Feature and impact of guideline-directed medication prescriptions for heart failure with reduced ejection fraction accompanied by chronic kidney disease.

Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

2018 TSOC guideline focused update on diagnosis and treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension.

Left Atrial or Left Atrial Appendage Thrombus Resolution After Adjustment of Oral Anticoagulant Treatment.

BACKGROUND: There are few reports about non-vitamin K antagonist oral anticoagulant (NOAC) treatment for resolution of left atrium (LA) or left atrial appendage (LAA) thrombus. LAA thrombus is an important cause of cardiogenic cerebral thromboembolism, and the detection rate increases due to more and more patients receiving catheter ablation. However, the results from NOAC use for LA or LAA thrombus are still unknown in real-world practice. The aim of this study was to discover the resolution of LA or LAA thrombus after anticoagulant treatment in real-world practice. METHOD: From January 2013 to December 2016, a total 864 patients underwent transesophageal echocardiography (TEE), and 41 cases of LA or LAA thrombus were detected in our hospital. Among them, a total of 22 patients underwent follow-up TEE to detect the resolution of LA or LAA thrombus. RESULT: The average age of the study patients was 72.0 ± 11 years old, and 61% were male. The average CHA2DS2-VASc scores were 3.76 ± 2.01 points. A total of 22 patients underwent follow-up TEE, and 19 (86.4%) patients presented LA or LAA thrombus resolution. The average resolution duration was 258.47 ± 218.17 days. One-year all-cause mortality was 4.9%, and the incidence of ischemic stroke was 4.9%. Most physicians favored titration of the dosage of NOAC or warfarin in real-world practice. CONCLUSION: In real-world practice, most physicians favored titration of the dosage of NOAC or warfarin for LA or LAA thrombus. LA or LAA thrombus could exist if the patient received a reduced dose of NOAC. High frequency of LAA or LA thrombi could resolve, and a low incidence of ischemic stroke occurred after adjustment of oral anticoagulant treatment.

Intracoronary Transfusion of Circulation-Derived CD34+ Cells Improves Left Ventricular Function in Patients With End-Stage Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention.

OBJECTIVE: This study tested the hypothesis that intra-coronary transfusion of circulation-derived autologous CD34+ cells can improve ischemia-related left ventricular dysfunction in patients with severe diffuse coronary artery disease refractory to medication and unsuitable for coronary intervention. DESIGN: A prospective, randomized, double-blinded phase I clinical trial. SETTING: Tertiary care center. PATIENTS: Thirty-eight patients with severe diffuse coronary artery disease were randomized into group 1 and group 2 receiving CD34+ cell infusion with dosages of 1.0 x 107 and 3.0 x 107 cells/vessel, respectively, after subcutaneous G-CSF injection (5 µg/kg twice a day for 4 d). INTERVENTIONS: Cardiac catheterization and intra-coronary administration of CD34+ cells. MEASUREMENTS AND MAIN RESULTS: This clinical trial was to test effectiveness and safety of these two different dosages of CD34+ cells in the setting of severe diffuse coronary artery disease. Blood samples were collected for endothelial progenitor cell culture before and after granulocyte colony-stimulating factor injection for matrigel-assay and comparison of levels of soluble angiogenesis factors (vascular endothelial growth factor, epithelial growth factor, hepatocyte growth factor, angiopoietin-1, and transforming growth factor-ß). Procedural safety was 100% with all patients uneventfully discharged. The numbers of endothelial progenitor cells in blood samples from coronary sinus after transfusion were higher than those in circulation, and the circulatory level was higher after granulocyte colony-stimulating factor treatment (all p < 0.001). Cardiac MRI and three-dimensional echocardiography at 6 month and angiographic follow-up at 9 month showed improvement in left ventricular ejection fraction (p < 0.001) and consistent increase in neovascularization (p < 0.001), respectively, in both groups. Despite good correlation in angiogenesis between 9-month angiography and matrigel-assay (p < 0.001), no significant correlation was noted in of soluble angiogenesis factor levels. Angina and heart failure were improved in both groups at 12-month follow-up (all p < 0.001). The survival rate at 18.5-month follow-up was 94.7% (n = 36). CONCLUSIONS: CD34+ cell therapy was safe and efficacious in improving heart function for patients with severe diffuse coronary artery disease unsuitable for coronary intervention and with poor response to pharmacotherapy.

