Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration-resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Early diagnosis of malignant spinal cord compression (SCC) is crucial because pretreatment neurological status is the major determinant of outcome. In metastatic castration-resistant prostate cancer, SCC is a clinically significant cause of disease-related morbidity and mortality. We investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis. METHODS: We did a parallel-group, open-label, randomised, controlled, phase 3, superiority trial. Patients with metastatic castration-resistant prostate cancer were recruited from 45 National Health Service hospitals in the UK. Eligible patients were aged at least 18 years, with an Eastern Co-operative Oncology Group performance status of 0-2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months. Participants were randomly assigned (1:1), using a minimisation algorithm with a random element (balancing factors were treatment centre, alkaline phosphatase [normal vs raised, with the upper limit of normal being defined at each participating laboratory], number of previous systemic treatments [first-line vs second-line or later], previous spinal treatment, and imaging of thorax and abdomen), to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 h after screening MRI in the intervention group. Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician's recommendation) and 6-monthly spinal MRI. All patients were followed up every 3 months, and then at month 30 and 36. The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being 1 year after randomisation. The study is registered with ISRCTN, ISRCTN74112318, and is now complete. FINDINGS: Between Feb 26, 2013, and April 25, 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. Median age was 74 years (IQR 68 to 79), 222 (53%) of 420 patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48 ng/mL (IQR 17 to 162). Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable scans in the intervention group. As of data cutoff (April 23, 2020), at a median follow-up of 22 months (IQR 13 to 31), time to cSCC was not significantly improved with screening (hazard ratio 0·64 [95% CI 0·37 to 1·11]; Gray's test p=0·12). 1-year cSCC rates were 6·7% (95% CI 3·8-10·6; 14 of 210 patients) for the control group and 4·3% (2·1-7·7; nine of 210 patients) for the intervention group (difference -2·4% [95% CI -4·2 to 0·1]). Median time to cSCC was not reached in either group. No serious adverse events were reported within 24 h of screening. INTERPRETATION: Despite the substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up. Routine use of screening MRI and pre-emptive treatment to prevent cSCC is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis. FUNDING: Cancer Research UK.

Absence of potential gadolinium toxicity symptoms following 22,897 gadoteric acid (Dotarem®) examinations, including 3,209 performed on renally insufficient individuals.

OBJECTIVES: Recent safety concerns regarding gadolinium-based contrast agents (GdCAs) concluded with the suspension of some agents from the European market, yet a clinical consequence remains unknown. We used electronic health records to investigate the incidence of potential toxicity to gadoteric acid (Dotarem®) within our local population, including those with renal insufficiency (RI). METHODS: Data for patients who underwent contrast-enhanced MRI were identified, stratified by renal function at time of scan and retrospectively followed using routinely collected health data. Searches performed were: records of hypersensitivity reactions; diagnoses of nephrogenic systemic fibrosis (NSF); onset of chronic pain, a symptom that has been associated with NSF and the theorised gadolinium deposition disease (GDD); and post-contrast acute kidney injury (PC-AKI). Comparisons were made between patients and controls (those who underwent non-contrast scans) via chi-square and ANOVA statistical tests. RESULTS: Of the 22,897 contrast-enhanced MRI scans performed locally from 2004-2016 (adult, n = 22,325 and paediatric, n = 572), 14% were performed on patients with RI (30 ≤ eGFR < 60, n = 2,622; 15 ≤ eGFR < 30, n = 464; eGFR < 15, n = 123). Two adult patients (0.01%) suffered hypersensitivity reactions. Zero cases of NSF were reported, with an average follow-up time of 6.0 ± 2.5 years (range, 8 months-15 years). Analysis failed to highlight statistically higher rates of chronic pain onset post-MRI (adult: p = 0.777, paediatric: p = 0.578), or PC-AKI (adult: p = 0.566, paediatric: p = 0.841), in the patient groups compared to controls. CONCLUSIONS: These data indicate that administration of gadoteric acid to RI patients does not result in a higher rate of signs or symptoms that may be associated with gadolinium toxicity when compared to controls. KEY POINTS: • Following 22,897 administrations of gadoteric acid to a local population, there was no association with symptoms that may be associated with gadolinium toxicity. • Zero cases of nephrogenic systemic fibrosis were reported following 3,209 gadoteric acid administrations to a cohort of renally insufficient patients. • A low number of hypersensitivity reactions were observed (0.01%) and no higher rate of chronic pain or post-contrast acute kidney injury were noted when compared with a control cohort of non-contrast-enhanced examinations.

