Myocardial T1 and extracellular volume fraction mapping at 3 tesla

Background

To compare 11 heartbeat (HB) and 17 HB modified lock locker inversion recovery (MOLLI) pulse sequence at 3T and to establish preliminary reference values for myocardial T1 and the extracellular volume fraction (ECV).

Methods

Both phantoms and normal volunteers were scanned at 3T using 11 HB and 17 HB MOLLI sequence with the following parameters: spatial resolution = 1.75 × 1.75 × 10 mm on a 256 × 180 matrix, TI initial = 110 ms, TI increment = 80 ms, flip angle = 35°, TR/TE = 1.9/1.0 ms. All volunteers were administered Gadolinium-DTPA (Magnevist, 0.15 mmol/kg), and multiple post-contrast MOLLI scans were performed at the same pre-contrast position from 3.5-23.5 minutes after a bolus contrast injection. Late gadolinium enhancement (LGE) images were also acquired 12-30 minutes after the gadolinium bolus.

Results

T1 values of 11 HB and 17 HB MOLLI displayed good agreement in both phantom and volunteers. The average pre-contrast myocardial and blood T1 was 1315 ± 39 ms and 2020 ± 129 ms, respectively. ECV was stable between 8.5 to 23.5 minutes post contrast with an average of 26.7 ± 1.0%.

Conclusion

The 11 HB MOLLI is a faster method for high-resolution myocardial T1 mapping at 3T. ECV fractions are stable over a wide time range after contrast administration.     

Cardiac T2-mapping using a fast gradient echo spin echo sequence - first in vitro and in vivo experience

Background

The aim of this study was the evaluation of a fast Gradient Spin Echo Technique (GraSE) for cardiac T2-mapping, combining a robust estimation of T2 relaxation times with short acquisition times. The sequence was compared against two previously introduced T2-mapping techniques in a phantom and in vivo.

Methods

Phantom experiments were performed at 1.5 T using a commercially available cylindrical gel phantom. Three different T2-mapping techniques were compared: a Multi Echo Spin Echo (MESE; serving as a reference), a T2-prepared balanced Steady State Free Precession (T2prep) and a Gradient Spin Echo sequence. For the subsequent in vivo study, 12 healthy volunteers were examined on a clinical 1.5 T scanner. The three T2-mapping sequences were performed at three short-axis slices. Global myocardial T2 relaxation times were calculated and statistical analysis was performed. For assessment of pixel-by-pixel homogeneity, the number of segments showing an inhomogeneous T2 value distribution, as defined by a pixel SD exceeding 20 % of the corresponding observed T2 time, was counted.

Results

Phantom experiments showed a greater difference of measured T2 values between T2prep and MESE than between GraSE and MESE, especially for species with low T1 values. Both, GraSE and T2prep resulted in an overestimation of T2 times compared to MESE. In vivo, significant differences between mean T2 times were observed. In general, T2prep resulted in lowest (52.4 ± 2.8 ms) and GraSE in highest T2 estimates (59.3 ± 4.0 ms). Analysis of pixel-by-pixel homogeneity revealed the least number of segments with inhomogeneous T2 distribution for GraSE-derived T2 maps.

Conclusions

The GraSE sequence is a fast and robust sequence, combining advantages of both MESE and T2prep techniques, which promises to enable improved clinical applicability of T2-mapping in the future. Our study revealed significant differences of derived mean T2 values when applying different sequence designs. Therefore, a systematic comparison of different cardiac T2-mapping sequences and the establishment of dedicated reference values should be the goal of future studies.     

Systolic ShMOLLI myocardial T1-mapping for improved robustness to partial-volume effects and applications in tachyarrhythmias

Background

T1-mapping using the Shortened Modified Look-Locker Inversion Recovery (ShMOLLI) technique enables non-invasive assessment of important myocardial tissue characteristics. However, tachyarrhythmia may cause mistriggering and inaccurate T1 estimation. We set out to test whether systolic T1-mapping might overcome this, and whether T1 values or data quality would be significantly different compared to conventional diastolic T1-mapping.

