Safety and efficacy of the Amplatzer Amulet and Watchman 2.5 for left atrial appendage occlusion: A systematic review and meta-analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulation (OAC) to decrease the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF); however, certain complications remain a concern. Amplatzer Amulet and Watchman are the two most popular used devices for preventing stroke in patients with NVAF. We assessed the safety and efficacy of LAAO using the Amplatzer Amulet and Watchman. METHODS: A meta-analysis was conducted to compare the safety and efficacy outcomes associated with the use of the Amplatzer Amulet and Watchman 2.5. The Newcastle-Ottawa Scale has been utilized to assess the quality of study. RESULTS: The meta-analysis includes seven studies involving 2926 patients (1418 patients with an amulet and 1508 with a Watchman 2.5). Generally, adverse event rates for both systems were minimal. No significant differences between the two devices were found in safety (pericardial effusion, device embolization, and cardiac tamponade) or efficacy outcomes (death, TIA, stroke, major/minor bleeding, device leak, and thromboembolic events). CONCLUSIONS: The data suggest LAAO is a safe procedure, regardless of which device was used. LAAO devices generally have low complication rates. Outcomes were comparable between the two groups with no significant differences in their safety or efficacy.

Prostaglandin E1 reduces apoptosis and improves the homing of mesenchymal stem cells in pulmonary arterial hypertension by regulating hypoxia-inducible factor 1 alpha.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with oxidative stress and affects the survival and homing of transplanted mesenchymal stem cells (MSCs) as well as cytokine secretion by the MSCs, thereby altering their therapeutic potential. In this study, we preconditioned the MSCs with prostaglandin E1 (PGE1) and performed in vitro and in vivo cell experiments to evaluate the therapeutic effects of MSCs in rats with PAH. METHODS: We studied the relationship between PGE1 and vascular endothelial growth factor (VEGF) secretion, B-cell lymphoma 2 (Bcl-2) expression, and C-X-C chemokine receptor 4 (CXCR4) expression in MSCs and MSC apoptosis as well as migration through the hypoxia-inducible factor (HIF) pathway in vitro. The experimental rats were randomly divided into five groups: (I) control group, (II) monocrotaline (MCT) group, (III) MCT + non-preconditioned (Non-PC) MSC group, (IV) MCT + PGE1-preconditioned (PGE1-PC) MSC group, and (V) MCT+PGE1+YC-1-PCMSC group. We studied methane dicarboxylic aldehyde (MDA) levels, MSC homing to rat lungs, mean pulmonary artery pressure, pulmonary artery systolic pressure, right ventricular hypertrophy index, wall thickness index (%WT), and relative wall area index (%WA) of rat pulmonary arterioles. RESULTS: Preconditioning with PGE1 increased the protein levels of HIF-1 alpha (HIF-1α) in MSCs, which can reduce MSC apoptosis and increase the protein levels of CXCR4, MSC migration, and vascular endothelial growth factor secretion. Upon injection with PGE1-PCMSCs, the pulmonary artery systolic pressure, mean pulmonary artery pressure, right ventricular hypertrophy index, %WT, and %WA decreased in rats with PAH. PGE1-PCMSCs exhibited better therapeutic effects than non-PCMSCs. Interestingly, lificiguat (YC-1), an inhibitor of the HIF pathway, blocked the effects of PGE1 preconditioning. CONCLUSIONS: Our findings indicate that PGE1 modulates the properties of MSCs by regulating the HIF pathway, providing insights into the mechanism by which PGE1 preconditioning can be used to improve the therapeutic potential of MSCs in PAH.

Effects of Ulinastatin on Perioperative Inflammatory Response and Pulmonary Function in Cardiopulmonary Bypass Patients.

The aim of this study was to investigate whether ulinastatin (UTL) has protective effects on perioperative proinflammatory cytokines and lung injury in cardiopulmonary bypass (CPB) patients. The study included 60 patients undergoing CPB who were randomly divided into a UTL group and a control group. Blood routine examination and inflammatory cytokines concentrations were detected after anesthetic induction (T1), immediately after aortic valve opening (T2), and 4 (T3) and 24 (T4) hours after weaning from CPB. Flow cytometry was used to detect TLR4 and HSP70 expressions. Arterial blood gas and respiratory function were analyzed at the same time points. Compared with the control group, the levels of IL-2, IL-8, TNF-α, NE, TLR4, PA - aDO2, and RI at T2 were significantly lower, whereas HSP70, PaO2, OI, Cd, and Cs were higher in the UTL group (all P < 0.05). Relative to the control group at T3, white blood cell count, TLR4, IL-2, IL-6, IL-8, TNF-α, NE, and RI decreased significantly, whereas IL-10, HSP70, PaO2, OI, and Cs increased in the UTL group (all P < 0.05). At T4, IL-2, IL-6, IL-8, TNF-α, TLR4, and PaCO2 in the UTL group were significantly lower, and PaO2, IL-10, HSP70, and Cs were higher than in the control group (all P < 0.05). Our data show strong evidence that UTL suppresses proinflammatory cytokine elevation and upregulates release of anti-inflammatory mediators, reducing pulmonary injury and improving pulmonary function after CPB.

