Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post–Transcatheter Aortic Valve Implantation Death
Year: 2023
Type: article
Study design: Observational Study
Abstract: Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long‐term follow‐up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre–transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post–transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25–1.90]; P <0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Conclusions Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post–transcatheter aortic valve implantation recovery, rehabilitation, and survival.
Authors: Andrew S. Perry, Shilin Zhao, Venkatesh Murthy, Deepak K. Gupta, William F. Fearon, Juyong B. Kim, Samir Kapadia, Dharam J. Kumbhani, Linda Gillam, Brian Whisenant, Nishath Quader, Alan Zajarias, Ravinder R. Mallugari, Daniel E. Clark, Jay N. Patel, Holly Gonzales, Frederick G. Welt, Anthony A. Bavry, Megan Coylewright, Robert N. Piana, Anna Vatterott, Natalie Jackson, Robert E. Gerszten, Brian R. Lindman, Ravi Shah, Sammy Elmariah
Institutions: Vanderbilt University, Vanderbilt University Medical Center, University of Michigan, Stanford Medicine, Cleveland Clinic, The University of Texas Southwestern Medical Center, Morristown Medical Center, Intermountain Healthcare, Intermountain Medical Center, Barnes-Jewish Hospital, Saint Thomas Health, University of Utah Hospital, Erlanger Health System, Broad Institute, Beth Israel Deaconess Medical Center, Harvard University, Massachusetts Institute of Technology, University of California, San Francisco
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,700
Funders: American Heart Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Edwards Lifesciences, Boston Scientific Corporation, Siemens Healthineers, Norsk Institutt for Vannforskning, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Award: G1357828253
OpenAlex ID: W4381598854