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OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable. more...

To investigate the potential predictors and clinical significance of periprocedural myocardial infarction (PMI), as defined by the latest Fourth Universal Definition of Myocardial Infarction (2018), following rotational atherectomy (RA).PMI is not uncommon in patients undergoing RA, although the predictors and prognostic impact are unknown.Data from 229 consecutive patients who had undergone RA before drug-eluting stent (DES) implantation in a single center were analyzed. Patients' demographic information, clinical, angiographic, and procedural characteristics, and 1-year follow-up outcomes were collected retrospectively.The overall incidence of PMI in patients undergoing RA was 48.5%. Age (adjusted odds ratio [OR]: 1.024, 95% confidence interval [CI]: 1.001-1.047, p = 0.043) and ejection fraction (adjusted OR: 0.977, 95% CI: 0.962-0.993, p = 0.004) were independent predictors of PMI in RA, although PMI was not associated with an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs) at the 1-year follow-up in patients undergoing RA.Age and ejection fraction were independently associated with an elevated risk of PMI in patients undergoing RA. However, post-RA microinfarcts were not associated with an increased risk of MACCEs over the short-term follow-up period. more...

A PrS/pDNA/RAPA nanocomposite coating of a drug-coated balloon inhibits neointimal hyperplasia and facilitates endothelial regeneration after balloon-induced vascular injuries.

Drug-coated balloons (DCBs) offer potential to deliver drugs to treat coronary lesions but without leaving permanent implants behind. Paclitaxel and sirolimus are anti-proliferation drugs that are commonly used in commercially available DCBs. However, these drugs present significant cytotoxicity concern and low efficacy more...

Percutaneous coronary intervention (PCI) is the mainstream treatment to widen narrowed or obstructed coronary arteries due to pathological conditions. However, the post-operational neointimal hyperplasia occurs because of endothelium denudation during surgical procedures and the following inflammation. MicroRNAs (miRs) are new therapeutics of great potential for cardiovascular diseases. However, miRs easily degrade in vivo. A vehicle that can maintain their bioactivities and extend their retention at the site of delivery is prerequisite for miRs to play their roles as therapeutic reagents. Here, we reported the use of the Laponite hydrogels to deliver miR-22 that are modulators of phenotypes of smooth muscle cells (SMCs). The Laponite hydrogels allow a homogenous distribution of miR-22 within the gels, which had the capacity to transfect SMCs in vitro. Upon the injection of the miR-22 incorporated in the Laponite hydrogels in vivo, miR-22 could be well retained surrounding arteries for at least 7 days. Moreover, the miR-22 loading Laponite hydrogels inhibited the neointimal formation, reduced the infiltration of the macrophages, and reversed the adverse vascular ECM remodeling after the balloon-induced vascular injuries by upregulation of miR-22 and downregulation of its target genes methyl-CpG binding protein 2 (MECP2). The application of the Laponite hydrogels for miR local delivery may offer a novel strategy to treat cardiovascular diseases. more...

Background Intrastent haematoma after dilatation of in-stent restenosis (ISR) is rarely reported and the optimal treatment for this condition remains unclear. Case summary We present the case of an 87-year-old man with in-stent subtotal occlusion of left circumflex. He experienced chest pain after drug-eluting balloon was released in the stent. Intravascular ultrasound revealed intrastent haematoma, which was not relieved with a cutting balloon but completely sealed by an Endeavor Resolute stent. Discussion Intrastent haematoma after dilatation of ISR is rare. Reimplantation of stent seems the best method to solve this problem. Intravascular ultrasound imaging may provide insight into the cause of ISR and guide the treatment. more...

