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.

Efecto del posacondicionamiento isquémico remoto sobre la fracción de eyección del ventrículo izquierdo en pacientes con infarto de miocardio con elevación del segmento ST sometidos a intervención coronaria percutánea primaria / Effect of remote ischemic postconditioning on left ventricular ejection fraction in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Resumen Antecedentes: En los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST), el acondicionamiento isquémico puede ayudar a limitar la remodelación ventricular. Objetivos: Investigar el efecto del posacondicionamiento isquémico remoto (PAIR) en la función del ventrículo izquierdo durante la intervención coronaria percutánea primaria (ICPP) en pacientes con IAMCEST. Material y métodos: Estudio de intervención pre y posprueba con un total de 60 pacientes con IAMCEST. Los pacientes fueron divididos en dos grupos: con y sin PAIR. Resultados: En el seguimiento de seis meses se observó una diferencia significativa en la fracción de eyección del ventrículo izquierdo en pacientes con ICPP, la cual fue mayor en el grupo con PAIR en comparación con el grupo sin PAIR: 1.0 (−1.0 a 4.3) versus −1.0 (−4.0 a –1.3), p = 0.033. En la medición de seis meses, el volumen sistólico final del ventrículo izquierdo en los pacientes sin PAIR fue mayor en comparación con el grupo homólogo: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. Conclusiones: PAIR muestra efectos favorables en la función ventricular izquierda y, por lo tanto, en el futuro podría ser una estrategia cardioprotectora potencial contra la lesión por isquemia-reperfusión en pacientes con IAMCEST.

Abstract Background: Ischemic conditioning may help patients with ST-segment elevation myocardial infarction (STEMI) to limit ventricular remodeling. Objectives: To investigate the effect of remote ischemic postconditioning (RIPC) on left ventricular function during primary percutaneous coronary intervention (PPCI) in patients with STEMI. Material and methods: Pre- and post-test intervention study with a total of 60 STEMI patients. Patients were divided in two groups: with and without RIPC. Results: At 6-month follow-up evaluation, a significant difference in left ventricular ejection fraction was observed in patients who underwent PPCI, which was higher in the group with RIPC in comparison with the group without RIPC: 1.0 (−1.0 to 4.3) vs. −1.0 (−4.0 to –1.3), p = 0.033. In addition, at 6-month measurement, left ventricular end-systolic volume in patients without RIPC: was higher in comparison with their counterparts: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. Conclusions: RIPC shows favorable effects on left ventricular function and, therefore, in the future, it could be a potential cardioprotective strategy against ischemia-reperfusion injury in STEMI patients.

Caracterización clínica de insuficiencia cardiaca en pacientes internados en el Instituto Nacional de Cardiología, Paraguay

Introducción: la insuficiencia cardiaca es una de las enfermedades cardiovasculares más prevalentes en la población general y el estadio obligatorio de todas las patologías cardiovasculares, la cual irá en aumento a medida que crezca la expectativa de vida de la población. Objetivo: determinar las características de pacientes con insuficiencia cardiaca internados en el Instituto Nacional de Cardiología de Paraguay, durante un periodo de tres meses del año 2020. Metodología: estudio descriptivo de una muestra de 140 pacientes con diagnóstico de insuficiencia cardiaca. Los criterios para establecer este diagnóstico fueron clínicos y/o ecocardiográficos. Resultados: la media de edad fue 66 años, 57% del sexo masculino. El 88% de los pacientes presentaron hipertensión arterial. La etiología más frecuente fue la isquémica (26%), la mayoría consultó en clase funcional III y presentó fracción de eyección reducida, calculándose una prevalencia institucional 7,2%. Conclusión: el perfil del paciente con diagnóstico de insuficiencia cardiaca que consulta en este servicio es de un hombre de aproximadamente 66 años en clase funcional III, con fracción de eyección reducida y de etiología isquémica, cuyas patologías de base son hipertensión arterial y diabetes mellitus.

Introduction: Heart failure is one of the most prevalent cardiovascular diseases in the general population and the mandatory stage of all cardiovascular pathologies, which will increase as the life expectancy of the population grows. Objective: To determine the characteristics of patients with heart failure hospitalized at the National Institute of Cardiology of Paraguay, during a period of three months of the year 2020. Methodology: Descriptive study of a sample of 140 patients diagnosed with heart failure. The criteria to establish this diagnosis were clinical and/or echocardiographic. Results: The average age was 66 years, 57% male, and 88% of the patients had arterial hypertension. The most frequent etiology was ischemic (26%), the majority consulted in functional class III and presented reduced ejection fraction, calculating an institutional prevalence of 7.2%. Conclusion: The profile of the patient with a diagnosis of heart failure who consults in this service is that of a man of approximately 66 years old, in functional class III, with reduced ejection fraction and ischemic etiology, whose underlying pathologies are arterial hypertension and diabetes mellitus.

