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.

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)).

Mechanism of Jiming Powder in ameliorating heart failure with preserved ejection fraction based on metabolomics / 中国中药杂志

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.

Role of cardiopulmonary ultrasound in predicting the occurrence of heart failure with preserved ejection fraction in patients with acute myocardial infarction / 中华超声影像学杂志

Objective:To evaluate the left ventricular diastolic function and pulmonary congestion in patients with acute myocardial infarction (AMI) with preserved left ventricular ejection fraction (LVEF) by cardiopulmonary ultrasound (CPUS), and to explore the value of CPUS in predicting the occurrence of heart failure with preserved ejection fraction (HFpEF) in AMI patients with preserved LVEF during hospitalization.Methods:A total of eighty-four patients with AMI with preserved LVEF (≥50%) who received optimal emergency reperfusion therapy on admission at Beijing Chaoyang Hospital Affiliated to Capital Medical University from August 2021 to March 2022 were enrolled. All patients completed comprehensive cardiopulmonary ultrasonography within 12 hours after reperfusion therapy and LVEF, left atrial maximum volume(LAV), peak flow velocity of tricuspid valve regurgitation (V TR), peak flow velocity of mitral valve in early diastole (E), peak velocity of mitral valve annulus on septal side and left ventricular lateral side in early diastole and other conventional echocardiography parameters were obtained, and then the left atrial volume index (LAVI), the mean peak velocity of the mitral valve annulus on the septal side and left ventricular lateral side in early diastole (e′) and E/e′ were calculated; lung ultrasound parameters(the number of B lines) were obtained; the left ventricular global long-axis strain (GLS) was obtained using speckle tracking imaging (STE). The predictive power of CPUS parameters for HFpEF during hospitalization in AMI patients with preserved LVEF were analyzed. Results:①The incidence of HFpEF during hospitalization was 40.4% (34/84). ②The number of B lines and LAVI were independently correlated with the occurrence of HFpEF during hospitalization( P<0.05). ③The ROC curve analysis showed that the area under the curve (AUC) of the number of B lines and LAVI for predicting the occurrence of HFpEF during hospitalization were 0.766 and 0.690, respectively. The number of B lines combined with LAVI had the best predictive performance in predicting the occurrence of HFpEF during hospitalization, with the largest AUC of 0.903, which was significantly better than the number of B lines and LAVI ( P<0.05). Conclusions:The number of B lines combined with LAVI can effectively predict the occurrence of HFpEF during hospitalization in AMI patients with preserved LVEF, which is helpful to further improve the clinical management of AMI patients at risk of HFpEF.

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.

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.

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

Cardiac Structural and Functional Features in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction:A Study Based on Propensity Score Matching / 中国医学科学院学报

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e') (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e' ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.

Dilemas de la insuficiencia cardíaca con fracción de eyección preservada / Dilemmas of heart failure with preserved ejection fraction / Dilemas da insuficiência cardíaca com fração de ejeção preservada

La insuficiencia cardíaca con fracción de eyección preservada (ICFEp) y reducida presentan marcadas diferencias. Mientras que la última tiene un algoritmo diagnóstico y terapéutico desde hace años, con guías y fármacos que mejoran su pronóstico, la ICFEp no solo presenta dificultades para llegar al diagnóstico, sino que tampoco hay fármacos que hayan demostrado disminuir la mortalidad. En esta revisión se hace un abordaje amplio de la ICFEp, comenzando por definirla y distinguirla de la disfunción diastólica. Se describe el gold standard para su diagnóstico invasivo y se analizan los scores no invasivos recientemente desarrollados que estiman la probabilidad de tener la enfermedad. A través del análisis de las comorbilidades frecuentemente asociadas, se describen los mecanismos fisiopatológicos implicados. Asimismo, se detallan los fenotipos propuestos para agrupar pacientes y diseñar ensayos clínicos con fármacos que prueben disminuir la mortalidad. Por último, se reseñan las medidas terapéuticas no farmacológicas y farmacológicas recomendadas.