Methods

Native T1 maps were acquired using ShMOLLI at 1.5 T (Magnetom Avanto, Siemens Healthcare) in 10 healthy volunteers (5 male) in sinus rhythm, at varying prescribed trigger delay (TD) times: 0, 50, 100 and 150 ms (all “systolic”), 340 ms (MOLLI TD 500 ms, the conventional TD for ShMOLLI) and also “end diastolic”. T1 maps were also acquired using a shorter readout, to explore the effect of reducing image readout time and sensitivity to systolic motion. The feasibility and image quality of systolic T1-mapping was tested in 15 patients with tachyarrhythmia (n = 13 atrial fibrillation, n = 2 sinus tachycardia; mean HR range 93–121 bpm).

Results

In healthy volunteers, systolic readout increased the thickness of myocardium compared to the diastolic readout. There was a small overall effect of TD on T1 values (p = 0.04), with slightly shorter T1 values in systole compared to diastole (maximum difference 10 ms). While there were apparent gender differences (with no effect of TD on T1 values in males, more marked differences in females, and exaggeration of this effect in thinner myocardial segments in females), dilatation and erosion of contours suggested that the effect of TD on T1 in females was almost entirely due to more partial-volume effects in diastole. All T1 maps were of excellent quality, but systolic TD and shorter readout were associated with less variability in segmental T1 values. In tachycardic patients, systolic acquisitions produced consistently excellent T1 maps (median R² = 0.993).

Conclusions

In healthy volunteers, systolic ShMOLLI T1-mapping reduces T1 variability and reports clinically equivalent T1 values to conventional diastolic readout; slightly shorter T1 values in systole are mostly explained by reduced partial-volume effects due to the increase in functional myocardial thickness. In patients with tachyarrhythmia, systolic ShMOLLI T1-mapping is feasible, circumvents mistriggering and produces excellent quality T1 maps. This extends its clinical applicability to challenging rhythms (such as rapid atrial fibrillation) and aids the investigation of thinner myocardial segments. With further validation, systolic T1-mapping may become a new and convenient standard for myocardial T1-mapping.     

Demands,values, and burnout: Relevance for physicians

OBJECTIVE

T o explore the interaction between workload and values congruence (personal values with health care system values) in the context of burnout and physician engagement and to explore the relative importance of these factors by sex, given the distinct work patterns of male and female physicians.

DESIGN

National mailed survey.

SETTING

Canada.

PARTICIPANTS

A random sample of 8100 Canadian physicians (response rate 40%, N = 3213); 2536 responses (from physicians working more than 35 hours per week) were analyzed.

MAIN OUTCOME MEASURES

Levels of burnout, values congruence, and workload, by sex, measured by the Maslach Burnout Inventory—General Scale and the Areas of Worklife Scale.

RESULTS

Results showed a moderate level of burnout among Canadian physicians, with relatively positive scores on exhaustion, average scores on cynicism, and mildly negative scores on professional efficacy. A series of multiple regression analyses confirmed parallel main effect contributions from manageable workload and values congruence. Both workload and values congruence predicted exhaustion and cynicism for men and women (P = .001). Only values congruence provided a significant prediction of professional efficacy for both men and women (P = .001) These predictors interacted for women on all 3 aspects of burnout (exhaustion, cynicism, and diminished efficacy). Howevever, overall levels of the burnout indicators departed only modestly from normative levels.

CONCLUSION

W orkload and values congruence make distinct contributions to physician burnout. Work overload contributes to predicting exhaustion and cynicism; professional values crises contribute to predicting exhaustion, cynicism, and low professional efficacy. The interaction of values and workload for women in particular has implications for the distinct work-life patterns of male and female physicians. Specifically, the congruence of individual values with values inherent in the health care system appeared to be of greater consequence for women than for men.     

Three-dimensional balanced steady state free precession myocardial perfusion cardiovascular magnetic resonance at 3T using dual-source parallel RF transmission: initial experience

Background

The purpose of this study was to establish the feasibility of three-dimensional (3D) balanced steady-state-free-precession (bSSFP) myocardial perfusion cardiovascular magnetic resonance (CMR) at 3T using local RF shimming with dual-source RF transmission, and to compare it with spoiled gradient echo (TGRE) acquisition.

