Implications of left atrial volume index in patients with three-vessel coronary disease: A 6.6-year follow-up cohort study.

BACKGROUND: Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD. METHODS: This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. RESULTS: During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). CONCLUSIONS: LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

First-in-human evaluation of a novel ultrathin sirolimus-eluting iron bioresorbable scaffold: 3-year outcomes of the IBS-FIM trial.

BACKGROUND: The first-generation polymeric bioresorbable scaffolds resulted in higher than acceptable 3-year rates of device-related adverse outcomes. AIMS: We aimed to assess the intermediate-term safety and performance of a novel ultrathin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) in non-complex coronary lesions. METHODS: The prospective, single-arm, open-label IBS first-in-human study enrolled 45 patients, each with a single de novo lesion. Enrolled patients were randomly assigned to 2 follow-up cohorts. Angiographic and imaging follow-up with intravascular ultrasound and optical coherence tomography (OCT) were conducted at 6 and 24 months in cohort 1 (n=30) and at 12 and 36 months in cohort 2 (n=15). Clinical follow-up was conducted at 1, 6 and 12 months, and annually thereafter up to 5 years. The coprimary outcomes were target lesion failure (TLF) and angiographic late lumen loss (LLL) at 6 months. RESULTS: A total of 45 patients were enrolled between April 2018 and January 2019. The mean age was 53.2 years, 77.8% were male, and 26.7% had diabetes. The TLF rates were 2.2% at 6 months and 6.7% at 3 years, which in all cases were due to clinically indicated target lesion revascularisation. No deaths, myocardial infarctions or stent thromboses occurred during 3-year follow-up. In-scaffold LLL was 0.33±0.27 mm at 6 months and 0.37±0.57 mm at 3 years. By OCT, the proportion of covered struts was 99.8% at 6 months and 100% after 1 year. The 3-year strut absorption rate was 95.4%. CONCLUSIONS: In this first-in-human experience, an ultrathin IBS was safe and effective for the treatment of de novo non-complex coronary lesions up to 3-year follow-up.

Effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial ischemia-reperfusion injury in mini-swine.

OBJECTIVE: To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model. METHODS: Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol. About (3.54 +/- 0.90) x 10(8) bone marrow mononuclear cells (MNC group, n = 9) or (1.16 +/- 1.07) x 10(7) endothelial progenitor cells (EPC group, n = 7) was infused into the affected coronary segment of the swine. The other mini-swine were infused with phosphate buffered saline as control (n = 7). Echocardiography and hemodynamic studies were performed before and 4 weeks after cell infusion. Myocardium infarction size was calculated. Stem cell differentiation was analyzed under a transmission electromicroscope. RESULTS: Left ventricular ejection fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control group 4 weeks after cell infusion, respectively (P < 0.05). The systolic parameters increased in MNC and EPC groups but decreased in the control group. However, the diastolic parameters demonstrated no significant change in the three groups (P > 0.05). EPC decreased total infarction size more than MNC did (1.60 +/- 0.26 cm2 vs. 3.71 +/- 1.38 cm2, P < 0.05). Undermature endothelial cells and myocytes were found under transmission electromicroscope. CONCLUSIONS: Transplantation of either MNC or EPC may be beneficial to cardiac systolic function, but might not has obvious effect on diastolic function. Intracoronary infusion of EPC might be better than MNC in controlling infarction size. Both MNC and EPC may stimulate angiogenesis, inhibit fibrogenesis, and differentiate into myocardial cells.

Effects of intracoronary autologous bone marrow cells on left ventricular function in acute myocardial infarction: a systematic review and meta-analysis for randomized controlled trials.