Augmentation of autophagy by atorvastatin via Akt/mTOR pathway in spontaneously hypertensive rats.

Autophagy is activated in hypertension-induced cardiac hypertrophy. However, the mechanisms and significance of an activated autophagy are not clear. This study was designed to determine the role of atorvastatin (ATO) in cardiac autophagy and associated benefits on cardiac remodeling and left ventricular function in spontaneously hypertensive rats (SHRs). Twenty-eight male SHRs at 8 weeks of age were randomized to treatment with vehicle (saline solution; SHR+V) or ATO (SHR+ATO; 50 mg kg(-1) per day) for 6 or 12 months. Age-matched male Wistar-Kyoto (WKY) rats were used as normotensive controls. Cardiac magnetic resonance was used to evaluate cardiac function and structure. Compared with WKY rats, SHRs showed significant left ventricle (LV) dysfunction, remodeling and increases in cardiomyocyte size, which were all attenuated by 6 and 12 months of ATO treatment. Compared with WKY rats, autophagy was activated in the hearts of SHRs and this effect was amplified by chronic ATO treatment, particularly following 12 months of treatment. Protein expression levels of microtubule-associated protein-1 light chain 3-II and beclin-1, the biomarkers of an activated cardiac autophagy, were significantly elevated in ATO-treated versus vehicle-treated SHRs and control WKY rats. Cardiac Akt and phosphorylated mammalian target of rapamycin (mTOR) expression were also increased in the hearts of SHR versus WKY rats, and this effect was attenuated by ATO treatment. These findings suggest that ATO-mediated improvements in LV function and structure in SHRs may be, in part, through its regulation of cardiac autophagy via the Akt/mTOR pathway.

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Valve replacement in pediatric patients: a single center experience.

BACKGROUND: Reconstructive surgery is the primary goal in pediatric patients with valve disease. However, in cases with irreparable valve lesions, valve replacement is the only option. This study aimed to retrospectively analyze the clinical experience of heart valve prosthesis replacement in children. METHODS: Between January 1990 and July 2009, 35 pediatric patients (16 boys, 19 girls) underwent mechanical valve replacement in Shandong University Qilu Hospital. The ages ranged from 2.5 to 14 years (mean, (8.8 ± 3.8) years) and body weight varied from 11 to 37 kg (mean, (22.1 ± 5.2) kg). Mechanical valve replacement was performed because of congenital heart disease in 23 patients, rheumatic disease in ten patients and infective endocarditis in two patients. St. Jude bileaflet mechanical valves were implanted in all the 35 patients including mitral valve replacement (MVR) in 18, aortic valve replacement (AVR) in 12, tricuspid valve replacement (TVR) in two, AVR and MVR in two and MVR and TVR in one. The size of the prostheses ranged between 19 and 27 mm. All patients received long-term anticoagulation treatment with sodium warfarin, aiming to maintain an international normalized ratio between 1.5 to 2.0. Follow-up was performed in all the patients with a total follow-up of 119.4 patient-years. RESULTS: The operative mortality was 8.57% (3/35). One patient, who underwent cardiac debridement and AVR, died 2 hours after being admitted to the intensive care unit because of severe low cardiac output syndrome and ventricular fibrillation. Two patients died of cardiogenic shock and renal failure during initial hospitalization after the operation. One patient who received replacement of a tricuspid valve developed complete heart block requiring temporary pacing and recovered sinus rhythm 4 days later. Thirty-two patients survived and their cardiac function was in New York Heart Association (NYHA) class I to class II when discharged. Late events included hemorrhage and endocarditis. Two patients required reoperation. No late deaths occurred during the follow-up. CONCLUSIONS: Mechanical valve replacement remains an acceptable treatment option in children when the valve reparation is impossible or unsuccessful. The operative mortality and incidence of any valve-related events such as endocarditis, reoperation, thromboembolism or anticoagulation-related bleeding are acceptable.

[Hemodynamic performance of newly developed composite stentless porcine aortic valve: in vitro testing and in vivo experiment with sheep].

