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Aortic stenosis (AS) is the most common valvular heart condition in the United Kingdom and the Western world. Surgery for severe AS prior to symptom onset is controversial. Conventionally changes in valve area and gradient are used to time intervention but myocardial changes may be more predictive of surgical need.
This study aims to elucidate the role of diffuse myocardial fibrosis as a prognostic marker, implementing a novel, non-invasive MRI technique to measure it.
Design: The investigators will measure diffuse myocardial fibrosis in 150 patients with severe narrowing of the aortic valve before and one year after valve replacement. Expected outcomes: Diffuse myocardial fibrosis measured by MRI scanning will predict outcome after surgery in aortic stenosis. Anticipated Health Benefits: Identify patients with higher post operative morbidity and mortality, who may benefit from earlier valve replacement.
Surgery for severe aortic stenosis (AS) prior to symptom onset is controversial. Conventionally changes in valve area and gradient are used to time intervention but myocardial changes may be more predictive of surgical need. This study aims to elucidate the role of diffuse myocardial fibrosis as a prognostic marker, implementing a novel, non-invasive technique to measure it.
AS is the most common valvular heart condition in the United Kingdom and the Western world. Its prevalence rises with age - about 3% aged over 75 have severe AS. During a period of progressive valve narrowing, the left ventricle (LV) adapts to the increased pressure with increasing concentric muscle hypertrophy. However, eventually this remodelling becomes maladaptive and the LV less compliant, leading to symptoms (breathlessness, chest pain, and loss of consciousness). This heralds a significant increase in morbidity and mortality. Consequently aortic valve replacement (AVR) in symptomatic patients is a Class I indication. In most asymptomatic patients however, prophylactic surgery is controversial: the risk of surgery is thought to be greater than watchful waiting, although there is no randomised data to support this approach. Conversely, diffuse myocardial fibrosis is thought to play a key role in functional deterioration, symptom development and possibly outcome in AS. Unfortunately, assessment of AS severity, including hemodynamic parameters such as peak velocity and mean gradient, poorly predict symptom development and/or optimal timing of surgery.
A non-invasive technique to quantify diffuse myocardial fibrosis against the gold standard of myocardial biopsy has been developed and validated in patients with AS: Cardiovascular magnetic resonance (CMR) with T1 mapping uses the extracellular tracer gadolinium to measure the extracellular volume (ECV), which closely reflects the degree of diffuse fibrosis. An important observation in a previous cohort (Flett et al European Heart Journal Cardiovascular Imaging 2012) was the fate of patients with severe fibrosis: they were more symptomatic at baseline, improved the most post-operatively and yet carried a trend towards increased mortality at six months. To unravel this, this study aims to track diffuse fibrosis in the RELIEF-AS study with a larger cohort (n=150) and for longer (12 months) to understand how to use diffuse fibrosis as a prognostic marker.
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| Measure | Description | Time Frame |
|---|---|---|
| Cardiovascular death | 12 months | |
| Major adverse cardiovascular events (MACE) | MACE: hospitalisation with heart failure, chest pain, syncope, arrhythmia or stroke | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Functional improvement | Improvement in 6 minute walk test. | 12 months |
| Regression of diffuse myocardial fibrosis | Diffuse myocardial fibrosis measured by T1 mapping by CMR |
| Measure | Description | Time Frame |
|---|---|---|
| LV remodeling post AVR | LV remodeling post AVR measured by CMR and transthoracic echocardiography. | 12 months |
Inclusion Criteria:
Exclusion Criteria:
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Patients with severe aortic stenosis awaiting valve replacement recruited from cardiology outpatient department or as cardiology inpatients.
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| Name | Affiliation | Role |
|---|---|---|
| James C Moon, MD | University College, London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Heart Hospital, University College London Hospitals | London | W1G 8PH | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20585010 | Background | Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010 Jul 13;122(2):138-44. doi: 10.1161/CIRCULATIONAHA.109.930636. Epub 2010 Jun 28. | |
| 22634740 |
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| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| ID | Term |
|---|---|
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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Serum and Plasma; myocardial biopsy obtained intra-operatively.
| 12 months |
| Flett AS, Sado DM, Quarta G, Mirabel M, Pellerin D, Herrey AS, Hausenloy DJ, Ariti C, Yap J, Kolvekar S, Taylor AM, Moon JC. Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study. Eur Heart J Cardiovasc Imaging. 2012 Oct;13(10):819-26. doi: 10.1093/ehjci/jes102. Epub 2012 May 25. |
| 31280289 | Derived | Bhuva AN, Treibel TA, De Marvao A, Biffi C, Dawes TJW, Doumou G, Bai W, Patel K, Boubertakh R, Rueckert D, O'Regan DP, Hughes AD, Moon JC, Manisty CH. Sex and regional differences in myocardial plasticity in aortic stenosis are revealed by 3D model machine learning. Eur Heart J Cardiovasc Imaging. 2020 Apr 1;21(4):417-427. doi: 10.1093/ehjci/jez166. |
| 30250733 | Derived | Smith A, Moravcova S, Treibel TA, Colque-Navarro P, Mollby R, Moon JC, Hamilton-Davies C. Relationship between endotoxin core, staphylococcal and varicella antibody levels and outcome following aortic valve replacement surgery: a prospective observational study. Perioper Med (Lond). 2018 Sep 20;7:20. doi: 10.1186/s13741-018-0101-z. eCollection 2018. |
| 29471937 | Derived | Treibel TA, Kozor R, Schofield R, Benedetti G, Fontana M, Bhuva AN, Sheikh A, Lopez B, Gonzalez A, Manisty C, Lloyd G, Kellman P, Diez J, Moon JC. Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis. J Am Coll Cardiol. 2018 Feb 27;71(8):860-871. doi: 10.1016/j.jacc.2017.12.035. |
| 29153564 | Derived | Treibel TA, Kozor R, Fontana M, Torlasco C, Reant P, Badiani S, Espinoza M, Yap J, Diez J, Hughes AD, Lloyd G, Moon JC. Sex Dimorphism in the Myocardial Response to Aortic Stenosis. JACC Cardiovasc Imaging. 2018 Jul;11(7):962-973. doi: 10.1016/j.jcmg.2017.08.025. Epub 2017 Nov 15. |
| D014694 |
| Ventricular Outflow Obstruction |