Newby, David

Dweck, Marc

Bing, Rong

other

2022-02-07T14:00:46Z

2022-02-07T14:00:46Z

2021-12-08

Background Aortic stenosis is the commonest valve disease in the Western world, progresses inexorably over years and has no effective lifestyle or drug treatments. Left untreated, aortic stenosis leads to symptoms such as breathlessness and chest pain, followed by cardiac failure and death. Aortic valve replacement (AVR) is the only treatment, for which surgery has been the default technique for decades. Transcatheter aortic valve implantation (TAVI), a much less invasive strategy, has substantially expanded the population in whom we now consider AVR. Importantly, the implantation of a prosthetic valve should be considered a means of converting a patient with severe native valve disease to a patient with a well-functioning prosthesis, rather than a cure for valve disease per se. There are potential complications that can arise following successful valve replacement, including valve thrombosis and structural valve degeneration. Given the above, several controversies and questions exist. These include: 1) What is the optimal method of assessing aortic stenosis severity in low-flow states and in valves where fibrosis contributes significantly to valve obstruction? 2) Are there deleterious effects on myocardial health from aortic stenosis that occur prior to symptom onset or a fall in ejection fraction, and that provide prognostic information? 3) Are there drug therapies that can retard the progression of aortic stenosis? 4) Are there novel methods of detecting bioprosthetic valve thrombus that may provide insight into mechanisms governing valve durability? Methods In study one, we developed a unique method of assessing the anatomy of the aortic valve and the severity of aortic stenosis using contrast-enhanced computed tomography (CT). This method has several advantages over non-contrast CT aortic valve calcium scoring (CT-AVC) – the current standard flow-independent measure of aortic stenosis severity – which include spatial resolution, anatomical definition and the ability to quantify non-calcific leaflet thickening in addition to calcific volume. This technique was applied in a post-hoc analysis of a prospectively recruited population of patients with aortic stenosis enrolled in a randomised controlled trial. Patients had undergone standardised echocardiography, non-contrast CT and contrast-enhanced CT. In study two, we investigated a novel echocardiographic measurement, first-phase ejection fraction (EF1), in aortic stenosis. This parameter is the ejection fraction measured at the time of peak aortic velocity, rather than across the entire cardiac cycle, and is a measure of early left ventricular contractility which can be impaired in aortic stenosis. This technique was applied in a post-hoc analysis of a prospectively recruited population of patients with aortic stenosis enrolled in an observational study. Patients had undergone standardised echocardiography and cardiac magnetic resonance (CMR). Subsequent AVR and death were captured from medical records. In study three, we undertook a double-blind randomised controlled clinical trial of the anti-osteoporotic drugs denosumab and alendronic acid to determine whether they could slow disease progression in aortic stenosis. This hypothesis arose from a body of pre-clinical and observational data suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms to aortic valve calcification, and that modification of the receptor activator of nuclear kappa B (RANK) ligand/RANK/osteoprotegerin axis might ameliorate valvular calcification. Patients were randomised in a 2:1:2:1 ratio to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly) or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, CT-AVC and 18F-sodium fluoride (18F-NaF) positron emission tomography and computed tomography (PET-CT). The primary endpoint was the calculated 24-month change in CT-AVC. In study four, we undertook the first ever cardiac study of 18F-GP1. This is a novel radiotracer that binds to the glycoprotein IIb/IIIa receptor, which are upregulated on activated platelets. We investigated whether 18F-GP1 PET-CT could detect thrombus formation on bioprosthetic aortic valves. First, ex vivo validation of 18F-GP1 binding was conducted in explanted bioprosthetic valves leaflets using histology (Movat’s pentachrome), immunohistochemistry (CD41) and autoradiography (18F-GP1). Second, patients with bioprosthetic aortic valve prostheses who were not on anticoagulation were enrolled and underwent standardised echocardiography and 18F-GP1 PET-CT. Patients with normal native aortic valves who had undergone 18F-GP1 PET-CT as part of a contemporaneous study formed a control cohort. Two