Predictive Value of Apoptotic Factor M30 for Negative Left Ventricular Remodeling in Patients Undergoing Primary Percutaneous Coronary Intervention

Research Article

Austin Cardiol. 2021; 6(1): 1028.

Predictive Value of Apoptotic Factor M30 for Negative Left Ventricular Remodeling in Patients Undergoing Primary Percutaneous Coronary Intervention

Yusuf J¹, Mukhopadhyay S¹*, Viadya PN¹, Gautam A¹, Mehta V¹, Gupta MD¹ and Mahajan B²

¹Department of Cardiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India

²Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India

*Corresponding author:Mukhopadhyay S, Department of Cardiology, First Floor, Academic Block, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi-110002, India; Email: saibalmukhopadhyay@yahoo.com

Received: April 14, 2021; Accepted: May 07, 2021; Published: May 14, 2021

Abstract

Background: Left Ventricular Negative Remodeling (LVNR) following Primary Percutaneous Coronary Intervention (PPCI) is an important cause of LV systolic dysfunction due to Irreversible Myocardial Injury (IMI). Both necrosis and apoptosis contribute to IMI and LVNR. We assessed the role of specific apoptotic marker M30 in predicting LVNR in patients of anterior wall ST Elevation Myocardial Infarction (STEMI) undergoing PPCI within 12 hours of symptom onset.

Methods: This prospective study was done on 100 consecutive patients of anterior wall STEMI (87 men and 13 women, mean age 52.15±12.08 years) meeting our inclusion and exclusion criteria. Blood sample for M30 was drawn at 24 hours after symptom onset, when it reaches peak level. Transthoracic echo was done in each patient at 24 hours after PPCI and at 6 months. LVNR was defined as ≥20% increase in LV end diastolic volume at 6 months after PPCI.

Results: 44 patients (44%) developed LVNR at 6 months post PPCI. Diabetes mellitus (p=0.032), symptom onset to balloon time (p=0.059), CPK-MB (p=0.007) and M30 level (p=0.012) were independent predictors of LVNR. The cutoff value of M30 for predicting LVNR was 81.18u/ml with positive predictive value of 70.4% (AUC 85.3, p<0.001).

Conclusion: In patients of anterior wall STEMI undergoing PPCI, the apoptotic marker M30 is useful for early prediction of LVNR. This can assist in better risk stratification of patients after successful PPCI and identify the subgroup of patients who require more intensive medical follow up with antiremodeling drugs to attenuate the development of LVNR.

Keywords: Left ventricular negative remodeling, apoptotic biomarker; STelevation myocardial infarction; primary angioplasty percutaneous coronary intervention; CPK-MB; M30

Abbreviations

LVNR: Left Ventricular Negative Remodeling; IMI: Irreversible Myocardial Injury; PPCI: Primary Percutaneous Coronary Intervention; STEMI: ST-Elevation Myocardial Infarction; CPKMB: Creatine Phosphokinase-Myocardial Band; CK: Cytokeratin; LVEDV: Left Ventricular End Diastolic Volume; LAD: Left Anterior Descending Artery; TIMI: Thrombolysis in Myocardial Infarction; ACEI: Angiotensin Converting Enzyme Inhibitors; ARBs: Angiotensin Receptor Blockers; TTE: Trans-Thoracic Echocardiography; LVESV: Left Ventricular End Systolic Volume; LVEF: Left Ventricular Ejection Fraction; WMSI: Wall Motion Score Index; NT-ProBNP: N-Terminal-Pro-B-Type Natriuretic Peptide; ELISA: Enzyme Linked Immunosorbant Assay; SPSS: Statistical Package for the Social Science; SD: Standard Deviation; IQR: Inter- Quartile Range; ROC: Receiver Operating Characteristics; AUC: Area Under the Curve; BMI: Body Mass Index; GDMT: Guideline Directed Medical Therapy

Introduction

Left Ventricular Negative Remodeling (LVNR) i.e. progressive LV dilatation in spite of successful Primary Percutaneous Coronary Intervention (PPCI) is a major clinical problem in the modern era of ST-Elevation Myocardial Infarction (STEMI) management [1]. The most important predictor of LVNR following STEMI is the infarct size [2]. Both necrosis and apoptosis causing irreversible myocardial injury contribute to LVNR after STEMI [3]. The peak level of the necrotic biomarker Creatine Phosphokinase-Myocardial Band (CPKMB) following PPCI has been shown to be good predictor of infarct size and subsequent development of LVNR [4]. Turkoglu C, et al. [5] have shown that peak serum level of apoptotic factor M30 is also an independent predictor of LVNR at 6 months following PPCI. Both animal [6] and human studies [7] have shown that apoptosis occurs in 5-30% of cells in the infarct area during an acute coronary syndrome. Apoptosis and necrosis are morphologically distinct pathways leading to cardiomyocyte loss during ischemia and reperfusion [8].

During apoptosis, a number of intracellular proteins are cleaved by caspases. A neo-epitope in Cytokeratin (CK)-18, termed M30 antigen becomes available at an early caspase cleavage event during apoptosis and is not detected in vital or necrotic cells. A monoclonal antibody M30 specifically recognizes this M30 antigen. A fragment of CK18 (termed M65 antigen) is also released from cells during necrosis [9]. In accordance with other described studies [10], Senturk et al [11] and Turkoglu C et al [5] had assessed both M30 and M65 in patients of STEMI as marker of apoptosis and necrosis respectively. Turkoglu C et al [5] had shown M30 to be an independent predictor of LVNR in the European population, No study till date has been carried out in the Southeast Asian population to define the cut off value of M30 in this ethnic group. As the Body Mass Index (BMI) of our population is much lower than that of the studied European population, we carried out a pilot study to assess the cut off value of M30 in our population.

Methods

In this prospective study, 100 consecutive patients presenting with first episode of anterior wall STEMI within 12 hours of symptom onset to our emergency were studied. Flow chart of study design is shown in Figure 1. We have excluded the patients who were in (i) Killip class- IV, (ii) had presented with systolic blood pressure <90 mm Hg, (iii) presented with failed thrombolysis, (iv) had past history of myocardial infarction/ PCI/ coronary artery bypass surgery, (v) associated significant valvular heart disease, (vi) renal/liver failure, (vii) pregnancy, (viii) unprotected left main disease, (ix) flow in Left Anterior Descending artery (LAD) greater than TIMI-2, (x) expired within 24 hours of PPCI prior to echocardiographic evaluation for the study , (xi) poor transthoracic echo (TTE) window or (xii) had malignancy detected for which patients were under active treatment.