Heart failure with preserved and reduced ejection fraction have significant differences. While the latter has had a diagnostic and therapeutic algorithm for years, with guidelines and drugs that improve its prognosis, heart failure with preserved ejection fraction (HFpEF) not only presents difficulties in reaching a diagnosis, but also there are no drugs that have been proven to be effective in reducing mortality. In this review, a broad approach to HFpEF is made, beginning by defining it and distinguishing it from diastolic dysfunction. The gold standard for its invasive diagnosis is described and recently developed non-invasive scores that estimate the probability of having the disease are analyzed. Through the analysis of the frequently associated comorbidities, the pathophysiological mechanisms involved are described. Likewise, the phenotypes proposed to group patients and design clinical trials with drugs that try to reduce mortality are detailed. Finally, the recommended non-pharmacological and pharmacological therapeutic measures are outlined.

A insuficiência cardíaca com fração de ejeção preservada (ICFEp) e reduzida apresentam diferenças marcantes. Enquanto esta última conta com um algoritmo diagnóstico e terapêutico há anos, com diretrizes e medicamentos que melhoram seu prognóstico, a ICFEp não só apresenta dificuldades no diagnóstico, mas nenhum há medicamentos que tenham demonstrado reduzir a mortalidade. Nesta revisão, é feita uma abordagem ampla da ICFEp, começando por defini-la e distinguindo-a da disfunção diastólica. O padrão ouro para seu diagnóstico invasivo é descrito e são analisados os escores não invasivos recentemente desenvolvidos que estimam a probabilidade de ter a doença. Através da análise de comorbidades frequentemente associadas, são descritos os mecanismos fisiopatológicos envolvidos. Da mesma forma, são detalhados os fenótipos propostos para agrupar pacientes e desenhar ensaios clínicos com medicamentos que podem ser mostradas para reduzir a mortalidade. Por fim, são delineadas as medidas terapêuticas não farmacológicas e farmacológicas recomendadas.

La tercera cara de la moneda en el manejo de la falla cardíaca / The third side of the coin in the management of heart failure

Resumen En las últimas décadas, el manejo de la insuficiencia cardíaca ha tenido avances significativos nunca antes vistos en la historia de la cardiología, lo cual ha elevado el pronóstico de vida de los pacientes con falla cardíaca, a niveles cercanos a los de un individuo sano. Para ello se han empleado múltiples alternativas farmacológicas, como los inhibidores de la enzima convertidora de angiotensina (IECA), los antagonistas de los receptores de angiotensina (ARA II), los bloqueadores de los receptores mineralocorticoides, los bloqueadores de los receptores IF I, los inhibidores de la neprilisina y los betabloqueadores, asociadas al desarrollo de la cardiología intervencionista y la cirugía cardiovascular a nivel coronario, valvular, remodelado cardíaco y dispositivos de estimulación, asistencia, resincronización y cardioversión miocárdica. Sin embargo, hay un importante escenario en el manejo de la falla cardíaca que, en ocasiones, por diversas circunstancias, se deja de lado o se pospone como terapia de primera línea concomitante a las ya expuestas. Este artículo intenta describir la importancia que tienen dichas terapias -a las que hemos llamado la tercera cara de la moneda en el manejo de la falla cardíaca- a la luz de la evidencia actual.

Abstract In the last decades the management of heart failure has seen significant advance as never before in the history of cardiology, raising the life expectancy of patients with heart failure to levels close to those of healthy individuals. For such a task, multiple pharmacological alternatives have been employed: angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor antagonists (ARB), mineralocorticoid receptor antagonists, I-F channel antagonists, neprilysin inhibitors, beta blockers, associated to the development of interventionist cardiology and cardiac surgery at coronary level, valvular level, cardiac remodeling, and devices for stimulation, assistance, resynchronization and myocardial cardioversion. However, there is an important stage in the management of heart failure that occasionally, due to varied circumstances, is set aside or put off as a front-line therapy accompanying the ones already mentioned. This article attempts to describe the importance that said therapies have in light of current evidence, which we have called: the third side of the coin in the management of heart failure.

