12 results found
Simoes Monteiro de Marvao A, McGurk K, Zheng S, et al., 2021, Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy, Journal of the American College of Cardiology, Vol: 78, Pages: 1097-1110, ISSN: 0735-1097
Background: Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomereencoding genes, but little is known about the clinical significance of these variants in thegeneral population.Objectives: To compare lifetime outcomes and cardiovascular phenotypes according to thepresence of rare variants in sarcomere-encoding genes amongst middle-aged adults.Methods: We analysed whole exome sequencing and cardiac magnetic resonance (CMR)imaging in UK Biobank participants stratified by sarcomere-encoding variant status.Results: The prevalence of rare variants (allele frequency <0.00004) in HCM-associatedsarcomere-encoding genes in 200,584 participants was 2.9% (n=5,712; 1 in 35), and theprevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was0.25% (n=493, 1 in 407). SARC-HCM-P/LP variants were associated with increased risk ofdeath or major adverse cardiac events compared to controls (HR 1.69, 95% CI 1.38 to 2.07,p<0.001), mainly due to heart failure endpoints (HR 4.23, 95% CI 3.07 to 5.83, p<0.001). In21,322 participants with CMR, SARC-HCM-P/LP were associated with asymmetric increasein left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) buthypertrophy (≥13mm) was only present in 18.4% (n=9/49, 95% CI 9 to 32%). SARC-HCMP/LP were still associated with heart failure after adjustment for wall thickness (HR 6.74,95% CI 2.43 to 18.7, p<0.001).Conclusions: In this population of middle-aged adults, SARC-HCM-P/LP variants have lowaggregate penetrance for overt HCM but are associated with increased risk of adversecardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absoluteevent rates are low, identification of these variants may enhance risk stratification beyondfamilial disease.
Onwordi EC, Whitehurst T, Mansur A, et al., 2021, The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study, Translational Psychiatry, Vol: 11, Pages: 1-9, ISSN: 2158-3188
Glutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we investigated whether synaptic vesicle glycoprotein 2 A (SV2A) levels are related to glutamatergic markers and NAA in healthy volunteers (HV) and schizophrenia patients (SCZ). Forty volunteers (SCZ n = 18, HV n = 22) underwent [11C]UCB-J positron emission tomography and proton magnetic resonance spectroscopy (1H-MRS) imaging in the left hippocampus and anterior cingulate cortex (ACC) to index [11C]UCB-J distribution volume ratio (DVR), and creatine-scaled glutamate (Glu/Cr), glutamate and glutamine (Glx/Cr) and NAA (NAA/Cr). In healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glu/Cr, in both the hippocampus and ACC. Furthermore, in healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glx/Cr, in both the hippocampus and ACC. There were no significant relationships between [11C]UCB-J DVR and NAA/Cr in the hippocampus or ACC in healthy volunteers or patients. Therefore, an appreciable proportion of the brain 1H-MRS glutamatergic signal is related to synaptic density in healthy volunteers. This relationship is not seen in schizophrenia, which, taken with lower synaptic marker levels, is consistent with lower levels of glutamatergic terminals and/or a lower proportion of glutamatergic relative to GABAergic terminals in the ACC in schizophrenia.
Onwordi EC, Halff E, Whitehurst T, et al., 2020, The relationship between synaptic density marker SV2A and glutamate: a multimodal positron emission tomography and magnetic resonance spectroscopy imaging study, 33rd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S296-S296, ISSN: 0924-977X
Osimo EF, Brugger SP, de Marvao A, et al., 2020, Cardiac structure and function in schizophrenia: cardiac magnetic resonance imaging study, British Journal of Psychiatry, Vol: 217, Pages: 450-457, ISSN: 0007-1250
BACKGROUND: Heart disease is the leading cause of death in schizophrenia. However, there has been little research directly examining cardiac function in schizophrenia. AIMS: To investigate cardiac structure and function in individuals with schizophrenia using cardiac magnetic resonance imaging (CMR) after excluding medical and metabolic comorbidity. METHOD: In total, 80 participants underwent CMR to determine biventricular volumes and function and measures of blood pressure, physical activity and glycated haemoglobin levels. Individuals with schizophrenia ('patients') and controls were matched for age, gender, ethnicity and body surface area. RESULTS: Patients had significantly smaller indexed left ventricular (LV) end-diastolic volume (effect size d = -0.82, P = 0.001), LV end-systolic volume (d = -0.58, P = 0.02), LV stroke volume (d = -0.85, P = 0.001), right ventricular (RV) end-diastolic volume (d = -0.79, P = 0.002), RV end-systolic volume (d = -0.58, P = 0.02), and RV stroke volume (d = -0.87, P = 0.001) but unaltered ejection fractions relative to controls. LV concentricity (d = 0.73, P = 0.003) and septal thickness (d = 1.13, P < 0.001) were significantly larger in the patients. Mean concentricity in patients was above the reference range. The findings were largely unchanged after adjusting for smoking and/or exercise levels and were independent of medication dose and duration. CONCLUSIONS: Individuals with schizophrenia show evidence of concentric cardiac remodelling compared with healthy controls of a similar age, gender, ethnicity, body surface area and blood pressure, and independent of smoking and activity levels. This could be contributing to the excess cardiovascular mortality observed in schizophrenia. Future studies should investigate the contribution of antipsychotic medication to these changes.
