Tomas Bjerner

Prevalence and pathophysiological mechanisms of elevated cardiac troponin I levels in a population-based sample of elderly subjects

AIMS To evaluate the prevalence of cardiac troponin I (cTnI) elevation in an elderly community population and the association of cTnI levels with cardiovascular risk factors, vascular inflammation, atherosclerosis, cardiac performance, and areas indicative of infarcted myocardium identified by cardiac magnetic resonance imaging. METHODS AND RESULTS cTnI elevation defined as cTnI levels >0.01 microg/L (Access AccuTnI, Beckman Coulter) was found in 21.8% of the study participants (n = 1005). cTnI > 0.01 microg/L was associated with cardiovascular high-risk features, the burden of atherosclerosis in the carotid arteries, left-ventricular mass, and impaired left-ventricular systolic function. No associations were found between cTnI and inflammatory activity, diastolic dysfunction, or myocardial scars. Male gender (OR 1.6; 95% CI 1.1-2.4), ischaemic ECG changes (OR 1.7; 95% CI 1.1-2.7), and NT-pro-brain natriuretic peptide levels (OR 1.4; 95% CI 1.1-1.7) independently predicted cTnI > 0.01 microg/L. cTnI > 0.01 microg/L correlated also to an increased cardiovascular risk according to the Framingham risk score. CONCLUSION cTnI > 0.01 microg/L is relatively common in elderly subjects and is associated with cardiovascular high-risk features and impaired cardiac performance. Cardiac troponin determined by a highly sensitive assay might thus serve as an instrument for the identification of subjects at high cardiovascular risk in general populations.

Prevalence of Unrecognized Myocardial Infarction Detected With Magnetic Resonance Imaging and its Relationship to Cerebral Ischemic Lesions in Both Sexes

OBJECTIVES The purpose of this study was to investigate the prevalence of unrecognized myocardial infarction (UMI) detected with magnetic resonance imaging (MRI) and whether it is related to cerebral ischemic lesions on MRI in an elderly population-based cohort. BACKGROUND There is a correlation between stroke and recognized myocardial infarction (RMI) and between stroke and UMI detected with electrocardiography, whereas the prevalence of stroke in subjects with MRI-detected UMI is unknown. METHODS Cerebral MRI and cardiac late-enhancement MRI were performed on 394 randomly selected 75-year-old subjects (188 women, 206 men). Images were assessed for cerebral ischemic lesions and myocardial infarction (MI) scars. Medical records were scrutinized. Subjects with MI scars, with or without a hospital diagnosis of MI, were classified as RMI or UMI, respectively. RESULTS UMIs were found in 120 subjects (30%) and RMIs in 21 (5%). The prevalence of UMIs (p = 0.004) and RMIs (p = 0.02) was greater in men than in women. Men with RMI displayed an increased prevalence of cortical and lacunar cerebral infarctions, whereas women with UMI more frequently had cortical cerebral infarctions (p = 0.003). CONCLUSIONS MI scars are more frequent in men than in women at 75 years of age. The prevalence of RMI is related to that of cerebral infarctions.

The Exactness of Left Ventricular Segmentation in Cine Magnetic Resonance Imaging and Its Impact on Systolic Function Values

Purpose: To evaluate the impact of exactness of the segmentation of the left ventricle (LV), using cine magnetic resonance imaging (MRI). Material and methods: Steady-state free-precession cine MRI was performed on 100 randomly selected subjects. Myocardial borders were outlined on short-axis images using three methods: method 1 was computer assisted, excluding papillary muscles from the left ventricular mass (LVM); method 2 was similar but included papillary muscles; and method 3 was manually traced including papillary muscles. LV end-systolic (ES) and end-diastolic (ED) masses and volumes, ejection fraction (EF), stroke volume (SV), and cardiac output (CO) were calculated from these measurements. The difference between the ES and ED LVM was used to estimate the exactness of the methods. Results: Method 3 was the most exact, and method 1 was the least exact. The three methods generated differing EF, SV, and CO measurements. With an ES–ED LVM difference exceeding 20 g, the mean SV measurement error was 8.8±3.6 ml. Conclusion: Manual tracing proved more exact than computer-assisted quantification. Exactness had an impact on EF, SV, and CO measurements, and the ES–ED LVM difference can be used to identify assessments that would benefit from more exact segmentation.

