Stroke prevention strategies for cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Stroke is a much-feared complication of cardiac surgery, but existing literature on preventive strategies is fragmented. Hence, a systematic review and meta-analysis of stroke prevention strategies for cardiac surgery was conducted. METHODS: An electronic literature search was conducted to retrieve randomized controlled trials (RCTs) investigating perioperative interventions for cardiac surgery, with stroke as an outcome. Random-effects meta-analyses were conducted to generate risk ratios (RRs), 95% confidence intervals (95% CI), and forest plots. Descriptive analysis and synthesis of literature was conducted for interventions not amenable to meta-analysis, focusing on risks of stroke, myocardial infarction and study-defined major adverse cardiovascular events (MACE). RESULTS: Fifty-six RCTs (61 894 patients) were retrieved. Many included trials were underpowered to detect differences in stroke risk. Among pharmacological therapies, only preoperative amiodarone was shown to reduce stroke risk in one trial. Concomitant left atrial appendage closure (LAAC) significantly reduced stroke risk (RR = 0.55, 95% CI = 0.36-0.84, P = 0.006) in patients with preoperative atrial fibrillation, and there was no difference in on-pump versus off-pump coronary artery bypass grafting (CABG) (RR = 0.94, 95% CI = 0.64-1.37, P = 0.735). Much controversy exists in literature on the timing of carotid endarterectomy relative to CABG in patients with severe carotid stenosis. The use of preoperative remote ischemic preconditioning was not found to reduce rates of stroke or MACE. CONCLUSION: This review presents a comprehensive synthesis of existing interventions for stroke prevention in cardiac surgery, and identifies gaps in research which may benefit from future, large-scale RCTs. LAAC should be considered to reduce stroke incidence in patients with preoperative atrial fibrillation.

Predicting late aortic complications after acute type A dissection surgery with volumetric measurements in a Singapore cohort.

Introduction: This study was conducted to evaluate the efficacy of postoperative computed tomography (CT) measurements of aortic lumen volumes in predicting aortic-related complications following acute type A aortic dissection (ATAAD) repair. Methods: We conducted a single-institution retrospective aortic volumetric analysis of patients after ascending aorta replacement performed during 2001-2015. The volumetric measurements of total lumen (total-L), true lumen (TL), false lumen (FL), as well as the TL:FL ratio from the first and second postoperative computer angiograms were obtained. A generalised structural equation model was created to analyse the predictive utility of TL:FL ratio. Results: One hundred and twenty-five patients underwent surgical intervention, of whom 97 patients were eventually discharged and analysed for postoperative complications. A total of 19 patients were included in the final analysis. Patients with late postoperative aortic complications had a significantly higher FL volume and total-L volume on the first (FL volume P = 0.041, total-L volume P = 0.05) and second (FL volume P = 0.01, total-L volume P = 0.007) postoperative scans. The odds of having aortic complications were raised by 1% with a 1 cm3 increase in total-L volume and by 2% with a 1 cm3 increase in FL volume. The TL:FL ratio was significantly lower in patients who developed complications. Conclusion: Postoperative CT volumetric measurements in patients who developed complications are characterised by a significant increase in the FL volume and total-L volume from the first postoperative scans. Patients with disproportionately expanded FL presenting with TL:FL ratios less than 1 were associated with aortic complications. Hence, the TL:FL ratio may be a reliable and useful parameter to monitor postoperative disease progression and to evaluate the risk of late complications in ATAAD patients.

Effects of antibiotic treatment and phagocyte infiltration on development of Pseudomonas aeruginosa biofilm-Insights from the application of a novel PF hydrogel model in vitro and in vivo.

