The changes of VPCs in a 24-h ambulatory ECG were observed at baseline and after 12 weeks of treatment; the parameters are summarized in Table 2. Compared with the placebo group, the total number of VPCs in 24 h at the week 12 visit was significantly lower in the SSYX group (1538 ± 2187 vs. 2746 ± 3889, P < 0.05) and the mean reduction value of VPCs was much higher in the SSYX group (ΔVPCs −2145 ± 2848 vs. −841 ± 3411, P < 0.05). Calculated with the formula (week 12 value − baseline value)/baseline value, the SSYX group had a higher reduction rate at −0.51 ± 0.59 versus −0.22 ± 0.82 in the placebo group (P < 0.05). To evaluate the favorable effects of SSYX administration with a powerful method, the patients at four different VPCs reduction percentage levels were analyzed. According to Table 2, the number of patients at reduction percentages of 90%, 70%, 50%, and 30% was significantly higher in the SSYX group than in the placebo group (P < 0.05).
Figure 2 summarizes the results of the echocardiogram analysis. At baseline, patients in the two groups demonstrated no significant difference in the LVEF and LVEDD. At the 12 weeks visit, the SSYX group had more improvement in cardiac function with a higher mean change in LVEF (ΔLVEF 4.75 ± 7.13 vs. 3.30 ± 6.53, P < 0.05) as compared with the placebo group. However, there was no significant decrease in the LVEDD in both groups.
After 12 weeks of treatment, the plasma NT-proBNP changed in both groups showed a significant decrease in the NT-proBNP level, which were 208 (Q1, Q3: 56, 839) versus 399 (Q1, Q3: 144, 1705) in the SSYX group (P < 0.05) and 287 (Q1, Q3: 67, 1182) versus 418 (Q1, Q3: 147, 1346) in the placebo group (P < 0.05). Because there is a consensus on the accuracy of NT-proBNP for heart failure (HF) at a cutoff value of 125 pg/ml, the subgroup analysis was performed in the patients with NT-proBNP ≥125 pg/ml before and after the treatment. There were 174 patients in the SSYX group and 177 patients in the placebo group with no difference in the value of NT-proBNP at baseline; 12 weeks of SSYX treatment resulted in a significant larger reduction in NT-proBNP as compared to the placebo (−122 [Q1, Q3: −524, 0] vs. −75 [Q1, Q3: −245, 0], P < 0.05).
The NYHA class was evaluated at baseline and each visit of the 4th, 8th, and 12th weeks of treatment. The following three categories were used to assess changes in the symptoms of HF: improvement, no change, and deterioration. Improvement was defined as the NYHA class improving at least one grade, and deterioration was defined as the NYHA class worsening at least one grade. As shown in Figure 2, there were no significant differences in the NYHA functional class between the two groups at baseline and at the 4th week visit. At the 8th and 12th week visits, the percentage of patients in NYHA Classes I, II, and III was significantly different in the two groups; the SSYX group had superior improvements, with improvement percentages of 32.6% and 40.5% in the SSYX group versus 21.8% and 25.7% in placebo group (P < 0.05, respectively).
The 6MWD test was performed at baseline and at the 12th week visit. There was no difference between the two groups at baseline; compared with the placebo group, patients receiving SSYX treatment had a greater increase in the 6MWD at week 12 (Δ6MWD 35.1 ± 38.6 vs. 17.2 ± 45.6, P < 0.05).
The MLHFQ was completed at each visit. There was a gradual improvement in the quality of life during the entire treatment period, and SSYX compared to placebo resulted in greater changes in the scores at the 4th, 8th, and 12th week visits (ΔMLHFQ −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).
The assessments of safety and tolerability were based on spontaneous reports of adverse events, vital signs, and laboratory measurements. CCEs were defined as death, cardiac arrest with resuscitation, readmission for HF, worsening HF with an intravenous pharmacological agent for more than 4 h, stroke or cases in which the patient ceased active treatments because of worsening HF. Overall, 2.2% and 3.5% of patients in the SSYX and placebo groups experienced CCEs (P = 0.403). One patient died and four patients were readmitted to the hospital for HF in the SSYX group. In the placebo group, one patient died, six patients were readmitted to the hospital for HF, and one patient received implantable cardioverter defibrillator treatment for worsening HF. The total number of adverse events was 39 in the SSYX group versus 52 in the placebo group (P = 0.134). The analysis of drug-induced adverse events revealed no differences between the two groups. There was no report of any serious adverse events related to the study drugs.
