The microcirculatory characteristics of the heart and lung meridians: Study protocol clinical trial (SPIRIT Compliant).

INTRODUCTION: The aim of the present study is to compare the microcirculatory difference of different meridians by using laser doppler flowmetry and investigate the specificity for the meridian-visceral association and site-to-site association between 2 specific meridians. METHODS AND ANALYSIS: The Lung and Heart meridians are chosen as 2 specific studied meridians. 120 participants will be enrolled and divided into the healthy control group, chronic stable angina pectoris group and healthy intervention group. Laser doppler flowmetry will be used to assess the blood perfusion of the Heart and Lung meridians. The specificity for the meridian-visceral association will be investigated by comparing the microcirculatory difference between the Heart and Lung meridians in the healthy control group and chronic stable angina pectoris group. Besides, participants in the healthy intervention group will receive 2 sessions of moxibustion in the Heart meridian and Lung meridian, respectively, to explore the specificity for the site-to-site association on the body surface. Primary outcomes will be blood flow curve and blood perfusion units of relevant sites along the Heart and Lung meridians. Statistical analysis will be conducted by third party statisticians. ETHICS AND DISSEMINATION: Ethics approval (approval No: ZSLL-KY-2019-001A-01) has been obtained from the Ethics Committee of the Third Affiliated Hospital of Zhejiang Chinese Medical University. The study findings will be disseminated through presentation at peer-reviewed medical journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04244812.

Shenzhu Guanxin Recipe Granules () for Improving Exercise Tolerance in Patients with Stable Angina (SERIES Trial): A Protocol of Multicenter, Randomized, Double-Blind, Placebo Parallel Controlled Clinical Trial.

BACKGROUND: Many patients with chronic angina experience anginal episodes despite successful recanalization, antianginal and antiischemic medications. Empirical observations suggested that Shenzhu Guanxin Recipe Granules (, SGR), a Chinese herbal compound, exerted potential impacts on increased treadmill exercise performance and angina relieve. However, there has been no systematic study to clarify the impact of SGR on exercise tolerance in patients with stable angina. The SERIES (ShEnzhu guanxin Recipe for Improving Exercise tolerance in patients with Stable angina) trial is designed to determine the effects of SGR on exercise duration, electrocardiographic (ECG) evidence of myocardial ischemia, and incidence of major adverse cardiac events (MACE) in stable anginal patients. METHODS: A total of 184 eligible patients with stable angina will be randomly assigned to receive placebo or SGR (10 g/day for 12 weeks) in a 1:1 ratio. The primary outcome will be the change from baseline in total exercise tolerance duration, time to onset of angina and ECG ischemia during exercise treadmill testing performed over a 12-week study period. The secondary outcome will include ECG measures, the occurrence and composite of MACE and the Seattle Angina Questionnaire score. Moreover, the coronary microcirculation will be evaluated to explore the possible effects in response to treatment of SGR. After the procedure, all participants will be followed up by interview at 3 and 6 months, enquiring about any cardiac events, hospitalizations, cardiac functional level and medication usage. Additionally, the occurrence of adverse events will be evaluated at each follow-up. DISCUSSION: This study may provide novel evidence on the efficacy of SGR in improving exercise tolerance and potentially reducing clinical adverse events. (Trial registration No. ChiCTR-TRC-14004504).

A review of the mechanism of action of Dantonic® for the treatment of chronic stable angina.

Chronic stable angina (CSA) presents as a complication of coronary heart disease, leading to a high incidence and mortality rate worldwide. Dantonic® or Compound Danshen Dripping Pills (CDDP) is a well-known traditional Chinese medicine used for the treatment of myocardial ischemic diseases, such as angina pectoris (AP), myocardial infarction, and sudden death. Dantonic® has been extensively utilized in clinical practice in China for more than 14 years and has proved to be an effective therapy for the treatment of many myocardial ischemic diseases since its approval by CFDA in 1994. Clinical studies in China have shown that Dantonic® is an effective and safe drug for the treatment of angina pectoris manifested with ameliorating anginal symptoms and showing few adverse effects. Nevertheless, the mechanism of Dantonic® for the treatment of angina has been underestimated. Therefore, in this review, we mainly focus on discussing the pharmacological mechanism of action (MoA) of Dantonic® for the treatment of CSA, including the promotion of coronary microcirculation, the optimization of myocardial energy metabolism, and the inhibition of platelet aggregation.

