Epicardial transplantation of autologous atrial appendage micrografts: evaluation of safety and feasibility in pigs after coronary artery occlusion.

Objectives. Several approaches devised for clinical utilization of cell-based therapies for heart failure often suffer from complex and lengthy preparation stages. Epicardial delivery of autologous atrial appendage micrografts (AAMs) with a clinically used extracellular matrix (ECM) patch provides a straightforward therapy alternative. We evaluated the operative feasibility and the effect of micrografts on the patch-induced epicardial foreign body inflammatory response in a porcine model of myocardial infarction. Design. Right atrial appendages were harvested and mechanically processed into AAMs. The left anterior descending coronary artery was ligated to generate acute infarction. Patches of ECM matrix with or without AAMs were transplanted epicardially onto the infarcted area. Four pigs received the ECM and four received the AAMs patch. Cardiac function was studied by echocardiography both preoperatively and at 3-week follow-up. The primary outcome measures were safety and feasibility of the therapy administration, and the secondary outcome was the inflammatory response to ECM. Results. Neither AAMs nor ECM patch-related complications were detected during the follow-up time. AAMs patch preparation was feasible according to time and safety. Inflammation was greatly reduced in AAMs when compared with ECM patches as measured by the amount of infiltrated inflammatory cells and area of inflammation. Immunohistochemistry demonstrated an increased CD3+ cell density in the AAMs patch infiltrate. Conclusions. Epicardial AAMs transplantation demonstrated safety and clinical feasibility. The use of micrografts significantly inhibited ECM-induced foreign body inflammatory reactivity. Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can suppress acute inflammatory reactivity.

Perioperative Bleeding Requiring Blood Transfusions is Associated With Increased Risk of Stroke After Transcatheter and Surgical Aortic Valve Replacement.

OBJECTIVES: The authors aimed to investigate the impact of severe bleeding and use of red blood cell (RBC) transfusion on the development of postoperative stroke after surgical (SAVR) and transcatheter aortic valve replacement (TAVR), taken from the FinnValve registry. DESIGN: Nationwide, retrospective observational study. SETTING: Five Finnish university hospitals participated in the registry. PARTICIPANTS: A total of 6,463 patients who underwent SAVR (n = 4,333) or TAVR (n = 2,130). INTERVENTIONS: Patients who underwent TAVR or SAVR with a bioprosthesis with or without coronary revascularization. MEASUREMENTS AND MAIN RESULTS: The incidence of postoperative stroke after SAVR was 3.8%. In multivariate analysis, the number of transfused RBC units (odds ratio [OR], 1.098; 95% confidence interval [CI], 1.064-1.133) was one of the independent predictors of postoperative stroke. The incidence of stroke increased, along with the severity of perioperative bleeding, according to the European Coronary Artery Bypass Grafting (E-CABG) bleeding grades were as follows: grade 0, 2.2% (reference group); grade 1, 3.4% (adjusted OR, 1.841; 95% CI, 1.105-3.066); grade 2, 5.5% (adjusted OR, 3.282; 95% CI, 1.948-5.529); and grade 3, 14.8% (adjusted OR, 7.103; 95% CI, 3.612-13.966). The incidence of postoperative stroke after TAVR was 2.5%. The number of transfused RBC units was an independent predictor of stroke after TAVR (adjusted OR, 1.155; 95% CI, 1.058-1.261). The incidence of postoperative stroke increased, along with the severity of perioperative bleeding, as stratified by the E-CABG bleeding grades: E-CABG grade 0, 1.7%; grade 1, 5.3% (adjusted OR, 1.270; 95% CI, 0.532-3.035); grade 2, 10.0% (adjusted OR, 2.898; 95% CI, 1.101-7.627); and grade 3, 30.0% (adjusted OR, 10.706; 95% CI, 2.389-47.987). CONCLUSIONS: Perioperative bleeding requiring RBC transfusion and/or reoperation for intrathoracic bleeding is associated with an increased risk of postoperative stroke after SAVR and TAVR. Patient blood management and meticulous preprocedural planning and operative technique aiming to avoid significant perioperative bleeding may reduce the risk of cerebrovascular complications.

