Effects of Traditional Chinese Medicine Shensong Yangxin Capsules on Heart Rhythm and Function in Congestive Heart Failure Patients with Frequent Ventricular Premature Complexes: A Randomized, Double-blind, Multicenter Clinical Trial.

BACKGROUND: Pharmacological therapy for congestive heart failure (CHF) with ventricular arrhythmia is limited. In the study, our aim was to evaluate the effects of Chinese traditional medicine Shensong Yangxin capsules (SSYX) on heart rhythm and function in CHF patients with frequent ventricular premature complexes (VPCs). METHODS: This double-blind, placebo-controlled, multicenter study randomized 465 CHF patients with frequent VPCs to the SSYX (n = 232) and placebo groups (n = 233) for 12 weeks of treatment. The primary endpoint was the VPCs monitored by a 24-h ambulatory electrocardiogram. The secondary endpoints included the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) classification, 6-min walking distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and composite cardiac events (CCEs). RESULTS: The clinical characteristics were similar at baseline. SSYX caused a significantly greater decline in the total number of VPCs than the placebo did (-2145 ± 2848 vs. -841 ± 3411, P < 0.05). The secondary endpoints of the LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group (ΔLVEF at 12th week: 4.75 ± 7.13 vs. 3.30 ± 6.53; NYHA improvement rate at the 8th and 12th week: 32.6% vs. 21.8%, 40.5% vs. 25.7%; mean level of NT-proBNP in patients with NT-proBNP ≥125 pg/ml at 12th week: -122 [Q1, Q3: -524, 0] vs. -75 [Q1, Q3: -245, 0]; Δ6MWD at 12th week: 35.1 ± 38.6 vs. 17.2 ± 45.6; ΔMLHFQ at the 4th, 8th, and 12th week: -4.24 ± 6.15 vs. -2.31 ± 6.96, -8.19 ± 8.41 vs. -3.25 ± 9.40, -10.60 ± 9.41 vs. -4.83 ± 11.23, all P < 0.05). CCEs were not different between the groups during the study period. CONCLUSIONS: In this 12-week pilot study, SSYX was demonstrated to have the benefits of VPCs suppression and cardiac function improvement with good compliance on a background of standard treatment for CHF. TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR-TRC-12002061 (http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov, NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).

The Efficacy and Safety of Wenxin Keli in Patients with Frequent Premature Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial.

BACKGROUND: Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort. METHODS: We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis. RESULTS: At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantli greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%,P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%,P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported. CONCLUSIONS: Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC-related symptoms in patients without structural heart diseases and had no severe side effects.

Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts.

BACKGROUND: Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. METHODS: Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. RESULTS: At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. CONCLUSIONS: Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.

[Seven core principles for treatment of hypertension].

The seven core principles (SeCP) for treatment of hypertension were (1) early identification, early diagnosis, early and life-long treatment; (2) application of long-acting and slow-released anti-hypertension drugs to control blood pressure smoothly; (3) use low dosage and combined therapy; (4) individual and racial therapy; (5) integrated traditional Chinese and Western medicine; (6) life style improvement; (7) enhancing compliance. Being more comprehensive and detailed than the Seventh Report of the Joint National Committee (JNC-7), the 2003' European Society of Hypertension/European Society of Cardiology (ESH/ESC2003), the report of the fourth working party of the British Hypertension Society (2004-BHS IV), and the 2004' Chinese Guideline of Hypertension (CGH2004), the programmatic SeCP should be promoted in clinical practice for hypertension patients and doctors to follow and apply.

[Beneficial effects of Tong-xin-luo (herb) on myocardial no-reflow after acute myocardial infarction and reperfusion: experiment of mini-swine model].