Pillinger T, Osimo EF, de Marvao A, et al., 2019, Cardiac structure and function in patients with schizophrenia taking antipsychotic drugs: an MRI study, Translational Psychiatry, Vol: 9, ISSN: 2158-3188
Cardiovascular disease (CVD) is a major cause of excess mortality in schizophrenia. Preclinical evidence shows antipsychotics can cause myocardial fibrosis and myocardial inflammation in murine models, but it is not known if this is the case in patients. We therefore set out to determine if there is evidence of cardiac fibrosis and/or inflammation using cardiac MRI in medicated patients with schizophrenia compared with matched healthy controls. Thirty-one participants (14 patients and 17 controls) underwent cardiac MRI assessing myocardial markers of fibrosis/inflammation, indexed by native myocardial T1 time, and cardiac structure (left ventricular (LV) mass) and function (left/right ventricular end-diastolic and end-systolic volumes, stroke volumes, and ejection fractions). Participants were physically fit, and matched for age, gender, smoking, blood pressure, BMI, HbA1c, ethnicity, and physical activity. Compared with controls, native myocardial T1 was significantly longer in patients with schizophrenia (effect size, d = 0.89; p = 0.02). Patients had significantly lower LV mass, and lower left/right ventricular end-diastolic and stroke volumes (effect sizes, d = 0.86-1.08; all p-values < 0.05). There were no significant differences in left/right end-systolic volumes and ejection fractions between groups (p > 0.05). These results suggest an early diffuse fibro-inflammatory myocardial process in patients that is independent of established CVD-risk factors and could contribute to the excess cardiovascular mortality associated with schizophrenia. Future studies are required to determine if this is due to antipsychotic treatment or is intrinsic to schizophrenia.
Berry A, Jarral O, Dawes T, et al., 2019, Aortic root surgery is associated with deterioration in left ventricular function and physical quality of life, SCMR 22nd Annual Scientific Sessions
Shirvani S, Tokarczuk P, Statton B, et al., 2019, Motion-corrected multiparametric renal arterial spin labelling at 3T: Reproducibility and effect of vasodilator challenge, European Radiology, Vol: 29, Pages: 232-240, ISSN: 0938-7994
ObjectivesWe investigated the feasibility and reproducibility of free-breathing motion-corrected multiple inversion time (multi-TI) pulsed renal arterial spin labelling (PASL), with general kinetic model parametric mapping, to simultaneously quantify renal perfusion (RBF), bolus arrival time (BAT) and tissue T1.MethodsIn a study approved by the Health Research Authority, 12 healthy volunteers (mean age, 27.6 ± 18.5 years; 5 male) gave informed consent for renal imaging at 3 T using multi-TI ASL and conventional single-TI ASL. Glyceryl trinitrate (GTN) was used as a vasodilator challenge in six subjects. Flow-sensitive alternating inversion recovery (FAIR) preparation was used with background suppression and 3D-GRASE (gradient and spin echo) read-out, and images were motion-corrected. Parametric maps of RBF, BAT and T1 were derived for both kidneys. Agreement was assessed using Pearson correlation and Bland-Altman plots.ResultsInter-study correlation of whole-kidney RBF was good for both single-TI (r2 = 0.90), and multi-TI ASL (r2 = 0.92). Single-TI ASL gave a higher estimate of whole-kidney RBF compared to multi-TI ASL (mean bias, 29.3 ml/min/100 g; p <0.001). Using multi-TI ASL, the median T1 of renal cortex was shorter than that of medulla (799.6 ms vs 807.1 ms, p = 0.01), and mean whole-kidney BAT was 269.7 ± 56.5 ms. GTN had an effect on systolic blood pressure (p < 0.05) but the change in RBF was not significant.ConclusionsFree-breathing multi-TI renal ASL is feasible and reproducible at 3 T, providing simultaneous measurement of renal perfusion, haemodynamic parameters and tissue characteristics at baseline and during pharmacological challenge.