High Flow-Mediated Vasodilatation Predicts Pulmonary Edema in Liver Transplant Patients.

BACKGROUND: Early pulmonary edema is common after orthotopic liver transplantation. Associated pathogenic mechanisms might involve increased activity of cardiac-inhibitory systems due to increased vasodilator production, mainly nitric oxide (NO). NO is primarily responsible for flow-mediated vasodilatation (FMD). We investigated the incidence of pulmonary edema in liver transplant patients and its correlation with FMD. METHODS: We prospectively evaluated traditional risk factors, Doppler echocardiographic findings, derived hemodynamic data, and brachial artery nitroglycerin-induced vasodilatation (NTD) and FMD within 1 week prior to liver transplantation in 54 consecutive liver transplant patients with cirrhosis. Post-transplantation chest roentgenography was performed daily. In-hospital outcomes, transfusion volume of blood components, and hemodynamic data during surgery and at the intensive care unit were analyzed. RESULTS: Twenty-nine patients (53.7%) developed radiological pulmonary edema within 1 week of transplantation. Diffuse-type interstitial and alveolar pulmonary edema constituted 13 cases (24.1%). Patients with pulmonary edema had higher pretransplantation Child-Turcotte-Pugh scores (p = 0.01), cardiac output (p = 0.03), FMD (p < 0.01), NTD (p = 0.01), and FMD/NTD ratio (p = 0.02). Although the total volume of intravenous fluid transfused was higher in the pulmonary edema group, the net fluid retention during surgery was statistically insignificant. The lengths of intensive care unit stay and hospitalization, as well as mortality rates, were not different in these groups. CONCLUSIONS: The high incidence of pulmonary edema after living donor liver transplantation was associated with a high FMD and FMD/NTD ratio at pretransplantation. FMD is the only significant predictor associated with pulmonary edema. However, we observed no alteration in mortality rates. KEY WORDS: Cirrhotic cardiomyopathy; Flow-mediated vasodilatation; Liver transplantation; Pulmonary edema.

Outcomes of patients with Killip class III acute myocardial infarction after primary percutaneous coronary intervention.

OBJECTIVES: Little is known about the outcomes of patients with Killip class III acute ST-segment elevation myocardial infarction in the reperfusion era. This study investigated the short- and long-term outcomes of these patients who underwent primary percutaneous coronary intervention. METHODS: Between January 2002 and November 2009, a total of 1,278 consecutive patients with acute ST-segment elevation myocardial infarction underwent primary percutaneous coronary intervention. Of these patients, 230 (17.0%) with Killip III, 216 (16.9%) with Killip II, and 832 (65.1%) with Killip I upon presentation were prospectively recruited. RESULTS: Angiographic study showed significantly lower final thrombolysis in myocardial infarction 3 flow in patients with Killip III compared with those with Killip II and I (83.5% vs. 94.9% vs. 95.7%, p<.0001). The incidence of multiple vessel disease was also notably higher in Killip III than in Killip II and I (65.7% vs. 13.9% vs. 53.8%, p<.001). Besides, the incidence of advanced congestive heart failure (defined as greater than or equal to New York Heart Association functional class 3) during hospitalization was remarkably higher in Killip III compared to Killip II and I (71.3% vs. 13.9% vs. 6.6%, p<.001). Furthermore, the 30-day mortality and 1-yr cumulative mortality were notably higher in Killip III than in Killip II and I (20.0% vs. 4.2% vs. 1.7%, p<.001 and 31.7% vs. 7.9% vs. 4%, p<.001, respectively). Multivariate analysis showed that Killip III was independently predictive of 30-day and 1-yr mortality (all p < .04). CONCLUSION: Killip III remains strongly and independently predictive of 30-day and 1-yr mortality in ST-segment elevation myocardial infarction patients even undergoing primary percutaneous coronary intervention.

Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction.

BACKGROUND: We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model. METHODS: Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 µL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h. RESULTS: In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05). CONCLUSION: MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.

Autologous transplantation of adipose-derived mesenchymal stem cells markedly reduced acute ischemia-reperfusion lung injury in a rodent model.