Background and purpose: Bacterial biofilm infections are major health issues as the infections are highly tolerant to antibiotics and host immune defenses. Appropriate biofilm models are important to develop and improve to make progress in future biofilm research. Here, we investigated the ability of PF hydrogel material to facilitate the development and study of Pseudomonas aeruginosa biofilms in vitro and in vivo. Methods: Wild-type P. aeruginosa PAO1 bacteria were embedded in PF hydrogel situated in vitro or in vivo, and the following aspects were investigated: 1) biofilm development; 2) host immune response and its effect on the bacteria; and 3) efficacy of antibiotic treatment. Results: Microscopy demonstrated that P. aeruginosa developed typical biofilms inside the PF hydrogels in vitro and in mouse peritoneal cavities where the PF hydrogels were infiltrated excessively by polymorphonuclear leukocytes (PMNs). The bacteria remained at a level of ~106 colony-forming unit (CFU)/hydrogel for 7 days, indicating that the PMNs could not eradicate the biofilm bacteria. ß-Lactam or aminoglycoside mono treatment at 64× minimal inhibitory concentration (MIC) killed all bacteria in day 0 in vitro biofilms, but not in day 1 and older biofilms, even at a concentration of 256× MIC. Combination treatment with the antibiotics at 256× MIC completely killed the bacteria in day 1 in vitro biofilms, and combination treatment in most of the cases showed significantly better bactericidal effects than monotherapies. However, in the case of the established in vivo biofilms, the mono and combination antibiotic treatments did not efficiently kill the bacteria. Conclusion: Our results indicate that the bacteria formed typical biofilms in PF hydrogel in vitro and in vivo and that the biofilm bacteria were tolerant against antibiotics and host immunity. The PF hydrogel biofilm model is simple and easy to fabricate and highly reproducible with various application possibilities. We conclude that the PF hydrogel biofilm model is a new platform that will facilitate progress in future biofilm investigations, as well as studies of the efficacy of new potential medicine against biofilm infections.

Meta-Analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Narrowing.

Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) for patients with left main coronary artery disease (LMCAD) have reported conflicting results. We performed a systematic review up to May 23, 2021, and 1-stage reconstructed individual patient data meta-analysis (IPDMA) to compare outcomes between both groups. The primary outcome was 10-year all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, and unplanned revascularization at 5 years. We performed individual patient data meta-analysis using published Kaplan-Meier curves to provide individual data points in coordinates and numbers at risk were used to increase the calibration accuracy of the reconstructed data. Shared frailty model or, when proportionality assumptions were not met, a restricted mean survival time model were fitted to compare outcomes between treatment groups. Of 583 articles retrieved, 5 RCTs were included. A total of 4,595 patients from these 5 RCTs were randomly assigned to PCI (n = 2,297) or CABG (n = 2,298). The cumulative 10-year all-cause mortality after PCI and CABG was 12.0% versus 10.6%, respectively (hazard ratio [HR] 1.093, 95% confidence interval [CI] 0.925 to 1.292; p = 0.296). PCI conferred similar time-to-MI (restricted mean survival time ratio 1.006, 95% CI 0.992 to 1.021, p=0.391) and stroke (restricted mean survival time ratio 1.005, 95% CI 0.998 to 1.013, p = 0.133) at 5 years. Unplanned revascularization was more frequent after PCI than CABG (HR 1.807, 95% CI 1.524 to 2.144, p <0.001) at 5 years. This meta-analysis using reconstructed participant-level time-to-event data showed no statistically significant difference in cumulative 10-year all-cause mortality between PCI versus CABG in the treatment of LMCAD.

Sleep apnea and recurrent heart failure hospitalizations after coronary artery bypass grafting.