Prevalence and Distribution of Atherosclerosis in a Low- to Intermediate-Risk Population: Assessment with Whole-Body MR Angiography.

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort. © RSNA, 2018 Online supplemental material is available for this article.

Pulmonary arterial stiffening in COPD and its implications for right ventricular remodelling.

BACKGROUND: Pulmonary pulse wave velocity (PWV) allows the non-invasive measurement of pulmonary arterial stiffening, but has not previously been assessed in COPD. The aim of the current study was to assess PWV in COPD and its association with right ventricular (RV) remodelling. METHODS: Fifty-eight participants with COPD underwent pulmonary function tests, 6-min walk test and cardiac MRI, while 21 healthy controls (HCs) underwent cardiac MRI. Thirty-two COPD patients underwent a follow-up MRI to assess for longitudinal changes in RV metrics. Cardiac MRI was used to quantify RV mass, volumes and PWV. Differences in continuous variables between the COPD and HC groups was tested using an independent t-test, and associations between PWV and right ventricular parameters was examined using Pearson's correlation coefficient. RESULTS: Those with COPD had reduced pulsatility (COPD (mean±SD):24.88±8.84% vs. HC:30.55±11.28%, p=0.021), pulmonary acceleration time (COPD:104.0±22.9ms vs. HC: 128.1±32.2ms, p<0.001), higher PWV (COPD:2.62±1.29ms-1 vs. HC:1.78±0.72ms-1, p=0.001), lower RV end diastolic volume (COPD:53.6±11.1ml vs. HC:59.9±13.0ml, p=0.037) and RV stroke volume (COPD:31.9±6.9ml/m2 vs. HC:37.1±6.2ml/m2, p=0.003) with no difference in mass (p=0.53). PWV was not associated with right ventricular parameters. CONCLUSIONS: While pulmonary vascular remodelling is present in COPD, cardiac remodelling favours reduced filling rather than increased afterload. Treatment of obstructive lung disease may have greater effect on cardiac function than treatment of pulmonary vascular disease in most COPD patients KEY POINTS: • Pulmonary pulse wave velocity (PWV) is elevated in COPD. • Pulmonary PWV is not associated with right ventricular remodelling. • Right ventricular remodelling is more in keeping with that of reduced filling.

Research cardiac magnetic resonance imaging in end stage renal disease - incidence, significance and implications of unexpected incidental findings.

OBJECTIVES: Left ventricular mass (LVM) at cardiac magnetic resonance imaging (CMR) is a frequent end point in clinical trials in nephrology. Trial participants with end stage renal disease (ESRD) may have a greater frequency of incidental findings (IF). We retrospectively investigated prevalence of IF in previous research CMR and reviewed their subsequent impact on participants. METHODS: Between 2002 and 2006, 161 ESRD patients underwent CMR in a transplant assessment study. Images were used to assess LV mass and function. In the current study a radiologist reviewed the scans for IF. Review of patient records determined the subsequent clinical significance of IF. RESULTS: There were 150 IF in 95 study participants. Eighty-four (56 %) were new diagnoses. One hundred and two were non-cardiac. Fifteen were suspicious of malignancy. There was a clinically significant IF for 14.9 % of the participants. In six cases earlier identification of an IF may have improved quality of life or survival. CONCLUSIONS: Without radiology support clinically important IF may be missed on CMR. Patients undergoing CMR in trials should be counselled about the frequency and implications of IF. Patients with ESRD have a higher prevalence of IF than reported in other populations. Nephrology studies require mechanisms for radiologist reporting and strategies for dealing with IF. KEY POINTS: • Incidental findings on research cardiac magnetic resonance imaging can have significant consequences. • We considered incidental findings in historical renal cardiac resonance imaging clinical trials. • Incidental findings are common and important in the chronic kidney disease population. • Without radiology support, clinically significant incidental findings may be missed on imaging. • Study protocols, approvals and consent processes should take account of possible findings.