Objective To investigate whether ABO blood groups is associated with the severity of coronary artery disease (CAD). Methods Between January 2015 and December 2017, 1425 first diagnosed CAD patients confirmed by selective coronary angiography were recruited into this cross-sectional study, and their baseline characteristics, ABO blood groups, Gensini score were collected. Multiple linear regression analysis was performed to test the association between the severity of CAD and ABO blood groups. Results The Gensini score was significantly higher in the blood group A than in the non-A groups (41.2 ± 32 vs. 38 ± 27; P = 0.026). After adjusting for age, male, smoking, family history of CAD, hypertension, diabetes mellitus and hypercholesterolemia, multivariate linear regression indicated that blood group A was associated with the severity of CAD (β = 3.298, 95% CI: 0.91–6.505, P = 0.044). In diabetes group, A blood type was also associated with increased Gensini score (P = 0.02) after adjusting for age, male, family history of CAD, hypercholesterolemia, smoking and hypertension. Conclusion In this cross-sectional study, the data indicated that blood group A was an independent risk factor of severity of CAD in Chinese population and Chinese patients with type 2 diabetes. more...

Rationale: Restoration of coronary artery blood flow is the most effective means of ameliorating myocardial damage triggered by ischemic heart disease. However, coronary reperfusion elicits an increment of additional injury to the myocardium. Accumulating evidence indicates that the unfolded protein response (UPR) in cardiomyocytes is activated by ischemia/reperfusion (I/R) injury. Xbp1s (spliced X-box binding protein 1), the most highly conserved branch of the unfolded protein response, is protective in response to cardiac I/R injury. GRP78 (78 kDa glucose-regulated protein), a master regulator of the UPR and an Xbp1s target, is upregulated after I/R. However, its role in the protective response of Xbp1s during I/R remains largely undefined. Objective: To elucidate the role of GRP78 in the cardiomyocyte response to I/R using both in vitro and in vivo approaches. Methods and Results: Simulated I/R injury to cultured neonatal rat ventricular myocytes induced apoptotic cell death and strong activation of the UPR and GRP78. Overexpression of GRP78 in neonatal rat ventricular myocytes significantly protected myocytes from I/R-induced cell death. Furthermore, cardiomyocyte-specific overexpression of GRP78 ameliorated I/R damage to the heart in vivo. Exploration of underlying mechanisms revealed that GRP78 mitigates cellular damage by suppressing the accumulation of reactive oxygen species. We go on to show that the GRP78-mediated cytoprotective response involves plasma membrane translocation of GRP78 and interaction with PI3 kinase, culminating in stimulation of Akt. This response is required as inhibition of the Akt pathway significantly blunted the antioxidant activity and cardioprotective effects of GRP78. Conclusions: I/R induction of GRP78 in cardiomyocytes stimulates Akt signaling and protects against oxidative stress, which together protect cells from I/R damage. more...

The close proximity of esophagus to the left atrial posterior wall predisposes esophagus to thermal injury during catheter ablation for atrial fibrillation (AF). In this retrospective study, we aimed to investigate risk factors of esophageal injury (EI) caused by catheter ablation for AF. Patients who underwent first-time AF ablation from July 2013 to June 2018 were included. The esophagus was visualized by oral soluble contrast during ablation for all patients and a subset of patients were selected to undergo endoscopic ultrasonography (EUS) to estimate EI post ablation. Degree of EI was categorized as Kansas City classification: type 1: erythema; type 2: ulcers (2a: superficial ulcers; 2b: deep ulcers); type 3: perforation (3a: perforation without communication with the atria; 3b: atrioesophageal fistula [AEF]). Of 3,852 patients, 236 patients (61.5 ± 9.7 years; male, 69%) received EUS (EUS group) and 3616 (63.2 ± 10.9 years; male, 61.1%) without EUS (No-EUS group). In EUS group, EI occurred in 63 patients (type 1 EI in 35 and type 2 EI in 28), and no type 3 EI was observed during follow up. In a multivariable logistic regression analysis, an overlap between the ablation lesion and esophagus was an independent predictor of EI (odds ratio, 21.2; 95% CI: 6.23–72.0; P more...

