Prognostic Signicance of Right Ventricular Global Longitudinal Strain in Acute Myocardial Infarction and Angiographic Correlation

Objectives of this study were to evaluate right ventricular function using two dimensional speckle tracking echocardiography among patients who were admitted with acute myocardial infarction and treated with primary angioplasty, association between right ventricular strain global longitudinal strain and major adverse cardiovascular events and to analyse the angiographic results of all patients. This was a prospective observational study conducted in 200 consecutive patients admitted with acute inferior wall myocardial infarction and treated with primary angioplasty. Right ventricular global longitudinal strain was measured by two dimensional speckle tracking echocardiography and angiographic results of all patients were recorded. All patients were followed up till discharge / death. Categorical data were compared using Chi-square test or Fisher’s exact test. Logistic regression was done to nd out the major adverse cardiovascular outcomes predictive by RVGLS. P < 0.05 was considered statistically signicant. right for wall , right longitudinal in predicting major adverse cardiovascular and analyse results of all


Introduction
Right ventricular ischemia due to acute inferior wall myocardial infarction is a major predictor of short and long adverse cardiovascular outcomes like arrhythmias, cardiogenic shock, heart failure and death 1 . The incidence of right ventricular involvement in acute inferior wall myocardial infarction varies from 30-50% 2. Due to complex anatomy and asymmetric shape of the right ventricle earliest recognition of right ventricular dysfunction is challenging and conventional echocardiographic measures of right ventricular function assessment like fractional area change ,tricuspid annular plane systolic excursion are abnormal only after overt dysfunction sets in 3 . Longitudinal strain measured by speckle tracking echocardiography bridges this gap by detecting ventricular dysfunction at a subclinical stage and aids the clinician in planning an earliest interventional strategy and reduce in-hospital mortality 4,5 .
This study was designed to evaluate right ventricular function using myocardial deformation techniques(two dimensional speckle tracking echocardiography ) in patients who were successfully treated for their rst acute inferior wall myocardial infarction , to assess the accuracy of right ventricular global longitudinal strain in predicting major adverse cardiovascular events and to analyse the angiographic results of all patients.

Materials And Methods
This was a prospective observational study conducted in the Department of cardiology, Government TD Medical College and hospital, Alappuzha from 1-10-2019 to 1-11-2020. This study was conducted in accordance with the declaration of Helsinki and was approved by Institutional Ethics Committee (Reg no: ECR/ 122/Inst/KL/2013/RR-2016).
200 consecutive patients diagnosed with acute inferior wall myocardial infarction presenting within 12hrs of symptom onset, and had underwent primary angioplasty were included in the study. Patients with history of bundle branch block, prior history of myocardial infarction, percutaneous trans-luminal coronary angioplasty, acute stent thrombosis and patients with history of pulmonary hypertension (valvular heart disease, lung disease, and cardiomyopathy) renal, hepatic, hematological disorders and malignancy were excluded from the study.
PRIMARY OBJECTIVE of the study was to evaluate right ventricular function using myocardial deformation techniques (two dimensional speckle tracking echocardiography) among patients who were successfully treated for their rst acute inferior wall myocardial infarction.
The secondary objectives of this study were: 1. To assess right ventricular global longitudinal strain in predicting major adverse cardiovascular events like heart failure, arrhythmias, recurrent angina, arrhythmia, re-infarction, target lesion revascularisation and prolonged hospital stay and death 2. To analyse the angiographic results of all patients Demographic data, history of comorbid illnesses were collected with the help of a structured questionnaire. Right ventricular global longitudinal strain was measured by two dimensional speckle tracking echocardiography (GE VIVID E9-ECHOPAC software e) after primary angioplasty and coronary angiographic results of all patients were recorded. Informed consent was obtained from all individual participants included in the study. All patients were followed up till discharge / death. Target lesion revascularisation -Patients who underwent repeat intervention after revascularisation in the culprit lesion due to recurrent symptoms and electrocardiographic features of reinfarction • Duration of hospital stay (prolonged hospital stay de ned as hospital stay more than 5 days.
• Death SAMPLE SIZE: Due to gross variation in the prevalence of right ventricular infarction in inferior wall myocardial infarction conducted in various studies and due to COVID-19 pandemic , all patients admitted with acute inferior wall infarction in department of cardiology, Government TD medical college and hospital, Alappuzha from October 2019 -September 2020 were included in the study.

STATISTICS:
All the data collected were coded and keyed in Microsoft Excel sheet were re-checked and analysed using SPSS Statistics V22.
• Quantitative variables were summarised using mean and standard deviation or median and interquartile range (IQR), depending on the normality of distribution.

•
Categorical variables were represented using frequency and percentage.
• Categorical data were compared using Chi-square test or Fisher's exact test.
• Logistic regression was done to nd out the major adverse cardiovascular outcomes predictive by RVGLS. P < 0.05 was considered statistically signi cant.