Gender and the Outcome of Postcardiotomy Veno-arterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: There is a paucity of sex-specific data on patients' postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO). The present study sought to assess this issue in a multicenter study. DESIGN: Retrospective, propensity score-matched analysis of an international registry. SETTING: Multicenter study, tertiary university hospitals. PARTICIPANTS: Data on adult patients undergoing postcardiotomy VA-ECMO. MEASUREMENTS AND MAIN RESULTS: Between January 2010 and March 2018, patients treated with postcardiotomy VA-ECMO at 17 cardiac surgery centers were analyzed. Index procedures considered were coronary artery bypass graft surgery, isolated valve surgery, their combination, and proximal aortic root surgery. Hospital and five-year mortality constituted the endpoints of interest. Propensity score matching was adopted with logistic regression. A total of 358 patients (mean age: 63.3 ± 12.3 years; 29.6% female) were identified. Among 94 propensity score-matched pairs, women had a higher hospital mortality (70.5% v 56.4%, p = 0.049) compared with men. Logistic regression analysis showed that women (odds ratio [OR], 1.87; 95% confidence interval [CI] 1.10-3.16), age (OR, 1.06; 95%CI 1.04-1.08) and pre-ECMO arterial lactate (OR, 1.09; 95%CI 1.04-1.16) were independent predictors of hospital mortality. No differences between female and male patients were observed for other outcomes. Among propensity score-matched pairs, one-, three-, and five-year mortality were 60.6%, 65.0%, and 65.0% among men, and 71.3%, 71.3%, and 74.0% among women, respectively (p = 0.110, adjusted hazard ratio, 1.27; 95%CI 0.96-1.66). CONCLUSIONS: In postcardiotomy VA-ECMO, female patients demonstrated higher hospital mortality than men. Morbidity and late mortality were similar between the two groups.

Cerebral Oximetry Monitoring in Patients Undergoing Surgery for Stanford Type A Aortic Dissection.

OBJECTIVES: The aim of this study was to evaluate the prognostic impact of cerebral regional oxygen saturation (crSO2) in patients undergoing surgery for Stanford type A aortic dissection (TAAD). DESIGN: Observational, retrospective, institutional study. SETTING: University hospital. PARTICIPANTS: A total of 152 patients who underwent surgery for TAAD from June 2009 to December 2018 at the authors' institution. INTERVENTIONS: Surgery for TAAD using continuous perioperative monitoring of crSO2 with near-infrared cerebral oximetry (INVOS, Medtronic, MN). MEASUREMENTS AND RESULTS: The rates of postoperative stroke/global brain ischemia were 22.4% and of hospital mortality 14.5%. Age, hemoglobin, and cardiogenic shock were independent predictors of nadir crSO2 from both frontal areas at arrival to the operating room. Repeated measures test showed that changes in crSO2 between the first measurement at operating room arrival, at the start of surgery, and at the end of surgery were not significant when measured on the right frontal area (p = 0.632), left frontal area (p = 0.608), as a nadir value from both frontal areas (p = 0.690), and as a difference between frontal areas (p = 0.826) in patients with and without major neurologic complications. Patients who had a nadir crSO2 <40% anytime during the perioperative period, had a numerically higher rate of major neurologic complications (27.3% v 20.4%, p = 0.354), but this difference did not reach statistical significance. The incidence of nadir of crSO2 value <40% at operating room arrival (5.9%, p = 1.000), at the start of surgery (5.3%, p = 0.685), and at the end of surgery (1.3%, p = 1.000) was rather low and not associated with these adverse events. CONCLUSIONS: Derangements in crSO2 detected by cerebral oximetry before and during surgery for TAAD did not predict postoperative stroke and/or global brain ischemia.

Outcomes of surgery for extensive infective endocarditis.

