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We investigated the effect of repeated remote ischaemic post‐conditioning (RIPoC) on the organ distribution of the intramyocardially injected MSCs in rat myocardial ischemia model. Myocardial ischemia of adult female Sprague‐Dawley rats was induced by 30‐min. obstruction of the left anterior descending coronary artery. Repeated RIPoC was induced after ischemia with three cycles of 5‐min. occlusion and reperfusion of the limb with the frequency of half a day, 1 or 2 days, respectively. Compared with that by single RIPoC, repeated RIPoC transiently reduced oxidative stress, lipid peroxidation and inflammation in ischaemic myocardium; the gene expression of stromal cell‐derived factor‐1 alpha (SDF‐1α) was consistently induced by repeated RIPoC procedures. A total of 4 × 106 male bone marrow‐derived MSCs were intramyocardially injected into ischaemic myocardium at 1 week after reperfusion. Three weeks later, immunohistological examination and quantitative reverse transcriptase polymerase chain reaction demonstrated that repeated RIPoC significantly increased MSCs retention in myocardium and decreased MSCs distribution over the lungs, spleen and liver; echocardiography assessment revealed that further cardiac function enhancement imposed by repeated RIPoC procedure. Furthermore, blockade with the anti‐CXCR4 antibody before cell transplantation markedly attenuated the benefits of therapeutic efficacy and cardiac function. Repeated RIPoC enhanced MSCs engraftment in ischaemic myocardium and reduced the distribution of MSCs over peripheral organs in a frequency‐effect way, but it reached a ceiling of maximal effect when applied with every 1 day. The SDF1α‐CXCR4 interaction played a major role in MSCs systemic redistribution induced by repeated RIPoC.

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation.

Aims Although the number of hospitals performing cardiac surgery has increased rapidly in China, information regarding the trends in coronary artery bypass grafting (CABG) outcomes remains unknown. Methods and results We used data from the Chinese Cardiac Surgery Registry, the largest registry system that accounts for nearly 50% of total annual CABG volume in China, to assess trends of in-hospital mortality and major complication rates for patients receiving isolated CABG in 102 urban teaching hospitals in China from 25 January 2004 through 31 December 2013 (except 2006 and 2009). Using a mixed effects model, we estimated annual trends in each of these two outcomes overall and by age groups (18-64 and 65 years or older), adjusted for patient characteristics. We also assessed the trends in pre-operative, post-operative, and total length of stay (LOS). The study included 40 652 patients across 102 hospitals. Between 2004 and 2013, patients' mean age decreased from 62.7 to 61.4 years, in-hospital mortality decreased from 2.8% to 1.6% (difference, 1.3%, 95% CI: 0.70-1.85), and major complication rates decreased from 7.8% to 3.8% (difference, 4.0%; 95% CI: 3.05-4.90). The reduction in mortality and major complication rates were consistent across age groups. Between 2004 and 2013, the median (inter-quartile range) pre-operative LOS remained unchanged, post-operative LOS declined from 12.0 (8.0) to 10.0 (7.0) days, and total LOS declined from 22.0 (13.0) to 20.0 (12.0) days. Conclusion Isolated CABG-related in-hospital mortality, major complication rates, and LOS have improved in urban teaching hospitals in China over the last decade.

The mechanisms that promote the generation of new coronary vasculature during cardiac homeostasis and after injury remain a fundamental and clinically important area of study in the cardiovascular field. Recently, it was reported that mesenchymal-to-endothelial transition (MEndoT) contributes to substantial numbers of coronary endothelial cells after myocardial infarction. Therefore, the MEndoT has been proposed as a paradigm mediating neovascularization and is considered a promising therapeutic target in cardiac regeneration. Here, we show that preexisting endothelial cells mainly beget new coronary vessels in the adult mouse heart, with essentially no contribution from other cell sources through cell-lineage transdifferentiation. Genetic-lineage tracing revealed that cardiac fibroblasts expand substantially after injury, but do not contribute to the formation of new coronary blood vessels, indicating no contribution of MEndoT to neovascularization. Moreover, genetic-lineage tracing with a pulse-chase labeling strategy also showed that essentially all new coronary vessels in the injured heart are derived from preexisting endothelial cells, but not from other cell lineages. These data indicate that therapeutic strategies for inducing neovascularization should not be based on targeting presumptive lineage transdifferentiation such as MEndoT. Instead, preexisting endothelial cells appear more likely to be the therapeutic target for promoting neovascularization and driving heart regeneration after injury.

A fully implantable axial left ventricular assist device LAP31 was developed for Chinese or other heart failure patients who need partial support. Based on the 5-Lpm total cardiac blood output of Chinese without heart failure disease, the design point of LAP31 was set to a flow rate of 3 Lpm with 100-mmHg pressure head. To achieve the required pressure head and good hemolytic performance, a structure that includes a spindly rotor hub and a diffuser with splitter and cantilevered main blades was developed. Computational fluid dynamics (CFD) was used to analyze the hydraulic and hemodynamic performance of LAP31. Then in vitro hydraulics experiments were conducted. The numerical simulation results show that LAP31 could generate a 1 to 8 Lpm flow rate with a 60.9 to 182.7 mmHg pressure head when the pump was rotating between 9,000 and 12,000 rpm. The average scalar shear stress of the blood pump was 21.7 Pa, and the average exposure time was 71.0 milliseconds. The mean hemolysis index of LAP31 obtained using Heuser's hemolysis model and Giersiepen's model was 0.220% and 3.89 × 105% respectively. After adding the splitter blades, the flow separation at the suction surface of the diffuser was reduced. The cantilever structure reduced the tangential velocity from 6.1 to 4.7–1.4 m/s within the blade gap by changing the blade gap from shroud to hub. Subsequently, the blood damage caused by shear stress was reduced. In conclusion, the hydraulic and hemolytic characteristics of the LAP31 are acceptable for partial support.