Insuficiencia cardiaca con fracción de eyección reducida: interrogantes comunes en la práctica médica

Introducción: la insuficiencia cardíaca es un síndrome clínico complejo con síntomas y signos que resultan de cualquier alteración estructural o funcional del llenado ventricular o la eyección de sangre. La prevalencia de insuficiencia cardiaca exhibe una variabilidad de 0,2% a 17,7% en naciones industrializadas Materiales y métodos: se realizó una revisión utilizando base de datos como: PubMed, Scopus, Embase, Cochrane Library, Scielo, incluyendo estudios de tipo observacionales, artículos de revisión, ensayos clínicos, y guías clínicas sobre el manejo de pacientes con insuficiencia cardiaca con fracción de eyección reducida. Resultados y conclusiones: la terapia en la insuficiencia cardíaca con fracción de eyección ventricular izquierda (FEVI) reducida busca contrarrestar los mecanismos deletéreos contrarreguladores. La disfunción sistólica del ventrículo izquierdo implica una FEVI ≤ 40%, mientras que la insuficiencia cardíaca se diagnostica por síntomas y signos de congestión, no solo por la FEVI. Los péptidos natriuréticos ayudan en el diagnóstico, pero niveles elevados pueden tener causas no cardíacas. La hipotensión arterial no contraindica el inicio del tratamiento farmacológico. La lesión renal aguda en estos pacientes indica un mal pronóstico, pero los diuréticos de asa de Henle pueden mejorar la función renal. Durante exacerbaciones agudas por insuficiencia cardiaca, no se deben suspender los medicamentos recomendados, ya que su continuidad reduce la mortalidad y las readmisiones. Terapias como la ivabradina, digoxina, hidralazina e isosorbida dinitrato no han demostrado beneficios en insuficiencia cardiaca y FEVI reducida. Sin embargo, vericiguat y omecamtiv mecarbil obtuvieron resultados significativos en reducción de muertes y hospitalizaciones por IC. Además, se recomienda el desfibrilador automático implantable para prevenir muerte cardíaca súbita. El uso de soporte mecánico circulatorio y el trasplante cardiaco debe ser considera en pacientes con IC avanzada que no responde adecuadamente al tratamiento farmacológico.

Introduction: Heart failure is a complex clinical syndrome with symptoms and signs resulting from any structural or functional alteration of ventricular filling or blood ejection. The prevalence of heart failure varies from 0.2% to 17.7% in industrialized nations. Materials and methods: A review was carried out using databases such as: PubMed, Scopus, Embase, Cochrane Library, Scielo, including observational studies, review articles, clinical trials, and clinical guidelines on the management of patients with heart failure with reduced ejection fraction. Results and conclusions: Therapy in heart failure with reduced left ventricular ejection fraction (LVEF) seeks to counteract deleterious counterregulatory mechanisms. Left ventricular systolic dysfunction implies an LVEF ≤ 40%, while heart failure is diagnosed by symptoms and signs of congestion, not LVEF alone. Natriuretic peptides aid in diagnosis, but elevated levels may have non-cardiac causes. Arterial hypotension does not contraindicate the start of pharmacological treatment. Acute kidney injury in these patients indicates a poor prognosis, but Henle loop diuretics may improve renal function. During acute exacerbations of heart failure, recommended medications should not be discontinued, because they reduce mortality and readmissions. Therapies such as ivabradine, digoxin, hydralazine, and isosorbide dinitrate have not demonstrated benefits in heart failure and reduced LVEF. However, vericiguat and omecamtiv mecarbil obtained significant results in reducing deaths and hospitalizations due to HF. Additionally, implantable cardioverter-defibrillator is recommended to prevent sudden cardiac death. The use of mechanical circulatory support and cardiac transplantation should be considered in patients with advanced HF that does not respond adequately to pharmacological treatment.

Cardiac Outcome of Children With SARS-CoV-2 Related Multisystem Inflammatory Syndrome

Objective: To study the cardiac outcomes of patients with multisystem inflammatory syndrome in children (MIS-C) after 6-month of diagnosis. Methods: This review of hospital records was conducted on MIS-C patients (aged <21 years) who completed a six-month follow-up. The baseline demographic, clinical, laboratory, and treatment characteristics during the acute phase, and echocardiographic findings during follow-up were collected. Results: 116 patients (61.2% male, median age 7 years) with MIS-C were included in the study. At the time of admission, cardiac abnormalities were present in 70.7% of MIS-C patients, and the most common cardiac abnormalities were valve failure (50.9%), followed by ventricular dysfunction (39.7%), and pericardial effusion (23.3%). Six month after diagnosis, cardiac abnormalities were found in 10.3% of patients, and patients had lower rates of ventricular dysfunction (P<0.001), valve failure (P<0.001), pericardial effusion (P<0.001), and coronary involvement (P<0.001) as compared to the baseline. Intravenous immunoglobulin (IVIG) and steroid treatment significantly reduced the odds of occurrence of ventricular dysfunction (P=0.002), valve failure (P=0.004), and low ejection fraction (P=0.002) in comparison to IVIG treatment alone. Conclusion: While most MIS-C patients had abnormal echocardiographic findings at admission, only 10.3% of patients had cardiac abnormalities during follow up.

