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Author: Stefan Neubauer (380)


Feb
2018

Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies, and cardiovascular outcomes with new classes of glucose lowering therapies.

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Feb
2018

Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10-20,000 fold improvements in MR signal, enabling cardiac metabolite mapping.To determine whether hyperpolarized MR using [1-C]pyruvate can assess the local cardiac inflammatory response following MI.

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Feb
2018

Abnormal aortic flow patterns in bicuspid aortic valve disease (BAV) may be partly responsible for the associated aortic dilation. Aortic valve replacement (AVR) may normalize flow patterns and potentially slow the concomitant aortic dilation. We therefore sought to examine differences in flow patterns post AVR.

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Jan
2018

Rheumatoid arthritis (RA) is a multi-system, autoimmune disorder and confers one of the strongest risks for cardiovascular disease (CVD) morbidity and mortality.
To assess myocardial function and vascular stiffness in RA patients with and without cardiovascular risk factors (CVRFs) using cardiovascular magnetic resonance (CMR).
23 RA patients with no CVRFs (17 female, mean age 52±13 years), 46 RA patients with CVRFs (32 female, mean age 53± 12), 50 normal controls (32 female, mean age 50±11 years), and 13 controls with CVRFs (7 female, mean age 55±7 years), underwent CMR at 1.

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Dec
2017

Creatine buffers cellular ATP via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine synthesis.

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Dec
1969

Cardiac phosphorus magnetic resonance spectroscopy (31P-MRS) provides unique insight into the mechanisms of heart failure. Yet, clinical applications have been hindered by the restricted sensitivity of the surface radiofrequency-coils normally used. These permit the analysis of spectra only from the interventricular septum, or large volumes of myocardium, which may not be meaningful in focal disease.

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Oct
2017

Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction.

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Dec
1969

The UK Biobank is a large-scale population-based study utilising cardiovascular magnetic resonance (CMR) to generate measurements of atrial and ventricular structure and function. This study aimed to quantify the association between modifiable cardiovascular risk factors and cardiac morphology and function in individuals without known cardiovascular disease.
Age, sex, ethnicity (non-modifiable) and systolic blood pressure, diastolic blood pressure, smoking status, exercise, body mass index (BMI), high cholesterol, diabetes, alcohol intake (modifiable) were considered important cardiovascular risk factors.

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Sep
2017

Native T1-mapping provides quantitative myocardial tissue characterization for cardiovascular diseases (CVD), without the need for gadolinium. However, its translation into clinical practice is hindered by differences between techniques and the lack of established reference values. We provide typical myocardial T1-ranges for 18 commonly encountered CVDs using a single T1-mapping technique - Shortened Look-Locker Inversion Recovery (ShMOLLI), also used in the large UK Biobank and Hypertrophic Cardiomyopathy Registry study.

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Nov
2017

Background Ultrasound imaging is able to quantify carotid arterial wall structure for the assessment of cerebral and cardiovascular disease risks. We describe a protocol and quality assurance process to enable carotid imaging at large scale that has been developed for the UK Biobank Imaging Enhancement Study of 100,000 individuals. Design An imaging protocol was developed to allow measurement of carotid intima-media thickness from the far wall of both common carotid arteries.

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Feb
2018

In vivo mapping of the myocardial T1 relaxation time has recently attained wide clinical validation of its potential utility. In this review, we address the basic principles of the T1 mapping techniques, with particular attention to the emerging application of vasodilatory stress agents to interrogate the myocardial microvascular compartment, and differences between commonly used T1 mapping methods when applied in clinical practice.

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Feb
2018

UK Biobank, a large cohort study, plans to acquire 100,000 cardiac MRI studies by 2020. Although fully-automated left ventricular (LV) analysis was performed in the original acquisition, this was not designed for unsupervised incorporation into epidemiological studies. We sought to evaluate automated LV mass and volume (Siemens syngo InlineVF versions D13A and E11C), against manual analysis in a substantial sub-cohort of UK Biobank participants.

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Dec
1969

The creatine kinase (CK) phosphagen system is fundamental to cellular energy homeostasis. Cardiomyocytes express three CK isoforms, namely the mitochondrial sarcomeric CKMT2 and the cytoplasmic CKM and CKB. We hypothesized that augmenting CK in vitro would preserve cell viability and function and sought to determine efficacy of the various isoforms.