STUDY OBJECTIVES: Sleep apnea is prevalent in patients undergoing coronary artery bypass grafting (CABG). We investigated the relationship between sleep apnea and recurrent heart failure hospitalizations in patients undergoing nonurgent CABG. METHODS: Between November 2013 and December 2018, 1,007 patients completed a sleep study prior to CABG and were followed up until April 2020. Recurrent heart failure hospitalizations were analyzed by Poisson, negative binomial, Andersen-Gill, and joint frailty models, with partial and full adjustment for covariates. RESULTS: At an average follow-up of 3.3 years, the number of patients with 0, 1, or ≥ 2 heart failure hospitalizations were 908 (90.2%), 62 (6.2%), and 37 (3.7%), respectively. The total number of heart failure hospitalizations was 179, comprising 62 (35%) first and 117 (65%) repeat events. The numbers of heart failure hospitalizations for the sleep apnea (n = 513, 50.9%) and nonsleep apnea groups were 127 and 52, respectively. Negative binomial regression demonstrated that sleep apnea was associated with recurrent heart failure hospitalizations (fully adjusted rate ratio, 1.71; 95% confidence interval [CI], 1.12-2.62; P = .013). Similar results were found in Poisson (1.63; 95% CI, 1.15-2.31; P = .006), Andersen-Gill (1.66; 95% CI, 1.01-2.75; P = .047), and joint frailty models (1.72; 95% CI, 1.00-3.01; P = .056). CONCLUSIONS: In patients after CABG, repeat events accounted for two-thirds of heart failure hospitalizations. Sleep apnea was independently associated with recurrent heart failure hospitalizations. CITATION: Teo YH, Tam WT, Koo C-Y, et al. Sleep apnea and recurrent heart failure hospitalizations after coronary artery bypass grafting. J Clin Sleep Med. 2021;17(12):2399-2407.

Minimally invasive tricuspid valve surgery and concomitant MAZE procedure with closure of LA appendage through an ASD.

Utilization of the ASD as a gateway to reach the left heart in tricuspid valve surgery may facilitate the use of a mini right thoracotomy and single atriotomy approach, avoiding the need for bi-atrial incisions and/or median sternotomy.

Sleep apnea and diabetes mellitus are independently associated with cardiovascular events and hospitalization for heart failure after coronary artery bypass grafting.

The relative and combined effects of sleep apnea with diabetes mellitus (DM) on cardiovascular outcomes in patients undergoing coronary artery bypass grafting (CABG) remain unknown. In this secondary analysis of data from the SABOT study, 1007 patients were reclassified into four groups based on their sleep apnea and DM statuses, yielding 295, 218, 278, and 216 patients in the sleep apnea (+) DM (+), sleep apnea (+) DM (-), sleep apnea (-) DM (+), and sleep apnea (-) DM (-) groups, respectively. After a mean follow-up period of 2.1 years, the crude incidence of major adverse cardiac and cerebrovascular event was 18% in the sleep apnea (+) DM (+), 11% in the sleep apnea (+) DM (-), 13% in the sleep apnea (-) DM (+), and 5% in the sleep apnea (-) DM (-) groups. Using sleep apnea (-) DM (-) as the reference group, a Cox regression analysis indicated that sleep apnea (+) and DM (+) independently predicted MACCEs (adjusted hazard ratio, 3.2; 95% confidence interval, 1.7-6.2; p = 0.005) and hospitalization for heart failure (adjusted hazard ratio, 12.6; 95% confidence interval, 3.0-52.3; p < 0.001). Sleep apnea and DM have independent effects on the prognosis of patients undergoing CABG.Clinical trial registration: ClinicalTrials.gov identification no. NCT02701504.

Functional reservoir microcapsules generated via microfluidic fabrication for long-term cardiovascular therapeutics.

Cardiovascular disease is a chronic disease that leads to impaired cardiac function and requires long-term management to control its progression. Despite the importance of hydrogels for therapeutic applications, a contradiction between the size of a hydrogel and the amount of loaded drug has been encountered when using conventional fabrication methods. In this study, biocompatible reservoir microcapsules (diameter ∼100 µm) with a large liquid core and polymeric shell were fabricated via a one-step phase separation of poly(ethylene glycol)diacrylate (PEGDA) and dextran within pre-gel droplets through microfluidics. By controlling the process of phase separation, high drug-loading efficiency (∼80%) for long-term release (30 days) of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was achieved. Drug molecules were dispersed within the liquid core at a concentration above saturation solubility for sustained delivery via regulation of the shells. Effective therapeutic enhancement of human umbilical vein endothelial cell (HUVEC) and umbilical artery smooth muscle cell (SMC) proliferation and tube formation in vitro promoted rapid cell proliferation and increased the number of migrated cells by ∼1.7 times. Moreover, in vivo blood vessel regeneration for cardiovascular control induced by sustained dual-drug (VEGF and PDGF) delivery to the rat heart was achieved, showing the effectiveness of long-term protein delivery in improving cardiac function and significantly reducing ventricular wall thickness and fibrosis of the infarct region. The ratio of heart tissue scarring was reduced to 11.2% after microcapsule treatment compared with 21.4% after saline treatment in the rat model. By using these reservoir microcapsules, similar sustained delivery of proteins, mRNAs and biologic drugs could be developed for the treatment of a range of long-term chronic diseases and regenerative medicine.

