3), RWMA was noted in 23 cases constituting 54.8%, and 19 cases (45.2%) didn’t show any RWMA. RWMA was analyzed based on segment involvement. They were stratified into 2 groups Basal and Mid & basal region involvement. In the basal group, the inferior region was involved in 11.9% of cases(n=5), the inferoseptal region was involved in 9.5% of cases(n=4) and the inferolateral region was involved in 9.5% of cases(n=4). Among the Mid & basal group, 33.3% of cases(n=14) presented with inferior region, Inferolateral region in 26.2% of cases(n=11), inferoseptal region in 11.9% of cases(n=5), and lateral region involved in 4.8% cases(n=2).

Table 3: Distribution of Regional Wall Motion Abnormalities

In our study, mitral regurgitation was present in 18 cases (42.9%) and absent in 24 cases(57.9%). Of those 18 cases, 16 cases (38.1%) had only mild MR 2 cases (4.8%) had moderate MR and none of them had severe MR. For analytical purposes, co-dominant LCX were grouped with dominant LCX. There was evidence of 45.2% of cases(n=19) with dominant LCX and 54.8% of cases(n=23) with non-dominant LCX. Out of 19 Dominant LCX cases, 47.4% of cases (n=9) presented with RWMA, and out of 23 Non-Dominant LCX cases, 60.9% of cases (n=14) were presented with RWMA (Table 4).

Table 4: Comparison of RWMA with Nondominant and Dominant LCX

Among the study population of 42 cases, central LCX stenosis was found in 29 cases, and peripheral LCX stenosis was found in 13 cases. Under central stenosis, 35.7% cases had Proximal LCX stenosis,47.6% of cases had Obtuse Marginal branch LCX stenosis,2.48% of cases had Ramus branch stenosis. About 31% of cases(n=13) were found with Distal LCX stenosis. Out of 29 cases of Central LCX stenosis, 65.5% of cases(n=19) were presented with RWMA which was statistically significant(p=0.04). Among 13 cases of Peripheral LCX stenosis, 30.8% of cases(n=4) had RWMA (Table 5).

Table 5: Comparison of RWMA with central and peripheral LCX stenosis

In 2D speckle tracking echocardiographic findings of 42 cases, the mean value of GLS was -15.6 ± 3.3 which was found to be in the low normal range. The mean GLS in Dominant LCX was -15.3 + 3.6 and non-dominant LCX was -15.8+3.1. The mean value of RLSLCX(-8.3+3.8) was compared with the mean value of RLSLAD -17.3  ±  4.5 and RLSRCA -17.2  ±  4.2 and proved the mean value of RLSLCX was significantly reduced depicted in table 6.

Table 6: Comparison of Strain Echo parameters with Non-Dominant and Dominant LCX

In our study, the mean GLS of central LCX stenosis was -15.5  ± 3.3 and peripheral LCX stenosis was -15.6  ±  3.4. Similarly, the mean RLS LCX of central stenosis is - 8.1  ±  3.6 and peripheral stenosis was -8.8  ± 4.4, out of which dominant LCX was - 9.2  ± 3.5 and non-dominant LCX was -7.6  ± 3.9 depicted in table 7.

Table 7: Comparison of Strain ECHO parameters with Central and Peripheral LCX stenosis

In our study, the mean GLS of STEMI cases was -16.11 ± 3.46, NSTEMI cases were - 14.96 ± 3.48 and Unstable angina was -16.40 ± 2.54. The mean RLS LCX of STEMI cases was -8.64+3.68, NSTEMI cases were -7.54 ± 4.06 and Unstable angina was -10.92  ± 2.70 (Table 8).

Table 8: Comparison of ACS with GLS average and RLS LCX.

Out of 42 isolated LCX stenosis cases, 13 cases had RWMA their mean GLS was -15.85 ± 3.35 and the mean RLS LCX was -8.53 ± 3.90 (Table 9).

Table 9: Comparison of GLS average and RLSLCX with RWMA

On visual observation, all our 42 patients had impaired regional longitudinal strain of LCX territory in the bull’s eye pattern (Figure 2).

Figure 2: Global Longitudinal Strain (Bulls Eye pattern)

In this study, the relationship between the site of LCX stenosis ECG changes and two-dimensional strain echocardiogram using speckle tracking was analyzed. There was evidence of significant lateral lead ECG changes in 18 cases of central LCX stenosis out of which 10 cases had dominant LCX. The inferior lead ECG changes in 15 cases of peripheral LCX stenosis out of which 9 cases had nondominant LCX. Isolated disease of the left circumflex coronary artery does not appear to cause severe left ventricular dysfunction, as the mean ejection fraction in our study was 54.09% and this is similar to the previous study by Rod J L. et al. [9] In our study mitral regurgitation was present in 18 cases (42.9%) and absent in 24 cases(57.9%). Of those 18 cases, 38.1% of cases had mild MR 4.8 % of cases had moderate MR and none of them had severe MR. Usually, mitral regurgitation occurs in patients with significant LV dysfunction. This correlates with the observation that most of the patients with isolated left circumflex coronary artery disease have adequate left ventricular function and only trivial to mild MR. In our study, on echocardiographic evaluation, a statistically significant difference was noted in the presence of RWMA between central and peripheral stenosis. Patients with central stenosis had higher evidence of RWMA. Gensini scores in studies have suggested that the most common site of LCX stenosis was proximal [10, 11]. The site of stenosis reflects the sites of predilection for atherosclerosis in patients with isolated circumflex disease and includes proximal and distal circumflex segments and proximal portions of the major branches. In our study, 35.7% of cases of the study population were found with proximal LCX stenosis of which 7.1% cases were found with 100% occlusion. Stenosis of Obtuse Marginal LCX branch was found in 47.6% of cases out of which 11.9% were found with 100% OM branch occlusion. About 31% of cases were found with Distal LCX stenosis out of which 4.8% of cases were observed with 100% distal LCX occlusion.