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Aug
2017

CMR T1 mapping is a quantitative imaging technique allowing the assessment of myocardial injury early after ST-segment-elevation myocardial infarction. We sought to investigate the ability of acute native T1 mapping to differentiate reversible and irreversible myocardial injury and its predictive value for left ventricular remodeling.
Sixty ST-segment-elevation myocardial infarction patients underwent acute and 6-month 3T CMR, including cine, T2-weighted (T2W) imaging, native shortened modified look-locker inversion recovery T1 mapping, rest first pass perfusion, and late gadolinium enhancement.

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Jul
2017

Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo.

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Jan
2018

Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD.

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Sep
2017

Metabolic remodeling in hypertrophied and failing myocardium: a review.

Am J Physiol Heart Circ Physiol 2017 Sep 23;313(3):H597-H616. Epub 2017 Jun 23.
Mark A Peterzan, Craig A Lygate, Stefan Neubauer, Oliver J Rider
The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling plays within HF and the conditions known to transition toward HF, including "pathological" hypertrophy. In this review, we discuss metabolic phenotype and metabolic signaling in the contexts of pathological hypertrophy and HF.

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Dec
1969

Abnormal flow patterns in the aortas of those with bicuspid aortic valves (BAVs) are increasingly recognized as important in the pathogenesis of aortic dilatation but pulmonary flow patterns in bicuspidvalves have not been studied. Bicuspidvalve disease is rare and a small numbers of case reports describe concomitant pulmonary artery dilation similar to the dilation of the ascending aorta, which is often seen in BAVs disease. We examined three cases of bicuspidvalve disease, 10 healthy volunteers and 10 patients with BAV disease but a tricuspidvalve.

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Jun
2017

Cardiovascular magnetic resonance imaging has become the gold standard for evaluating myocardial function, volumes, and scarring. Additionally, cardiovascular magnetic resonance imaging is unique in its comprehensive tissue characterization, including assessment of myocardial edema, myocardial siderosis, myocardial perfusion, and diffuse myocardial fibrosis. Cardiovascular magnetic resonance imaging has become an indispensable tool in the evaluation of congenital heart disease, heart failure, cardiac masses, pericardial disease, and coronary artery disease.

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May
2017

A 70-year-old man presented with prolonged cardiac chest pain and was awaiting coronary artery bypass surgery following angiography showing extensive multivessel disease. Following further chest pain, cardiac magnetic resonance imaging showed extensive, contained, ventricular rupture, which was managed aggressively with combined bypass surgery and rupture repair.

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Dec
1969

The aim of the study was to investigate the interobserver agreement for categorical and quantitative scores of liver fibrosis.
Sixty-five consecutive biopsy specimens from patients with mixed liver disease etiologies were assessed by three pathologists using the Ishak and nonalcoholic steatohepatitis Clinical Research Network (NASH CRN) scoring systems, and the fibrosis area (collagen proportionate area [CPA]) was estimated by visual inspection (visual-CPA). A subset of 20 biopsy specimens was analyzed using digital imaging analysis (DIA) for the measurement of CPA (DIA-CPA).

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Dec
1969

Non-alcoholic fatty liver disease and the risk of progression to steatohepatitis, cirrhosis and hepatocellular carcinoma have been identified as major public health concerns. We have demonstrated the feasibility and potential value of measuring liver fat content by magnetic resonance imaging (MRI) in a large population in this study of 4,949 participants (aged 45-73 years) in the UK Biobank imaging enhancement. Despite requirements for only a single (≤3min) scan of each subject, liver fat was able to be measured as the MRI proton density fat fraction (PDFF) with an overall success rate of 96.

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Mar
2017

To determine whether changes in cerebral structure are present after preeclampsia that may explain increased cerebrovascular risk in these women.
We conducted a case control study in women between 5 and 15 years after either a preeclamptic or normotensive pregnancy. Brain MRI was performed.

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Apr
2017

To assess cardiovascular magnetic resonance (CMR) measured myocardial perfusion reserve (MPR) and exercise testing in asymptomatic patients with moderate-severe AS.
Multi-centre, prospective, observational study, with blinded analysis of CMR data. Patients underwent adenosine stress CMR, symptom-limited exercise testing (ETT) and echocardiography and were followed up for 12-30 months.

