Background and Aims:
Haemodynamic unloading of the left ventricle by Transcatheter Aortic Valve Implantation (TAVI) leads to an immediate adaptive response of the whole organism. To better understand these adaptation processes and to identify possible targets for drug-based therapeutic interventions, we performed an RNAseq in patients before and after TAVI.
Methods:
We collected whole blood PAXgene stabilized samples via the TAVI-biobank of the Clinic for Cardiology UKSH Campus Kiel from patients undergoing TAVI. Samples were obtained directly prior to TAVI and about three months later. We isolated the RNA according to manufacturer protocols and sequenced them using the Illumina method on the Novaseq6000 plattform. The reads were processed using the nf-core/smrnaseq(v 1.1.0) pipeline. All further analysis was conducted in R (4.4.1) and python using google colab.
Results:
We analyzed samples from 46 patients, median age was 80 years (IQR 75-84 yrs), 54% were female. Mean AVA was 0.7 cm², 33% had a reduced ejection fraction prior to TAVI. Patients received third generation valve of the CoreValve (58%) or Sapien (33%) platforms, 9% received a Navitor ™ valve. We initially identified 20944 RNAs, which were reduced to 18106 after quality control filtering. Using Benjamini–Hochberg correction for multiple testing, we identified 560 significantly regulated RNAs in paired pre- and post-TAVR samples, of which 325 were downregulated. Gene Ontology enrichment analysis revealed that the most overrepresented biological processes were mitochondrion organization, proteasome-mediated ubiquitin-dependent protein catabolic processes, and canonical NF-κB signal transduction. KEGG pathway enrichment showed that neurodegenerative disease pathways were among the most significantly enriched categories.
Conclusion:
Using RNAseq we could demonstrate a shift in energy metabolism, change of protein quality control and degradation and modulation of inflammatory/immune processes. Notably, the enrichment of aging-associated pathways suggests that valve replacement may modulate biological processes typically dysregulated during aging. This highlights a potential regulatory effect of TAVR beyond cardiac function, warranting further investigation into its role in age-related molecular remodeling.