Results
200 patients were enrolled for the study of which were 102 (51%) patients and 98 (49 %) patients were males and females respectively. The baseline characteristics of the study population are summarised in table 1 Triple vessel disease involving the, RCA, LCX and LAD was found in 22.5% (n=45) of the study population.
The echocardiographic and angiographic characteristics of the study population are summarised in table  2   Table 2: Echocardiographic and angiographic characteristics COMPLICATIONS: Atrioventricular Blocks were the most common complication observed in 33.5% of the study population. 24 patients (12%) had complete heart block at presentation and 3 patients (1.5%) developed Mobitz type 2 atrioventricular block ( gure 1).  21 patients (52.5% ) in the age group of 60-70 years and 29 patients (64.4%) above 70 years had a low RV GLS .The difference observed in the incidence of abnormal RV GLS between the various subgroups of age were not statistically signi cant (p=0.589).
The difference observed in RV GLS among individuals with risk factors like hypertension , diabetes , thyroid disorders ,CVA , smoking ,alcoholism were not statistically signi cant ( Table 3) Association of wall involved with RV GLS: About 58.7% (n=61) of the individuals with inferior, right ventricular and posterior wall myocardial infarction (IW+RV+PW) had low RV GLS that was statistically signi cant (p<0.001). (Table 4) Association of angiographic lesions with RV GLS: Patients with triple vessel disease had relatively higher incidence of low RV GLS the difference observed in RV GLS between the three different angiographic pro les were statistically signi cant (p<0.001) ( Table  4) Association of complications with RV GLS: The difference observed in RV GLS among patients who developed complications like arrhythmias, heart failure, target lesion revascularisation and prolonged hospital stay were found to be statistically signi cant. (Table 4) The difference observed in RV GLS between patients who developed recurrent angina, re-infarction and death did not differ signi cantly from patients who had no complications.
In multivariate analysis, RVGLS was predictive of two complications namely target lesion revascularisation and arrhythmias (Table 5) The ROC curve for RV GLS to predict major adverse cardiovascular events was to the left of the reference line (> 45 degree diagonal of the ROC space) ( gure 3) indicating good sensitivity and likelihood ratio to predict major adverse cardiovascular events The AUC (Area under the curve) for RV GLS was 0.915 which indicates that RV GLS has good accuracy to predict major adverse cardiovascular events (Table 6) From our study, the optimal cut off score for RV GLS in predicting major adverse cardiovascular outcomes was -14.8 %with a sensitivity of 0.813 and speci city of 0.868.

Discussion
Patients with low RV GLS had signi cantly higher incidence of major adverse cardiovascular events like arrhythmias , ventricular failure , target lesion revascularisation and prolonged hospital stay, angiographic triple vessel disease , low TAPSE and S' . In multivariate analysis RVGLS was found to be predictive of hemodynamically signi cant arrhythmias and target lesion revascularisation. (Table 5).
The difference observed in RV GLS among the baseline characteristics like age, sex, diabetes mellitus, systemic hypertension, thyroid illness, stroke, smoking and alcoholism were not statistically signi cant. There was no signi cant association between RV GLS and re-infarction, recurrent angina and mortality.
The study population comprised nearly equal proportion of males and females with two third (62.5%) of the individuals over 50 years. Risk factors for cardiopulmonary disease like diabetes, hypertension, and hypercholesterolemia were present in more than 50% of the study population. Though 60% of diabetics and 70% of hypertensive were found to have low GLS, the difference observed was not statistically signi cant (diabetes à P=0.061, hypertension àP=0.107). The traditional risk factors for developing coronary artery disease independently as well as synergistically could alter measures of right ventricular function assessment by speckle tracking that might have implications in predicting the prognosis of these patients. The normal values of RV GLS differs according to the age, sex and demographics, the usual range being for women (−26.7 ± 3.1) , for men (−24.7 ± 2.6 ).
The mean RV GLS of the study population ranges from -13% to -20% , with very low values of RV GLS observed in patients with cardiogenic shock complicated by complicated by complete heart block (70%) and ventricular tachycardia (66%)(P=0. Among 45 patients (ventricular tachycardia, Mobitz type 2 AV block and complete heart block) 32 patients (16%) with low RV GLS, developed hemodynamic compromise with cardiogenic shock and required inotropic support. The plausible explanation for higher incidence of arrhythmias and need for inotropic support in patients with low RV GLS could be mechanical and electrical heterogeneity of right ventricular myocardium which serves as a substrate for development for arrhythmias 10,11,12 . Though the incidence of reinfarction, recurrent angina and death were proportionately higher in individuals with low RV GLS the difference observed was not statistically signi cant. The incidence of reinfarction and recurrent angina depends on factors like patient delay, system delay, previous infarction, comorbid illnesses, procedural characteristics like slow ow, edge dissection and the thrombus burden at the time of angioplasty. The incidence of target lesion revascularisation and the duration of hospital stay was higher in individuals with lower right ventricular global longitudinal strain and the difference observed was statistically signi cant (P=0.029).

