Publications by authors named "Gerry P McCann"

151 Publications

Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

JAMA Cardiol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.

Importance: Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear.

Objective: To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls.

Design, Setting, And Participants: This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA.

Exposures: Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year).

Main Outcome And Measures: The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index).

Results: Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events.

Conclusions And Relevance: In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.
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http://dx.doi.org/10.1001/jamacardio.2021.4690DOI Listing
November 2021

Interrelationship between micronutrients and cardiovascular structure and function in type 2 diabetes.

J Nutr Sci 2021 4;10:e88. Epub 2021 Oct 4.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Micronutrients are important for normal cardiovascular function. They may play a role in the increased risk of cardiovascular disease observed in people with type 2 diabetes (T2D) and T2D-related heart failure. The aims of this study were to (1) examine micronutrient status in people with T2D healthy controls; (2) assess any changes following a nutritionally complete meal replacement plan (MRP) compared with routine care; (3) determine if any changes were associated with changes in cardiovascular structure/function. This was a secondary analysis of data from a prospective, randomised, open-label, blinded end-point trial of people with T2D, with a nested case-control [NCT02590822]. Anthropometrics, cardiac resonance imaging and fasting blood samples (to quantify vitamins B, B, B, D and C; and iron and ferritin) were collected at baseline and 12 weeks following the MRP or routine care. Comparative data in healthy controls were collected at baseline. A total of eighty-three people with T2D and thirty-six healthy controls were compared at baseline; all had micronutrient status within reference ranges. Vitamin B was higher (148⋅9 . 131⋅7; 0⋅01) and B lower (37⋅3 . 52⋅9; 0⋅01) in T2D . controls. All thirty participants randomised to routine care and twenty-four to the MRP completed the study. There was an increase in vitamins B, B, D and C following the MRP, which were not associated with changes in cardiovascular structure/function. In conclusion, changes in micronutrient status following the MRP were not independently associated with improvements in cardiovascular structure/function in people with T2D.
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http://dx.doi.org/10.1017/jns.2021.82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532075PMC
October 2021

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.

Lancet Respir Med 2021 11 7;9(11):1275-1287. Epub 2021 Oct 7.

Hywel Dda University Health Board, Wales, UK; University of Swansea, Swansea, UK; Respiratory Innovation Wales, Llanelli, UK.

Background: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes.

Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107).

Findings: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity.

Interpretation: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care.

Funding: UK Research and Innovation and National Institute for Health Research.
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http://dx.doi.org/10.1016/S2213-2600(21)00383-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497028PMC
November 2021

MRI and CT coronary angiography in survivors of COVID-19.

Heart 2021 Oct 6. Epub 2021 Oct 6.

Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Objectives: To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19.

Methods: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis.

Results: In 52 patients (median age: 54 (IQR 51-57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms.

Conclusions: Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities.

Trial Registration Number: NCT04625075.
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http://dx.doi.org/10.1136/heartjnl-2021-319926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503921PMC
October 2021

A pilot randomised controlled trial of a structured, home-based exercise programme on cardiovascular structure and function in kidney transplant recipients: the ECSERT study design and methods.

BMJ Open 2021 10 5;11(10):e046945. Epub 2021 Oct 5.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients (KTRs). CVD risk scores underestimate risk in this population as CVD is driven by clustering of traditional and non-traditional risk factors, which lead to prognostic pathological changes in cardiovascular structure and function. While exercise may mitigate CVD in this population, evidence is limited, and physical activity levels and patient activation towards exercise and self-management are low. This pilot study will assess the feasibility of delivering a structured, home-based exercise intervention in a population of KTRs at increased cardiometabolic risk and evaluate the putative effects on cardiovascular structural and functional changes, cardiorespiratory fitness, quality of life, patient activation, healthcare utilisation and engagement with the prescribed exercise programme.

Methods And Analysis: Fifty KTRs will be randomised 1:1 to: (1) the intervention; a 12week, home-based combined resistance and aerobic exercise intervention; or (2) the control; usual care. Intervention participants will have one introductory session for instruction and practice of the recommended exercises prior to receiving an exercise diary, dumbbells, resistance bands and access to instructional videos. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the intervention implementation. Outcomes, to be assessed prior to randomisation and postintervention, include: cardiac structure and function with stress perfusion cardiac MRI, cardiorespiratory fitness, physical function, blood biomarkers of cardiometabolic health, quality of life and patient activation. These data will be used to inform the power calculations for future definitive trials.

Ethics And Dissemination: The protocol was reviewed and given favourable opinion by the East Midlands-Nottingham 2 Research Ethics Committee (reference: 19/EM/0209; 14 October 2019). Results will be published in peer-reviewed academic journals and will be disseminated to the patient and public community via social media, newsletter articles and presentations at conferences.

Trial Registration Number: NCT04123951.
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http://dx.doi.org/10.1136/bmjopen-2020-046945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493915PMC
October 2021

Sex and ethnic differences in the cardiovascular complications of type 2 diabetes.