Predictors of Rehospitalization in Patients with Chronic Heart Failure a Single Center Study in Moroccan Patients

Chronic heart failure (HF) is a major problem of public health in Morocco with few studies exploring HF particularities in this country where the prevalence of HF is estimated to be around 2.2%. Objective: The aim of this study was to evaluate the correlation between frequency of rehospitalization in our population with age, left ventricular ejection fraction (LVEF), heart rate (HR), and QRS duration, Since the number of rehospitalizations is strongly correlated to mortality as shown by many studies. Materials and Methods: Patients with HF were enrolled in this retrospective case control study regardless of their LVEF, patients with recent (<3months) myocardial infarction were excluded. They were all examined and questioned in the heart failure unit of our hospital between the period of October 2022 and December 2022. The correlations were calculated by PEARSON index using R Statistical Software. Results: 224 patients were included. The mean patient age was 59 years (57.2-63;IC 95%) with a male predominance of 60.1 % (56.8-71; IC 95%). 35.5% and 32.2% of patients were treated for hypertension and diabetes respectively. The mean LVEF was 35.2% (33.96-36.91;IC 95%). A positive correlation was found between rehospitalization frequency and age and high heart rate (+ 0.42 p = 0,04;+0.322, p<0.005) respectively . Conversely a negative correlation was found with LVEF (-0.312, p<0.005) while there was a positive correlation with QRS duration but without significance (+0.162 , p=0.03). Conclusion: This study shows strong correlation between rehospitalization and advanced age, higher HR and lower LVEF.

Incidence, determinants, and outcomes of recovered left ventricular ejection fraction (LVEF) in patients with non-ischemic systolic heart failure; a hospital-based cohort study

Background: The data on incidence of recovered Left Ventricular Ejection Fraction (LVEF) and outcome in patients with non ischemic systolic heart failure is limited. We report the incidence, determinants and mortality in patients with recovered LVEF. Methods: The 369 patients with HFrEF with LVEF of less than 40% of non ischemic etiology with available follow up echocardiography study at one year were enrolled. The baseline data of clinical characteristics and treatment was recorded prospectively and were followed up annually for mean of 3.6 years (range 2 to 5 years) to record all cause death and LVEF measured echocardiographically. The recovered, partially recovered and no recovery of LVEF was defined based on increase in LVEF to 50% and more, 41% to 49% and to persistently depressed LVEF to 40% or lower respectively. Results: The LVEF recovered in 36.5%% of the cohort at 5 years. The rate of recovery of LVEF was slower in patients with no recovery of LVEF at one year compared to cohort with partially recovered LVEF (18% vs.53%) at five year. The Baseline LVEF was significantly associated with recovered LVEF, odd ratio (95% C.I.) 1.09(1.04, 1.14). The cumulative mortality at five years was significantly lower in cohort with recovered LVEF (18.1% vs. 57.1%). Conclusions: One third of the patients had recovered LVEF and was significantly associated with baseline LVEF and lower mortality rate.

Caracterización del síndrome coronario agudo en pacientes octogenarios

Introducción: La edad representa uno de los mayores predictores de riesgo de complicaciones cardiovasculares en pacientes con síndrome coronario agudo. La prevalencia de este síndrome en el grupo de los pacientes octogenarios es elevada. Métodos: Estudio prospectivo de cohortes analítico de todos los pacientes ingresados en la unidad de cuidados coronarios intensivos del Hospital Universitario "Comandante Manuel Fajardo" de la Habana, entre el año 2016 y el 2020. Objetivo: Caracterizar la población de pacientes octogenarios con síndrome coronario agudo y las posibles asociaciones entre la ocurrencia de complicaciones intrahospitalarias no letales y los factores de riesgo cardiovasculares. Resultados: Prevaleció el sexo femenino (64,2 %), los antecedentes de hipertensión arterial (89,7 %), cardiopatía isquémica (66,7 %), y el tabaquismo (32 %). Se encontraron asociaciones estadísticas significativas entre el tipo de síndrome coronario agudo y la presencia de complicaciones cardiovasculares de cualquier tipo (p=0,006); el aumento de la creatinina se asoció con la presencia de complicaciones hemodinámicas (Mdn=97; Rango=97,52; p=0,012), así como también la fracción de eyección del ventrículo izquierdo mostró una asociación muy significativa con la presencia de complicaciones cardiovasculares de cualquier tipo (Mdn=59; Rango=63,3; p<0,001) y hemodinámicas (Rango=55,2; p<0,001). Conclusiones: Se caracterizó la población de pacientes octogenarios con síndrome coronario agudo con elevación del segmento ST se asoció con un aumento de las complicaciones cardiovasculares intrahospitalarias, de la misma manera que sucedió con el valor de la fracción de eyección del ventrículo izquierdo.