patients with clinically confirmed obstructive bioprosthetic valve thrombosis, recruited as part of a proof-of-concept case series by collaborators in Germany, were also included in the analysis. Results In study one, 164 patients with aortic stenosis were included for analysis (78% male; 41 mild, 89 moderate, 34 severe). We demonstrated that non-calcific and calcific aortic valve leaflet volumes on contrast-enhanced CT correlated well with echocardiographic peak aortic jet velocity (r=0.67, p<0.001). In particular, quantification of the total non-calcific and calcific leaflet volume demonstrated better correlation with echocardiographic peak aortic velocity than non-contrast CT-AVC in women (r=0.72 and r=0.38 respectively). In study two, 149 patients with aortic stenosis were included for analysis (70% male; 34 mild, 40 moderate, 75 severe). We demonstrated that EF1 can be impaired despite a normal overall ejection fraction, that a low EF1 is associated with increased global left ventricular afterload and more myocardial fibrosis, and that there is a potential for EF1 to improve following AVR. Importantly, a low EF1 was associated with future AVR or death, independent of mean aortic valve gradient (hazard ratio 5.6, 95% confidence interval 3.4-9.1). In study three, we enrolled and randomised 150 patients (mean age 72±8 years, 21% female, peak aortic jet velocity 3.36 [interquartile range 2.93 to 3.82] m/s) to denosumab (n=49), alendronic acid (n=51) or placebo tablet or injection (total n=50). Despite an unequivocal pharmacodynamic effect of the active drugs, as confirmed by a halving of the serum C-terminal telopeptide concentration at 6 months in the denosumab and alendronic acid arms, we found no differences in 24-month change in CT-AVC between denosumab and placebo (343 [198 to 804] Agatston Units (AU) versus 354 [76 to 675] AU, p=0.41), or alendronic acid and placebo (326 [138 to 813] AU versus 354 [76 to 675] AU, p=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-NaF aortic valve uptake. In study four, we undertook 18F-GP1 PET-CT in 75 participants (53 with bioprosthetic valves, median time from implantation 37 [12 to 80] months; 22 with normal native valves). All bioprosthetic valves, but no native aortic valves, demonstrated focal 18F-GP1 uptake in the valve leaflets. On multivariable analysis, higher 18F-GP1 uptake was independently associated with duration of valve implantation (p=0.002) and hypoattenuated leaflet thickening (p=0.004) but not with valve type. One patient had suspected clinical valve thrombosis, confirmed on 18F-GP1 PET-CT, in addition to the two patients with known obstructive valve thrombosis. All 3 were anticoagulated for 3 months, leading to resolution of symptoms, improvement in mean valve gradients and a reduction in 18F-GP1 uptake. Extra-valvular 18F-GP1 uptake was evident across a range of extra-valvular prosthetic material such as aortic interposition grafts and pacemaker leads. Conclusions We have demonstrated that contrast-enhanced CT assessments of non-calcific and calcific aortic valve leaflet volumes correlated well with echocardiographic assessments of aortic stenosis severity. This technique has clear benefits over non-contrast CT-AVC. We envisage the potential for standard integration of contrast-enhanced leaflet volume assessments into routine TAVI workflows, where a large proportion of patients have discordant echocardiographic findings, and in patients where the contribution of fibrosis, rather than purely calcium, may lead to underestimation of stenosis severity as assessed by CT-AVC. We went on to show that EF1 is a potentially useful echocardiographic measure of early left ventricular systolic dysfunction that may help risk stratification in patients with asymptomatic severe aortic stenosis. This is pertinent in the current era where early AVR is being tested in several randomised controlled trials. Additionally, we conclusively demonstrate in a randomised controlled trial that neither denosumab nor alendronic acid substantially affect the progression of aortic stenosis. This was a disappointing result but an important finding that also highlights the importance of randomised controlled trials when investigating causal relationships. Finally, 18F-GP1 PET-CT may have utility in identifying focal areas of thrombus and distinguishing them from other causes of hypoattenuation on CT as well as providing a novel approach to explore factors that may influence valve thrombogenicity and durability. Taken together, these four studies have provided incremental advances in the diagnosis, assessment and follow-up of patients with aortic stenosis as well as generated major impetus for future clinical studies in this important and topical field.

