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Preprint
Integrating molecular and clinical variables to predict myocardial recovery
bioRxiv
20 Apr 2024
PMID: 38659908
Abstract
Mechanical unloading and circulatory support with left ventricular assist devices (LVADs) mediate significant myocardial improvement in a subset of advanced heart failure (HF) patients. The clinical and biological phenomena associated with cardiac recovery are under intensive investigation. Left ventricular (LV) apical tissue, alongside clinical data, were collected from HF patients at the time of LVAD implantation (n=208). RNA was isolated and mRNA transcripts were identified through RNA sequencing and confirmed with RT-qPCR. To our knowledge this is the first study to combine transcriptomic and clinical data to derive predictors of myocardial recovery. We used a bioinformatic approach to integrate 59 clinical variables and 22,373 mRNA transcripts at the time of LVAD implantation for the prediction of post-LVAD myocardial recovery defined as LV ejection fraction (LVEF) ≥40% and LV end-diastolic diameter (LVEDD) ≤5.9cm, as well as functional and structural LV improvement independently by using LVEF and LVEDD as continuous variables, respectively. To substantiate the predicted variables, we used a multi-model approach with logistic and linear regressions. Combining RNA and clinical data resulted in a gradient boosted model with 80 features achieving an AUC of 0.731±0.15 for predicting myocardial recovery. Variables associated with myocardial recovery from a clinical standpoint included HF duration, pre-LVAD LVEF, LVEDD, and HF pharmacologic therapy, and LRRN4CL (ligand binding and programmed cell death) from a biological standpoint. Our findings could have diagnostic, prognostic, and therapeutic implications for advanced HF patients, and inform the care of the broader HF population.
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Details
- Title
- Integrating molecular and clinical variables to predict myocardial recovery
- Creators
- Joseph R Visker - University of UtahBen J Brintz - University of UtahChristos P Kyriakopoulos - Intermountain Medical CenterYanni Hillas - University of UtahIosif Taleb - Intermountain Medical CenterRachit Badolia - University of UtahThirupura S Shankar - University of UtahJunedh M Amrute - Washington University in St. LouisJing LingRana Hamouche - University of UtahEleni Tseliou - Intermountain Medical CenterSutip Navankasattusas - University of UtahOmar Wever-PinzonGregory S Ducker - University of UtahWilliam L Holland - University of UtahScott A Summers - University of UtahSteven C Koenig - University of LouisvilleThomas C Hanff - University of UtahKory J Lavine - Washington University in St. LouisSrinivas Murali - Allegheny Health NetworkStephen Bailey - Allegheny Health NetworkRami Alharethi - Lake City VA Medical CenterCraig H Selzman - University of UtahPalak ShahMark S Slaughter - University of LouisvilleManreet K Kanwar - Allegheny Health NetworkStavros G Drakos - Intermountain Medical Center
- Publication Details
- bioRxiv
- Publisher
- American Physical Society (APS); United States
- Grant note
- R35 HL161185 / NHLBI NIH HHS
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- Cardiothoracic Surgery; Medicine (Graduate); Cardiology
- Other Identifier
- 991021932104404721