The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina.

BACKGROUND: Despite advances in the treatment of cardiovascular diseases in recent decades, patients experience high levels of depression, anxiety, stress, and insomnia. Since the calming effect of Melissa officinalis (MO) has been known, this study aimed to determine the effects of MO supplementation on depression, anxiety, stress, and sleep disturbances in patients with chronic stable angina (CSA). METHODS: In this double-blind placebo-controlled clinical trial, 80 patients with CSA were divided randomly into two groups (taking 3 g MO supplement or placebo daily for 8 weeks). The shortened 21-item version of the depression, anxiety and stress scale (DASS-21) test and Pittsburgh sleep quality index were done before and after the intervention. RESULTS: At the end of the study, the intervention group receiving MO capsules had a significant reduction in scores of depression, anxiety, stress, and total sleep disturbance, compared with the placebo group (P < 0.05). CONCLUSIONS: The results showed that 8-week supplementation with 3 g MO can decrease depression, anxiety, stress, and sleep disorder in patients with CSA.

Different network pharmacology mechanisms of Danshen-based Fangjis in the treatment of stable angina.

Danshen (Salvia miltiorrhiza) preparations such as Danhong injection, Danshen injection, Salvianolate injection, compound Danshen injection and Sodium Tanshinone IIA Sulfonate (STS) injection are widely used in China to treat stable angina (angina pectoris) caused by coronary heart disease. In this study we compared the network pharmacological mechanisms of the 5 Danshen preparations. Following a literature search performed in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, China Biology Medicine (CBM) database, China Conference Paper Database, Wanfang Database, VIP Database and Conference Proceedings Citation Index (through January 2015), 444 randomized controlled trial publications detailing the use of the 5 Danshen-based injections for treating stable angina were identified, and their combined data were analyzed using a network meta-analysis. All of the 5 Danshen-based preparations were effective in treating stable angina with clinical improvement rates of 72.4%-91.6% and electrocardiogram (ECG) improvement rates of 54.5%-71.6%. According to both clinical improvement and ECG improvement, the 5 Danshen-based preparations were ranked as follows: Danhong injection > Salvianolate injection > STS injection > compound Danshen injection > Danshen injection. There were no significant differences among the safety profiles of the 5 Danshen preparations. The meta-analysis results were further examined using a network pharmacology approach and functional enrichment analysis, which revealed that Danshen and Danhong injections affected 4 and 15 signaling pathways, respectively, and that the 4 signaling pathways affected by Danshen were a subset of those influenced by Danhong. Therefore, Danhong injection affected some unique signaling pathways that might regulate lipoprotein metabolism, oxidation, and inflammation, and protect vascular endothelia, reflecting the multi-component and multi-target characteristics of this traditional formula and its strengths in treating complex diseases.

[Chaotic Features on Excess/Deficiency Syndrome of Chronic Stable Angina Pectoris Based on Analyzing Approximate Entropy of Heart Rate Variability].