DISCUSSION
In the present study of CHF patients with frequent VPCs, we demonstrated that, combination with usual care and therapy for CHF, 12 weeks of SSYX treatment had more significant suppression of VPCs and improvement of cardiac function. These results suggest that SSYX might benefit CHF patients by improving ventricular electrostability and reversing ventricular remodeling.
Frequent VPCs are commonly encountered in patients with CHF, and they always produce a less efficient ventricular contraction in aggravating ventricular dysfunction. On the other hand, as the cardiac function worsens, the frequency of VPCs and complexity of ventricular dysrhythmias increase.[11121314] Therefore, the therapy that is given to break the vicious cycle is considered to be crucial. VPCs provide an arrhythmogenic substrate with a ventricular electrical instability that is the potential cause of malignant arrhythmia and cardiovascular mortality.[15] Therefore, many studies have been conducted to suppress frequent VPCs by either AADs or catheter ablation. Unfortunately, in spite of substantial effort focusing on drug development, few AADs are available for clinical use because the benefits of VPCs suppression in CHF patients are usually counteracted by the negative inotropic and proarrhythmic effects of AADs, which also failed to improve survival. At present, among the Class IA, IB, IC, II, III, and IV AADs, only amiodarone seems to improve the ventricular function as well as has an antiarrhythmic effect in CHF patients with VPCs without increasing the mortality rate.[1617] However, the extracardiac side effects of amiodarone, including effects on the thyroid, lungs, and liver, have hampered its clinical utility. β-blockers are a cornerstone of pharmacotherapy for CHF; however, the VPCs response to β-blockers changes to a variable extent, and they are rarely completely suppressed in CHF patients.[18192021] Therefore, the pharmacological treatment options in CHF patients with frequent VPCs are limited.
The recorded description that palpitation was diagnosed as symptomatic premature beats around 600 BC with pulse palpation from the early Chinese physicians.[22] Chinese medicinal herbs have been used over the past centuries in China for treating arrhythmia and increased in popularity as complementary and alternative therapeutic agents used worldwide. However, few have been subjected to the rigorous evaluation processes. SSYX is a well-known compound with antiarrhythmic effects described in the Chinese Materia Medica textbook.[23] According to the method of ultra-fast liquid chromatography combined with quadrupole time-of-flight mass spectrometry, the 12 herb materials of SSYX that were definitely identified or tentatively characterized could be classified into seven fractions, including saponins, phenolic acids, tanshinones, lignans, terpenoids, alkaloids, and flavonoids. The characteristic behaviors were investigated, and 11 representative compounds were found.[2425] Previous pharmacological studies revealed that SSYX suppresses arrhythmias that are induced by toxic chemical compounds or ischemia-reperfusion injury in animal models.[2627] SSYX was found to block multiple ion channels in isolated ventricular myocytes, inhibiting the sodium current, L-type calcium current, transient outward potassium current, delayed rectifier current, and inward rectifier potassium current.[5] In a randomized, double-blind, controlled multicenter trial conducted in patients with or without organic heart disease, SSYX compared with placebo or mexiletine had a significant therapeutic efficacy in reducing VPCs and alleviating VPCs-related symptoms.[28] Another randomized controlled trial of SSYX combined with routine pharmacotherapy in chronic HF revealed that SSYX further normalizes the heart rate variability (HRV) and heart rate turbulence (HRT) as well as reduces the incidences of VT and AF compared with the routine pharmacotherapy for HF alone.[29]