Ther Adv Endocrinol Metab 2021 4;12:20420188211034297. Epub 2021 Aug 4.

Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Diabetes mellitus represents a global health concern affecting 463 million adults and is projected to rapidly rise to 700 million people by 2045. Amongst those with type 2 diabetes (T2D), there are recognised differences in the impact of the disease on different sex and ethnic groups. The relative risk of cardiovascular complications between individuals with and without T2D is higher in females than males. People of South Asian heritage are two to four times more likely to develop T2D than white people, but conversely not more likely to experience cardiovascular complications. Differences in the pathophysiological responses in these groups may identify potential areas for intervention beyond glycaemic control. In this review, we highlight key differences of diabetes-associated cardiovascular complications by sex and ethnic background, with a particular emphasis on South Asians. Evidence assessing therapeutic efficacy of new glucose lowering drugs in minority groups is limited and many major cardiovascular outcomes trials do not report ethnic specific data. Conversely, lifestyle intervention and bariatric surgery appear to have similar benefits regardless of sex and ethnic groups. We encourage future studies with better representation of women and ethnic minorities that will provide valuable data to allow better risk stratification and tailored prevention and management strategies to improve cardiovascular outcomes in T2D.
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http://dx.doi.org/10.1177/20420188211034297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365016PMC
August 2021

Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

J Am Coll Cardiol 2021 Aug;78(6):545-558

Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany.

Background: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined.

Objectives: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality.

Methods: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome.

Results: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m) and small (LVEDVi ≤55 mL/m) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort.

Conclusions: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.
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http://dx.doi.org/10.1016/j.jacc.2021.05.047DOI Listing
August 2021

Clinical associations with stage B heart failure in adults with type 2 diabetes.

Ther Adv Endocrinol Metab 2021 17;12:20420188211030144. Epub 2021 Jul 17.

Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK.

Background: There is a high prevalence of asymptomatic (American Heart Association Stage B) heart failure (SBHF) in people with type 2 diabetes (T2D). We aimed to identify associations between clinical characteristics and markers of SBHF in adults with T2D, which may allow therapeutic interventions prior to symptom onset.

Methods: Adults with T2D from a multi-ethnic population with no prevalent cardiovascular disease [ = 247, age 52 ± 12 years, glycated haemoglobin A1c (HbA1c) 7.4 ± 1.1% (57 ± 12 mmol/mol), duration of diabetes 61 (32, 120) months] underwent echocardiography and adenosine stress perfusion cardiovascular magnetic resonance imaging. Multivariable linear regression analyses were performed to identify independent associations between clinical characteristics and markers of SBHF.

Results: In a series of multivariable linear regression models containing age, sex, ethnicity, smoking history, number of glucose-lowering agents, systolic blood pressure (BP) duration of diabetes, body mass index (BMI), HbA1c, serum creatinine, and low-density lipoprotein (LDL)-cholesterol, independent associations with: left ventricular mass:volume were age (β = 0.024), number of glucose-lowering agents (β = 0.022) and systolic BP (β = 0.027); global longitudinal strain were never smoking (β = -1.196), systolic BP (β = 0.328), and BMI (β = -0.348); myocardial perfusion reserve were age (β = -0.364) and male sex (β = 0.458); and aortic distensibility were age (β = -0.629) and systolic BP (β = -0.348). HbA1c was not independently associated with any marker of SBHF.

Conclusions: In asymptomatic adults with T2D, age, systolic BP, BMI, and smoking history, but not glycaemic control, are the major determinants of SBHF. Given BP and BMI are modifiable, these may be important targets to reduce the development of symptomatic heart failure.
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http://dx.doi.org/10.1177/20420188211030144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287269PMC
July 2021

A comparison of liver fat fraction measurement on MRI at 3T and 1.5T.

PLoS One 2021 13;16(7):e0252928. Epub 2021 Jul 13.

Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.

Purpose: Volumetric liver fat fraction (VLFF) measurements were made using the HepaFat-Scan® technique at 1.5T and 3T to determine the agreement between the measurements obtained at the two fields.

Methods: Sixty patients with type 2 diabetes (67% male, mean age 50.92 ± 6.56yrs) and thirty healthy volunteers (50% male, mean age 48.63 ± 6.32yrs) were scanned on 1.5T Aera and 3T Skyra (Siemens, Erlangen, Germany) MRI scanners on the same day using the HepaFat-Scan® gradient echo protocol with modification of echo times for 3T (TEs 2.38, 4.76, 7.14 ms at 1.5T and 1.2, 2.4, 3.6 ms at 3T). The 3T analyses were performed independently of the 1.5T analyses by a different analyst, blinded from the 1.5T results. Data were analysed for agreement and bias using Bland-Altman methods and intraclass correlation coefficients (ICC). A second cohort of 17 participants underwent interstudy repeatability assessment of VLFF measured by HepaFat-Scan® at 3T.