OBJECTIVE: Extensive infective endocarditis (EIE) involving the valve annulus or the intervalvular fibrous body (IFB) is a treatment challenge. We sought to clarify the outcomes of patients undergoing surgery for EIE. METHODS: We retrospectively reviewed all 197 consecutive patients who underwent an operation for infective endocarditis (IE) between 2005 and 2016 in the Helsinki University Hospital. Thirty-five (18%) patients had EIE, of which 17 (9%) infection extended to IFB. RESULTS: Patients with EIE had higher EuroSCORE II (24.4% vs. 12.4% p < .001), higher frequency of diabetes (29% vs. 13% p = .017), more often NYHA Class IV (83% vs. 56% p = .02), aortic (97% vs. 45% p < .001), multivalve (40% vs. 11% p < .001), and prosthetic valve IE (37% vs. 9% p < .001), and underwent more often emergency surgery (46% vs. 29% p = .042). Thirty-day mortality was 9% in the EIE group and 7% in the non-EIE group (p = .720). Survival of patients with EIE at 5 years was 60% and with non-EIE 71% (p = .029). The frequency of complications was higher in EIE (54%) than in non-EIE patients (25%) (p < .001), due to the higher need for permanent pacemaker implantations (34% vs. 4% p < .001). Freedom from re-operations at 5 years was 91% in the EIE group and 97% in the non-EIE group (p = .203). CONCLUSIONS: Early mortality of surgery for EIE was comparable with non-EIE. Midterm survival was lower after surgery for EIE than after surgery for non-EIE but there was no difference in survival of patients with IE limited to the valve annulus amenable to patch repair and patients with endocarditis requiring IFB reconstruction.

Epitranscriptomics of Ischemic Heart Disease-The IHD-EPITRAN Study Design and Objectives.

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.

The origin of plasma neutrophil gelatinase-associated lipocalin in cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is common after heart surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is produced in injured kidney. NGAL has been used as an early plasma biomarker for AKI in patients undergoing heart surgery. Neutrophils contain all isoforms (25-kDa, 45-kDa and 145-kDa) but the kidney produces almost exclusively the 25-kDa isoform of NGAL. We investigated first, whether there is association between NGAL and neutrophil activation, and second whether activated neutrophils are a significant source of circulating NGAL in plasma in patients undergoing cardiac surgery. METHODS: Two separate patient cohorts were studied: 1) the "kinetic cohort" (n = 29) and 2) the "FINNAKI cohort" (n = 306). As NGAL is strictly co-localized with lactoferrin in neutrophils, NGAL and lactoferrin were measured with enzyme-linked immunosorbent assay in all patients. In sixty-one patients of the "FINNAKI cohort" Western blot was used to separate NGAL isoforms according to their molecular size. Mann-Whitney U, Kruskal-Wallis H, Pearson's and Spearman's tests were used as appropriate. RESULTS: There was strong intraoperative association between NGAL and lactoferrin at all four time-points in the "kinetic cohort". In the "FINNAKI cohort", NGAL and lactoferrin concentrations correlated preoperatively (R = 0.59, p < 0.001) and at admission to the intensive care unit (R = 0.69, p < 0.001). At admission to intensive care unit, concentrations of NGAL and lactoferrin were higher in AKI than in non-AKI patients (NGAL: p < 0.001; lactoferrin: p < 0.029). In Western blot analyses, neutrophil specific 45-kDa isoform (median 41% [IQR 33.3-53.1]) and mostly neutrophil derived 145-kDa isoform (median 53.5% [IQR 44.0-64.9%]) together represented over 90% of total NGAL in plasma. Potentially kidney derived NGAL isoform (25-kDa) accounted for only 0.9% (IQR 0.3 - 3.0%) of total NGAL in plasma. There were no statistically significant differences in the distribution of NGAL isomers between AKI and non-AKI patients. CONCLUSIONS: Plasma NGAL during cardiac surgery is associated with neutrophil activation. Based on molecular size, the majority of circulating NGAL is derived from neutrophils. Neutrophil activation is a confounding factor when interpreting increased plasma NGAL in cardiac surgery.