Objective To analyze the chaotic degree of excess/deficiency syndrome (ES/DS) in chronic stable angina pectoris (CSAP) patients by observing 24-h dynamic changes of approximate en- tropy index of heart rate variability per hour, and to observe dynamic changing features. Methods From November 2009 to June 2011, a total of 187 CSAP patients were assigned to ES (36 cases) , DS (42 ca- ses) , intermingled syndrome of deficiency and excess (109 cases, abbreviated as intermingled ES/DS) according to TCM syndrome differentiation standards.24 h dynamic electrocardiograms were collected u- sing USA DMS dynamic ECG, which was then divided into 24 continuous period by hour. The approximate entropy algorithm (by hour) was respectively calculated. The approximate entropy diurnal variation trend was analyzed in patients with different TCM syndromes. These results were controlled with 30 healthy subjects who had normal physical examinations at the same hospital. Results The approximate entropy mean value of each hour throughout the day was lower, as compared with the healthy group (F=7. 847, P <0. 01). Although no statistical difference existed among ES, DS, intermingled ES/DS (F =1. 585, P = 0. 208), the approximate entropy mean value showed the tendency of ES >intermingled ES/DS > ES. From 8:00 a.m. to 7:00 a.m. on the next day, the variation tendency of four-group curves all showed that the approximate entropy level changed as time went by (F =2. 655, P <0. 01). Besides, the approximate en- tropy diurnal variation of ES, DS, intermingled ES/DS showed a similar trend (F =1. 011 ,P =0. 457) , but different from the healthy group (F = 1. 583, P = 0. 003). The curve in the healthy group showed "two peaks and one valley" type [one peak from 10:00 to 14:00, and the other peak from 22:00 to 02:00]. The curve for ES, DS, intermingled ES/DS showed an inverted dipper type [only a peak at night, and a relatively stable curve from 8:00 to 19:00]. Compared with the normal group, the day peak disappeared in CSAP patients, and the daytime approximate entropy was significantly reduced (F = 10. 315, P <0. 01). Conclusions Compared with the healthy group, the approximate entropy of CSAP patients decreased, which means the chaotic degree reduced. The adaptability of the cardiovascular system to external envi- ronment changes was weakened, which was more obviously seen at daytime than at night. The chaotic degree showed gradually decreasing trend (ES > DS >intermingled DS/ES).

Management of Stable Angina - Current Guidelines: A Critical Appraisal.

Guidelines provide recommendations to improve patient outcomes, but many of the recommendations made for treating patients with stable angina are opinion based rather than evidence based. Risk stratification to predict patients at an increased risk of myocardial infarction (MI) and sudden ischemic death, and selection of patients for possible revascularization, is based on expert opinion. Randomized trials have compared optimal medical therapy to revascularization, after the coronary anatomy was known, and yet routine coronary angiography to exclude left main disease is not recommended. What exactly is optimal antianginal treatment varies considerably from one country's guideline recommendations to another. None of the antianginal drugs reduce mortality or MI and these drugs are equally effective in treating angina pectoris; and yet beta-blockers and calcium channel blockers are recommended as first line therapy. Double and triple therapy with different classes of antianginal drugs is also expert opinion based rather than evidence based. Recommendations to reduce the incidence of MI and sudden death are appropriate; however the use of a potent, high dose statin, is recommended by AHA/ACC and NICE guidelines for all patients with ischemic heart disease, while the European guidelines recommend a target LDL goal in patients with coronary artery disease (CAD). Management of patients with stable angina pectoris with normal coronary arteries remains ambiguous. This short review critically appraises the recommendations for managing patients with stable angina pectoris.

Diagnosing coronary artery disease by sound analysis from coronary stenosis induced turbulent blood flow: diagnostic performance in patients with stable angina pectoris.

Optimizing risk assessment may reduce use of advanced diagnostic testing in patients with symptoms suggestive of stable coronary artery disease (CAD). Detection of diastolic murmurs from post-stenotic coronary turbulence with an acoustic sensor placed on the chest wall can serve as an easy, safe, and low-cost supplement to assist in the diagnosis of CAD. The aim of this study was to evaluate the diagnostic accuracy of an acoustic test (CAD-score) to detect CAD and compare it to clinical risk stratification and coronary artery calcium score (CACS). We prospectively enrolled patients with symptoms of CAD referred to either coronary computed tomography or invasive coronary angiography (ICA). All patients were tested with the CAD-score system. Obstructive CAD was defined as more than 50 % diameter stenosis diagnosed by quantitative analysis of the ICA. In total, 255 patients were included and obstructive CAD was diagnosed in 63 patients (28 %). Diagnostic accuracy evaluated by receiver operating characteristic curves was 72 % for the CAD-score, which was similar to the Diamond-Forrester clinical risk stratification score, 79 % (p = 0.12), but lower than CACS, 86 % (p < 0.01). Combining the CAD-score and Diamond-Forrester score, AUC increased to 82 %, which was significantly higher than the standalone CAD-score (p < 0.01) and Diamond-Forrester score (p < 0.05). Addition of the CAD-score to the Diamond-Forrester score increased correct reclassification, categorical net-reclassification index = 0.31 (p < 0.01). This study demonstrates the potential use of an acoustic system to identify CAD. The combination of clinical risk scores and an acoustic test seems to optimize patient selection for diagnostic investigation.