https://hdl.handle.net/1842/38539

http://dx.doi.org/10.7488/era/1803

en

The University of Edinburgh

Bing R, Dweck M. Management of asymptomatic severe aortic stenosis: check or all in? Heart. 2020 Nov 4:heartjnl-2020-317160. doi: 10.1136/heartjnl-2020-317160.

Bing R, Dweck MR. The quest for an aortic stenosis cure. Heart. 2020 Sep 11:heartjnl-2020- 317421.

Bing R, Dweck M. Myocardial fibrosis – why image, how to image and clinical implications. Heart. 2019. doi: 10.1136/heartjnl-2019-315560.

Bing R, Cavalcante JL, Everett RJ, Clavel MA, Newby DE, Dweck MD. Imaging and impact of myocardial fibrosis in aortic stenosis. J Am Coll Cardiol Img. Feb 2019, 12 (2) 283-296; doi: 0.1016/j.jcmg.2018.11.026.

Kwiecinski J, Tzolos E, Cartlidge TRG, Fletcher A, Doris MK, Bing R, Tarkin JM, Seidman MA, Gulsin GS, Cruden NL, Barton AK, Uren NG, Williams MC, Van Beek EJR, Leipsic J, Dey D, Makkar RR, Slomka PJ, Rudd JHF, Newby DE, Sellers SL, Berman DS, Dweck MR. Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients with Transcatheter Aortic Valve Implantation. Circulation. 2021 Aug 29. doi: 10.1161/CIRCULATIONAHA.121.056891.

Shah ASV, Lee KK, Pérez JAR, Campbell D, Astengo F, Logue J, Gallacher PJ, Katikireddi SV, Bing R, Alam SR, Anand A, Sudlow C, Fischbacher CM, Lewsey J, Perel P, Newby DE, Mills NL, McAllister DA. Clinical burden, risk factor impact and outcomes following myocardial infarction and stroke: A 25-year individual patient level linkage study. Lancet Reg Health Eur. 2021 Aug;7:100141. doi: 10.1016/j.lanepe.2021.100141.

Bing R, Andrews JP, Williams MC, van Beek EJR, Lucatelli C, MacNaught G, Clark T, Koglin N, Stephens AW, MacAskill MG, Tavares AA, Dhaliwal K, Dorward DA, Lucas C, Dweck MR, Newby DE. In vivo Thrombosis Imaging in Patients Recovering from COVID 19 and Pulmonary Embolism. Am J Respir Crit Care Med. 2021 Aug 10. doi: 10.1164/rccm.202011-4182IM.

Tzolos E, Bing R, Newby DE, Dweck MR. Categorising myocardial infarction with advanced cardiovascular imaging. Lancet. 2021 Aug 7;398(10299):e9. doi: 10.1016/S0140- 6736(21)01329-5.

Kwak S, Everett RJ, Treibel TA, Yang S, Hwang D, Ko T, Williams MC, Bing R, Singh T, Joshi S, Lee H, Lee W, Kim YJ, Chin CWL, Fukui M, Al Musa T, Rigolli M, Singh A, Tastet L, Dobson LE, Wiesemann S, Ferreira VM, Captur G, Lee S, Schulz-Menger J, Schelbert EB, Clavel MA, Park SJ, Rheude T, Hadamitzky M, Gerber BL, Newby DE, Myerson SG, Pibarot P, Cavalcante JL, McCann GP, Greenwood JP, Moon JC, Dweck MR, Lee SP. Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis. J Am Coll Cardiol. 2021 Aug 10;78(6):545-558. doi: 10.1016/j.jacc.2021.05.047.

Gu H, Bing R, Chin C, Fang L, White AC, Everett R, Spath N, Park E, Chambers JB, Newby DE, Chiribiri A, Dweck MR, Chowienczyk P. First-phase ejection fraction by cardiovascular magnetic resonance predicts outcomes in aortic stenosis. J Cardiovasc Magn Reson. 2021 Jun 10;23(1):73. doi: 10.1186/s12968-021-00756-x

Gu H, Bing R, Chin C, Fang L, White A, Everett R, Spath N, Park E, Chambers J, Newby D, Chiribiri A, Dweck M, Chowienczyk P. First-phase ejection fraction by CMR predicts outcomes in aortic stenosis. J Cardiovasc Magn Reson. 2021

Sengupta PP, Shrestha S, Kagiyama N, Hamirani Y, Kulkarni H, Yanamala N, Bing R, Chin CWL, Pawade TA, Messika-Zeitoun D, Tastet L, Shen M, Newby DE, Clavel MA, Pibarot P, Dweck MR; Artificial Intelligence for Aortic Stenosis at Risk International Consortium. A Machine-Learning Framework to Identify Distinct Phenotypes of Aortic Stenosis Severity. JACC Cardiovasc Imaging. 2021 May 11:S1936-878X(21)00286-2. doi: 10.1016/j.jcmg.2021.03.020.