Effects of inaccuracies in arterial path length measurement on differences in MRI and tonometry measured pulse wave velocity.

BACKGROUND: Carotid-femoral pulse wave velocity (cf-PWV) and aortic PWV measured using MRI (MRI-PWV) show good correlation, but with a significant and consistent bias across studies. The aim of the current study was to evaluate whether the differences between cf.-PWV and MRI-PWV can be accounted for by inaccuracies of currently used distance measurements. METHODS: One hundred fourteen study participants were recruited into one of 4 groups: Type 2 diabetes melltus (T2DM) with cardiovascular disease (CVD) (n = 23), T2DM without CVD (n = 41), CVD without T2DM (n = 25) and a control group (n = 25). All participants underwent cf.-PWV, cardiac MRI and whole body MR angiography(WB-MRA). 90 study participants also underwent aortic PWV using MRI. cf.-PWVEXT was performed using a SphygmoCor device (Atcor Medical, West Ryde, Australia). The true intra-arterial pathlength was measured using the WB-MRA and then used to recalculate the cf.-PWVEXT to give a cf.-PWVMRA. RESULTS: Distance measurements were significantly lower on WB-MRA than on external tape measure (mean diff = -85.4 ± 54.0 mm,p < 0.001). MRI-PWV was significantly lower than cf.-PWVEXT (MRI-PWV = 8.1 ± 2.9 vs. cf.-PWVEXT = 10.9 ± 2.7 ms-1,p < 0.001). When cf.-PWV was recalculated using the inter-arterial distance from WB-MRA, this difference was significantly reduced but not lost (MRI-PWV = 8.1 ± 2.9 ms-1 vs. cf.-PWVMRA 9.1 ± 2.1 ms-1, mean diff = -0.96 ± 2.52 ms-1,p = 0.001). Recalculation of the PWV increased correlation with age and pulse pressure. CONCLUSION: Differences in cf.-PWV and MRI PWV can be predominantly but not entirely explained by inaccuracies introduced by the use of simple surface measurements to represent the convoluted arterial path between the carotid and femoral arteries.

Workflow optimisation for multimodal imaging procedures: a case of combined X-ray and MRI-guided TACE.

This study presents a framework for workflow optimisation of multimodal image-guided procedures (MIGP) based on discrete event simulation (DES). A case of a combined X-Ray and magnetic resonance image-guided transarterial chemoembolisation (TACE) is presented to illustrate the application of this method. We used a ranking and selection optimisation algorithm to measure the performance of a number of proposed alternatives to improve a current scenario. A DES model was implemented with detail data collected from 59 TACE procedures and durations of magnetic resonance imaging (MRI) diagnostic procedures usually performed in a common MRI suite. Fourteen alternatives were proposed and assessed to minimise the waiting times and improve workflow. Data analysis observed an average of 20.68 (7.68) min of waiting between angiography and MRI for TACE patients in 71.19% of the cases. Following the optimisation analysis, an alternative was identified to reduce waiting times in angiography suite up to 48.74%. The model helped to understand and detect 'bottlenecks' during multimodal TACE procedures, identifying a better alternative to the current workflow and reducing waiting times. Simulation-based workflow analysis provides a cost-effective way to face some of the challenges of introducing MIGP in clinical radiology, highligthed in this study.

Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design.

BACKGROUND: Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. METHODS: The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. CONCLUSIONS: This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF. Trial registration Clinical Trials.gov: NCT02397421. Registered 12th March 2015.

3T MRI investigation of cardiac left ventricular structure and function in a UK population: The tayside screening for the prevention of cardiac events (TASCFORCE) study.