Sleep apnoea and cardiovascular outcomes after coronary artery bypass grafting.

OBJECTIVE: Patients with advanced coronary artery disease are referred for coronary artery bypass grafting (CABG) and it remains unknown if sleep apnoea is a risk marker. We evaluated the association between sleep apnoea and major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing non-emergent CABG. METHODS: This was a prospective cohort study conducted between November 2013 and December 2018. Patients from four public hospitals referred to a tertiary cardiac centre for non-emergent CABG were recruited for an overnight sleep study using a wrist-worn Watch-PAT 200 device prior to CABG. RESULTS: Among the 1007 patients who completed the study, sleep apnoea (defined as apnoea-hypopnoea index ≥15 events per hour) was diagnosed in 513 patients (50.9%). Over a mean follow-up period of 2.1 years, 124 patients experienced the four-component MACCE (2-year cumulative incidence estimate, 11.3%). There was a total of 33 cardiac deaths (2.5%), 42 non-fatal myocardial infarctions (3.7%), 50 non-fatal strokes (4.9%) and 36 unplanned revascularisations (3.2%). The crude incidence of MACCE was higher in the sleep apnoea group than the non-sleep apnoea group (2-year estimate, 14.7% vs 7.8%; p=0.002). Sleep apnoea predicted the incidence of MACCE in unadjusted Cox regression analysis (HR 1.69; 95% CI 1.18 to 2.43), and remained statistically significant (adjusted HR 1.57; 95% CI 1.09 to 2.25), after adjustment for age, sex, body mass index, left ventricular ejection fraction, diabetes mellitus, hypertension, chronic kidney disease and excessive daytime sleepiness. CONCLUSION: Sleep apnoea is independently associated with increased MACCE in patients undergoing CABG. TRIAL REGISTRATION NUMBER: NCT02701504.

Meta-analysis of the benefit of beta-blockers for the reduction of isolated atrial fibrillation incidence after cardiac surgery.

Objectives: Postoperative atrial fibrillation (POAF) is a common problem of cardiac surgery. Beta-blockers are recognized as effective prophylactic agents available for POAF management. To better understand its effect on isolated atrial fibrillation after cardiac surgery, a meta-analysis was conducted. Methods: Randomized controlled trials (RCTs) were searched and filtered by comparing the efficacy of beta-blockers and control users in isolated POAF for cardiac surgery. Seventeen RCTs were identified and analyzed by typical meta-analysis methods. The search was performed from inception to May 31, 2020. Subgroup analyses were conducted for type of surgery and beta-blocker, starting time and route of administration of beta-blocker, and dosage of intravenous landiolol hydrochloride. Results: Beta-blockers were effective in reducing isolated POAF risk (risk ratio [RR], 0.52 [0.41, 0.66], P = .31, I2 = 12%). In subgroup analyses, beta-blocker administration during postoperative period (RR, 0.43 [0.29, 0.62], P = .84, I2 = 0%) and on-pump coronary artery bypass graft (RR, 0.34 [0.04, 3.15], P = .56, I2 = 0%) had lowest risk of isolated POAF incidence. Intravenous landiolol hydrochloride at 2 µg/kg/min also had low risk of isolated POAF occurrence. Conclusions: Beta-blocker treatment helps to reduce isolated atrial fibrillation incidence after cardiac surgery. Our subgroup analyses also reveal postoperative beta-blocker administration after on-pump coronary artery bypass graft surgery is most effective in reducing isolated POAF risk. Intravenous landiolol hydrochloride at a dosage of 2 µg/kg/min has also displayed favorable results. Further trials may be required to explore these factors.

