Impact of Left Ventricular Hypertrophy on Troponin Release During Acute Myocardial Infarction: New Insights From a Comprehensive Translational Study

Abstract

BackgroundBiomarkers are frequently used to estimate infarct size (IS) as an endpoint in experimental and clinical studies. Here, we prospectively studied the impact of left ventricular (LV) hypertrophy (LVH) on biomarker release in clinical and experimental myocardial infarction (MI).Methods and ResultsST‐segment elevation myocardial infarction (STEMI) patients (n=140) were monitored for total creatine kinase (CK) and cardiac troponin I (cTnI) over 72 hours postinfarction and were examined by cardiac magnetic resonance (CMR) at 1 week and 6 months postinfarction. MI was generated in pigs with induced LVH (n=10) and in sham‐operated pigs (n=8), and serial total CK and cTnI measurements were performed and CMR scans conducted at 7 days postinfarction. Regression analysis was used to study the influence of LVH on total CK and cTnI release and IS estimated by CMR (gold standard). Receiver operating characteristic (ROC) curve analysis was performed to study the discriminatory capacity of the area under the curve (AUC) of cTnI and total CK in predicting LV dysfunction. Cardiomyocyte cTnI expression was quantified in myocardial sections from LVH and sham‐operated pigs. In both the clinical and experimental studies, LVH was associated with significantly higher peak and AUC of cTnI, but not with differences in total CK. ROC curves showed that the discriminatory capacity of AUC of cTnI to predict LV dysfunction was significantly worse for patients with LVH. LVH did not affect the capacity of total CK to estimate IS or LV dysfunction. Immunofluorescence analysis revealed significantly higher cTnI content in hypertrophic cardiomyocytes.ConclusionsPeak and AUC of cTnI both significantly overestimate IS in the presence of LVH, owing to the higher troponin content per cardiomyocyte. In the setting of LVH, cTnI release during STEMI poorly predicts postinfarction LV dysfunction. LV mass should be taken into consideration when IS or LV function are estimated by troponin release.

High sensitivity cardiac troponins: Can they help in diagnosing myocardial ischaemia?

“…CAD enhanced myocardial release of troponin, which, however, was documented also in patients without significant CAD. Moreover, according with previous reports, 26,27 it must be emphasized that in our study LVH markedly increased myocardial release of troponin induced by stress. In a recent study evaluating the impact of LVH on troponin release during myocardial infarction, it was estimated that the peak of hs-cTnI overestimates infarct size by approximately 30% in the presence of LVH.…”

“…In a recent study evaluating the impact of LVH on troponin release during myocardial infarction, it was estimated that the peak of hs-cTnI overestimates infarct size by approximately 30% in the presence of LVH. 26 However, even more critical is the issue of small increments of troponin in patients with chest pain and LVH, given the high prevalence (20–25%) of LVH in the general population 26 and the possibility of false-positive diagnoses of myocardial infarction in this setting. In addition, small increments in circulating troponin I 27 and T 28 have been reported, in patients with LVH, even in the absence of chest pain and any other acute pathology.…”

“…The first cause is simply a greater content of troponin (both structurally bound to contractile apparatus and in a free cytosolic pool, see below) in hypertrophied cardiomyocytes. 26 However, the most important mechanism explaining minor and transient increments of troponin in patients without myocardial infarction is probably coronary microvascular dysfunction associated with LVH, which impairs coronary vasodilator reserve and predisposes to stress-induced myocardial ischaemia, also in absence of obstructive CAD. 29 It is interesting to note that hypertension, by itself, was not able to enhance stress-induced release of troponin, which was markedly increased only in patients with LVH.…”

Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction

“…Multiple logistic regression analysis showed, however, that the concentrations of CK-MB, cTnI, NT-proBNP and CRP were not independent predictors of LVR. Although acute-phase cTnI and CRP concentrations have been reported to predict LVR [25], cTnI release during STEMI was reported to be poorly predictive of post-MI LV dysfunction [26]. In contrast, serial measurements of B-type natriuretic peptide, cTnI, and CRP were found to be predictive of LVR after acute MI [27].…”

Response of the human myocardium to ischemic injury and preconditioning: The role of cardiac and comorbid conditions, medical treatment, and basal redox status

“…Earlier reports showed that the hypertrophied myocardium exhibits an accelerated loss of high-energy phosphate content and a greater accumulation of tissue lactate and hydrogen ions during ischemia as well as an accelerated calcium overload during early reperfusion [19,20]. It should be noted that the infarct size in patients with LV hypertrophy may be significantly overestimated when based on the determination of cardiac enzymes such as the peak and AUC plasma values of cardiac troponin I [21]. In the present study, the results were expressed based on the weight of the myocardial tissue, thus avoiding this source of potential error.…”