Singh T, Bing R. Antiplatelet therapy after percutaneous coronary intervention: is less more (more or less)? Heart. 2021 May 13. doi: 10.1136/heartjnl-2021-319126

Pawade TA*, Doris MK*, Bing R*, White AC, Forsyth L, Evans E, Graham C, Williams MC, van Beek EJR, Fletcher A, Adamson PD, Andrews JPM, Cartlidge TRG, Jenkins WSA, Syed M, Fujisawa T, Lucatelli C, Fraser W, Ralston SH, Boon N, Prendergast B, Newby DR, Dweck MRD. Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial. Circulation. 2021 Apr 29. doi: 10.1161/CIRCULATIONAHA.121.053708.

Cartlidge TR*, Bing R*, Kwiecinski J, Guzzetti E, Pawade TA, Doris MK, Adamson PD, Massera D, Lembo M, Peeters FECM, Couture C, Berman DS, Dey D, Slomka P, Pibarot P, Newby DE, Clavel MA, Dweck MR. Contrast-enhanced computed tomography assessment of aortic stenosis. Heart. 2021 Jan 29:heartjnl-2020-318556. doi: 10.1136/heartjnl-2020- 318556

Fletcher AJ, Lembo M, Kwiecinski J, Syed MBJ, Nash J, Tzolos E, Bing R, Cadet S, MacNaught G, van Beek EJR, Moss AJ, Doris MK, Walker NL, Dey D, Adamson PD, Newby DE, Slomka PJ, Dweck MR. Quantifying microcalcification activity in the thoracic aorta. J Nucl Cardiol. 2021 Jan 20. doi: 10.1007/s12350-020-02458-w.

Williams MC, Massera D, Moss AJ, Bing R, Bularga A, Adamson PD, Hunter A, Alam S, Shah ASV, Pawade T, Roditi G, van Beek EJR, Nicol ED, Newby DE, Dweck MR. Prevalence and clinical implications of valvular calcification on coronary computed tomography angiography. Eur Heart J Cardiovasc Imaging. 2020 Dec 11:jeaa263. doi: 10.1093/ehjci/jeaa263.

Doris MK, Meah MN, Moss AJ, Andrews JPM, Bing R, Gillen R, Weir N, Syed M, Daghem M, Shah A, Williams MC, van Beek EJR, Forsyth L, Dey D, Slomka PJ, Dweck MR, Newby DE, Adamson PD. Coronary 18F-Fluoride Uptake and Progression of Coronary Artery Calcification. Circ Cardiovasc Imaging. 2020 Dec;13(12):e011438. doi: 10.1161/CIRCIMAGING.120.011438. Epub 2020 Dec 10.

Bing R, Dweck M. Management of asymptomatic severe aortic stenosis: check or all in? Heart. 2020 Nov 4:heartjnl-2020-317160. doi: 10.1136/heartjnl-2020-317160.

Lee KK, Bing R, Kiang J, Bashir S, Spath N, Stelzle D, Mortimer K, Bularga A, Doudesis D, Joshi SS, Strachan F, Gumy S, Adair-Rohani H, Attia EF, Chung MH, Miller MR, Newby DE, Mills NL, McAllister DA, Shah ASV. Adverse health effects associated with household air pollution: a systematic review, meta-analysis, and burden estimation study. Lancet Glob Health. 2020 Nov;8(11):e1427-e1434. doi: 10.1016/S2214-109X(20)30343-0.

Bing R, Adamson PD. Cardiac catheterisation laboratory in a global pandemic: ceding centre stage. Heart. 2020 Oct 14:heartjnl-2020-318263. doi: 10.1136/heartjnl-2020-318263.

Doris MK, Jenkins W, Robson P, Pawade T, Andrews JP, Bing R, Cartlidge T, Shah A, Pickering A, Williams MC, Fayad ZA, White A, van Beek EJ, Newby DE, Dweck MR. Computed tomography aortic valve calcium scoring for the assessment of aortic stenosis progression. Heart. 2020 Oct 5:heartjnl-2020-317125.