Endoplasmic reticulum (ER) stress, a feature of many conditions associated with pulmonary hypertension (PH), is increasingly recognized as a common response to promote proliferation in the walls of pulmonary arteries. Increased expression of Lipocalin-2 in PH led us to test the hypothesis that Lipocalin-2, a protein known to sequester iron and regulate it intracellularly, might facilitate the ER stress and proliferation in pulmonary arterial smooth muscle cells (PASMCs). In this study, we observed greatly increased Lcn2 expression accompanied with increased ATF6 cleavage in a standard rat model of pulmonary hypertension induced by monocrotaline. In cultured human PASMCs, Lcn2 significantly promoted ER stress (determined by augmented cleavage and nuclear localization of ATF6, up-regulated transcription of GRP78 and NOGO, increased expression of SOD2, and mild augmented mitochondrial membrane potential) and proliferation (assessed by Ki67 staining and BrdU incorporation). Lcn2 promoted ER stress accompanied with augmented intracellular iron levels in human PASMCs. Treatment human PASMCs with FeSO4 induced the similar ER stress and proliferation response and iron chelator (deferoxamine) abrogated the ER stress and proliferation induced by Lcn2 in cultured human PASMCs. In conclusion, Lcn2 significantly promoted human PASMC ER stress and proliferation by augmenting intracellular iron. The up-regulation of Lcn2 probably involved in the pathogenesis and progression of PH.

The MitraFix valve (MitrAssist Lifesciences, Shanghai, China) consists of a D-shaped nitinol frame and 3 bovine pericardium leaflets ([Figures 1A and 1B][1]). The 30-F transapical delivery system has 2 built-in echogenic markers for height and D-shape orientation, which facilitate implanting the

BackgroundWe previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). MethodsA total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. ResultsThere were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-p...

Device thrombosis inside ventricular assist devices remains a limitation to their long-term clinical use. Thrombosis potential exists in almost all ventricular assist devices because the device-induced high shear stress and vortices can activate platelets, which then aggregate and adhere to the surfaces inside the ventricular assist device. To decrease the device thrombosis potential of long-term use of ventricular assist devices, a methodology entitled platelet adhesion emulation for predicting the thrombosis potential and thrombosis position inside the ventricular assist devices is developed. The platelet adhesion emulation methodology combines numerical simulations with in vitro experiments by correlating the structure of the flow passage components within the ventricular assist device with the platelet adhesion to estimate the thrombosis potential and location, with the goal of developing ventricular assist devices with optimized antithrombotic performance. Platelet adhesion emulation is aimed at decreasing the device thrombus potential of ventricular assist devices. The platelet adhesion emulation effectiveness is validated by simulating and testing an axial left ventricular assist device. The blood velocity relative to the surfaces of the flow passage components is calculated to estimate the platelet adhesion potential, indicating the probability of thrombus formation on the surfaces. Platelet adhesion emulation experiments conducted in a mock circulation loop with pump prototypes show the distribution of platelet adhesion on the surfaces. This methodology of emulating the device thrombosis distribution indicates the potential for improving the component structure and reducing the device thrombosis of ventricular assist devices.

Pump thrombosis potential exists in most blood pumps and limits their clinical use. To improve the pump thrombosis performance of blood pumps, a method for emulating the platelet deposition on the flow passage component surfaces inside blood pumps was presented and tested. The method emulates the blood platelet deposition, employing laser-induced fluorescence tracing technology. The blood pump was rotated in a mock circulation loop with deionized water filled with fluorescent particles. The component surfaces were then explored via laser. The fluorescent particles were induced by laser and imaged in a charge-coupled device (CCD) camera to show the distribution of fluorescent particles gathering on the blood pump component surfaces. The activated platelet deposition was emulated by fluorescent particle gathering. The experiment showed obvious particle gathering on the interface surfaces and cross-sectional surface (perpendicular to the flow). This platelet deposition estimation (PDE) method can be easily incorporated in the in vitro testing phase to analyze and decrease a pump's thrombosis potential before animal experimentation, thereby reducing the cost of blood pump development. This methodology of emulating blood platelet deposition indicates its potential for improving flow passage component structure and reducing device thrombosis of blood pumps.

Background Arrhythmogenic Cardiomyopathy (AC) is one of main causes of sudden cardiac death in young people with limited understanding of molecular mechanism. LncRNAs are emerging as important regulators of cardiovascular diseases, but their roles in AC remain elusive. Purpose This study is to identify novel lncRNAs in AC genome wide and investigate their functions. Methods and results Extremely deep RNA-seq was performed for AC right ventricles (RVs, n=9) and left ventricles (LVs, n=6), normal RVs (n=5) and LVs (n=6), and dilated cardiomyopathy (DCM) RVs (n=4). Novel lncRNAs were accurately identified with epigenetic annotations. In comparison with normal and DCM, 1,925 novel lncRNAs transcripts specifically upregulated in AC RVs were identified. Most of AC-specific lncRNAs were highly expressed in heart, located in distal regions (>3 kb) from coding gene and marked by H3K4me1 or H3K27ac, indicating that these lncRNAs might act as cis-elements to regulate gene expression. Enrichment analysis revealed that AC-specific lncRNAs were associated with AC phenotypes like RV enlargement and dysfunction. Interestingly, their potential target genes were significantly enriched in lipid metabolism and calcium signaling pathways. In-vitro experiments demonstrated that LncRNA AC1, a novel AC-specific lncRNA, was significantly positively correlated with adipogenic genes expression. And overexpression of LncRNA AC1 promoted adipogenic genes expression and droplet deposition in human derived iPSC-CM and cardiac fibroblast. ESC-AC lncRNA study abstract Conclusion We identified novel AC-specific lncRNAs related to adipogenesis and validated them in-vitro. Our findings also provide fundamental resource for the potential development of basic translation study for AC. Acknowledgement/Funding This study was supported by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-015)

Use of partially bioabsorbable occluders for atrial septal defect closure appears to circumvent potential late complications of metallic occluders ([1][1],[2][2]), which are amply used worldwide. However, there have been no studies on the use of either partially or fully bioabsorbable occluders for

Arrhythmogenic cardiomyopathy (ACM) is a familial cardiomyopathy featured by fibrofatty replacement of cardiomyocytes. Responsible genetic factors are not discernible in approximately one-third of ACM probands. To investigate this further, we performed whole genome sequencing in 14 mutation-negative ACM probands who underwent cardiac transplantation, and we identified one ACM proband with a rare homozygous missense variant in PNPLA2 (c.245G > A, p.G82D), a rate-limiting enzyme that hydrolyzes triglycerides into fatty acids and diacylglycerol. Bioinformatic analysis suggested that this missense variant may lead to loss of function and therefore impair lipid catabolism. Genetic screening in this proband's family also inferred that the homozygous variant cosegregated with disease. To validate the pathogenicity of this variant and confirm its association with ACM, we established a knockin mouse model carrying the orthologous human homozygous PNPLA2 variant. Interestingly, mice with the homozygous variant presented with arrhythmias and significant cardiac dysfunction at 12 weeks, whereas heterozygous mice were not affected. Moreover, those homozygous mice suffered sudden death and/or heart failure by the age of 14 weeks. Pathological examination showed that extensive lipogenesis in cardiomyocytes and cardiac fibrosis were prominent in the myocardium. Herein, our data demonstrated that the homozygous missense variant PNPLA2 (c.245G > A, p.G82D) associated with a recessive form of ACM.