The mechanisms underlying atrial fibrillation (AF) initiation and pulmonary vein isolation (PVI) effectiveness remain unclear. Ganglionated plexus (GPs) have been implicated in AF initiation and maintenance. In this study, we evaluated the impact of GP ablation in patients with PV firing after PVI. Patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation therapy with PVI were screened. Amongst 840 cases over a 3.75 year period, 12 cases were identified with persistent PV firing (left = 4 and right = 8) after PVI was achieved and left atrial sinus rhythm restored. Adjacent GP ablation was performed anatomically and followed if necessary by additional PV ablation. In eight patients, PV firing was terminated during GP ablation outside of the circumferential ablation line. In one patient, additional PV ablation resulted in cessation of PV firing and in the remaining three patients, firing could not be terminated by GP ablation or additional PVI. GP ablation outside of wide antral circumferential line frequently results in the cessation of rapid firing from electrically isolated PVs. These observations suggest that interactions between left atrium and PV beyond electrical conduction warrant consideration in AF mechanisms. This article is protected by copyright. All rights reserved. more...

Background Earlier vascular healing after drug-eluting stent (DES) implantation may reduce the incidence of late stent thrombosis and provide theoretical evidence to shorten dual antiplatelet therapy duration in patients with high bleeding risks. The BuMA supreme stent is a newly developed DES-coated with the sirolimus by using the international patent electronic grafted eG™ technology. Previous randomized trials showed that BuMA stents had better stent-strut coverage at 3-month follow-ups, which were evaluated by optical coherence tomography (OCT). However, there have been a limited number of studies that are directly evaluating the extent of neointima formation at the first and second months after stent implantation in high-bleeding-risk patients with coronary artery disease. This clinical trial is designed to demonstrate the non-inferiority of the BuMA supreme stent compared to the XIENCE stent in early neointimal formation. Methods/design This is a prospective, multicenter, randomized trial. Forty patients will be assigned into the first-month OCT group, and another 40 patients into the second-month OCT group. The patients in each cohort will be randomized again into two groups in a 1:1 ratio, either being implanted with the BuMA Supreme stent or the Xience V/Prime/Xpedition stent. The primary endpoint is stent-strut neointimal coverage rate (%) at the first and second months, respectively. Secondary endpoints include neointimal hyperplasia area/volume, neointimal hyperplasia thickness, stent-strut malapposition rate, late lumen loss (LLL), restenosis rate, device/lesion/clinical success rate, device-oriented composite endpoints at the first and second months, stent thrombosis and other serious adverse events and bleeding events at follow-up. Discussion The results will provide the first accurate imaging evidence on neointimal formation of the BuMA Supreme stent and the Xience stent at 1–2 months post PCI. The result should inspire further exploration and adjustment of DAPT treatments. Trial registration ClinicalTrials.gov, ID: NCT02747329. Registered on 21 April 2016. Last updated 17 May 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3361-0) contains supplementary material, which is available to authorized users. more...

Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be beneficial for chronic heart failure. However, whether QL can also improve endothelial cell function in diabetic rats remains unknown. Here, we investigated the effect of QL treatment on endothelial dysfunction by comparing the effect of QL to that of benazepril (Ben) in diabetic Sprague-Dawley rats for 8 weeks. Cardiac function was evaluated by echocardiography and catheterization. Assays for acetylcholine-induced, endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation, serum nitric oxide (NO), and nitric oxide synthase (NOS) as well as histological analyses were performed to assess endothelial function. Diabetic rats showed significantly inhibited cardiac function and EDR, decreased expression of serum NO and phosphorylation at Ser1177 on endothelial NOS (eNOS), and impaired endothelial integrity after 8 weeks. Chronic treatment for 8 weeks with either QL or Ben prevented the inhibition of cardiac function and EDR and the decrease in serum NO and eNOS phosphorylation caused by diabetes. Moreover, either QL or Ben suppressed inducible NOS (iNOS) protein levels as well as endothelial necrosis compared with the diabetic rats. Additionally, QL prevented the increase in angiotensin-converting enzyme 1 and angiotensin II receptor type 1 in diabetes. Thus, chronic administration of QL improved serum NO production, EDR, and endothelial integrity in diabetic rat aortas, possibly through balancing eNOS and iNOS activity and decreasing renin–angiotensin system expression. more...