BACKGROUND: This study tested the hypothesis that autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) can effectively attenuate acute pulmonary ischemia-reperfusion (IR) injury. METHODS: Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus intravenous transplantation of 1.5 × 106 autologous ADMSCs at 1h, 6h, and 24h following IR injury). The duration of ischemia was 30 minutes, followed by 72 hours of reperfusion prior to sacrificing the animals. Blood samples were collected and lungs were harvested for analysis. RESULTS: Blood gas analysis showed that oxygen saturation (%) was remarkably lower, whereas right ventricular systolic pressure was notably higher in group 2 than in group 3 (all p < 0.03). Histological scoring of lung parenchymal damage was notably higher in group 2 than in group 3 (all p < 0.001). Real time-PCR demonstrated remarkably higher expressions of oxidative stress, as well as inflammatory and apoptotic biomarkers in group 2 compared with group 3 (all p < 0.005). Western blot showed that vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, oxidative stress, tumor necrosis factor-α and nuclear factor-κB were remarkably higher, whereas NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1 activities were lower in group 2 compared to those in group 3 (all p < 0.004). Immunofluorescent staining demonstrated notably higher number of CD68+ cells, but significantly fewer CD31+ and vWF+ cells in group 2 than in group 3. CONCLUSION: ADMSC therapy minimized lung damage after IR injury in a rodent model through suppressing oxidative stress and inflammatory reaction.

Six-year clinical follow-up after treatment of diffuse in-stent restenosis with cutting balloon angioplasty followed by intracoronary brachytherapy with liquid rhenium-188-filled balloon via transradial approach.

BACKGROUND: Long-term follow-up studies revealed a significant decline in the benefits of intracoronary radiation for in-stent restenosis. METHODS AND RESULTS: A total of 25 study and 25 contemporaneous control patients with diffuse in-stent restenosis who underwent cutting balloon angioplasty (CBA) transradially, followed by subsequent intracoronary irradiation with a liquid ß-emitter Rhenium-188 (¹88Re)-filled balloon were enrolled in the study. The mean clinical follow-up durations were 64.9 ± 13.0 and 66.3 ± 13.8 months for the irradiated and control patients, respectively. Six-month angiographic restenosis was observed in 16% (4 of 25) of the patients in the irradiated group and 48% (12 of 25) of the patients in the control groups (P = 0.03). The 6-month major adverse cardiac events (MACE) rate was 12% and 44%, respectively (P = 0.025). The 3-year follow-up angiography was performed in 16 of 21 (76%) irradiated patients and in 4 of 13 (31%) control patients who had no significant restenosis at the 6-month angiographic follow-up. Restenosis occurred in 1 of 16 (7%) irradiated patients and 2 of 4 (50%) control patients. Late target lesion revascularization was performed in 1 irradiated and 2 control patients. The MACE rate within 6 years was significantly reduced in the irradiated group (20% vs. 56%, P = 0.019). CONCLUSIONS: Brachytherapy using ¹88Re-filled balloon following CBA for diffuse in-stent restenotic native coronary arteries is effective in reducing target lesion restenosis and improving long-term outcomes.

Comparison of drug-eluting stent with bare metal stent for distal de novo unprotected left main coronary artery stenosis. A propensity score-matched cohort study.

BACKGROUND: Percutaneous coronary intervention (PCI) with stent implantation is now considered a safe and feasible treatment for stenosis of the unprotected left main coronary artery (ULMCA). Because few studies have focused on de novo distal ULMCA lesions, a propensity score-matched cohort study was conducted to compare bare metal stents (BMS) with drug-eluting stents (DES) for long-term outcomes following PCI. METHODS AND RESULTS: This study reviewed the outcomes of patients undergoing PCI with DES (n=127) or BMS (n=51) for distal de novo ULMCA stenosis. The baseline demographic, angiographic and procedural characteristics differed between the 2 groups, indicating potential selection bias. The propensity score-matched cohort showed that the DES group had significantly less target lesion revascularization (TLR) and major adverse cardiovascular events (MACE) following PCI than the BMS group. Furthermore, heart failure (HF) of New York heart Association functional class III/IV was associated with an increased risk of TLR and MACE, whereas implantation of DES in patients with significant HF led to more favorable outcomes. CONCLUSIONS: Lower rates of TLR and MACE occurred in patients following PCI with DES implantation than with BMS implantation for distal ULMCA stenosis. Implantation of DES in patients with significant HF may improve the unfavorable outcome. When PCI is chosen to manage distal ULMCA stenosis, DES is the preferred stent type.