Assessment of myocardial blood volume and water exchange: theoretical considerations and in vivo results

The measured signal response in contrast‐enhanced myocardial perfusion imaging has been shown to be affected by the rate of water exchange between the intravascular and extravascular compartments, the effect being particularly significant when intravascular contrast agents are used. In the present study, the T1 relaxation rates were measured in eight pigs in blood and myocardium using a Look‐Locker sequence after repeated injections of the intravascular contrast agent NC100150. The selection of myocardial region of interest was automated based on a minimum chi‐square method. The intra‐ and extravascular water exchange rates and the myocardial blood volume were calculated from the measured relaxation rates by applying a two‐compartment water exchange limited model that accounts for biexponential longitudinal relaxation. The following (mean ± SD) values were obtained for the exchange frequency (f), the extravascular residence time (τe), the intravascular residence time (τi) and blood volume (BV), respectively: f = 1.39 ± 0.52 s‐1, τe = 708 ± 264 ms, τi = 107 ± 63 ms, and BV = 11.2 ± 2.1 mL/100 g. The mean value of f was found to be about 15% higher if biexponential relaxation was not accounted for, supporting the hypothesis that significant biexponential relaxation in tissues with large blood volume can lead to an overestimation of water exchange rates unless corrected for. Magn Reson Med 49:828–837, 2003.

In and ex vivo MR evaluation of acute myocardial ischemia in pigs by determining R1 in steady state after the administration of the intravascular contrast agent NC100150 injection.

Rationale and Objectives:To study the dose response in perfused and nonperfused myocardium by measuring relaxation rate (R1) in a steady-state situation after injection of the intravascular contrast agent NC100150 Injection in pigs and whether the dose response differs in vivo and ex vivo. Materials and Methods:The left anterior descending artery was occluded. R1 was measured using a Look-Locker sequence for 2 dose groups (2 mg Fe/kg bw, n = 4, and 5 mg Fe/kg bw, n = 5) and a control group (n = 3). Results:A significant increase in R1 was found in perfused myocardium after contrast agent injection, in contrast to nonperfused myocardium. There was a significantly larger difference in R1 between perfused and nonperfused myocardium in the 5 mg Fe/kg bw dose group compared with the other 2 groups. The difference in R1 between perfused and nonperfused myocardium was significantly higher in vivo than ex vivo. Conclusion:A nearly linear R1 dose response was found in perfused myocardium in vivo. The dose response ex vivo was less steep possibly due to larger water exchange limitations.

Evaluation of nonperfused myocardial ischemia with MRI and an intravascular USPIO contrast agent in an ex vivo pig model.

The ultrasmall superparamagnetic iron oxide (USPIO) preparation NC100150 Injection (Clariscan; Nycomed Imaging, Oslo, Norway) was tested for its ability to delineate nonperfused myocardium under steady‐state conditions. An experimental animal model of focal myocardial ischemia induced by ligation of the distal part of the left anterior descending artery was used. The contrast agent was administered in four doses: 0, 4, 8, and 12 mg Fe/kg body weight. Magnetic resonance examination ex vivo, including T1‐, T2‐, and T2*‐weighted sequences, was performed. Nonperfused myocardium was determined by fluorescein. The best delineation of nonperfused myocardium was found with a T1‐weighted inversion recovery/turbo spin‐echo sequence and doses of 4 and 8 mg Fe/kg body weight, where 95% of the volume was discernible at the dose of 4 mg Fe/kg body weight. The results suggest that steady‐state imaging by T1‐weighted sequence with the use of NC100150 Injection to delineate nonperfused myocardium is feasible. J. Magn. Reson. Imaging 2000;12:866–872.

High in-plane resolution T2-weighted magnetic resonance imaging of acute myocardial ischemia in pigs using the intravascular contrast agent NC100150 injection.