A Data Mining-Based Study on Medication Rules of Chinese Herbs to Treat Heart Failure with Preserved Ejection Fraction / 中国结合医学杂志

OBJECTIVE@#To summarize the medication rules of Chinese herbs to treat heart failure with preserved ejection fraction (HFPEF) based on data mining and to provide references for clinical utilization.@*METHODS@#The China National Knowledge Infrastructure (CNKI), Wanfang database (Wanfang), VIP database (VIP), Chinese Biomedical Literature (CBM), PubMed, Embase, and Cochrane Library databases were searched from inception to October 2021 to identify relevant literature on treating HFPEF with Chinese herbs. Microsoft Excel 2019 was used to set up a database, and then, association rule analysis and hierarchical cluster analysis were performed by using apriori algorithm and hclust function respectively in R-Studio (Version 4.0.3).@*RESULTS@#A total of 182 qualified papers were included, involving a total of 92 prescriptions, 130 Chinese herbs, and 872 individual herbs prescribed, with an average of 9.5 herbs per prescription. The six most frequently prescribed herbs were Astragali Radix (Huangqi), Salviae Miltiorrhizae Radix Et Rhizoma (Danshen), Poria (Fuling), Glycyrrhizae Radix Et Rhizoma (Gancao), Cinnamomi Ramulus (Guizhi), and Ginseng Radix Et Rhizoma (Renshen). There were 35 herbs used more than 5 times, involving 11 efficacy categories. The top three categories were deficiency-tonifying herbs, blood-activating and stasis-removing herbs, and dampness-draining diuretic herbs. The most commonly used herbs were mainly warm and sweet. The primary meridian tropisms were Lung Meridian, Heart Meridian and Spleen Meridian. Association rule analysis yielded 26 association rules, such as Astragali Radix (Huangqi) & Salviae Miltiorrhizae Radix Et Rhizoma (Danshen), Poria (Fuling), Cinnamomi Ramulus (Guizhi) & Atractylodis Macrocephalae Rhizoma (Baizhu). Hierarchical cluster analysis yielded four herb classes, and their functions were mainly qi-replenishing and yang-warming, blood-activating and diuresis-inducing.@*CONCLUSIONS@#HFPEF is the syndrome of root vacuity and tip repletion, and its core pathogenesis is "deficiency", "stasis", and "water", with "deficiency" being the most principal, which is closely related to Xin (heart), Fei (Lung), and Pi (Spleen). The treatment of this disease occurs by improving qi, warming yang, activating blood and inducing diuresis. Astragali Radix (Huangqi) with Salviae Miltiorrhizae Radix Et Rhizoma (Danshen) is the basic combination of herbs applied.

Advances in extracardiac mechanisms for heart failure with preserved ejection fraction / 中南大学学报(医学版)

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with highly heterogeneous clinical symptoms, and its incidence has been increasing in recent years. Compared with heart failure with reduced ejection fraction (HFrEF), HFpEF has a worse prognosis. Traditional therapies targeting the internal mechanisms of the heart show limited or inefficacy on HFpEF, and new therapeutic targets for HFpEF are expected to be found by focusing on the extracardiac mechanisms. Recent studies have shown that cardiopulmonary pathophysiological interaction exacerbates the progression of HFpEF. Hypertension, systemic vascular injury, and inflammatory response lead to coronary microvascular dysfunction, myocardial hypertrophy, and coronary microvascular remodeling. Acute kidney injury affects myocardial energy production, induces oxidative stress and catabolism of myocardial protein, which leads to myocardial dysfunction. Liver fibrosis mediates heart injury by abnormal protein deposition and inflammatory factors production. Skeletal muscle interacts with the sympathetic nervous system by metabolic signals. It also produces muscle factors, jointly affecting cardiac function. Metabolic syndrome, gut microbiota dysbiosis, immune system diseases, and iron deficiency promote the occurrence and development of HFpEF through metabolic changes, oxidative stress, and inflammatory responses. Therefore, the research on the extracardiac mechanisms of HFpEF has certain implications for model construction, mechanism research, and treatment strategy formulation.

An Autopsy Case of Transthyretin-Related Cardiac Amyloidosis (TTR-CA), Which Fell into Low-Output Syndrome after Cardiac Surgery / 日本心臓血管外科学会雑誌

We present the case of 83-year-old male patient. He was under observation as an outpatient with mild to moderate aortic stenosis and regurgitation since 75 years old. He underwent surgery because of repeated hospitalization by heart failure due to progressive aortic valve stenosis and regurgitation, mitral valve stenosis and regurgitation, and tricuspid regurgitation. Elective aortic valve replacement, mitral valve replacement and tricuspid valve repair was performed. Even though his condition after surgery was stable, suddenly feature like low output syndrome appeared on day 6, and led to a mortality on day 8 after operation. Ejection fraction was kept above 50 percent before and after surgery, which indicated to Heart Failure with preserved Ejection Fraction (HFpEF). After autopsy examination, by immunohistochemical staining identified transthyretin, we demonstrated previously undiagnosed transthyretin-related cardiac amyloidosis (TTR-CA).