[Impacts on neutrophil to lymphocyte ratio in patients of chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6)].

OBJECTIVE: To observe the clinical efficacy on chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6) and explore the impacts of acupuncture on peripheral blood neutrophil to lymphocyte ratio (NLR) in the patients of stable angina pectoris. METHODS: Thirty patients of chronic stable angina pectoris met the inclusive criteria were randomized into an acupuncture group (15 cases) and a medication group (15 cases), and a healthy control group (15 cases of the same ages) was set up separately. In the acupuncture group, at the same time of the basic medication, acupuncture was applied to bilateral Neiguan (PC 6), once every two days, 3 days a week, totally for 4 weeks. In the medication group, the basic medication was applied, without acupuncture intervention. In the healthy control group, no any intervention was applied. The attack frequency of angina pectoris, dose of nitrogly-cerin, the evaluation of visual analogue scale (VAS), Seattle angina questionnaire (SAQ), the six-minute walking test (6MWT), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were observed before and after treatment in the subjects. Additionally, the peripheral blood cells were detected to analyze specifically the changes in NLR before and after treatment and observe the relationship between NLR and clinical efficacy. RESULTS: Compared with the medication group, the attack frequency of angina pectoris was reduced within 30 days (P<0.01); the dose of nitroglycerin was reduced (P<0.01); VAS was reduced (P<0.01) and SAQ was increased (P<0.05) in the acupuncture group. The differences in 6 MWT, SAS and SDS were not significant between the two groups after treatment (all P>0.05). Additionally, compared with the medication group, in 30 days of acupuncture, NLR was reduced apparently in the acupuncture group (P<0.05). CONCLUSION: Acupuncture relieves the clinical symptoms of chronic stable angina pectoris, but has not apparent effects on motor ability and psychological health. Corresponding to that before treatment, the decreased NRL in the patients of acupuncture group suggests the potential good prognosis on coronary heart disease after acupuncture.

Traditional Chinese medicine for stable angina pectoris via TCM pattern differentiation and TCM mechanism: study protocol of a randomized controlled trial.

BACKGROUND: Stable angina pectoris is experienced as trans-sternal or retro-sternal pressure or pain that may radiate to the left arm, neck or back. Although available evidence relating to its effectiveness and mechanism are weak, traditional Chinese medicine is used as an alternative therapy for stable angina pectoris. We report a protocol of a randomized controlled trial using traditional Chinese medicine to investigate the effectiveness, mechanism and safety for patients with stable angina pectoris. METHODS/DESIGN: This is a north-east Chinese, multi-center, multi-blinded, placebo-controlled and superiority randomized trail. A total of 240 patients with stable angina pectoris will be randomly assigned to three groups: two treatment groups and a control group. The treatment groups will receive Chinese herbal medicine consisting of Yi-Qi-Jian-Pi and Qu-Tan-Hua-Zhuo granule and Yi-Qi-Jian-Pi and Qu-Tan-Hua-Yu granule, respectively, and conventional medicine. The control group will receive placebo medicine in addition to conventional medicine. All 3 groups will undergo a 12-week treatment and 2-week follow-up. Four visits in sum will be scheduled for each subject: 1 visit each in week 0, week 4, week 12 and week 14. The primary outcomes include: the frequency of angina pectoris attack; the dosage of nitroglycerin; body limited dimension of Seattle Angina Questionnaire. The secondary outcomes include: except for the body limited dimension of SAQ, traditional Chinese medicine pattern questionnaire and so on. Therapeutic mechanism outcomes, safety outcomes and endpoint outcomes will be also assessed. DISCUSSION: The primary aim of this trial is to develop a standard protocol to utilize high-quality EBM evidence for assessing the effectiveness and safety of SAP via TCM pattern differentiation as well as exploring the efficacy mechanism and regulation with the molecular biology and systems biology. CLINICAL TRIALS REGISTRATION: ChiCTR-TRC-13003608, registered 18 June 2013.

