Metrics details
The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery
We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery
We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres
A total of 250 patients were included (68 ± 12 years
with pre-operative mean aortic valve area 0.93 ± 0.32cm2
LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years
Multivariable analysis showed that increasing age (HR 1.04
presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively
higher indexed left ventricular stroke volume (HR 0.98
P = 0.043) and higher left atrial ejection fraction (HR 0.98
P = 0.083) associated with mortality and developed a risk score with good discrimination
This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality
This model can help clinicians individualising medical and surgical care
Trial Registration ClinicalTrials.gov Identifier: NCT00930735 and ClinicalTrials.gov Identifier: NCT01755936
there is currently no dedicated risk score derived specifically for patients undergoing surgical aortic valve replacement (SAVR) for estimating long-term mortality to allow clinicians to facilitate precision medicine
mortality remains high and Euroscore II and STS models whilst predicting in-hospital and 30-day mortality
they lack the inclusion of myocardial fibrosis in their models which is a known risk factor
although individual predictors have already been investigated including LVEF and midwall fibrosis
no score is currently available to bring all those parameters together in predicting risk
In this study we investigated the additional role of LGE-CMR in developing a mortality risk score for patients undergoing SAVR in two institutions
and identified predictors of survival following aortic valve replacement
Consecutive patients with aortic stenosis undergoing LGE-CMR and subsequent SAVR were recruited from two large prospective observational registries: the Royal Brompton Hospital of Imperial College
UK including patients from 2003–2016 (ClinicalTrials.gov Identifier: NCT00930735
June 30th 2009) and the Edinburgh Heart Centre
Royal Infirmary of University of Edinburgh
UK including patients from 2013 to 2016 (ClinicalTrials.gov Identifier: NCT01755936
The present study is not associated with the objectives of these trials and does not report results associated with or generated from these trials
It uses clinical data generated from these trials to investigate the specific objective mentioned above
The study was conducted in accordance with the Declaration of Helsinki after local research ethics approval and written patient consent
Medical history and demographic characteristics were collected following patient interviews and review of the hospital and community records
Coronary artery disease was defined as prior coronary revascularization or the presence of significant coronary artery stenosis as assessed by invasive or computed tomography coronary angiography by > 50% lumen diameter narrowing
steady-state free precession sequences were used for aortic valve planimetry (two orthogonal coronal views were taken
and then sagittal “valve stack” imaging starting at ~ 10 mm below the level valve and extending to ~ 10 mm above the level of the valve)
and assessment of biventricular volumes and LV mass
Ten to fifteen minutes after injection of 0.1 mmol/kg of gadolinium contrast agent (Gadovist
Germany) inversion recovery–prepared spoiled gradient echo images were acquired in standard long- and short-axis views to detect areas of LGE
communication with primary care and through the Office of National Statistics
where there is compulsory registration of all deaths
All statistical analyses were carried out using STATA (14
Variables are expressed as mean ± standard deviation (SD)
median and interquartile range (IQR) or counts and percentages as appropriate
The follow-up time for each patient was calculated from the day of CMR to the date of death or their most recent evaluation
The annual event rate was calculated by dividing the number of patients reaching the endpoint by the total follow-up period for that endpoint
The cumulative probability for the occurrence of an outcome was estimated using the Kaplan–Meier method
No variable had more than 10% of data missing
multiple imputation was undertaken in variables with any missing data as described in Supplementary Material Methods
UK National Ethics approval from London and Lothian were obtained
Institutional Board approval from Edinburgh Royal Infrimary and Royal Brompton Hospital and written informed patient consent were obtained
Edinburgh 39) were included in this study: age 68 ± 12 years
There were 161 patients with isolated SAVR
A total of 168 (67%) patients had severe aortic stenosis while 82 (33%) had moderate aortic stenosis
All the patients with moderate aortic stenosis had a concomitant CABG
Coronary artery disease was present in 114 (46%) and 37 (15%) patients had low flow (defined by LV stroke volume < 35mls/m2) (Table 1)
CMR was performed at a median of 56 days before the operation (range 14–184)
The patients were followed for a mean 6.0 ± 3.3 years
having moved abroad and censored at the last time known to be alive
Kaplan–Meier estimator plot of survival in patients with no gadolinium enhancement
midwall enhancement and infarction pattern enhancement
This plot indicates significantly worse prognosis in the patients with either form of enhancement (midwall or infarction) out to 10 years (log rank P = 0.029)
Patients with a mixed pattern of LGE were categorized according to the predominant pattern of fibrosis
The presence of either midwall fibrosis or infarction pattern fibrosis was associated with worse outcome when compared to absence of fibrosis (Fig. 1)
Observed vs predicted risk of mortality for patients following SAVR
The observed (black) vs predicted (grey) risk of mortality for patients following SAVR out to 10 years in clinically relevant risk groups is shown
The predictions for the risk of death at 10 years can be obtained by the following equation:
and infarction LGE are assigned the value 1 if present or zero if absent
emphasising the importance of regular review and medical optimisation following surgery
Although generic models for predicting survival after open heart surgery exist and are used in clinical practice to identify high risk patients
these are not designed specifically for SAVR and importantly are not specific for estimating long-term survival
