Ablação por Cateter para Fibrilação Atrial em Pacientes com Fração de Ejeção do Ventrículo Esquerdo ≤ 45%: Uma Metanálise de Ensaios Clínicos Randomizados / Catheter Ablation for Atrial Fibrillation in Patients with Left Ventricular Ejection Fraction ≤ 45%: A Meta-Analysis of Randomized Controlled Trials

Resumo Fundamento A fibrilação atrial (FA) e a insuficiência cardíaca (IC) coexistem frequentemente, resultando em desfechos adversos. No entanto, permanecem controvérsias quanto à eficácia da ablação por cateter (AC) em pacientes com FA com disfunção ventricular esquerda grave. Objetivos O objetivo deste estudo foi realizar uma metanálise de ensaios prospectivos randomizados e controlados para avaliar a eficácia da AC versus terapia médica (TM) em pacientes com FA com fração de ejeção do ventrículo esquerdo (FEVE) ≤45%. Métodos Procuramos na literatura estudos que comparassem AC com TM em pacientes com FA com FEVE ≤45%. Foi realizada uma metanálise de 7 ensaios clínicos, incluindo 1.163 pacientes com FA e IC. A análise de subgrupo foi realizada com base na FEVE basal. Todos os testes foram bilaterais; apenas o valor p <0,05 foi considerado estatisticamente significativo. Resultados Descobrimos que a AC estava associada a menor mortalidade por todas as causas (taxa de risco: 0,52, IC 95%: 0,37 a 0,72; p<0,01) e maiores melhorias na FEVE (diferença média: 4,80%, IC 95%: 2,29% a 7,31%; p<0,01) em comparação com TM. Os pacientes do grupo AC apresentaram menor risco de hospitalização por IC e recorrência de FA e qualidade de vida significativamente melhor do que aqueles do grupo TM. Os resultados da análise de subgrupo indicaram que pacientes com disfunção ventricular esquerda mais leve melhoraram a FEVE após a ablação de FA (diferença média: 6,53%, IC 95%: 6,18% a 6,88%; p<0,01) em comparação com pacientes com doença mais grave (diferença média : 2,02%, IC 95%: 0,87% a 3,16%; p<0,01). Conclusões Nossa metanálise demonstrou que a AC foi associada a melhorias significativas nos resultados de pacientes com FA com FEVE ≤45%. Além disso, pacientes com FA com disfunção ventricular esquerda mais leve poderiam se beneficiar mais com a AC.

Abstract Background Atrial fibrillation (AF) and heart failure (HF) frequently coexist, resulting in adverse outcomes. However, controversies remain regarding the efficacy of catheter ablation (CA) in AF patients with severe left ventricular dysfunction. Objectives The purpose of this study was to perform a meta-analysis of prospective randomized controlled trials to evaluate the efficacy of CA versus medical therapy (MT) in AF patients with left ventricular ejection fraction (LVEF) ≤45%. Methods We searched the literature for studies that compared CA to MT in AF patients with LVEF ≤45%. A meta-analysis of 7 clinical trials was performed, including 1163 patients with AF and HF. Subgroup analysis was performed based on baseline LVEF. All tests were 2-sided; only the p-value <0.05 was considered statistically significant. Results We found that CA was associated with lower all-cause mortality (risk ratio: 0.52, 95% CI: 0.37 to 0.72; p<0.01) and greater improvements in LVEF (mean difference: 4.80%, 95% CI: 2.29% to 7.31%; p<0.01) compared to MT. Patients in the CA group had a lower risk of HF hospitalization and AF recurrence and a significantly better quality of life than those in the MT group. The results of subgroup analysis indicated that patients with milder left ventricular dysfunction improved LVEF after AF ablation (mean difference: 6.53%, 95% CI: 6.18% to 6.88%; p<0.01) compared to patients with more severe disease (mean difference: 2.02%, 95% CI: 0.87% to 3.16%; p<0.01). Conclusions Our meta-analysis demonstrated that CA was associated with significant improvements in outcomes of AF patients with LVEF ≤45%. Additionally, AF patients with milder left ventricular dysfunction could benefit more from CA.