Methods

Dynamic contrast-enhanced 3D bSSFP perfusion imaging was performed on a 3T MRI scanner equipped with dual-source RF transmission technology. Images were reconstructed using k-space and time broad-use linear acquisition speed-up technique (k-t BLAST) and compartment based principle component analysis (k-t PCA).

Results

In phantoms and volunteers, local RF shimming with dual source RF transmission significantly improved B1 field homogeneity compared with single source transmission (P = 0.01). 3D bSSFP showed improved signal-to-noise, contrast-to-noise and signal homogeneity compared with 3D TGRE (29.8 vs 26.9, P = 0.045; 23.2 vs 21.6, P = 0.049; 14.9% vs 12.4%, p = 0.002, respectively). Image quality was similar between bSSFP and TGRE but there were more dark rim artefacts with bSSFP. k-t PCA reconstruction reduced artefacts for both sequences compared with k-t BLAST. In a subset of five patients, both methods correctly identified those with coronary artery disease.

Conclusion

Three-dimensional bSSFP myocardial perfusion CMR using local RF shimming with dual source parallel RF transmission at 3T is feasible and improves signal characteristics compared with TGRE. Image artefact remains an important limitation of bSSFP imaging at 3T but can be reduced with k-t PCA.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-014-0090-0) contains supplementary material, which is available to authorized users.     

Myocardial first-pass perfusion imaging with hybrid-EPI: frequency-offsets and potential artefacts

Background

First-pass myocardial perfusion is often imaged with a tailored hybrid centric interleaved echo-planar-imaging sequence, providing rapid image acquisition with good contrast enhancement. The centric interleaved phase-encode order minimises the effective time-of-echo but it is sensitive to frequency-offsets. This short article aims to show possible artefacts that might originate with this sequence, in the context of first-pass perfusion imaging, when frequency-offsets are present. Non-uniform magnitude modulation effects were also analysed.

Methods

Numerical and phantom simulations were used to illustrate the effects of frequency-offsets and non-uniform magnitude modulation with this sequence in a typical perfusion protocol. In vivo data was post-processed to analyse the h-EPI’s sensitivity to the frequency-offsets.

Results

The centric phase-order was shown to be highly sensitive to frequency-offsets due to its symmetrical phase slope. Resulting artefacts include blurring, and splitting of the image into two identical copies along the phase-encode direction. It was also shown that frequency-offsets can introduce signal loss and ghosting of the right ventricle signal into the myocardium. The in vivo results were confirmed by numerical and phantom simulations. Magnitude modulation effects were found to be small.

Conclusions

Imaging first-pass myocardial perfusion with an hybrid centric echo-planar-imaging sequence can be corrupted with ghosting and splitting of the image due to frequency-offsets.     

Cardiac and hepatic iron and ejection fraction in thalassemia major: Multicentre prospective comparison of combined Deferiprone and Deferoxamine therapy against Deferiprone or Deferoxamine Monotherapy

Background

Due to the limited data available in literature, the aim of this multi-centre study was to prospectively compare in thalassemia major (TM) patients the efficacy of combined deferiprone (DFP) and deferoxamine (DFO) regimen versus either DFP and DFO in monotherapy by cardiovascular magnetic resonance (CMR) over a follow up of 18 months.

Methods

Among the first 1135 TM patients in the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated those who had received either combined regimen (DFO + DFP, N=51) or DFP (N=39) and DFO (N=74) monotherapies between the two CMR scans. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images.

Results

The percentage of patients that maintained a normal global heart T2* value was comparable between DFP+DFO versus both monotherapy groups. Among the patients with myocardial iron overload at baseline, the changes in the global heart T2* and in biventricular function were not significantly different in DFP+DFO compared with the DFP group. The improvement in the global heart T2* was significantly higher in the DFP+DFO than the DFO group, without a difference in biventricular function. Among the patients with hepatic iron at baseline, the decrease in liver iron concentration values was significantly higher with combination therapy than with either monotherapy group.