Rationale and Objectives:The intravascular contrast agent NC100150 injection was tested for its ability to demarcate nonperfused myocardium in a porcine model of coronary occlusion. Materials and Methods:A T2-weighted fast spin echo sequence was acquired ex vivo and in vivo during first pass and steady-state circulation of the contrast agent in 2 dosages (2 and 5 mg Fe/kg bw) or saline. Results:Ex vivo, in the high-dose group, the volume of nonperfused myocardium determined from T2-weighted images was 99% of that determined from photographs where perfused myocardium stained with fluorescein. A significantly higher contrast to noise ratio between perfused and nonperfused myocardium was found (both ex and in vivo in steady state) compared with the control group. During first pass, a significant reduction in signal intensity (74 ± 18%) was found in perfused myocardium after contrast injection. Conclusion:NC100150 injection, combined with T2-weighted turbo spin echo imaging, allowed detailed visualization of non-perfused myocardium in the steady state, which corresponded to the area at risk as determined by fluorescein.

Unrecognized myocardial scars detected by delayed-enhanced MRI are associated with increased levels of NT-proBNP.

ObjectivesPatients with unrecognized myocardial infarction (UMI) scars detected by delayed–enhanced magnetic resonance imaging (DE-MRI) have a decreased left ventricular ejection fraction and an increased left ventricular mass. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of heart failure, and troponin I (TnI) is a marker of myocardial injury. The primary aim of this study was to investigate whether NT-proBNP plasma levels (in addition to ejection fraction) differed in patients with UMI scars compared with normal participants. The second aim was to compare whether the TnI levels differed in those two groups. MethodsData from the Prospective Investigation of Vasculature in Uppsala Seniors study were used. The participants who had undergone cardiac MRI were included in this study (n=248). Patients were divided into three groups depending on the existence of a myocardial infarction (MI) scar in DE-MRI and their earlier history of MI. In all the patients, a peripheral blood sample was collected and the plasma levels of NT-proBNP and TnI were determined. ResultsPatients with UMI had higher plasma levels of NT-proBNP (median 140.2 ng/l; 25th–75th percentiles: 79–225.5) than no-MI participants (median 94.9 ng/l; 25th–75th percentiles: 59.2–144.2; P=0.01) and lower levels than patients with recognized MI (median 310.4 ng/l; 25th–75th percentiles: 122.6–446.5; P=0.02). Plasma TnI values did not differ among the three groups. ConclusionPatients with UMI scars detected by DE-MRI have increased plasma levels of NT-proBNP that is known to correlate with an increased risk of future cardiovascular adverse events.

Dobutamine-induced stress affects intracellular uptake of manganese: a quantitative magnetic resonance imaging study in pigs.

To determine whether there are differences in increase in longitudinal relaxation rate (ΔR1) in the myocardium between bolus administration of Mn2+ ions during rest and during dobutamine‐induced stress and, additionally, to determine whether there are differences in ΔR1 between bolus injection and infusion of Mn2+ ions during dobutamine‐induced stress.

Severe mitral regurgitation--relations between magnetic resonance imaging, echocardiography and natriuretic peptides

Background. Assessment of the severity of mitral regurgitation by echocardiography can be technically demanding in certain patients and supplementary methods are therefore desirable. This study addressed the agreement between magnetic resonance imaging (MRI) and echocardiography, and their relations to natriuretic peptides (NT-proANP and NT-proBNP), in quantifying severe mitral regurgitation. Methods. Eighteen patients with severe mitral regurgitation scheduled for surgery underwent MRI, echocardiography and assay of natriuretic peptides preoperatively for clinical assessment. Results. MRI and echocardiography were comparable in measuring severity of regurgitation qualitatively but not quantitatively, mitral regurgitant fraction (mean difference 27.5 (11) ml). There was a correlation between increasing regurgitant fraction on MRI and increased levels of plasma NT-proANP and NT-proBNP. In echocardiography, increasing vena contracta width and increasing PISA correlated to increased levels of plasma NT-proANP and NT-proBNP. No other correlation was found between measures on MRI and echocardiography and natriuretic peptides. Conclusions. MRI and echocardiography were comparable grading the severity of mitral regurgitation with qualitative measures but not with quantitative measures. MRI might be a complement to echocardiography when a more distinct measure of the regurgitant volume is needed, as in paravalvular leakage.