In our study, SSYX showed antiarrhythmic effects that were similar to those in basic and clinical studies, leading to a significant decrease in the total number of VPCs and demonstrating a greater reduction compared to placebo. On the other hand, the proarrhythmic effects of SSYX were assessed by a comparison of variety of complexity in VPCs and total arrhythmia. SSYX had a downward trend in monomorphic, polymorphic, multifocal, paired, bigeminy, or trigeminy VPCs and in NSVT. Neither severe arrhythmia nor malignant arrhythmia was observed in the 24-h ambulatory ECG. We found that SSYX-mediated suppression of the frequency VPCs resulted in an improvement in the cardiac function. SSYX treatment improved the NYHA classification and increased the LVEF. SSYX also helped reduce the plasma NT-proBNP and enhance the 6MWD and quality of life. All of the data showed that SSYX performs better than placebo. Previous studies have reported that eliminating VPCs with catheter ablation or suppressing VPCs with amiodarone improves or normalizes the ventricular function.[1630ventricular premature complexes in patients with reduced (<48%) left ventricular ejection fraction Am J Cardiol. 2012;110:852–6 doi: 10.1016/j.amjcard.2012.05.016','400');" onMouseOut="javascript:ImageWrapperControl_ImageMouseOut();">3132] Therefore, suppressing VPCs by SSYX led to a benign effect on cardiac function. However, in addition, we speculated that the SSYX-mediated cardiac function improvements were not only due to inhibition of VPCs but also from other underlying regulatory mechanisms. More recently, basic and clinical studies have reported that SSYX provides some regulatory effects on the intermediate interaction between the mechanical and electrical function of the heart. In our rabbit models of MI or HF, 8 weeks of treatment with SSYX powder revealed that SSYX could reverse electrical remodeling with a shortening action potential duration and transmural dispersion of repolarization.[7] In a diabetes rat model, 4 weeks of SSYX administration markedly improved the impaired cardiac function and attenuated the cardiac fibrosis and collagen deposition with the suppression of transforming growth factor-β1/Smad signaling pathway.[89] An MI rabbits’ research found that SSYX inhibited ventricular neural remodeling by reducing the densities of growth associated protein 43 and tyrosine hydroxylase positive nerve fibers.[10] Another study in the paroxysmal AF canine model revealed that SSYX has association with regulating the imbalance of autonomic nerve activity.[33] As mentioned previously, SSYX normalized the HRV and HRT in a chronic HF clinical trial, suggesting that SSYX treatment might rebuild the balance of the autonomic nervous system. The results from the basic and clinical research data suggest that SSYX might modulate the neurohormonal, structural, and functional remodeling to improve cardiac function, except for enhancing myocardial electrical stability.
Although the exactly active ingredients and the clearly mechanism of SSYX on VPCs and CHF remain unknown, some researches of part of the compositions involved in SSYX may explain part of the underlying pharmacodynamic profiles. Ginseng, the emperor herb in SSYX, has been revealed a number of beneficial properties in cardiac protection as protecting the ischemia-reperfusion injury, attenuating myocardial hypertrophy, and blunting the remodeling and HF processes.[34] Tanshinones from the S. miltiorrhiza in SSYX were demonstrated to suppress ischemic arrhythmias as well as prevent cardiac injury, hypertrophy, and atherogenesis. Downregulation of miR-1 and consequent recovery of Kir2.1, activation of KCNQ1/KCNE1 potassium channels may account partially for the efficacy of tanshinone IIA in arrhythmia suppression.[353637] Since SSYX is a complicated herbal composition, larger validation studies are needed to provide further evidence for its active ingredients and mechanisms.
Study limitations
In our study, 24-h ECG was used to evaluate the situation of VPCs. However, the frequency of VPCs is also subjected to daily or periodic variations, so prolonged period up to 72 h or even 7 days ECG is proposed to be more convincing. Since 12-week period in our study is a short time point, a larger scale and a longer term as 12 months of a rigorous designed clinical trial should be carried out for a more comprehensive analysis of SSYX in CHF patients with VPCs.
CONCLUSIONS
On a background of routine pharmacotherapy in CHF patients with frequent VPCs, SSYX treatment showed more significant VPCs suppression and further cardiac functional improvement. The bidirectional benefits of the mutual promotion of SSYX in mechanical and electrical functions are derived from the comprehensive modulations of neurohormonal, structural, and electrical remodeling. A rigorous clinical trial that evaluates the long-term outcomes, including all-cause or cardiovascular mortality, is needed to validate that SSYX provides clinical benefits to CHF patients with frequent VPCs following this study.
Financial support and sponsorship
The study was supported by a grant from the 973 Program of China (No.2012CN518606).
Conflicts of interest
Shijiazhuang Yiling Pharmaceutical Co., Ltd., (Shijiazhuang, China) provided the Shensong Yangxin capsules.
