Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ±â€Š5.95 vs -1.82 ±â€Š4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).

Effect of Intracoronary Plus Low-Dose Intravenous Tirofiban in Elderly Patients with Acute Myocardial Infarction.

BACKGROUND: To investigate the efficacy and safety of low-dose tirofiban in elderly patients undergoing primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI). METHODS: One hundred and four patients aged 70 years and above undergoing PPCI for AMI were divided into control (n=52) and study (n=52) groups. All patients received bolus intracoronary injection of tirofiban (10µg/kg), which was followed by intravenous infusion at 0.15µg/kg/min in the control group and at 0.075µg/kg/min in the study group for 24h. RESULTS: There was no statistically significant difference between the study group and the control group in patients with complete ST segment resolution (84.2% vs. 85.7%, P=0.851), peak high-sensitive cardiac troponin T level (5.1±1.9 vs. 5.8±2.6µg/L, P=0.123), scores of thrombus in the infarct-related artery (0.98±0.51 vs. 1.12±0.59, P=0.214), and patients with TIMI grade 3 flow (86.0% vs. 88.2%, P=0.737) after PPCI. There were no statistically significant differences between the two groups in left ventricular ejection fraction (57.1±6.3 vs. 57.7±6.1, P=0.611) and composite major adverse cardiovascular events rate (P =0.778) at 90 days after PCI. The total bleeding rate in the study group was lower than in the control group (P=0.048). CONCLUSION: In elderly patients with AMI undergoing primary PCI, low and standard dose of tirofiban exerts similar effects on platelet aggregation, coronary flow, infarct size, left ventricular systolic function and short-term clinical outcomes. Low dose regimen is associated with a lower bleeding rate than the standard dose.

Effect of ß3-adrenergic receptor on atrial L-type Ca(2+) current in rats with chronic heart failure.

OBJECTIVES: To investigate the effect of selective ß3-adrenoreceptor agonist BRL-37344 on L-type Ca(2+) current (Ica,L) and mRNA expression of L-type Ca(2+) channel α2δ-2 (Cacna2d2) in rats with chronic heart failure (CHF). METHODS: Twenty-four male Wistar rats were divided into normal control (n=6) and CHF group (n=18), which were further divided into CHF control and BRL group (0.4nmol/kg, IV, twice weekly for four weeks). Echocardiography was performed to assess the structure and function of the left atrium (LA). RESULTS: The LA in the BRL group (4.4 ± 0.2mm) was larger than in the normal control (3.5 ± 0.3mm, P<0.01) or CHF control (4.0 ± 0.2mm, P<0.05) group. The LA ejection fraction in the BRL group (36.2 ± 4.2%) was lower than in the normal control (58.0 ± 3.1%, P<0.01) or CHF control group (42.3 ± 4.8%, P<0.05). There was no difference in Ica,L density between the BRL group and CHF control group (8.3 ± 1.7 vs. 8.2 ± 2.6 pA/pF, P>0.05), which was higher than in the normal control group (6.0 ± 1.8 pA/pF, P<0.01). There was no difference in the mRNA expression of α2δ-2 (Cacna2d2) between the BRL group and CHF control group (0.264 ± 0.005 vs. 0.243 ± 0.017, P>0.05), which was also higher than in the normal control group (0.137 ± 0.013, P<0.01). CONCLUSION: ß3-Adrenoreceptor stimulation with BRL-37344 was associated with an increase in LA diameter and a decrease in LA function in chronic heart failure. These structural and function changes were not related to Ica,L or L-type Ca(2+) channel α2δ-2 (Cacna2d2) subunit in the LA myocytes.

Upregulation of ß3-adrenergic receptor expression in the atrium of rats with chronic heart failure.

