Mechanisms of Excess Risk in Aortic Stenosis

  • End date
    Dec 1, 2025
  • participants needed
  • sponsor
    University College, London
Updated on 7 May 2021


Aortic stenosis (AS) is caused by narrowing of one of the main heart valves. Replacing the valve is the only treatment to prevent the heart from failing or death. The timing of replacement is currently often too late - half of patients are left with permanent scarring and a quarter die within 3.5 years.

Studies are underway to see if earlier replacement makes a difference. But for those with scarring of the heart, there is currently no tailored treatment. I want to change this by understanding why and how patients with scar are dying and what the investigators can do to prevent this.

In this study, the investigators will use a heart scan (MRI) to detect scarring before valve replacement. After replacement, patients will receive a tiny monitor (paper clip size), which the investigators inject underneath the skin. This monitor continuously checks the heartbeat and can detect increased body fluid due to heart failure. The investigators will monitor patients for an average of 3 years to see if scarring is linked to abnormal heart rhythms and heart failure.

Once the investigators know how and why, the investigators can target patients with available medications and design studies using specialised treatments, eg defibrillator implantation, to protect patients with scar from dying.


Valvular heart disease (VHD) affects around 1.5 million people above the age of 65 across the UK and is set to nearly double by 2050. Aortic Stenosis (AS) is the most common VHD in the UK, affecting 3% of those over 75 with more than 11,000 people requiring aortic valve replacement (AVR) in the UK each year (>100,000 world-wide). Current guidelines recommend AVR to improve survival and symptom status when AS symptoms emerge or there is a reduction in left ventricle (LV) function (1), but years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators, and others, have shown that these changes lead to an excess in morbidity and mortality, but the mechanisms of increased risk is unclear.

Patients undergoing aortic valve replacement for severe aortic stenosis have a shorter life expectancy compared with the general population (2). Years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators and others have shown that these changes to the heart muscle are associated with poor outcome. But the mechanism of how heart muscle damage leads to excess mortality is poorly understood.

The proposed study will enhance our understanding of the residual risk after AVR and reveal the modes and substrate of mortality. Heart failure and heart rhythm disturbances (arrhythmias) are likely downstream effects of heart muscle damage, but without understanding the mode of death (heart failure, arrhythmia or other), the investigators are unable to target therapeutic strategies to improve outcomes.

Condition Aortic Stenosis, Heart failure, Congestive Heart Failure, Heart failure, Heart disease, Heart disease, Cardiac Disease, VALVULAR HEART DISEASE, Heart Valve Disease, Congestive Heart Failure, Heart Valve Disease, Cardiac Disease, aortic valve stenosis, cardiac failure, congestive heart disease, Non-Sustained VT, Non-Sustained VT
Treatment echocardiogram, Implantable loop recorder, 6 Minute Walk Test, Cardiac MRI scan, Serum biomarkers (High sensitivity troponin, NT-proBNP
Clinical Study IdentifierNCT04627987
SponsorUniversity College, London
Last Modified on7 May 2021


Yes No Not Sure

Inclusion Criteria

Patients with symptomatic severe aortic stenosis referred for surgical or transcatheter AVR (one out of: effective orifice area [EOA] <1.0 cm2 , indexed EOA of 0.6cm/m2, peak velocity >4.0 m/s or mean gradient >40mmHg)

Exclusion Criteria

More than moderate valve disease other than AS
Diagnosis of dilated or hypertrophic cardiomyopathy, pregnancy/breast feeding
eGFR <30ml/min, CMR incompatible devices
Inability to complete the protocol
Other conditions that would prevent participation in the study
Adenosine perfusion will not be performed in patients with AV block, severe asthma/COPD or LVEF<40%
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