Extracorporeal Membrane Oxygenation Uses in Refractory Cardiogenic Shock After Open-Heart Surgery

ABSTRACT Introduction: Extracorporeal membrane oxygenation (ECMO) is the first-line therapy for temporary mechanical circulatory support allowing cardiac and pulmonary recovery or as a bridge to further therapeutic alternatives. The aim of this study was to report clinical outcomes in adult patients with refractory cardiac failure after open-heart surgery undergoing ECMO in a single center with an ECMO unit in Chile. Methods: We retrospectively analyzed adults with refractory cardiac failure after open-heart surgery who required a venoarterial (VA) ECMO between 2016 and 2021. Results: Of 16 patients with VA ECMO, 60% were men (n=10), 90% had hypertension (n=14), 69% had < 30% of left ventricular ejection fraction (n=11), and the mean European System for Cardiac Operative Risk Evaluation II score was 12 ± 11%. ECMO support with central cannulation accounts for 81% (n=13), and an intra-aortic balloon pump was used in nine patients (56%). The mean time of support was 4.7 ± 2.6 days (1.5 - 12 days). ECMO weaning was achieved in 88% of patients, and in-hospital mortality was 44% (n=7) after discharge. The freedom from all-cause mortality at one year of follow-up of the entire cohort was 38% (n=6). Conclusion: VA ECMO is now a well-known life-saving therapeutic option, but mortality and morbidity remain high. Implementation of an ECMO program with educational training is mandatory in order to find the proper balance between patient benefits, ethical considerations, and public health financial input in South America.

Evolução da Captação Miocárdica de 18F-FDG em Paciente com Diagnóstico de Cardiotoxicidade / Progression of Myocardial 18F-FDG Uptake in a Patient with Cardiotoxicity

Resumo O objetivo deste relato é mostrar a evolução da cardiotoxicidade (CTX) por quimioterápicos em paciente com linfoma por exames de imagens, destacando a importância da captação miocárdica de flúor-18 fluordeoxiglicose (18F-FDG) pela tomografia por emissão de pósitrons, acoplada à tomografia computadorizada (PET/CT). Feminino, 43 anos, com linfoma uterino, submetida a histerectomia, três esquemas de quimioterapia (QT), sucessivamente, e radioterapia. Apresentou episódios de insuficiência cardíaca aguda dois anos após QT. Ecocardiograma mostrou redução da fração de ejeção do ventrículo esquerdo (FEVE). Análise retrospectiva do 18F-FDG PET/CT observou elevação da captação miocárdica em todos os exames durante o seguimento oncológico. Apesar da remissão oncológica, a paciente desenvolveu IC com FEVE reduzida. Durante a QT, ocorreu aumento difuso e significativo da captação miocárdica de 18F-FDG, que precedeu a queda do desempenho cardíaco, e pareceu refletir alterações metabólicas nos cardiomiócitos relacionadas à CTX. A análise da captação miocárdica de 18F-FDG modificaria o desfecho cardiológico da paciente? Esse questionamento é relevante, visto que outros pacientes podem se beneficiar desse método como marcador precoce de CTX. Os exames de imagem são imprescindíveis no acompanhamento de pacientes com risco de CTX. O ecocardiograma permanece como principal auxílio diagnóstico, porém o 18F-FDG PET/CT pode estar surgindo como uma poderosa ferramenta para um diagnóstico mais precoce dessa condição clínica.

Abstract The objective of this case report was to present the progression of chemotherapy-induced cardiotoxicity in a patient with lymphoma, highlighting the importance of myocardial fluor-18-fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography coupled with computed tomography (PET/CT). 43-year-old female patient with uterine lymphoma, who underwent hysterectomy followed by three chemotherapy regimens and radiotherapy. The patient had episodes of acute heart failure two years after chemotherapy. Echocardiogram revealed a reduction in left ventricular ejection fraction (LVEF). A retrospective analysis of 18F-FDG PET/CT showed an increase in myocardial uptake in all tests performed during oncologic treatment. Despite disease remission, the patient developed heart failure with reduced LVEF. During chemotherapy, there was a diffuse, significant increase in myocardial 18F-FDG uptake, which preceded the decrease in myocardial performance and seemed to reflect metabolic changes in cardiomyocytes, related to cardiotoxicity. Would an analysis of myocardial 18F-FDG uptake yield a different cardiac outcome in this patient? This question is relevant, considering that other patients may benefit from the use of PET as an early marker of cardiotoxicity. Imaging tests are essential in the follow-up of patients at risk of cardiotoxicity. Although echocardiography remains the main imaging test in the diagnosis of cardiotoxicity, 18F-FDG PET/CT may be a powerful tool for the early diagnosis of this condition.