Results: A small, but statistically significant mean bias of 0.48% was observed between 3T and 1.5T with 95% limits of agreement -2.2% to 3.2% VLFF. The ICC for agreement between field strengths was 0.983 (95% CI 0.972-0.989). In the repeatability cohort studied at 3T the repeatability coefficient was 4.2%. The ICC for agreement was 0.971 (95% CI 0.921-0.989).

Conclusion: There is minimal bias and excellent agreement between the measures of VLFF using the HepaFat-Scan® at 1.5 and 3T. The test retest repeatability coefficient at 3T is comparable to the 95% limits of agreement between 1.5T and 3T suggesting that measurements can be made interchangeably between field strengths.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252928PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277031PMC
October 2021

Early invasive versus non-invasive assessment in patients with suspected non-ST-elevation acute coronary syndrome.

Heart 2021 Jul 7. Epub 2021 Jul 7.

Department of Cardiovascular Sciences and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK

Non-ST-elevation acute coronary syndrome (NSTE-ACS) comprises a broad spectrum of disease ranging from unstable angina to myocardial infarction. International guidelines recommend a routine invasive strategy for managing patients with NSTE-ACS at high to very high-risk, supported by evidence of improved composite ischaemic outcomes as compared with a selective invasive strategy. However, accurate diagnosis of NSTE-ACS in the acute setting is challenging due to the spectrum of non-coronary disease that can manifest with similar symptoms. Heterogeneous clinical presentations and limited uptake of risk prediction tools can confound physician decision-making regarding the use and timing of invasive coronary angiography (ICA). Large proportions of patients with suspected NSTE-ACS do not require revascularisation but may unnecessarily undergo ICA with its attendant risks and associated costs. Advances in coronary CT angiography and cardiac MRI have prompted evaluation of whether non-invasive strategies may improve patient selection, or whether tailored approaches are better suited to specific subgroups. Future directions include (1) better understanding of risk stratification as a guide to investigation and therapy in suspected NSTE-ACS, (2) randomised clinical trials of non-invasive imaging versus standard of care approaches prior to ICA and (3) defining the optimal timing of very early ICA in high-risk NSTE-ACS.
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http://dx.doi.org/10.1136/heartjnl-2020-318778DOI Listing
July 2021

Multi-modality assessment and role of left atrial function as an imaging biomarker in cardiovascular disease.

Int J Cardiovasc Imaging 2021 Nov 24;37(11):3355-3369. Epub 2021 Jun 24.

Department of Cardiovascular Sciences, University of Leicester, National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK.

The left atrium (LA) plays a vital role in maintaining normal cardiac function. LA volume and function have been utilised as important imaging biomarkers, with their prognostic value demonstrated in multiple cardiac conditions. More recently, there has been a sharp increase in the number of publications utilising LA strain by echocardiography and cardiac magnetic resonance (CMR) imaging. However, little is known about its prognostic value or reproducibility as a technique. In this review, we aim to highlight the conventional and novel imaging techniques available for LA assessment, using echocardiography and CMR, their role as an imaging biomarker in cardiovascular disease, the reproducibility of the techniques and the current limitations to their clinical application. We identify a need for further standardisation of techniques, with establishment of 'normal' cut-offs before routine clinical application can be made.
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http://dx.doi.org/10.1007/s10554-021-02316-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557157PMC
November 2021

Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19: protocol design of COVID-HEART-a UK, multicentre, observational study.

J Cardiovasc Magn Reson 2021 06 10;23(1):77. Epub 2021 Jun 10.

Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK.

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear.

Methods: COVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile). Baseline assessment will be whilst recovering in-hospital or recently discharged, and include cardiovascular magnetic resonance (CMR) imaging, quality of life (QoL) assessments, electrocardiogram (ECG), serum biomarkers and genetics. Assessment at 6-months includes repeat CMR, QoL assessments and 6-min walk test (6MWT). The CMR protocol includes cine imaging, T1/T2 mapping, aortic distensibility, late gadolinium enhancement (LGE), and adenosine stress myocardial perfusion imaging in selected patients. The main objectives of the study are to: (1) characterise the extent and nature of myocardial involvement in COVID-19 patients with an elevated troponin, (2) assess how cardiac involvement and clinical outcome associate with recognised risk factors for mortality (age, sex, ethnicity and comorbidities) and genetic factors, (3) evaluate if differences in myocardial recovery at 6 months are dependent on demographics, genetics and comorbidities, (4) understand the impact of recovery status at 6 months on patient-reported QoL and functional capacity.

Discussion: COVID-HEART will provide detailed characterisation of cardiac involvement, and its repair and recovery in relation to comorbidity, genetics, patient-reported QoL measures and functional capacity.

Clinical Trial Registration: ISRCTN 58667920. Registered 04 August 2020.
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http://dx.doi.org/10.1186/s12968-021-00752-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190746PMC
June 2021

Assessment of stunned and viable myocardium using manganese-enhanced MRI.

Open Heart 2021 06;8(1)

Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK.

Objective: In a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling.

Methods: Healthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model.

Results: After manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium.

Conclusions: Through visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases.

