Interleukin-33/ST2 axis involvement in atrial remodeling and arrhythmogenesis.

Interleukin (IL)-33, a cytokine involved in immune responses, can activate its receptor, suppression of tumorigenicity 2 (ST2), is elevated during atrial fibrillation (AF). However, the role of IL-33/ST2 signaling in atrial arrhythmia is unclear. This study explored the pathological effects of the IL-33/ST2 axis on atrial remodeling and arrhythmogenesis. Patch clamping, confocal microscopy, and Western blotting were used to analyze the electrical characteristics of and protein activity in atrial myocytes (HL-1) treated with recombinant IL-33 protein and/or ST2-neutralizing antibodies for 48 hrs. Telemetric electrocardiographic recordings, Masson's trichrome staining, and immunohistochemistry staining of the atrium were performed in mice receiving tail vein injections with nonspecific immunoglobulin (control), IL-33, and IL-33 combined with anti-ST2 antibody for 2 weeks. IL-33-treated HL-1 cells had a reduced action potential duration, lower L-type Ca2+ current, greater sarcoplasmic reticulum (SR) Ca2+ content, increased Na+/Ca2+ exchanger (NCX) current, elevation of K+ currents, and increased intracellular calcium transient. IL-33-treated HL-1 myocytes had greater activation of the calcium-calmodulin-dependent protein kinase II (CaMKII)/ryanodine receptor 2 (RyR2) axis and nuclear factor kappa B (NF-κB) / NLR family pyrin domain containing 3 (NLRP3) signaling than did control cells. IL-33 treated cells also had greater expression of Nav1.5, Kv1.5, NCX, and NLRP3 than did control cells. Pretreatment with neutralizing anti-ST2 antibody attenuated IL-33-mediated activation of CaMKII/RyR2 and NF-κB/NLRP3 signaling. IL-33-injected mice had more atrial ectopic beats and increased AF episodes, greater atrial fibrosis, and elevation of NF-κB/NLRP3 signaling than did controls or mice treated with IL-33 combined with anti-ST2 antibody. Thus, IL-33 recombinant protein treatment promotes atrial remodeling through ST2 signaling. Blocking the IL-33/ST2 axis might be an innovative therapeutic approach for patients with atrial arrhythmia and elevated serum IL-33.

Mechanical or biological heart valve for dialysis-dependent patients? A meta-analysis.

OBJECTIVE: The optimal selection of prosthetic heart valve for dialysis-dependent patients remains controversial. We investigated the comparative effectiveness and safety of mechanical prosthesis (MP) and bioprosthesis (BP) for these patients. METHODS: After the systematic review, we included studies that involved patients on dialysis undergoing aortic valve replacement or mitral valve replacement (MVR) and reported comparative outcomes of MP and BP. Meta-analysis was performed using random-effects model. We conducted a subgroup analysis based on the valve position and postoperative international normalized ratio (INR), which was extracted from either tables or methods of each study. A meta-regression was used to examine the effects of study-level covariates. RESULTS: We included 24 retrospective studies without randomized-controlled trials, involving 10,164 participants (MP = 6934, BP = 3230). Patients undergoing aortic valve replacement with MP exhibited a better long-term survival effectiveness (hazard ratio, 0.64; 95% confidence interval [CI], 0.47-0.86). Conversely, studies including MVR demonstrated little difference in survival (hazard ratio, 0.90; 95% CI, 0.73-1.12). A meta-regression revealed that age had little effect on long-term survival difference between MP and BP (ß = -0.0135, P = .433). MP had a significantly greater bleeding risk than did BP when INR was above 2.5 (incidence rate ratio, 10.58; 95% CI, 2.02-55.41). However, when INR was below 2.5, bleeding events were comparable (incidence rate ratio, 1.73; 95% CI, 0.78-3.82). The structural valve deterioration rate was significantly lower in MP (risk ratio, 0.24; 95% CI, 0.14-0.44). CONCLUSIONS: MP is a reasonable choice for dialysis-dependent patients without additional thromboembolic risk requiring aortic valve replacement, for its better long-term survival, durability, and noninferior bleeding risk compared with BP. Conversely, BP might be an appropriate selection for patients with MVR, given its similar survival rate and lower bleeding risk. Although our meta-regression demonstrates little influence of age on long-term survival difference between MP and BP, further studies stratifying patients based on age cut-off are mandatory.