Telemedicine and patients with heart failure: evidence and unresolved issues

ABSTRACT Heart failure is the leading cause of cardiac-related hospitalizations. Limited access to reevaluations and outpatient appointments restricts the application of modern therapies. Telemedicine has become an essential resource in the healthcare system because of its countless benefits, such as higher and more frequent appointments and faster titration of medications. This narrative review aimed to demonstrate the evidence and unresolved issues related to the use of telemedicine in patients with heart failure. No studies have examined heart failure prevention; however, several studies have addressed the prevention of decompensation with positive results. Telemedicine can be used to evaluate all patients with heart failure, and many telemedicine platforms are available. Several strategies, including both noninvasive (phone calls, weight measurement, and virtual visits) and invasive (implantable pulmonary artery catheters) strategies can be implemented. Given these benefits, telemedicine is highly desirable, particularly for vulnerable groups. Although some questions remain unanswered, the development of new technologies can complement remote visits and improve patient care.

Effect of Ticagrelor on Left Ventricular Function in Patients with Mildly Reduced Ejection Fraction after Acute Myocardial Infarction

Abstract Background There are limited data about the effect of new P2Y12 inhibitors on left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI). Objectives We aimed to investigate the effect of ticagrelor on left ventricular function, compared to clopidogrel in patients with heart failure with mildly reduced ejection fraction (HFmrEF) after AMI. Methods In this cross-sectional, single-center study, we included 251 patients with LVEF between 40% and 50% after AMI before discharge. The patients were divided into 2 groups according to the use of ticagrelor (166 patients) and clopidogrel (85 patients). At the end of the 12-month period, LVEF changes were assessed by echocardiography. P < 0.05 was considered statistically significant. Results The mean LVEF before discharge was 46.5% ± 3.6%, and no difference was observed between the ticagrelor and clopidogrel groups (p = 0.20). At the end of the first year, the mean LVEF of the patients increased to 49.8% ± 7.6% in both groups. The use of ticagrelor (β ± SE = 2.05 ± 0.93; p = 0.029), low creatinine level (β ± SE = −10.44 ± 2.35; p < 0.001), low troponin level (β ± SE = −0.38 ± 0.14; p = 0.006), and low heart rate (β ± SE = −0.98 ± 0.33; p = 0.003) were found to be independent predictors of the increase in LVEF (β ± SE 2.05 ± 0.93; 95% confidence interval: 0.21 to 3.90; p = 0.029). Conclusion In our study, ticagrelor improved left ventricular function in 12 months follow-up compared to clopidogrel in patients with HFmrEF after AMI.

Perfil clínico, farmacoterapêutico e laboratorial de pacientes internados com insuficiência cardíaca aguda / Clinical, pharmacotherapeutic and laboratory profile of hospitalized patients with acute heart failure / Perfil clínico, farmacoterapéutico y de laboratorio de los pacientes hospitalizados com insuficiência cardíaca aguda

A insuficiência cardíaca aguda (ICA) é uma das causas mais comuns de internação hospitalar, associada a um alto risco de mortalidade. O tratamento atual é principalmente sintomático, sendo os exames laboratoriais realizados, a fim de complementar a avaliação clínica no diagnóstico e auxiliar no estabelecimento do perfil de risco admissional e prognóstico. Este estudo teve como objetivo caracterizar o perfil clínico, farmacoterapêutico e laboratorial de pacientes internados com insuficiência cardíaca aguda em hospital referência regional. Trata-se de um estudo transversal retrospectivo, descritivo, de abordagem quantitativa. Os participantes do estudo foram aqueles com alta médica por ICA pela classificação Internacional de Doenças (CID-10), admitidos na sala de emergência. Excluindo-se a participação de pacientes com tempo de internação inferior a 24 horas, menores de 18 anos. Para análise estatística foi usado o programa SPSS versão 21.0. Quanto ao perfil farmacoterapêutico, os medicamentos mais frequentes foram os que atuam no aparelho cardiovascular e aparelho digestivo e metabolismo, sendo a furosemida o fármaco mais frequente. A análise entre as alterações laboratoriais e a escala de ADHERE, revelou diferença estatística significativa entre os pacientes com risco baixo e risco intermediário/alto nos valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), ureia (p=0,000), potássio (p=0,004), TTPA (p=0,004) e RNI (p=0,021). Concluiu-se que os medicamentos frequentemente corresponderam ao tratamento recomendado no manejo inicial de pacientes com ICA. O risco de mortalidade intra-hospitalar intermediário/alto de acordo com a escala de ADHERE estavam associados com alterações laboratoriais dos pacientes com ICA.