Outcome of early vs delayed surgery for infective mitral endocarditis.

BACKGROUND AND AIM OF THE STUDY: Timing of surgery for infective endocarditis is controversial. The objective of this study was to report the outcomes of early vs delayed surgery (DS) of mitral endocarditis. METHODS: We retrospectively reviewed all patients treated surgically for mitral endocarditis between 2005 and 2016 in a single center. We analyzed midterm outcomes of early surgery (ES; surgery within 7 days or less of prior directed antibiotic treatment) in comparison to DS (surgery after more than 7 days of prior directed antibiotic treatment). RESULTS: Survival of all patients was 87% at one and 72% at 5 years. Mean follow-up time was 4.0 ± 3.1 years. Thirty-three (36.3%) patients were in the ES and 58 (63.7%) were in the DS group. Patients with ES were younger (47.4 vs 55.3 years), were in New York Heart Association class III or IV more frequently (97.0 vs 65.5%), and had higher EuroScore2 (15.6 vs 8.6%). The ES group had lower freedom from valve reoperation (98.2 vs 87.2%; P = .035) and the composite endpoint of >2 + regurgitation or reoperation at 5 years (98.2 vs 72.7%; P = .004). CONCLUSIONS: ES was associated with a higher rate of reoperations and the composite endpoint of recurrent MR or reoperation.

Minimal volume ventilation during robotically assisted mitral valve surgery.

INTRODUCTION: A minimal volume ventilation method for robotically assisted mitral valve surgery is described in this study. In an attempt to reduce postoperative pulmonary dysfunction, 40 of 174 patients undergoing robotically assisted mitral valve surgery were ventilated with a small tidal volume during cardiopulmonary bypass. METHODS: After propensity score matching, 31 patients with minimal volume ventilation were compared with 54 patients with no ventilation. Total ventilation time, PaO2/FiO2 ratio, arterial lactate concentration, and the rate of unilateral pulmonary edema in the matched minimal ventilation and standard treatment groups were evaluated. RESULTS: Patients in the minimal ventilation group had shorter ventilation times, 12.0 (interquartile range: 9.9-15.0) versus 14.0 (interquartile range: 12.0-16.3) hours (p = 0.036), and lower postoperative arterial lactate levels, 0.99 (interquartile range: 0.81-1.39) versus 1.28 (interquartile range: 0.99-1.86) mmol/L (p = 0.01), in comparison to patients in the standard treatment group. There was no difference in postoperative PaO2/FiO2 ratio levels or in the rate of unilateral pulmonary edema between the groups. CONCLUSION: Minimal ventilation appeared beneficial in terms of total ventilation time and blood lactatemia, while there was no improvement in arterial blood gas measurements or in the rate of unilateral pulmonary edema. The lower postoperative arterial lactate levels may suggest improved lung perfusion among patients in the minimal volume ventilation group. The differences in the ventilation times were in fact small, and further studies are required to confirm the possible advantages of the minimal volume ventilation method in robotically assisted cardiac surgery.

Follow-up of intramyocardial bone marrow mononuclear cell transplantation beyond 10 years.

Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center trial in 2006-2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (- 15.1%; 95% CI - 23 to - 6.7% vs. - 7.3%; 95% CI - 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades.

[Neurologic complications in cardiac surgery patients]. / Sydänleikkauspotilaiden neurologiset komplikaatiot.

Cerebral infarction and hypoxic-ischemic brain damage (HIE) may impair the recovery of a patient from otherwise successful cardiac operation. Severe neurologic complications occur in approximately 2 to 5% of cardiac surgery patients. The major risk factors can be recognized. The most common cause of cerebral infarction is a calcific embolus released during manipulation of atheromatotic aorta. HIE results from cerebral circulatory deficiency and subsequent hypoxia in the cerebral tissue. The development of complications can be prevented by restricting aortic manipulation and by optimizing the perfusion technique and other treatment during the operation.