PURPOSE: To scan a volunteer population using 3.0T magnetic resonance imaging (MRI). MRI of the left ventricular (LV) structure and function in healthy volunteers has been reported extensively at 1.5T. MATERIALS AND METHODS: A population of 1528 volunteers was scanned. A standardized approach was taken to acquire steady-state free precession (SSFP) LV data in the short-axis plane, and images were quantified using commercial software. Six observers undertook the segmentation analysis. RESULTS: Mean values (±standard deviation, SD) were: ejection fraction (EF) = 69 ± 6%, end diastolic volume index (EDVI) = 71 ± 13 ml/m2 , end systolic volume index (ESVI) = 22 ± 7 ml/m2 , stroke volume index (SVI) = 49 ± 8 ml/m2 , and LV mass index (LVMI) = 55 ± 12 g/m2 . The mean EF was slightly larger for females (69%) than for males (68%), but all other variables were smaller for females (EDVI 68v77 ml/m2 , ESVI 21v25 ml/m2 , SVI 46v52 ml/m2 , LVMI 49v64 g/m2 , all P < 0.05). The mean LV volume data mostly decreased with each age decade (EDVI males: -2.9 ± 1.3 ml/m2 , females: -3.1 ± 0.8 ml/m2 ; ESVI males: -1.3 ± 0.7 ml/m2 , females: -1.7 ± 0.5 ml/m2 ; SVI males: -1.7 ± 0.9 ml/m2 , females: -1.4 ± 0.6 ml/m2 ; LVMI males: -1.6 ± 1.1 g/m2 , females: -0.2 ± 0.6 g/m2 ) but the mean EF was virtually stable in males (0.6 ± 0.6%) and rose slightly in females (1.2 ± 0.5%) with age. CONCLUSION: LV reference ranges are provided in this population-based MR study at 3.0T. The variables are similar to those described at 1.5T, including variations with age and gender. These data may help to support future population-based MR research studies that involve the use of 3.0T MRI scanners. J. Magn. Reson. Imaging 2016;44:1186-1196.

Efficacy of the Ulnar-Basilic Arteriovenous Fistula for Hemodialysis: A Systematic Review.

BACKGROUND: The fistula first initiative has promoted arteriovenous fistulas (AVFs) as the vascular access of choice. To preserve as many future access options as possible, multiple guidelines advocate that the most distal AVF possible should be created in the first place. Generally, snuff box and radiocephalic (RC) are accepted and well-described sites for AVFs; however, the forearm ulnar-basilic (UB) AVF is seldom used or recommended. The aim of this study is to assess and systematically review the evidence base for the creation of the UB fistula and to critically appraise whether more attention should be given to this site. METHODS: Electronic databases were searched for studies involving the creation of UB fistulas for dialysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes for this study were 1-year primary and secondary patency rates. Secondary outcomes were rates of hemodialysis access-induced distal ischemia (HAIDI) and infection. RESULTS: After strict inclusion and/or exclusion criteria by 2 reviewers, 8 studies were included in our review. Weighted-pooled data reveal 1-year primary patency rate for UB AVFs of 53.0% (95% confidence interval [CI]: 40.1-65.8%) with a secondary patency rate of 72.0% (95% CI: 59.2-83.3). HAIDI and infection rates were low. CONCLUSIONS: Our review has shown that the UB AVF may be a viable alternative when a RC AVF is not possible, and dialysis is not required urgently. It has adequate 1-year primary and secondary patency rates and extremely low risk of HAIDI. While it may be more challenging for both surgeons and dialysis nurses to make it a successful vascular access it offers a further option of distal access which may be overlooked.

Whole body cardiovascular magnetic resonance imaging to stratify symptomatic and asymptomatic atherosclerotic burden in patients with isolated cardiovascular disease.