Reduced effects of cardiac extracorporeal shock wave therapy on angiogenesis and myocardial function recovery in patients with end-stage coronary artery and renal diseases.

BACKGROUND: Growing evidence have shown cardiac extracorporeal shock wave therapy (ESWT) improve clinical symptoms and left ventricular ejection fraction (LVEF) for patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary interventions. However, little is known whether cardiac ESWT remains effective on symptomatic relief and improvement of LVEF for the EnD-CAD patients with end-stage renal disease (ESRD). METHODS: This was a small-scale prospective study. Between August 2016 and January 2019, a total of 16 subjects received cardiac ESWT for their EnD-CAD. They were divided into two groups according to ESRD or not, i.e., EnD-CAD group (n = 8) and EnD-CAD/ESRD group (n = 8). Clinical symptoms including angina and dyspnea, levels of circulating endothelial progenitor cells (EPC), LVEF, and adverse events were regularly followed up for one year to compare safety and efficacy of cardiac ESWT between the EnD-CAD patients with or without ESRD. RESULTS: All participants tolerated cardiac ESWT without any relevant side effects such as skin allergic reaction, local redness/tenderness or cardiac arrhythmia. There were similar baseline comorbidities and clinical features between two groups, but the EnD-CAD/ESRD group had significantly higher serum potassium level as well as lower renal function and lipid profile (all p-values <0.03). After cardiac ESWT, the patients in both groups had significant improvement in angina and dyspnea at 1 year (all p-values <0.03). However, the EnD-CAD/ESRD group did not have increase in either circulating EPC levels or LVEF at 6 months (mean change in LVEF: -4.00% ± 8.32%, p = 1.000). In contrast, the EnD-CAD group had gradually improving levels of circulating EPC surface markers and increased LV systolic function (mean change in LVEF: +4.87% ± 8.76%, p = 0.092). Notably, patients in the EnD-CAD/ESRD group suffered from high incidental clinical adverse events before and after enrollment into the ESWT study (75% vs. 25%, p = 0.132). CONCLUSION: Although cardiac ESWT provided improvement of clinical symptoms in the EnD-CAD patients, its long-term effects on the angiogenesis and LVEF were reduced for those high-risk patients with concomitant EnD-CAD and ESRD. TRIAL REGISTRATION: none.

Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy.

BACKGROUND: We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC) and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM). METHODS: Adult Lewis rats (n = 8 per group) were divided into group 1 (normal control), group 2 (saline-treated DCM rats), group 3 [2.0 × 106 ADMSC implanted into left ventricular (LV) myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally), and group 5 (DCM rats with combined ADMSC-sildenafil). Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90. RESULTS: The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p < 0.002). Conversely, oxidative index was highest in group 2, and also higher in groups 3 and 4 than in group 5 (p < 0.0003). The mRNA expressions of interleukin (IL)-10, Gro/IL-8, endothelial nitric oxide synthase, and Bcl-2 were lowest in group 2, and lower in groups 3 and 4 compared with group 5 (p < 0.0001). The mRNA expressions of matrix metalloproteinase-9, Bax, caspase 3, and stromal-cell derived factor-1α were highest in group 2, and higher in groups 3 and 4 than in group 5 (p < 0.0004). Apoptosis and fibrosis in LV myocardium were most prominent in group 2 and higher in groups 3 and 4 than in group 5, whereas angiogenesis and LV ejection fraction were lowest in group 2 and lower in groups 3 and 4 than in group 5 (p < 0.003). CONCLUSION: Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function.

Sildenafil limits monocrotaline-induced pulmonary hypertension in rats through suppression of pulmonary vascular remodeling.