Introduction: Age represents one of the greatest predictors of risk of cardiovascular complications in patients with acute coronary syndrome. The prevalence of this syndrome in the group of octogenarian patients is high. Objective: To characterize the population of octogenarian patients with acute coronary syndrome and the possible associations between the occurrence of non-lethal intrahospital complications and cardiovascular risk factors. Methods: This is a prospective analytical cohort study of all patients admitted to the intensive coronary care unit of Manuel Fajardo University Hospital in Havana, from 2016 to 2020. Results: The female sex (64.2%), a history of arterial hypertension (89.7%), ischemic heart disease (66.7%), and smoking habits (32%) outweighed. Significant statistical associations were found between the type of acute coronary syndrome and the presence of cardiovascular complications of any type (p=0.006); the increase in creatinine was associated with the presence of hemodynamic complications (Mdn=97; Range=97.52; p=0.012), as well as the left ventricular ejection fraction showed a highly significant association with the presence of cardiovascular complications of any type (Mdn=59; Range=63.3; p<0.001) and hemodynamic (Range=55.2; p<0.001). Conclusions: The octogenarian population of patients with ST-segment elevation acute coronary syndrome was characterized and was associated with an increase in in-hospital cardiovascular complications, in the same way that it happened with the value of the left ventricular ejection fraction.

Effect of iron dextran dispersible tablets on heart failure patients with iron deficiency / 中国临床药理学与治疗学

AIM: To evaluate the clinical effect of Iron Dextran Dispersible Tablets on patients with chronic heart failure who reduced ejection fraction after 24 weeks. METHODS: From January 2020 to June 2022, forty-five patients with heart failure complicated with iron deficiency and reduced ejection fraction were selected as the research objects. According to the random number table, they were randomly divided into control group and observation group.The control group was given routine anti-heart failure treatment such as Sacubitril Calsartan sodium tablets, while the observation group was given iron dextran dispersible tablets 50 mg three times a day on the basis of the anti-heart failure treatment of the control group for 8 weeks. The 6-minute walking distance, Hemoglobin, Serum Ferritin, N-terminal B-type natriuretic peptide precursor, Left Ventricular Ejection Fraction, Left Ventricular end Diastolic Diameter and 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) overall summary score and clinical summary score were compared between the two groups. RESULTS: There was no significant difference in baseline data between the two groups (P > 0.05). After treatment, the 6-minute walking distance in the observation group was longer than that in the control group, while the serum ferritin level in the observation group was higher than that in the control group. The N-terminal pro-B-type natriuretic peptide level in the two groups was lower than that before treatment, and the left ventricular end diastolic diameter was shorter than that before treatment, and the left ventricular ejection fraction, clinical comprehensive score and symptom score were higher than that before treatment. The difference was statistically significant (P 0.05). CONCLUSION: Iron Dextran Dispersible Tablets can improve the exercise endurance and quality of life of patients with chronic heart failure who reduced ejection fraction after 24 weeks.

Effects and mechanism of Ginseng Yixin granules (QSYXG) for heart failure with preserved ejection fraction based on the network pharmacology and molecular docking strategy / 中国临床药理学与治疗学

AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.

Research progress in sodium calcium exchanger and heart failure with preserved ejection fraction / 中国临床药理学与治疗学

Sodium calcium exchanger (NCX) is encoded by the SCL8 family genes and belongs to the cation/Ca

Efficacy and safety of Qili Qiangxin Capsule in the adjuvant treatment of ischemic cardiomyopathy with heart failure: a systematic review and meta-analysis / 数字中医药（英文）