A tool for estimating long-term survival following SAVR is therefore needed to enable individualised decisions for patients
We have developed and internally validated a risk score using the most significant variables that can be used to identify patients at risk of overall mortality after SAVR
We have used a pragmatic cohort of patients undergoing routine guideline-based surgery to ensure our findings are clinically relevant reflecting the routine patient demographics
The aim of this work was not to identify the correct surgical “window” for patients with AS
but to identify pre-operative predictors of survival
a model looking at overall mortality in patients who have undergone surgical SAVR based on the existing guidelines is able to identify patients with a high risk of mortality
High-risk patients may benefit from more frequent medical care by physicians and cardiologists
This model will also allow clinicians to consider longer-term outcomes in patients
as currently the use of Euroscore II and STS only allows short-term outcome prediction
One important novel finding is the prognostically beneficial use of antiplatelet therapy
In the UK if patients take antiplatelet therapy before surgery this is continued long-term unless anticoagulation is needed
Multivariable analysis showed use of antiplatelets was associated with an almost 50% reduction in overall mortality
independently of presence or absence of coronary disease
This suggests that patients with AS undergoing SAVR may represent a cohort of patients at high vascular risk who might benefit from antiplatelet therapy in the long term
As our cohort of patients was elderly and the vast majority received a tissue bioprosthesis (> 90%) we estimate that the continuation of aspirin or clopidogrel could also have had an impact in reducing tissue thrombosis and hence improve survival
We provide a validated score with predictive variables for calculating mortality risk out to 10 years
to identify patients at higher risk following the SAVR that could benefit from being followed up in the hospital cardiology outpatients or the community more closely
this score is applicable not only to the patients with severe AS undergoing SAVR but also to the patients with moderate AS and co-existent CAD undergoing SAVR and CABG
as our model is derived from prognostically important risk factors
it subsequently enables early identification of the patients that carry high risk of mortality post intervention
the individual patient might still fare much better with surgery than medical management
the aim of the score is to facilitate more tailored post-operative management
as this falls out of the scope and purpose of the model
this score could be routinely utilised for selecting patients for transcatheter aortic valve replacement in preference to the non-specific Euroscore II and STS
although evidence from randomised controlled trials would be invaluable in validating this
our results indicate that use of an antiplatelet at the time of CMR is associated with significantly improved mortality
This is a novel finding suggesting SAVR patients represent a cohort with high vascular risk
that might benefit from antiplatelet therapy independently from other comorbidities
This work lends support to this hypothesis and further studies will be needed
it is uncertain whether this risk score will be valid in this population
or whether a different risk score needs to be designed
this score is robust and internally validated using the strongest statistical validation mechanism possible
In this large prospective registry-based study with the longest follow-up to date
we show that the risk of mortality in patients following SAVR remains high
We identify that the age of the patient at the time of SAVR
presence of any myocardial fibrosis and use of antiplatelet therapy can be utilised to provide an estimate of mortality for such patients through a risk score
and help guide management both before and after surgery
All data can be obtained following reasonable request to the corresponding author
Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample
Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study
Calcific aortic stenosis: a disease of the valve and the myocardium
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2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
2017 ESC/EACTS guidelines for the management of valvular heart disease
Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis
Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease
Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis
Prognostic significance of LGE by CMR in aortic stenosis patients undergoing valve replacement
Midwall fibrosis and 5-year outcome in moderate and severe aortic stenosis
Myocardial scar and mortality in severe aortic stenosis: data from the BSCMR valve consortium
Chin, C. W. L. et al. Myocardial fibrosis and cardiac decompensation in aortic stenosis. JACC Cardiovasc. Imaging. https://doi.org/10.1016/j.jcmg.2016.10.007 (2016)
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Magnetic resonance to assess the aortic valve area in aortic stenosis
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Left atrial dilation in patients with heart failure and preserved ejection fraction: Insights from cardiovascular magnetic resonance
Early anticoagulation of bioprosthetic aortic valves in older patients
Prospective evaluation of clinical outcomes in all-comer high-risk patients with aortic valve stenosis undergoing medical treatment
transcatheter or surgical aortic valve implantation following heart team assessment
Prognostic implications in patients with symptomatic aortic stenosis and preserved ejection fraction: Japanese multicenter aortic stenosis
Long-term outcomes following surgical aortic bioprosthesis implantation
An evaluation of penalised survival methods for developing prognostic models with rare events
A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD)
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On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data
Impact of stroke volume on severe aortic stenosis in patients with normal left ventricular function
Mangner, N. et al. Predictors of mortality and symptomatic outcome of patients with low-flow severe aortic stenosis undergoing transcatheter aortic valve replacement. J. Am. Heart Assoc. https://doi.org/10.1161/JAHA.117.007977 (2018)