Emerging roles of the RNA modifications N6-methyladenosine and adenosine-to-inosine in cardiovascular diseases.

Cardiovascular diseases lead the mortality and morbidity disease metrics worldwide. A multitude of chemical base modifications in ribonucleic acids (RNAs) have been linked with key events of cardiovascular diseases and metabolic disorders. Named either RNA epigenetics or epitranscriptomics, the post-transcriptional RNA modifications, their regulatory pathways, components, and downstream effects substantially contribute to the ways our genetic code is interpreted. Here we review the accumulated discoveries to date regarding the roles of the two most common epitranscriptomic modifications, N6-methyl-adenosine (m6A) and adenosine-to-inosine (A-to-I) editing, in cardiovascular disease.

Long-term outcomes after ascending aortic replacement and aortic root replacement for type A aortic dissection.

OBJECTIVES: We investigated whether the selective use of supracoronary ascending aorta replacement achieves late outcomes comparable to those of aortic root replacement for acute Stanford type A aortic dissection (TAAD). METHODS: Patients who underwent surgery for acute type A aortic dissection from 2005 to 2018 at the Helsinki University Hospital, Finland, were included in this analysis. Late mortality was evaluated with the Kaplan-Meier method and proximal aortic reoperation, i.e. operation on the aortic root or aortic valve, with the competing risk method. RESULTS: Out of 309 patients, 216 underwent supracoronary ascending aortic replacement and 93 had aortic root replacement. At 10 years, mortality was 33.8% after aortic root replacement and 35.2% after ascending aortic replacement (P = 0.806, adjusted hazard ratio 1.25, 95% confidence interval, 0.77-2.02), and the cumulative incidence of proximal aortic reoperation was 6.0% in the aortic root replacement group and 6.2% in the ascending aortic replacement group (P = 0.65; adjusted subdistributional hazard ratio 0.53, 95% confidence interval 0.15-1.89). Among 71 propensity score matched pairs, 10-year survival was 34.4% after aortic root replacement and 36.2% after ascending aortic replacement surgery (P = 0.70). Cumulative incidence of proximal aortic reoperation was 7.0% after aortic root replacement and 13.0% after ascending aortic replacement surgery (P = 0.22). Among 102 patients with complete imaging data [mean follow-up, 4.7 (3.2) years], the estimated growth rate of the aortic root diameter was 0.22 mm/year, that of its area 7.19 mm2/year and that of its perimeter 0.43 mm/year. CONCLUSIONS: When stringent selection criteria were used to determine the extent of proximal aortic reconstruction, aortic root replacement and ascending aortic replacement for type A aortic dissection achieved comparable clinical outcomes.

Differential Cognitive Functioning and Benefit From Surgery in Patients Undergoing Coronary Artery Bypass Grafting and Carotid Endarterectomy.

Background: Stenosing atherosclerosis in both coronary and carotid arteries can adversely affect cognition. Also their surgical treatments, coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA), are associated with cognitive changes, but the mechanisms of cognitive decline or improvement may not be the same. This study was designed to compare the cognitive profile and outcome in patients undergoing surgical treatment for coronary or carotid disease. Methods: A total of 100 CABG patients and 44 CEA patients were recruited in two previously reported studies. They were subjected to a comprehensive neuropsychological examination prior to surgery and in the acute (3-8 days) and stable (3 months) phase after operation. A group of 17 matched healthy controls were assessed with similar intervals. We used linear mixed models to compare cognitive trajectories within six functional domains between the CABG, CEA and control groups. Postoperative cognitive dysfunction (POCD) and improvement (POCI) were determined with the reliable change index method in comparison with healthy controls. Results: Before surgery, the CEA patients performed worse than CABG patients or healthy controls in the domains of executive functioning and processing speed. The CABG patients exhibited postoperative cognitive dysfunction more often than the CEA patients in most cognitive domains in the acute phase but had regained their performance in the stable phase. The CEA patients showed more marked postoperative improvement in executive functioning than the CABG group in the acute phase, but the difference did not reach significance in the stable phase. Conclusion: Our findings suggest that anterior cerebral dysfunction in CEA patients impairs preoperative cognition more severely than global brain dysfunction in CABG patients. However, CEA may have more beneficial effects on cognition than CABG, specifically in executive functions mainly operated by the prefrontal lobes. In addition, the results underline that POCD is a heterogeneous condition and dependent on type of revascularization surgery.