Conclusions

In TM patients at the dosages used in the real world, the combined DFP+DFO regimen was more effective in removing cardiac iron than DFO, and was superior in clearing hepatic iron than either DFO or DFP monotherapy. Combined therapy did not show an additional effect on heart function over DFP.     

Gradient Spin Echo (GraSE) imaging for fast myocardial T2 mapping

Background

Quantitative Cardiovascular Magnetic Resonance (CMR) techniques have gained high interest in CMR research. Myocardial T2 mapping is thought to be helpful in diagnosis of acute myocardial conditions associated with myocardial edema. In this study we aimed to establish a technique for myocardial T2 mapping based on gradient-spin-echo (GraSE) imaging.

Methods

The local ethics committee approved this prospective study. Written informed consent was obtained from all subjects prior to CMR. A modified GraSE sequence allowing for myocardial T2 mapping in a single breath-hold per slice using ECG-triggered acquisition of a black blood multi-echo series was developed at 1.5 Tesla. Myocardial T2 relaxation time (T2-RT) was determined by maximum likelihood estimation from magnitude phased-array multi-echo data. Four GraSE sequence variants with varying number of acquired echoes and resolution were evaluated in-vitro and in 20 healthy volunteers. Inter-study reproducibility was assessed in a subset of five volunteers. The sequence with the best overall performance was further evaluated by assessment of intra- and inter-observer agreement in all volunteers, and then implemented into the clinical CMR protocol of five patients with acute myocardial injury (myocarditis, takotsubo cardiomyopathy and myocardial infarction).

Results

In-vitro studies revealed the need for well defined sequence settings to obtain accurate T2-RT measurements with GraSE. An optimized 6-echo GraSE sequence yielded an excellent agreement with the gold standard Carr-Purcell-Meiboom-Gill sequence. Global myocardial T2 relaxation times in healthy volunteers was 52.2 ± 2.0 ms (mean ± standard deviation). Mean difference between repeated examinations (n = 5) was −0.02 ms with 95% limits of agreement (LoA) of [−4.7; 4.7] ms. Intra-reader and inter-reader agreement was excellent with mean differences of −0.1 ms, 95% LoA = [−1.3; 1.2] ms and 0.1 ms, 95% LoA = [−1.5; 1.6] ms, respectively (n = 20). In patients with acute myocardial injury global myocardial T2-RTs were prolonged (mean: 61.3 ± 6.7 ms).

Conclusion

Using an optimized GraSE sequence CMR allows for robust, reliable, fast myocardial T2 mapping and quantitative tissue characterization. Clinically, the GraSE-based T2-mapping has the potential to complement qualitative CMR in patients with acute myocardial injuries.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-015-0127-z) contains supplementary material, which is available to authorized users.     

Metformin overdose causes platelet mitochondrial dysfunction in humans

Introduction

We have recently demonstrated that metformin intoxication causes mitochondrial dysfunction in several porcine tissues, including platelets. The aim of the present work was to clarify whether it also causes mitochondrial dysfunction (and secondary lactate overproduction) in human platelets, in vitro and ex vivo.

Methods

Human platelets were incubated for 72 hours with saline or increasing doses of metformin (in vitro experiments). Lactate production, respiratory chain complex activities (spectrophotometry), mitochondrial membrane potential (flow-cytometry after staining with JC-1) and oxygen consumption (Clark-type electrode) were then measured. Platelets were also obtained from ten patients with lactic acidosis (arterial pH 6.97 ± 0.18 and lactate 16 ± 7 mmol/L) due to accidental metformin intoxication (serum drug level 32 ± 14 mg/L) and ten healthy volunteers of similar sex and age. Respiratory chain complex activities were measured as above (ex vivo experiments).

Results

In vitro, metformin dose-dependently increased lactate production (P < 0.001), decreased respiratory chain complex I activity (P = 0.009), mitochondrial membrane potential (P = 0.003) and oxygen consumption (P < 0.001) of human platelets. Ex vivo, platelets taken from intoxicated patients had significantly lower complex I (P = 0.045) and complex IV (P < 0.001) activity compared to controls.

