Mechanisms of Excess Risk in Aortic Stenosis
Mechanisms of Excess Risk in Aortic Stenosis
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.
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%.