Heat shock attenuates VEGF expression in three-dimensional myoblast sheets deteriorating therapeutic efficacy in heart failure.

BACKGROUND: Myoblast sheet transplantation is a promising novel treatment for ischemic heart failure. The aim of this study was to test the hypothesis that heat shock (HS) pre-treatment affects the angiogenic properties of myoblast sheets in vivo and in vitro. MATERIAL/METHODS: We studied HS preconditioning of L6 myoblast sheets in relation to their apoptosis, proliferation, and vascular endothelial growth factor (VEGF)-associated responses under normoxia and under hypoxia in vitro. In vivo evaluation of their therapeutic effect was performed with 60 male Wistar rats divided into 3 groups (20 each): sole left anterior descending (LAD) ligation (control); LAD ligation and non-conditioned sheet transplantation (L6 No-Shock); and LAD ligation and L6-heat shock conditioned sheet transplantation (L6 Heat-Shock). Left ventricular function was evaluated by echocardiography after 3, 10, and 28 days. RESULTS: Expression of HSP70/72 was strongly induced 24 hours after HS, and thereafter it decreased notably during 72 hours in hypoxia. Under normal growth conditions, HSP70/72 expression remained stable. HS delayed apoptosis-associated caspase-3 expression during 24-hour hypoxia compared to non-treated controls. However, VEGF expression reduced significantly in the heat shock pretreated sheets. Ejection fraction of the L6-myoblast HS pre-treatment group (L6 Heat-Shock) decreased gradually during follow-up, in the same pattern as the controls. However, these functional parameters improved in the L6-myoblast normal sheet group (L6 No-Shock) at the tenth day and remained significantly better. CONCLUSIONS: HS protects myoblast sheets from hypoxia-associated apoptosis in vitro, but reduces VEGF expression of the sheet, leading to lower therapeutic effect in heart failure.

Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome.

Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes. Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell-cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery. Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.

Epicardial Transplantation of Autologous Cardiac Micrografts During Coronary Artery Bypass Surgery.

Background: Cardio-regenerative cell therapies offer additional biologic support to coronary artery bypass surgery (CABG) and are aimed at functionally repairing the myocardium that suffers from or is damaged by ischemia. This non-randomized open-label study assessed the safety and feasibility of epicardial transplantation of atrial appendage micrografts (AAMs) in patients undergoing CABG surgery. Methods: Twelve consecutive patients destined for CABG surgery were included in the study. Six patients received AAMs during their operation and six patients were CABG-operated without AAMs transplantation. Data from 30 elective CABG patients was collected for a center- and time-matched control group. The AAMs were processed during the operation from a biopsy collected from the right atrial appendage. They were delivered epicardially onto the infarct scar site identified in preoperative late gadolinium enhancement cardiac magnetic resonance imaging (CMRI). The primary outcome measures at the 6-month follow-up were (i) patient safety in terms of hemodynamic and cardiac function over time and (ii) feasibility of therapy administration in a clinical setting. Secondary outcome measures were left ventricular wall thickness, change in myocardial scar tissue volume, changes in left ventricular ejection fraction, plasma concentrations of N-terminal pro-B-type natriuretic peptide levels, NYHA class, number of days in hospital and changes in the quality of life. Results: Epicardial transplantation of AAMs was safe and feasible to be performed during CABG surgery. CMRI demonstrated an increase in viable cardiac tissue at the infarct site in patients receiving AAMs treatment. Conclusions and Relevance: Transplantation of AAMs shows good clinical applicability as performed during cardiac surgery, shows initial therapeutic effect on the myocardium and has the potential to serve as a delivery platform for cardiac gene therapies. Trial Registration:ClinicalTrials.gov, identifier: NCT02672163.