Acute heart failure (AHF) is one of the most common causes of hospitalization, associated with a high risk of mortality. The current treatment is mainly symptomatic, and laboratory tests are carried out in order to complement the clinical evaluation in the diagnosis and help in establishing the admission and prognostic risk profile. This study aimed to characterize the clinical, pharmacotherapeutic and laboratory profile of patients hospitalized with acute heart failure in a regional reference hospital. This is a retrospective, descriptive, cross-sectional study with a quantitative approach. Study participants were those discharged due to AHF according to the International Classification of Diseases (ICD-10), admitted to the emergency room. Excluding the participation of patients with hospitalization time of less than 24 hours, under 18 years old. For statistical analysis, SPSS version 21.0 was used. As for the pharmacotherapeutic profile, the most frequent drugs were those that act on the cardiovascular and digestive systems and metabolism, with furosemide being the most frequent drug. The analysis between laboratory changes and the ADHERE scale revealed a statistically significant difference between patients at low risk and intermediate/high risk in hemoglobin (p=0.005), TGO (p=0.001), creatinine (p=0.000) values, urea (p=0.000), potassium (p=0.004), APTT (p=0.004) and INR (p=0.021). It was concluded that the medications often corresponded to the recommended treatment in the initial management of patients with AHF. Intermediate/high risk of in-hospital mortality according to the ADHERE scale were associated with laboratory alterations in patients with AHF.

La insuficiencia cardiaca aguda (ICA) es una de las causas más frecuentes de hospitalización, asociada a un alto riesgo de mortalidad. El tratamiento actual es principalmente sintomático y se realizan pruebas de laboratorio para complementar la evaluación clínica en el diagnóstico y ayudar a establecer el perfil de riesgo de ingreso y pronóstico. Este estudio tuvo como objetivo caracterizar el perfil clínico, farmacoterapéutico y de laboratorio de pacientes hospitalizados con insuficiencia cardíaca aguda en un hospital regional de referencia. Se trata de un estudio retrospectivo, descriptivo, transversal con enfoque cuantitativo. Los participantes del estudio fueron los dados de alta por ICA según la Clasificación Internacional de Enfermedades (CIE-10), ingresados en urgencias. Se excluye la participación de pacientes con tiempo de hospitalización menor a 24 horas, menores de 18 años. Para el análisis estadístico se utilizó SPSS versión 21.0. En cuanto al perfil farmacoterapéutico, los fármacos más frecuentes fueron los que actúan sobre los sistemas cardiovascular, digestivo y el metabolismo, siendo la furosemida el fármaco más frecuente. El análisis entre los cambios de laboratorio y la escala ADHERE reveló una diferencia estadísticamente significativa entre los pacientes de riesgo bajo e intermedio/alto en los valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), urea (p =0,000), potasio (p=0,004), APTT (p=0,004) e INR (p=0,021). Se concluyó que los medicamentos correspondían muchas veces al tratamiento recomendado en el manejo inicial de pacientes con ICA. El riesgo intermedio/alto de mortalidad hospitalaria según la escala ADHERE se asoció con alteraciones de laboratorio en pacientes con ICA.

Pratiques de prise en charge de l'hypertension artérielle au Centre Hospitalier et Universitaire d' Abomey-Calavi au Bénin / NA

