A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study.

AIMS/HYPOTHESIS: Cu(II)-selective chelation with trientine ameliorates cardiovascular and renal disease in a model of diabetes in rats. Here, we tested the hypothesis that Cu(II)-selective chelation might improve left ventricular hypertrophy (LVH) in type 2 diabetic patients. METHODS: We performed a 12 month randomised placebo-controlled study of the effects of treatment with the Cu(II)-selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given orally twice daily) on LVH in diabetic patients (n = 15/group at baseline) in an outpatient setting wherein participants, caregivers and those assessing outcomes were blinded to group assignment. Using MRI, we measured left ventricular variables at baseline, and at months 6 and 12. The change from baseline in left ventricular mass indexed to body surface area (LVM(bsa)) was the primary endpoint variable. RESULTS: Diabetic patients had LVH with preserved ejection fraction at baseline. Trientine treatment decreased LVM(bsa) by 5.0 +/- 7.2 g/m(2) (mean +/- SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants were analysed; p = 0.0056 compared with placebo) and by 10.6 +/- 7.6 g/m(2) at month 12 (when nine trientine-treated and 13 placebo-treated participants were analysed; p = 0.0088), whereas LVM(bsa) was unchanged by placebo treatment. In a multiple-regression model that explained ~75% of variation (R (2) = 0.748, p = 0.001), cumulative urinary Cu excretion over 12 months was positively associated with trientine-evoked decreases in LVM(bsa). CONCLUSIONS/INTERPRETATION: Cu(II)-selective chelation merits further exploration as a potential pharmacotherapy for diabetic heart disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12609000053224 FUNDING: The Endocore Research Trust; Lottery Health New Zealand; the Maurice and Phyllis Paykel Trust; the Foundation of Research, Science and Technology (New Zealand); the Health Research Council of New Zealand; the Ministry of Education (New Zealand) through the Maurice Wilkins Centre for Molecular Biodiscovery; and the Protemix Corporation.

4D modelling for rapid assessment of biventricular function in congenital heart disease.

Although more patients with congenital heart disease (CHD) are now living longer due to better surgical interventions, they require regular imaging to monitor cardiac performance. There is a need for robust clinical tools which can accurately assess cardiac function of both the left and right ventricles in these patients. We have developed methods to rapidly quantify 4D (3D + time) biventricular function from standard cardiac MRI examinations. A finite element model was interactively customized to patient images using guide-point modelling. Computational efficiency and ability to model large deformations was improved by predicting cardiac motion for the left ventricle and epicardium with a polar model. In addition, large deformations through the cycle were more accurately modeled using a Cartesian deformation penalty term. The model was fitted to user-defined guide points and image feature tracking displacements throughout the cardiac cycle. We tested the methods in 60 cases comprising a variety of congenital heart diseases and showed good correlation with the gold standard manual analysis, with acceptable inter-observer error. The algorithm was considerably faster than standard analysis and shows promise as a clinical tool for patients with CHD.

An interactive tool for rapid biventricular analysis of congenital heart disease.

Cardiac malformations are the most common birth defect. Better interventions in early life have improved mortality for children with congenital heart disease, but heart failure is a significant problem in adulthood. These patients require regular imaging and analysis of biventricular (left and right ventricular) function. In this study, we describe a rapid method to analyse left and right ventricular shape and function from cardiac MRI examinations. A 4D (3D+time) finite element model template is interactively customized to the anatomy and motion of the biventricular unit. The method was validated in 17 patients and 10 ex-vivo hearts. Interactive model updates were achieved through preconditioned conjugate gradient optimization on a multithread system, and by precomputing points predicted from a coarse mesh optimization.

Wall shear stress is the primary mechanism of energy loss in the Fontan connection.

Long-term outcome following the Fontan operation may be affected by the amount of energy lost as blood flows through the anastomosis geometry. A method for detailed quantification of energy loss is applied to computational simulations of the flow in an atriopulmonary and a total cavopulmonary model. Five types of flow (near wall, slow recirculation, medium speed vortices, collision, and streamlined flow) are identified and their energy losses quantified. The presence of recirculation regions decreases the efficiency of the atriopulmonary model, and a region of increased energy loss is seen in the collision region in the total cavopulmonary model. However, the most significant energy loss is through wall shear stress, which is maximal in areas where there is rapid, near wall flow.

Left ventricular mass and volume: fast calculation with guide-point modeling on MR images.

The authors describe a fast method for calculating left ventricle (LV) mass and volumes from multiplanar magnetic resonance (MR) images. Mathematic models were fitted to a small number of user-selected guide points in 15 healthy volunteers, 13 patients after myocardial infarction, and a canine model of mitral regurgitation in eight dogs. Errors between model and manual contours were small (LV mass, 1.8 g +/- 4.9 [mean +/- SD]; end-diastolic volume, 2.2 mL +/- 4.6; end-systolic volume, 2.3 mL +/- 3.8). Estimates of global function could be obtained in 6 minutes, a time saving of 5-10 times over estimates with manual contouring.

Identification of the fascia propria by magnetic resonance imaging and its relevance to preoperative assessment of rectal cancer.

UNLABELLED: If rectal cancer does not penetrate the fascia propria of the rectum and the rectum is removed with the fascial envelope intact (extrafascial excision), then local recurrence of the cancer will be minimal. Modern imaging techniques have identified a fascial plane surrounding the rectum and mesorectum, and it has been suggested that this is the fascia propria. The aim of this study was to identify whether this plane is the rectal fascia propria and whether tumor invasion through this fascia can be identified preoperatively. METHODS: Two separate experiments were performed: 1) pelvic magnetic resonance imaging was performed before and after dissection and marking of the plane of extrafascial dissection of the rectum of a cadaver; and 2) magnetic resonance imaging was performed in 43 rectal cancer patients preoperatively. Two radiologists independently reported the depth of tumor invasion in relation to the fascia propria. The tumors were resected by extrafascial excision, and a pathologist independently reported the relation of the tumor to the fascia propria. RESULTS: The marker inserted in the extrafascial plane showed that the plane visualized on pelvic magnetic resonance imaging was the fascia propria dissected in extrafascial excision of the rectum. The magnetic resonance imaging detected tumor penetration through the fascia propria with a sensitivity of 67 percent, a specificity of 100 percent, and an accuracy of 95 percent. CONCLUSION: The surgical fascia propria can be identified on preoperative magnetic resonance imaging in patients with rectal cancer. Tumor invasion through this fascia can be detected on magnetic resonance imaging. This method of assessment offers a new way to select those patients who require preoperative radiotherapy.