Low-flow/low-gradient- aortenklappenstenose: Klinisches und diagnostisches spektrum
Clinical implication of mitral annular plane systolic excursion for patients with cardiovascular disease
Assessment of subclinical left ventricular dysfunction in aortic stenosis
Prediction models need appropriate internal
Magnetic resonance imaging phantoms for quality-control of myocardial T1 and ECV mapping: specific formulation
long-term stability and variation with heart rate and temperature
Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease
Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients
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The authors would like to acknowledge the support from the research nurses from the NIHR Biomedical Research Unit
Royal Brompton and Harefield Hospitals and Imperial College London
This work was supported by the NIHR Biomedical Research Unit
the British Heart Foundation (BH FS/15/29/31492; CER FS/14/13/30619; RE DEN CH/09/002; MRD FS/14/78/31020); DEN was also supported by a Wellcome Trust Senior Investigator Award (WT103782AIA)
These authors jointly supervised this work: Marc R
Royal Brompton Hospital and National Heart and Lung Institute
analysed data and drafted the first manuscript
analysed data and substantially revised the first draft
analysed and interpreted data and revised the draft
analysed and interpreted data and substantially revised the manuscript
analysed data and substantially revised the first draft
designed the work and substantially revised the manuscript
designed the work and substantially revised the first draft
conceived the idea and substantially revised the first draft
All authors read and approved the final manuscript and agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work
even ones in which the author was not personally involved
and the resolution documented in the literature
Dr Vassiliou is an Editorial Board Member of Scientific Reports
Pennell has received research funding from Siemens and La Jolla; has served as a consultant to Bayer; and is a director of and shareholder in CVIS
Prasad has received honoraria for talks from Bayer Schering
All others authors declare no conflict of interest
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«We began today with Met Curator Dita Amory's lecture on azulejos
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Portugal began producing its own decorative tiles
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Large azulejo panels were also featured in the homes of wealthy families
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Portugal was the world's largest producer of decorative tiles
where the local vinho verde (wine) is made
Lecturer Paddy Bowe led us on a tour of the enchanting gardens
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the group enjoyed a delicious wine tasting paired with various fruit
we dined over candlelight at the Alpendurada Monastery
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Regeneration of the magnificent Grade I listed Piece Hall in Halifax has been made possible with Hardscape paving and landscaping
As part of a £19million conservation scheme
the Piece Hall has undergone a major transformation to revive the cultural
The Piece Hall was originally built to support the trading of ‘pieces’ of cloth
The historic site is one of the last remaining examples of eighteenth century architecture of its kind
Landscaping materials supplier Hardscape played an integral role in the regeneration project, working alongside Gillespies landscape architects and GRAHAM Construction to restore the central courtyard to its former glory
Supported by Calderdale Council and a number of key conservation and heritage foundations
the redesign includes three levels of shops
Widely recognised as Yorkshire’s most important secular building
the regeneration of the Piece Hall was a major undertaking for all involved
Hardscape was tasked with bringing Gillespies’ architectural vision to life
transforming the courtyard to create an attractive
open and accessible central square for both residents and visitors to congregate
The landscaping needed to provide a contemporary and flexible space that could host a seasonal programme of events and festivals and accommodate an increased footfall
As the project was supported by the Heritage Lottery Fund
it was of paramount importance that materials were sourced from within Europe and that the style
texture and finish would be sympathetic with the original design of the main building
Hardscape provided a range of premium landscaping products to complement the site’s heritage and enhance the original eighteenth century design
This included six bespoke water features and more than 40 granite and timber benches
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fountain designers and landscape architects
Hardscape designed and detailed six water fountains
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Hardscape invited the GRAHAM Construction team to visit their quarries and manufacturing facilities in the Alpendurada region in Portugal
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As groundworks completed in different parts in the courtyard
Hardscape had to respond quickly by arranging the delivery of materials required for that specific section
Hardscape worked closely with GRAHAM to build individual schedules by dividing the courtyard into four quarters which enabled the quarries in Portugal to co-ordinate the speedy manufacture of materials
The Piece Hall’s new look was revealed at a grand opening ceremony in August 2017
More than 22,000 people walked through the gates for the event and the feedback was resoundingly positive
managing director at Hardscape, said: 'The regeneration of the Piece Hall provides a new shared space to bring the local community together and we hope the new courtyard will continue to inspire this spirit of collaboration for years to come
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our Pennant sandstone harmonises with the building fabric of the Piece Hall and proves the value of considered public realm investment. I wish to thank my team at Forest of Dean Stone Firms and all at Hardscape for delivering such a powerful space.'
For more information or technical support visit: www.hardscape.co.uk
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