Conclusions

Depending on dose, metformin can cause mitochondrial dysfunction and lactate overproduction in human platelets in vitro and, possibly, in vivo.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT 00942123","term_id":"NCT00942123"}}NCT 00942123.     

Does intra-aortic balloon support for myocardial infarction with cardiogenic shock improve outcome?

Expanded abstract

Citation

Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, Richardt G, Hennersdorf M, Empen K, Fuernau G, Desch S, Eitel I, Hambrecht R, Fuhrmann J, Böhm M, Ebelt H, Schneider S, Schuler G, Werdan K; IABP-SHOCK II Trial Investigators: Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012, 367:1287-1296.

Background

In the current international guidelines, intra-aortic balloon pump (IABP) counterpulsation is considered a class I treatment for acute myocardial infarction complicated by cardiogenic shock. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials.

Methods

Objective

To test the hypothesis that IABP counterpulsation, as compared with the best available medical therapy alone, results in a reduction in mortality among patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization is planned.

Design

Randomized, prospective, open-label, multicenter trial.

Setting

Thirty-seven centers in Germany.

Subjects

All adults had acute myocardial infarction complicated by cardiogenic shock and were expected to undergo early revascularization (by means of percutaneous coronary intervention or bypass surgery).

Intervention

After enrollment, 600 patients were randomly assigned to intra-aortic balloon counterpulsation (IABP group, 301 patients) or no IABP counterpulsation (control group, 299 patients).

Outcomes

The primary efficacy endpoint is 30-day all-cause mortality.

Results

At 30 days, 119 patients in the IABP group (39.7%) and 123 patients in the control group (41.3%) had died (relative risk with IABP, 0.96; 95% confidence interval, 0.79 to 1.17; P = 0.69). There were no significant differences in secondary endpoints or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function.

Conclusions

The use of IABP counterpulsation did not significantly reduce 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock for whom an early revascularization strategy was planned.     

The protein binding substance Ibuprofen does not affect the T1 time or partition coefficient in contrast-enhanced cardiovascular magnetic resonance

Background

Contrast enhanced cardiovascular magnetic resonance (CMR) with T1 mapping enables quantification of diffuse myocardial fibrosis. Various factors, however, can interfere with T1 measurements. The purpose of the current study was to assess the effect of co-medication with a typical protein binding drug (Ibuprofen) on T1 values in vitro and in vivo.

Methods

50 vials were prepared with different concentrations of gadobenate dimeglumine, Ibuprofen and human serum albumin in physiologic NaCl solution and imaged at 1.5T with a spin echo sequence at multiple TRs to measure T1 values and calculate relaxivities. 10 volunteers (5 men; 31±6.3 years) were imaged at 1.5T. T1 values for myocardium and blood pool were determined for various time points after administration of 0.15mmol/kg gadobenate dimeglumine using a modified look-locker inversion-recovery sequence before and after administration of Ibuprofen over 24 hours. The partition coefficient was calculated as ΔR1_myocardium/ΔR1_blood, where R1=1/T1.

Results

In vitro no significant correlation was found between relaxivity and Ibuprofen concentration, neither in absence (r=−0.15, p=0.40) nor in presence of albumin (r=−0.32, p=0.30). In vivo there was no significant difference in post contrast T1 times of myocardium and blood, respectively and also in the partition coefficient between exam 1 and 2 (p>0.05). There was good agreement of the T1 times of myocardium and blood and the partition coefficient, respectively between exam 1 and 2.

Conclusions

Contrast enhanced T1 mapping is unaffected by co-medication with the protein binding substance Ibuprofen and has an excellent reproducibility.     

Distribution of C-Peptide and Its Determinants in North American Children at Risk for Type 1 Diabetes

OBJECTIVE

To determine basal and stimulated C-peptide percentiles in North American children and adolescents at risk for type 1 diabetes (T1D) and to examine factors associated with this distribution in the Diabetes Prevention Trial–Type 1 (DPT-1).

RESEARCH DESIGN AND METHODS

We included 582 subjects aged 4–18 years at randomization in the DPT-1 trials. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and every 6 months during the 5-year follow-up period. The percentile values of C-peptide after baseline OGTT were estimated according to age, BMI Z score (BMIZ), and/or sex categories. Conditional quantile regression was used to examine the relationship between C-peptide percentiles and various independent variables.

