Multiparametric cardiovascular magnetic resonance for the assessment of cardiac function and metabolism in hypertrophy and heart failure

Both hypertrophied and failing hearts are characterised by pathological left ventricular (LV) remodelling, impaired myocardial energy status and alteration in substrate metabolism. Cardiac magnetic resonance imaging (CMR) and magnetic resonance spectroscopy (MRS) are powerful tools in the characterisation of these disease conditions. More recent techniques have allowed assessment of myocardial steatosis using 1H-MRS and tissue oxygenation using blood oxygen level dependent (BOLD) CMR.
In hypertrophy and heart failure, studies on steatosis and the relationship with other parameters such as myocardial function and fibrosis, especially in humans are limited. I therefore investigated the presence of steatosis in severe aortic stenosis (AS) and dilated cardiomyopathy (DCM), and further assessed its relation to contractile function. This study found that myocardial triglyceride (TG) content is increased in both symptomatic and asymptomatic AS patients (lipid/water ratio 0.89±0.42% in symptomatic AS; 0.75±0.36% in asymptomatic AS vs. controls 0.45±0.17%, both p<0.05) and DCM patients (lipid/ratio 0.64±0.44% vs. controls 0.40±0.13%, p=0.03). Circumferential strain was lower in both AS (-16.4±2.5% in symptomatic AS; -18.9±2.9% in asymptomatic AS vs. controls 20.7±2.0%, both p<0.05) and DCM patients (-12.3±3.4% vs. controls -20.9±1.7%, p<0.001). In AS, myocardial contractility is related to the degree of steatosis, and were both reversible following aortic valve replacement (AVR), lipid/water ratio 0.92±0.41% vs. pre AVR 0.45±0.17%, p=0.04 and circumferential strain -17.2±2.0% vs. pre AVR -19.5±3.2%, p=0.04. A novel finding of this study was significant correlation of MRS-measured TG content with histological staining of TG of the myocardium, taken from endomyocardial biopsy during AVR. In DCM, myocardial TG was independently associated with LV dilatation and correlated significantly with hepatic TG, which suggests that both cardiac and hepatic steatosis might be a common feature in the failing heart.
Additionally, although the hypertrophied heart is characterised by impaired perfusion, it is unknown if this is severe enough to translate into tissue deoxygenation and ischaemia. I assessed this by using adenosine vasodilator stress test and BOLD-CMR in patients with severe AS. It was found that AS patients had reduced perfusion (myocardial perfusion reserve index-MPRI 1.0±0.3 vs. controls 1.7±0.3, p<0.001), and blunted tissue oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change 4.8±9.6% vs. controls 18.2±11.6%, p=0.001) during stress. Importantly, there was a substantial improvement in perfusion and oxygenation towards normal after AVR, MPRI 1.5±0.4, p=0.005 vs. pre AVR and BOLD SI change 16.4±7.0%, p=0.014 vs. pre AVR.
Overall, the work in this thesis supports the powerful role of CMR in assessing LV function and elucidating metabolic mechanisms in the hypertrophied and failing heart.

Keywords: aortic stenosis
metabolism
cardiovascular magnetic resonance
cardiac function
dilated cardiomyopathy
Advisor: Neubauer, S
Karamitsos, T
Ashrafian, H