A Novel Minimally Invasive Technique of Temporary Caval Occlusion for Right Heart Surgery.

Right heart surgery is challenging in the minimally invasive cardiac surgery setting, particularly in terms of caval isolation procedures in patients with enlarged and pressurized atria. We describe a novel minimally invasive caval occlusion technique with the use of a balloon catheter designed for temporary large vessel occlusion. A patient with a large ostium secundum atrial septal defect and significant shunt flow underwent a successful minimally invasive closure of the pathological connection between atria with a bovine pericardial patch. The utilized occlusion technique provided excellent visibility of the surgical site and may facilitate minimally invasive procedures in various clinical scenarios.

Left atrial appendage mass.

Left atrial (LA) masses are known to be associated with peripheral embolization. Accurate identification of etiology is crucial because treatment strategies may differ. We present the case of a young woman, who was initially diagnosed with a LA thrombus and anticoagulated. The diagnosis was revised to a primary cardiac tumor after review of the echocardiographic findings. Surgical excision revealed an atrial myxoma in an unusual location.

Global Unmet Needs in Cardiac Surgery.

More than 6 billion people live outside industrialized countries and have insufficient access to cardiac surgery. Given the recently confirmed high prevailing mortality for rheumatic heart disease in many of these countries together with increasing numbers of patients needing interventions for lifestyle diseases due to an accelerating epidemiological transition, a significant need for cardiac surgery could be assumed. Yet, need estimates were largely based on extrapolated screening studies while true service levels remained unknown. A multi-author effort representing 16 high-, middle-, and low-income countries was undertaken to narrow the need assessment for cardiac surgery including rheumatic and lifestyle cardiac diseases as well as congenital heart disease on the basis of existing data deduction. Actual levels of cardiac surgery were determined in each of these countries on the basis of questionnaires, national databases, or annual reports of national societies. Need estimates range from 200 operations per million in low-income countries that are nonendemic for rheumatic heart disease to >1,000 operations per million in high-income countries representing the end of the epidemiological transition. Actually provided levels of cardiac surgery range from 0.5 per million in the assessed low- and lower-middle income countries (average 107 ± 113 per million; representing a population of 1.6 billion) to 500 in the upper-middle-income countries (average 270 ± 163 per million representing a population of 1.9 billion). By combining need estimates with the assessment of de facto provided levels of cardiac surgery, it emerged that a significant degree of underdelivery of often lifesaving open heart surgery does not only prevail in low-income countries but is also disturbingly high in middle-income countries.

The Effect of Scaffold Modulus on the Morphology and Remodeling of Fetal Mesenchymal Stem Cells.

Hydrogel materials have been successfully used as matrices to explore the role of biophysical and biochemical stimuli in directing stem cell behavior. Here, we present our findings on the role of modulus in guiding bone marrow fetal mesenchymal stem cell (BMfMSC) fate determination using semi-synthetic hydrogels made from PEG-fibrinogen (PF). The BMfMSCs were cultivated in the PF for up to 2 weeks to study the influence of matrix modulus (i.e., cross-linking density of the PF) on BMfMSC survival, morphology and integrin expression. Both two-dimensional (2D) and three-dimensional (3D) culture conditions were employed to examine the BMfMSCs as single cells or as cell spheroids. The hydrogel modulus affected the rate of BMfMSC metabolic activity, the integrin expression levels and the cell morphology, both as single cells and as spheroids. The cell seeding density was also found to be an important parameter of the system in that high densities were favorable in facilitating more cell-to-cell contacts that favored higher metabolic activity. Our findings provide important insight about design of a hydrogel scaffold that can be used to optimize the biological response of BMfMSCs for various tissue engineering applications.

Dual delivery of VEGF and ANG-1 in ischemic hearts using an injectable hydrogel.