OBJECTIVES: To investigate the expression of ß(3)-adrenergic receptor (ß(3)-AR) in the atrium of rats with chronic heart failure (CHF). METHODS: The heart failure rat model was established by aortic constriction. Thirty-six male Wistar rats were divided into Sham group (n = 10) and heart failure model group (n = 26), which were further divided into CHF control (CHF group) and BRL group. The rats in the BRL group were treated with a selective ß(3)-AR agonist, BRL-37344 (4.0 nmol/kg, twice weekly) for 4 weeks. RESULTS: In the BRL group, the left ventricular end-systolic pressure (83.21 ± 13.0 vs 101.50 ± 12.12 mm Hg) and the absolute values of the maximal rate of rise and fall of left ventricular pressure ([±dP/dtmax] 2.81 ± 0.04 vs 0.35 ± 0.04 and -2.72 ± 0.06 vs -3.33 ± 0.06) were lower than in the CHF group (P < .01). The left atrial mass index (LAMI) in the BRL group (0.4132 ± 0.0306) was higher than that in the CHF (0.3212 ± 0.0136) or Sham group (0.2683 ± 0.0145; P < .01). The levels of the left atrial ß(3)-AR messenger RNA (mRNA) expression in the BRL group (0.932 ± 0.055) was higher than that in the CHF (0.706 ± 0.043) or Sham group (0.310 ± 0.020; P < .01). In all animals, there was a positive correlation between the level of ß(3)-AR mRNA expression and the left or right atrial mass index (correlation coefficient ranged from 0.744 to 0.937). CONCLUSION: There is a significant increase in the ß(3)-AR mRNA expression in the atrium of rats with heart failure. The level of ß(3)-AR mRNA expression was associated with the AMI and was enhanced by a selective ß(3)-AR agonist, BRL-37344.

Low-dose nesiritide improves renal function in heart failure patients following acute myocardial infarction.

This study was designed to investigate the effect of low-dose nesiritide on renal function and major cardiac events in patients with acute decompensated heart failure following acute myocardial infarction. Sixty patients were randomized into nesiritide (loading dose 0.5 microg/kg, maintenance dose 0.0075 microg/kg/min) and nitroprusside groups. Compared with the nitroprusside group, the nesiritide group had a greater heart rate reduction (P < 0.05), higher 24 h urine volume (P < 0.001), and more significant alleviation in dyspnea (P < 0.001). The prevalence of hypotension in the nesiritide group was lower than in the nitroprusside group (7.4% vs 28.5%, P < 0.05). The nesiritide group had a greater reduction in serum noradrenaline, angiotensin II, aldosterone, endothelin, and N-terminal prohormone brain natriuretic peptide (all P < 0.01). The mean serum creatinine in the nesiritide group was reduced (109.4 +/- 26.6 vs 102.8 +/- 21.6 micromol/l, P < 0.01), whereas it remained unchanged in the nitroprusside group (106.8 +/- 20 vs 106.0 +/- 19.2 micromol/l, P > 0.05). The rehospitalization or mortality rate was similar between the two groups 3 months after the therapy (P > 0.05). We conclude that low-dose nesiritide is more effective in suppressing the activation of the sympathetic and renin-angiotensin systems. It also improves the clinical symptoms and enhances renal function, but its effect on hospital readmission or mortality rate needs further investigation.

Age-related change of serum angiogenic factor levels in patients with coronary artery disease.

OBJECTIVE: Vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and -2 regulate angiogenesis and might be important in myocardial collateral development. Elevated levels of angiogenic growth factors in patients with coronary artery disease (CAD) have been reported. However, the age-related change of angiogenic growth factors in patients with CAD remains unclear. METHODS AND RESULTS: Serum VEGF, Ang-1 and -2 levels were measured by enzyme-linked immunosorbent assay kits. Serum VEGF, Ang-1 and -2 levels in patients with CAD were significantly higher than those in healthy control subjects. In patients aged <61 years and 61 to 70 years, serum Ang-1 and -2 levels were significantly higher than in patients aged >70 years, serum Ang-2 levels in patients aged <61 years were significantly higher than in patients aged from 61 to 70 years. Serum VEGF levels were not significantly different in the three age groups. Serum VEGF, Ang-1 and -2 levels were not significantly different across the age groups in healthy subjects. Regression analysis showed that there was a negative correlation between age and Ang-1 and -2 in patients with CAD. CONCLUSION: Serum Ang-1 and -2 levels, but notVEGF levels in patients with CAD, are decreased along with advancing age.

Effect of intracoronary tirofiban in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

BACKGROUND: To investigate the efficacy of intracoronary tirofiban during primary percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS). METHODS AND RESULTS: The 118 patients aged 70 years and above (average age 75+/-2) were divided into study (n = 58, intracoronary bolus tirofiban) and control (n = 57, intravenous tirofiban) groups. The culprit vessels were targeted with primary PCI in all patients. Compared with the control group, the study group showed better Thrombolysis In Myocardial Infarction (TIMI) flow grades and TIMI myocardial perfusion grades (TMPG) immediately after PCI (p = 0.016 and 0.026, respectively). The 14-day composite major adverse cardiac events rate was lower in the study group (3.5% vs 17.5%, p = 0.030), but was similar between the 2 groups at 30 days following PCI (7.0% vs 1.7%, p = 0.350). The left ventricular ejection fraction in the study group was higher than in the control group 30 days following PCI (67.4+/-6.2% vs 60.7+/-4.6%, p = 0.033). The 14-day bleeding complication (p = 0.201) and platelet reduction rates (p = 0.984) were similar between the 2 groups. CONCLUSION: In patients with ACS undergoing primary PCI, intracoronary bolus administration of tirofiban is superior to intravenous bolus injection for improving coronary flow, myocardial perfusion and short-term clinical outcomes.

