Charlotte Ebeling Barbier

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.

Investigation of Hepatobiliary Disposition of Doxorubicin Following Intrahepatic Delivery of Different Dosage Forms

Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI-TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28-53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15-22)% and 4.2 (3.2-5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580-660) and 5000 (3900-5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.

Total atherosclerotic burden by whole body magnetic resonance angiography predicts major adverse cardiovascular events

OBJECTIVE The purpose of the present study was to investigate the relationship between the Total Atherosclerotic Score (TAS), a measurement of the overall atherosclerotic burden of the arterial tree by whole body magnetic resonance angiography (WBMRA), and the risk of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, stroke and/or coronary revascularization, assuming that TAS predicts MACE. METHODS AND RESULTS 305 randomly selected 70 year-old subjects (47% women) underwent WBMRA. Their atherosclerotic burden was evaluated and TAS > 0, that is atherosclerotic changes, were found in 68% of subjects. During follow-up (mean 4.8 years), MACE occurred in 25 subjects (8.2%). Adjusting for multiple risk factors, TAS was associated with MACE (OR 8.86 for any degree of vessel lumen abnormality, 95%CI 1.14-69.11, p = 0.037). In addition, TAS improved discrimination and reclassification when added to the Framingham risk score (FRS), and ROC (Receiver Operator Curve) increased from 0.681 to 0.750 (p = 0.0421). CONCLUSION In a population-based sample of 70 year old men and women WBMRA, with TAS, predicted MACE independently of major cardiovascular risk factors.

Cardiac Troponin I Associated with the Development of Unrecognized Myocardial Infarctions Detected with MRI

BACKGROUND Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI. METHODS After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments. RESULTS New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17-3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028). CONCLUSIONS hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.

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.

Longterm follow-up after transarterial chemotherapy for hepatocellular carcinoma in a Scandinavian centre

BACKGROUND Transarterial chemotherapy infusion (TAI) with lipiodol is a palliative treatment for hepatocellular carcinoma. The aim of this study was to describe the outcomes of TAI from a single scandinavian centre between 1995 to 2008. METHODS The study is a retrospective analyse of prospectively collected data. TAI (doxorubicin, 50 mg with lipiodol) was administrated every 6 weeks. After 5 treatments, a CT scan was performed, and if the disease was stable, (RECIST score) treatment was continued. RESULTS 57 patients with HCC were treated with TAI. Median age; 72 years (52-84), 41 (71%) men. 52 (91%) had Child-Pugh score A, and 5 (9%) had Child-Pugh B. Nine (16%) patients had a BCLC score A, 19 (33%) B, 29 (51%) C, while none was classified as BCLC D. Twenty nine (51%) patients had a tumour size ≥ 10 cm. In total 254 treatments were performed, a median of 4 (1-20) per patient. Treatment mortality was 0%. In 30 (53%) patients the treatment strategy was not completed due to deteriorating clinical conditions. Median survival was 17 months (2-108), 2, 3, and 5-years survival was 34%, 22%, and 13%, respectively. Patients that responded to treatment (n = 23) had a median survival of 26 (13-108) months compared to 8 (2-48) months for those not fulfilling the treatment plan, p < 0.05. Tumour size ≥ 10 cm, AFP ≥ 400 µg/l, and Child-Pugh class B or C were negative prognostic factors for survival, p < 0.05. CONCLUSIONS The 5 year survival was 13%, and median survival 17 months. Treatment mortality was 0%. Patients that responded to treatment (40%) had a median survival of 26 months. TAI provides good palliation but selection of patients is crucial.

Several sources of error in estimation of left ventricular mass with M-mode echocardiography in elderly subjects

Abstract Introduction. M-mode echocardiography estimates of the left ventricular mass (LVM) were greater than magnetic resonance imaging (MRI) estimates. There are substantial differences between the methods both in the means of measuring and the calculation formula. The aim of this study was to investigate whether any difference in estimates of LVM between M-mode echocardiography and MRI is due to the means of measuring or to the calculation formula, using MRI as the gold standard. Material and methods. M-mode echocardiography and MRI were performed on 229 randomly selected 70-year-old community-living subjects. LVM was calculated from echocardiography (LVMecho) and from MRI (LVMMRI) measurements using standard techniques. Additionally LVM was calculated with the echocardiography formula from echo-mimicking measurements made on MR images (LVMMRI/ASE). Results. There were significant differences between all three LVM estimates in women, in men, and in the entire population. Echocardiography estimated LVM to be larger than did MRI, and the LVMMRI/ASE estimate was larger than the LVMMRI. The difference between LVMMRI and LVMMRI/ASE was larger than the difference between LVMecho and LVMMRI/ASE. There was a low correlation between LVMecho and LVMMRI (R2 = 0.46) as well as between LVMMRI/ASE and LVMMRI (R2 = 0.65). Conclusion. The means of measuring and the calculation formula both independently add to the error in LVM estimation with M-mode echocardiography. The error of the calculation formula seems to be greater than the error of the means of measuring in a population of community-living elderly men and women.

Apolipoprotein B/A-I ratio related to visceral but not to subcutaneous adipose tissue in elderly Swedes.

OBJECTIVE To investigate whether the amount of visceral (VAT) or subcutaneous adipose tissue (SAT) independently of the other can determine the apolipoprotein (apo)B/A-I ratio. METHODS VAT and SAT areas were assessed using magnetic resonance imaging in 247 randomly selected 70-year-old men and women who did not use lipid-lowering drugs. Their adipose tissue areas were compared to their apoB and apo A-I levels and to their apoB/A-I ratios. RESULTS The VAT area and the gender were significantly related to the apoB/A-I ratio whereas the SAT area was not. There was a positive relationship between the VAT area and the apoB/A-I ratio. CONCLUSION A positive relationship was established between the amount of VAT and the apoB/A-I ratio, whereas there was no relationship between the amount of SAT and the apoB/A-I ratio. This observation supports the notion that VAT is metabolically active.

Treatment of acute portomesenteric venous thrombosis with thrombectomy through a transjugular intrahepatic portosystemic shunt: a single-center experience

Background Acute portomesenteric venous thrombosis (PMVT) is a potentially life-threatening condition and urgent treatment is required. Purpose To retrospectively evaluate the efficacy and safety of treating acute PMVT by the creation of a transjugular intrahepatic portosystemic shunt (TIPS) followed by thrombectomy. Material and Methods Six patients (all men, age range = 39–51 years) presenting with acute PMVT were treated with transjugular thrombectomy (TT) through a TIPS created in the same session. The intervention included iterated venography through the TIPS one to three times within the first week after diagnosis and repeated thrombectomy if needed (n = 5). Results Recanalization was successful with persistent blood flow through the main superior mesenteric vein, portal vein, and TIPS in all six patients. Five patients were treated primarily with thrombectomy through a TIPS with clinical improvement. The final patient was initially treated with surgical thrombectomy and bowel resection. TIPS and TT was performed two days after surgery due to re-thrombosis but the patient deteriorated and died of multi-organ failure. Procedure-related complications were transient hematuria (n = 3) and transient encephalopathy (n = 2). In-hospital time was <14 days in four of the five patients with primary TIPS and TT. No sign of re-thrombosis was noted during follow-up (mean = 18 months, range = 8–28 months). Conclusion Thrombectomy through a TIPS is feasible and can be effective in recanalization and symptom-relief in acute PMVT.