Is Pulmonary Vein Firing an Epiphenomenon?Introduction Rapid firing in pulmonary veins (PVs) is a leading cause of paroxysmal atrial fibrillation. We hypothesized that PV firing (PV-F) should continue after circumferential PV isolation (CPVI) because the PV tissue responsible for PV-F remains intact. Methods and Results In Group-1 (n = 92), isoproterenol (ISP) and adenosine triphosphate (ATP) were co-administered to provoke PV-F before and after CPVI. The site of rapid focal discharge that initiated atrial fibrillation (AF) defined PV-F versus non-PV-F. Additional 17 patients with PV-F induced by ISP+ATP before CPVI were enrolled into Group-2 and various pacing maneuvers were used in conjunction to ISP+ATP to provoke PV-F after CPVI. In Group-1, AF was induced in 47/81 (58.0%) and 16/88 (18.2%) patients before and after CPVI, respectively (P < 0.01). Before CPVI, 43/47 (91.5%) of the rapid firing originated from PV. After successful CPVI, 88/92 patients were in sinus rhythm and non-PV-F was induced in 14/88 patients. PV-F was induced in 2/88 patients, which was eliminated by ganglionated plexus ablation outside the CPVI line. In Group-2, various pacing maneuvers with ISP+ATP only induced PV-F in 1/17 patients after CPVI. Conclusion Marked suppression of PV-F after CPVI strongly suggests that the real source of PV-F is located in the atrium. PV-F may be an epiphenomenon. more...

The study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) for treating patients with single de novo coronary lesions compared with the durable polymer everolimus-eluting stent (EES) XIENCE V.A total of 458 patients with single de novo native coronary lesions ≤24 mm in length and a coronary artery ≥2.25 to ≤4.0 mm in diameter were enrolled in the TARGET I study, a prospective, randomised, non-inferiority trial. The primary endpoint was in-stent late lumen loss (LLL) at nine-month follow-up. The secondary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, target vessel myocardial infarction (TVMI), or ischaemia-driven target lesion revascularisation (iTLR). Patients were centrally randomised to treatment with either biodegradable polymer SES (n=227) or durable polymer EES (n=231). The nine-month in-stent LLL of the biodegradable polymer SES was comparable to the EES group (0.13 ± 0.24 mm vs. 0.13 ± 0.18 mm, p=0.94; difference and 95% confidence interval 0.00 [-0.04, 0.04] mm; p for non-inferiority0.0001). Cardiac death (0.4% vs. 0.0%), TVMI (1.3% vs. 1.7%), iTLR (0.4% vs. 0.4%) and TLF (2.2% vs. 2.2%) were similar between the biodegradable polymer SES and durable polymer EES groups at 12-month follow-up (all p0.05). No definite/probable stent thrombosis was observed in both of these groups.In the multicentre TARGET I trial, the novel abluminal groove-filled biodegradable polymer SES FIREHAWK was non-inferior to the durable polymer EES XIENCE V with respect to the primary endpoint of in-stent LLL at nine months for treating patients with single de novo coronary lesions. The incidences of clinical endpoints were low in both of the stents at 12-month follow-up. (ClinicalTrials.gov identifier: NCT01196819). more...

The mechanisms underlying atrial fibrillation (AF) initiation and pulmonary vein isolation (PVI) effectiveness remain unclear. Ganglionated plexus (GPs) have been implicated in AF initiation and maintenance. In this study, we evaluated the impact of GP ablation in patients with pulmonary vein (PV) firing after PVI.Patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation therapy with PVI were screened. Among 840 cases over a 3.75-year period, 12 cases were identified with persistent PV firing (left = 4 and right = 8) after PVI was achieved and left atrial sinus rhythm restored. Adjacent GP ablation was performed anatomically and followed if necessary by additional PV ablation.In eight patients, PV firing was terminated during GP ablation outside of the circumferential ablation line. In one patient, additional PV ablation resulted in cessation of PV firing and in the remaining three patients, firing could not be terminated by GP ablation or additional PVI.GP ablation outside of wide antral circumferential line frequently results in the cessation of rapid firing from electrically isolated PVs. These observations suggest that interactions between left atrium and PV beyond electrical conduction warrant consideration in AF mechanisms. more...