BACKGROUND: Experimental and clinical studies have suggested that intracoronary infusion of bone marrow-derived stem/progenitor cells (BMC) may improve left ventricular function after acute myocardial infarction (AMI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of BMC therapy on global left ventricular function in AMI. METHODS: A systematic literature search of MEDLINE, Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PUBMED from their inception to March 2007 was conducted using specific search terms. Reference lists of papers and reviews on the topic were further searched. Finally, six randomized controlled trials that comprised 517 patients were eligible for further meta-analysis. We used a standardized protocol to extract information on the included studies. RESULTS: Compared with the control groups, BMC therapy produced a slight improvement of the follow-up left ventricular ejection fraction (LVEF) [2.53%, 95% confidence interval (CI): 0.67-4.39, P=0.008] between 3 and 6 months. Similarly, BMC therapy also significantly improved the LVEF change from baseline to follow-up [2.88%, 95%CI: 1.69-4.08, P=0.000] compared to control groups, and the heterogeneity across the studies with regards to the follow-up LVEF (P=0.696) and the LVEF change (P=0.179). Major adverse cardiovascular events, including ventricular arrhythmia, rehospitalization for heart failure, and the composite of other cardiovascular events (cardiac death, recurrent myocardial infarction, infarct-vessel revascularization procedure, and stroke), were not significantly different between BMC therapy and control groups [relative risk (RR): 1.19, 95%CI: 0.68-2.06; RR: 1.79, 95%CI: 0.62-5.17; and RR: 1.05, 95%CI: 0.81-1.35, respectively]. CONCLUSION: On the basis of present evidence, intracoronary BMC infusion in patients with AMI seems to be safe and associated with slight improvement of the left ventricular ejection fraction at 3-6 months' follow-up.

[Effect of intracoronary transplantation of autologous bone marrow mononuclear cells on myocardial ischemia reperfusion injury in mini-swine model].

OBJECTIVE: To investigate the therapeutic effectiveness of intracoronary transplantation of autologous bone marrow mononuclear cells (BM-MNC) on myocardial ischemia reperfusion injury in mini-swine model. METHODS: Myocardial ischemia reperfusion injury model was established by ligating in 16 mini-swines, which were further randomized into two groups: (3.54 +/- 0.90) x 10(8) BM-MNC was intracoronarily transplanted in BM-MNC group (n = 9), and phosphate buffer saline was intracoronarily applied in the control group (n = 7). Ultrasonic cardiograhpy, hemodynamics, neovascular density, and myocardium infarction size were evaluated before and 4 weeks after transplantation. RESULTS: In BM-MNC group, left ventricular ejection fraction (LVEF), intra-ventricular septa, lateral wall and anterior wall, cardiac output (CO) and + dp/dt(max) had no significant differences before and 4 weeks after transplantation (P > 0.05). In the control group, LVEF, intraventricular septa, lateral wall and anterior wall, CO, and + dp/dt(max) significantly decreased 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and- dp/dt(max) had no significant differences before and after cell transplantation. Capillary density was significantly larger in the BM-MNC group than in the control group [(13.39 +/- 6.96) /HP vs. (3.50 +/- 1.90) /HP]. The percentage and size of myocardial infarction was significantly lower in the BM-MNC group than in the control group. CONCLUSION: Transplantation of BM-MNC into the myocardial ischemic reperfusion-injury area can increase capillary density and decrease infarction area, and thus remarkably improve cardiac systolic function.

Implantation of autologous bone marrow mononuclear cells into ischemic myocardium enhances coronary capillaries and systolic function in miniswine.

OBJECTIVE: To investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction. METHODS: Sixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54 +/- 0.90) X 10(8) BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation. RESULTS: In BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or +dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and +dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and -dp/dtmax, did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 +/- 6.96)/high power field vs. (3.50 +/- 1.90)/high power field, P < 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P < 0.05). CONCLUSIONS: Transplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.

[Autologous bone marrow mononuclear cells and peripheral endothelial progenitor cells differentiation in myocardial ischemia reperfusion injury region in swine].

OBJECTIVE: To investigate the differentiation status of autologous bone marrow mononuclear cells (BM-MNC) and peripheral endothelial progenitor cells (EPC) transplanted into myocardial ischemia reperfusion injury region in swine. METHODS: BM-MNC marked with PKH26 (n = 9), EPC marked with CM-DiI (n = 7), phosphate buffer saline (control, n = 7) were transplanted into myocardial ischemia reperfusion injury region of swine by intracoronary artery injection. Specimens were harvested 4 weeks after injection for histological analysis (HE, immunochemical stain for vWF, alpha-sarcomeric-actin and fibronectin antibody). Cell differentiation was observed under transmission electronmicroscope. RESULTS: The number of small blood vessels was similar between BM-MNC group and EPC group (13.39 +/- 6.96/HP vs.12.39 +/- 4.72/HP, P < 0.05), but was significantly higher than that of control group (P < 0.05). Responsive intensity of immunochemical stain for fibronectin antibody was significantly lower in BM-MNC and EPC groups than that in control group. Responsive intensity of immunochemical stain for alpha-sarcomeric-actin antibody was similar among the three groups. Cluster cells were observed in one swine from BM-MNC group which might relate to the proliferation of stem cells in situ. Immature endothelial cells and myocytes were also detected by transmission electronmicroscope in BM-MNC and EPC group. CONCLUSION: BM-MNC and EPC transplanted into myocardial ischemia reperfusion injury region in swine stimulated the formation of blood vessels and inhibited fibrogenesis.