Value of radiographic esophageal imaging in determining an optimal atrial septal puncture site for percutaneous balloon mitral valvuloplasty.

OBJECTIVE: To investigate the value of radiographic esophageal imaging in facilitating transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty. SUBJECTS AND METHODS: A total of 468 patients were randomized into either the study group (n = 234), in which radiographic esophageal imaging by the oral administration of a contrast media took place, or the control group (n = 234), in which the Ross technique was used. Of the 468 patients, 203 were males and 265 were females. The average ages of the study and control groups were 53 +/- 16 and 51 +/- 17 years, respectively. The patients had severe left atrial enlargement, as measured using 2-dimensional echocardiography. RESULTS: In the study group, the left atrial impression on the esophagus was clearly seen, and was used to identify the puncture site on the right atrial side for the passage of the transseptal catheter. In the control group, the left atrial silhouette was not clearly shown by fluoroscopy in 112 patients (47.5%). The success rate of transseptal catheterization in the study group was higher than in the control group (99.6 vs. 45.7%, p = 0.0001). There were no complications in the study group, but pericardial tamponade occurred in 1 patient in the control group. CONCLUSION: Radiographic esophageal imaging facilitates the identification of an optimal atrial transseptal puncture site, and improves the success rate of transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty.

Effects of folic acid on cardiac myocyte apoptosis in rats with streptozotocin-induced diabetes mellitus.

BACKGROUND: The effect of folic acid on cardiac myocyte apoptosis secondary to diabetes is unknown. METHODS: Diabetic rats were divided into diabetic control (DC, n = 11), low-dose (LDF, 0.4 mg/kg/day, n = 12) and high-dose (HDF, 1.2 mg/kg/day, n = 12) folic acid groups. Non-diabetic rats (n = 11) were used as the normal control (NC). RESULTS: After 11 weeks of treatment, compared with the NC group, the DC group showed a reduced blood levels of reactive oxygen species (ROS, P < 0.01). The rate of cardiac myocyte apoptosis in the diabetic control group was also greater than in the non-diabetic control group (P < 0.01). In folic acid-treated rats, the blood levels of ROS was higher than in the diabetic control group (P < 0.05). There was a dose-dependent reduction in the rate of cardiac myocyte apoptosis in the folic acid groups (P < 0.01), and this was accompanied by an increased level of anti-apoptotic protein Bcl-2 and decreased level of pro-apoptotic protein Bax and Fas (P < 0.01). CONCLUSIONS: Dietary folic acid supplementation diminishes the cardiac myocyte apoptosis in streptozotocin-induced diabetes. The apoptosis suppression is accompanied by an increase in the expression of Bcl-2 and a decrease in Bax and Fas.

Effect of beta-blockers on beta3-adrenoceptor expression in chronic heart failure.

OBJECTIVES: To investigate the expression of beta(3)-adrenoceptors in rats with chronic heart failure, and to explore the effect of beta-blockers on beta(3)-adrenoceptor expression. MATERIALS AND METHODS: Thirty-two male Wistar rats were divided into Sham (n = 10) and heart failure (n = 22) groups. The heart failure group was treated with normal saline (Heart Failure Control, n = 6), Metoprolol (n = 8) or Carvedilol (n = 8) for 3 months. RESULTS: The left ventricular end systolic pressure (LVESP) and the absolute values of maximal rate of rise and fall of left ventricular pressure (+/-dP/dt max) in the heart failure group were lower than in the Sham group (P < 0.01), whereas the left ventricular end diastolic pressure (LVEDP) was higher (P < 0.01). The LVESP and dP/dtmax in the Carvedilol group were higher than the Metoprolol group whereas LVEDP was lower (P < 0.01). The left ventricular mass index (LVMI) in the Carvedilol group was less than the Metoprolol and Heart Failure Control groups (P < 0.01). The level of beta(3)-adrenoceptor expression in the study groups was significantly higher than the Sham group (P < 0.01). beta(3)-adrenoceptor expression in the Carvedilol group was lower than the Heart Failure Control and Metoprolol groups (P < 0.01). CONCLUSION: beta(3)-adrenoceptor expression is increased in the failing ventricles in rats. Carvedilol is more effective than Metoprolol for improving the hemodynamics and in attenuating ventricular remodeling after heart failure. Carvedilol, rather than Metoprolol, diminishes beta(3)-adrenoceptor expression in the failing ventricles.