[Using functional brain imaging technique to study central mechanism of acupuncture therapy for chronic stable angina pectoris in view of heart-brain correlation].

Heart-brain correlation is an important component of Chinese medicine about the theory of zang-fu organs, which is still valuable for acupuncture clinical practice. Nowadays, increasing evidence supports the close association between the heart-brain axis, central autonomic nerve network and cardiovascular diseases, as well as the extensive regulative effects of acupuncture intervention on the heart-brain axis, functional connectivity of the brain, automatic nerve activities and cardiac functions. Therefore, the authors of the present paper hold that from the viewpoint of the heart-brain relationship, and by combining non-invasive functional brain imaging techniques with the patients' subjective and objective clinical indexes, our researchers will possibly and systematically reveal the underlying central mechanisms of acupuncture therapy in the treatment of chronic stable angina pectoris. However, the concrete biochemical mechanism should be proved via other advanced biological techniques.

Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life.

OBJECTIVE: This study aimed to evaluate the effects of short-term (60-d) oral supplementation with calcium fructoborate, resveratrol, and their combination on the clinical and biological statuses of subjects with stable angina pectoris. METHODS: A randomized, double-blinded, active-controlled, parallel clinical trial was conducted in three groups of subjects. Of the total number of subjects included in study (n = 166), 87 completed the 60-d test treatment study period and 29 followed in parallel their usual medical care and treatment. The primary outcomes were inflammation biomarkers (high-sensitivity C-reactive protein), left ventricular function markers (N-terminal prohormone of brain natriuretic peptide), and lipid markers (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triacylglycerols). Quality of life was assessed by the Canadian Cardiovascular Society angina class and the number of angina attacks per week. RESULTS: There was a significant decrease of high-sensitivity C-reactive protein in all groups at the 30-d and 60-d visits. This decrease was greater (39.7% at 60 d) for group 3 (calcium fructoborate), followed by group 2 (resveratrol plus calcium fructoborate, 30.3% at 60 d). The N-terminal prohormone of brain natriuretic peptide was significantly lowered by resveratrol (group 1, 59.7% at 60 d) and by calcium fructoborate (group 3, 52.6% at 60 d). However, their combination (group 2) was the most effective and induced a decrease of 65.5%. Lipid markers showed slight changes from baseline in all groups. The improvement in the quality of life was best observed for subjects who received the resveratrol and calcium fructoborate mixture (group 2). CONCLUSION: The results indicate that the combination of resveratrol and calcium fructoborate has beneficial effects in patients with angina

Advances in the management of stable angina.

OBJECTIVE: To describe the approved uses, pharmacology, pharmacodynamics, pharmacokinetics, efficacy, safety, and place in therapy of ranolazine, the first new antianginal drug therapy introduced in more than 20 years for the treatment of chronic angina. SUMMARY: The mechanism of action of ranolazine is unknown, but it may involve inhibition of the late sodium current in the myocardium, thereby preventing sodium-induced intracellular calcium overload during ischemia. This mechanism differs from that of other antianginal agents, which primarily affect myocardial oxygen supply or demand through hemodynamic effects. Ranolazine undergoes extensive metabolism, primarily by cytochrome P-450 (CYP) 3A4, so interactions with drugs that are moderate to potent inhibitors of CYP3A4 need to be considered. Ranolazine is also a P-glycoprotein (P-gp) substrate and inhibitor, and it may interact with other P-gp substrates and inhibitors. In patients with an inadequate response to other antianginal agents, the addition of ranolazine to existing antianginal therapy increases exercise duration and the time to angina on an exercise treadmill test, and it decreases the frequency of angina attacks and nitroglycerin use. The drug produces antianginal effects without significantly affecting either heart rate or blood pressure. Ranolazine prolongs the QT interval on the electrocardiogram, but the overall electrophysiologic effects of the drug suggest that it is not expected to cause torsades de pointes. CONCLUSION: Ranolazine has a unique mechanism of action that may be complementary to that of conventional antianginal agents in the treatment of chronic angina. An understanding of the potential for drug interactions, disease interactions, and contraindications is needed to ensure safe and effective use of the drug.