Ischemic heart disease remains the leading cause of mortality and morbidity worldwide despite improved possibilities in medical care. Alongside interventional therapies, such as coronary artery bypass grafting, adjuvant tissue-engineered and cell-based treatments can provide regenerative improvement. Unfortunately, most of these advanced approaches require multiple lengthy and costly preparation stages without delivering significant clinical benefits.We evaluated the effect of epicardially delivered minute pieces of atrial appendage tissue material, defined as atrial appendage micrografts (AAMs), in mouse myocardial infarction model. An extracellular matrix patch was used to cover and fix the AAMs onto the surface of the infarcted heart. The matrix-covered AAMs salvaged the heart from infarction-induced loss of functional myocardium and attenuated scarring. Site-selective proteomics of injured ischemic and uninjured distal myocardium from AAM-treated and untreated tissue sections revealed an increased expression of several cardiac regeneration-associated proteins (i.e. periostin, transglutaminases and glutathione peroxidases) as well as activation of pathways responsible for angio- and cardiogenesis in relation to AAMs therapy.Epicardial delivery of AAMs encased in an extracellular matrix patch scaffold salvages functional cardiac tissue from ischemic injury and restricts fibrosis after myocardial infarction. Our results support the use of AAMs as tissue-based therapy adjuvants for salvaging the ischemic myocardium.

An implantable axial blood pump was designed according to the circulation assist requirement of severe heart failure patients of China. The design point was chosen at 3 L/min flow rate with 100 mm Hg pressure rise when the blood pump can provide flow rates of 2-7 L/min. The blood pump with good hemolytic and anti-thrombogenic property at widely operating range was designed by developing a structure that including the spindly rotor impeller structure and the diffuser with splitter blades and cantilevered main blades. Numerical simulation and particle image velocimetry (PIV) experiment were conducted to analyze the hydraulic, flow fields and hemolytic performance of the blood pump. The results showed that the blood pump could provide flow rates of 2-7 L/min with pressure rise of 60.0-151.3 mm Hg when the blood pump rotating from 7 000 to 11 000 r/min. After adding the splitter blades, the separation flow at the suction surface of the diffuser has been reduced efficiently. The cantilever structure changed the blade gap from shroud to hub that reduced the tangential velocity from 6.2 m/s to 4.3-1.1 m/s in blade gap. Moreover, the maximum scalar shear stress of the blood pump was 897.3 Pa, and the averaged scalar shear stress was 37.7 Pa. The hemolysis index of the blood pump was 0.168% calculated with Heuser's hemolysis model. The PIV and simulated results showed the overall agreement of flow field distribution in diffuser region. The blood damage caused by higher shear stress would be reduced by adopting the spindle rotor impeller and diffuser with splitter blades and cantilevered main blades. The blood could flow smoothly through the axial blood pump with satisfactory hydraulics performance and without separation flow.根据中国终末期心衰患者对左心辅助泵辅助人体血液循环的要求，设计以 3 L/min 流量、100 mm Hg 压升为设计点，流量范围为 2～7 L/min 的微型可植入轴流血泵。该血泵采用纺锤形的转子叶轮结构以及带分流叶片、悬臂叶片的尾导结构，以使血泵在较宽的压力流量范围内具有良好的溶血和抗血栓特性。本文用数值模拟及粒子成像测速（PIV）的方法分析血泵的水力学特性、流场及溶血特性。结果表明：血泵转速为 7 000～11 000 r/min 时，在 2～7 L/min 的流量范围内可提供 60.0～151.3 mm Hg 的压升；分流叶片抑制了尾导的尾缘吸力面处的流动分离；悬臂式叶片结构将转子叶片的叶尖间隙变为尾导叶片的叶根间隙，间隙的切线速度由 6.2 m/s 降至 4.3～1.1 m/s；血泵的最大标量剪切应力值为 897.3 Pa，平均剪切应力值为 37.7 Pa；采用 Heuser 溶血模型得到的溶血指数为 0.168%；PIV 试验所得泵内尾导区域的流场速度分布与数值计算得到的流场特征吻合良好。本研究所设计的轴流血泵的尾导具有分流叶片和悬臂叶片，流道内血流无较大分离流动，降低了剪切力对血液的破坏，溶血性能良好，压力流量性能满足临床需要。.

Hypoplastic right heart syndrome(HRHS) is characterized by hypoplastic right ventricle (RV); Numerous transcriptional cascades in the second heart field (SHF) regulate RVdevelopment. The relationship of SHF gene variants with human HRHS remains unknown. The whole lengths of 17 SHF genes were sequenced in 16 HRHS, and the selected single-nucleotide variants (SNVs) were then genotyped in HRHS, other congenital heart disease (CHD) and healthy control. Luciferase assay was performed to verify the effect of FOXC2: rs34221221A>GandTBX20: rs59854940C>Gat the transcription level. There were 151 (12.86%) novel SNVs after sequence analysis, of which three were in exons (one was synonymous SNV and two were nonsynonymous SNVs), two in promoter, and most SNVs (89.95%) were in intronic regions. Genotype analyses revealed that the minor alleles of FOXC2: rs34221221 A>G and TBX20: rs59854940 C>G could increase HRHS risk (P

Objective To investigate a technical method for harvesting and using the descending branch of the lateral circumflex femoral artery (DLCFA) in coronary artery bypass grafting (CABG). Methods Between January 2017 and January 2019, 40 patients (36 in the planed selection group and 4 in the temporary decision group) with mean age of 49.1 ± 7.5 years received DLCFA as an arterial conduit in CABG. In all patients, the DLCFA was successfully harvested via an anterior thigh incision. Depending on the location of the target vessel, the DLCFA was used as a free graft or a composite graft. Results Of the 44 patients in the planned selection group, DLCFA harvesting was abandoned in 8 patients because computed tomographic angiography revealed anatomical variation or stenosis of the superficial femoral artery. Of the 5 patients in the temporary decision group, harvesting was abandoned in 1 because of short length and thin caliber. On an average, 3.7 ± 0.9 distal anastomoses were created during CABG, with no adverse effects. The length of the harvested DLCFA was 9.9 ± 1.7 cm, with an average proximal lumen diameter of 3.4 ± 0.7 mm. The DLCFA was used as a free graft in 26 patients and as a “Y”-shape composite graft in 14 patients. Total arterial CABG was performed in 75% of the patients. Conclusions The DLCFA is an alternative conduit for CABG. It can be harvested easily and safely. However, preoperative computed tomographic angiography examination is necessary for the smooth application of the DLCFA, and an appropriate strategy for graft establishment should be considered.