Acknowledgments
The authors gratefully acknowledge the contribution of the following sites (and staffs): The First Affiliated Hospital of Zhengzhou University (Chun-Guang Qiu, Zheng-Bin Wang); Chongqing Zhongshan Hospital (Xia Mei, Xiang-Qing Zheng, and Yong-Mei Li); Dongfeng General Hospital (Han-Dong Yang, Xin-Wen Min, and Ji-Shun Chen); Nanjing Drum Tower Hospital, Nanjing University Medical School (Wei Xu, Rong-Fang Lan, and Ning Zhang); The People's Hospital of Liaoning Province (Ying Liu and Xing-Ke Qiao); The First Hospital of Hebei Medical University (Yue Xia, Guo-Qing Qi, and Qing-Wen Zhang); Jiangxi Provincial People's Hospital (Guo-Tai Sheng and Yu Tang); The First College of Clinical Medical Science, China Three Gorges University (Jun Yang, Song Li, and Jia-Wang Ding); First Affiliated Hospital of Guangxi Medical University (Wei-Feng Wu, Yu-Ming Chen, and Xian-Zeng Xu); The Central Hospital of Enshi Autonomous Prefecture (Yuan-Hong Li, Xin Ji, and Chang-Jiang Zhang); Jinzhou Central Hospital (Shan Jiang, Chun-Hong Qu, and Bo Zhang); West China Hospital of Sichuan University (De-Jia Huang, Hong-De Hu); Xiangyang Central Hospital (Wen-Wei Liu, Bin Li, and Rui Zhu); Jingzhou Central Hospital (Xin Li, Gang Hu, and Li Zhang); Suizhou Central Hospital (Jin Qian, Wei Yao, and Neng Wang); The First Affiliated Hospital of Nanchang University (Ze-Qi Zheng and Yuan Wen); Ruijin Hospital, Shanghai Jiao Tong University (Li-Qun Wu, Rong Tao, and Yu-Cai Xie); Wuhan Asia Heart Hospital (Yang-Yang Dai, Xin-Hui Yang, and Jun Yin); Shanghai First People's Hospital (Fang Wang, Ying Wu, and Wei-Chun Xi); Chongqing the Fourth Hospital (Rui-Hua Yue and Ying Zhang); Beijing Anzhen Hospital, Capital Medical University (Chang-Sheng Ma, Qiang Lyu, and Tai-Yang Luo); The General Hospital of Shenyang Military Region (Zu-Lu Wang and Jing Liu); China-Japan Friendship Hospital (Yong Wang, Hong Jiang, and Ying Zhou); Zhongshan Hospital of Fudan University (Juan Peng, Ji Zhao, and Yuan Zhang); People's Liberation Army 252 Hospital (Xue-Bin Cao, Zhao-Chuan Liu, and Hong-Tao Liu); Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine (Ying Wang and Fang Liu); Wuxi No. 2 People's Hospital (Yan Jin, Wen-Chao Quan, and Zheng-Jie Yang); Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (De-Yu Fu, Ming-Tai Gui, and Lei Yao); and Shandong Jiaotong Hospital (Tian Wang and Hai-Yan Meng).
REFERENCES
1. Anastasiou-Nana MI, Menlove RL, Mason JWWestern Enoximone Study Group. . Quantification of prevalence of asymptomatic ventricular arrhythmias in patients with heart failure Ann Noninvasive Electrocardiol. 1997;2:346–53 doi: 10.1111/j.1542-474X.1997.tb00199.x
2. Lee YH, Zhong L, Roger VL, Asirvatham SJ, Shen WK, Slusser JP, et al Frequency, origin, and outcome of
ventricular premature complexes in patients with or without heart diseases Am J Cardiol. 2014;114:1373–8 doi: 10.1016/j.amjcard.2014.07.072
3. Chen KJ, Lu AP. Situation of integrative medicine in China: Results from a national survey in 2004 (in Chinese) Chin J Integr Med. 2006;12:161–5 doi: 10.1007/BF02836514
4. Chang HM, But PP, Yao SC, Wang LL, Yeung SC Pharmacology and Applications of Chinese Materia Medica. 2000;1 Singapore World Scientific
5. Li N, Ma KJ, Wu XF, Sun Q, Zhang YH, Pu JL. Effects of Chinese herbs on multiple ion channels in isolated ventricular myocytes Chin Med J. 2007;120:1068–74
6. Ding B, Dai Y, Hou YL, Yao XS. Spiroalkaloids from Shensong Yangxin capsule J Asian Nat Prod Res. 2015;17:559–66 doi: 10.1080/10286020.2015.1047354