beta(3)-Adrenoceptor antagonism improves clinical outcomes of chronic heart failure.

Chronic heart failure (CHF) is a leading cause of morbidity and mortality throughout the world. The pathogenesis of CHF is complex but beta(1)-adrenoceptors are critical in the process, because beta(1)-adrenoceptor blockers have been shown to significantly reduce the mortality and hospitalization rates in patients with CHF. Recent animal and human studies have demonstrated that there is an over expression of beta(3)-adrenoceptors in the failing heart, and stimulation of these receptors leads to further depression in ventricular function. We hypothesize that beta(3)-adrenoceptors and their over activities are one of the critical mechanisms of CHF, and addition to conventional heart failure therapies, beta(3)-adrenoceptor antagonism would further improve cardiac function and clinical outcomes.

Prevalence of overweight and smoking patients with coronary heart disease in rural China.

OBJECTIVE: To investigate the prevalence of overweight and/or smoking patients with coronary artery disease in rural China. DESIGN: A prospective survey with qualitative, open-ended questionnaires. SETTING: Tertiary referral centre. SUBJECTS: 158 hospitalised patients (71 men and 87 women) with established coronary heart disease. MAIN OUTCOME MEASURES: To determine the prevalence of overweight and/or smoking hospitalised patients who had a definitive diagnosis of coronary artery disease and to determine participants understanding of these risk factors. RESULTS: Being overweight and smoking cigarettes were found in 32.7% and 15.2% of the participants, respectively. More than 70% of the overweight participants had neither knowledge nor counselling on their weight before the study. Most smokers believed smoking was harmful to their health and cardiac condition, and had tried unsuccessfully to quit smoking. CONCLUSIONS: There was a high prevalence of overweight and/or smoking patients with coronary heart disease. A systematic approach is urgently required to educate patients and primary care physicians, and to improve the management of being overweight and smoking cigarettes.

Predictive factors for an effective beta-blocker therapy in Chinese patients with congenital long QT syndrome: A multivariate regression analysis.

OBJECTIVE: To investigate the factors that may predict the effectiveness of beta-blocker therapy for congenital long QT syndrome (LQTS) in a Chinese patient population. METHODS: Twenty-six LQTS patients were treated with oral propranolol (n=16) or metoprolol tartrate (n=10) for 38 months. Clinical symptoms, heart rate, corrected QT interval (QTc) and left ventricular ejection fraction were assessed before and after the therapy. RESULTS: Cardiac events were reduced by more than 50% in 22 patients with beta-blocker therapy. The average number of syncopes/patient and the average frequency of syncopes/patient/year in the responders were reduced from 16.2+/-5.1 to 1.1+/-0.9 (P<0.01) and from 4.5+1.2 to 0.7+0.6 (p<0.01), respectively. The QTc was also reduced from 0.56+/-0.06 s to 0.50+/-0.03 s. There was no significant difference in the reduction of syncopes and QTc in patients treated with propranolol and metoprolol tartrate. Multivariate regression analysis showed no correlation between the reduction in syncopal attacks and patients' age, sex, heart rate or left ventricular function (P>0.05). QTc reduction was the only independent predictive factor for syncope control (R=0.81, P<0.001). CONCLUSIONS: Oral beta-blockers are an effective therapy for Chinese patients with LQTS. A significant reduction in QTc is highly indicative of treatment success with beta-blockers.

Using left atrial esophagus impression after a barium swallow to determine the optimal septal puncture site during percutaneous balloon mitral valvuloplasty.