CaMKII and Arrhythmias. Background: CaMKII activation is proarrhythmic in heart failure where myocardium is stretched. However, the arrhythmogenic role of CaMKII in stretched ventricle has not been well understood. Objective: We tested abnormal impulse inducibility by stretch current in myocytes isolated from CaMKIIδ knockout (KO) mouse left ventricle (LV) where CaMKII activity is reduced by ≈ 62%. Methods and Results: Action potentials were recorded by whole-cell patch clamp, and abnormal impulses were induced in LV myocytes by a simulation of stretch-activated channel (SAC) current. SAC activation failed to induce abnormal impulses in wild type (WT) myocytes but steadily produced early after-depolarizations and automaticity in KO myocytes in which an increase in L-type calcium channel (LTCC) current (ICa) and a reduction of sarcoplasmic reticulum Ca2+ leak and action potential duration (APD) were observed. The abnormal impulses were not suppressed by CaMKII inhibitor AIP whereas a low concentration of nifedipine eliminated abnormal impulses without shortening APD, implicating ICa in promoting stretch-induced abnormal impulses. In addition, APD prolongation by LTCC opener S(-)Bay K 8644 or isoproterenol facilitated abnormal impulse induction in WT ventricular myocytes even in the presence of CaMKII inhibitor AIP, whereas APD prolongation by K+ channel blocker 4-aminopyridine promoted abnormal impulses in KO myocytes but not in WT myocytes. Conclusion: ICa activation plays a central role in stretch-induced abnormal impulses and APD prolongation is arrhythmogenic only when ICa is highly activated. At increased ICa activation, CaMKII inhibition cannot suppress abnormal impulse induction. (J Cardiovasc Electrophysiol, Vol. 24, pp. 457-463, April 2013) more...

Endothelial injury usually underlies the initial pathologic step of cardiovascular diseases. Primary endothelial cell (EC) apoptosis and secondary hyperproliferation both contribute to the development of atherosclerosis and luminal occlusion. In order to investigate the effects of resveratrol (RSV) on EC apoptosis, we applied high shear stress (HSS) with proinflammatory factors [tumor necrosis factor alpha (TNF-α) plus cycloheximide] to human pulmonary microvascular ECs (PMVECs) through an artificial capillary system. Intracellular reactive oxygen species (ROS) was measured by spectrofluorometry using dihydrorhodamine 123 fluorescent probe. Apoptosis and proliferation was determined by flow cytometric analysis. Protein expression was examined by Western blot. HSS plus inflammation significantly raised the ROS and the apoptosis level of PMVECs, which could be diminished by RSV pretreatment. In a 7-days incubation assay, RSV effectively inhibited the initial increase in apoptosis and thereby prevented subsequent PMVEC hyperproliferation induced by HSS plus inflammation. Mercaptosuccinate, a glutathione peroxidase (GPx-1) inhibitor or nicotinamide, a silent information regulator 2/sirtuin 1 (SIRT1) inhibitor could attenuate the antiapoptotic action of RSV on PMVECs; and RSV treatment upregulated GPx-1 and SIRT1 expression in PMVECs. In conclusion, RSV, probably by activating SIRT1 signaling pathway, inhibits the oxidative-stress-dependent phenotypical shift of ECs induced by HSS and proinflammatory factors in vitro. more...

Noninducibility of atrial fibrillation (AF) by additional electrograms-guided ablation may benefit the clinical outcome. This report illustrates the effect of adenosine triphosphate (ATP) injection on AF inducibility after pulmonary vein (PV) isolation. AF was triggered twice by ATP without PV reconnection. Meanwhile, complex fractionated atrial electrograms (CFAEs) were observed, and ablation targets on these sites appeared to be essential to the AF elimination. It suggests that CFAEs may contribute to the initiation of some AF. ATP may be useful to induce AF after proven PV isolation, and further ablation might be necessary to ensure efficacy after circumferential PV isolation. (PACE 2010; 33:248–251) more...