7. Wang X, Duan HN, Hu J, Dang S, Huo YP, Lv H, et al Effects of Shensong Yangxin (SSYX) on cardiac function and electrophysiological characteristics in rabbits (in Chinese) Chin J Card Arrhythm. 2012;16:415–9 doi: 10.3760/cma.j.issn.1007-6638.2012.06.004
8. Shen N, Li X, Zhou T, Bilal MU, Du N, Hu Y, et al Shensong Yangxin capsule prevents diabetic myocardial fibrosis by inhibiting TGF-ß1/Smad signaling J Ethnopharmacol. 2014;157:161–70 doi: 10.1016/j.jep.2014.09.035
9. Shen DF, Wu QQ, Ni J, Deng W, Wei C, Jia ZH, et al Shensongyangxin protects against pressure overload-induced cardiac hypertrophy Mol Med Rep. 2016;13:980–8 doi: 10.3892/mmr.2015.4598
10. Jiang XB, Huang CX, Huang H, Wang X, Xiong L, Dang S. Effects of Shensong Yangxin on neural remodeling after myocardial infarction in rabbits (in Chinese) Chin J Card Pacing Electrophysiol. 2014;28:59–62 doi: 10.13333/j.cnki.cjcpe.2014.01.015
11. Kanei Y, Friedman M, Ogawa N, Hanon S, Lam P, Schweitzer P. Frequent premature ventricular complexes originating from the right ventricular outflow tract are associated with left ventricular dysfunction Ann Noninvasive Electrocardiol. 2008;13:81–5 doi: 10.1111/j.1542-474X.2007.00204.x
12. Agarwal SK, Simpson RJ Jr, Rautaharju P, Alonso A, Shahar E, Massing M, et al Relation of
ventricular premature complexes to heart failure (from the Atherosclerosis Risk In Communities [ARIC] Study) Am J Cardiol. 2012;109:105–9 doi: 10.1016/j.amjcard.2011.08.009
13. Chugh SS, Shen WK, Luria DM, Smith HC. First evidence of premature ventricular complex-induced cardiomyopathy: A potentially reversible cause of heart failure J Cardiovasc Electrophysiol. 2000;11:328–9 doi: 10.1111/j.1540-8167.2000.tb01802.x
14. Kjekshus J. Arrhythmias and mortality in
congestive heart failure Am J Cardiol. 1990;65:42I–8I doi: 10.1016/0002-9149(90)90125-K
15. Ruberman W, Weinblatt E, Goldberg JD, Frank CW, Shapiro S. Ventricular premature beats and mortality after myocardial infarction N Engl J Med. 1977;297:750–7 doi:10.1056/NEJM197710062971404
16. Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, et al Amiodarone in patients with
congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in
Congestive Heart Failure N Engl J Med. 1995;333:77–82 doi: 10.1056/NEJM199507133330201
17. Shiga T, Hosaka F, Wakaumi M, Matsuda N, Tanizaki K, Kajimoto K, et al Amiodarone decreases plasma brain natriuretic peptide level in patients with heart failure and ventricular tachyarrhythmia Cardiovasc Drugs Ther. 2003;17:325–33 doi: 10.1023/A:1027343606509
18. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group N Engl J Med. 1996;334:1349–55 doi: 10.1056/NEJM199605233342101
19. Exner DV, Reiffel JA, Epstein AE, Ledingham R, Reiter MJ, Yao Q, et al Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial J Am Coll Cardiol. 1999;34:325–33 doi: 10.1016/S0735-1097(99)00234-X
20. Aronson D, Burger AJ. Concomitant beta-blocker therapy is associated with a lower occurrence of ventricular arrhythmias in patients with decompensated heart failure J Card Fail. 2002;8:79–85 doi: 10.1054/jcaf.2002.32946
21. Chen T, Koene R, Benditt DG, Lü F. Ventricular ectopy in patients with left ventricular dysfunction: Should it be treated? J Card Fail. 2013;19:40–9 doi: 10.1016/j.cardfail.2012.11.004
22. Ng GA. Treating patients with ventricular ectopic beats Heart. 2006;92:1707–12 doi: 10.1136/hrt.2005.067843
23. Wu Y. Construction of the vessel-collateral theory and its guidance for prevention and treatment of vasculopathy Front Med. 2011;5:118–22 doi: 10.1007/s11684-011-0140-z