We hypothesize that sildenafil attenuates pulmonary hypertension through suppressing pulmonary vascular remodeling. Thirty male adult Sprague-Dawley rats were randomized to receive saline injection (Group 1), subcutaneous monocrotaline (MCT) (60 mg/kg) (Group 2), and MCT plus oral sildenafil (30 g/kg per day) (Group 3) 5 days after MCT administration. By Day 35, Western blot showed lower connexin43 and membranous protein kinase C epsilon expressions but higher oxidative stress in right ventricle in Group 2 compared with the other groups. Additionally, pulmonary Smad1/5 was lowest, whereas connexin43 and Smad3 were highest in Group 2. Pulmonary mRNA expressions of tumor necrosis factor-alpha, caspase-3, plasminogen activator inhibitor-1, and transforming growth factor-beta were higher, whereas bone morphogenetic protein Type II receptor, Bcl-2, and endothelial nitric oxide synthase were lower in Group 2 than in the other groups. Similarly, mRNA expressions of tumor necrosis factor-alpha, caspase-3, and beta-myosin heavy chain were increased, whereas Bcl-2, endothelial nitric oxide synthase, and alpha-myosin heavy chain expressions in right ventricle were reduced in Group 2 compared with the other groups. Number of lung arterioles was lowest, whereas number of arterioles with muscularization of the medial layer was highest in Group 2. Right ventricle systolic pressure and weight were elevated in Group 2 compared with the other groups. In conclusion, sildenafil effectively alleviates MCT-induced pulmonary hypertension through suppressing pulmonary vascular remodeling.

Primary percutaneous coronary intervention lowers the incidence of ischemic mitral regurgitation in patients with acute ST-elevated myocardial infarction.

BACKGROUND: The impact of primary percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI) on the incidence of ischemic mitral regurgitation (IMR) is unclear. METHODS AND RESULTS: Between January 2000 and December 2004, 318 patients presenting with first acute STEMI were enrolled in this study. Two hundred and twelve (66.67%) patients received PCI (PCI group), and 106 age- and Killip class-matched patients received medical management (non-PCI group). The median duration of follow up was 40.46 months. Compared to the non-PCI group, the PCI group had 14.6% (9.9% vs 24.5%) fewer patients with moderate or severe IMR (P<0.001). Univariate analysis demonstrated IMR was significantly associated with advanced age, higher Killip score, and posterior myocardial infarction (MI). Moreover, IMR was strongly associated with a lower left ventricular (LV) ejection fraction, larger left atrial dimension (LAd), and a larger LV end-systolic and LV end-diastolic volumes (LVEDV) (all P<0.01). Multivariate analysis revealed the odds of IMR in the PCI group was 0.208 times those of the non-PCI group (P<0.001). Additionally, moderate or severe IMR was independently correlated with advanced age, inferior MI, Killip class ≥3, larger LAd, and larger LVEDV (all P<0.05). Furthermore, long-term survival time was longer in the PCI group without IMR than in the non-PCI group with IMR (all P<0.01). CONCLUSIONS: PCI for first acute STEMI was associated with lower incidence of IMR. Advanced age, inferior MI, Killip class ≥3, larger LAd and LVEDV were risk factors associated with IMR development.

Shock wave-pretreated bone marrow cells further improve left ventricular function after myocardial infarction in rabbits.

BACKGROUND: We tested whether shock wave (SW) offers additional benefits in improving left ventricular (LV) function after acute myocardial infarction (AMI) in rabbits receiving SW-treated autologous bone marrow-derived mononuclear cells (BMDMNCs) transplantation. METHODS AND RESULTS: Saline (750 microL; group 2), BMDMNCs (1.0 x 10(7); group 3), or preimplant SW-treated BMDMNCs (group 4) were implanted into the infarct area of male rabbits 15 minutes after left coronary artery ligation, whereas eight rabbits without AMI served as controls (group 1; n = 8 per group). The results showed that in infarct area of LV, protein expressions of Cx43 and cytochrome C in mitochondria and endothelial nitric oxide synthase mRNA expression were lower in group 2 than in other groups, and decreased in group 3 as compared with groups 1 and 4 (all p values < 0.01). Conversely, mRNA expressions of endothelin-1 and matrix metalloproteinase-9, mitochondrial oxidative stress, and total fibrotic area were higher in group 2 than in other groups (all p values < 0.05). Furthermore, 6-month LV function by 2-D echo/angiogram showed significant impairment in group 2 than in other groups and in group 3 than in groups 1 and 4 (all p values < 0.005). CONCLUSIONS: Application of SW-treated autologous BMDMNCs is superior to BMDMNCs alone for preserving LV function after AMI.

