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The Long Noncoding RNA Landscape of the Ischemic Human Left Ventricle
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
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Duration of Postoperative Atrial Fibrillation After Cardiac Surgery Is Associated With Worsened Long-Term Survival
Background. Studies of the effects of postoperative atrial fibrillation (poAF) on long-term survival are con- flicting, 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 asso- ciated 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).
Postoperative atrial fibrillation (poAF) is observed in 26% to 32% of patients after isolated coronary artery bypass graft (CABG) surgery, and 30% to 50% of patients after isolated valve or combined valve and CABG sur- gery [1]. Several clinical risk factors for poAF have been identified, including older age [2, 3], male sex [2], and obesity [4]. Comorbidities such as history of prior atrial fibrillation (AF) [5], hypertension [3], congestive heart failure [5], chronic obstructive lung disease [5], and chronic kidney disease [6] have also been associated with poAF. Furthermore, valve repair or replacement and an increased aortic cross-clamp time also contribute to an increased risk of poAF [2, 5]. More recently, several
Accepted for publication May 2, 2016.
Address correspondence to Dr Body, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115; email: [email protected].
! 2016 by The Society of Thoracic Surgeons Published by Elsevier
Results. Patients with poAF were older and had a higher burden of comorbidities. Survival was signifi- cantly worse for patients with poAF than for the matched control group (hazard ratio 1.43, 95% confi- dence 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 comor- bidity burden, prolonged poAF is still associated with decreased survival. Therefore, vigilance is warranted in monitoring and treating patients with prolonged poAF after cardiac surgery