Bing R, Dweck MR. The quest for an aortic stenosis cure. Heart. 2020 Sep 11:heartjnl-2020- 317421.

Bularga A, Bing R, Shah AS, Adamson PD, Behan M, Newby DE, Flapan A, Uren N, Cruden N. Clinical outcomes following balloon aortic valvuloplasty. Open Heart. 2020 Sep;7(2):e001330. doi: 10.1136/openhrt-2020-001330

Dweck MR, Bularga A, Hahn RT, Bing R, Lee KK, Chapman AR, White A, Salvo GD, Sade LE, Pearce K, Newby DE, Popescu BA, Donal E, Cosyns B, Edvardsen T, Mills NL, Haugaa K. Global evaluation of echocardiography in patients with COVID-19. Eur Heart J Cardiovasc Imaging. 2020 Jun 18:jeaa178. doi: 10.1093/ehjci/jeaa178.

Singh T, Bing R, Dweck M, van Beek E, Mills N, Williams M, Villines T, Newby D, Adamson P. Exercise Electrocardiography and Computed Tomography Coronary Angiography for Patients With Suspected Stable Angina Pectoris: A Post Hoc Analysis of the Randomized SCOT-HEART Trial2020 Jun 3;5(8):1-10. doi: 10.1001/jamacardio.2020.1567

Bing R, Hamra M, Newby D. Cold feet, warm heart. Heart. 2020 Jul;106(13):959-1032. doi: 10.1136/heartjnl-2020-316815.

Shah ASV, McAllister DA, Gallacher P, Astengo F, Perez JAR, Hall J, Lee KK, Bing R, Anand A, Nathwani D, Mills NL, Newby DE, Marwick C, Cruden NLM. Incidence, Microbiology and Outcomes in Patient Hospitalized with Infective Endocarditis. Circulation. 2020;10.1161/CIRCULATIONAHA.119.044913

Bing R*, Gu H*, Chin C, Fang L, White A, Everett R, Spath N, Park E, Jenkins W, Shah A, Mills N, Flapan A, Chamber J, Newby D, Chowienczyk P*, Dweck M*. Determinants and prognostic value of echocardiographic first-phase ejection fraction in aortic stenosis. Heart. 2020. 10.1136/heartjnl-2020-316684.

Bing R, Mitchell A, Newby D. Chest pain – when in doubt….Heart. 2020 May;106(9):690- 706. doi: 10.1136/heartjnl-2019-316458.

Bing R, Behan M, Pessotto R, Cruden N, Northridge D. Percutaneous repair of ventricular ruptures. JACC Case Reports. 2020. doi: 10.1016/j.jaccas.2019.11.088.

Calin A, Mateescu A, Popescu A, Bing R, Dweck M, Popescu B. Role of advanced left ventricular imaging in adults with aortic stenosis. Heart. 2020. doi: 10.1136/heartjnl-2019- 315211

Meah M, Bing R, Newby D. Primacy of coronary CT angiography as the gatekeeper for the cardiac catheterization laboratory. Am Heart J. 2020. doi: 10.1016/j.ahj.2020.01.017.

Bing R, Singh T, Dweck M, Mills N, Williams M, Adamson P, Newby D. Validation of European Society of Cardiology pre-test probabilities for obstructive coronary artery disease in suspected stable angina. Eur Heart J Qual Care Clin Outcomes. 2020. doi: 10.1093/ehjqcco/qcaa006.

Bing R, Loganath K, Adamson P, Newby D, Moss A. Non-invasive imaging of high-risk coronary plaque: the role of computed tomography and positron emission tomography. Br J Radiol. 2019 Dec 18:20190740. doi: 10.1259/bjr.20190740.

Bing R, Dweck M. Myocardial fibrosis – why image, how to image and clinical implications. Heart. 2019. doi: 10.1136/heartjnl-2019-315560

Bing R, Dweck M. Aortic valve and coronary 18F-sodium fluoride activity – a common cause? J Nucl Cardiol. 2019. doi: 10.1007/s12350-019-01901-x

Adamson PD, Williams MC, Dweck MR, Mills NL, Boon NA, Daghem M, Bing R, Moss AJ, Mangion K, Flather M, Forbes J, Hunter A, Norrie J, Shah ASV, Timmis AD, van Beek EJR, Ahmadi AA, Leipsic J, Narula J, Newby DE, Roditi G, McAllister D, Berry C. Mechanisms of Improved Five-year Outcomes After Coronary CT Angiography in Patients with Stable Chest Pain. J Am Coll Cardiol. 2019;74(16):2058-70.

