Additive value of three dimensions Echocardiography parameters to GRACE Score for predicting Left ventricular remodeling following revascularization in acute anterior ST- elevation myocardial infarction – A comparison of primary angioplasty and Streptokinase-based pharmaco-invasive Strategy

INTRODUCTION

ST-Segment elevation myocardial infarction, usually occurs when a fibrin-rich clot completely blocks an epicardial coronary artery, and accounts for about 25-40% cases of acute coronary syndrome (ACS). ¹

Primary PCI  is the recommended reperfusion therapy for (STEMI), because feasibility sometimes makes it difficult to implement this strategy in developing countries, the pharmacoinvasive strategy, in which the patient is given a fibrinolysis and then undergoes coronary angiography (within 3-24 hours after successful fibrinolytic therapy), is seen as an alternative to Primary PCI When it is not available on time. ²

Left ventricular remodeling after myocardial infarction is a complex process, including dilation of the Infarcted area, progressive hypertrophy in non-infarcted area and it is precursor for development of heart failure, which is an important prognostic indicator for mortality, there for LVR is a primary target for treatment after acute myocardial infarction. ³

Analysis of the left ventricular volumes, geometry has been performed by two dimensional echocardiography (2D ECO), and this method has limitations related to morphological and functional analysis of heart structures and possibility for foreshortening during image acquisition. ⁴

 3D echocardiogram can give structural analysis for the heart in multiple spatial levels, LV volumes calculated by 3D echocardiogram software , are three  times more accurate than 2D echocardiogram with Closer approximation to measurements obtained with better spatial resolution ways, such as 64 - Ultra-fast channel computed tomography and nuclear magnetic resonance ^.5

we aimed by this work was to compare reperfusion strategies in patients presented by acute anterior STEMI treated by PPCI versus pharmaco-invasive strategy regarding the effect on LV remodeling detected by 3D Echocardiography parameter in addition to clinical assessment by GRACE risk score.

PATIENTS AND METHODS

This study included 100 patients presented by acute anterior STEMI. This research was carried out at Bab Al Sheria hospital (Al-Azhar University), between April 2019 to January 2021.

The patients were classified into two groups: Group (1): 50 patients treated with pharmaco-invasive strategy post successful thrombolytic therapy, and Group (2): 50 patients treated with primary PCI.

Inclusion criteria: patients with acute anterior STEMI presented with in 12hours of chest pain onset, treated by primary PCI  (door to balloon in 90 minutes) or A streptokinase-based pharmacoinvasive strategy (patients receive streptokinase within 30 minutes of presentation and then coronary angiography done within 3-24 hours after thrombolytic therapy).

Exclusion criteria:  patients had history of myocardial infarction, and Previous PCI or Coronary bypass graft, poor echo-window, arrhythmia( atrial fibrillation in particular, as it interferes with the proper analysis of the three-dimensional echo.), mechanical complications of myocardial infarction,  circulatory instability, significant valvular, or congenital heart disease or myocardial diseases, inability to follow up and severe non-cardiovascular disease, i.e. (hepato-cellular failure, renal failure, cancer patients receiving chemotherapy) was excluded from the study.

The protocol and all corresponding documents were approved by Ethical and Research committee, Faculty of Medicine, Al-Azhar University and patients provided informed consents. All subjects were exposed to full history taking, general and local cardiac examination, and GRACE risk score assessment.

Acute STEMI was diagnosed according to criteria described in the fourth universal definition of MI when at least two contiguous leads with ST-segment elevation ≥ 2.5mm in men < 40 years, ≥2mm in men≥ 40 years, or≥1.5mm in women in leads V2–V3 and/or ≥ 1mm in the other leads [in the absence of left ventricular (LV) hypertrophy or left bundle branch block LBBB)].⁶

Vascular (coronary angiographic) assessment:

 Coronary angiography was performed. (CAG) to detect coronary artery lesions using a device (Allura Xper FD20, Philips Medical Systems). Infarction related artery confirmation based on result CAG and PCI was done to restore blood flow, we assessed patency of Infarction-related artery, severity of coronary artery disease, TIMI flow (Coronary Artery based on visual evaluation of contrast opacity rate in the affected artery, divided into TIMI 0 And the I And the II And the III) before and after PCI and no reflow(acute reduction in coronary flow In the absence of Dissection, thrombosis, spasm, or high-grade residual stenosis of the target lesion. ⁷

Echocardiography

 Standard two-dimensional and three dimensions echocardiography were done at baseline (within 24 h after PCI), and at 3-months follow-up. We defined the LV remodeling at three months as an increase in LV end-diastolic volumes (LVEDV) of greater than 20% from baseline study.⁸

Echocardiographic examination was performed usingPhilips I E33 X Matrix ultrasound machine (S5-1 and X5-1 multi frequency (1 - 5 MHz) matrix array transducers, ECG-gated examination mostly was used to help us during image acquisition and later analysis. Measurements and calculations of different cardiac chambers and ejection fractions were made according to the recent recommendations of the American Society of Echocardiography.⁴

Resting transthoracic echocardiography (2D TTE):

Themotion-mode modality(M-mode) was taken from parasternal long axis view to measure linear internal dimensions of the left ventricle (LVIDd, LVIDs), It is carefully obtained perpendicular to the LV long axis, and measured at the level of the MV leaflet tips, The left ventricular volumes were calculated from apical 4-chamber and 2-chamber views according to modified Simpson’s method ,Ejection fraction (EF) was calculated from estimation EDV and ESV using the following formula: EF = (EDV – ESV) / EDV). Resting regional wall motion abnormality assessment by two observer from all acquired 2-D views, The 16 segment model of myocardial segmentation was used; each segment is then scored, using the following criteria: Normokinesia (1 point): normal wall thickening and endocardial excursion, Hypokinesia (2 points): reduced wall thickening, reduced endocardial excursion, Akinesia (3 points): absence of either wall thickening or endocardial excursion and Dyskinesia (4 points): systolic outward stretching or thinning ⁴

Measurements by3D Echocardiography:

3D images were acquired in real time (RT) by X5‑1 probe, All echocardiographic images were digitally stored; measurements of LV volumes done offline using (QLAB advanced software package (Q Lab Version 9.0 3DQAdvanced software, Philips), by two independent observer. The acquisition of the 3D images was carried out after the 2D echocardiographic study. The 3D images were obtained in expiratory apnea with the image attached to the ECG record. The full volume data of the LV was organized into orthogonal four, two chamber, and short axis views. End diastolic and end systolic frames were selected. Mitral annular and apical points were placed on these images. Semi‑automated LV endocardial border detection software on Q Lab outlined the endocardial borders in these three planes. The software then used sequence analysis to track the endocardium in all frames and then automatically calculate a true 3D EDV, ESV, and EF from the moving 3D endocardial shell, the left ventricular remodeling was defined as an increase in 3D echocardiographic LV end-diastolic volume (LVEDV) of greater than 20% from baseline study⁹ (Figur 1).

Fig 1: Advanced cardiac 3D quantification.

Statistical analysis:

 Recorded data were analyzed using the SPSS; version 20.0, Quantitative data were expressed as mean± standard deviation (SD). Qualitative data were expressed as frequency and percentage. Probability (P-value) P-value 0.05 was considered insignificant. Receiver operating characteristic (ROC curve) analysis used to find the overall predictively of parameter in and to find out the best cut-off value with detection of sensitivity and specificity at this cut-off value.

RESULTS

In terms of demographic data, there were statistically negligible differences between the two groups, mean age in Group I was 56.70±6.16 years compared to 54.70±7.97 years in Group II with (p-value 0.163). Thirty seven patients (74%) in Group I were males and 13 patients (26%) were females, while in group II 37 patients (74%) and 13 patients (26%) were male and female respectively. Also, the two groups were comparable in body mass index with the mean in each of Group I and Group II was 33.03±2.69 Kg/m2compared to 32.91±2.30 Kg/m2 respectively with (p-value 0.805). As regard risk factors, there were insignificant difference between the two groups (p >0.05 non-significant) (Table 1).

Two dimensional echocardiographic data: the two groups were comparable according to conventional (2DTTE) parameters at baseline and follow up studies, the mean LVEDD ±SD in Group I at baseline study was 5.39±0.24 cm and in follow up study after three months was 5.36±0.50cm, while the mean LVEDD±SD in group II at baseline was 5.36±0.28 cm and at follow up it was 5.30±0.45 cm (p-value=0.427). The mean LVESD ±SD in Group I at baseline study was 4.16±0.29 cm and at follow up study was 4.07±0.57cm, while the mean LVESD±SD in group II at baseline study was 4.90±0.65 cm and follow up after three months was 4.59±0.56 cm (p-value 0.353), mean EF% in group I at baseline study was (39.78±4.30%) and at follow up was 43.28±6.14% ,while mean EF% in group II at baseline study was 41.12±3.45% and at follow up was 45.04±5.74%, (p-value 0.142 ). Also, the two groups were comparable according to degree of mitral regurgitation at baseline and follow up studies , in group I 38 patients (76%) and 12 patients (24%) had mild and moderate mitral regurgitation respectively compared to Group II were 41 patients (82%) and 9 patients (18%) had mild and moderate mitral regurgitation respectively (p=0.461).