Objective@#To evaluate the efficacy and safety of Qili Qiangxin Capsule (QLQXC) combined with western medicine in patients with ischemic cardiomyopathy (ICM) comorbid with heart failure (HF) for clinical application.@*Methods@#We searched relevant references in Chinese databases including China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), Wanfang Database, and China Biology Medicine (CBM), as well as English databases including PubMed and Embase, from the foundation of the database to January 8, 2023, without language restrictions. All statistical analyses, including subgroup and sensitivity analyses, were performed using the Review Manager (version 5.4) and Stata (version 15.0).@*Results@#QLQXC combined with western medicine significantly increased the endpoints of overall response rate (ORR) (P< 0.000 01), left ventricular ejection fraction (LVEF) (P< 0.000 01), the score of Minnesota Living with Heart Failure Questionnaire (MLHFQ) (P = 0.000 2), and 6-minute walking distance (6MWD) (P < 0.000 01), decreased left ventricular end-diastolic diameter (LVEDD) (P < 0.000 01), left ventricular end-systolic diameter (LVESD) (P = 0.03), and pro-brain natriuretic peptide (pro-BNP) (P < 0.000 01), and reduced the incidence of rehospitalization (P = 0.000 3) and adverse events (AEs) (P = 0.000 6) compared with those under the conventional western therapy alone. Nonetheless, no significant difference was observed in reducing the mortality between the QLQXC combined with western medicine group and the western medicine group (P = 0.30).@*Conclusion@#The combination therapy of QLQXC with western medicine can potentiate cardiac function and raise the quality of life in patients with ICM comorbid with HF.

The clinical effect of sacubitril valsartan combined with dapagliflozin in heart failure with reduced ejection fraction and non-diabetes patients / 西安交通大学学报(医学版)

【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.

Study on pharmacoeconomic evaluation of vericiguat in the treatment of heart failure with reduced ejection fraction / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of vericiguat combined with standard treatment in the treatment of heart failure with reduced ejection fraction （HFrEF）. METHODS Based on the results of the VICTORIA trial and related literature， a three-state （including stable state of heart failure， hospitalized state of heart failure and death state） Markov model was constructed. The cycle length was 1 month， the time horizon was 20 years， the discount rate was 5%， and one time China’s per capita gross domestic product （GDP） in 2021 was the willing-to-pay （WTP） threshold. Cost-utility analysis was performed to evaluate the cost-effectiveness of vericiguat combined with standard treatment in the treatment of HFrEF. The output indicators included quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER）. The robustness of the results of the basic analysis was verified by one-way sensitivity analysis and probability sensitivity analysis. RESULTS The ICER of vericiguat combined with the standard treatment plan compared to the standard treatment plan alone was 444 341.95 yuan/QALY， which was more than WTP of this study （80 976 yuan/QALY）. One-way sensitivity analyses showed that the probability of cardiovascular death in both groups was the main influencing parameter for the robustness of the model， but they had little influence on the results of the basic analysis. The probabilistic sensitivity analysis displayed that under the WTP threshold of this study， the possibility of vericiguat combined with the standard treatment plan being more cost-effective was 2.6%. CONCLUSIONS Compared with the standard treatment plan， vericiguat combined with the standard treatment plan is not cost-effective in patients with HFrEF.

Effect of Jiawei Shenqi Yixin Prescription on Cardiovascular Risk Factors in Patients with Heart Failure with Preserved Ejection Fraction and Insulin Resistance / 中国实验方剂学杂志