Trial Registration Numbers: NCT03607669; EudraCT number 2016-003782-25.
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http://dx.doi.org/10.1136/openhrt-2021-001646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186753PMC
June 2021

A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass.

Kidney Int 2021 06 8;99(6):1478-1486. Epub 2021 Apr 8.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; National Institute of Health Research Leicester Biomedical Research Centre, University of Leicester, Leicester, UK; National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health, Loughborough University, Loughborough, UK. Electronic address:

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated.
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http://dx.doi.org/10.1016/j.kint.2021.02.027DOI Listing
June 2021

Epicardial adipose tissue in obesity-related cardiac dysfunction.

Heart 2021 May 13. Epub 2021 May 13.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

Obesity is associated with the development of heart failure and is a major risk factor for heart failure with preserved ejection fraction (HFpEF). Epicardial adipose tissue (EAT) is a unique visceral fat in close proximity to the heart and is of particular interest to the study of cardiac disease. Small poorly differentiated adipocytes with altered lipid:water content are associated with a proinflammatory secretome and may contribute to the pathophysiology observed in HFpEF. Multimodality imaging approaches can be used to quantify EAT volume and characterise EAT composition. Current research studies remain unclear as to the magnitude of effect that EAT plays on myocardial dysfunction and further work using multimodality imaging techniques is ongoing. Pharmacological interventions, including glucagon-like peptide 1 receptor agonists and sodium-dependent glucose linked transporter 2 inhibitors have shown promise in attenuating the deleterious metabolic and inflammatory changes seen in EAT. Clinical studies are ongoing to explore whether these therapies exert their beneficial effects by modifying this unique adipose deposit.
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http://dx.doi.org/10.1136/heartjnl-2020-318242DOI Listing
May 2021

Benefits of sodium glucose cotransporter 2 inhibitors across the spectrum of cardiovascular diseases.

Heart 2021 May 10. Epub 2021 May 10.

Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Groby Road, Leicester, UK.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a class of medications with positive cardiovascular (CV) effects across a spectrum of patients with and without type 2 diabetes (T2D). In heart failure with reduced ejection fraction, there is clear evidence that SGLT2i reduce hospitalisations and mortality regardless of the presence of diabetes, and they are now recognised as the fourth pillar of pharmacological management. Recent trial data also indicate promising effects in heart failure with preserved ejection fraction. In patients with T2D and atherosclerotic CV diseases, multiple CV outcomes trials have shown reductions in major adverse CV events. Meta-analysis of these trials also shows lower rates of incident and recurrent atrial fibrillation with SGLT2i. Concerns regarding utilisation in patients with chronic kidney disease have been allayed in trials showing SGLT2i in fact have renoprotective effects. Questions still remain regarding the safety of SGLT2i in the acute heart failure setting and immediately post myocardial infarction, as well as in patients with more advanced stages of chronic kidney disease. Furthermore, studies are underway evaluating SGLT2i in patients with heart valve disease, where positive effects on left ventricular remodelling may, for example, improve functional mitral regurgitation. In this review, we summarise the available evidence of recent CV outcomes trials of SGLT2i, focusing particularly on the application of these agents across various CV diseases. We detail evidence to support increased utilisation of these drugs, which in many cases will reduce mortality and improve quality of life in patients routinely encountered by the CV specialist physician.
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http://dx.doi.org/10.1136/heartjnl-2021-319185DOI Listing
May 2021

Differences in native T1 and native T2 mapping between patients on hemodialysis and control subjects.

Eur J Radiol 2021 Jul 1;140:109748. Epub 2021 May 1.

Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.

Purpose: Myocardial native T1 is a potential measure of myocardial fibrosis, but concerns remain over the potential influence of myocardial edema to increased native T1 signal in subjects prone to fluid overload. This study describes differences in native T2 (typically raised in states of myocardial edema) and native T1 times in patients on hemodialysis by comparing native T1 and native T2 times between subjects on hemodialysis to an asymptomatic control group. Reproducibility of these sequences was tested.

Methods: Subjects were recruited prospectively and underwent 3 T-cardiac MRI with acquisition of native T1 and native T2 maps. Between group differences in native T1 and T2 maps were assessed using one-way ANOVAs. 30 subjects underwent test-retest scans within a week of their original scan to define sequence reproducibility.

Results: 261 subjects completed the study (hemodialysis n = 124, control n = 137). Native T1 times were significantly increased in subjects on hemodialysis compared to control subjects (1259 ms ± 51 vs 1212 ms ± 37, p < 0.01). There was no difference in native T2 times between subjects on hemodialysis and control subjects (39.5 ms ± 2.5 vs 39.5 ms ± 2.3, p = 0.9). These differences were unchanged after adjustment for relevant baseline differences (age, sex and hemoglobin). Inter-study reproducibility for native T1 and T2 mapping was excellent (coefficient of variability 0.9 % and 2.6 % respectively).