Acute myocardial infarction (MI) caused by ischemia is the most common cause of cardiac dysfunction. While growth factor therapy is promising, the retention in the highly vascularized myocardium is limited and prevents sustained activation needed for adequate cellular responses. Here, we demonstrated the use of polyethylene glycol-fibrinogen (PF) hydrogels for sustained dual delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) to enhance myocardial repair and function. VEGF and ANG-1 were incorporated in PF hydrogels and their in vitro characteristics were studied. Acute MI was generated in a rodent model with rats randomly assigned to 4 groups; sham, saline, PF and PF-VEGF-ANG1 (n=10 each group). Saline or hydrogel was injected in infarct and peri-infarct areas of the myocardium. After 4weeks, myocardial function was assessed using echocardiography. Tissue samples were harvested for Hematoxylin and Eosin, Masson Trichrome and capillary staining to assess the extent of fibrotic scar and arteriogenesis. Both VEGF and ANG-1 were released in a sustained and controlled manner over 30days. PF-VEGF-ANG1 treated animals showed the best improvement in cardiac function, highest degree of cardiac muscle preservation, and arteriogenesis. This study demonstrates that PF hydrogels can simultaneously provide mechanical support to attenuate adverse myocardial remodelling, and a pro-angiogenic benefit from the sustained VEGF and ANG1 delivery that culminates in a restorative effect following MI. The utility of this synergistic, biomaterial-based growth factor delivery may have clinical implications in the prevention of post-MI cardiac dysfunction. STATEMENT OF SIGNIFICANCE: Acute myocardial infarction (MI) caused by ischemia is the most common cause of cardiac dysfunction. Here, we demonstrated the use of polyethylene glycol-fibrinogen (PF) hydrogels for sustained dual delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) to enhance myocardial repair and function. Treated animals showed the best improvement in cardiac function, highest degree of cardiac muscle preservation, and arteriogenesis. This study demonstrates that PF hydrogels can simultaneously provide mechanical support to attenuate adverse myocardial remodelling, and a pro-angiogenic benefit from the sustained VEGF and ANG1 delivery that culminates in a restorative effect following MI.

Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction.

Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium. Biomaterials comprising such scaffolds should mimic the cardiac tissue in terms of composition, structure, mechanical support, and most importantly, bioactivity. Nonetheless, natural biomaterial-based gels may suffer from limited mechanical strength, which often fail to provide the long-term support required by the heart for contraction and relaxation. Here we present newly-developed injectable scaffolds, which are based on solubilized decellularized porcine cardiac extracellular matrix (pcECM) cross-linked with genipin alone or engineered with different amounts of chitosan to better control the gel's mechanical properties while still leveraging the ECM biological activity. We demonstrate that these new biohybrid materials are naturally remodeled by mesenchymal stem cells, while supporting high viabilities and affecting cell morphology and organization. They exhibit neither in vitro nor in vivo immunogenicity. Most importantly, their application in treating acute and long term chronic MI in rat models clearly demonstrates the significant therapeutic potential of these gels in the long-term (12weeks post MI). The pcECM-based gels enable not only preservation, but also improvement in cardiac function eight weeks post treatment, as measured using echocardiography as well as hemodynamics. Infiltration of progenitor cells into the gels highlights the possible biological remodeling properties of the ECM-based platform. STATEMENT OF SIGNIFICANCE: This work describes the development of new injectable scaffolds for cardiac tissue regeneration that are based on solubilized porcine cardiac extracellular matrix (ECM), combined with natural biomaterials: genipin, and chitosan. The design of such scaffolds aims at leveraging the natural bioactivity and unique structure of cardiac ECM, while overcoming its limited mechanical strength, which may fail to provide the long-term support required for heart contraction and relaxation. Here, we present a biocompatible gel-platform with custom-tailored mechanical properties that significantly improve cardiac function when injected into rat hearts following acute and chronic myocardial infarction. We clearly demonstrate the substantial therapeutic potential of these scaffolds, which not only preserved heart functions but also alleviated MI damage, even after the formation of a mature scar tissue.