Three dimensional echocardiographic data:

LV remodeling was diagnosed in 17 patients (34%) in group I and in 15 patients (30%) in group II p-value=0.668 (Table 2).

Although, there were statistically considerable differences between changes occurred at baseline and follow up 3D dimensions echocardiographic LVED volume (P=0.026), and WMSI (P=0.015) in group I and in LVED volume (P=0.0096), LVES volume (P=0.008), and WMSI (P=0.022) in group II, there were insignificant differences between all 3D echocardiographic parameters between the two study groups at baseline studies (table-3). The only exception was LVES volume in baseline study, where it was 75.06±17.83 ml in group I, and was 71.58±16.85 ml in group II (p-value= 0.033).

 Average left ventricular end diastolic volume (LVEDV) at baseline studies, in group I (pharmaco-invasive) was 120.72±10.84 ml, and in group II (primary PCI) it was 116.97±10.24 ml, while at follow up studies, it was 126.56±20.47 ml in group I and in group II it was 123.16±18.21ml. P values for comparisons of all parameters between two study groups were >0.05. 0.078). Left ventricular end systolic volume (LVESV) at baseline in group I was 73.46±9.48 ml, while in group II it was 69.69±7.87 ml (p-value= 0.033), at follow up studies, it was 75.06±17.83 ml in group I, and was 71.58±16.85 ml in group II (P=0.318). Both groups also were comparable in ejection fraction% with the mean in Group I at baseline was 40.00±3.37%,while in group II mean EF% at baseline was 40.56±3.41% and follow up values was 41.60±5.60% in group I, while in group II it was 42.99±6.18% (P values > 0.05).

 Mean Wall motion score index (WMSI) in group I at baseline was (1.95±0.17) and in group II mean WMSI at baseline was (1.94±0.18) , and at follow up it was (1.85±0.26) in group I, while and follow up was (1.84±0.27) in group II (P values > 0.05) (Table 3).

short term follow up clinical outcome: bleeding risk  occurred in 5patients (10%) in group I, and one patient (2%) in group II ,(P-value=0.022),No patients had re-infarction in both groups, acute CVA occurred in 3 (6.0%) in group I compared to 4 (8.0%) in group II,(p-value=0.695), Heart failure symptoms occurred in 8 (16.0%) in group I and group II (p-value=1.000) (Table 4).

ROC curve to predict Left ventricular remodeling using the Grace Score used to define the best cut off value of GRACE score which was ≥139in group I, with sensitivity of 100% specificity of 57.6% positive predictive value of 54.8%, negative predictive value of 100% with diagnostic accuracy of 83%, in group II was ≥142, with sensitivity of 86.7% specificity of 60% positive predictive value of 48.1%, negative predictive value of 91.3% with diagnostic accuracy of 75.6% and in all patients groups best cut off value of Grace Score which was ≥142, with sensitivity of 93.7% specificity of 58.8% positive predictive value of 51.7%, negative predictive value of 95.2% with diagnostic accuracy of 79.1%. (Tables 5 and 6),Figure (2)

Fig 2: Receiver-operating characteristic (ROC) curve for prediction of Left ventricular remodeling using the Grace Score in all patients

Coronary angiography results: total occlusion of left anterior descending coronary artery (LAD); was found in 30 patients (60%) in group II, compared to 8 patients (16%) in group I, (p-value<0.001), TIMI III flow post revascularization obtained in 33 (66.0%) in group I and in 29 (58.0%) in group II,(p-value= 0.670),No reflow occurred in 5 patients in group I, and in 6 patients in group II, (p-value=0.749).

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Table 1: Comparison between Group I and Group II according to demographic data and risk factors.

Table 2: Comparison between group I and Group II according to percentage of left ventricular remodeling (LVR).

Table 3: Differences between baseline and follow up studies according to 3D three dimensions echocardiographic parameters in both groups.

Table 4: Comparison between Group I and Group II, according to short term Clinical Follow up..

Table 5: Comparison between subgroups Ia and Ib according to GRACE Score in group I

Table 6: Comparison between subgroups IIa and IIb according to GRACE Score in group II