Myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction.
BACKGROUND
Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function.


METHODS
Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion (myocardial perfusion reserve index-MPRI) and oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change) during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and 31P MR spectroscopy, respectively.


RESULTS
AS patients had reduced MPRI (1.1 ± 0.3 vs. controls 1.7 ± 0.3, p < 0.001) and BOLD SI change during stress (5.1 ± 8.9% vs. controls 18.2 ± 10.1%, p = 0.001), as well as reduced PCr/ATP (1.45 ± 0.21 vs. 2.00 ± 0.25, p < 0.001) and LV strain (-16.4 ± 2.7% vs. controls -21.3 ± 1.9%, p < 0.001). Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (-19.4 ± 2.5%) improved significantly.


CONCLUSIONS
Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand-supply balance to preserve myocardial energetics and LV function are promising future therapies.
Masliza
M
Mahmod
Jane M
JM
Francis
Nikhil
N
Pal
Andrew
A
Lewis
Sairia
S
Dass
Ravi
R
De Silva
Mario
M
Petrou
Rana
R
Sayeed
Stephen
S
Westaby
Matthew D
MD
Robson
Houman
H
Ashrafian
Stefan
S
Neubauer
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Oxford OX3 9DU, UK. theo.karamitsos@cardiov.ox.ac.uk.
Theodoros D
TD
Karamitsos
D000241:Adenosine; D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D001024:Aortic Valve Stenosis / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003326:Coronary Circulation; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D019028:Magnetic Resonance Imaging, Cine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D014665:Vasodilator Agents; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left
D015415:Biomarkers; D014665:Vasodilator Agents; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D000241:Adenosine