ObjectiveTo observe the effect of Jiawei Shenqi Yixin prescription on cardiovascular risk factors in the patients with heart failure with preserved ejection fraction and insulin resistance. MethodFrom January 2021 to January 2022， a total of 82 patients with heart failure with preserved ejection fraction were enrolled in the ward of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. The patients were randomly assigned into two groups （ 41 cases） and received the same basic treatment. The observation group was additionally treated with Jiawei Shenqi Yixin prescription for 8 weeks. The clinical efficacy， traditional Chinese medicine （TCM） efficacy， cardiac function indexes ［NT-probrain natriuretic peptide （NT-proBNP） and 6-min walking test （6MWT）］， echocardiographic parameters ［left atrial volume index （LAVI）， left ventricular mass index （LVMI）， peak early diastolic to peak late diastolic mitral flow velocity （E/A） ratio］， insulin resistance-related indexes ［fasting insulin （FINS）， fasting plasma glucose （FPG）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， homeostatic model assessment of insulin resistance （HOMA-IR）， triglyceride-glucose index （TYG）， and triglyceride to high-density lipoprotein cholesterol （TG/HDL-C） ratio］， inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， adiponectin （ADP）， and C-reactive protein （CRP）］， vascular endothelial function indicators ［nitric oxide （NO）， endothelial nitric oxide synthase （eNOS）， inducible nitric oxide synthase （iNOS）， and endothelin-1 （ET-1）］， and the safety of treatment were determined. In addition， Pearson correlation analysis was performed to analyze the correlations of insulin resistance， inflammatory cytokines， and vascular endothelial factors with the mitigation of heart failure. ResultIn terms of clinical efficacy， the therapy of the observation group was significantly effective in 26 patients， effective in 12 patients， ineffective in 3 patients， with the total effective rate of 92.68%， the therapy of the control group was significantly effective in 14 patients， effective in 12 patients， and ineffective in 15 patients， with the total effective rate of 63.41%. The clinical total effective rate of the observation group was higher than that of the control group （χ2=11.6， P<0.05）. In terms of TCM efficacy， the therapy of the observation group was significantly effective in 26 patients， effective in 11 patients， and ineffective in 4 patients， with the total effective rate of 90.24%； the therapy of the control group was significantly effective in 9 patients， effective in 13 patients， and ineffective in 19 patients， with the total effective rate of 53.66%. The TCM total effective rate of the observation group was higher than that of the control group （χ2=8.19， P<0.05）. Compared with those before treatment， the levels of NT-proBNP， LAVI， LVMI， FPG， FINS， HOMA-IR， TYG， TG/HDL-C， TNF-α， IL-6， CRP， ET-1， and iNOS in two groups declined after treatment （P<0.05）， while the levels of 6MWT， E/A， ADP， NO， and eNOS elevated （P<0.05）. After treatment， the observation group had lower levels of NT-proBNP， LAVI， LVMI， FPG， FINS， HOMA-IR， TYG， TG/HDL-C， TNF-α， CRP， and ET-1 （P<0.05） and higher levels of 6MWT， E/A， ADP， and NO than the control group （P<0.05）. In addition， the increase in 6MWT after treatment was positively correlated with the increase in NO and the decrease in ET-1. The decrease in LVMI after treatment was positively correlated with the increase in NO and the decrease in FINS. The increase in left ventricular ejection fraction after treatment was positively correlated with the decreases in TNF-α and TYG （P<0.05）. Adverse reactions were observed in neither group. ConclusionJiawei Shenqi Yixin prescription can significantly mitigate the symptoms， reduce inflammation， and improve vascular endothelial function in the patients with heart failure with preserved ejection fraction and insulin resistance， being safe without causing adverse reactions.

Material Basis and Molecular Mechanism of Linggui Qihua Prescription Against Myocardial Fibrosis in Heart Failure with Preserved Ejection Fraction / 中国实验方剂学杂志

ObjectiveTo explore the material basis and molecular mechanism of Linggui Qihua prescription （LGQH） against myocardial fibrosis in heart failure with preserved ejection fraction （HFpEF）. MethodLiquid chromatography-mass spectrometry （LC-MS） was used to qualitatively analyze the active components of LGQH. AutoDock software was employed for molecular docking between the active components of LGQH and target proteins including α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， matrix metalloproteinase-9 （MMP-9）， and tissue inhibitor of metalloproteinase-1 （TIMP-1）. In vivo experiments were conducted on 40 spontaneously hypertensive rats （SHRs） aged 4 weeks， which were divided into an HFpEF group， an Entresto group （0.018 g·kg-1）， and low- and high-dose LGQH groups （3.87， 7.74 g·kg-1）. A high-fat， high-salt， and high-sugar diet was administered for 16 weeks along with intraperitoneal injection of streptozotocin solution for 8 weeks to establish an HFpEF model in rats. The blank group consisted of 10 Wistar Kyoto （WKY） rats and 10 SHRs. After successful modeling， the WKY， SHR， and HFpEF groups were given equal volumes of normal saline， while the other three groups received predetermined interventions. Daily oral gavage was performed for 6 weeks. After intervention， echocardiography was conducted to measure left ventricular （LV） anterior wall thickness （LVAWd）， LV posterior wall thickness （LVPWd）， LV internal diameter at end-diastole （LVIDd）， LV ejection fraction （LVEF）， isovolumic relaxation time （IVRT）， early diastolic peak velocity of mitral valve inflow （E）， and early diastolic mitral annular velocity （e'）. The E/e' ratio was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum atrial natriuretic peptide （ANP）， B-type natriuretic peptide （BNP）， and galectin-3 （Gal-3）. Myocardial fibrosis was observed through Masson staining of pathological sections， and collagen volume fraction （CVF） and perivascular fibrosis ratio （PFR） were calculated. Real-time polymerase chain reaction （PCR） and Western blot were employed to detect LV myocardial mRNA and protein expression of α-SMA， ColⅠ， ColⅢ， MMP-9， and TIMP-1. ResultLC-MS identified 13 active components in LGQH. Molecular docking indicated stable binding of the 13 compounds with five target proteins. In vivo experiments showed that compared with the blank group， the HFpEF group had significantly increased LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR. LV myocardial α-SMA， ColⅠ， and ColⅢ mRNA and protein expression was significantly upregulated， while MMP-9/TIMP-1 mRNA and protein ratios were significantly downregulated （P<0.05， P<0.01）. Compared with the HFpEF group， LGQH might dose-dependently reduce LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR， downregulated myocardial α-SMA， ColⅠ， ColⅢ mRNA expression， α-SMA， and ColⅠ protein expression， and upregulated MMP-9/TIMP-1 mRNA and protein expression （P<0.05， P<0.01）. ConclusionLGQH contains multiple active components and may inhibit myocardial fibrosis in HFpEF rats. It may further alleviate LV hypertrophy， dilation， and diastolic dysfunction， making it an effective Chinese medicinal prescription for treating HFpEF.

Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF).@*METHODS@#Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO2), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups.@*RESULTS@#After the 12-week intervention, patients in group C showed significant declines in peakVO2, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01).@*CONCLUSIONS@#Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).

Application of extracorporeal membrane oxygenation in early allograft dysfunction after heart transplantation / 器官移植

Objective To evaluate the effect of extracorporeal membrane oxygenation (ECMO) on early allograft dysfunction (EAD) after heart transplantation. Methods Clinical data of 614 heart transplant recipients were retrospectively analyzed. All recipients were divided into the ECMO group (n=43) and non-ECMO group (n=571) according to postoperative application of ECMO. In the ECMO group, the conditions of recipients undergoing ECMO after heart transplantation were summarized. Perioperative status and long-term prognosis of recipients were compared between two groups. Results Among 43 recipients undergoing ECMO, 17 cases underwent thoracotomy due to bleeding, 10 cases of infection, 4 cases of venous thrombosis of the lower limbs, and 1 case of stroke, respectively. Twenty-six recipients were recovered and discharged after successful weaning from ECMO, six died during ECMO support, six died after weaning from ECMO, five received retransplantation due to unsuccessful weaning from ECMO, and only one survived after retransplantation. Compared with the non-ECMO group, intraoperative cardiopulmonary bypass duration was significantly longer, the proportion of recipients requiring postoperative intra-aortic balloon pump (IABP), dialysis due to renal insufficiency, reoperation for hemostasis, infection, mechanical ventilation time≥96 h and tracheotomy was significantly higher, and the length of postoperative intensive care unit (ICU) stay was significantly longer in the ECMO group (all P < 0.05). The survival rate after discharge and 90-d survival rate in the ECMO group were 63% and 96%, significantly lower than 97% and 100% in the non-ECMO group (both P < 0.05). Survival analysis showed that the long-term survival rate in the ECMO group was significantly lower than that in the non-ECMO group (P < 0.05). After excluding the recipients who died within 90 d after heart transplantation, no significant difference was observed in the long-term survival rate (P > 0.05). Conclusions ECMO is an effective treatment of EAD after heart transplantation. The short-term survival rate of recipients using ECMO after heart transplantation is lower than that of those who do not use ECMO, and there is no significant difference in long-term survival of recipients surviving 90 d after heart transplantation.

Relação entre a Razão Nitrogênio Ureico/Creatinina e Prognóstico de Insuficiência Cardíaca em Todo o Espectro da Fração de Ejeção / Relationship between BUN/Cr and Prognosis of HF Across the Full Spectrum of Ejection Fraction

Resumo Fundamento Em pacientes com insuficiência cardíaca (IC), devido à relativa deficiência do volume sanguíneo, a ativação do sistema neuro-hormonal leva à vasoconstrição renal, que afeta o teor de nitrogênio ureico (NU) e creatinina (C) no organismo, sendo que NU e C são facilmente afetados por outros fatores. Portanto, a razão NU/C pode ser utilizada como mais um marcador para o prognóstico da IC. Objetivo Explorar o prognóstico do desfecho adverso da IC no grupo NU/C alta em comparação com o grupo NU/C baixa em todo o espectro da fração de ejeção. Métodos De 2014 a 2016, pacientes sintomáticos hospitalizados com IC foram recrutados e acompanhados para observar desfechos cardiovasculares adversos. Foram realizadas análise logística e a análise COX para determinar a significância. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados Na análise de regressão logística univariada, o grupo NU/C alta apresentou maior risco de desfecho adverso na insuficiência cardíaca com fração de ejeção reduzida (ICFEr) e insuficiência cardíaca com fração de ejeção preservada (ICFEp). A análise de regressão logística multivariada mostrou que o risco de morte cardíaca no grupo ICFEr foi maior do que no grupo NU/C baixa, enquanto o risco de morte por todas as causas foi significativo apenas em 3 meses (p<0,05) (Ilustração Central). O risco de morte por todas as causas no grupo NU/C alta no grupo ICFEP foi significativamente maior do que no grupo NU/C baixa em dois anos. Conclusão O grupo NU/C alta está relacionado ao risco de mau prognóstico da ICFEP, não sendo inferior ao valor preditivo da fração de ejeção do ventrículo esquerdo (FEVE).