BACKGROUND: The aim of this study was to use whole body cardiovascular magnetic resonance imaging (WB CVMR) to assess the heart and arterial network in a single examination, so as to describe the burden of atherosclerosis and subclinical disease in participants with symptomatic single site vascular disease. METHODS: 64 patients with a history of symptomatic single site vascular disease (38 coronary artery disease (CAD), 9 cerebrovascular disease, 17 peripheral arterial disease (PAD)) underwent whole body angiogram and cardiac MR in a 3 T scanner. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cine and late gadolinium enhancement images of the left ventricle were obtained. RESULTS: Asymptomatic atherosclerotic disease with greater than 50% stenosis in arteries other than that responsible for their presenting complain was detected in 37% of CAD, 33% of cerebrovascular and 47% of PAD patients. Unrecognised myocardial infarcts were observed in 29% of PAD patients. SAS was significantly higher in PAD patients 24 (17.5-30.5) compared to CAD 4 (2-11.25) or cerebrovascular disease patients 6 (2-10) (ANCOVA p < 0.001). Standardised atheroma score positively correlated with age (ß 0.36 p = 0.002), smoking status (ß 0.34 p = 0.002), and LV mass (ß -0.61 p = 0.001) on multiple linear regression. CONCLUSION: WB CVMR is an effective method for the stratification of cardiovascular disease. The high prevalence of asymptomatic arterial disease, and silent myocardial infarctions, particularly in the peripheral arterial disease group, demonstrates the importance of a systematic approach to the assessment of cardiovascular disease.

MRI of the left atrium at 3T: evaluation of measurement reproducibility in healthy volunteers and patients with cardiovascular disease.

Background Left ventricular (LV) function has traditionally been the focus for cardiac magnetic resonance imaging (MRI) investigations, but similar methods can also be applied to the left atrium (LA). Previous studies elsewhere have almost entirely involved the use of 1.5T systems, but 3T MRI can provide faster data acquisition with thinner image slices, and may be more suitable for quantifying the structure and function of the LA. Purpose To evaluate 3T-MRI for LA volume assessments in: (i) healthy volunteers (HV); (ii) patients with LV-hypertrophy and ischemia (LVHI); and (iii) patients with LV-hypertrophy and diabetes (LVHD). Material and Methods Participants were imaged using a balanced steady-state free precession sequence. Healthy volunteers were scanned twice and patients were scanned on one occasion. Volumes were segmented by two observers, and coefficients of repeatability (CoR) were derived. Results For LA volumes (indexed to body surface area), CoRs were in the range of 1.3-4.6 mL/m2. The LVHI patients had enlarged LA volumes (diastolic, 46.4 mL/m2; systolic, 25.9 mL/m2) and reduced ejection fraction (EF) (44.9%) relative to the HV (diastolic, 39.0 mL/m2; systolic, 17.8 mL/m2; EF, 54.5%) and LVHD groups (diastolic, 41.4 mL/m2; systolic, 20.2 mL/m2; EF, 50.7%). LA volumes were moderately correlated with LV mass in the HV group (R2 = 0.59 for LA end-systolic volume), but became weaker (R2 ≤ 0.17) for patient groups. Conclusion 3T-MRI derived LA volume measurements are simple and repeatable, and can elicit clear differences between LVHI patients and HVs. These MRI endpoints provide scope for improved radiological interpretation of LA structure and function, and the high degree of repeatability validates their use for longitudinal investigations where precision work is essential.

Cohort comparison study of cardiac disease and atherosclerotic burden in type 2 diabetic adults using whole body cardiovascular magnetic resonance imaging.

BACKGROUND: Whole body cardiovascular MR (WB CVMR) combines whole body angiography and cardiac MR assessment. It is accepted that there is a high disease burden in patients with diabetes, however the quantification of the whole body atheroma burden in both arterial and cardiac disease has not been previously reported. In this study we compare the quantified atheroma burden in those individuals with and without diabetes by clinical cardiovascular disease (CVD) status. METHODS: 158 participants underwent WB CVMR, and were categorised into one of four groups: (1) type 2 diabetes mellitus (T2DM) with CVD; (2) T2DM without CVD; (3) CVD without T2DM; (4) healthy controls. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cardiac MR and late gadolinium enhancement images of the left ventricle were obtained for assessment of mass, volume and myocardial scar assessment. RESULTS: 148 participants completed the study protocol--61% male, with mean age of 64 ± 8.2 years. SAS was highest in those with cardiovascular disease without diabetes [10.1 (0-39.5)], followed by those with T2DM and CVD [4 (0-41.1)], then those with T2DM only [3.23 (0-19.4)] with healthy controls having the lowest atheroma score [2.4 (0-19.4)]. Both groups with a prior history of CVD had a higher SAS and left ventricular mass than those without (p < 0.001 for both). However after accounting for known cardiovascular risk factors, only the SAS in the group with CVD without T2DM remained significantly elevated. 6% of the T2DM group had evidence of silent myocardial infarct, with this subcohort having a higher SAS than the remainder of the T2DM group [7.7 (4-19) vs. 2.8 (0-17), p = 0.024]. CONCLUSIONS: Global atheroma burden was significantly higher in those with known cardiovascular disease and without diabetes but not in those with diabetes and cardiovascular disease suggesting that cardiovascular events may occur at a lower atheroma burden in diabetes.