Background Studies found that patients who underwent coronary artery bypass grafting (CABG) often fail to receive optimal evidence-based secondary prevention medications. We evaluated the effectiveness of a smartphone-based quality improvement effort on improving the prescription of medical therapies. Methods In this cluster-randomized controlled trial, 60 hospitals were randomized to a control arm (n = 30) or to an intervention arm using smartphone-based multifaceted quality improvement interventions (n = 30). The primary outcome was the prescription of statin. The secondary outcomes were prescription of beta-blocker, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker (ACE inhibitor or ARB), and optimal medical therapy for eligible patients. Results Between June 1, 2015 and September 15, 2016, a total of 10,006 CABG patients were enrolled (5,653 in 26 intervention and 4,353 in 29 control hospitals, 5 hospitals withdrew). Statin prescribing rate was 87.8% in the intervention arm and 84.4% in the control arm. We saw no evidence of an effect of intervention on statin prescribing in the intention-to-treat analysis (odds ratio [OR], 1.31; 95% confidence interval (CI), 0.68-2.54; P = .43) or in key patient subsets. The prescription rates of ACE inhibitor or ARB and optimal medical therapy were comparable between study groups, while beta-blocker was more often prescribed in the intervention arm. Post hoc analysis demonstrated a greater increase in statin prescribing rate over time in the intervention arm. Conclusions A smartphone-based quality improvement intervention compared with usual care did not increase statin prescribing for patients who received CABG. New studies focusing on the best practice of this technique may be warranted.

Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients. We detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality. In 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P

Transcriptional factors and signaling factors in the second heart field (SHF) contribute to cardiac development. However, the associations of intronic gene variants in the SHF with congenital heart disease (CHD) remain ununderstood. Ten single nucleotide polymorphisms (SNPs) from our previous sequencing data were selected and then genotyped in 383 CHD patients and 384 healthy controls in a Chinese population. Genotype analyses revealed that minor alleles in

Recent studies indicated that osteopontin (OPN) was involved in the genesis and progression of pulmonary arterial hypertension (PAH); however, its role in congenital heart disease-associated PAH (CHD/PAH) remains unknown. Our results showed that OPN was increased in lungs and plasma of patients with Eisenmenger syndrome; moreover, OPN and αVβ3-integrin expression levels were augmented in rat lungs exposed to systemic-to-pulmonary shunt. Cell culture assay demonstrated that distal pulmonary arterial smooth muscle cells (PASMCs) from rat lungs suffering from volume and pressure overload exhibited enhanced proliferation compared with those from healthy rats. Mechanical stretch (20% at 1 Hz) increased OPN expression and activated ERK1/2 and protein kinase B (Akt) signal pathway in distal PASMCs from healthy rats. Interestingly, OPN enhanced the proliferation and migration of PASMCs while blocking αVβ3-integrin with neutralizing antibody LM609 or Arg-Gly-Asp peptidomimetic antagonist cyclo(Ala-Arg-Gly-Asp-3-aminomethylbenzoyl) (XJ735), rectified the proliferative and migratory effects of OPN, which were partially mediated via ERK1/2 and Akt signaling pathways. Furthermore, surgical correction of systemic-to-pulmonary shunt, particularly XJ735 supplementation after surgical correction of systemic-to-pulmonary shunt, significantly alleviated the pulmonary hypertensive status in terms of pulmonary hemodynamic indices, pulmonary vasculopathy, and right ventricular hypertrophy. In summary, OPN alteration in lungs exposed to systemic-to-pulmonary shunt exerts a deteriorative role in pulmonary vascular remodeling through modulating the proliferation and migration of PASMCs, at least in part, via ανβ3-ERK1/2 and ανβ3-Akt signaling pathways. Antagonizing OPN receptor ανβ3-integrin accelerated the regression of pulmonary vasculopathy after surgical correction of systemic-to-pulmonary shunt, indicating a potential therapeutic strategy for patients with CHD/PAH.-Meng, L., Liu, X., Teng, X., Gu, H., Yuan, W., Meng, J., Li, J., Zheng, Z., Wei, Y., Hu, S. Osteopontin plays important roles in pulmonary arterial hypertension induced by systemic-to-pulmonary shunt.

Owing to the prevalence and high mortality rates of cardiac diseases, a more detailed characterization of the human heart is necessary; however, this has been largely impeded by the cellular diversity of cardiac tissue and limited access to samples. Here, we show transcriptome profiling of 21,422 single cells-including cardiomyocytes (CMs) and non-CMs (NCMs)-from normal, failed and partially recovered (left ventricular assist device treatment) adult human hearts. Comparative analysis of atrial and ventricular cells revealed pronounced inter- and intracompartmental CM heterogeneity as well as compartment-specific utilization of NCM cell types as major cell-communication hubs. Systematic analysis of cellular compositions and cell-cell interaction networks showed that CM contractility and metabolism are the most prominent aspects that are correlated with changes in heart function. We also uncovered active engagement of NCMs in regulating the behaviour of CMs, exemplified by ACKR1+-endothelial cells, injection of which preserved cardiac function after injury. Beyond serving as a rich resource, our study provides insights into cell-type-targeted intervention of heart diseases.

Remote ischaemic preconditioning (RIPC) as adjuvant to selective heart surgery attenuates cardiac injury and atrial fibrillation (AF) occurrence. We investigated its effect on sinus rhythm (SR) restoration rate in permanent AF patients undergoing Cox maze (CM) radiofrequency ablation with concomitant mitral valve surgery. From May 2013 to May 2017, 206 patients with rheumatic valve disease concomitant with permanent AF were randomized to receive prosthesis valve replacement and CM radiofrequency ablation procedure with (n = 104) or without (n = 102) RIPC (intermittent arm ischaemia through three cycles of 5-min inflation, followed by 5-min deflation of a blood pressure cuff). The primary end point of the study was freedom from cumulative AF without using antiarrhythmic drugs 1 year after operation; the secondary end points included inflammation reaction index over 48 h postoperatively and clinical outcomes. Baseline characteristics and preoperative data did not differ between groups. The SR restoration rates were significantly higher in the RIPC group, 85.6%, 83.7%, and 82.7%, than those in the control group, 72.5%, 70.6%, and 69.6%, at discharge, 6 months and 12 months, respectively, after the radiofrequency ablation procedure (P