Abstract Background In patients with heart failure (HF), due to the relative deficiency of blood volume, neurohormone system activation leads to renal vasoconstriction, which affects the content of blood urea nitrogen (BUN) and creatinine (Cr) in the body, while BUN and Cr are easily affected by other factors. Therefore, BUN/Cr can be used as another marker for the prognosis of HF. Objective Explore the prognosis of adverse outcome of HF in the high BUN/Cr group compared with the low BUN/Cr group across the full spectrum of ejection fraction. Methods From 2014 to 2016, symptomatic hospitalized HF patients were recruited and followed up to observe adverse cardiovascular outcomes. Logistic analysis and COX analysis were performed to determine significance. p-values <0.05 were considered statistically significant. Results In the univariate logistic regression analysis, the high BUN/Cr group had a higher risk of adverse outcome in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Multivariate logistic regression analysis showed that the risk of cardiac death in the HFrEF group was higher than that in the low BUN/Cr group, while the risk of all-cause death was significant only in 3 months (p<0.05) (Central Illustration). The risk of all-cause death in the high BUN/Cr in the HFpEF group was significantly higher than that in the low BUN/Cr group at two years. Conclusion The high BUN/Cr group is related to the risk of poor prognosis of HFpEF, and is not lower than the predictive value of left ventricular ejection fraction (LVEF).

Neuromodulação Vagal Auricular e sua Aplicabilidade em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida / Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction

Resumo Fundamento O desequilíbrio do sistema nervoso autônomo (SNA) na insuficiência cardíaca (IC) cria um ciclo vicioso, o excesso de atividade simpática e a diminuição da atividade vagal contribuindo para a piora da IC. A estimulação elétrica transcutânea de baixa intensidade do ramo auricular do nervo vago (taVNS) é bem tolerada e abre novas possibilidades terapêuticas. Objetivos Gerar hipótese da aplicabilidade e benefício da taVNS na IC através da comparação intergrupos de parâmetros ecocardiográficos, teste de caminhada de 6 min, variabilidade da frequência cardíaca pelo Holter (SDNN e rMSSD), questionário de qualidade de vida de Minnesota e classe funcional pela New York Heart Association. Métodos Estudo clínico prospectivo, duplo cego, randomizado com metodologia sham, unicêntrico. Avaliados 43 pacientes e alocados em 2 grupos: o Grupo 1 recebeu taVNS (frequências 2/15 Hz) e Grupo 2 recebeu sham. Nas comparações, valores de p<0,05 foram considerados significativos. Resultados Na fase pós-intervenção, observou-se que o Grupo 1 se manteve com melhor rMSSD (31 x 21; p = 0,046) e atingiu melhor SDNN (110 vs. 84, p = 0,033). Ao compararmos os parâmetros intragrupos, antes e após intervenção, observou-se que todos melhoraram significativamente no grupo 1 e não houve diferenças no grupo 2. Conclusão A taVNS é uma intervenção segura, de fácil execução e que sugere provável benefício na IC pela melhora na variabilidade da frequência cardíaca, o que indica melhor equilíbrio autonômico. Novos estudos com maior número de pacientes são necessários para responder às questões levantadas por esse estudo.

Abstract Background The autonomic nervous system (ANS) imbalance in heart failure (HF) creates a vicious cycle, excess sympathetic activity, and decreased vagal activity contributing to the worsening of HF. Low-intensity transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) is well tolerated and opens new therapeutic possibilities. Objectives To hypothesize the applicability and benefit of taVNS in HF through intergroup comparison of echocardiography parameters, 6-minute walk test, Holter heart rate variability (SDNN and rMSSD), Minnesota quality of life questionnaire, and functional class by the New York Heart Association. In comparisons, p values <0.05 were considered significant. Methods Prospective, double-blind, randomized clinical study with sham methodology, unicentric. Forty-three patients were evaluated and divided into 2 groups: Group 1 received taVNS (frequencies 2/15 Hz), and Group 2 received sham. In comparisons, p values <0.05 were considered significant. Results In the post-intervention phase, it was observed that Group 1 had better rMSSD (31 x 21; p = 0.046) and achieved better SDNN (110 vs. 84, p = 0.033). When comparing intragroup parameters before and after the intervention, it was observed that all of them improved significantly in group 1, and there were no differences in group 2. Conclusion taVNS is a safe to perform and easy intervention and suggests a probable benefit in HF by improving heart rate variability, which indicates better autonomic balance. New studies with more patients are needed to answer the questions raised by this study.