Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used in advanced heart failure patients. Recent studies suggest that low socioeconomic status (SES) predicts worst survival after heart transplantation. Both individual-level and neighborhood-level SES (nSES) have been linked to cardiovascular health; however, the impact of SES in CF-LVAD patients remains unknown. We hypothesized that SES is a major determinant of CF-LVAD candidacy and postimplantation outcomes. A retrospective chart review was conducted on 362 patients between February 2009 and May 2016. Neighborhood-level SES was measured using the American Community Survey data and the Agency for Healthcare Research and Quality SES index score. Individual-level SES was self reported. Kaplan–Meier survival analysis and multivariable Cox proportional hazards regression determined survival statistics. Patients in the highest SES tertile were older (58 ± 13 vs. 53 ± 14; p < 0.001), less likely to be black or Hispanic (26% vs. 70%; p < 0.001), more likely to be married (87% vs. 65%; p < 0.001), more likely to have private insurance (50% vs. 39%; p < 0.001), and more likely to have employment (29% vs. 15%; p < 0.001) compared with patients in the lowest tertile. Low nSES was associated with a decreased risk of death (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.347–0.970; p = 0.038) in comparison to the high nSES. However, after adjusting for baseline clinical morbidities, the relationship was no longer present. When selecting patients for a LVAD, SES should not be thought of as an immutable risk factor. Carefully selected low-SES patients could be safely implanted with CF-LVAD with outcomes comparable to high-SES patients.
Introduction:
Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression and have been implicated in various biological processes. Modulating lncRNA levels could be a plausible strategy for the treatment of heart failure (HF), however the specific lncRNAs responsible for cardiac reverse remodeling remain largely unknown.
Hypothesis:
Myocardial lncRNAs mediate reverse remodeling through
cis
-regulation of the neighboring mRNAs
Methods:
RNA sequencing was performed using total RNA isolated from failing human myocardium before (n=21) and after (n=12) left ventricular assist device (LVAD) implantation as well as from non-failing controls (n=5). Mapped reads for all GENCODE v26 lncRNAs were calculated. Differentially regulated mRNAs and lncRNAs were identified using a fold-change cut-off of 2 and a false discovery rate of 5%. Pearson correlation coefficient was used to determine the relationship between lncRNA and neighboring mRNAs.
Results:
81 incident HF and 47 reverse remodeling lncRNAs were identified (Figure 1A). 46 HF lncRNAs (56.8%) were normalized following LVAD support and showed reciprocal regulation in the pre- vs. post-LVAD myocardium (Figure 1B). Recovery lncRNAs included recently described Myheart (originating in the MYH7 locus) as well as novel lncRNAs (NPPA-AS1, RORB-AS1, lnc-TECRL). Majority of the antisense, intergenic, and intronic myocardial lncRNAs demonstrated a positive correlation with neighboring genes suggesting
cis
-regulation by lncRNAs during cardiac reverse remodeling (Figure 1C).
Conclusions:
Myocardial lncRNAs are dynamically regulated during myocardial remodeling (HF) and reverse remodeling with LVAD support. Mechanical unloading is accompanied by partial normalization of the pathological lncRNA signature. Further studies will determine mechanisms by which neighboring protein coding genes are regulated by lncRNAs in the failing human heart.
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