Metabolic Dysfunction in Aortic Stenosis: A Key Piece of the Pathophysiological Puzzle

Aortic stenosis (AS) places an increased load on the myocardium, which according to Laplace's law, must increase its thickness to maintain normal wall tension.Indeed, an increase in left ventricular wall thickness has been regarded as one of the hallmarks of well-compensated aortic stenosis.However, myocardial function is not normal in the hypertrophied myocardium of patients with severe AS.It has been known for many years that LV strain is reduced in these patients, even when LV ejection fraction is completely normal.1 The myocardium in patients with severe AS also shows evidence of metabolic dysfunction, 2 lipid accumulation and fibrosis.3 This has been demonstrated directly using magnetic resonance imaging and spectroscopy, 2 and indirectly through metabolic profiling of the serum.4 It has not been clear, however, when these changes begin to develop, whether they are seen early in the course of AS, and whether they are fully reversible.The ability of transcatheter-based techniques to replace the aortic valve with low morbidity and mortality, 5 makes the need to answer these questions highly compelling.The study by Monga and colleagues in this issue of the journal is, therefore, an extremely important and welcomed study.6 The investigators studied 74 subjects with AS, ranging from mild to severe disease.All subjects underwent cine MRI, including tagged cine images for LV strain calculation, T1 mapping, late gadolinium enhancement and MR spectroscopy.The spectroscopy protocol included P31 spectroscopy to measure high energy phosphates, specifically the PCr/ATP ratio, and proton spectroscopy to measure myocardial lipid content.In addition, 13 healthy volunteers underwent the same protocol.The subjects were analyzed in groups based on