Previous studies have underlined the importance of endothelial dysfunction and microvascular occlusion in the pathogenesis of pulmonary artery hypertension (PAH). Since the endothelial progenitor cells (EPCs) are involved in maintaining endothelial homeostasis, we observed the change of peripheral EPCs in canines before and after PAH onset. PAH was induced by intra-pulmonary artery injection of dehydromonocrotaline (DHMC) in nine beagles. Before and 48 h and 6 weeks after DHMC injection, 40 ml peripheral blood was obtained from the femoral vein. Circulating EPCs were identified as CD133 + KDR + cells and numerated by fluorescence-activated cell sorter; the EPCs functional capacity was determined by in vitro tubule-forming assay. The senescence of EPCs was determined by beta-galactosidase staining. At each time point, 2 ml blood from femoral artery was obtained for arterial oxygen pressure (PaO(2)). Forty-eight hours after DHMC injection, treated beagles suffered from hypoxemia; however, both the number and the tubule-forming capacity of EPCs were transiently raised. Six weeks later, PAH was confirmed by obviously high mean pulmonary arterial pressure (20.2 +/- 1.64 vs. 11.3 +/- 2.0 mmHg, p0.05) and low PaO(2) (69.30 +/- 9.15 vs. 95.94 +/- 1.43 mmHg, p0.01) in beagles after DHMC treatment, and their EPCs exhibited a predominant decrease in either the number (206.1 +/- 26.8 vs. 632.8 +/- 42.8 cells/ml blood, p0.01) or the tubule-forming capacity (21.1 +/- 2.8 vs. 11.2 +/- 2.8 tubules/x200 field, p0.01). Additionally, senescence-associated beta-galactosidase-positive EPCs were significantly increased. Our data suggested that, after the acute stage of DHMC injury to pulmonary vessels, the EPCs from PAH beagles suffered from exhaustion and senescence. more...

Endothelial apoptosis underlies the pathophysiology of pulmonary arterial hypertension (PAH). Some factors/cytokines released by endothelial progenitor cells (EPC) have been revealed as potent inhibitors of apoptosis. The aim of this study was to investigate the effects of EPC on pulmonary microvascular endothelial cell (PMVEC) survival with the PAH condition.PMVEC apoptosis was induced by high shear stress (HSS) with serum starvation or pro-inflammatory factors in an artificial capillary system. EPC were delivered into monocrotaline-induced PAH nude rats.PMVEC apoptosis under HSS and serum starvation conditions was significantly inhibited by EPC conditioned medium (CM). It was attenuated by vascular endothelial growth factor (VEGF)-A or -B blocking. EPC CM promoted PMVEC proliferation, which was weakened by VEGF-A or interleukin (IL)-8 blocking. The EPC CM caused less apoptosis of PMVEC induced by HSS plus pro-inflammatory factors. The anti-apoptotic effect of EPC CM was attenuated by blockade of either vascular endothelial growth factor receptor (VEGFR)-1 or -2. However, the pro-proliferating effect appeared to be weakened only by VEGFR-2 blocking. Both Erk1/2 and Akt phosphorylation were enhanced by EPC CM. VEGFR-2 blockage led to significant inhibition of Erk1/2 and Akt activation; VEGFR-1 blockage only of Erk1/2 activation. Human-origin VEGF co-localized with incorporated EPC in small pulmonary arterioles, and EPC transplantation resulted in down-regulation of caspase-3 expression.The VEGF-A/B-VEGFR-1/2-Erk1/2 signal pathway took major responsibility for the anti-apoptotic effects of EPC on PMVEC, and VEGF-A-VEGFR-2-Akt for pro-proliferating effects. Growth factors, secreted in a paracrine manner by transplanted EPC, inhibited cell apoptosis in PAH lung. more...