Natural myocardial ECM patch drives cardiac progenitor based restoration even after scarring.

OBJECTIVE: To evaluate the regenerative capacity of non-supplemented and bioactive patches made of decellularized porcine cardiac extracellular matrix (pcECM) and characterize the biological key factors involved in possible cardiac function (CF) restoration following acute and 8weeks chronic MI. BACKGROUND: pcECM is a key natural biomaterial that can affect cardiac regeneration following myocardial infarction (MI), through mechanisms, which are still not clearly understood. METHODS: Wistar rats underwent MI and received pcECM patch (pcECM-P) treatment in either acute or chronic inflammatory phases. Treated, sham operated (no MI), and control (MI without treatment) animals, were compared through echocardiography, hemodynamics, pathological evaluation and analyses of various mRNA and protein level markers. RESULTS: Our results show that in both acute and long-term chronic MI models, pcECM promotes significant cardiac function improvement, which is correlated to progenitor (GATA4(+), c-kit(+)) and myocyte (MYLC(+), TRPI(+)) recruitment. Interestingly, recruited progenitors, isolated using laser capture microdissection (LCM), expressed both early and late cardiomyocyte (CM) differentiation markers, suggesting differentiation towards the CM lineage. Recruited CM-like cells organized in a partially striated and immature muscle fiber arrangement that presented connexin43 -a crucial mediator of cardiac electrical conductivity. Concomitantly, pcECM was rapidly vascularized, and induced a constructive remodeling process as indicated by increased M2/M1 macrophage phenotypic ratio and pathological evaluation. CONCLUSIONS: Acellular pcECM patch implants alone, i.e., without added biologics, are bioactive, and exert potent efficacy, stimulating biological regenerative processes that cooperatively lead to a cardiac progenitor-based restoration of function, even after scar tissue had already formed. STATEMENT OF SIGNIFICANCE: MI ('heart attack') remains the leading cause of heart failure and death in developed-countries. Restoration of cardiac function requires active turnover of damaged heart contracting cells (CM), however, CM endogenous regeneration is not efficient and is a matter of controversy. We show that a bioactive biomaterial alone-decellularized heart tissue (pcECM)-without added cells or growth factors, can elicit a complex regenerative response even after irreversible scarring. The pcECM patch induces macrophage polarization towards constructive remodeling and cardiomyocyte progenitor cell (GATA4(+), c-kit(+)) recruitment (evidenced at both mRNA and protein levels) resulting in de novo immature striated-like muscle patterns (MLC(+), TrpI(+), connexin43(+)). We, therefore, suggest this bioactive pcECM can model cardiac regeneration, and serve as a candidate for fast-track clinical application.

A Score for Predicting Acute Kidney Injury After Coronary Artery Bypass Graft Surgery in an Asian Population.

OBJECTIVE: To develop a scoring system to predict acute kidney injury in Asian patients after coronary artery bypass grafting. DESIGN: A retrospective analysis of data collected in an institutional cardiac database. SETTING: A tertiary academic hospital in a large metropolitan city. PARTICIPANTS: The study comprised 954 patients with coronary artery disease. INTERVENTIONS: All patients underwent coronary artery bypass surgery with cardiopulmonary bypass but did not undergo any other concomitant procedures. MEASUREMENTS AND MAIN RESULTS: The main outcome measured was acute kidney injury as defined by the Acute Kidney Injury Network criteria. The following 6 clinical variables were independent predictors of kidney injury: age>60 years, diabetes requiring insulin, estimated glomerular filtration rate<60 mL/min/1.73 m(2), ejection fraction<40%, cardiopulmonary bypass time>140 minutes, and aortic cross-clamp time>100 minutes. These variables were used to develop the Singapore Acute Kidney Injury score. CONCLUSION: The Singapore Acute Kidney Injury score is a simple way to predict, at the time of admission to the intensive care unit, an Asian patient's risk of developing acute kidney injury after coronary artery bypass surgery.