Background This study aims to compare the midterm outcomes of left ventricular reconstruction with those of left ventricular reconstruction plus mitral valve surgery in patients with left ventricular aneurysm due to anterior myocardial infarction and moderate mitral regurgitation. Methods A total of 523 patients (75 who underwent left ventricular reconstruction plus mitral valve surgery and 448 who underwent left ventricular reconstruction) with concomitant moderate mitral regurgitation were included in the study population. All-cause mortality was considered the primary endpoint. Major adverse cardiovascular and cerebrovascular events, including death, myocardial infarction, stroke, and subsequent mitral valve surgery, were considered secondary endpoints. Multivariable proportional hazards Cox regression models were used to assess the associations between groups and outcomes. In the sensitivity analysis we excluded patients who did not undergo coronary artery bypass graft and repeated the statistical analysis above. Results The median follow-up time among all patients was 41 months. There was no significant difference between the left ventricular reconstruction plus mitral valve surgery and the left ventricular reconstruction groups with regard to all-cause mortality (P = .208) and major adverse cardiovascular and cerebrovascular events (P = .817) after adjustment for covariates. In the sensitivity analysis there was no significant difference between the left ventricular reconstruction plus mitral valve surgery and left ventricular reconstruction groups with regard to all-cause mortality (P = .158) and major adverse cardiovascular and cerebrovascular events (P = .651) after adjustment for covariates. Conclusions The clinical outcomes of left ventricular reconstruction are comparable with those of left ventricular reconstruction plus mitral valve surgery in patients with left aneurysm and moderate mitral regurgitation.

Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in postcardiotomy cardiac shock (PCS). The factors that affect mortality in patients who receive ECMO for PCS remain unclear. In this study, we analyzed the outcomes, predictive factors and complications of ECMO use for PCS. Methods A total of 152 adult subjects who received VA-ECMO for PCS in Fuwai Hospital were consecutively included. We retrospectively collected the baseline characteristics, outcomes and complications. Baseline characteristics were compared between survivors with non-survivors, and logistic regression was performed to identify predictive factors for in-hospital mortality. Results The mean age of the subjects was 49.5 ± 14.1 years, with a male dominancy of 73.7%. The main surgical procedures were heart transplantation (32.2%), coronary artery bypass graft (17%) and valvular surgery (11.8%). Intra-aortic balloon pumping (IABP) was initiated concurrently with ECMO in 32.2% subjects and sequentially in 18.4% subjects. The ECMO weaning rate was 56.6%, and the in-hospital mortality was 52.0%. When compared with non-survivors, survivors had less hypertension (15.1% vs. 35.4%, p = 0.004), secondary thoracotomy before ECMO initiation (19.2% vs. 39.2%, p = 0.007), pre-ECMO cardiac arrest/ventricular fibrillation (11.0% vs. 34.2%, p = 0.001), bedside implantation of ECMO (11.0% vs. 41.8%, p

Adverse events caused by flow-induced thrombus formation around the bearing/shaft of an axial blood pump remain a serious problem for axial blood pumps. Moreover, excessive anticoagulation with thrombosis around the bearing potentially increases the risk of postoperative gastrointestinal bleeding. The purpose of this study is to analyze the influence of the bearing structure on the thrombosis potential of an axial blood pump. The bearing/shaft structure was embedded into an axial blood pump numerical model. The numerical simulation and analysis are focused on the low wall shear stresses, recirculation, and residence time close to the bearing region to evaluate the potential for thrombosis around the bearing. Then, the flow field near the blood pump bearing was tested via in vitro particle image velocimetry experiments to verify the numerical results. The simulation results showed that after embedding the bearing/shaft structure a recirculation zone appeared in the outlet guide vane bearing/shaft region, the residence time increased 11-fold in comparison to the pump without the bearing/shaft structure, the scalar shear stress in the shaft surface was less than 7.8 Pa, and the stress accumulation was less than 0.10 Pa s. The numerical results showed that platelets that flow through the bearing region are exposed to significantly lower wall shear stress and a longer residence time, leading to activated platelet adhesion. The reduced stress accumulation and increased time in the bearing region lead to increased platelet activation.

Background To meet the demand of increasing surgical volume and changing of patient’s risk profiles of coronary artery bypass grafting in China, we developed a new risk model that predicts in-hospital mortality. Methods The analysis included patients who underwent coronary artery bypass grafting between January 2013 and December 2016 at 87 hospitals in the Chinese Cardiac Surgery Registry. Patients in years 2013 to 2015 were randomly divided into training (n = 31,297 [75%]) and test (n = 10,432 [25%]) samples; 2016 patients (n = 15047) comprised the validation sample. Demographic and clinical risk factors were identified. The Harrell C statistic was used to evaluate model discrimination, and the Hosmer-Lemeshow goodness-of-fit test was used to assess calibration. Results The 56,776 patients were a mean age of 61.8 (SD, 8.8) years, and 24.6% were women. Overall, in-hospital mortality was 2.1%. The final model included 21 risk factors represented by 16 unique variables. The model achieved good discrimination, with a C statistic of 0.79 (95% confidence interval [CI], 0.77-0.80) in the training sample, 0.79 (95% CI, 0.76-0.82) in the test sample, and 0.78 (95% CI, 0.76-0.81) in the validation sample. Model calibration was good according to the Hosmer-Lemeshow test (P > .05 in the 3 samples). Compared with the European System for Cardiac Operative Risk Evaluation 2011 revision (EuroSCORE II) and the Sino(Chinese) System for Coronary artery bypass grafting Operative Risk Evaluation (SinoSCORE), the model had better discrimination and calibration. Conclusions We developed and evaluated a model with 16 risk factors that predicted in-hospital mortality risk after coronary artery bypass grafting in China. This updated model may help surgeons and hospitals better identify high-risk patient.