Heart failure with Normal and Reduced Ejection Fraction – Assessment and Shared Care Management

@#Non-alcoholic fatty liver disease (NAFLD) has become the commonest chronic liver disease in the world. Overall improvement in public health, active screening of blood products, and universal vaccination of hepatitis B have led to a drop in incidence of hepatitis B and C worldwide. NAFLD is strongly associated with metabolic syndrome. With the rise in overweight status and obesity worldwide, it is not surprising that NAFLD is on the rise. Diagnosis of NAFLD requires confirmation of fatty infiltration in liver, as well as liver damage such as elevated liver enzymes and presence of fibrosis. Currently, the best treatment for NAFLD is weight loss, and the proven method would be dieting with regular exercises. Vitamin E and pioglitazoles are promising medications for treating NAFLD, but each medication has their shortcomings. Until more studies are conducted, lifestyle modification remains the only reliable way to treat NAFLD. Family physicians ought to look out for cardiovascular diseases, as well as being vigilant in cancer screening, as NAFLD is associated with higher risks of ischemic heart disease and cancer.

Establishment of a model of heart failure with preserved ejection fraction and ultrasonic evaluation of cardiac structural characteristics / 中华超声影像学杂志

Objective:To evaluate the pathological features of a heart failure with preserved ejection fraction(HFpEF) model, which is established by spontaneously hypertensive rats (SHR) through high-fat diet and diabetic factors.Methods:Twenty specific pathogen-free grade(SPF grade) and 14-week-old SHR rats were randomly divided into SHR group (normal diet) and HFpEF group [high-fat diet combined with intraperitoneal injection of streptozotocin (STZ, 25 mg/kg) were used to create a diabetic complex model] with 10 rats in each group. Ten SPF and 14-week-old WKY rats with the same genetic background were set as blank control group (WKY group). All rats were fed for 8 weeks. Echocardiography was performed to measure cardiac parameters: peak velocity of early diastolic mitral inflow(E), peak velocity of late diastolic mitral inflow(A), and the early diastolic mitral annulus e′ in the same cardiac cycle, left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), left atrial diameter, right atrial diameter and interventricular septal thickness(IVST). Serological testing included glucose (GLU) and glycosylated serum protein (GSP); Enzyme-linked immunoassay (ELISA) testing included insulin (INS), glucagon (PG), C-peptide (CP), leptin (LEP), atrial natriuretic peptide (ANP) and B-type brain natriuretic peptide (BNP). The rat heart tissue was stained with HE, and the morphological changes of atrial/ventricular tissue were observed under an optical microscope.Results:The pathological characteristics of HFpEF was established in SHR rats fed with high fat and diabetes. Echocardiography showed that compared with the WKY group, the values of E, E/A and E/e′ in the HFpEF group were significantly increased (all P<0.01), and e′and LAEF were significantly reduced (all P<0.01). In the HFpEF group, the anteroposterior and tranverse dimensions of the left atrium and the long-axis dimension of the right atrium increased to varying degrees (all P<0.05), and the IVST was also significantly increased ( P<0.01). At the same time, atrial wall was thickened obviously, myocardial cells were disordered, and myocardial fibers were broken. Compared with the WKY group, the levels of serum markers ANP and BNP in HFpEF group were significantly increased (all P<0.01), and the levels of serum insulin-related indicators INS, PG, CP, LEP, GSP, and GLU increased to varying degrees (all P<0.01). Conclusions:The composite model established by SHR rats through high-fat diet and diabetic factors can simulate the Doppler echocardiographic changes and pathological features of HFpEF, as well as abnormal changes in serum related markers and insulin indicators.

