Establishing the role of serum cardiac markers in diagnosis of acute chest pain (A Study of 200 cases)

Introduction: Acute myocardial infarction (AMI) continues to be a major health problem in industrialized and developing countries like India despite progressive research in diagnostic and management over last three decades. AMI has typically been diagnosed on the basis of triad of clinical syndromes of chest pain, electrocardiogram (ECG) changes and elevated serum enzyme activity. Due to high cardiac specificity of ckmb, cTnI, these biomarkers have become the recommended biomarkers for the diagnosis of myocardial injury. Aims: To study changes in serum cardiac markers and determine the sensitivity and specificity of Highly sensitive Troponin I, CK-MB and LDH. Material and Methods: It was undertaken from November-2015 to December-2016 during which 200 patients were studied. All the patients having complaint of acute chest pain admitted in the emergency wards are included. Serum level of cardiac Troponin I was determined by using vidashigh sensitive troponin i (human cardiac specific) enzyme immunoassay kit, CK-MB was determined by the vitros 250 fully automated biochemistry analyser, serum level of LDH was determined by ldh- (p-l) reagent kit (kinatic procedure). Result: In present study, out of 200 patients who admitted for complaining of acute chest pain, 110 patients actually diagnosed to have acute myocardial infarction. Sensitivity and specificity of hs Troponin I for diagnosis of acute myocardial infarction was 100%. CK-MB was 89.1% and 88.8% and LDH was 65.4% and 60% respectively. Conclusion: Among the cardiac markers studied hs Troponin I is the most specific and sensitive for diagnosis of acute myocardial infarction. As CK-MB levels become normal within 2-3 days, it is helpful in diagnosis of reinfarction.


Introduction
Coronary heart disease (CHD) is a major public health problem in developed countries and it is becoming more common worldwide. Acute coronary syndromes (ACSs) are attacks in which blood flow in coronary arteries is abruptly reduced or stopped, usually due to fissuring or rupture of atherosclerotic plaques and subsequent thrombosis, leading to myocardial ischemia. If this process leads to myocardial cell necrosis, the result is a myocardial infarction (MI) [1].
The early (30 days) mortality rate from AMI is approximately 30 percent, with more than half of these deaths occurring before individual reaches the hospital [2]. Accurate identification of the cause of chest pain is a challenge to the emergency physician because a significant proportion of patients with acute coronary syndrome (ACS) present atypically [3]. In 1979, in addition to symptoms and ECG changes, WHO recognized officially the use of biomarkers in the diagnosis of acute MI, by demonstration of typical rising and falling pattern [4]. In the middle of 1980s, mass assay of CK-MB instead of catalytic activity was developed [5]. CK-MB was the marker of choice (gold standard) in the diagnosis of acute MI in 1980s [6]. Assays for cardiac troponins were developed in the late 1980s and early 1990s [7]. Accuracy of ECG diagnosis of AMI is not more than 80 percent and it is often found that in cases of early AMI the ECG could be normal. So the enzyme estimation has become of immense utility in early diagnosis. For specific diagnosis, combination of several enzymes is used. Due to high cardiac specificity of cTnT and cTnI, these biomarkers have become the recommended biomarkers for the diagnosis of acute myocardial injury [8]. High sensitive cardiac troponin T (hs-cTnT) is a modification of 4th generation cTnT69 [9].  In present study, we collected samples of 200 patients  admitted with the complain of acute chest pain and  measured the following markers, Highly sensitive  Troponin I (HS-TROP I), CK-MB and LDH.

Material and Methods
Study Design: This is a prospective study of 200 cases. Study setting: The study was carried out in tertiary care centre affiliated with Gujarat adani institute of medical science.
All the patients having complaint of acute chest pain admitted in the emergency wards are included. The diagnosis was based upon the ECG findings, complains, other relevant clinical findings and serum cardiac markers. Serum estimation of Highly sensitive Troponin I, CK-MB, and LDH was done. Blood samples were collected in plain bulb, at the time of admission and serum were separated by centrifugation.