Conclusions: The increased native T1 signal demonstrated in subjects on hemodialysis occurs independently of differences in native T2 and the two parameters are not orthogonal. Elevated native T1 in patients on hemodialysis may be driven by water related to myocardial fibrosis rather than edema from volume overload.
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http://dx.doi.org/10.1016/j.ejrad.2021.109748DOI Listing
July 2021

The Underrepresentation of Females in Studies Assessing the Impact of High-Dose Exercise on Cardiovascular Outcomes: a Scoping Review.

Sports Med Open 2021 Apr 29;7(1):30. Epub 2021 Apr 29.

NIHR Leicester Biomedical Research Centre for Cardiovascular Disease, Glenfield Hospital, University of Leicester, Leicester, UK.

High-dose exercise-induced cardiac outcomes may vary between sexes. However, many studies investigating the cardiovascular effects of high-dose exercise have excluded or under-recruited females. This scoping review aimed to describe the recruitment of females in studies assessing the impact of high-dose exercise on cardiovascular outcomes and describe how this has changed over time. This scoping review followed the protocol outlined by Arksey and O'Malley and is reported as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines. The OVID and EMBASE databases were searched for studies that assessed the effects of high-dose exercise on cardiovascular outcomes. Both professional and nonprofessional groups were included. The review found 2973 studies, and 250 met the inclusion criteria including cumulatively 17,548,843 subjects. Over half the studies (n = 127) excluded females entirely, and only 8 (3.2%) studies recruited all-female participants. The overall mean percentage of females recruited was 18.2%. The mean percentage was 14.5% in studies conducted before 2011 and 21.8% in studies conducted after 2011. Females are an underrepresented group in studies assessing the cardiovascular outcomes related to high-dose exercise. As cardiovascular outcomes vary between sexes, translating findings from a largely male-based evidence may not be appropriate. Future investigators should aim to establish and overcome barriers to female recruitment.
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http://dx.doi.org/10.1186/s40798-021-00320-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085142PMC
April 2021

Response by Chan et al to Radico et al Regarding Article, "Effect of the 2017 European Guidelines on Reclassification of Severe Aortic Stenosis and Its Influence on Management Decisions for Initially Asymptomatic Aortic Stenosis".

Circ Cardiovasc Imaging 2021 04 9;14(4):e012487. Epub 2021 Apr 9.

Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, United Kingdom.

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http://dx.doi.org/10.1161/CIRCIMAGING.121.012487DOI Listing
April 2021

Regional variation in cardiovascular magnetic resonance service delivery across the UK.

Heart 2021 Dec 25;107(24):1974-1979. Epub 2021 Mar 25.

Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.

Objectives: To examine service provision in cardiovascular magnetic resonance (CMR) in the UK. Equitable access to diagnostic imaging is important in healthcare. CMR is widely available in the UK, but there may be regional variations.

Methods: An electronic survey was sent by the British Society of CMR to the service leads of all CMR units in the UK in 2019 requesting data from 2017 and 2018. Responses were analysed by region and interpreted alongside population statistics.

Results: The survey response rate was 100% (82 units). 100 386 clinical scans were performed in 2017 and 114 967 in 2018 (15% 1-year increase; 5-fold 10-year increase compared with 2008 data). In 2018, there were 1731 CMR scans/million population overall, with significant regional variation, for example, 4256 scans/million in London vs 396 scans/million in Wales. Median number of clinical scans per unit was 780, IQR 373-1951, range 98-10 000, with wide variation in mean waiting times (median 41 days, IQR 30-49, range 5-180); median 25 days in London vs 180 days in Northern Ireland). Twenty-five units (30%) reported mean elective waiting times in excess of 6 weeks, and 8 (10%) ≥3 months. There were 351 consultants reporting CMR, of whom 230 (66%) were cardiologists and 121 (34%) radiologists; 81% of units offered a CMR service for patients with pacemakers and defibrillators.

Conclusions: This survey provides a unique, contemporary insight into national CMR delivery with 100% centre engagement. The 10-year growth in CMR usage at fivefold has been remarkable but heterogeneous across the UK, with some regions still reporting low usage or long waiting times which may be of clinical concern.
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http://dx.doi.org/10.1136/heartjnl-2020-318667DOI Listing
December 2021

Plasma P-selectin is a predictor of mortality in heart failure with preserved ejection fraction.

ESC Heart Fail 2021 06 10;8(3):2328-2333. Epub 2021 Mar 10.

Department of Cardiovascular Sciences, University of Leicester, National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK.

Aims: The aim of the study was to assess the association of P-selectin with outcomes in heart failure with preserved ejection fraction (HFpEF).