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Jan
2017

With multifaceted imaging capabilities, cardiovascular magnetic resonance (CMR) is playing a progressively increasing role in the management of various cardiac conditions. A global registry that harmonizes data from international centers, with participation policies that aim to be open and inclusive of all CMR programs, can support future evidence-based growth in CMR.
The Global CMR Registry (GCMR) was established in 2013 under the auspices of the Society for Cardiovascular Magnetic Resonance (SCMR).

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Feb
2017

Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45-74.

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Jan
2017

Transvalvular peak pressure drops are routinely assessed noninvasively by echocardiography using the Bernoulli principle. However, the Bernoulli principle relies on several approximations that may not be appropriate, including that the majority of the pressure drop is because of the spatial acceleration of the blood flow, and the ejection jet is a single streamline (single peak velocity value).
We assessed the accuracy of the Bernoulli principle to estimate the peak pressure drop at the aortic valve using 3-dimensional cardiovascular magnetic resonance flow data in 32 subjects.

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Jan
2017

Perfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the "splenic switch-off" sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium.

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Nov
2017

Myocardial Fibrosis in Aortic Stenosis.

JACC Cardiovasc Imaging 2017 Nov 21;10(11):1334-1336. Epub 2016 Dec 21.
Stefan Neubauer, Sacha Bull

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Dec
1969

Increased blood pressure (BP) variability is a cardiovascular risk marker for young individuals and may relate to the ability of their aorta to buffer cardiac output. We used a multimodality approach to determine relations between central and peripheral arterial stiffness and BP variability.
We studied 152 adults (mean age of 31 years) who had BP variability measures based on SD of awake ambulatory BPs, 24-h weighted SD and average real variability (ARV).

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Jul
2017

The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease.
Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy.

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Oct
2016

Lone atrial fibrillation (AF) may reflect a subclinical cardiomyopathy that persists after sinus rhythm (SR) restoration, providing a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function and energetics in patients with AF but no significant comorbidities.
Fifty-three patients with symptomatic paroxysmal or persistent AF and without significant valvular disease, uncontrolled hypertension, coronary artery disease, uncontrolled thyroid disease, systemic inflammatory disease, diabetes mellitus, or obstructive sleep apnea (ie, lone AF) undergoing ablation and 25 matched control subjects in SR were investigated.

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Nov
2016

Purpose To test whether the increased signal-to-noise ratio of phosphorus 31 (P) magnetic resonance (MR) spectroscopy at 7 T improves precision in cardiac metabolite quantification in patients with dilated cardiomyopathy (DCM) compared with that at 3 T. Materials and Methods Ethical approval was obtained, and participants provided written informe consent. In a prospective study,P MR spectroscopy was performed at 3 T and 7 T in 25 patients with DCM.

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Jul
2017

We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant kin human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert B1+-mapping to determine the per-voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing.
Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations.

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Dec
2016

Metformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment on heart and liver pyruvate metabolism in rats in vivo. Both oral treatment for 4 weeks and a single intravenous metformin infusion significantly increased the cardiac [1-C]lactate:[1-C]pyruvate ratio but had no effect on the [1-C]bicarbonate +CO:[1-C]pyruvate ratio, an index of pyruvate dehydrogenase flux.

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Dec
1969

The electrocardiogram (ECG) is the most commonly used tool to screen for left ventricular hypertrophy (LVH), and yet current diagnostic criteria are insensitive in modern increasingly overweight society. We propose a simple adjustment to improve diagnostic accuracy in different body weights and improve the sensitivity of this universally available technique.
Overall, 1295 participants were included-821 with a wide range of body mass index (BMI 17.

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Aug
2016

Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction.

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Feb
2017

To propose a simple multicompartment model of the liver and use Bloch-McConnell simulations to demonstrate the effects of iron and fibrosis on shortened-MOLLI (shMOLLI) Tmeasurements. Liver Tvalues have shown sensitivity to inflammation and fibrosis, but are also affected by hepatic iron content. Modified Look-Locker inversion recovery (MOLLI) Tmeasurements are biased by the lower Tassociated with high iron.

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Jul
2016

Type 2 diabetes (T2D) and obesity are associated with nonalcoholic fatty liver disease, cardiomyopathy, and cardiovascular mortality. Both show stronger links between ectopic and visceral fat deposition, and an increased cardiometabolic risk compared with subcutaneous fat.
This study investigated whether lean patients (Ln) with T2D exhibit increased ectopic and visceral fat deposition and whether these are linked to cardiac and hepatic changes.

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