Method Used:
The serum level of cardiac Troponin I was determined by using VIDAS HIGH SENSITIVE troponin i (human cardiac specific) enzyme immunoassay kit.
The reference range for hs Troponin I with this kit is <19 ng/l. The measurement range of High sensitivity Troponin I with this kit is from 4.9 to 40,000 ng/l.

Results
This study involves the changes in serum cardiac markers (hs-Troponin I, CK-MB, LDH) in patients admitting for the chest pain in emergency department.  From above data it is found that out of 110 patients who actually diagnosed to have acute myocardial infarction, hs Troponin I was elevated in all 110 patients. While in 90 patients who diagnosed to have other condition than acute myocardial infarction, hs Troponin I was elevated in none of them. So, in present study for hs Troponin I Sensitivity was 100% and Specificity was 100% for diagnosis of acute myocardial infarction. From above data it was found that out of 110 patients who actually diagnosed to have acute myocardial infarction, CK-MB was elevated in all 98 patients. In 12 patients in spite of having acute myocardial infarction it remained in normal range. While in 90 patients who diagnosed to have other condition than acute myocardial infarction, CK-MB was elevated in 10 patients and in 80 patients it remained in normal range.
So, in present study for CK-MB Sensitivity was 89.1% and Specificity was 88.8% for diagnosis of acute myocardial infarction.

Discussion
Present study involves the changes in serum cardiac markers (hsTroponin I, CK-MB, LDH) in patients admitting for the acute chest pain in emergency department.

Demographic profile of the patients: (mean age -59.04)
In present study, out of 200 patients admitted for acute chest pain 144 patient were in age group of 40 to 70 years, 20 patients were in age group of 20 to 40 years and 36 patients were more than 70 years of age. This results are comparable to other studies: Astudy was conducted on changing age distribution of first ever acute myocardial infarction among men and women. They found that the median age at which the index AMI occurred rose significantly (p<.0001); from 64 to 66 years of age among men, and from 72 to 77 years of age in women [10].
A study was conducted on age and gender differences in incidence and case fatality trends for myocardial infarction. They concluded that trends in MI incidence differed by sex and age; in the age group 35-79 years a marked decrease was observed among men but an increase was observed among women, while no change was observed among older patients. MI severity and case fatality were clearly reduced for both sexes. Their data suggested that the burden of CHD is shifting from middle-aged men toward middle-aged women and elderly patients [11].

Changes in hsTroponin I in patients complaining of acute chest pain
In present study, it was found that out of 110 patients who actually diagnosed to have acute myocardial In present study, sensitivity and specificity of hs Troponin I for diagnosis of acute myocardial infarction was 100%.
These results are comparable to other studies: A study was conducted on comparative analysis of cardiac Troponin I and Creatine Kinase-MB as markers of acute myocardial infarction. They concluded that cTnI is an excellent marker for detecting and ruling out AMI, because it has better specificity and a wider diagnostic window than the accepted standard, CK-MB [12].
A study on rapid diagnosis of acute myocardial infarction. Consecutive 150 patients admitted to the coronary care unit was studied. They concluded that measurement of CTn-I accurately detects MI in patients and should facilitate the diagnosis and management of such patients [13].
A study of cardiac troponin-i as a diagnostic marker in comparison with creatine kinase-MB in myocardial infarction. They found that the diagnostic efficiency of cardiac troponin-I is 97%, and creatine kinase -MB is 63% in diagonosis of acute MI. So they concluded that serum cardiac troponin-I is highly sensitive and specific cardiac marker which can substantially improve the early diagnosis of acute mycocardial infarction [14].
A study on Role of CK-MB and Troponin-I in Diagnosing Non-ST-Elevation Myocardial Infarction. They concluded that Troponin-I can identify the minimal cardiac damage which will be useful for the physician to start immediate intervention [15].