Moss A, Dweck M, Doris M, Andrews J, Bing R, Forsythe R, Cartlidge T, Pawade T, Daghem M, Raftis J, Williams M, van Beek E, Forsythe R, Lewis S, Lee R, Shah A, Mills N, Newby D, Adamson P. Ticagrelor to reduce myocardial injury in patients with high-risk coronary artery plaque. J Am Coll Cardiol Img. 2019;10.1016/j.jcmg.2019.05.023.

Daghem M, Bing R, Dweck M, Fayad Z. Non-Invasive Imaging to Assess Atherosclerotic Plaque Composition and Disease Activity. J Am Coll Cardiol Img. 2019;10.1016/j.jcmg.2019.03.033.

Moss AJ, Doris MK, Andrews JPM, Bing R, Daghem M, van Beek EJR, Forsyth L, Shah ASV, Williams MC, Sellers S, Leipsic J, Dweck MR, Parker RA, Newby DE, Adamson PD. Molecular coronary plaque imaging using 18F-Fluoride. Circ Cardiovasc Imaging. 2019 Aug;12(8):e008574.

Lee KK, Stelzle D, Bing R, Anwar M, Strachan F, Bashir S, Newby DE, Shah JS, Chung MH, Bloomfield GS, Longenecker CT, Bagchi S, Kottilil S, Blach S, Razavi H, Mills PR, Mills NL, McAllister DA, Shah ASV. Global burden of atherosclerotic cardiovascular disease in hepatitis C virus infection: a systematic review, meta-analysis, and modelling study. Lancet Gastroenterol Hepatol. 2019. doi: 10.1016/S2468-1253(19)30227-4.

Bing R, Driessen RS, Knaapen P, Dweck MR. The clinical utility of hybrid imaging for the identification of vulnerable plaque and vulnerable patients. J Cardiovasc Comput Tomogr. 2019;10.1016.

Bing R, Henderson J, Hunter A, Williams M, Moss A, Shah A, McAllister D, Dweck M, Newby D, Mills N, Adamson P. Clinical determinants of plasma cardiac biomarkers in patients with stable chest pain. Heart. 2019. doi: 10.1136/heartjnl-2019-314892.

Fukui M, Bing R, Dweck MD, Cavalcante J. Assessment of aortic stenosis by cardiac magnetic resonance imaging. Quantification of flow, characterization of myocardial injury, transcatheter aortic valve replacement planning and more. Magn Reson Imaging Clin N Am. 2019 Aug;27(3):427-437. doi: 10.1016/j.mric.2019.04.004.

Bing R, Dweck MD. Myocardial fibrosis in classical low-flow low-gradient severe aortic stenosis - the missing piece of the puzzle? Circ Cardiovasc Imaging. 2019 May;12(5):e009187. doi: 10.1161/CIRCIMAGING.119.009187.

Bing R, Everett R, Tuck C et al. Rationale and design of the randomized, controlled Early Valve Replacement Guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis (EVOLVED) trial. Am Heart J. 2019 Mar 15;212:91-100. doi: 10.1016.

Bing R, Cavalcante JL, Everett RJ, Clavel MA, Newby DE, Dweck MD. Imaging and impact of myocardial fibrosis in aortic stenosis. J Am Coll Cardiol Img. Feb 2019, 12 (2) 283-296; doi: 0.1016/j.jcmg.2018.11.026.

Dweck M, Bing R. Diffuse myocardial fibrosis in aortic stenosis – time to act? J Am Coll Cardiol Img. 2019 Jan;12(1):120-122. doi: 10.1016/j.jcmg.2018.06.026

Bing R, Cruden N. Risk assessment for non-cardiac surgery after coronary stenting – keeping it simple. Eur Heart J Qual Care Clin Outcomes. 2019 Jan 1;5(1):1-3. doi: 10.1093/ehjqcco/qcy043.

aortic stenosis

aortic valve replacement treatment

contrast-enhanced computed tomography

heart scaning

18F-GP1

18F-GP1 binding

valve stiffening

Valve and the ventricle: advances in the assessment and management of aortic stenosis

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy