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Shekar, Prem

Introduction: Acute kidney injury (AKI) after cardiac surgery increases length of hospital stay and in-hospital mortality. A significant number of patients undergoing cardiac surgical procedures require perioperative intra-aortic balloon pump (IABP) support. Use of an IABP has been linked to an increased incidence of perioperative renal dysfunction and death. This might be due to dislodgement of atherosclerotic material in the descending thoracic aorta (DTA). Therefore, we retrospectively studied the correlation between DTA atheroma, AKI and in-hospital mortality. Methods: A total of 454 patients were retrospectively matched to one of four groups: -IABP/-DTA atheroma, +IABP/-DTA atheroma, -IABP/+DTA atheroma, +IABP/+DTA atheroma. Patients were then matched according to presence/absence of DTA atheroma, presence/absence of IABP, performed surgical procedure, age, gender and left ventricular ejection fraction (LVEF). DTA atheroma was assessed through standard transesophageal echocardiography (TEE) imaging studies of the descending thoracic aorta. Results: Basic patient characteristics, except for age and gender, did not differ between groups. Perioperative AKI in patients with -DTA atheroma/+IABP was 5.1% versus 1.7% in patients with -DTA atheroma/-IABP. In patients with +DTA atheroma/+IABP the incidence of AKI was 12.6% versus 5.1% in patients with +DTA atheroma/-IABP. In-hospital mortality in patients with +DTA atheroma/-IABP was 3.4% versus 8.4% with +DTA atheroma/+IABP. In patients with +DTA atheroma/+IABP in hospital mortality was 20.2% versus 6.4% with +DTA atheroma/-IABP. Multivariate logistic regression identified DTA atheroma > 1 mm (P = *0.002, odds ratio (OR) = 4.13, confidence interval (CI) = 1.66 to 10.30), as well as IABP support (P = *0.015, OR = 3.04, CI = 1.24 to 7.45) as independent predictors of perioperative AKI and increased in-hospital mortality. DTA atheroma in conjunction with IABP significantly increased the risk of developing acute kidney injury (P = 0.0016) and in-hospital mortality (P = 0.0001) when compared to control subjects without IABP and without DTA atheroma. Conclusions: Perioperative IABP and DTA atheroma are independent predictors of perioperative AKI and in-hospital mortality. Whether adding an IABP in patients with severe DTA calcification increases their risk of developing AKI and mortality postoperatively cannot be clearly answered in this study. Nevertheless, when IABP and DTA are combined, patients are more likely to develop AKI and to die postoperatively in comparison to patients without IABP and DTA atheroma.

Heart failure remains one of the most common causes of morbidity and mortality worldwide. The advent of mechanical circulatory support devices has allowed significant improvements in patient survival and quality of life for those with advanced or end-stage heart failure. We provide a general overview of past and current mechanical circulatory support devices encompassing options for both short- and long-term ventricular support.

Introduction: Right ventricular failure remains a major cause of mortality during acute pulmonary embolism. Right ventricular function can be assessed with transesophageal echocardiography. However, due to the complex right ventricular anatomy, only a few echocardiographic parameters are reliable and easily obtainable intraoperatively. Tricuspid annular plane systolic excursion is a validated parameter of global right ventricular function. Methods: Data from 81 patients with acute pulmonary embolus undergoing pulmonary embolectomy were evaluated. Transesophageal echocardiography derived parameters of right ventricular function were obtained and compared to tricuspid annular plane systolic excursion measurements. Patients were then divided into two groups (TAPSE < 18 mm and ≥18 mm). Results: The patient population consisted of 46 males and 35 females, mean age 61.0 ± 12.9 years. Patients in the TAPSE <18 mm group had significantly larger diastolic (p=0.0015) and systolic (p=0.0031) right ventricular diameters, lower right ventricular fractional area change (p=0.0065) and greater degrees of tricuspid regurgitation (p=0.0001) compared to patients with TAPSE ≥18 mm. In addition, all patients who needed intraoperative cardiopulmonary resuscitation (11/81) or died intraoperatively (8/81) belonged to the TAPSE <18 mm group. Logistic regression analysis confirmed TAPSE <18 mm as an independent risk factor for intraoperative cardiopulmonary resuscitation and death. Conclusions: Transesophageal echocardiography derived TAPSE is easily obtainable and correlates well with other standardized parameters of right ventricular function. TAPSE <18 mm is an independent predictor of intraoperative cardiopulmonary resuscitation and death in patients undergoing emergent pulmonary embolectomy.