Introduction: Emerging data have suggested that right ventricular (RV) apical pacing results in progressive left ventricular (LV) dysfunction and contributes to the development of heart failure (HF). This study aimed to investigate the prevalence and clinical predictors for the development of new-onset HF after long-term RV apical pacing in patients with acquired atrioventricular (AV) block who require permanent pacing. Methods: We studied the clinical outcomes after long-term RV apical pacing for acquired AV block in 304 patients without a prior history of HF. All patients had >90% ventricular pacing as determined by device diagnostic data. Results: After a median follow-up of 7.8 years, 79 patients (26.0%) developed new-onset HF after RV apical pacing. Univariate Cox-regression analysis revealed that older age at the time of pacemaker implantation (P < 0.001), the presence of coronary artery disease (CAD) (P < 0.001) or atrial fibrillation (P = 0.03), VVI pacemaker (P < 0.001), wider paced QRS duration (P < 0.001), and new-onset myocardial infarction (P < 0.001) were predictors for HF. Multivariate analysis revealed that older age at implantation (Hazard ratio [HR] 1.06, 95% confidential interval [CI] 1.04–1.09, P < 0.001), CAD (HR 1.98, 95% CI 1.12–3.50, P < 0.05), and a wider paced QRS duration (HR 1.27 for each 10 ms increment, 95% CI 1.11–1.45, P = 0.001) were independent predictors of HF. Furthermore, cardiovascular mortality was significantly increased in those with HF (36.7% vs. 2.7%, P < 0.001). Conclusions: After a median follow-up of 7.8 years, permanent RV apical pacing was associated with HF in 26% of patients. Elderly age at the time of implant, a wider paced QRS duration and the presence of CAD independently predicted new-onset HF. More importantly, HF after RV apical pacing was associated with a higher cardiovascular mortality. more...

A 53-year-old female was admitted in October 2000 with acute onset of dyspnoea. Chest X-ray showed pulmonary oedema. Electrocardiography (ECG) showed sinus tachycardia. Echocardiography (ECHO) revealed diffuse hypokinesia of the left ventricle (LV) and LV enlargement. The patient showed significant clinical improvement after inotropic, diuretic, and vessel dilatory treatment. In May 2005, the patient was admitted again with dyspnoea. ECHO showed hypokinesia of LV middle and basal segments with normal chamber diameter. ECG showed ST depression in V2–V6 lead (Fig. 1A). The patient refused coronary angiography and was discharged. In May 2010, the patient had a third relapse of dyspnoea. ECG showed sinus tachycardia and ST elevation of II, III, AVF and V2–V6 lead (Fig. 1B). Coronary angiography showed normal coronary arteries. Left ventriculography showed apical akinesia and basal hyperkinesia (Fig. 2). In July 2011, the patient had a fourth relapse of dyspnoea. ECG showed ST depression in II, III, aVF and V2–V6 lead (Fig. 1C). ECHO revealed posterior and lateral basal hypokinesia. This time we found a mass located at the right adrenal gland by computed tomography scan (Fig. 3). Mass excision was performed and pathologic examination disclosed a grey-red mass measuring 75 × 45 × 35 mm with complete capsule. Histopathologic examination confirmed adrenal pheochromocytoma (Fig. 4). Follow-up ECHO revealed normalised wall motion abnormalities. The patient remains asymptomatic three years after the operation. Pheochromocytoma can cause cardiac manifestations including a transient, reversible cardiomyopathy that is called catecholamine cardiomyopathy (Zelinka T et al. Horm Metab Res, 2012; 44: 379–384). It can resemble Takotsubo cardiomyopathy as during the third hospi talisation (Ueda H et al. Int J Cardiol, 2011; 149: e50–e52), as well as inverted-Takotsubo cardiomyopathy as during the second hospitalisation (Kim S et al. Clin Cardiol, 2010; 33: 200–205). The ECGs are non-specific (Mitsuma W et al. Am J Cardiol, 2007; 100: 106–109). Our case appears unique and LV wall motion abnormalities during four episodes that are different in the same patient requires the vigilance of clinicians. Tumour resection is most helpful for this patient. more...