BACKGROUND: Transseptal catheterization is the key to a successful percutaneous balloon mitral valvuloplasty (PBMV). The primary aim of the study was to investigate new methods of transseptal catheterization for PBMV. METHODS: Eighty-four patients with rheumatic mitral stenosis were randomized into two groups for PBMV. In the study group, the left atrial (LA) impression on the esophagus after a barium swallow was used as a reference of LA silhouette to determine the septal puncture site. In the control group, the LA silhouette under a normal fluoroscopic view was used for the determination of septal puncture site. RESULTS: In the study group, the average length of esophagus impression after a barium swallow was similar to the size of the left atrium measured by angiography (43.8+/-0.6 mm versus 44.1+/-0.7 mm, n=42, P>0.05). The success rate of atrial septum puncture in the study and control groups were 100% and 64.3%, respectively (P<0.01). Transseptal catheterization was subsequently achieved using the barium swallow approach in the 15 initially unsuccessful patients from the control group. PBMV was successful in the 84 patients with significant reduction in LA pressure and improvement of clinical symptoms. CONCLUSIONS: Transseptal catheterization in patients undergoing PBMV can be safely and effectively performed using the barium swallow approach.

Predictors of long-term success in catheter ablation of atrioventricular nodal reentrant tachycardia: a multivariate regression analysis.

BACKGROUND: To investigate the predictors of long-term success after catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: One-hundred and fourteen consecutive patients underwent slow pathway ablation using anteroseptal (n=24), midseptal (n=65) and posteroseptal approach (n=25). The correlation between ablation approaches, electrophysiological characteristics during and after ablation and the recurrence rate of AVNRT was analyzed by a multivariate regression analysis. RESULTS: During ablation, transient AV block in the anteroseptal, midseptal and posteroseptal approach occurred in 8.3, 4.6 and 0%, respectively (P<0.01). AVNRT recurred in seven patients after 5 years follow-up. Five recurrences (20.8%) were from anteroseptal approach group and two (3.1%) were from midseptal approach group. Multivariate regression analysis revealed that anteroseptal ablation approach and residual dual atrioventricular nodal pathway following apparently successful ablation were the predictors for recurrence of AVNRT (R=0.645, P<0.001). CONCLUSION: Anteroseptal approach of slow pathway ablation is associated with a higher incidence of transient AV block and AVNRT recurrence than other approaches. Residual dual atrioventricular nodal pathway after apparently successful ablation also carries a high risk of recurrence.

Percutaneous balloon angioplasty of inferior vena cava in Budd-Chiari syndrome-R1.

This study was to evaluate the clinical effects of percutaneous balloon angioplasty of Budd-Chiari syndrome (BCS) caused by inferior vena cava (IVC) obstruction. Between 1993 and 1999, 28 men and 14 women with mean age of 44+/-12 years underwent percutaneous balloon angioplasty for primary BCS. Color Doppler ultrasound and venography showed membranous and segmental obstruction of IVC in 29 and 13 patients, respectively. Fourteen patients also had left- and/or mid-hepatic vein obstruction. Angioplasty of IVC was successful in 41 patients (97.6%), resulting in a reduction of pressure gradient between IVC and the right atrium from 15.0+/-2.5 to 5.5+/-0.8 mmHg (P<0.01). A stent was placed in the site of obstruction in the patient with unsuccessful balloon angioplasty. Patients with successful angioplasty or stent placement had significant improvement in clinical symptoms indicated by a reduction in hepatomegaly and the degree of ascites. No specific attempt was made to treat the occluded left- and/or mid-hepatic vein due to the presence of potent right hepatic vein. Over the follow-up period of 32+/-12 months, restenosis of IVC occurred in only one patient (2.4%), which was redilated successfully. Percutaneous balloon angioplasty is a safe and effective therapy for Budd-Chiari syndrome caused by IVC obstruction, therefore should be the first choice of treatment for this condition.

Angiographic characteristics of the coronary artery in patients with type 2 diabetes.

OBJECTIVES: To investigate the adverse effect of type 2 diabetes on coronary artery anatomy. PATIENTS AND METHODS: The coronary angiograms of 1564 consecutive patients were analyzed. The coronary lesions of patients with and without type 2 diabetes were compared. RESULTS: Seventy-four diabetic and 824 nondiabetic patients were found to have coronary artery disease. Diabetic patients had more multivessel (48.7% versus 34.7%, P<0.01), multilesion (64.9% versus 46.1%, P<0.05), extensive (51.4% versus 7.8%, P<0.01) and small vessel disease (95.2% versus 39.8%, P<0.01) than nondiabetic patients. CONCLUSIONS: Type 2 diabetes is a significant risk factor for coronary artery disease. These findings may provide useful information for the future development of therapeutic strategies.