Background: Allele-specific expression (ASE) is differential expression of each of the two chromosomal alleles of an autosomal gene. We assessed ASE patterns in the human left atrium (LA, n = 62) and paired samples from the left ventricle (LV, n = 76) before and after ischemia, and tested the utility of differential ASE to identify genes associated with postoperative atrial fibrillation (poAF) and myocardial ischemia. Methods: Following genotyping from whole blood and whole-genome sequencing of LA and LV samples, we called ASE using sequences overlapping heterozygous SNPs using rigorous quality control to minimize false ASE calling. ASE patterns were compared between cardiac chambers and with a validation cohort from cadaveric tissue. ASE patterns in the LA were compared between patients who had poAF and those who did not. Changes in ASE in the LV were compared between paired baseline and post-ischemia samples. Results: ASE was found for 3404 (5.1%) and 8642 (4.0%) of SNPs analyzed in the LA and LV, respectively. Out of 6157 SNPs with ASE analyzed in both chambers, 2078 had evidence of ASE in both LA and LV (p < 0.0001). The SNP with the greatest ASE difference in the LA of patients with and without postoperative atrial fibrillation was within the gelsolin (GSN) gene, previously associated with atrial fibrillation in mice. The genes with differential ASE in poAF were enriched for myocardial structure genes, indicating the importance of atrial remodeling in the pathophysiology of AF. The greatest change in ASE between paired post-ischemic and baseline samples of the LV was in the zinc finger and homeodomain protein 2 (ZHX2) gene, a modulator of plasma lipids. Genes with differential ASE in ischemia were enriched in the ubiquitin ligase complex pathway associated with the ischemia-reperfusion response. Conclusions: Our results establish a pattern of ASE in the human heart, with a high degree of shared ASE between cardiac chambers as well as chamber-specific ASE. Furthermore, ASE analysis can be used to identify novel genes associated with (poAF) and myocardial ischemia. Electronic supplementary material The online version of this article (doi:10.1186/s13073-016-0381-1) contains supplementary material, which is available to authorized users.

Background: Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity and mortality. Analyzing the tissue-specific gene expression in the left atrium (LA) can identify novel genes associated with AF and further the understanding of the mechanism by which previously identified genetic variants associated with AF mediate their effects. Methods: LA free wall samples were obtained intraoperatively immediately prior to mitral valve surgery in 62 Caucasian individuals. Gene expression was quantified on mRNA harvested from these samples using RNA sequencing. An expression quantitative trait loci (eQTL) analysis was performed, comparing gene expression between different genotypes of 1.0 million genetic markers, emphasizing genomic regions and genes associated with AF. Results: Comparison of whole-genome expression between patients who later developed poAF and those who did not identified 23 differentially expressed genes. These included genes associated with the resting membrane potential modified by potassium currents, as well as genes within Wnt signaling and cyclic GMP metabolism. The eQTL analysis identified 16,139 cis eQTL relationships in the LA, including several involving genes and single nucleotide polymorphisms (SNPs) linked to AF. A previous relationship between rs3744029 and MYOZ1 expression was confirmed, and a novel relationship between rs6795970 and the expression of the SCN10A gene was identified. Conclusions: The current study is the first analysis of the human LA expression landscape using high-throughput RNA sequencing. Several novel genes and variants likely involved in AF pathogenesis were identified, thus furthering the understanding of how variants associated with AF mediate their effects via altered gene expression. Trial registration ClinicalTrials.gov ID: NCT00833313, registered 5. January 2009 Electronic supplementary material The online version of this article (doi:10.1186/s12920-017-0270-5) contains supplementary material, which is available to authorized users.

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: scbody@partners.org. ! 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.

Thoracic aortic disease, including thoracic aor- tic aneurysm (TAA), is frequently seen in patients with bicuspid aortic valve (BAV). We hypothesized that BAV morphotype would be associated with aortic aneurysm phe- notypes but that other patient variables would signiicantly modify this relationship. 829 patients between 18 and 90 years with BAV and available raw imaging of the aortic valve and the ascending aorta to its mid-portion prior to aortic valve and aortic surgery were examined. The sinuses of Valsalva and proximal ascending aorta were measured from 2-dimensional co-planar echocardiographic images. We observed strong associations between patient habitus and raw and normalized dimensions of the aortic root and ascending aorta. Patients with R–L morphotype presented at an older age with larger aortic root but similar ascend- ing aortic dimensions. After accounting for patient mor- phometric characteristics and severity of aortic valve dis- ease, patients with R–L valve morphotype were marginally more likely to have an aortic root aneurysm (86% vs. 78%; P=0.043), deined as aortic root dimension Z score ≥3 We observed only small diferences in aortic dimensions between BAV morphotypes, that are eclipsed by variation in patient habitus. We interpret these indings to mean that BAV patients will not likely beneit from therapies based on aortic valve morphotype. Rather, we propose that all BAV patients should undergo longitudinal follow-up, inde- pendent of valve morphotype. Guidelines for aortic surgery based upon dimensions alone may be improved by con- sidering patient characteristics such as age, body size and other characteristics.