Efficacy and safety analysis of ivabradine hydrochloride treatment of Chinese patients with chronic heart failure: subgroup analysis of Chinese patients in the SHIFT study / 中华心血管病杂志

Objective@#To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the If inhibitor ivabradine trial (SHIFT).@*Method@#A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes).@*Results@#A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, P<0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), HR=0.56, 95%CI 0.33-0.97, P=0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), P=0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes).@*Conclusions@#Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study.@*Clinical Trial Registry@#International standard randomized controlled trials registry, ISRCTN 70429960.

Transcatheter aortic valve implantation:the preliminary experience from West China Hospital / 中国介入心脏病学杂志

Objective To discuss the preliminary experience of transcatheter aortic valve implatantion in patients with severe aortic valve stenosis. Methods The baseline characteristics, hemodynamic changes and clinical outcomes of the patients received TAVI in our institution were analyzed. Results A total of 36 patients underwent TAVI between April 2012 and March 2014. The mean age was (73.4±8.7) years and 24 (66.7%) of them were men. The mean logistic EuroSCORE was (20.6±9.9)%. 25(70%) patients had bicuspid aortic valves. TAVI was successful in 35 patients (97.2%) and valve-in-valve implantation was required in 4 (11.1%) of them. After the procedure, the mean aortic-valve gradient reduced to (10.5±5.7) mmHg. In 2 patients (5.6%), there was marginal moderate periprosthetic leak. At 30 days, the survival rate was 97.2%. Two patients (5.6%) developed who later showed fuel recovery, without significant sequela. Permanent pacemakers were implanted in 10 patients (27.8%) due to the onset of third-degree atrioventricular block after TAVI. To date, the median follow-up duration has exceeded 323 days. 2 patients died of cancer on 374 days and 680 days after TAVI, respectively. Conclusions TAVI is feasible, safe and effective in treating severe stenosis of bicuspid as well as tricuspid aortic valve in selected Chinese patients unsuitable for surgery.

Adipocytokines: factors with various suggested functions / 生物医学工程学杂志

Fat accumulation has been shown to play important roles in the development of obesity-related disorders such as atherosclerosis, diabetes mellitus and hypertension. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine functions. These are achieved predominantly through release of adipocytokines, which include several novel molecules released by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells, like TNF-alpha and IL-6. Adipocytokines may affect cardiovascular, hepatic, muscular and metabolic function. In this review, the recent research work of adipocytokines will be discussed.

Molecular mechanism of the changes in ventricular electrical remodeling caused by mechano-electrical feedback in rabbits with congestive heart failure / 生物医学工程学杂志

This study sought to explore the relationship between the change in ventricular electrical remodeling caused by mechano-electrical feedback and the expression of L-type Ca2+ -channel and/or sarcoplasmic reticulum Ca2+ -ATPase in the rabbits with congestive heart failure (CHF). 138 rabbits were divided into two groups (CHF and control). We measured the ventricular monophasic action potential duration (MAPD) and ventricular effective refractory period (VERP) during ventricular pacing at the stimulus frequency of 220/240/260 bpm in these rabbits. Rapid atrial pacing (260/min) was given for 30 minutes. The MAPD and VERP were measured again. Then ventricular fibrillation was induced by S1S2S3 program stimulation. We extracted the total RNA from the myocardium respectively and detected L-type Ca2+ -channel mRNA and sarcoplasmic reticulum Ca2+ -ATPase mRNA by use of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). In group CHF, with the increasing of preload/afterload, L-type Ca2+ -channel mRNA was up regulated after rapid atrial pacing when compared with that in control groups (P < 0.05). There was no significant change in sarcoplasmic reticulum Ca2+ -ATPase mRNA after rapid atrial pacing when compared with controls (P > or = 0.05). The changes in MAPD90 and VERP were related with the extent of L-type Ca2+ -channel mRNA up regulation. But the changes in MAPD90 and VERP were not significantly related with the extent of sarcoplasmic reticulum Ca2+ -ATPase mRNA up regulation. These findings suggest that Mechano-Electrical Feedback could increase the regional changes of ventricular electrical remodeling in rabbits with CHF and so to predispose them to ventricular arrhythmia. The changes may be related with the up regulation of L-type Ca2+ -channel mRNA, but not with sarcoplasmic reticulum Ca2+ -ATPase mRNA.