OBJECTIVE: To investigate the effects of a newly developed composite stentless porcine aortic valve constructed from noncoronary leaflets of three porcine aortic valves. METHODS: Fresh porcine hearts with ascending aorta were obtained from a slaughterhouse. The porcine aortic roots with ascending aorta and anterior leaflet of mitral valve and partial ventricular septum were dissected out and were pressurized to maintain their natural anatomical shapes with the leaflets floating freely at zero-pressure. Three noncoronary leaflets fixed in 0.6% glutaraldehyde were carefully matched for size and symmetry to construct a novel composite stentless porcine aortic valve. The lower margin and outside of the valve was covered with a piece of bovine pericardium. The novel stentless valves were tested in vitro pulsatile flow to detect the effective orifice area (EOA) and mean pressure difference (DeltaP) of the valve compared with the stented bovine pericardial bioprostheses of the same size. Sixteen male juvenile sheep underwent implantation of the novel valves in the supra-annular position in under cardio-pulmonary bypass. The intraoperative and postoperative echocardiography and pathological specimen were given to evaluate the hemodynamic performance and observed in the respects of a long-term survival, function of valve and pathological specimen. RESULTS: Since novel valves had the unfavorable muscle-based right coronary leaflet characteristic of porcine valve removed it had larger EOA. Pulsatile flow testing indicated that the EOA of the 3 novel valves was (3.47 +/- 0.15), (3.69 +/- 0.11), and (3.92 +/- 0.18) cm2 respectively, all significantly greater than those of the stented bovine pericardial bioprosthesis [(2.00 +/- 0.16), (2.21 +/- 0.26), and (2.37 +/- 0.42) cm2 respectively] at each integral simulated cardiac output between 3 - 6 L/min (all P < 0.05), while the DeltaP levels of the novel valves were (2.35 +/- 0.41), (3.10 +/- 0.20), and (3.56 +/- 0.16) mm Hg respectively, all significantly lower than those of the stented bovine pericardial bioprosthesis [(4.98 +/- 0.46), (6.82 +/- 1.27), and (8.40 +/- 1.83) mm Hg respectively, all P < 0.05]. Twelve of the sixteen sheep survived after operation. Five of them had lived for more than 90 days, 3 more than 180 days, and 2 more than 360 days. The intra-operative echocardiographic analyses showed low DeltaP [(3.90 +/- 0.78) mm Hg] and no regurgitation in all sheep. After 15 to 360 days, all valves performed excellently. The sheep were postoperatively sacrificed in 5 d, 15 d, 45 d, 90 d, 180 d, or 300 d respectively. Necropsy revealed the valves had a low to mild level of calcification, without periprosthetic leakage and overgrowth of fibrous tissue. CONCLUSION: The newly developed composite stentless porcine aortic valves show excellent hemodynamic performance with lower transvalvular pressure gradient and are relatively easy to implant.

[Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule in cardiac allografts and significance thereof: experiment with rats].

OBJECTIVE: To investigate the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in allograft with chronic rejection (CR) after heart transplantation. METHODS: Seventy-two SD rats receiving transplantation of the heats of 71 Wistar rats were divided into 4 equal groups: Group A, undergoing heterotopic cervical heart transplantation (transplanted with donor's heart subcutaneously at the neck) and receiving none intervention, and with the transplanted hearts taken out 3 d after transplantation to the end of CR; Group B, injected intravenously with the splenocytes (SPCs) of the donors on day 0, injected with cyclophomide (CP) on d2, transplanted with the donor hearts on d15, with the transplanted hearts taken out 15 - 120 days after transplantation; Group C, transplanted with the donor's heart and injected intraperitoneally with cyclosporine A (Cs A) 10 mg/kg every other day for 8 - 10 times, and with the transplanted hearts taken out 60 d after transplantation to the end of CR; and Group D, injected intravenously with the SPCs of the donors on day 0, injected with CP on d2, transplanted with the donor hearts on d15, with the transplanted hearts taken out 150 - 420 days after transplantation. Immunohistochemical method was used to detect the expression of ICAM-1 and VCAM-1 in the allografts. RESULTS: The cardiac allograft survival time of Group B was the longest. Less ICAM-1 and VCAM-1 expression and lymphocyte infiltration were observed in SPC and CP-pretreated group. Reversely, protein expression levels of ICAM-1 and VCAM-1 were both high and significant lymphocyte infiltration was seen in Groups B and D. There was no significant difference in the expression of ICAM-1 and VCAM-1 between Groups A and C (P > 0.05). CONCLUSION: The expression levels of ICAM-1 and VCAM-1 are associated with the occurrence and development of rejection and have positive correlation with the severity of graft rejection. Determination of ICAM-1 and VCAM-1 can predict the function of allograft and provide evidence for early diagnosis and prevention of CR.