Metabolites left from certain cellular processes may be markers of left ventricular (LV) remodeling and myocardial distress, as shown in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis.
Blood samples taken immediately before and 24 hours after TAVR were used for metabolimic profiling via liquid chromatography and mass spectrometry. It turned out that baseline long-chain acylcarnitines, intermediates of fatty acid metabolism, were tied to maladaptive cardiac remodeling, according to a group led by Sammy Elmariah, MD, MPH, of Massachusetts General Hospital in Boston.
After adjusting for other factors (age, sex, diabetes status, renal function, and B-type natriuretic peptide), mean β values of acylcarnitines C16, C18:1, C18:2, C18, and C26 were independently associated with LV mass index, the authors described in their study published online in JAMA Cardiology.
“Similarly, with the exception of C18:2 acylcarnitine, each of the long-chain acylcarnitines distinguished between patients with and without severe LV hypertrophy,” Elmariah’s group reported. Circulating levels of C18:2 acylcarnitine were still associated with LV ejection fraction before and after multivariable adjustment.
Within 24 hours of TAVR, circulating levels of C16 decreased by 30.2%, C18:1 by 42.7%, C18:2 by 37.3%, and C18 by 38.3%, suggestive of an alleviation of cardiac pressure overload with the procedure.
“In symptomatic patients with severe aortic stenosis undergoing TAVR, circulating levels of long-chain acylcarnitines were independently associated with measures of maladaptive LV remodeling, and metabolic perturbations lessened after procedure completion,” the authors concluded.
“Clinical practice currently relies on clinical symptoms or the presence of overt LV failure to guide the timing of aortic valve replacement for aortic stenosis. This approach often identifies a late-stage cohort in whom maladaptive remodeling may be advanced and irreversible,” they suggested. “There is therefore an unmet clinical need for objective methods to identify early, reversible stages of maladaptive LV remodeling and to inform timely aortic valve replacement.”
Blood metabolite levels did not independently relate to relative wall thickness.
The study included 44 consecutive patients undergoing transfemoral TAVR at a single institution (81.9 years old on average, 52% women).
Such a small sample size was a major caveat to the analyses performed, as was the lack of validation or complete statistical adjustment for the predictive value of plasma acylcarnitines.
Elmariah disclosed institutional research support from Siemens, Boehringer Ingelheim Pharmaceuticals, and the American Heart Association; and consulting fees from Medtronic and Edwards Lifesciences.