RESULTS

The basal and stimulated C-peptide levels increased significantly as age and BMIZ increased (P < 0.05). Both age and BMIZ had a stronger impact on the upper quartile of C-peptide distributions than the lower quartile. Sex was only significantly associated with stimulated C-peptide. Higher stimulated C-peptide levels were generally observed in girls compared with boys at the same age and BMIZ (P < 0.05). HLA type and number of positive antibodies and antibody titers (islet cell antibody [ICA], insulin autoantibody, GAD65A, and ICA512A) were not significantly associated with C-peptide distribution after adjustment for age, BMIZ, and sex.

CONCLUSIONS

Age-, sex-, and BMIZ-specific C-peptide percentiles can be estimated for North American children and adolescents at risk for T1D. They can be used as an assessment tool that could impact the recommendations in T1D prevention trials.     

Cardiovascular magnetic resonance by non contrast T1-mapping allows assessment of severity of injury in acute myocardial infarction

Background

Current cardiovascular magnetic resonance (CMR) methods, such as late gadolinium enhancement (LGE) and oedema imaging (T2W) used to depict myocardial ischemia, have limitations. Novel quantitative T1-mapping techniques have the potential to further characterize the components of ischemic injury. In patients with myocardial infarction (MI) we sought to investigate whether state-of the art pre-contrast T1-mapping (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery.

Methods

3T CMR including T2W, T1-mapping and LGE was performed in 41 patients [of these, 78% were ST elevation MI (STEMI)] with acute MI at 12-48 hour after chest pain onset and at 6 months (6M). Patients with STEMI underwent primary PCI prior to CMR. Assessment of acute regional wall motion abnormalities, acute segmental damaged fraction by T2W and LGE and mean segmental T1 values was performed on matching short axis slices. LGE and improvement in regional wall motion at 6M were also obtained.

Results

We found that the variability of T1 measurements was significantly lower compared to T2W and that, while the diagnostic performance of acute T1-mapping for detecting myocardial injury was at least as good as that of T2W-CMR in STEMI patients, it was superior to T2W imaging in NSTEMI. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental T1 values (P < 0.01). The index of salvaged myocardium derived by acute T1-mapping and 6M LGE was not different to the one derived from T2W (P = 0.88). Furthermore, the likelihood of improvement of segmental function at 6M decreased progressively as acute T1 values increased (P < 0.0004).

Conclusions

In acute MI, pre-contrast T1-mapping allows assessment of the extent of myocardial damage. T1-mapping might become an important complementary technique to LGE and T2W for identification of reversible myocardial injury and prediction of functional recovery in acute MI.     

Evaluation of effects of ischaemia on the albumin cobalt binding (ACB) assay in patients exposed to trauma

Background

In the emergency department (ED), the diagnosis of acute myocardial ischaemia is very difficult because of the absence of a rapid, reliable diagnostic test. The albumin cobalt binding (ACB) assay is a good candidate as a marker for for detection of myocardial ischaemia, as it is an easy and rapid test. To date, however, the way in which alterations in metal binding sites of human serum albumin depend on ischaemic events has not been reported in detail.

Methods

We studied 92 patients admitted to the ED within 1 hour after exposure to trauma. Trauma patients divided into two groups according to their Injury Severity Score (ISS): group 1 comprised mildly injured patients who had ISS trauma score <15 (n = 60), and group 2 comprised moderately injured patients with ISS trauma score >15 (n = 32). The blood specimens of 30 healthy volunteers were studied as a control group.

Results

Group 2 showed significantly increased ACB levels (0.63 (0.18) absorbance units (ABSU)) compared with group 1 (0.54 (0.14) ABSU) (p<0.05) and controls (0.39 (0.05) ABSU) (p<0.01). Group 1 showed significantly enhanced ACB values compared with controls (0.54 (0.14) v 0.39 (0.05) ABSU) (p<0.01).

Conclusion

Consequently, trauma enhances ACB levels, which may affect the diagnostic performance of the ACB assay, and this effect can limit the ability of the assay for detection of myocardial ischaemia in patients exposed to trauma.     