L'hypertension artérielle est une maladie à forte progression reste un problème de santé publique. Mais, les pratiques de sa prise en charge se heurtent à différents obstacles. Cette recherche questionne les problèmes qui caractérisent les pratiques de prise en charge de l'hypertension artérielle au Centre Hospitalier et Universitaire d'Abomey-Calavi au Bénin. Pour y parvenir, nous avons opté pour une analyse basée sur les méthodes quantitatives et qualitatives. L'échantillon est constitué de 130 personnes enquêtées. De l'analyse des résultats collectés, des difficultés éprouvées entre patients et agents de santé dans la prise en charge de l'hypertension artérielle, se caractérise par le manque de relation soignant-soigné. De même, 90% des enquêtés estiment avoir peu de ressources humaines qualifiées et du faible pouvoir d'achat des patients pour faire face aux coûts élevés du traitement de l'hypertension (86,75%). Ainsi, le manque de plateau technique et les frais de consultations spécialisées posent problèmes y compris les suivis de l'éducation hygiéno-diététique. Cet état de fait compromet les pratiques de prise en charge et les formations globales que le système soin est supposé assurer aux usagers qui le fréquentent. Ces résultats suggèrent l'urgence de formations pour le renforcement des capacités pour repérer la précarité et la réorganisation des mesures de prise en charge de l' hypertension artérielle dans le périmètre sanitaire béninois.

Arterial hypertension remains a rapidly growing public health problem. However, management practices face a number of obstacles. This research questions the problems that characterize arterial hypertension management practices at the Centre Hospitalier et Universitaire d'Abomey-Calavi in Benin. To achieve this, we opted for an analysis based on quantitative and qualitative methods. The sample consisted of 130 respondents. From the analysis of the results collected, of the difficulties experienced between patients and health workers in the management of arterial hypertension, most of those surveyed claimed to have a complexity that characterizes the training of health workers. Similarly, 90% of respondents felt that they had few non-cardiologist practitioners, and that patients had little purchasing power to meet the high costs of treating hypertension (86.75%). As a result, the cost of specialized consultations and complementary examinations poses a problem, including follow-up health and diet education. This state of affairs compromises management practices and the comprehensive training that the healthcare system is supposed to provide for its users. These results suggest the urgent need for training to identify precariousness, and the reorganization of hypertension management measures within the Beninese health perimeter.

Research Progress in the Effect of His-Purkinje Conduction System Pacing on Cardiac Function / 中山大学学报(医学科学版)

Cardiac pacing is an effective treatment for cardiac pacing and conduction dysfunction and severe heart failure. However， the conventional right ventricular pacing may increase the incidences of heart failure and atrial fibrillation， and biventricular pacing has a relatively high non-response rate. As a new technique of physiological pacing， a number of studies in recent years have been conducted to show the stability of pacing parameters and good cardiac synchronization of his-purkinje system pacing. This article reviews the current status of research and progress in the effects of his-purkinje conduction system pacing on cardiac function， so as to provide a theoretical basis for promoting the development of this technology.

Effect of Yixintai on Mitochondrial Fission Proteins Fis1 and Mff in Rat Model of Chronic Heart Failure / 中国实验方剂学杂志

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg-1， respectively） Yixintai， and trimetazidine （10 mg·kg-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

Pharmacoeconomics of ivabradine in the treatment of CHF in the context of “Quadruple Therapy” / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system. METHODS Based on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS The results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%. CONCLUSIONS When using 3 times China’s 2022 GDP per capita （257 094 yuan/ QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost- effective.

The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway / 中医杂志

ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group， Shenqi Jianxin Formula group， MCC950 group and the combination group （Shenqi Jianxin Formula plus MCC950）， with 8 rats in each group. In Shenqi Jianxin Formula group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （P＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in Shenqi Jianxin Formula group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （P＜0.05）. Compared with Shenqi Jianxin Formula group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （P＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （P＜0.05）. ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.

Analysis of the Treatment Strategy of Heart Failure with Preserved Ejection Fraction Based on ZHANG Boli's Theory of “Damp-turbidity and Phlegm-rheum Type of Diseases” / 中医杂志

Professor ZHANG Boli believed that the core pathogenesis of heart failure with preserved ejection fraction （HFpEF） is weak pulse at yang and wiry pulse at yin. By referring to the theory of “damp-turbidity and phlegm-rheum type of diseases”， he proposed that yin pathogens of damp-turbidity and phlegm-rheum may damage yang qi in each stage of HFpEF， thus aggravating the trend of weak pulse at yang and wiry pulse at yin， which played an important role in the deterioration of HFpEF. Therefore， Professor ZHANG Boli advocated that importance should be attached to the elimination of yin pathogen and the protection of yang qi during the various stages of HFpEF in order to delay the aggravation of weak pulse at yang and wiry pulse at yin； he put forward the idea of staged treatment that “yin pathogen should be dispelled and yang qi should be demonstrated”； and he formulated the treatment strategy of treating the disease as early as possible， eliminating pathogens and protecting yang， interrupting the disease trend， using warm-like medicinals， and activating blood circulation， to enrich the theoretical system of traditional Chinese medicine in the treatment of HFpEF.