The ventricular assist pumps do not always function at the design point; instead, these pumps may operate at unfavorable off-design points. For example, the axial ventricular assist pump FW-2, in which the design point is 5 L/min flow rate against 100 mm Hg pressure increase at 8,000 rpm, sometimes works at off-design flow rates of 1 to 4 L/min. The hemolytic performance of the FW-2 at both the design point and at off-design points was estimated numerically and tested in vitro. Flow characteristics in the pump were numerically simulated and analyzed with special attention paid to the scalar sheer stress and exposure time. An in vitro hemolysis test was conducted to verify the numerical results. The simulation results showed that the scalar shear stress in the rotor region at the 1 L/min off-design point was 70% greater than at the 5 L/min design point. The hemolysis index at the 1 L/min off-design point was 3.6 times greater than at the 5 L/min design point. The in vitro results showed that the normalized index of hemolysis increased from 0.017 g/100 L at the 5 L/min design point to 0.162 g/100 L at the 1 L/min off-design point. The hemolysis comparison between the different blood pump flow rates will be helpful for future pump design point selection and will guide the usage of ventricular assist pumps. The hemolytic performance of the blood pump at the working point in the clinic should receive more focus.

ObjectiveThis study aims to report our preliminary experience and anatomic findings in the surgical treatment and postoperative management of hypertrophic obstructive cardiomyopathy.MethodsThis study included 277 patients with hypertrophic obstructive cardiomyopathy (168 [60.65%] were male), with a median age of 47 years (interquartile range, 35-54 years), who underwent surgical myectomy performed by 1 surgeon in Fuwai Hospital between May 2010 and April 2015. The median follow-up was 14 months (interquartile range, 7-24 months).ResultsA total of 127 patients (45.85%) underwent concomitant procedures, and 2 patients (0.72%) died in the early perioperative days. The left ventricular outflow gradient decreased from 78 mm Hg (interquartile range, 61-100 mm Hg) to 11 mm Hg (interquartile range, 8-15 mm Hg) when discharged (P

Objective The objective of this study was to assess the feasibility of percutaneous balloon pulmonary valvuloplasty (PBPV) under echocardiographic guidance only. Setting PBPV has become the preferred choice for pulmonary valve stenosis (PS). We report the first-in-human successful PBPV under only echocardiography guidance for isolated PS. Methods From March 2013 to December 2014, 34 patients with congenital PS underwent PBPV with echocardiography as the only imaging modality in the ordinary operation room or catheter lab. Outpatient follow-up including chest radiography, electrocardiography, and transthoracic echocardiography (TTE) was conducted at 1, 3, 6, and 12 months. Results All 34 patients successfully underwent PBPV under echocardiography guidance without radiation and contrast agent. The pulmonic transvalvular pressure gradient dropped from 62.8 ± 10.1 mm Hg to 14.7 ± 4.2 mm Hg measured on catheterization (P

Background In light of the burgeoning volume and certain variation of in-hospital outcomes of cardiac operations in China, a large patient-level registry was needed. We generated the Chinese Cardiac Surgery Registry (CCSR) database in 2013 to benchmark, continuously monitor, and provide feedback of the quality of adult cardiac operations. We report on the design of this database and provide an overview of participating sites and quality of data. Methods We established a network of participating sites with an adult cardiac surgery volume of more than 100 operations per year for continuous web-based registry of in-hospital and follow-up data of coronary artery bypass grafting (CABG) and valve operations. After a routine data quality audit, we report the performance and quality of care back to the participating sites. Results In total, 87 centers participated and submitted 46,303 surgical procedures from January 2013 to December 2014. The timeliness rates of the short-list and in-hospital data submitted were 73.6% and 70.2%, respectively. The completeness and accuracy rates of the in-hospital data were 97.6% and 95.1%, respectively. We have provided 2 reports for each site and 1 national report regarding the performance of isolated CABG and valve operations. Conclusions The newly launched CCSR with a national representativeness network and good data quality has the potential to act as an important platform for monitoring and improving cardiac surgical care in mainland China, as well as facilitating research projects, establishing benchmarking standards, and identifying potential areas for quality improvements (ClinicalTrials.gov No. NCT02400125).

This study was aimed to investigate the clinical features and mutations in the PRKAR1A gene of a multigenerational kindred including 17 individuals at risk for Carney complex. Eight patients were diagnosed with Carney complex among the 17 individuals (47.1%). Among the 8 affected patients, 4 had cardiac myxomas, 8 had skin pigmentation, and 3 had diabetes. Genomic DNA sequencing in 14 surviving patients showed 6 had the same germline mutation in the sixth intron and affected the splice site. cDNA sequencing and DNAMAN software showed 159 bases were absent, resulting in the absence of the amino acids 249 to 301 from the protein. All 6 patients with this PRKAR1A gene mutation had skin pigmentation. In conclusion, the present study reported for the first time an intronic splice site mutation in the PRKAR1A gene of a Chinese family with Carney complex, which probably caused skin pigmentation observed in affected family members.

Cardiac cells marked by c-Kit or Kit, dubbed cardiac stem cells (CSCs), are in clinical trials to investigate their ability to stimulate cardiac regeneration and repair. These studies were initially motivated by the purported cardiogenic activity of these cells. Recent lineage tracing studies using Kit promoter to drive expression of the inducible Cre recombinase showed that these CSCs had highly limited cardiogenic activity, inadequate to support efficient cardiac repair. Here we reassess the lineage tracing data by investigating the identity of cells immediately after Cre labeling. Our instant lineage tracing approach identifies Kit-expressing cardiomyocytes, which are labeled immediately after tamoxifen induction. In combination with long-term lineage tracing experiments, these data reveal that the large majority of long-term labeled cardiomyocytes are pre-existing Kit-expressing cardiomyocytes rather than cardiomyocytes formed de novo from CSCs. This study presents a new interpretation for the contribution of Kit(+) cells to cardiomyocytes and shows that Kit genetic lineage tracing over-estimates the cardiogenic activity of Kit(+) CSCs.

Several earlier studies attempted to predict cardiovascular events in patients with obstructive hypertrophic cardiomyopathy (HCM) who underwent surgical myectomy; however, conclusions were inconsistent [(1,2)][1]. We sought to ascertain the prognostic predictors in these patients. We recruited and

Aims Arrhythmogenic cardiomyopathy (AC) shows large heterogeneity in its clinical, genetic, and pathological presentation. This study aims to provide a comprehensive atlas of end-stage AC and illustrate the relationships among clinical characteristics, genotype, and pathological profiles of patients with this disease. Methods and results We collected 60 explanted AC hearts and performed standard pathology examinations. The clinical characteristics of patients, their genotype and cardiac magnetic resonance imaging findings were assessed along with pathological characteristics. Masson staining of six representative sections of each heart were performed. Digital pathology combined with image segmentation was developed to calculate distribution of myocardium, fibrosis, and adipose tissue. An unsupervised clustering based on fibrofatty distribution containing four subtypes was constructed. Patients in Cluster 1 mainly carried desmosomal mutations (except for desmoplakin) and were subjected to transplantation at early age; this group was consistent with classical ‘desmosomal cardiomyopathy’. Cluster 2 mostly had non-desmosomal mutations and showed regional fibrofatty replacement in right ventricle. Patients in Cluster 3 showed parallel progression, and included patients with desmoplakin mutations. Cluster 4 is typical left-dominant AC, although the genetic background of these patients is not yet clear. Multivariate regression analysis revealed precordial QRS voltage as an independent indicator of the residual myocardium of right ventricle, which was validated in predicting death and transplant events in the validation cohort (n = 92). Conclusion This study provides a novel classification of AC with distinct genetic backgrounds indicating different potential pathogenesis. Cluster 1 is distinct in genotype and clinicopathology and can be defined as ‘desmosomal cardiomyopathy’. Precordial QRS amplitude is an independent indicator reflecting the right ventricular remodelling, which may be able to predict transplant/death events for AC patients.