[Electrocardiogram analysis in high risk population of unexplained sudden death in Yunnan province].

OBJECTIVE: The purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province. METHOD: The electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women]. RESULTS: The incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern. CONCLUSION: The significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.

[Effects of intracoronary transplantation of autologous bone marrow mononuclear cells or endothelial progenitor cells in mini-swine model of myocardial ischemia-reperfusion].

OBJECTIVE: To compare the effects of intracoronary transplantation of autologous bone marrow mononuclear cells (BM-MNC) or peripheral endothelial progenitor cells (EPC) in mini-swine model of myocardial ischemia-reperfusion. METHODS: The Mini-swine acute myocardial infarction and reperfusion model was created with 90 min occlusion of the left anterior descending coronary artery followed by reperfusion and the animals were then divided into BM-MNC group (3.54 x 10(8) +/- 0.90 x 10(8), n = 9), EPC group (1.16 x 10(7) +/- 1.07 x 10(7), n = 7) and control group (saline, n = 7). Echocardiography, hemodynamic measurements and myocardium infarction size were evaluated before and 4 weeks after intracoronary cell transplantations. RESULTS: The net decrease from baseline to 4 weeks after transplantation of left ventricular ejection fraction (LVEF), left ventricular end systolic pressure, cardiac output and +dp/dt(max) were significantly attenuated post BM-MNC and EPC therapy compared to control group (all P < 0.05) and were similar between BM-MNC and EPC groups. Transplantation of BM-MNC and EPC also significantly decreased myocardial infarction size compared to control group. CONCLUSION: Autologous intracoronary transplantation of BM-MNC or EPC in this model equally improved cardiac systolic function and reduced infarction area.

[Clinical evaluation of risk factors for coronary heart disease].

OBJECTIVE: To explore the relationship between risk factors for coronary heart disease (CHD) and coronary artery lesions. METHOD: Potential risk factors were studied in 341 patients underwent coronary angiography. RESULTS: (1) Coronary angiography showed coronary artery lesions in 214 patients (lesion group), and no lesion in 127 patients (non-lesion group). There was significant difference in age, past history of diabetes, family history of CHD, smoking history, high-density lipoprotein cholesterol (HDL-C), lower-density lipoprotein cholesterol (LDL-C), ratio of total cholesterol to HDL-C (TC/HDL-C), lipoprotein(a) [Lp(a)], fibrinogen (Fbg) and high-sensitivity C-reactive protein (hs-CRP) between two groups (P < 0.05). (2) There was significant correlation between severity of coronary artery lesions and hs-CRP, Lp(a), TC/HDL-C, Fbg, hyperlipidemia, TC, LDL-C and TG (with coefficients of correlation of 0.338, 0.250, 0.241, 0.207, 0.167, 0.147, 0.140 and 0.139; respectively, P < 0.05). (3) Analysis of receiver operating characteristics (ROC) curve for patients with coronary angiography and risk factors for CHD showed that the areas under ROC curve were 0.810, 0.669, 0.626, 0.625, 0.619 and 0.618 for hs-CRP, TC/HDL-C, Lp(a), Fbg, LDL-C and past history of hyperlipidemia, respectively. CONCLUSIONS: Past history of hyperlipidemia was a predictor for occurrence of CHD. Ratio of TC/HDL-C and blood level of Lp(a) could be used as predictors in screening for high blood lipid, which were much stronger than others. It is suggested that hs-CRP had an excellent predictive value in current coronary inflammatory lesions.