Mechanism of Active Ingredients of Astragalus Membranacus in Treating Heart Failure： A Review / 中国实验方剂学杂志

Heart failure is one of the main cardiovascular system diseases at present， and it is a clinical syndrome caused by changes in cardiac structure and function， resulting in impaired ejection function or ventricular filling. Therefore， heart failure has become the most important cardiovascular disease in the 21st century. In recent years， the incidence of heart failure is increasing， and the survival rate of patients with heart failure is very low. Traditional Chinese medicine has rich experience in preventing and treating heart failure. With the modernization of traditional Chinese medicine， more and more attention has been paid to the research， development， and application of active ingredients in traditional Chinese medicine. Traditional Chinese medicine has unique advantages in improving the heart function of patients with heart failure by treating multiple targets and multiple pathways through syndrome differentiation. Astragalus membranacus， a traditional Chinese medicine， is a kind of medicine that benefits Qi and blood circulation and removes evil spirits. It has the functions of improving myocardial energy metabolism and hemodynamics， protecting myocardial muscle， and promoting angiogenesis. Astragalus membranaceus is often used to treat patients with heart failure， yielding remarkable results. In recent years， it has been found that astragaloside， Astragalus polysaccharide， quercetin， calyx isoflavones， and other main active ingredients of Astragalus membranacus can improve cardiac function and treat heart failure by inhibiting inflammatory response， myocardial apoptosis， and myocardial fibrosis. This paper reviewed the research progress of the action and mechanism of the active ingredients of Astragalus membranacus in the treatment of heart failure by studying relevant literature， with a view to providing a reference for its further research， development， and application in the prevention and treatment of heart failure.

Effect of Linggui Zhugantang on Mitochondrial Fusion-fission and Sirt3/ AMPK Signaling Pathway in Chronic Heart Failure Rats After Myocardial Infarction / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

Mechanism of Yi-xin-yin oral liquid according to homotherapy for heteropathy theory based on UHPLC-Q-TOF/MS combined with network pharmacology and molecular docking techniques / 中国临床药理学与治疗学

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Advances in the study of ω-3 PUFA in heart failure / 中国临床药理学与治疗学

Free fatty acids, as important energy metabolism substrates for the heart, play an important role in various cardiovascular diseases; ω-3 PUFA, as an important branch of free fatty acids, has been confirmed by more and more researches to be closely related to cardiovascular diseases. Heart failure, as a common cardiovascular problem, seriously affects people's quality of life. Studies have shown that ω-3 PUFA plays a significant role in the development of heart failure. In this paper, we try to review the metabolism, pathogenesis and therapeutic significance of ω-3 PUFA in heart failure.

Research progress of Parkin protein regulating mitochondrial homeostasis through ubiquitination in cardiovascular diseases / 中国药理学通报

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Role of Macrophage Activation and Polarization in Myocardial Fibrosis and Intervention of Traditional Chinese Medicine / 中国实验方剂学杂志

Myocardial fibrosis （MF） is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells， the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself， and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research， scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system （RAAS） system and the inflammatory process， repairing the extracellular matrix， managing oxidative stress， and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process， macrophage activation is beneficial， but excessive activation will be harmful. In the early stage of MF， appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF， appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient， or the balance of M1/M2 macrophage polarization is broken， the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin， as well as regulating Qi and activating blood， but there are also some heat-clearing， dampness-drying， and detoxification products. Therefore， the occurrence of MF may be caused by Qi and Yin deficiency， damp heat accumulation， and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF， this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF， so as to provide a reference for the treatment of MF with traditional Chinese medicine.

Research progress on natural medicines and active compounds in the treatment of heart failure / 药学实践杂志

Heart failure is the terminal stage of various cardiovascular diseases and a leading cause of death. For a long time, natural medicines have been used to treat heart failure（HF） with remarkable effects. In this paper, the Traditional Chinese Medicine compound patents in the national patent database were mined, common Traditional Chinese Medicines for the clinical treatment of HF were selected, and the single active ingredient contained in them was analyzed, which provided some valuable tips for the development of drugs for the treatment of heart failure.