Background: The histologic difference between alcoholic cardiomyopathy (ACM) and idiopathic dilated cardiomyopathy (IDCM) is unclear. The present study aimed to identify the quantitative pathologic features of ACM compared with IDCM. Methods: Specimens from 6 regions (anterior left ventricle [LV], lateral LV, inferior LV, interventricular septum [IVS], anterior right ventricle [RV], and inferior RV) were sampled from each explanted heart. Specimens from 4 healthy donor hearts were obtained as normal control. Tissues were sectioned and Masson trichrome stained. Histomorphometry was performed to evaluate the amount of myocyte, fibrosis, fatty tissue, and interstitium by Image-Pro Plus 6.0 (Media Cybernetics). Results: A total of 408 specimens were obtained from 34 ACMs and 34 IDCMs; 8 specimens were obtained from 4 healthy donor hearts. Compared to healthy donor hearts, we observed an increase in fibrosis which replaces myocytes in myocardium of end-stage cardiomyopathy. The overall myocyte ratio in myocardium was 69.5 ± 8.7% in ACM vs 71.9 ± 7.4% in IDCM (P

Background Cardiomyocytes derived from animals and induced pluripotent stem cells (iPSCs) are two main cellular models to study cardiovascular diseases, however, neither provides precise modeling of the response of mature human cardiomyocytes to disease or stress conditions. Therefore, there are emerging needs for finding an optimized primary human cardiomyocytes isolation method to provide a bona fide cellular model. Methods and results Previous established protocols for the isolation of primary human cardiomyocytes are limited in their application due to relatively low cell yield and the requirement of tissue integrity. Here, we developed a novel, simplified method to isolate human cardiomyocytes robustly with improved viability from tissue slicing. Isolated cardiomyocytes showed intact morphology, retained contractility, ion flux, calcium handling, and responses to neurohormonal stimulation. In addition, we assessed the metabolic status of cardiomyocytes from different health conditions. Conclusion We present a novel, simplified method for isolation of viable cardiomyocytes from human tissue. Electronic supplementary material The online version of this article (10.1186/s12967-018-1649-6) contains supplementary material, which is available to authorized users.

Characterizing the stem cells responsible for lung repair and regeneration is important for the treatment of pulmonary diseases. Recently, a unique cell population located at the bronchioalveolar-duct junctions has been proposed to comprise endogenous stem cells for lung regeneration. However, the role of bronchioalveolar stem cells (BASCs) in vivo remains debated, and the contribution of such cells to lung regeneration is not known. Here we generated a genetic lineage-tracing system that uses dual recombinases (Cre and Dre) to specifically track BASCs in vivo. Fate-mapping and clonal analysis showed that BASCs became activated and responded distinctly to different lung injuries, and differentiated into multiple cell lineages including club cells, ciliated cells, and alveolar type 1 and type 2 cells for lung regeneration. This study provides in vivo genetic evidence that BASCs are bona fide lung epithelial stem cells with deployment of multipotency and self-renewal during lung repair and regeneration.

Background The totally thoracoscopic procedure for mitral valve (MV) disease is a minimally invasive method. We investigated the procedure’s feasibility, safety and effectiveness when it was performed by an experienced operator. Methods We retrospectively analysed 53 consecutive patients with MV disease treated between December 2014 and April 2017 by minimally invasive procedures. The procedures were performed on femoral artery-vein bypass through three 2–4 cm incisions, with one additional penetrating point on the right chest wall under totally thoracoscopic visual guidance and surveillance of transoesophageal echocardiography. Results Two patients who underwent intraoperative conversion to sternotomy were excluded due to indivisible pleural cavity adhesion. Of the others (38 female patients, average age, 49 ± 14 years, left ventricular ejection fraction, 59 ± 7%), 34 received MV replacement for rheumatic mitral lesions, which was redone for one patient after the discovery of serious paravalvular leakage, 17 received MV repair for mitral regurgitation (with 4 secondary to atrial septum defect, 2 diagnosed with left atrial myxoma, and 2 redone for mitral valve replacement due to repair failure), 28 received additional tricuspid valvuloplasty, and one patient received a Warden procedure. The cardiopulmonary bypass and aortic cross clamp times were 144 ± 39 min and 80 ± 22 min, respectively. Postoperational chest tube drainage in the first 48 h was 346 ± 316 ml. The ventilation time and intensive care unit stay length were 11 ± 11 h and 23 ± 2 h, respectively. One patient died of disseminated intravascular coagulation and prosthesis thrombosis with fear of anticoagulation-related bleeding. Conclusions The totally thoracoscopic procedure on mitral valves by an experienced surgeon is technically feasible, safe, effective and worthy of widespread adoption in clinical practice.