Spiral Laminar Flow is Associated with a Reduction in Disturbed Shear in Patient-Specific Models of an Arteriovenous Fistula.

PURPOSE: Areas of disturbed shear that arise following arteriovenous fistula (AVF) creation are believed to contribute to the development of intimal hyperplasia (IH). The presence of helical flow can suppress areas of disturbed shear, which may protect the vasculature from IH. Therefore, the aim of this study is to determine if helical flow, specifically spiral laminar flow (SLF), is present in patient-specific AVF models and is associated with a reduction in exposure to disturbed shear. METHODS: Four AVF were imaged using MRI within the first two weeks following fistula creation. Patient-specific boundary conditions were obtained using phase-contrast MRI and applied at the inlet and outlets of each model. Computational fluid dynamics was used to analyse the hemodynamics in each model and compare the helical content of the flow to the distribution of disturbed shear. RESULTS: BC-1 and RC-2 are characterised by the presence of SLF, which coincides with the lowest distribution of disturbed shear. Contrastingly, SLF is absent from BC-2 and RC-1 and experience the largest amount of disturbed shear. Interestingly, BC-2 and RC-1 developed an anastomosis stenosis, while BC-1 and RC-2 remained stenosis free. CONCLUSION: These findings are in agreement with previous clinical studies and further highlight the clinical potential of SLF as a prognostic marker for a healthy AVF, as its presence correlates with an overall reduction in exposure to disturbed shear and a decrease in the incidence of AVF dysfunction, albeit in a small sample size.

Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease.

Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD and LVH. We randomly assigned 67 subjects to allopurinol at 300 mg/d or placebo for 9 months; 53 patients completed the study. We measured left ventricular mass index (LVMI) with cardiac magnetic resonance imaging (MRI), assessed endothelial function by flow-mediated dilation (FMD) of the brachial artery, and evaluated central arterial stiffness by pulse-wave analysis. Allopurinol significantly reduced LVH (P=0.036), improved endothelial function (P=0.009), and improved the central augmentation index (P=0.015). This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD. Because LVH and endothelial dysfunction associate with prognosis, these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH.

Tayside Screening For Cardiac Events (TASCFORCE) study: a prospective cardiovascular risk screening study.

PURPOSE: Risk factor-based models struggle to accurately predict the development of cardiovascular disease (CVD) at the level of the individual. Ways of identifying people with low predicted risk who will develop CVD would allow stratified advice and support informed treatment decisions about the initiation or adjustment of preventive medication, and this is the aim of this prospective cohort study. PARTICIPANTS: The Tayside Screening for Cardiac Events (TASCFORCE) study recruited men and women aged≥40 years, free from known CVD, with a predicted 10-year risk of coronary heart disease<20%. If B-type natriuretic peptide (BNP) was greater than their gender median, participants were offered a whole-body contrast-enhanced MRI (WBCE-MRI) scan (cardiac imaging, whole-body angiography to determine left ventricular parameters, delayed gadolinium enhancement, atheroma burden). Blood, including DNA, was stored for future biomarker assays. Participants are being followed up using electronic record-linkage cardiovascular outcomes. FINDINGS TO DATE: 4423 (1740, 39.3% men) were recruited. Mean age was 52.3 years with a median BNP of 7.50 ng/L and 15.30 ng/L for men and women, respectively. 602 had a predicted 10-year risk of 10%-19.9%, with the remainder<10%. Age, female sex, ex-smoking status, lower heart rate, higher high-density lipoprotein and lower total cholesterol were independently associated with higher log10 BNP levels. Mean left ventricular mass was 129.2 g and 87.0 g in men and women, respectively. FUTURE PLANS: The TASCFORCE study is investigating the ability of a screening programme, using BNP and WBCE-MRI, at the time of enrolment, to evaluate prediction of CVD in a population at low/intermediate risk. Blood stored for future biomarker analyses will allow testing/development of novel biomarkers. We believe this could be a new UK Framingham study allowing study for many years to come. CLINICAL TRIAL REGISTRATION: ISRCTN38976321.