Sex Steroids Affect Triglyceride Handling, Glucose-Dependent Insulinotropic Polypeptide, and Insulin Sensitivity: A 1-week randomized clinical trial in healthy young men

OBJECTIVE

To evaluate metabolic effects of sex steroids in nonfasting and fasting conditions, independent from changes in body composition.

RESEARCH DESIGN AND METHODS

A randomized clinical trial was performed to create contrasting sex steroid levels in healthy young men: by letrozole (aromatase inhibitor) to lower estradiol (E₂) and increase testosterone (group T, n = 10) versus letrozole plus E₂ patches to lower T and raise E₂ (group E, n = 10). Mixed meals and hyperinsulinemic-euglycemic clamps were performed before and after a 1-week treatment period.

RESULTS

Following intervention, the postprandial triglyceride response displayed a diverging response with a decline in group T and an increase in group E; the postprandial glucose-dependent insulinotropic polypeptide (GIP) response increased in group T. Insulin sensitivity increased in group T but remained unaltered in group E.

CONCLUSIONS

In healthy young men, short-term changes in sex steroids affect postprandial triglyceride and GIP response and insulin sensitivity.Low testosterone has been shown to be a strong predictor of metabolic syndrome in men aged 20–40 years, although underlying biological mechanisms are poorly understood (1,2). Typically, low testosterone in the presence of disturbed glucose metabolism is combined with high estradiol (E₂) (3). Modifying steroid levels into low E₂ and high testosterone, by an aromatase inhibitor (AI) reducing conversion of testosterone into E₂ through aromatase (P450a), results in decreased fasting glucose and insulin levels in young men (4). Yet, nonfasting conditions might be relevant as well since humans spend the majority of time in this state, which might better predict cardiovascular risk (5). In the present study, short-term sex steroid effects were explored in both fasting and nonfasting conditions; men were randomly treated with an AI to lower E₂ and increase testosterone (group T) or an AI and E₂ patches to lower testosterone and raise E₂ (group E). E₂ patches in men cause downregulation of testosterone secretion through the feedback mechanism of the hypothalamic-pituitary-gonadal axis. A week is supposed to be sufficient to reach a steady state.     

Quantification of global myocardial oxygenation in humans: initial experience

Purpose

To assess the feasibility of our newly developed cardiovascular magnetic resonance (CMR) methods to quantify global and/or regional myocardial oxygen consumption rate (MVO₂) at rest and during pharmacologically-induced vasodilation in normal volunteers.

Methods

A breath-hold T₂ quantification method is developed to calculate oxygen extraction fraction (OEF) and MVO₂ rate at rest and/or during hyperemia, using a two-compartment model. A previously reported T₂ quantification method using turbo-spin-echo sequence was also applied for comparison. CMR scans were performed in 6 normal volunteers. Each imaging session consisted of imaging at rest and during adenosine-induced vasodilation. The new T₂ quantification method was applied to calculate T₂ in the coronary sinus (CS), as well as in myocardial tissue. Resting CS OEF, representing resting global myocardial OEF, and myocardial OEF during adenosine vasodilation were then calculated by the model. Myocardial blood flow (MBF) was also obtained to calculate MVO₂, by using a first-pass perfusion imaging approach.

Results

The T₂ quantification method yielded a hyperemic OEF of 0.37 ± 0.05 and a hyperemic MVO₂ of 9.2 ± 2.4 μmol/g/min. The corresponding resting values were 0.73 ± 0.05 and 5.2 ± 1.7 μmol/g/min respectively, which agreed well with published literature values. The MVO₂ rose proportionally with rate-pressure product from the rest condition. The T₂ sensitivity is approximately 95% higher with the new T₂ method than turbo-spin-echo method.

Conclusion

The CMR oxygenation method demonstrates the potential for non-invasive estimation of myocardial oxygenation, and should be explored in patients with altered myocardial oxygenation.     

Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis – a CMR study

Background

Myocardial edema is a substantial feature of the inflammatory response in human myocarditis. The relation between myocardial edema and myocardial mass in the course of healing myocarditis has not been systematically investigated. We hypothesised that the resolution of myocardial edema as visualised by T2-weighted cardiovascular magnetic resonance (CMR) is associated with a decrease of myocardial mass in steady state free precession (SSFP)-cine imaging.

Methods

21 patients with acute myocarditis underwent CMR shortly after onset of symptoms and 1 year later. For visualization of edema, a T2-weighted breath-hold black-blood triple-inversion fast spin echo technique was applied and the ratio of signal intensity of myocardium/skeletal muscle was assessed. Left ventricular (LV) mass, volumes and function were quantified from biplane cine steady state free precession images.11 healthy volunteers served as a control group for interstudy reproducibility of LV mass.

Results

In patients with myocarditis, a significant decrease in LV mass was observed during follow-up compared to the acute phase (156.7 ± 30.6 g vs. 140.3 ± 28.3 g, p < 0.0001). The reduction of LV mass paralleled the normalization of initially increased myocardial signal intensity on T2-weighted images (2.4 ± 0.4 vs. 1.68 ± 0.3, p < 0.0001).In controls, the interstudy difference of LV mass was lower than in patients (5.1 ± 2.9 g vs. 16.3 ± 14.2 g, p = 0.02) resulting in a lower coefficient of variability (2.1 vs 8.9%, p = 0.04).

Conclusion

Reversible abnormalities in T2-weighted CMR are paralleled by a transient increase in left ventricular mass during the course of myocarditis. Myocardial edema may be a common pathway explaining these findings.     

Characteristics of chronic pain patients in a rural teaching practice

Objective

To describe the characteristics of chronic noncancer pain (CNCP) patients taking oxycodone or its derivatives in a rural teaching practice.

Design

Characteristics of CNCP patients taking oxycodone over a 5-year period (September 2003 to September 2008) were compared with those of patients not taking opioid medications using a retrospective chart audit.

Setting

A rural teaching practice in southwestern Ontario.

Participants

A total of 103 patients taking chronic oxycodone therapy for CNCP and a random sample of 104 patients not taking opioid medication.

Main outcome measures

Number of visits, health problems, sex, and previous history of addiction and mental illness.

Results

Patients with CNCP taking oxycodone had significantly more health problems (P < .001), including drug and tobacco addictions. They had more than 3 times as many clinic visits during the same period of time as patients not taking opioid medication (mean of 39.0 vs 12.8 visits, P < .001).

Conclusion

Patients with CNCP in this rural teaching practice had significantly more health issues (P < .001) and were more likely to have a history of addiction than other patients were. They created more work with significantly more visits over the same period compared with the comparison group.     

Effect of Type 1 Diabetes on Carotid Structure and Function in Adolescents and Young Adults: The SEARCH CVD study

OBJECTIVE

Type 1 diabetes mellitus causes increased carotid intima-media thickness (IMT) in adults. We evaluated IMT in young subjects with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Participants with type 1 diabetes (N = 402) were matched to controls (N = 206) by age, sex, and race or ethnicity. Anthropometric and laboratory values, blood pressure, and IMT were measured. ANCOVA was used to assess differences controlling for demographic risk factors, cardiovascular risk factors, and HbA_1c.

RESULTS

Subjects were 18.9 ± 3.3 years old (50% male, 82.7% non-Hispanic white). Youth with type 1 diabetes had thicker bulb IMT, which remained significantly different after adjustment for demographics and cardiovascular risk factors. Age, sex, adiposity, and systolic blood pressure were consistent significant determinants of IMT. Adjustment for HbA_1c eliminated the difference, suggesting the difference was attributable to poor glycemic control.

CONCLUSIONS

Carotid IMT may be increased in youth with type 1 diabetes at high risk for cardiovascular disease. Better control of diabetes may be essential in preventing progression of atherosclerosis.Type 1 diabetes mellitus leads to increased carotid intima-media thickness (IMT) (1) and higher risk for cardiovascular disease later in life (2). Large studies of carotid ultrasound in youth with type 1 diabetes are lacking. We evaluated adolescents and young adults to determine if increased carotid IMT was present in subjects with type 1 diabetes.