The Prediction Model of Medical Expenditure Appling Machine Learning Algorithm in CABG Patients.

Most patients face expensive healthcare management after coronary artery bypass grafting (CABG) surgery, which brings a substantial financial burden to the government. The National Health Insurance Research Database (NHIRD) is a complete database containing over 99% of individuals' medical information in Taiwan. Our research used the latest data that selected patients who accepted their first CABG surgery between January 2014 and December 2017 (n = 12,945) to predict which factors will affect medical expenses, and built the prediction model using different machine learning algorithms. After analysis, our result showed that the surgical expenditure (X4) and 1-year medical expenditure before the CABG operation (X14), and the number of hemodialysis (X15), were the key factors affecting the 1-year medical expenses of CABG patients after discharge. Furthermore, the XGBoost and SVR methods are both the best predictive models. Thus, our research suggests enhancing the healthcare management for patients with kidney-related diseases to avoid costly complications. We provide helpful information for medical management, which may decrease health insurance burdens in the future.

Machine-Learning Techniques for Feature Selection and Prediction of Mortality in Elderly CABG Patients.

Coronary artery bypass surgery grafting (CABG) is a commonly efficient treatment for coronary artery disease patients. Even if we know the underlying disease, and advancing age is related to survival, there is no research using the one year before surgery and operation-associated factors as predicting elements. This research used different machine-learning methods to select the features and predict older adults' survival (more than 65 years old). This nationwide population-based cohort study used the National Health Insurance Research Database (NHIRD), the largest and most complete dataset in Taiwan. We extracted the data of older patients who had received their first CABG surgery criteria between January 2008 and December 2009 (n = 3728), and we used five different machine-learning methods to select the features and predict survival rates. The results show that, without variable selection, XGBoost had the best predictive ability. Upon selecting XGBoost and adding the CHA2DS score, acute pancreatitis, and acute kidney failure for further predictive analysis, MARS had the best prediction performance, and it only needed 10 variables. This study's advantages are that it is innovative and useful for clinical decision making, and machine learning could achieve better prediction with fewer variables. If we could predict patients' survival risk before a CABG operation, early prevention and disease management would be possible.

Vascular endothelial growth factor on Runt-related transcript factor-2 in aortic valve cells.

BACKGROUND: Calcific aortic valve disease is associated with ageing and high mortality. However, no effective pharmacological treatment has been developed. Vascular endothelial growth factor (VEGF) and its receptor are overexpressed in the calcified aortic valve tissue. However, the role of VEGF in calcific aortic valve disease pathogenesis and its underlying mechanisms remain unclear. MATERIALS AND METHODS: Runt-related transcription factor 2 expression and calcium-related signalling were investigated in porcine valvular interstitial cells with or without human VEGF-A recombinant protein (VEGF165 , 1-100 ng/mL) treatment and/or calmodulin-dependent kinase II (CaMKII) inhibitor (KN93, 10 µmol/L) and inositol triphosphate receptor inhibitor (2-aminoethyldiphenyl borate, 30 µmol/L) for 5 days. RESULTS: VEGF165 -treated cells had higher Runt-related transcription factor 2 expression and CaMKII/ adenosine 3',5'-monophosphate response element-binding protein (CREB) signalling activation than did control cells. KN93 reduced Runt-related transcription factor 2 expression and CREB phosphorylation in VEGF165 -treated cells. The 2-aminoethyldiphenyl borate also reduced Runt-related transcription factor 2 expression in VICs treated with VEGF165 . CONCLUSION: VEGF upregulated Runt-related transcription factor 2 expression in VICs by activating the IP3R/CaMKII/CREB signalling pathway.