In our study, we observed that among patients with NSTEMI ST-T changes were noted in inferior leads that correlated with the site of stenosis at peripheral LCX and they had mostly a non-dominant LCX. And if ST-T changes were noted predominantly in lateral leads then the site of occlusion was mostly central with a dominant LCX. The routine ECHO might show no RWMA in case of peripheral LCX stenosis, but STE resulted in a reduction of GLS average and RLS_LCX. So, we concluded that despite of site of occlusion, there will be a reduction of GLS average and RLS _LCX in both central and distal LCX stenosis in strain pattern though there is no RWMA in routine ECHO [12]. There was no sufficient data available on comparing the isolated LCX stenosis with longitudinal strain echocardiographic parameters. In 2D speckle tracking echocardiographic findings of our 42 cases, the mean value of GLS average was -15.6 ± 3.3 which was found to be at the low normal range, out of which GLS average in Dominant LCX was -15.3± 3.6 and non-dominant LCX was - 15.8 ± 3.1. The mean value of RLS_LCX (-8.3 ± 3.8) was compared with the mean value of RLS_LAD (-17.3 ± 4.5) and RLS_RCA (-17.2 ± 4.2) and proved the mean value of RLS_LCX was significantly reduced. The mean GLS of central LCX stenosis was -15.5 ± 3.3 and peripheral LCX stenosis was -15.6 ± 3.4 which was reduced. Similarly, the mean RLS _LCX of central stenosis is -8.1+3.6 and peripheral stenosis was -8.8 ± 4.4, out of which dominant LCX was - 9.2 ± 3.5 and non-dominant LCX was -7.6+3.9 which was also reduced. A landmark article by Caspar T et al14 reported that CAD was present in 33 patients (57%), LVEF was 60.7 ± 4.6% in group 1 (CAD), and 61.1 ± 5.0% in group 2 (no CAD). Global longitudinal strain (GLS) was altered in the first group with CAD (- 16.7 ± 3.4%) as compared to group 2 without CAD (- 22.4 ± 2.9%, p < 0.001). Maharajan S et al. [13] conducted an observational study on Global longitudinal strain in patients with ST-elevation myocardial infarction post-percutaneous coronary intervention using speckle tracking echocardiography. They found that the mean GLS of STEMI patients was -16.65 ± 3.02. In our study, the mean GLS of STEMI cases was -16.11 ± 3.46 which was nearly similar to the previous study.

Keddeas et al. [14] studied the role of 2D speckle-tracking echocardiography in predicting acute coronary occlusion in patients with non-ST-segment elevation myocardial infarction. They found variations in the mean GLS in the case of NSTEMI with or without total occlusion. The mean GLS of NSTEMI with total occlusion was -13.78 ± 4.08 and without total occlusion was -16.94 ± 3.88. In our study, there were 5 cases of NSTEMI with total occlusion which corresponds to central LCX. Out of which 2 cases were proximal LCS occlusion and 3 cases were OM branch of LCX occlusion. The mean GLS of NSTEMI with total occlusion was -14.68 ± 3.15 and of NSTEMI without total occlusion was -14.9 ± 3.48. The mean RLS_LCX of NSTEMI with total occlusion was -7.84 ± 4.12 and of NSTEMI without total occlusion was -7.53 ± 4.06. Due to the smaller sample size, we could not draw any conclusion on the role of STE in identifying the total occlusion of LCX. Giridharan S et al. [15] performed a study on Longitudinal Strain in patients with NSTEMI/Unstable angina with normal left ventricular function which was similar to our study where GLS had moderate accuracy in diagnosing ACS. In our study, out of 42 cases, 17 cases had normal LV function with a significant reduction in the longitudinal strain of LCX territory. In an original article published by Poorzand H et al. [16] LV GLS (mean ± S.D) of the normal group was -18.94 ± 3.91 and with LCX stenosis was -15.64 ± 3.42. They evaluated the value of LA strain in predicting coronary artery occlusion in patients who underwent selective coronary angiography. The amounts of LVESV, LV GLS, and Em-septal (early diastolic velocity) were significantly different between the normal subjects and patients with LCX stenosis. LA strain was lower in patients with LCX stenosis (16.03%, P value=0.042) in comparison with the normal subjects. The decrease was marginally significant, and this might be applicable in the practice.LA strain could have a specific predictive role for isolated coronary artery occlusion, including LCX lesions. Therefore, in patients presenting with chest pain, reduced LA strain without obvious reason, could be a clue for LCX stenosis

The study concluded that central stenosis of the proximal left circumflex (LCX) coronary artery was more common than peripheral stenosis of the distal LCX. ECG changes in the lateral leads were predominantly associated with central LCX stenosis, particularly involving the dominant LCX, whereas inferior lead changes were linked to peripheral LCX stenosis. Regional wall motion abnormalities were statistically proven to be associated with central LCX stenosis. Most patients with isolated LCX disease exhibited normal left ventricular (LV) function. However, a significant reduction in regional longitudinal strain (RLS) of the LCX was observed in these patients, regardless of the stenosis site. Despite normal LV ejection fractions, speckle tracking echocardiography (STE) demonstrated a reduction in mean global longitudinal strain (GLS) and RLS, irrespective of central or peripheral stenosis. Thus, the strain pattern can be considered a superior diagnostic tool for detecting peripheral LCX stenosis when routine 2D echocardiography appears normal.

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