Methods And Results: This is a prospective, observational study of 130 HFpEF patients who underwent clinical profiling, blood sampling, 6 min walk testing, Minnesota Living with Heart Failure Questionnaire evaluation, echocardiography, cardiovascular magnetic resonance imaging, calculation of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk scores, and blinded plasma P-selectin measurement. Patients were followed up for the endpoint of all-cause mortality. The HFpEF subgroup with higher P-selectin levels [overall median 26 372, inter-quartile range (19 360-34 889) pg/mL] was associated with lower age, higher heart rate, less prevalent atrial fibrillation, more frequent current smoking status, and lower right ventricular end-diastolic volumes. During follow-up (median 1428 days), there were 38 deaths. Following maximal sensitivity and specificity receiver operating characteristic curve analysis, P-selectin levels above 35 506 pg/mL were associated with greater risk of all-cause mortality [hazard ratio (HR) 2.700; 95% confidence interval (CI) 1.416-5.146; log-rank P = 0.002]. Following multivariable Cox proportional hazards regression analysis and when added to MAGGIC scores, only P-selectin (adjusted HR 1.707; 95% CI 1.099-2.650; P < 0.017) and myocardial infarction detected by cardiovascular magnetic resonance imaging (HR 2.377; 95% CI 1.114-5.075; P < 0.025) remained significant predictors. In a final model comprising all three parameters, only P-selectin (HR 1.447; 95% CI 1.130-1.853; P < 0.003) and MAGGIC scores (HR 1.555; 95% CI 1.136-2.129; P < 0.006) remained independent predictors of death. Adding P-selectin (0.618, P = 0.035) improved the area under the receiver operating characteristic curve for mortality prediction for MAGGIC scores (0.647, P = 0.009) to 0.710, P < 0.0001.

Conclusions: Plasma P-selectin is an independent predictor of mortality and provides incremental prognostic information beyond MAGGIC scores in HFpEF.
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http://dx.doi.org/10.1002/ehf2.13280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120355PMC
June 2021

Fulminant micro and macroangiopathic sequalae in a patient with COVID-19.

Eur Heart J Case Rep 2020 Dec 9;4(6):1-2. Epub 2020 Nov 9.

Department of Cardiology, Glenfield Hospital, University Hospitals of Leicester, Groby Rd, Leicester LE3 9QP, UK.

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http://dx.doi.org/10.1093/ehjcr/ytaa372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717199PMC
December 2020

Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial.

Diabetes Obes Metab 2021 06 26;23(6):1409-1414. Epub 2021 Feb 26.

Diabetes Research Centre, University of Leicester, Leicester, UK.

The mechanisms behind the beneficial cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared with dipeptidyl peptidase-4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP-1RA liraglutide (1.8 mg once-daily) and the DPP4i sitagliptin (100 mg once-daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs). LYDIA was a 26-week, randomized, active-comparator trial in 61 adults with type 2 diabetes and obesity (mean ± SD: age 43.8 ± 6.5 years, body mass index 35.3 ± 6.4 kg/m , HbA1c 7.5% ± 0.83% [58.5 ± 9.1 mmol/mol]). Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1-alpha (SDF-1ɑ), both of which are implicated in endothelial function, were higher at 26 weeks with liraglutide therapy compared with sitagliptin (mean between-group difference [95% CI]: 77.03 [18.29, 135.77] pg/mL, p = .010; and 996.25 [818.85, 1173.64] pg/mL, p < .001, respectively). There were no between-group differences in CPCs, nitric oxide, C-reactive protein, interleukin-6, tumour necrosis factor alpha and advanced glycation end-products. These analyses suggest a favourable impact of liraglutide on VEGF and SDF-1ɑ levels compared with sitagliptin. These factors may therefore be implicated in the differential cardiovascular effects observed between these agents in large cardiovascular outcome trials. However, these are secondary analyses from a previous trial and thus hypothesis-generating. Purposive trials are required to examine these findings further.
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http://dx.doi.org/10.1111/dom.14343DOI Listing
June 2021

Cardiovascular and systemic determinants of exercise capacity in people with type 2 diabetes mellitus.

Ther Adv Endocrinol Metab 2021 27;12:2042018820980235. Epub 2021 Jan 27.

Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE39QP, UK.

The global burden of heart failure (HF) is on the rise owing to an increasing incidence of lifestyle related diseases, predominantly type 2 diabetes mellitus (T2D). Diabetes is an independent risk factor for cardiovascular disease, and up to 75% of those with T2D develop HF in their lifetime. T2D leads to pathological alterations within the cardiovascular system, which can progress insidiously and asymptomatically in the absence of conventional risk factors. Reduced exercise tolerance is consistently reported, even in otherwise asymptomatic individuals with T2D, and is the first sign of a failing heart. Because aggressive modification of cardiovascular risk factors does not eliminate the risk of HF in T2D, it is likely that other factors play a role in the pathogenesis of HF. Early identification of individuals at risk of HF is advantageous, as it allows for modification of the reversible risk factors and early initiation of treatment with the aim of improving clinical outcomes. In this review, cardiac and extra-cardiac contributors to reduced exercise tolerance in people with T2D are explored.
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http://dx.doi.org/10.1177/2042018820980235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844448PMC
January 2021

Quality assurance of quantitative cardiac T1-mapping in multicenter clinical trials - A T1 phantom program from the hypertrophic cardiomyopathy registry (HCMR) study.

