Assessment of left ventricular function using serum cardiac troponin I measurements following myocardial infarction

Abstract

The prognosis and extent of injury to the myocardium have previously been assessed by increased serum creatine kinase (CK) MB levels. We report findings from 39 consecutive, acute myocardial infarction (AMI) patients presenting 4.5 h (range, 0.7–12.1 h) after the onset of chest pain. We compared CK MB mass (upper reference limit, 5.0 ng/ml) and cardiac troponin I (cTnI; upper reference limit, 0.8 ng/ml) (Stratus II, Dade International) in serial serum specimens obtained over 36 h after chest pain from AMI patients; within 6 h after onset of chest pain. While the appearance of the kinetics of CK MB and cTnI were similar during the initial 24 h following the onset of chest pain, cTnI was increased significantly (p<0.05) over CK MB after 9 to 12 h. Half-life determinations (mean±S.D.) in 22 of the 39 AMI patients demonstrated a significantly (p<0.01) shorter half-life in non-Q-wave infarcts [t_1/2 6.8 h (±5.6)] vs. Q-wave infarcts [t_1/2 20.4 h (±10.7)]. Further serial time versus marker (mean±S.D.) results were significantly correlated (p<0.001, r=0.66). Sixteen of twenty patients assessed by echocardiography had an abnormal left ventricular ejection fraction (LVEF); mean 37.6 (S.D. 15.2)%, ranging from 15.4 to 67.6%. LVEF was significantly and inversely correlated to peak CK MB (r=.50, p=0.03), as well as to peak cTnI (r=0.46, p=0.04). Based on these findings, cTnI shows excellent promise as a useful marker of infarct size, for the assessment of left ventricular function, and may potentially replace CK MB as the cardiac-specific marker for AMI detection.

Introduction

Troponin I (Tnl) is the subunit of the troponin complex that inhibits actomyosin ATPase activity. Three isoforms of Tnl have been described, a cardiac (cTnI) and two skeletal muscle [slow twitch (sTnI) and fast twitch (fTnI)] [1]. Each of the three Tnl isoforms is encoded by three different genes located on different chromosomes [2]. The skeletal isoforms show approximately 40% heterogeneity of primary sequence, while the cardiac isoform displays a similar degree of sequence heterogeneity compared to each skeletal isoform. Due to the presence of an additional 31 amino acids at the N-terminal region, cTnI (MW 24,000 Da) is uniquely different than either fTnI or sTnI (MW 19,800 Da). During human development, both sTnI and cTnI are expressed in the myocardium. At birth, however, only cTnI is expressed in the myocardium [3]. cTnI has been shown not to be expressed in any type of skeletal muscle, independent of developmental or disease stimuli [4]. Therefore, knowledge that cTnI is 100% tissue-specific for the myocardium makes it an excellent candidate to serve as a biochemical marker for detection of myocardial injury in serum.

cTnI has been shown to be a very sensitive and specific marker for acute myocardial infarction (AMI) 5, 6, 7, 8, 9. The early release kinetics for cTnI are similar to those of creatine kinase (CK) MB, in that it takes 4–8 h to increase above the upper reference limit. Thus, cTnI does not provide an earlier detection method for AMI than CK MB [10]. The initial cTnI rise is from the release of 3 to 6% cytoplasmic fraction of troponin in the cell following ischemic injury [8]. cTnI peaks between 14 and 36 h after onset of AMI and remains elevated for five to seven days after AMI. The mechanism for the lengthy time for elevations of cTnI is most likely due to the ongoing release of troponin from the 95 to 97% myofibril-bound fraction. The ongoing release and clearance thus gives the impression that cTnI has a long half-life. However, the true half-life of cTnI is less than 2 h [11]. Due to long time of increase of cTnI following onset of chest pain, it replaces lactate dehydrogenase (LD) isoenzymes for the detection of late-presenting AMI patients [11]. A recent study demonstrated that cTnI was more sensitive than the LD1/LD2 ratio (cutoffs of either 1.0 or 0.8) for the detection of MI up to seven days after admission [12]. The very low-to-undetectable cTnI values in serum from noncardiac-diseased and normal patients also permits the use of very low discrimination values compared to higher values of CK MB for the determination of myocardial injury. This is due to ongoing release of the small percentage of CK MB found in skeletal muscle 12, 13.

Numerous studies have determined the incidence of increased cTnI for the detection of cardiac injury in several patient groups that have often shown falsely increased CK MB concentrations. These have included patients with chest trauma [14], with cocaine-associated chest pain [15], and in the critically ill, intensive care patients [16], in renal disease [17]and in muscle trauma and disease patients [18]. Further reports have now described that analysis of cTnI has prognostic value in non-AMI patients. In patients with coronary syndromes, cTnI levels permit the early identification of patients with increased risk of cardiac events and death 19, 20.

Clinical studies have demonstrated a close relationship between the extent of injury to the myocardium (infarct size) following AMI and increased serum CK MB mass concentrations 21, 22. Similarly, significant correlations have been observed between CK MB estimated infarct sizing and left ventricular function determined by echocardiography [23]. Thus, the purpose of this study was to compare the increase in serum cTnI levels with CK MB mass for the assessment of left ventricular function determined by echocardiography following AMI. Furthermore, we examined the biological clearance of cTnI in serum following AMI.