Background The discovery of functional classes of long noncoding RNAs (lncRNAs) has expanded our understanding of the variety of RNA species that exist in cells. In the heart, lncRNAs have been implicated in the regulation of development, ischemic and dilated cardiomyopathy, and myocardial infarction. Nevertheless, there is a limited description of expression profiles for these transcripts in human subjects. Methods and Results We obtained left ventricular tissue from human patients undergoing cardiac surgery and used RNA sequencing to describe a lncRNA profile. We then identified a list of lncRNAs that were differentially expressed between pairs of samples before and after the ischemic insult of cardiopulmonary bypass. The expression of some of these lncRNAs correlates with ischemic time. Coding genes in close proximity to differentially expressed lncRNAs as well as coding genes that have coordinated expression with these lncRNAs are enriched in functional categories related to myocardial infarction including: heart function, metabolism, the stress response, and the immune system. Conclusions We describe a list of lncRNAs that are differentially expressed after ischemia in the human heart. These genes are predicted to function in pathways consistent with myocardial injury. As a result, lncRNAs may serve as novel diagnostic and therapeutic targets for ischemic heart disease. Clinical Trial Registration https://clinicaltrials.gov/; Unique Identifier: NCT00985049.

MicroRNAs (miRNAs) play a significant role in ischemic heart disease. Animal models of left ventricular (LV) ischemia demonstrate a unique miRNA profile; however, these models have limitations in describing human disease. In this study, we performed next-generation miRNA and mRNA sequencing on LV tissue from nine patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. Samples were obtained immediately after aortic cross clamping (baseline) and before aortic cross clamp removal (postischemic). Of 1,237 identified miRNAs, 21 were differentially expressed between baseline and postischemic LV samples including the upregulated miRNAs miR-339-5p and miR-483-3p and the downregulated miRNA miR-139-5p. Target prediction analysis of these miRNAs was integrated with mRNA expression from the same LV samples to identify anticorrelated miRNA-mRNA pairs. Gene enrichment studies of candidate mRNA targets demonstrated an association with cardiovascular disease, cell death, and metabolism. Therapeutics that intervene on these miRNAs and their downstream targets may lead to novel mechanisms of mitigating the damage caused by ischemic insults on the human heart.

Background. Studies of the effects of postoperative atrial fibrillation (poAF) on long-term survival are conflicting, likely because of comorbidities that occur with poAF and the patient populations studied. Furthermore, the effects of poAF duration on long-term survival are poorly understood. Methods. We utilized a prospectively collected data-base on outcomes of cardiac surgery at a large tertiary care institution between August 2001 and December 2010 with survival follow-up through June 2015 to analyze long-term survival of patients with poAF. In addition, we identified patient- and procedure-related variables associated with poAF, and estimated overall comorbidity burden using the Elixhauser comorbidity index. Survival was compared between patients with poAF (n [ 513) and a propensity score matched control cohort, both for all patients and separately for subgroups of patients with poAF lasting less than 2 days (n [ 218) and patients with prolonged poAF (n [ 265). Results. Patients with poAF were older and had a higher burden of comorbidities. Survival was significantly worse for patients with poAF than for the matched control group (hazard ratio 1.43, 95% confidence interval: 1.11 to 1.86). That was driven by decreased survival among patients with prolonged poAF (hazard ratio 1.97, 95% confidence interval: 1.37 to 2.80), whereas survival of patients with poAF for less than 2 days was not significantly different from that of matched controls (hazard ratio 0.91, 95% confidence interval: 0.60 to 1.39). Conclusions. After close matching based on comorbidity burden, prolonged poAF is still associated with decreased survival. Therefore, vigilance is warranted in monitoring and treating patients with prolonged poAF after cardiac surgery.