Int J Cardiol 2021 05 31;330:251-258. Epub 2021 Jan 31.

dept. Radiology and Nuclear Medicine, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.

Background: Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials.

Purpose: To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use.

Methods: MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites.

Results: T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions.

Conclusions: The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994017PMC
May 2021

Professor Anthony H. Gershlick.

Eur Heart J 2021 04;42(15):1455-1457

Professor of cardiology and BHF Medical Director, Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester UK.

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http://dx.doi.org/10.1093/eurheartj/ehaa1015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928977PMC
April 2021

Effect of the 2017 European Guidelines on Reclassification of Severe Aortic Stenosis and Its Influence on Management Decisions for Initially Asymptomatic Aortic Stenosis.

Circ Cardiovasc Imaging 2020 12 8;13(12):e011763. Epub 2020 Dec 8.

Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, United Kingdom (D.C.S.C., A.S., L.L.N., G.P.M.).

Background: The 2017 European Society of Cardiology guidelines for valvular heart disease included changes in the definition of severe aortic stenosis (AS). We wanted to evaluate its influence on management decisions in asymptomatic patients with moderate-severe AS.

Methods: We reclassified the AS severity of the participants of the PRIMID-AS study (Prognostic Importance of Microvascular Dysfunction in Asymptomatic Patients With AS), using the 2017 guidelines, determined their risk of reaching a clinical end point (valve replacement for symptoms, hospitalization, or cardiovascular death) and evaluated the prognostic value of aortic valve calcium score and biomarkers. Patients underwent echocardiography, cardiac magnetic resonance imaging, exercise tolerance testing, and biomarker assessment.

Results: Of the 174 participants, 45% (56/124) classified as severe AS were reclassified as moderate AS. This reclassified group was similar to the original moderate group in clinical characteristics, gradients, calcium scores, and remodeling parameters. There were 47 primary end points (41 valve replacement, 1 death, and 5 hospitalizations-1 chest pain, 2 dyspnea, 1 heart failure, and 1 syncope) over 368±156 days follow-up. The severe and reclassified groups had a higher risk compared with moderate group (adjusted hazard ratio 4.95 [2.02-12.13] and 2.78 [1.07-7.22], respectively), with the reclassified group demonstrating an intermediate risk. A mean pressure gradient ≥31 mm Hg had a 7× higher risk of the primary end point in the reclassified group. Aortic valve calcium score was more prognostic in females and low valve area but not after adjusting for gradients. NT-proBNP (N-terminal pro-brain-type natriuretic peptide) and myocardial perfusion reserve were associated with the primary end point but not after adjusting for positive exercise tolerance testing. Troponin was associated with cardiovascular death or unplanned hospitalizations.

Conclusions: Reclassification of asymptomatic severe AS into moderate AS was common using the European Society of Cardiology 2017 guidelines. This group had an intermediate risk of reaching the primary end point. Exercise testing, multimodality imaging, and lower mean pressure gradient threshold of 31 mm Hg may improve risk stratification. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01658345.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.011763DOI Listing
December 2020

The cardiovascular determinants of physical function in patients with end-stage kidney disease on haemodialysis.

Int J Cardiovasc Imaging 2021 Apr 30;37(4):1405-1414. Epub 2020 Nov 30.

Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Patients with end-stage kidney disease (ESKD) are often sedentary and decreased functional capacity associates with mortality. The relationship between cardiovascular disease (CVD) and physical function has not been fully explored. Understanding the relationships between prognostically relevant measures of CVD and physical function may offer insight into how exercise interventions might target specific elements of CVD. 130 patients on haemodialysis (mean age 57 ± 15 years, 73% male, dialysis vintage 1.3 years (0.5, 3.4), recruited to the CYCLE-HD trial (ISRCTN11299707), underwent cardiovascular phenotyping with cardiac MRI (left ventricular (LV) structure and function, pulse wave velocity (PWV) and native T1 mapping) and cardiac biomarker assessment. Participants completed the incremental shuttle walk test (ISWT) and sit-to-stand 60 (STS60) as field-tests of physical function. Linear regression models identified CV determinants of physical function measures, adjusted for age, gender, BMI, diabetes, ethnicity and systolic blood pressure. Troponin I, PWV and global native T1 were univariate determinants of ISWT and STS60 performance. NT pro-BNP was a univariate determinant of ISWT performance. In multivariate models, NT pro-BNP and global native T1 were independent determinants of ISWT and STS60 performance. LV ejection fraction was an independent determinant of ISWT distance. However, age and diabetes had the strongest relationships with physical function. In conclusion, NT pro-BNP, global native T1 and LV ejection fraction were independent CV determinants of physical function. However, age and diabetes had the greatest independent influence. Targeting diabetic care may ameliorate deconditioning in these patients and a multimorbidity approach should be considered when developing exercise interventions.
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http://dx.doi.org/10.1007/s10554-020-02112-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026413PMC
April 2021

Short-term adverse remodeling progression in asymptomatic aortic stenosis.