Evolution of pulmonary valve reconstruction with focused review of expanded polytetrafluoroethylene handmade valves.

OBJECTIVES: Many surgeons develop unique techniques for unmet needs for right ventricular outflow reconstruction to resolve pulmonary regurgitation after corrective surgery for congenital heart diseases. Expanded polytetrafluoroethylene (ePTFE) stands out as a reliable synthetic material, and clinical results with handmade ePTFE valves have been promising. This review focuses on the historical evolution of the use of ePTFE in pulmonary valve replacement and in the techniques for pioneering the translation of the handmade ePTFE trileaflet design for the transcatheter approach. METHODS: We searched for and reviewed publications from 1990 to 2020 in the Pubmed database. Nineteen clinical studies from 2005 to 2019 that focused on ePTFE-based valves were summarized. The evolution of the ePTFE-based valve over 3 decades and recent relevant in vitro studies were investigated. RESULTS: The average freedom from reintervention or surgery in the recorded ePTFE-based valve population was 90.2% at 5 years, and the survival rate was 96.7% at 3 years. CONCLUSIONS: Non-inferior clinical results of this ePTFE handmade valve were revealed compared to allograft or xenograft options for pulmonary valve replacement. Future investigations on transferring ePTFE trileaflet design to transcatheter devices should be considered.

Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis.

Cardiac surgery is complicated with atrial fibrillation (AF). Histone deacetylase (HDAC) inhibition reduces AF occurrence. In pericarditis, HDAC inhibition may modulate AF trigger and substrate. We recorded electrocardiograms in control and pericardiotomic (op) rabbits without and with an intraperitoneal injection of MPT0E014 (HDAC inhibitor). Conventional microelectrodes recorded action potentials (APs) in pulmonary veins (PVs), the right and left atrium (LA). Masson's trichrome was used to identify collagen fibers in PVs and the LA. Electrocardiograms showed frequent atrial premature contractions in op rabbits, but not in the other 3 groups. The beating rates in PVs and opPVs were decreased by MPT0E014 treatment. Spontaneous burst firings occurred in opPVs (36.4%), but not in control PVs. H2O2 induced greater burst firings in opPVs (72.7%) than in control PVs (11.1%), MPT0E014-treated PVs (16.7%), and MPT0E014-treated opPVs (12.5%). The AP duration at a repolarization extent of 90% (APD90) was shorter in the opLA than that in the control LA. In the presence of isoproterenol (1 µM), rapid atrial pacing (RAP, 20 Hz) induced a higher incidence of burst firings in the opLA (90%) than in the other groups. In contrast, acetylcholine (5 mM) and RAP induced a lower incidence of burst firing in the MPT0E014-treated LA (33.3%) than in the other groups. Fibrosis prevailed in opPVs and the opLA compared to the respective control PVs and LA, which was attenuated in those that received MPT0E014. In conclusion, a pericardiotomy increased fibrosis and arrhythmogenesis in PVs and the LA, which were prevented by HDAC inhibition.

Activated p300 acetyltransferase activity modulates aortic valvular calcification with osteogenic transdifferentiation and downregulation of Klotho.