Changes in CK-MB in patients complaining of acute chest pain
In present study it was found that out of 110 patients who actually diagnosed to have acute myocardial infarction, CK-MB was elevated in 98 patients.
In 12 patients in spite of having acute myocardial infarction it remained in normal range. While in 90 patients who diagnosed to have other condition than acute myocardial infarction, CK-MB was elevated in 10 patients and in 80 patients it remained in normal range.
In present study sensitivity and specificity of CK-MB for diagnosis of acute myocardial infarction was 89.1% and 88.8% respectively.
These results are comparable to other studies: A study on comparable detection of acute myocardial infarction by creatine kinase MB isoenzyme and cardiac troponin I. They concluded that cTnI and MBCK had statistically indistinguishable diagnostic accuracies for the detection of acute myocardial infarction [16].
Astudy was conducted on diagnostic marker cooperative study for the diagnosis of myocardial infarction. They found that with each marker as the diagnostic standard, CK-MB sub forms and myoglobin remained the most sensitive for early diagnosis. So they concluded that the CK-MB sub form assay alone or in combination with a troponin reliably triages patients with chest pain and should lead to improved therapy and reduced cost [17].
Astudy was conducted on evaluation of CK-MB isoform analysis for early diagnosis of myocardial infarction. They concluded that analysis of CK-MB by high-voltage electrophoresis is an effective method for rapid diagnosis of MI, with the isoform analysis enhancing early sensitivity [18].
A study was conducted,. They concluded that CK-MB and CTnT were the earliest was more compared to other serological markers. CK-MB is more helpful in the diagnosis of reinfarction [19].

Changes in LDH in patients complaining of acute chest pain
In present study, it was found that out of 110 patients who actually diagnosed to have acute myocardial infarction, LDH was elevated in all 72 patients. In 38 patients in spite of having acute myocardial infarction it remained in normal range.
While in 90 patients who diagnosed to have other condition than acute myocardial infarction, LDH was elevated in 36 patients and in 54 patients it remained in normal range. In present study sensitivity and specificity of LDH for diagnosis of acute myocardial infarction was 65.4% and 60% respectively.
A study on comparison of cardiac troponin I and lactate dehydrogenase isoenzymes for the late diagnosis of myocardial injury. In this study, the sensitivity of cardiac troponin I (cTnI) and LD1/LD2 were compared as late markers of myocardial injury over a 5day period in 36 patients admitted with a diagnosis of myocardial infarction to the coronary care unit. Over this period, the sensitivity of cTnI was significantly greater than that of LD1/LD2 (P <0.05). They concluded that cardiac troponin I (cTnI) has greater sensitivity than lactate dehydrogenase isoenzymes for delayed diagnosis of myocardial injury and is a more cost-effective test, the authors recommend it as a test of choice in this setting [21].
A study in which they emphasized on serological cardiac markers i.e., creatinine kinase-M& B chains (CK-MB), cardiac troponin-T (CTnT), Aspartate amino transferase (AST) and lactate dehydrogenase (LDH). They found that CK-MB and CTnT were the earliest serological markers to be detected in blood following AMI. Sensitivity of CTnT was more compared to other serological markers. Presence of CTnT was better diagnostic of AMI in vital period. CK-MB is more helpful in the diagnosis of reinfarction [19].
"These data suggest that LDH is a marker of myocardial damage but not as much sensitive and specific as hsTroponin I, CK-MB."

Conclusion
Based on present study, it is concluded that acute myocardial infarction require immediate diagnosis and intervention. In early diagnosis cardiac markers are very useful to differentiate acute myocardial infarction from other conditions. "Among the cardiac markers studied hs Troponin I is the most specific and sensitive for diagnosis of acute myocardial infarction. It can diagnose AMI as early as 2 hours after acute myocardial injury. Hence sensitivity and specificity of hs Troponin I is 100 %.
As CK-MB levels become normal within 2-3 days it is helpful in diagnosis of reinfarction. LDH are also the markers of myocardial damage. CK-MB and LDH although useful but they fails to identify the patients in the gray zone and very early phase of AMI." Funding: Nil, Conflict of interest: None initiated Permission from IRB: Yes