Eur Radiol 2021 Jun 19;31(6):3923-3930. Epub 2020 Nov 19.

Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Groby road, Leicester, LE3 9QP, UK.

Objectives: Aortic stenosis (AS) is characterised by a long and variable asymptomatic course. Our objective was to use cardiovascular magnetic resonance imaging (MRI) to assess progression of adverse remodeling in asymptomatic AS.

Methods: Participants from the PRIMID-AS study, a prospective, multi-centre observational study of asymptomatic patients with moderate to severe AS, who remained asymptomatic at 12 months, were invited to undergo a repeat cardiac MRI.

Results: Forty-three participants with moderate-severe AS (mean age 64.4 ± 14.8 years, 83.4% male, aortic valve area index 0.54 ± 0.15 cm/m) were included. There was small but significant increase in indexed left ventricular (LV) (90.7 ± 22.0 to 94.5 ± 23.1 ml/m, p = 0.007) and left atrial volumes (52.9 ± 11.3 to 58.6 ± 13.6 ml/m, p < 0.001), with a decrease in systolic (LV ejection fraction 57.9 ± 4.6 to 55.6 ± 4.1%, p = 0.001) and diastolic (longitudinal diastolic strain rate 1.06 ± 0.2 to 0.99 ± 0.2 1/s, p = 0.026) function, but no overall change in LV mass or mass/volume. Late gadolinium enhancement increased (2.02 to 4.26 g, p < 0.001) but markers of diffuse interstitial fibrosis did not change significantly (extracellular volume index 12.9 [11.4, 17.0] ml/m to 13.3 [11.1, 15.1] ml/m, p = 0.689). There was also a significant increase in the levels of NT-proBNP (43.6 [13.45, 137.08] pg/ml to 53.4 [19.14, 202.20] pg/ml, p = 0.001).

Conclusions: There is progression in cardiac remodeling with increasing scar burden even in asymptomatic AS. Given the lack of reversibility of LGE post-AVR and its association with long-term mortality post-AVR, this suggests the potential need for earlier intervention, before the accumulation of LGE, to improve the long-term outcomes in AS.

Key Points: • Current guidelines recommend waiting until symptom onset before valve replacement in severe AS. • MRI showed clear progression in cardiac remodeling over 12 months in asymptomatic patients with AS, with near doubling in LGE. • This highlights the need for potentially earlier intervention or better risk stratification in AS.
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http://dx.doi.org/10.1007/s00330-020-07462-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128853PMC
June 2021

Reproducibility of left atrial function using cardiac magnetic resonance imaging.

Eur Radiol 2021 May 30;31(5):2788-2797. Epub 2020 Oct 30.

Department of Cardiovascular Sciences, Cardiovascular Theme National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, University of Leicester, Groby Road, Leicester, LE3 9QP, UK.

Objectives: To determine the test-retest reproducibility and observer variability of CMR-derived LA function, using (i) LA strain (LAS) and strain rate (LASR), and (ii) LA volumes (LAV) and emptying fraction (LAEF).

Methods: Sixty participants with and without cardiovascular disease (aortic stenosis (AS) (n = 16), type 2 diabetes (T2D) (n = 28), end-stage renal disease on haemodialysis (n = 10) and healthy volunteers (n = 6)) underwent two separate CMR scans 7-14 days apart. LAS and LASR, corresponding to LA reservoir, conduit and contractile booster-pump function, were assessed using Feature Tracking software (QStrain v2.0). LAEF was calculated using the biplane area length method (QMass v8.1). Both were assessed using 4- and 2-chamber long-axis standard steady-state free precession cine images, and average values were calculated. Intra- and inter-observer variabilities were assessed in 10 randomly selected participants.

Results: The test-retest reproducibility was moderate to poor for all strain and strain rate parameters. Overall, strain and strain rate corresponding to reservoir phase (LAS_r, LASR_r) were the most reproducible, yielding the smallest coefficient of variance (CoV) (29.9% for LAS_r, 28.9% for LASR_r). The test-retest reproducibility for LAVs and LAEF was good: LAVmax CoV = 19.6% ICC = 0.89, LAVmin CoV = 27.0% ICC = 0.89 and total LAEF CoV = 15.6% ICC = 0.78. The inter- and intra-observer variabilities were good for all parameters except for conduit function.

Conclusion: The test-retest reproducibility of LA strain and strain rate assessment by CMR utilising Feature Tracking is moderate to poor across disease states, whereas LA volume and emptying fraction are more reproducible on CMR. Further improvements in LA strain quantification are needed before widespread clinical application.

Key Points: • LA strain and strain rate assessment using Feature Tracking on CMR has moderate to poor test-retest reproducibility across disease states. • The test-retest reproducibility for the biplane method of assessing LA function is better than strain assessment, with lower coefficient of variances and narrower limits of agreement on Bland-Altman plots. • Biplane LA volumetric measurement also has better intra- and inter-observer variability compared to strain assessment.
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http://dx.doi.org/10.1007/s00330-020-07399-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043954PMC
May 2021
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