Low socioeconomic status is associated with increased mortality for patients with cardiovascular disease; however, the effect of family socioeconomic status on the prognosis of children with congenital heart disease remains unclear, particularly in low-income and middle-income countries. We aimed to examine the association between family socioeconomic status and postoperative outcomes for paediatric patients with complex congenital heart disease (CCHD).In this observational cohort study, we enrolled children (aged7 years) who had CCHD surgery at Fuwai Hospital (Beijing, China) between May 1, 2012, and Dec 31, 2015. Patients who were discharged alive were followed up for up to 60 months, until May 4, 2017, for all-cause mortality and unplanned readmission events. Baseline family socioeconomic status was established using a composite of household income in the past year, and occupation and education level of each parent in the family. Cox proportional hazards regression was used to evaluate the relationship between socioeconomic status and prognosis.Of 2555 patients (median age at operation 0·88 years, IQR 0·56-1·92) enrolled, 2485 (97%) were discharged alive and were assessed at a median follow-up of 32·1 months (IQR 19·6-44·7). During follow-up, 180 (7%) patients died, and 748 (30%) patients had 1477 unplanned readmissions. Children with low family socioeconomic status (n=899) had higher unadjusted all-cause mortality and more unplanned readmission events than children with middle (n=819) or high (n=767) family socioeconomic status; 3-year overall survival was 88·5% (95% CI 86·3-90·7), 93·1% (91·1-95·1), and 96·3% (94·7-97·9), and 3-year unplanned-readmission-free survival was 56·3% (52·8-59·8), 68·4% (64·9-71·9), and 82·4% (79·5-85·3) across the socioeconomic tertiles (both log-rank p0·001). After adjustment for demographic factors, weight, cardiac diagnostic categories, operation types, and characteristics of the index hospital stay, hazard ratios were 2·66 (1·62-4·35) for all-cause mortality and 4·17 (3·31-5·25) for unplanned readmission for low versus high family socioeconomic status, and 1·95 (1·18-3·22) and 2·44 (1·94-3·07), respectively, for middle versus high family socioeconomic status.Low and middle family socioeconomic status is associated with worse prognosis after CCHD surgery than high family socioeconomic status. Measures to alleviate socioeconomic disparities are needed to improve postoperative prognosis of paediatric patients with CCHD in China.National Science Fund for Distinguished Young Scholars and National Key RD Program of China.

Platelet-derived growth factor receptor (PDGFR) signaling is involved in proliferation and survival in a wide array of cell types. The role of PDGFR signaling in heart regeneration is still unknown. We find that PDGFR-β signaling decreases in myocardium with age and that conditional activation PDGFR-β in cardiomyocytes promotes heart regeneration. Employing RNA sequencing, we show that the enhancer of zeste homolog 2 (Ezh2) can be upregulated by PDGFR-β signaling in primary cardiomyocytes. Conditional knockout of Ezh2 blocks cardiomyocyte proliferation and H3K27me3 modification during neonatal heart regeneration with Ink4a/Arf upregulation, even in mice with myocyte-specific conditional activation of PDGFR-β. We also show that PDGFR-β controls EZH2 expression via the phosphatidylinositol 3-kinase (PI3K)/p-Akt pathway in cardiomyocytes. Gene therapy with adeno-associated virus serotype 9 (AAV9) encoding activated PDGFR-β enhances adult heart regeneration and systolic function. Our data demonstrate that the PDGFR-β/EZH2 pathway is critical for promoting cardiomyocyte proliferation and heart regeneration, providing a potential target for cardiac repair.

Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the evidence comparing preservation solutions for heart preservation. Studies were searched in PubMed, Embase, the Cochrane Library, the Transplant Library, and the International Clinical Trials Registry Platform. The primary outcomes were patient survival and donor heart dysfunction. The secondary outcomes were in-hospital mortality and enzyme gene expression. The University of Wisconsin solution (UW) was associated with a significantly improved survival at 30 days and 90 days (hazard ratio = 1.16, 95% confidence interval [CI] = 1.11-1.22, P

Background The main goal of this study was to explore the feasibility of stratifying patients with secondary tricuspid regurgitation (TR) into different risk levels, and to compare the surgical outcomes of patients within different risk levels who underwent different tricuspid valve repair (TVP) approaches. Methods One hundred and one patients with left-sided valvular disease underwent either left-sided valvular replacement or repair, and 79 patients underwent concomitant TVP. Depending upon their tricuspid annulus diameter and tethering distances, the patients were assessed using 4 risk levels. The different surgical approaches were used in patients within different risk levels. Results Among the 101 patients, there were 32 patients within risk level I, 28 within risk level II, 20 within risk level III, 21 within risk level IV. In the first risk level, the patients with untreated tricuspid valves had no or mild TR after surgery. In the second and third risk levels, the patients treated with a modified De Vega procedure had mild TR at follow-up. In the fourth risk level, the patients treated with undersized annuloplasty rings exhibited an improved outcome. Conclusions The evaluation of both tricuspid annular diameter and tethering distance may help clinicians to stratify patients with secondary TR into different risk levels as a means of choosing an optimal TVP approach. The application of a modified De Vega procedure or an undersized annuloplasty ring in patients within appropriate risk level could improve the treatment for secondary TR.

Cardiac injury in neonatal 1-day-old mice stimulates a regenerative response characterized by reactive cardiomyocyte proliferation, which is distinguished from the fibrotic repair process in adults. Acute inflammation occurs immediately after heart injury and has generally been believed to exert a negative effect on heart regeneration by promoting scar formation in adults; however, little is known about the role of acute inflammation in the cardiac regenerative response in neonatal mice. Here, we show that acute inflammation induced cardiomyocyte proliferation after apical intramyocardial microinjection of immunogenic zymosan A particles into the neonatal mouse heart. We also found that cardiac injury-induced regenerative response was suspended after immunosuppression in neonatal mice, and that cardiomyocytes could not be reactivated to proliferate after neonatal heart injury in the absence of interleukin-6 (IL-6). Furthermore, cardiomyocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3), the major downstream effector of IL-6 signaling, decreased reactive cardiomyocyte proliferation after apical resection. Our results indicate that acute inflammation stimulates the regenerative response in neonatal mouse heart, and suggest that modulation of inflammatory signals might have important implications in cardiac regenerative medicine.

Objective: There is a lack of data focusing on non-communicable disease (NCD) mortality in the Chinese elderly population over the past decade. Methods: Using mortality data from the Chinese Health Statistics, we explored the crude and age-standardized mortality trend of three major NCDs in the Chinese population â¥65 years of age from 2002 to 2010, namely, malignant neoplasms, heart diseases, and cerebrovascular diseases. Subpopulations characterized as rural and urban residence, and by gender and age were examined separately. Results: Mortality increased with age and was higher among males than among females across the three NCDs, with the gender difference being most remarkable for malignant neoplasms and least for heart diseases mortality. Condition-specific crude mortalities increased between 2002 and 2010, overall and in all the pre-specified subpopulations. After age-standardization, rising trends were observed for people â¥65 years old, and condition-specific mortalities generally increased in rural regions and decreased in urban regions, especially for cerebrovascular diseases. Conclusions: There were increasing trends for mortality due to malignant neoplasms, heart diseases, and cerebrovascular diseases in China between 2002 and 2010, which were largely driven by the population aging. Disparities existed by rural and urban residence, gender, and age. Keywords: Trend, Mortality, Elderly, Non-communicable disease