COMPARISON OF RV GLS CUT OFF VALUES WITH PREVIOUS STUDIES:
In the study done by Park et al 13 , in a total of 282 consecutive inferior STEMI patients treated with primary PCI on follow-up for , 54 month), 59 patients (21%) had 1 or more major adverse cardiovascular event (MACE) (43 deaths, 7 nonfatal MI, 4 target vessel revascularization, and 6 heart failure admission).The best cut off value of GLSRV for the prediction of major adverse cardiovascular events was 15.5% ( p<0.001) with a sensitivity of 73% and a speci city of 65% .
Jurcut et al 14 , concluded that the cut off values for right ventricular global longitudinal strain to predict early mortality in patients with acute inferior wall infarction with right ventricular infarction was. RV GLS ≤ -14% with a sensitivity of 88.9% and a speci city of 62.5% (AUC: 0.817, P = 0.002) From our study , the optimal cut off score for RV GLS in predicting major adverse cardiovascular outcomes was -14.8 % (( AUC = 0.915 , a 95 % con dence interval 0.876-0.954 , p<0.001) with a sensitivity of 81.3 % and speci city of 86.8 %.
Inferior wall infarction results in cardiogenic shock more frequently than anterior wall infarction due to right ventricular involvement 15 , Bezold -jarish re ex 16  The clinical application of RVGLS highlighted in our study has been demonstrated in representative gure4 and gure5. Patient1 presented with inferior+right+posterior wall acute myocardial infarction. The conventional measures of assessment of right ventricular function namely TAPSE ( gure4a) and S' ( gure4b) were normal with values of 20mm and 0.12 m/s respectively. However, RVGLS was very low with a value of 13.2% ( gure4c,4d). The patient had angiographic triple vessel disease with a 90% discrete stenosis of the mid RCA( gure5a) , bifurcation lesion of LAD-D1(medina 1,1,1) gure5c) and a diffusely diseased LCX ( gure5b). The patient underwent primary angioplasty of the right coronary artery ( gure5d) and was planned for elective angioplasty of the left anterior descending artery later.

CLINICAL APPLICATIONS OF RVGLS :
In a study done by Hamada et al 21  Among patients presenting with inferior wall infarction and treated with primary angioplasty, RVGLS was superior to the conventional echocardiographic parameters in predicting recovery and late remodelling of the right ventricle that is associated with the occurrence of future cardiovascular events like recurrent heart failure, recurrent infarction due to stent thrombosis . 26 In patients presenting with NSTEMI, RVGLS was signi cantly associated with poor cardiovascular outcomes and hemodynamically signi cant arrhythmias 27 Abnormally low RV GLS may represent a dysynchrony in the right ventricle resulting in mechanical and electrical heterogeneity setting a milieu for development for recurrent arrhythmias and heart failure 28 . In the current study, statistical signi cant association of RV GLS were observed with parameters like ejection fraction, TAPSE, S', multivessel disease, arrhythmias and, target lesion revascularisation and duration of hospital stay.
Since strain imaging by speckle tracking analysis the contraction of the myocardium in three orthogonal planes (longitudinal, radial and circumferential), longitudinal strain can detect subclinical dysfunction at an early stage when the conventional parameters may be normal and obviating the limitations of conventional measures 29 .
Right ventricular global longitudinal strain measurement in acute coronary syndromes is an important predictor of complications like malignant ventricular arrhythmias, heart failure, reinfarction 30 that would help in risk stratifying the patients and plan an earliest appropriate interventional strategy.

Conclusion
The severity of acute myocardial infarction have been conventionally categorised based on clinical evaluation (KILLIP class) 31, electrocardiogram (Scarlovsky Birnbaum grading -myocardium at risk) 32 and echocardiogram (TAPSE, S') 33. Since right ventricular global longitudinal strain could identify right ventricular dysfunction at a subclinical stage RV GLS might be used in addition to the above conventional methods to risk stratify patients admitted with acute myocardial infarction, prevent the progression of salvageable myocardium to infarction and necrosis and could serve as an independent prognostic marker in predicting major adverse cardiovascular events and in hospital outcomes. This was a single centred prospective observational study with a small sample size.
The study population comprising mostly patients with cardiopulmonary risk factors could have resulted in higher incidence of complications (multivessel disease , heart failure and reinfarction).The study population had wide range of variation in absolute values of right ventricular global longitudinal strain and the cut-off values for RV GLS predictive of adverse outcomes were derived from a sample of 200 patients that may not be representative of a larger cohort in a tertiary care setting .

FUNDING:
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

COMPETING INTERESTS:
The authors have no relevant nancial or non-nancial interests to disclose.