Background
Aortic stenosis is the commonest valve disease requiring intervention in the
developed world. Current guideline-based management strategies are based
on historical observational data or expert opinion and may leave many patients
with irreversible myocardial damage and adverse outcomes following valve
intervention. The aims of this thesis are to investigate novel cardiac magnetic
resonance techniques and how they can be applied to improve our decision
making around the timing of valve intervention.
Methods and Results
Cardiac magnetic resonance imaging can detect two forms of myocardial
fibrosis non-invasively; diffuse fibrosis using T1 mapping and replacement
fibrosis with the late gadolinium enhancement technique. I devised a novel
measure of diffuse fibrosis, the indexed extracellular volume (iECV) and
showed that these techniques can be used to divide patients into three
categories according to the type and amount of fibrosis present: no fibrosis,
diffuse fibrosis and replacement fibrosis. Moreover, I demonstrated that there
was evidence of increasing left ventricular decompensation across these three
groups.
How fibrosis and left ventricular hypertrophy change over time has not been
well studied in patients with aortic stenosis. Using serial imaging scans, I
showed that hypertrophy and diffuse fibrosis gradually progress over time,
whilst replacement fibrosis accumulates rapidly once first established.
Following valve replacement, cellular hypertrophy regresses faster than
diffuse fibrosis, but replacement fibrosis appears permanent and irreversible.
I then proceeded to investigate T1 mapping measures in a large international
multicentre cohort of patients with aortic stenosis scheduled for valve
replacement. I showed that extracellular volume-based T1 mapping measures
were comparable across centres and therefore confirmed that multicentre
studies are feasible. Extracellular volume fraction was associated with a
decompensating ventricle and emerged as a powerful independent predictor
of all-cause mortality in this group.
Finally, I investigated the use of novel hybrid magnetic resonance and positron
emission tomography imaging in patients with aortic stenosis, showing that
this technique is feasible and well-tolerated. I tested novel attenuation
correction and motion correction methods and showed that this technique can
offer multiparametric imaging of valve, myocardium and coronary arteries in a
single scan.
Conclusion
I have defined the longitudinal changes in hypertrophy and myocardial fibrosis
in aortic stenosis and validated extracellular volume measures as prognostic
markers in this group. Moreover, I have described novel magnetic resonance
and positron emission tomography techniques and their potential to aid the
clinical assessment of patients with aortic stenosis