The Characteristics of Postoperative Mediastinitis During the Changing Phases of Cardiac Surgery.

BACKGROUND: Mediastinitis is a serious complication of open heart surgery associated with high mortality, considerable health care costs, and prolonged hospital stay. We examined characteristics and incidence of mediastinitis during 29 years when indications and patient material have been in a process of change. METHODS: This was a retrospective population-based study comprising all mediastinitis patients more than 16 years of age after open heart surgery between 1990 and 2018 from a population of 1.7 million. Patient records of 50 mediastinitis patients from 2004 to 2014 were reviewed and compared with 120 patients from 1990 to 1999. RESULTS: Annual mediastinitis rate varied 0% to 1.5% with a decreasing trend-from a level exceeding 1.2% to approximately 0.3%-over the study period. In 2004 to 2014 patients with mediastinitis were older, more often smokers, and more often had diabetes mellitus and renal insufficiency than in 1990 to 1999. No difference in length of hospital treatment, antibiotic prophylaxis or treatment, intensive care unit treatment, or mortality was observed between 1990 to 1999 and 2004 to 2014. Coronary artery bypass graft surgery became less common and valve replacement and hybrid operations more common among operations leading to mediastinitis. Staphylococcus aureus increased (from 25% to 56%, p = .005) whereas coagulase-negative staphylococci (46% to 23%, P < .001) and gram-negative bacteria (18% to 12%, P = .033) decreased as causative agents. Surgery for mediastinitis remained similar except introduction of vacuum-assisted closure treatment. CONCLUSIONS: The rate of mediastinitis decreased during these 29 years. No difference in 30-day mortality in mediastinitis was seen: 0.9% in 1990 to 1999 and 2% in 2004 to 2014.

Patient-Prosthesis Mismatch Worsens Long-Term Survival: Insights From the FinnValve Registry.

BACKGROUND: The impact of patient-prosthesis mismatch (PPM) on long-term outcome after surgical aortic valve replacement (SAVR) is controversial. We sought to investigate the incidence of PPM and its impact on survival and reinterventions in a Finnish nationwide cohort. METHODS: In the context of the nationwide FinnValve registry, we identified 4097 patients who underwent SAVR with a stented bioprosthesis with or without myocardial revascularization. The indexed effective orifice areas (EOAs) of surgical bioprostheses were calculated using literature-derived EOAs. PPM was graded as moderate (EOA 0.65-0.85 cm2/m2) or severe (EOA ≤0.65 cm2/m2). RESULTS: The incidence of PPM was 46.0%. PPM was moderate in 38.8% (n = 1579) patients and severe in 7.2% (n = 297) patients. Time-trend analysis showed that the proportion of PPM decreased significantly from 74% in 2009 to 18% in 2017 (P < .01). Severe PPM was associated with increased 5-year all-cause mortality (adjusted hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.07-2.76; P = .02). Severe PPM was not associated with an increased risk of repeat AVR (adjusted HR, 5.90; 95% CI, 0.95-36.5; P = .06). In a subanalysis of patients greater than or equal to 70 years of age, in comparison with no PPM, any PPM (adjusted HR, 1.23; 95% CI, 1.05-1.45; P = .01) and severe PPM (HR, 1.53; 95% CI, 1.17-2.00; P < 0.01) were associated with increased risk of 5-year mortality. CONCLUSIONS: Severe PPM after SAVR had a negative impact on survival. This study demonstrated that the effects of PPM should not be overlooked in elderly undergoing SAVR.

European registry of type A aortic dissection (ERTAAD) - rationale, design and definition criteria.

BACKGROUND: Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient's conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. METHODS: Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient's comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. DISCUSSION: The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073 .