OBJECTIVE: To evaluate the beneficial effects of Tong-xin-luo on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion. METHODS: Forty mini-swine were randomized into 5 equal groups: control group, low-dose group (pretreated with Tong-xin-luo 0.05 g.kg(-1).d(-1) for 3 days), medium-dose group (pretreated with Tong-xin-luo 0.2 g .kg(-1).d(-1) for 3 days), high-dose group (pretreated with Tong-xin-luo 0.5 g.kg(-1).d(-1) for 3 days), and sham-operation group. The swine in the former four groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion. Left ventricle systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP), rate of maximum pressure change in left ventricle (+/- dp/dt(max)), cardiac output (CO), and heart rate (HR) were measured 5 min before AMI in all groups and 180 min after AMI and 60 min after reperfusion in the groups 1-4. Coronary blood volume (CBV) was recorded 5 min before AMI in all groups and immediately and 60 min after reperfusion in the group 1-4. Myocardial contrast echography (MCE) was used before AMI, 3 h after AMI, and 60 min after reperfusion in the group 1-4 so as to calculate the left ventricle wall area (LVWA), ligation area (LS), and %LA. Sixty minutes after reperfusion thioflavin-S was injected into the left ventricle to dye the reperfusion area, then the descending anterior branch was re-ligated at the original site and Evan's blue was injected into the left ventricle to dye the area outside the reperfusion area blue. The heart was taken out immediately to undergo pathological examination and calculation of LVWA, LS, area of no-reflow (SNR), LA, ANR. necrosis area (NS), and NA. RESULTS: (1) In the control group, systolic and diastolic blood pressures (SBP and DBP), LVSP, +/- dp/dt(max), and CO significantly decreased (P < 0.05 or P < 0.01), while LVEDP significantly increased (P < 0.01) 3 hour after AMI, and then LVSP was significantly recovered while +/- dp/dt(max) further significantly decreased (both P < 0.05) 60 minutes after reperfusion. In the 3 Tongxinluo groups, the changes of LVSP, +/- dp/dt(max), CO and LVEDP were the same as those in the control group 3 hours after AMI, and 60 minutes after reperfusion, +/- dp/dt(max), CO and LVEDP were recovered significantly in the high-dose group to degrees better than those in the control group (all P < 0.05). (2) In the control group, the LS values measured by MCE in vivo and by pathological evaluation were similar (P > 0.05), and the SNR was 78.5% by MCE in vivo and was 82.3% by pathological evaluation with the final NS reaching 98.5% of LS. There was no significant difference in LS by both MCE and pathological evaluation between the Tongxinluo groups and control group, though the values of SNR by both methods in the medium and high-dose groups were 41.1% and 42.4% and 24.1% and 25.0% respectively, all significantly lower than those in the control group and low-dose group (P < 0.05 or P < 0.01) with the values in the high-dose group being significantly lower than those in the median-dose group (P < 0.05 and P < 0.01). The final NS of pathological evaluation was also significantly decreased to 90.2%and 81.2% of LS (P < 0.05). In the control group, CBV was significantly decreased to 45.8% and 50.6% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.01). In the high-dose group, CBV was also significantly decreased to 76% and 73.5% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.05), however, both significantly higher than those in the control group (both P < 0.01). CONCLUSION: Tongxinluo is effective in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area during AMI and reperfusion.

[The protective effects of Tong-xin-luo on myocardium and microvasculature after reperfusion in acute myocardial infarction].

