Troponin Release and Reversible LV Dysfunction

Study Questions:

Does a transient increase in left ventricular (LV) preload elicit cardiac troponin I (cTnI) release in the absence of ischemia?


The study authors infused intravenous phenylephrine (PE) (300 µg/min) for 1 hour, to increase LV end-diastolic pressure (LVEDP) to approximately 30 mm Hg, in propofol-anesthetized swine (n = 13). They assessed serial cTnI and echocardiographic function for 24 hours, and myocardial tissue was analyzed for apoptosis and necrosis. Because cTnI concentrations were not normally distributed, nonparametric testing (Friedman test with post hoc paired Wilcoxon signed rank test) was employed to assess differences in serum cTnI between sampling locations (i.e., coronary sinus vs. aorta) and time points.


The study authors found that PE infusion increased systolic blood pressure from 137 ± 14 mm Hg to 192 ± 11 mm Hg (mean ± standard deviation; p < 0.001) and increased LVEDP from 17 ± 2 mm Hg to 30 ± 5 mm Hg (p < 0.001). There was no significant change in heart rate (from 97 ± 15 bpm to 89 ± 20 bpm; p = 0.29). Myocardial flow measurements demonstrated no evidence of ischemia. Hemodynamics normalized rapidly after PE, but LV ejection fraction remained depressed (32 ± 21% vs. 58 ± 7%; p < 0.01), with normalization after 24 hours (51 ± 16%; p = 0.31). Baseline transcoronary cTnI release was low (16 ± 20 ng/L), but increased to 856 ± 956 ng/L (p = 0.01) 1 hour after LVEDP elevation. Circulating cTnI rose above the 99th percentile within 30 minutes (127 ± 54 ng/L; p < 0.01 vs. baseline), increasing further at 1 hour (509 ± 401 ng/L; p < 0.01 vs. baseline), and remained elevated at 24 hours (1,462 ± 1,691 ng/L). Pathological analysis demonstrated myocyte apoptosis at 3 hours (31.3 ± 11.9 myocytes/cm2 vs. 4.6 ± 3.7 myocytes/cm2; p < 0.01), which normalized after 24 hours (6.2 ± 5.6 myocytes/cm2; p = 0.46) without histological necrosis.


The study authors concluded that transient elevations of LVEDP lead to cTnI release, apoptosis, and reversible stretch-induced stunning in the absence of ischemia.


This is an important study because its results indicate that myocardial stretch elicited by a transient elevation in preload is accompanied by measurable cTnI release within the first hour after cessation of pressure overload that remains elevated for up to 24 hours. The findings of this study explain elevations in troponin seen in hypertensive heart failure in the absence of macrovascular coronary artery disease. Further studies are needed to confirm these important findings.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Novel Agents, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Apoptosis, Biological Markers, Blood Pressure, Coronary Artery Disease, Coronary Sinus, Echocardiography, Heart Failure, Heart Rate, Ischemia, Myocardial Stunning, Myocardium, Phenylephrine, Propofol, Stroke Volume, Troponin I, Ventricular Dysfunction, Left

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