A Randomized, Controlled Trial of the Effect of Allopurinol on Left Ventricular Mass Index in Hemodialysis Patients.

INTRODUCTION: Increased left ventricular mass index (LVMI) is associated with mortality in end-stage renal disease. LVMI regression may improve outcomes. Allopurinol has reduced LVMI in randomized controlled trials in chronic kidney disease, diabetes, and ischemic heart disease. This study investigated whether allopurinol would regress LVMI in hemodialysis patients. METHODS: This was a randomized placebo-controlled double-blind multicenter trial funded by the British Heart Foundation (PG/12/72/29743). A total of 80 patients undergoing regular maintenance hemodialysis were recruited from NHS Tayside, NHS Greater Glasgow and Clyde and NHS Ayrshire and Arran in Scotland, UK. Participants were randomly assigned on a 1:1 ratio to 12 months of therapy with allopurinol 300 mg or placebo after each dialysis session. The primary outcome was change in LVMI, as assessed by cardiac magnetic resonance imaging (CMRI) at baseline and 12 months. Secondary outcomes were change in BP, flow-mediated dilation (FMD), augmentation indices (AIx), and pulse wave velocity (PWV). RESULTS: A total of 53 patients, with a mean age of 58 years, completed the study and had CMRI follow-up data for analysis. Allopurinol did not regress LVMI (change in LVMI: placebo +3.6 ± 10.4 g/m2; allopurinol: +1.6 ± 11 g/m2; P = 0.49). Allopurinol had no demonstrable effect on BP, FMD, AIx, or PWV. CONCLUSION: Compared with placebo, treatment with allopurinol did not regress LVMI in this trial.

Allopurinol in Patients with Pulmonary Hypertension Associated with Chronic Lung Disease.

Background: Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD). Methods: We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT). Results: Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterial pressure 30 mm Hg, FEV1 60% and resting SpO2 96%. After 12 months, there was no significant difference in the change in RVM from baseline (allopurinol 1.85g vs placebo 0.97g with mean difference 0.88g, CI -4.77 to 3.01, p =0.7). There were also no significant changes in other cardiac parameters measured on MRI, in QOL, spirometry and 6MWT. Subgroup analysis showed that allopurinol significantly reduced RVM compared to placebo with -6.16g vs 0.75g and mean difference 6.92g (CI 1.14 to 12.69, p = 0.02) in COPD patients with more severe airflow limitation. Conclusion: Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation.

Dapagliflozin Versus Placebo on Left Ventricular Remodeling in Patients With Diabetes and Heart Failure: The REFORM Trial.

OBJECTIVE: To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI. RESEARCH DESIGN AND METHODS: We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI. Key secondary end points included other measures of LV remodeling and clinical and biochemical parameters. RESULTS: In our cohort, dapagliflozin had no effect on LVESV or any other parameter of LV remodeling. However, it reduced diastolic blood pressure and loop diuretic requirements while increasing hemoglobin, hematocrit, and ketone bodies. There was a trend toward lower weight. CONCLUSIONS: We were unable to determine with certainty whether dapagliflozin in patients with T2DM and HF had any effect on LV remodeling. Whether the benefits of dapagliflozin in HF are due to remodeling or other mechanisms remains unknown.