Prognostic value of R-wave voltage in patients with anterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

The prognostic value of integrated R-wave voltages of precordial leads (V(1)-V(6)) in patients with acute anterior wall ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) was investigated. Between July 2006 and October 2009, 292 patients with anterior wall STEMI with presentation < 12 hours underwent primary PCI. Thirty-four patients with electrocardiographic presentation of either complete right bundle branch block (BBB) or complete left BBB were categorized into group A, while the remaining 258 patients without BBB served as group B that was further subdivided into those with lower R-wave voltage (summation of V(1)-V(6) ≤ 1.7 mV) (group 1) and higher voltage (> 1.7 mV) (group 2) according to the ROC curve (sensitivity = 66.3%, specificity = 66%, P < 0.0001).While the procedural success rate was similar between groups A and B and groups 1 and 2, 30-day mortality was higher in group A than B (P ≤ 0.0001). Additionally, left ventricular ejection fraction (LVEF) was lower, whereas peak level of creatine phosphokinase (CPK), incidence of advanced congestive heart failure, and 30-day mortality were higher in group 1 than 2 (P < 0.01). Multivariate analysis revealed that lower R-wave voltage, multivessel disease, leukocyte count, peak CPK, and creatinine level were predictive of 30-day unfavorable clinical outcomes (all P < 0.01). R-wave voltage in precordial leads was a significant independent predictor of 30-day prognostic outcome in patients with anterior wall STEMI undergoing primary PCI.

Bone marrow-derived mononuclear cell therapy alleviates left ventricular remodeling and improves heart function in rat-dilated cardiomyopathy.

OBJECTIVES: This study hypothesized that bone marrow-derived mononuclear cell (BMDMNC) therapy may improve cardiac function through preventing cell death, alleviating left ventricular (LV) remodeling, and enhancing angio-/vasculo-genesis, as well as preserving LV contractility in a rat model of dilated cardiomyopathy (DCM). DESIGN: A model of DCM in Sprague-Dawley rats was used to investigate the effects of BMDMNC therapy on inflammatory and oxidative response, energy depression, cellular apoptosis, expressions of protein kinase C-(PKC)-epsilon, and connexin43 protein (Cx43) in LV myocardium and heart function. SETTING: An animal model research laboratory at Kaohsiung Chang Gung Memorial Hospital. MEASUREMENTS: The rats were divided into group 1 (normal control, n = 8), group 2 (saline-treated DCM, n = 10), and group 3 (1.2 x 10 BMDMNC implanted into LV anterior wall on day 35 after DCM induction, n = 10). The DCM and normal control rats were killed on day 90 following DCM induction. RESULTS: The results demonstrated that Cx43 protein expression and messenger RNA expressions of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, endothelial nitric oxide synthase, and interleukin-10 were higher, whereas messenger RNA expressions of endothelin-1 and matrix metalloproteinase-9 were lower in groups 1 and 3 than in group 2 (all p < 0.05). Additionally, expressions of PKC-epsilon in plasma membrane and mitochondria and LV function were conserved in group 1 and improved in group 3, whereas cardiomyocyte apoptosis, mitochondrial oxidative stress, and fibrosis of LV myocardium were reduced in groups 1 and 3 than in group 2 (all p < 0.005). CONCLUSION: BMDMNC therapy in DCM significantly improves LV function by limiting cellular apoptosis, inflammatory and oxidative responses, and by up-regulating expressions of Cx43, PKC-epsilon, and energy transcription factors.

Assessment of right ventricular function by real-time three-dimensional echocardiography improves accuracy and decreases interobserver variability compared with conventional two-dimensional views.

