[Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease].

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease / 中国中药杂志

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

[Effect of ligustrazine hydrochloride on coagulation reaction and inflammation reaction in single valve replacement patients with rheumatic heart disease undergoing cardiopulmonary bypass].

OBJECTIVE: To observe the protection effect of Ligustrazine Hydrochloride (LH) on coagulation reaction and inflammation reaction in single valve replacement patients with rheumatic heart disease undergoing cardiopulmonary bypass (CPB). METHODS: Totally 40 patients undergoing single valve replacement were recruited in the study and randomly assigned to the two groups, the treatment group and the control group, 20 in each group. In treatment group LH (3 mg/kg) was intravenously infused from the jugular vein. LH (3 mg/kg) was also added in the CPB priming. In the control group LH was replaced by equal amount of normal saline. Endothelial micro-particles (EMP) count was detected before CPB, 30 min after CPB, 1 h and 24 h after CPB finished. The coagulation reaction time (R), coagulation time (K), clotting formation velocity (alpha angle), maximum amplitude (MA), coagulation index (CI), platelet (PLT), hypersensitive C reactive protein (hs-CRP), IL-6, and IL-10 were detected before CPB, 1 h and 24 h after CPB finished. RESULTS: There was no statistical difference in aorta arresting time, period of CPB, post-operative drainage volume, plasma transfusion volume, post-operative respirator assistant time, and hospitalization time between the two groups (P >0.05). Compared with pre-CPB in the same group, the count of EMP was much higher at 30 min after CPB and 1 h after CPB finished (P < 0.01). R and K, hs-CRP, IL-6, and IL-10 increased at 1 h and 24 h after CPB finished (P <0.01,P < 0.05). The alpha angle,.MA, CI, and PLT decreased 1 h after CPB finished (P <0.01). The a angle increased, while CI and PLT decreased 24 h after CPB finished (P <0.05). Compared with the control group in the same period, the count of EMP was lower in the treatment group 30 min after CPB and 1 h after CPB finished (P <0. 05, P <0. 01). R and K values obviously decreased in treatment group 1 hour after CPB finished (P <0. 05), while a angle, MA, CI, and PLT increased (P <0. 05, P <0. 01). hs-CRP and IL-6 decreased in the treatment group 1 h and 24 h after CPB finished (P <0.05), while IL-10 increased (P <0.05). The count of PLT increased 24 h after CPB finished in the treatment group (P <0. 05). CONCLUSION: LH had certain protection effect on the vascular endothelium undergoing CPB, and lower excessive activation of coagulation reaction and inflammation reaction in patients undergoing CPB.

Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C). CONCLUSIONS: These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.

Reduced bone density in patients on long-term warfarin.

AIM: Vitamin K is an essential factor for carboxylation of bone matrix protein. Low vitamin K may be associated with reduced bone mineral density (BMD). The issue of whether long-term sodium warfarin therapy as oral anticoagulant that antagonizes vitamin K, results in decreased bone density, is controversial. Our purpose in this study was to assess the effects of warfarin on BMD. METHODS: We performed a case control study survey of bone density in 70 patients with rheumatic valvular heart disease 'mechanical valve replacement' on long-term warfarin compared with 103 randomly selected matched controls. RESULTS: There was a marked reduction in BMD (g/cm(2)) and T-score of lumbar spine between patients and controls (P = 0.048, 0.005). Duration of warfarin use was the only risk factor of significant importance respectively on spinal T-score (P < 0.03). CONCLUSIONS: Screening of patients on long-term warfarin for reduced bone density should be considered. We strongly suggest the prophylactic use of calcium-vitamin D supplements for these patients.

[Study on protective effect of shenfu injection on cardiac function of patients undergoing valve replacement].

