Niall G. Keenan

Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease.

Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow. Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease. However, the effects on myocardial perfusion are unknown. Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone. Twenty-two men (mean age 57 ± 9 [SD] years) were randomly assigned to oral testosterone undecanoate (TU; 80 mg twice daily) or placebo in a crossover study design. After each 8-week period, subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance, pulse-wave analysis, and endothelial function measurements using radial artery tonometry, blood sampling, anthropomorphic measurements, and quality-of-life assessment. Although no difference was found in global myocardial perfusion after TU compared with placebo, myocardium supplied by unobstructed coronary arteries showed increased perfusion (1.83 ± 0.9 vs 1.52 ± 0.65; p = 0.037). TU decreased basal radial and aortic augmentation indexes (p = 0.03 and p = 0.02, respectively), indicating decreased arterial stiffness, but there was no effect on endothelial function. TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference, but had no effect on hemostatic factors, quality of life, and angina symptoms. In conclusion, oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries, in line with previous intracoronary findings. The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia.

CMR of Ventricular Function

Cardiovascular magnetic resonance (CMR) is the reference standard for the assessment of ventricular dimensions, function, and mass in terms of accuracy and reproducibility. It has been thoroughly validated both ex vivo and against other imaging techniques. Measurements are highly accurate and no geometrical assumptions need to be made about the ventricle. A routine ventricular dataset of images can be acquired in less than 5 minutes and analyzed in about the same time. The field is rapidly advancing with increasing automation and simplification in both image acquisition and analysis. Using parallel and real time imaging techniques, good quality data can be obtained even in patients who are unable to hold their breath. While providing useful information in all patients with suspected heart failure, CMR should particularly be considered in those with poor echo windows, where it can also be combined with myocardial stress. Tagging techniques can provide highly detailed information about myocardial torsion and strain for individual myocardial segments. In a research environment, the very high degree of interscan reproducibility can dramatically reduce the number of patients needed to perform clinical trials.

Body Fat Is Associated With Reduced Aortic Stiffness Until Middle Age

Obesity is a major risk factor for cardiometabolic disease, but the effect of body composition on vascular aging and arterial stiffness remains uncertain. We investigated relationships among body composition, blood pressure, age, and aortic pulse wave velocity in healthy individuals. Pulse wave velocity in the thoracic aorta, an indicator of central arterial stiffness, was measured in 221 volunteers (range, 18–72 years; mean, 40.3±13 years) who had no history of cardiovascular disease using cardiovascular MRI. In univariate analyses, age (r=0.78; P<0.001) and blood pressure (r=0.41; P<0.001) showed a strong positive association with pulse wave velocity. In multivariate analysis, after adjustment for age, sex, and mean arterial blood pressure, elevated body fat% was associated with reduced aortic stiffness until the age of 50 years, thereafter adiposity had an increasingly positive association with aortic stiffness (&bgr;=0.16; P<0.001). Body fat% was positively associated with cardiac output when age, sex, height, and absolute lean mass were adjusted for (&bgr;=0.23; P=0.002). These findings suggest that the cardiovascular system of young adults may be capable of adapting to the state of obesity and that an adverse association between body fat and aortic stiffness is only apparent in later life.

Integrated Cardiac and Vascular Assessment in Takayasu Arteritis by Cardiovascular Magnetic Resonance

OBJECTIVE This study was undertaken to evaluate the value of cardiovascular magnetic resonance (CMR) in the assessment of patients with Takayasu arteritis (TA). METHODS Sixteen patients with TA and 2 populations comprising 110 normal volunteers were prospectively recruited. All patients with TA underwent a CMR protocol including measurement of carotid artery wall volume, assessment of left ventricular (LV) volumes and function, and late gadolinium enhancement for the detection of myocardial scarring. RESULTS Carotid artery wall volume, total vessel volume, and the wall:outer wall ratio were elevated in TA patients compared with controls (wall volume 1,045 mm(3) in TA patients versus 640 mm(3) in controls, P < 0.001; total vessel volume 2,268 mm(3) in TA patients versus 2,037 mm(3) in controls, P < 0.05; wall:outer wall ratio 48% in TA patients versus 32% in controls, P < 0.001). The lumen volume was reduced in TA (1,224 mm(3) versus 1,398 mm(3) in controls, P < 0.05). In TA, LV function was more dynamic, with reduced end-systolic volume (mean +/- 95% confidence interval ejection fraction 74 +/- 3% versus 67 +/- 1% in controls, P < 0.001; LV end-systolic volume 19 +/- 4 ml/m(2) versus 25 +/- 1 ml/m(2) in controls, P < 0.001). Myocardial late gadolinium enhancement was present in 4 (27%) of 15 patients, indicating previously unrecognized myocardial damage. CONCLUSION Our findings indicate that an integrated method of cardiovascular assessment by CMR in TA not only provides good delineation of vessel wall thickening, but has also demonstrated dynamic ventricular function, myocardial scarring, and silent myocardial infarction. CMR has benefits compared with other approaches for the assessment and followup of patients with TA, and has potential to identify patients most at risk of complications, allowing early preventative therapy.