Lycopene (Ly), the most common type of antioxidant in the majority of diet types, provides tolerance to ischemia/reperfusion injury. However, the underlying mechanism of the protective effects observed following Ly administration remains poorly investigated. The aim of the current study was to investigate whether Ly prevents damage to hypoxia/reoxygenation (HR)‑induced H9C2 myocardioblasts in an autophagy‑dependent manner. The levels of autophagic markers were detected using western blotting, the level of apoptosis was detected using western blotting and flow cytometry. The activation of autophagy was impaired via knockdown of the expression of 'microtubule‑associated protein 1‑light chain 3β (MAP1LC3B)' and 'Beclin 1'. After 16 h hypoxia, followed by 2 h reoxygenation, the expression levels of the microtubule‑associated protein 1A/1B‑light chain 3 (LC3) and Βeclin 1 autophagic biomarkers, and cell viability were reduced, whereas the percentage of apoptotic cells, and the expression levels of the Bax/B‑cell lymphoma 2 (Bcl‑2) and active caspase‑3 apoptotic biomarkers were increased. Pre‑incubation of the cells with different Ly concentrations reversed the HR‑induced inhibition of autophagy and cell viability, and the HR‑induced elevation in apoptotic levels. The induction of autophagy was accompanied by reduced apoptosis, and decreased expression levels of Bax/Bcl‑2 and active caspase‑3. In addition, the impairment of autophagy by silencing the expression of MAP1LC3B and Beclin 1 accelerated HR‑induced H9C2 cell apoptosis and the Ly‑mediated protective effects disappeared. Furthermore, Bax/Bcl‑2 and active caspase‑3 expression levels were increased. Moreover, Ly‑induced autophagy was associated with increased adenosine monophosphate kinase (AMPK) phosphorylation. Suppressed AMPK phosphorylation using compound C terminates Ly‑mediated cytoprotective effects. Ly treatment improves cell viability and reduces apoptosis as a result of the activation of the adaptive autophagic response on HR‑induced H9C2 myocardioblasts. AMPK phosphorylation may be involved in the progression. more...

To investigate the safety, medium-term and long-term efficacy of transradial percutaneous coronary intervention for unprotected left main coronary artery lesions with 6 French guiding catheter.Sixty-one patients with unprotected left main coronary artery lesions were treated by 6 French transradial percutaneous coronary intervention between January 2008 and December 2009. The mean age of patients was (66.03 ±10.02)years (44-87). Among 61 cases, 40 had hypertension and 14 had diabetes mellitus; 22 had a history of smoking. The average left ventricle ejection fraction was (62.96 ±12.15)% (range: 28-86) and the average plasma creatinine level was (82.92 ±18.30)μmol/L (range: 44-130). The major adverse cardiac events (MACE) after the procedure were evaluated.Procedural success was achieved in all cases. A total of 67 stents were implanted. No in-hospital death occurred. Mean clinical follow-up period was (26.25 ±5.92) months (range: 19-44 months). MACE developed in 6 cases (9.8%) during the follow-up period, including 2 death (3.3%) and 4 case of target lesion revascularization (6.6%). Compared with low-risk group (SYNTAX score33), MACE was increased in the high-risk group (SYNTAX score32).6 French transradial percutaneous coronary intervention for patients with unprotected left main coronary artery lesions is safe and feasible procedure with desirable medium-and long-term outcomes. more...

Cardiac resynchronization therapy (CRT) with biventricular pacing improves cardiac function, functional capacity and quality of life in selected patients with heart failure. The current study aimed to evaluate the efficacy of the intracardiac electrogram (IEGM)-based optimization method, QuickOpt(TM), in Chinese patients treated with CRT.Aortic time velocity integrals (AVTI) achieved at the sensed atrioventricular (AV), paced AV and interventricular (VV) interval settings recommended by both QuickOpt(TM) and standard echocardiographic optimization were measured in 101 patients. Consistency and the strength of the relationship between the two timing cycle optimization methods were assessed by intra-class correlation coefficient (ICC).The ICC showed good agreement and correlation with what the AVTI achieved at the optimal sensed AV (ICC = 0.9683 (0.9535 - 0.9785)), paced AV (ICC = 0.9642 (0.9475 - 0.9757)) and VV (ICC = 0.9730 (0.9602 - 0.9817)) interval settings determined by the two optimization methods. The average time required by echocardiographic optimization and by QuickOpt(TM) were (78.32 ± 32.40) minutes and (1.98 ± 1.64) minutes respectively (P0.0001).The QuickOpt(TM) algorithm provides a quicker, simpler and reliable alternative to the standard method for timing cycle optimization. more...