OBJECTIVE: To investigate the protective effect of Shenfu injection (SFI) on cardiac function of patients undergoing valve replacement operation under cardio-pulmonary bypass. METHODS: One hundred and twenty patients undergoing valve replacement operation under cardio-pulmonary bypass were randomly divided into the SFI group and the control group, 60 in each group. Intravenous infusion of 1 ml/kg SFI was given to the SFI group, 30 min before anesthesia, and to the control group, equal volume of normal saline was given instead. The following indices were observed: (1) the hemodynamic changes occurred in the operational period; (2) the dosage of vaso-active drugs used during and after operation; (3) the post-operational recovery time of patients. RESULTS: The mean arterial pressure and heart rate in the SFI group during operation were higher, while the central venous pressure was lower than those in the control group (P < 0.05). The dosage of vaso-active drugs, such as dopamine, dobutamine, sodium nitroprusside and lidocaine, used during and after operation was lower, and the extubation time and the intensive care unit (ICU) staying time were shorter in the SFI group when compared with those in the control group (P < 0.05). CONCLUSION: SFI has certain protective effects on the cardiac function of patients undergoing valve replacement operation under cardio-pulmonary bypass.

[Clinical study of Astragalus injection plus ligustrazine in protecting myocardial ischemia reperfusion injury].

OBJECTIVE: To investigate the mechanism of Astragalus injection plus ligustrazine in preventing the occurrence of myocardial ischemia reperfusion injury (MIRI) during open heart surgery of cardiopulmonary bypass, and the treating principle of MIRI in TCM. METHODS: Twenty-four patients suffering from either valvular heart diseases or congenital ventricular septal defect were randomly divided into three treated groups (Astragalus, ligustrazine, Astragalus plus ligustrazine) and the control group, 6 in each group. Blood samples were taken via subclavian central vein at the time before anesthesia (T1), 10 minutes of occlusion of aorta (T2), 10 minutes (T3) and 30 minutes (T4) after the release, and the end of operation (about 180 minutes after release, T5) respectively; EKG was observed, and the levels of asparate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of CK (CK-MB), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), nitric oxide (NO), nitric oxide synthetase (NOS) were determined. RESULTS: The treated groups could reduce the levels of AST, LDH, CK, CK-MB, MDA, SOD compared with the control group, particularly Astragalus plus ligustrazine, there had significant difference (P < 0.05, P < 0.01). In NO activity improvement, Astragalus plus ligustrazine won the best effect, Astragalus group the next. CONCLUSIONS: The mechanism of MIRI is Qi deficiency and blood stasis in TCM, its treating principles should be promoting Qi and removing the blood stasis. According to the authors' study, Astragalus plus ligustrazine could effectively protect against MIRI, which is better than using the 2 medicines separately.

[Clinical observation on treatment of postcardiotomic complications with Chinese herbal medicine based on syndrome differentiation with angiocardiopathy].

OBJECTIVE: To study the effect of Chinese herbal medicine (CHM) based on Syndrome Differentiation on postcardiotomic complications in patients with angiocardiopathy. METHODS: Aimed at the frequently encountered postcardiotomic complications including fever, cough and expectoration, belching, abdominal distension, palpitation, short breath, etc. CHM treatment was applied in combination with routine western drugs treatment (cardiac tonic, diuretics, vascular dilatator and anticoagulant). RESULTS: Twenty out of 22 patients with protracted fever and irresponsive to multi-antibiotics therapy were cured, the other one with hydrothorax received other therapy and the another one with drug fever was natural cured after stopping medication. Among 23 patients complicated mainly with respiratory symptoms, 17 were cured and 6 improved, among 15 with digestive symptoms, 12 cured and 3 improved, and among 7 with cardiovascular symptoms, 3 cured, 2 improved and 2 ineffective. CONCLUSION: CHM has good effect on postcardiotomic complications, it could improve the functional recovery of heart and lung.

[The chronocorrection of disorders in the blood coagulation rhythm with kurantil in patients with decompensated rheumatic heart defects]. / Khronokorrektsiia narushenii ritma gemokoaguliatsii kurantilom u bol'nykh s dekompensirovannymi revmaticheskimi porokami serdtsa.

The circadian pattern of hemocoagulation was studied in patients with decompensated rheumatic heart disease (DRHD) concurrent with stages I-II circulatory failure (CF) during complex treatment or medical treatment with disaggregants. Biorhythmological studies demonstrated that in patients with DRHD and CF chronotherapy with curantyl had some advantages over the traditional therapy during complex drug therapy. In these patients, the chronopatterns of circadian rhythms of hemocoagulative parameters tended to normalize under the influence of curantyl chronotherapy, by diminishing the signs of external desynchronization. Advantages of chronotherapy over the traditional treatment found in patients with DRHD and stages I-II CF, as manifested by its clinical effect in shorter periods (on days 4-5) when small daily and course doses of the drug were used. Based on the biorhythmological studies of hemostatic parameters, a method of curantyl chronotherapy was developed for patients with DRHD and stages I-II CF, which may optimize the therapeutical process in patients with this abnormality.