24. Liu M, Zhao S, Wang Y, Liu T, Li S, Wang H, et al Identification of multiple constituents in Chinese medicinal prescription Shensong Yangxin capsule by ultra-fast liquid chromatography combined with quadrupole time-of-flight mass spectrometry J Chromatogr Sci. 2015;53:240–52 doi: 10.1093/chromsci/bmu047
25. Liu M, Li S, Zhao S, Wang H, Wang H, Tu P. Studies on excretion kinetics of ten constituents in rat urine after oral administration of Shensong Yangxin capsule by UPLC-MS/MS Biomed Chromatogr. 2014;28:525–33 doi: 10.1002/bmc.3064
26. Wu YL Collateral Disease Theory in Practice. 2008 Beijing People's Medical Publishing House:238–42
27. Ren JY, Li LJ, Wang RJ, Chen H, Wu YL, Luo Y. Effects of Shen-song-yang-xin capsule on ventricular arrhythmias in ischemia/reperfusion: Experiment with rats (in Chinese) Nati Med J China. 2008;88:3440–3 doi: 10.3321/j.issn:0376-2491.2008.48.015
28. Zou JG, Zhang J, Jia ZH, Cao KJ. Evaluation of the traditional Chinese medicine Shensongyangxin capsule on treating premature ventricular contractions: A randomized, double-blind, controlled multicenter trial Chin Med J. 2011;124:76–83 doi: 10.3760/cma.j.issn.0366-6999.2011.1.015
29. Yang Z, Yu X, Yu ML. Effects of Shensongyangxin capsule on heart rate turbulence and heart rate variability in chronic heart failure Chin Med J. 2013;126:4389–91 doi: 10.3760/cma.j.issn.0366-6999.20130135
30. Penela D, Van Huls Van Taxis C, Aguinaga L, Fernández-Armenta J, Mont L, Castel MA, et al Neurohormonal, structural, and functional recovery pattern after premature ventricular complex ablation is independent of structural heart disease status in patients with depressed left ventricular ejection fraction: A prospective multicenter study J Am Coll Cardiol. 2013;62:1195–202 doi: 10.1016/j.jacc.2013.06.012
31. Lü F, Benditt DG, Yu J, Graf B. Effects of catheter ablation of “asymptomatic” frequent
ventricular premature complexes in patients with reduced (<48%) left ventricular ejection fraction Am J Cardiol. 2012;110:852–6 doi: 10.1016/j.amjcard.2012.05.016
32. Yokokawa M, Good E, Crawford T, Chugh A, Pelosi F Jr, Latchamsetty R, et al Recovery from left ventricular dysfunction after ablation of frequent premature ventricular complexes Heart Rhythm. 2013;10:172–5 doi: 10.1016/j.hrthm.2012.10.011
33. Zhao HY, Zhang SD, Zhang K, Wang X, Zhao QY, Zhang SJ, et al Effect of Shensong Yangxin on the progression of paroxysmal atrial fibrillation is correlated with regulation of autonomic nerve activity Chin Med J. 2017;130:171–8 doi: 10.4103/0366-6999.197997
34. Karmazyn M, Moey M, Gan XT. Therapeutic potential of
Ginseng in the management of cardiovascular disorders Drugs. 2011;71:1989–2008 doi: 10.2165/11594300-000000000-00000
35. Gao S, Liu Z, Li H, Little PJ, Liu P, Xu S. Cardiovascular actions and therapeutic potential of tanshinone IIA Atherosclerosis. 2012;220:3–10 doi: 10.1016/j.atherosclerosis.2011.06.041
36. Shan H, Li X, Pan Z, Zhang L, Cai B, Zhang Y, et al Tanshinone IIA protects against sudden cardiac death induced by lethal arrhythmias via repression of microRNA-1 Br J Pharmacol. 2009;158:1227–35 doi: 10.1111/j.1476-5381.2009.00377.x
37. Sun DD, Wang HC, Wang XB, Luo Y, Jin ZX, Li ZC, et al Tanshinone IIA: A new activator of human cardiac KCNQ1/KCNE1 (I(Ks)) potassium channels Eur J Pharmacol. 2008;590:317–21 doi: 10.1016/j.ejphar.2008.06.005
Edited by: Li-Min Chen
Keywords:Congestive Heart Failure; Randomized Controlled Trial; Shensong Yangxin Capsules; Ventricular Premature Complexes
© 2017 Chinese Medical Association
Source
Chinese Medical Journal130(14):1639-1647, July 20, 2017.
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