BACKGROUND: The calcific aortic valve (AV) disease is a common disease with the unclear mechanism, and optimal pharmacological treatment remains unavailable. Epigenetic modulation by histone acetyltransferase (HAT) plays a critical role in osteogenic transdifferentiation and atherosclerosis. The purposes of this study were to investigate whether HAT contributes to the pathophysiology of AV calcification and assess the therapeutic potential of HAT inhibition. METHODS: Porcine valvular interstitial cells (VICs) were treated with osteogenic medium (10ng/mL of tumor necrosis factor-α and 4mmol/L of high phosphate) for 7days. We analyzed the RNA and protein expression of myofibroblastic (α-SMA, vimentin, collagen 1A1, collagen 3, Egr-1, MMP2, MMP9) and osteoblastic markers (osteocalcin and alkaline phosphatase) in VICs, and studied the effects of a p300 inhibitor (C646, 10µmol/L) on calcification (Alizarin Red S staining), osteogenesis, HAT activity, the mitogen-activated protein kinase (MAPK) and Akt pathway, and Klotho expression on VICs. RESULTS: Osteogenic medium treated VICs had higher expressions of osteocalcin, alkaline phosphatase and acetylated lysine-9 of histone H3 (ac-H3K9) than control cells. C646 attenuated osteogenesis of VICs with simultaneous inhibition of the HAT activity of p300. There was neither significant increase of p300 protein nor p300 transcript during the osteogenesis process. Additionally, osteogenic medium treated VICs decreased the expression of Klotho, which is attenuated by C646. CONCLUSIONS: Activated HAT activity of p300 modulates AV calcification through osteogenic transdifferentiation of VICs with Klotho modulation. P300 inhibition is a potential therapeutic target for AV calcification.

Tetrandrine increased the survival rate of mice with lipopolysaccharide-induced endotoxemia.

BACKGROUND: Endotoxemia usually causes significant morbidity and mortality, and treatment of endotoxemia is often ineffective. The effects of tetrandrine (a bisbenzylisoquinoline alkaloid) on lipopolysaccharide (LPS)-induced endotoxemia were investigated in mice. METHODS: The peritoneal macrophages were stimulated with LPS and treated with or without tetrandrine. The amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 secreted by peritoneal macrophages were measured by enzyme-linked immunosorbent assay. Mice were intraperitoneally injected with LPS to induce endotoxemia and were treated or not treated with oral gavage with 150 mg/kg tetrandrine 1 hour before or after LPS injection. The survival rate of the mice was determined after they were treated with various regiments. The amounts of TNF-alpha, IL-1beta, IL-6, and IL-10 in the serum of the mice were measured by enzyme-linked immunosorbent assay, and the high mobility group box 1 (HMGB1) concentration was studied by Western blot analysis. RESULTS: Tetrandrine suppressed the LPS-induced increase of TNF-alpha, IL-1beta, and HMGB1 secretion by peritoneal macrophages but did not affect the IL-6 and IL-10 concentrations. The animals treated with tetrandrine either 1 hour before or after LPS injection had a 100% survival rate, which was significantly higher than that of the control group (40%) (p = 0.005). The LPS-induced increase in serum TNF-alpha, IL-1beta, and HMGB1 concentrations was reduced by tetrandrine treatment administered either 1 hour before or after LPS injection (p < 0.0001). In contrast, tetrandrine prolonged the LPS-induced elevation in serum IL-10 concentrations only mildly changed the serum IL-6 concentrations. CONCLUSIONS: Tetrandrine treatment either 1 hour before or 1 hour after LPS injection reduced the mortality rate of the mice with LPS-induced endotoxemia. The effects of tetrandrine on LPS-induced endotoxemia might be related to the suppression of TNF-alpha, IL-1beta, and HMGB1 concentrations.

Innominate artery cannulation for aortic surgery.

When disease involving the ascending aorta or aortic arch precludes ascending aortic cannulation, axillary artery cannulation is used for cardiopulmonary bypass. An additional incision and the relatively small caliber of the axillary artery are the drawbacks of this approach. Innominate artery cannulation using the same sternotomy wound is a simple and effective alternative.

Spiral saphenous vein graft for portal vein reconstruction in pancreatic cancer surgery.

The curative strategy for most pancreatic cancer is surgical resection. Extensive resection with lymph node dissection is the key to providing long-term survival. However, early diagnosis of pancreatic cancer is not always possible (ie, resectability is limited). One reason for such a nonresectable condition is vascular invasion or encasement. Portal vein involvement has been a contraindication for pancreatic cancer surgery for most general surgeons. Combining oncologic and vascular surgeons in the procedure has been a good solution. A multidisciplinary approach that includes general and vascular surgeons is appropriate in selected patients requiring vascular reconstruction at the time of pancreatectomy. The objective of this paper is to report a case in which spiral saphenous vein was used for portal vein reconstruction during pancreatic cancer resection.