OBJECTIVE: To evaluate the protective effects of Tongxinluo on myocardium and microvasculature after reperfusion in patients with acute myocardial infarction. METHODS: The research was performed on the patients with AMI whose initial ECG showed ST segment elevation and the patients received PCI or thrombolysis immediately after onset. These patients were classified randomly into two groups: control group in which the patients were given routine drug treatment (52 cases) and treatment group in which the patients were given routine drug plus Tongxinluo capsule (60 cases). We observed the abnormal movement of the ventricle wall in 2DE, and the change in LVEDV or LVEF on the 1st day, 7th day, 13th day, 3rd month, and 6th month after onset, which were compared with the result of DISA and SPECT for myocardial image. At the same time we also examined the blood NO and MDA levels on the 1st day, the 7th day and 13th day. RESULTS: (1) The recover rate for the abnormal movement of the ventricle segments in the treatment group were 11.86%, 18.12% and 18.79% respectively, which were higher than that of the control group (4.13%, 8.27% and 11.11% respectively) on the 1st week, the 2nd week, and the 1st month. At the 6th month the total recover rate for the abnormal movement of the ventricle segments of Tongxinluo group was 70.03%, which was significantly higher than that of the control group (51.68%). The WMSI was also decreased more than that of the control group. (2) The LVEDV in Tongxinluo group increased by 9.42% one week after onset, which was close to that of the control group (9.59%). There was no significant change (9.40% and 9.42% respectively) after two weeks and one month in Tongxinluo group, whereas it was increased continuously in the control group (11.84% and 12.33%). LVEDV in Tongxinluo group was decrease obviously after three and six months (3.62% and 5.07% respectively), which was close to the original level, whereas the result of the control group remained on a higher level (13.70% and 11.72% respectively). (3) LVEF of the Tongxinluo group was 53.32% before treatment, which was comparable with that of the control group (P = 0.45). There was no significant difference between the two groups after treatment for 1 week, 2 week and 1 month (P = 0.11, P = 0.13, P = 0.18, respectively). LVEF for the two groups was 58.27% and 53.40% respectively after three months and there was a statistical significance (P < 0.01). LVEF for the two groups was 58.33% and 53.82% respectively after 6 months and the difference remained statistically significant (P < 0.05). (4) The 2DE WMSI for the Tongxinluo group was 1.7552 after 12 hours to 24 hours of the CVR and there was no significant difference compared with that of the control group (WMSI = 1.5380, P = 0.6945). After 6 months, the WMSI decreased to 1.3767 in the Tongxinluo group, which was statistically different from that of the control group (WMSI = 1.5380, P < 0.01). The myocardium acquire isotope score index of the Tongxinluo group was 0.6075 at 6 months, which was significantly different from that of the control group (0.8781). (5) Ultrasonic humerus artery examination in static status showed that there was no significant difference on the diameter of blood vessel and the speed of blood stream between Tongxinluo group and control group with. The diameter of the blood vessel after artery pressure in Tongxinluo group was expanded, which was significantly different from that in the static status (P < 0.001) and that in control group (P < 0.001). The diameter of blood vessel after administration of nitroglycerin in both groups was expanded, which was significantly different from that in the static status (P < 0.001 and P < 0.05). However, Tongxinluo group was expand more obviously than that of the control group (P < 0.05). (6) The MDA level of the Tongxinluo group was decreased (all P < 0.05) and the NO level was increased (all P < 0.05) gradually from the 1st week to the 4th week; however, the MDA level of the control group was not decreased until the 4th week (P < 0.05), and the NO level of the control group was increased evidently at the 2nd week (P < 0.05). CONCLUSIONS: (1) After reperfusion in AMI patients, administration of routine drug combined with Tongxinluo is more effective than routine drug alone in the reduction of infarction size. (2) In Tongxinluo group, the recover time and the total recover rate of the abnormal movement of the ventricle segments were higher than the control group, and the WMSI were significantly decreased than the control group. (3) The improvement degree and the recover time on LVEDV in Tongxinluo group was superior to control group. (4) The improvement of LVEF in time and in degree was superior to control group. (5) The blood concentration of the MDA was decreased significantly in Tongxinluo group, while the NO level was increased significantly, and the time was superior to control group significantly.

Effects of xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with stable angina.