Changes of sarcolemma Na+/K+ ATPase and sarcoplasmic reticulum membrane Ca2+ ATPase activity after stem cell transplantation in chronic heart failure / 生物医学工程学杂志

To assess the changes of sarcolemma Na+/K+ ATPase (CMNKA) and sarcoplasmic reticulum membrane Ca2+ ATPase (SERCA) activities after stem cells transplantation in heart failure. Rabbit was used as heart failure model by intravenously injecting adriamycin. Autologous bone marrow mononuclear cells (BMCs), bone marrow mesenchymal stem cells (MSCs) or skeletal myoblasts (SMs) were introduced into coronary arteies through the root of aorta when two balloons occluding just above sinus of Valsalva. After 4 weeks, left ventricular ejection fraction (LVEF)was evaluated by echocardiography, and the activities of CMNKA and SERCA were measured by colorimeter. In BMCs (n=8)and MSCs (n=8) group, LVEF were significantly improved (P < 0.05). No significant improvement were seen in SMs group (n=6) compared to sham group (n=8). The CMNKA activity in all stem cells groups was significantly increased compared to sham group (P < 0.05). Meanwhile, in comparison with sham group, the incremental tendencies of SERCA activity were seen in stem cells groups. In conclusion, stem cells transplantation could increase the activities of CMNKA and SERCA in heart failure, a possible mechanism to improve heart function.

Changes of heart function after different cell type stem cell transplantation in chronic heart failure / 生物医学工程学杂志

To investigate the feasibility of introcoronary cell infusion into nonischemic heart failure (HF) heart and whether different types of stem cell transplantation would affect heart function to a similar degree. Japanese white ears rabbits were used as HF models by intravenous injection adriamycin. Autologous bone marrow mononuclear cells(BMCs), bone marrow stromal cells (MSCs), skeletal myoblasts (SMs) or culture medium were infused into coronary arteries respectively by occluding the root of ascending aorta. The mortality during and 4 weeks after the procedure the mortality was 7.1% and 16.7% respectively. After 4 weeks, the ejection fraction (EF) in BMCs group had significant improvement (P < 0.05, n=8). No significant difference was seen in MSCs (n =8), SMs (n=6) and sham groups (n=8) compared with pretransplantation (P > 0.05). In sham group,the left ventricular endostolic diameter (LVED) had significant enlargement (P < 0.05), No significant difference was seen in MBCs, MSCs and SMs groups compared with pretransplantation (P > 0.05). Immunofluorescence revealed de novo expression of cardiac troponin I in BMCs and MSCs groups, cardiac troponin I was not detected in SMs group. In conclusions, intracoronary cell transplantation could provide effective cell delivery into dilated cardiomyopathy hearts and could be a useful strategy for treating CHF, BMCs cell transplantation may be the first choice in all the above cell types.

Feasibility of stem cells transplantation through aorta in adriamycin-induced heart failure / 生物医学工程学杂志

Stem cells transplantation is a promising strategy for treating myocardial infarction and/or chronic heart failure; however, with respect to nonischemic heart failure, there are some limitations inherent in the current methods of transplantation. In this study, we investigated the feasibility of a novel method, i. e. transplantation through the root of aorta when the ascending aorta occluded above the sinus aortae. Japanese white ears rabbits were used as chronic heart failure models by intravenous injection of adriamycin. Autologous bone marrow mononuclear cells (MNC) were infused into the root of aorta when the ascending aorta was occluded by a couple of balloons above the sinus aortae. After 4 weeks, ejection fraction was significantly improved in MNC group. In conclusion, we have developed a unique method for efficient and safe cell transplantation based on infusion in aorta. This method, potentially suitable for nonischemic heart failure and could be used to achieve even and global supply of cells in heart.

Relation between coronary artery disease and polymorphism of angiotensin converting enzyme gene / 生物医学工程学杂志

This study was aimed to determine the relationship between coronary artery disease(CAD) and insertion/deletion(I/D) polymorphism of the angiotensin coverting enzyme(ACE) gene. The ACE genotypes of 105 patients with CAD (50 of them were accompanied by essential hypertension (EH)) and 102 healthy people were detected by polymerase chain reaction. The results showed that in terms of ACE genotypes, no significant difference was noted between CAD group and control group, nor was it observed between CAD group and CAD accompanied by EH group, and nor was it seen between CAD/CAD accompanied by EH group and control group. These findings suggest that there is no relationship between the polymorphism of ACE gene and CAD (including those accompanied by EH).