[Time organization of blood coagulation in patients with rheumatic heart disease involving circulation insufficiency]. / Vremennaia organizatsiia gemokoaguliatsii i ee korrektsiia u bol'nykh revmaticheskimi porokami serdtsa s nedostatochnost'iu krovoobrashcheniia.

Daily profiles of blood coagulation were studied in 20 normal subjects and 92 patients with rheumatic heart disease with stages I-III circulatory insufficiency before and after traditional therapy and chronotherapy with heparin and curantyl added to traditional therapy with antirheumatic agents, diuretics, and cardiac glycosides. Time organization of the hemostasis was disordered in patients with decompensated heart disease, but it is possible to correct it by chronotherapy with heparin and curantyl.

Simultaneous therapy with antiplatelet and anticoagulant drugs in symptomatic cardiovascular disease.

Twenty of approximately 1000 patients attending the arteriosclerosis clinic at MIT during a 13 year period were treated simultaneously with aspirin and warfarin for symptomatic atherosclerotic (19) or rheumatic (1) heart or vascular disease. The average duration of therapy was 5.8 years. Thirteen patients suffered from familial hyperlipoproteinemia; only one patient had none of the major risk factors for arteriosclerosis. Refractory symptoms were related to the central nervous system in 13, peripheral vascular system in 5 and the heart in 2. All twenty patients became asymptomatic or showed marked clinical improvement on aspirin plus warfarin therapy. While on this therapy, complications, both thrombotic and hemorrhagic, occurred in 7 of the 20 patients (graft embolus in 1, and bleeding in 6; with one death as a result of intracranial bleeding) and sudden death, probably from acute myocardial ischemia, in a further 2 patients. We conclude that when alternative therapies are impossible or have proven to be of no avail in patients suffering from the complications of advanced atherosclerosis, the simultaneous administration of aspirin and warfarin may be a therapeutic alternative, although very close and careful followup of the patients' prothrombin times and clinical status is essential.

Failure of sulphinpyrazone to affect platelet survival in patients with rheumatic heart valvular disease: a double blind study using 75Se-methionine labeled platelets.

We have investigated platelet survival time in 18 patients suffering from valvular heart disease. Platelet survival was performed using the 75Se-methionine method modified by us. Nine of our eighteen patients underwent surgery for heart valve replacement. Platelet survival time was performed before treatment and six months afterwards with placebo or sulfinpyrazone in a double blind study. Before treatment and surgery, platelet survival time was significantly reduced in patients with a history of embolism (P less than 0.0048). In patients receiving valve replacement, platelet survival time was shortened both in the sulfinpyrazone and placebo groups six months after surgery. Of the nine patients not receiving prostheses and with a thrombotic history, treatment with placebo and sulfinpyrazone resulted in improved platelet survival times.

[Study of the total nucleic acid content of lymphoid tissue plasma cells for assessing the immunodepressive action of various antirheumatic agents]. / Izuchenie summarnogo soderzhaniia nukleinovykh kislot plazmaticheskikh kletok limfoidnoi tkani dlia otsenki immunodepressivnogo deistviia razlichnykh protivorevmaticheskikh sredstv.

The influence of antirheumatic drugs, acetylsalicylic acid, diacetoxibenzoic acid, imurane and D-penicillamine, on the status of immunocompetent cells in experimental infectious-allergic carditis was studied morphologically in 70 rabbits. The immunosuppressive effect of all 4 drugs was established which was manifested by a decrease in the number of plasma cells in the lymphoid tissue and a decrease in the content of nucleic acids in their cytoplasm. D-penicillamine was the exception as after its use the content of nucleic acids in the cell cytoplasm was found to be increased which was considered to be due to clasmatosis of plasma cells, marginal karyolysis, damage of the nuclear membrane and release of nucleic acids from the nucleus into the cytoplasm. Acetylsalicylic acid and diacetooxybenzoic acid decrease RNA content in the cytoplasm of plasma cells less than imurane and do not cause cell degeneration with contamination of the extracellular environment with products of cells degeneration.