New Universal Definition of Myocardial Infarction: Applicable After Complex Percutaneous Coronary Interventions?

OBJECTIVES This study aimed to characterize myocardial infarction after percutaneous coronary intervention (PCI) based on cardiac marker elevation as recommended by the new universal definition and on the detection of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR). It is also assessed whether baseline inflammatory biomarkers are higher in patients developing myocardial injury. BACKGROUND Cardiovascular magnetic resonance accurately assesses infarct size. Baseline C-reactive protein (CRP) and neopterin predict prognosis after stent implantation. METHODS Consecutive patients with baseline troponin (Tn) I within normal limits and no LGE in the target vessel underwent baseline and post-PCI CMR. The Tn-I was measured until 24 h after PCI. Serum high-sensitivity CRP and neopterin were assessed before coronary angiography. RESULTS Of 45 patients, 64 (53 to 72) years of age, 33% developed LGE with infarct size of 0.83 g (interquartile range: 0.32 to 1.30 g). A Tn-I elevation >99% upper reference limit (i.e., myocardial necrosis) (median Tn-I: 0.51 μg/l, interquartile range: 0.16 to 1.23) and Tn-I > 3× upper reference limit (i.e., type 4a myocardial infarction [MI]) occurred in 58% and 47% patients, respectively. LGE was undetectable in 42% and 43% of patients with periprocedural myocardial necrosis and type 4a MI, respectively. Agreement between LGE and type 4a MI was moderate (kappa = 0.45). The levels of CRP or neopterin did not significantly differ between patients with or without myocardial injury, detected by CMR or according to the new definition (p = NS). CONCLUSIONS This study reports the lack of substantial agreement between the new universal definition and CMR for the diagnosis of small-size periprocedural myocardial damage after complex PCI. Baseline levels of CRP or neopterin were not predictive for the development of periprocedural myocardial damage.

An Inter-Landmark Approach to 4-D Shape Extraction and Interpretation: Application to Myocardial Motion Assessment in MRI

This paper presents a novel approach to shape extraction and interpretation in 4-D cardiac magnetic resonance imaging data. Statistical modeling of spatiotemporal interlandmark relationships is performed to enable the decomposition of global shape constraints and subsequently of the image analysis tasks. The introduced descriptors furthermore provide invariance to similarity transformations and thus eliminate pose estimation errors in the presence of image artifacts or geometrical inconsistencies. A set of algorithms are derived to address key technical issues related to constrained boundary tracking, dynamic model relaxation, automatic initialization, and dysfunction localization. The proposed framework is validated with a relatively large dataset of 50 subjects and compared to existing statistical shape modeling methods. The results indicate increased adaptation to spatiotemporal variations and imaging conditions.

Ultra-short echo time cardiovascular magnetic resonance of atherosclerotic carotid plaque

BackgroundMulti-contrast weighted cardiovascular magnetic resonance (CMR) allows detailed plaque characterisation and assessment of plaque vulnerability. The aim of this preliminary study was to show the potential of Ultra-short Echo Time (UTE) subtraction MR in detecting calcification.Methods14 ex-vivo human carotid arteries were scanned using CMR and CT, prior to histological slide preparation. Two images were acquired using a double-echo 3D UTE pulse, one with a long TE and the second with an ultra-short TE, with the same TR. An UTE subtraction (ΔUTE) image containing only ultra-short T2 (and T2*) signals was obtained by post-processing subtraction of the 2 UTE images. The ΔUTE image was compared to the conventional 3D T1-weighted sequence and CT scan of the carotid arteries.ResultsIn atheromatous carotid arteries, there was a 71% agreement between the high signal intensity areas on ΔUTE images and CT scan. The same areas were represented as low signal intensity on T1W and areas of void on histology, indicating focal calcification. However, in 15% of all the scans there were some incongruent regions of high intensity on ΔUTE that did not correspond with a high intensity signal on CT, and histology confirmed the absence of calcification.ConclusionsWe have demonstrated that the UTE sequence has potential to identify calcified plaque. Further work is needed to fully understand the UTE findings.

Population-based studies of myocardial hypertrophy: high resolution cardiovascular magnetic resonance atlases improve statistical power