de Marvao A, Biffi C, Walsh R, et al., 2018, Defining The Effects Of Genetic Variation Using Machine Learning Analysis Of CMRs: A Study In Hypertrophic Cardiomyopathy And In A Healthy Population, Joint Meeting of the British-Society-of-Cardiovascular-Imaging/British-Society-of-Cardiovascular-CT, British-Society-of-Cardiovascular-Magnetic-Resonance and British-Nuclear-Cardiac-Society on British Cardiovascular Imaging, Publisher: BMJ PUBLISHING GROUP, Pages: A7-A8, ISSN: 1355-6037
Jaijee S, Statton B, Quinlan M, et al., 2016, Right ventricular function in acute and chronic pulmonary hypertension using exercise cardiac magnetic resonance imaging, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1186-1186, ISSN: 0195-668X
Jaijee S, Quinlan M, Tokarczuk P, et al., 2016, DETERIORATION OF RIGHT VENTRICULAR FUNCTION ON EXERCISE DETECTED BY EXERCISE CARDIAC MAGNETIC RESONANCE IMAGING IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION, Annual Conference of the British-Cardiovascular-Society (BCS) on Prediction and Prevention, Publisher: BMJ PUBLISHING GROUP, Pages: A88-A89, ISSN: 1355-6037
Solanky BS, Abdel-Aziz K, Yiannakas MC, et al., 2013, In vivo magnetic resonance spectroscopy detection of combined glutamate-glutamine in healthy upper cervical cord at 3 T, NMR in Biomedicine, Vol: 26, Pages: 357-366, ISSN: 0952-3480
Yiannakas MC, Wheeler-Kingshott CAM, Berry AM, et al., 2010, A method for measuring the cross sectional area of the anterior portion of the optic nerve in vivo using a fast 3D MRI sequence., J Magn Reson Imaging, Vol: 31, Pages: 1486-1491
PURPOSE: To investigate the three-dimensional (3D) fast-recovery fast spin-echo accelerated (FRFSE-XL) sequence as a new application for measuring the intraorbital optic nerve (ION) mean cross-sectional area in vivo and to determine its value within a commonly used high resolution imaging protocol. MATERIALS AND METHODS: The entire ION was scanned in nine healthy volunteers (mean age 32 +/- 4 years) using the 3D FRFSE-XL sequence and a commonly used high resolution short-echo fast fluid-attenuated inversion-recovery (sTE fFLAIR) sequence with identical slice locations at 1.5T. The mean cross-sectional area from both sequences was measured on a slice-by-slice basis from 3 mm behind the globe to the orbital apex. The reproducibility of both techniques was assessed from repeated scans (scan-rescan) and repeated image analysis (intraobserver). RESULTS: Measurement of the mean cross-sectional area of the anterior 9 mm segment of the ION was only possible using the 3D FRFSE-XL sequence with a mean area of 11.6 +/- 2.2 mm(2) (scan rescan COV = 3.3 +/- 1.5, intraobserver COV = 2.4 +/- 0.02) whereas the remainder segment of the ION (i.e., 9 mm behind the globe to the orbital apex) could only be measured with the use of the sTE fFLAIR with a mean area of 8.5 +/- 1.7 mm(2) (scan rescan COV = 4.9 +/- 2.5 and intraobserver COV = 3.70 +/- 0.03). CONCLUSION: The 3D FRFSE-XL allows fast and reproducible measurement of the cross-sectional area of the anterior 9 mm segment of the ION, which is not possible using commonly used imaging sequences due to image degradation from motion, and is of complementary value to the existing imaging protocol for ION atrophy quantification.
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