BACKGROUND: Reduction of cholesterol and inflammation can be achieved by administration of a statin. Xuezhikang, an extract of cholestin, available from Chinese red yeast rice, could effectively modify the lipid profile. However, limited information is available regarding rapid effects of Xuezhikang on plasma C-reactive protein (CRP) and the lipid profile in patients with stable angina. We evaluated the short-term time course effects of lipid profile and CRP by Xuezhikang in patients with stable angina. METHODS: Forty-eight consecutive patients with stable angina were randomly assigned to 1200 or 2400 mg/day of Xuezhikang. Blood samples were drawn at days 0, 1, 7 and 14 for lipid profile and CRP levels in all patients, and hepatic enzymes were also evaluated at days 0 and 14. RESULTS: Both doses of Xuezhikang induced significant reductions in median CRP levels and in mean CRP levels at day 1 (13.0% with 1200 and 16.6% with 2400 mg/day; 14.7% with 1200 and 18.4% with 2400 mg/day), and at day 7 (18.3% with 1200 and 20.2% with 2400 mg/day; 18.5% with 1200 and 22.6% with 2400 mg/day) as well as at day 14 (28.6% with 1200 and 30.4% with 2400 mg/day; 21.7% with 1200 and 24.8% with 2400 mg/day) compared with baseline without a dose-dependent effect but a time-dependent manner. In addition, no changes were found at days 1 and 7 regarding lipid profile. However, both doses of Xuezhikang induced significant reductions in total cholesterol (TC, 13% and 22%), and low-density lipoprotein (LDL) cholesterol (23% and 32%) compared with baseline at day 14. The higher dose of Xuezhikang (2400 mg/day) resulted in significantly greater reductions in TC and LDL cholesterol compared with 1200 mg/day group (p<0.05, p<0.01, respectively). A less significant reduction was observed in triglycerides (TG) level (13% and 23%) compared with TC and LDL cholesterol. There was no significant difference in mean high-density lipoprotein (HDL) cholesterol levels compared with baseline in both groups. CONCLUSIONS: Xuezhikang resulted in rapid reduction of CRP within 24 h and lipid profile within 2 weeks, which may be clinically important for patients with coronary artery disease.

Comparative effects of carvedilol and losartan alone and in combination for preventing left ventricular remodeling after acute myocardial infarction in rats.

It has been verified that losartan has beneficial effects on ventricular remodeling (VRM) after acute myocardial infarction (AMI), but the effects of carvedilol alone or in combination with losartan on this condition have not been defined. The present study used rats to compare the effects of carvedilol and losartan alone and in combination for preventing VRM after AMI. After ligation of the left coronary artery, 100 surviving female Sprague-Dawley rats were randomly assigned to 1 of 4 groups: (1) AMI control (n=25), (2) carvedilol (Car, 1 mg x kg(-1) x day(-1)) (n=25), (3) losartan (Los, 3 mg x kg(-1) x day (-1)) (n=25), and (4) Car (1 mg x kg (-1). day(-1)) + Los (3 mg x kg(-1) x day (-1)) (n=25). A sham-operated group (n=17) was also randomly selected. Drugs were administered by gastric gavage for 4 weeks. After hemodynamic studies, the hearts were fixed and analyzed pathologically. Exclusive of the rats that had died or had an infarct size <35% or >55%, complete data were obtained for 65 rats, comprising AMI control (n=13), Car (n=12), Los (n=13), combination (n=14), and sham (n=13) groups. There were no significant differences in the size of infarct among the 4 AMI groups (45.8 approximately 46.7%, all p>0.05). Compared with the sham group, left ventricular (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all significantly increased (all p<0.001), whereas +/-dp/dt was significantly decreased (both p<0.001) in the AMI group. In comparison with the AMI group, LVEDP, LVV, LVW and STh were all significantly decreased (LVEDP: 12.7+/-2.3, 9.7+/-2.8, and 8.6+/-3.5 mmHg vs 20.6+/-2.7 mmHg, all p<0.001; LVV: 0.74+/-0.07, 0.76+/-0.07, and 0.70+/-0.09 ml vs 0.86+/-0.05 ml, all p<0.05; LVW: 668.4+/-52.0, 702.6+/-45.4, and 683.9+/-67.7 mg vs 787.3+/-76.7 mg, p<0.05 approximately 0.001; STh: 1.57+/-0.05, 1.48+/-0.07, and 1.46+/-0.07 mm vs 1.71+/-0.04 mm, all p<0.05), whereas +/-dp/dt was significantly increased (all p<0.05) in the Car, Los, and combination groups, with LVEDP decreasing more in both Los and the combination groups than in the Car group alone (p<0.05) and STh decreasing more in the combination group than in the Car group alone (p<0.05). Carvedilol and losartan alone and in combination all prevent VRM after AMI in rats, with almost equivalent effect.