BackgroundCardiac phenotypes, such as left ventricular (LV) mass, demonstrate high heritability although most genes associated with these complex traits remain unidentified. Genome-wide association studies (GWAS) have relied on conventional 2D cardiovascular magnetic resonance (CMR) as the gold-standard for phenotyping. However this technique is insensitive to the regional variations in wall thickness which are often associated with left ventricular hypertrophy and require large cohorts to reach significance. Here we test whether automated cardiac phenotyping using high spatial resolution CMR atlases can achieve improved precision for mapping wall thickness in healthy populations and whether smaller sample sizes are required compared to conventional methods.MethodsLV short-axis cine images were acquired in 138 healthy volunteers using standard 2D imaging and 3D high spatial resolution CMR. A multi-atlas technique was used to segment and co-register each image. The agreement between methods for end-diastolic volume and mass was made using Bland-Altman analysis in 20 subjects. The 3D and 2D segmentations of the LV were compared to manual labeling by the proportion of concordant voxels (Dice coefficient) and the distances separating corresponding points. Parametric and nonparametric data were analysed with paired t-tests and Wilcoxon signed-rank test respectively. Voxelwise power calculations used the interstudy variances of wall thickness.ResultsThe 3D volumetric measurements showed no bias compared to 2D imaging. The segmented 3D images were more accurate than 2D images for defining the epicardium (Dice: 0.95 vs 0.93, P < 0.001; mean error 1.3 mm vs 2.2 mm, P < 0.001) and endocardium (Dice 0.95 vs 0.93, P < 0.001; mean error 1.1 mm vs 2.0 mm, P < 0.001). The 3D technique resulted in significant differences in wall thickness assessment at the base, septum and apex of the LV compared to 2D (P < 0.001). Fewer subjects were required for 3D imaging to detect a 1 mm difference in wall thickness (72 vs 56, P < 0.001).ConclusionsHigh spatial resolution CMR with automated phenotyping provides greater power for mapping wall thickness than conventional 2D imaging and enables a reduction in the sample size required for studies of environmental and genetic determinants of LV wall thickness.

Usefulness of Left Atrial Volume Versus Diameter to Assess Thromboembolic Risk in Mitral Stenosis

In patients with mitral stenosis (MS) in sinus rhythm (SR), guidelines recommend anticoagulation if the left atrium is enlarged based on diameter measurements. We sought to compare the association of left atrial (LA) diameter and LA volume with markers of thromboembolic risk (peak LA appendage emptying velocity [LAAv] and LA spontaneous contrast density) measured during transesophageal echocardiography in 152 patients with moderate to severe MS. High thromboembolic risk was defined by a peak LAAv < 25 cm/s and/or dense spontaneous contrast. Mean LA diameter (50 ± 7 mm, 32 to 77) and LA volume (152 ± 70 ml, 67 to 720) were significantly correlated (r = 0.71, p < 0.0001), but the relation was curvilinear and the 95% confidence interval increased with LA diameter. In the subset of 80 patients in SR who underwent clinically indicated transesophageal echocardiography, body surface area (BSA)-indexed LA volume but not LA diameter differentiated patients with normal from those with low LAAv (86 ± 17 vs 71 ± 17 ml/m(2), p < 0.01, and 50 ± 6 vs 48 ± 6 mm, p = 0.13, respectively) and patients with dense spontaneous contrast from those with no or mild spontaneous contrast (81 ± 16 vs 63 ± 15 ml/m(2), p < 0.01, and 49 ± 6 vs 46 ± 5 mm, p = 0.11, respectively). BSA-indexed LA volume provided the highest area under the curve (0.85) for high thromboembolic risk and LA diameter the lowest (0.65). A BSA-indexed LA volume > 60 ml/m(2) provided an excellent 90% sensitivity despite 44% specificity, 76% positive predictive value, and 70% negative predictive value. Use of this threshold instead of 50 or 55 mm would have changed the indication for anticoagulation in 51% to 77% of patients. In conclusion, LA volume was more strongly associated with markers of thromboembolic risk than LA diameter, which poorly reflected LA size. Our results support the use of BSA-indexed LA volume to guide the decision for anticoagulation in patients with MS in SR, which may lead to significant change in the management of those patients. We suggest a threshold of 60 ml/m(2), which has good sensitivity, albeit with low specificity.

Effect of rosiglitazone on progression of atherosclerosis: insights using 3D carotid cardiovascular magnetic resonance.

BackgroundThere is recent evidence suggesting that rosiglitazone increases death from cardiovascular causes. We investigated the direct effect of this drug on atheroma using 3D carotid cardiovascular magnetic resonance.ResultsA randomized, placebo-controlled, double-blind study was performed to evaluate the effect of rosiglitazone treatment on carotid atherosclerosis in subjects with type 2 diabetes and coexisting vascular disease or hypertension. The primary endpoint of the study was the change from baseline to 52 weeks of carotid arterial wall volume, reflecting plaque burden, as measured by carotid cardiovascular magnetic resonance. Rosiglitazone or placebo was allocated to 28 and 29 patients respectively. Patients were managed to have equivalent glycemic control over the study period, but in fact the rosiglitazone group lowered their HbA1c by 0.88% relative to placebo (P < 0.001). Most patients received a statin or fibrate as lipid control medication (rosiglitazone 78%, controls 83%). Data are presented as mean ± SD. At baseline, the carotid arterial wall volume in the placebo group was 1146 ± 550 mm3 and in the rosiglitazone group was 1354 ± 532 mm3. After 52 weeks, the respective volumes were 1134 ± 523 mm3 and 1348 ± 531 mm3. These changes (-12.1 mm3 and -5.7 mm3 in the placebo and rosiglitazone groups, respectively) were not statistically significant between groups (P = 0.57).ConclusionTreatment with rosiglitazone over 1 year had no effect on progression of carotid atheroma in patients with type 2 diabetes mellitus compared to placebo.