Less invasive mitral valve surgery via right minithoracotomy.

BACKGROUND/PURPOSE: Current trends in cardiac surgical intervention are moving toward less invasiveness, with smaller wound or sternum-sparing, less pump time or off-pump, and beating rather than arrested heart. Data on the efficacy and safety of these newer less invasive techniques, as well as their cosmetic results, are limited. This study analyzed the results of a sternum-sparing mitral valve operation. METHODS: Thirty patients with mitral valve diseases, including 20 who underwent mitral valve repair and 10 mitral valve replacement, were enrolled. Cardiopulmonary bypass was established via femoral cannulation, and blood cardioplegic arrest was induced by using a percutaneous, transthoracic cross-clamp. The main surgical wound was made over the lateral border of the right breast. Two additional small wounds were required for the transthoracic aortic clamp and the mitral retractor. RESULTS: There was no operative mortality, and all patients had an uneventful recovery. Two patients underwent redo mitral surgery. Nine associated procedures were performed including tricuspid valve annuloplasty in six patients, tricuspid valve replacement in two patients and atrial septal defect repair in one patient. The length of the main wound was between 5.8 and 7.8 cm (mean, 7.1 cm). The mean cardiopulmonary bypass time and cross-clamp time were 91.1 and 43.7 minutes, respectively. Although the length of stay was not significantly reduced compared with traditional median sternotomy, all patients had satisfactory results with good cosmesis. CONCLUSION: Sternum-sparing mitral valve surgery appears to be a safe and effective alternative to conventional mitral valve surgery; it is less invasive and provides superior cosmetic results for patients.

Surgical resection of primary cardiac lymphoma.

Primary cardiac lymphoma is a rare cardiac malignancy. Surgical resection is rarely performed on this disease entity. We report a case of primary cardiac lymphoma with rapid progression. Debulking surgery was done extensively before final pathology was obtained. Complete remission was exhibited after several courses of chemotherapy.

Endoscopic radial artery harvest for coronary artery bypass surgery.

BACKGROUND/PURPOSE: Coronary artery bypass grafting (CABG) provides better long-term patency than percutaneous intervention in patients with significant coronary artery disease. The radial artery is the second most common arterial conduit used for CABG in Western countries. However, radial artery harvesting necessitates a large surgical wound and has gained few patients' acceptance in subtropical areas. This study investigated the use of the minimally invasive approach of endoscopic radial artery harvest for CABG, and the surgical results at the harvest site. METHODS: An endoscopic harvest program for radial arteries was implemented in this hospital in September 2003. During the first 12 months of the program until September 2004, 122 patients underwent the procedure. Preoperative evaluation included Allen's test and the modified palmar arch perfusion test. The age of patients ranged from 32 to 88 years old. Patients were excluded from participation if they had undergone recent transradial catheterization, had end-stage renal disease or documented peripheral artery occlusive disease. The VasoView system was utilized for the procedure. Details of the surgical techniques used were recorded and analyzed. RESULTS: Using the endoscopic technique, 122 radial arteries were harvested successfully. The mean resting length of the harvested radial artery was 15.7 cm. No obvious arterial injury was visually confirmed. All radial arteries were used for CABG, except for two which were noted to have atherosclerotic plaques causing stenoses. Forty-seven patients presented with mild numbness over the dorsum of the thumb base, which improved significantly during the 3-month follow-up. No arterial insufficiency in the forearms or hands was noted. CONCLUSION: Endoscopic harvest of the radial artery is technically demanding, but excellent results can be achieved. The endoscopic approach can provide suitable conduits in a less invasive way than the open harvest technique.