AIMS: Two-dimensional echocardiographic (2DE) assessment of right ventricular (RV) function is difficult, often resulting in inconsistent RV evaluation. Real-time three-dimensional echocardiography (RT3DE) allows the RV to be viewed in multiple planes, which can potentially improve RV assessment and limit interobserver variability when compared with 2DE. METHODS AND RESULTS: Twenty-five patients underwent 2DE and RT3DE. Views of 2DE (RV inflow, RV short axis, and apical four-chamber) were compared with RT3DE views by four readers. RT3DE data sets were sliced from anterior-posterior (apical view) and from base to apex (short axis) to obtain six standardized planes. Readers recorded the RV ejection fraction (RVEF) from 2DE and RT3DE images. RVEF recorded by RT3DE (RVEF(3D)) and 2D (RVEF(2D)) were compared with RVEF by disc summation (RVEF(DS)), which was used as a reference. Interobserver variability among readers of RVEF(3D) and RVEF(2D) was then compared. Overall, mean RVEF(DS), RVEF(3D), and RVEF(2D) were 37 +/- 11%, 38 +/- 10%, 41 +/- 10%, respectively. The mean difference of RVEF(3D)-RVEF(DS) was significantly less than RVEF(2D)-RVEF(DS) (3.7 +/- 4% vs. 7.1 +/- 5%, P = 0.0066, F-test). RVEF(3D) correlated better with RVEF(DS) (r = 0.875 vs. r = 0.69, P = 0.028, t-test). RVEF(3D) was associated with a 39% decrease in interobserver variability when compared with RVEF(2D) [standard deviation of mean difference: 3.7 vs. 5.1, (RT3DE vs. 2DE), P = 0.018, t-test]. CONCLUSIONS: RT3DE provides improved accuracy of RV function assessment and decreases interobserver variability when compared with 2D views.

Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats.

OBJECTIVES: Bone marrow-derived endothelial progenitor cells have been shown to circulate to damaged vascular endothelium and differentiate into mature endothelial cells. This study investigated whether bone marrow-derived endothelial progenitor cell therapy ameliorates monocrotaline (MCT)-induced pulmonary arterial hypertension in a rat model. DESIGN: Male Sprague-Dawley rats were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus autologous bone marrow-derived endothelial progenitor cell (1.2 x 10(6) cells) transplantation (group 2), and saline injection only (group 3). Mononuclear cells were obtained from femoral bone marrow of group 2 rats and isolated by Ficoll gradient centrifugation. The cells were cultured for 21 days in endothelial culture medium. SETTING: An animal research laboratory at Kaohsiung Chang Gung Memorial Hospital. MEASUREMENTS: Hemodynamics, ventricular weight, expressions of connexin43, endothelial nitric oxide synthase messenger RNA gene, Bcl-2, and number of alveolar sacs and small lung arterioles were measured. RESULTS: Hemodynamic measurements on day 28 after MCT treatment revealed the development of significantly increased pulmonary arterial hypertension in MCT-treated groups (p < .0001). The bone marrow-derived endothelial progenitor cells were intravenously transplanted in group 2 on day 28 after MCT-induced pulmonary arterial hypertension. By day 90 after MCT treatment, the right ventricular systolic blood pressure and right ventricular hypertrophy were significantly increased in group 1 compared with groups 2 and 3 (all p values <.01). In addition, connexin43 and endothelial nitric oxide synthase messenger RNA gene expressions of lung and right ventricle and Bcl-2 protein expression of right ventricle were significantly lower in group 1 than in groups 2 and 3 (all p values <.01). Furthermore, the number of alveolar sacs and small lung arterioles were significantly lower in group 1 than in groups 2 and 3 (all p values <.01). CONCLUSIONS: Autologous bone marrow-derived endothelial progenitor cell transplantation effectively ameliorates MCT-induced pulmonary arterial hypertension.

Impact of clopidogrel on suppression of circulating levels of soluble CD40 ligand in patients with unstable angina undergoing coronary stenting.

This study investigated whether a regimen that comprised a loading dose of 300 mg of clopidogrel followed by 75 mg/day could significantly suppress circulating levels of soluble CD40 ligand (sCD40L) in patients who had unstable angina and underwent coronary stenting. Study results showed that the clopidogrel loading dose substantially decreased the circulating level of sCD40L at 24 hours after stenting (p <0.0001). Combined with aspirin, 75 mg/day of clopidogrel continuously decreased sCD40L levels after coronary stenting.