Assessment of left ventricular function in heart failure with preserved ejection fraction patients by speckle tracking layer-specific strain combined with myocardial work technique / 中华超声影像学杂志

Objective:To assess the changes of left ventricular systolic function and global myocardial work in heart failure with preserved ejection fraction (HFpEF) patients by speckle tracking layer-specific strain combined with myocardial work technique and explore the diagnostic value of each parameter for HFpEF.Methods:From December 2019 to December 2020, 38 HFpEF patients (HFpEF group) and 38 healthy individuals with age- and sex-matched (control group) were enrolled consecutively in the Fourth Affiliated Hospital of Harbin Medical University. Conventional ultrasound parameters were collected. Layer-specific strain and myocardial work techniques were used to obtain the global longitudinal strain (GLS) of the left ventricular endocardium, mid-myocardium, and epicardium (GLSendo, GLSmid, GLSepi), global myocardial work index (GWI), global myocardial work efficiency (GWE), global constructive work (GCW), and global wasted work (GWW). The absolute difference of GLS(ΔGLS) between endocardium and epicardium were calculate.All parameters were analyzed statistically. ROC curves were plotted to compare the effectiveness of layer-specific strain and myocardial work parameters in predicting left ventricular systolic function impairment in HFpEF patients.Results:①Left atrial diameter, interventricular septum at end-diastole, left ventricular posterior wall at end-diastole, relative wall thickness, left ventricular mass index, and average early diastolic peak velocity (E)/early diastolic tissue velocity (e′) in HFpEF group were significantly higher compared with control subjects, while late diastolic peak velocity (A), E/A, and e′ were significantly lower (all P<0.05); E, left ventricular end-diastolic diameter, left ventricular end-diastolic volume, left ventricular end-systolic volume, fraction shortening, and left ventricular ejection fraction were not different between HFpEF and control groups (all P>0.05). ②The global longitudinal strain of the left ventricule was highest in the endocardium and lowest in the epicardium. ③Compared with control subjects, HFpEF patients demonstrated significantly decreased GLSendo, GLSmid, GLSepi, ΔGLS, GWI, GWE, GCW and increased GWW (all P<0.01). ④The ROC results showed that the area under the curve of ΔGLS and GWE for predicting left ventricular contractile function impairment in HFpEF group, was 0.884 and 0.882, respectively; The cutoff values were -5.8% and 95%; The sensitivity were 84.2% and 71.1%, and the specificity was 84.2% and 89.5%, respectively. ⑤The ROC curve of combining the two technologies showed that the maximum area under the curve of the ΔGLS in tandem with GWE was 0.944, the sensitivity was 81.6%, and the specificity was 97.4%. Conclusions:Both speckle tracking layer-specific strain and myocardial work techniques can sensitively detect left ventricular myocardial function impairment in HFpEF patients at an early stage. ΔGLS and GWE are more reliable indexes for predicting left ventricular systolic function damage in HFpEF patients. Combining the two techniques can improve the diagnostic performance in HFpEF patients.

Falla cardiaca con fracción de eyección preservada: generalidades y aproximación en el perioperatorio / Heart failure with preserved ejection fraction: overview and perioperative management / Falência cardíaca com fração de ejeção preservada: generalidades e abordagens no perioperatório

Resumen: La falla cardiaca con fracción de eyección preservada es frecuente y de difícil abordaje perioperatorio en población adulta. Es un síndrome clínico complejo con alteraciones estructurales y funcionales cardiacas con fracción de eyección del ventrículo izquierdo preservada (FEVI) ≥ 50 %. Los biomarcadores, la ecocardiografía, el cateterismo cardiaco y otros métodos no invasivos confirman el diagnóstico. Actualmente no existe manejo específico efectivo comparado al de la falla con FEVI reducida. Objetivo: Elaborar una revisión de la literatura sobre la falla cardiaca con fracción de eyección preservada y sus implicaciones anestésicas. Métodos: Se realizó una revisión no sistemática de la literatura en las siguientes bases de datos: Pubmed/Medline, LILACS, ScienceDirect. Resultados: La falla cardiaca con fracción de eyección preservada es una entidad común con una prevalencia entre 36,9 % y más del 50 % del total de pacientes. La fisiopatología incluye alteraciones diastólicas del ciclo cardiaco incluyendo las fases de relajación y de compliance ventricular. Desde el punto de vista anestésico se debe mantener el ritmo sinusal en arritmias, controlar la respuesta cronotrópica, evitar congestión pulmonar, manejar específicamente las etiologías-comorbilidades, conservar presiones de llenado ventricular y lograr estabilidad hemodinámica. Conclusión: Los pacientes con este síndrome representan un reto anestésico. El manejo incluye tratamiento específico de las etiologías, comorbilidades y fenotipos. A diferencia de la falla cardiaca con fracción de eyección reducida, no existen terapias que disminuyan la mortalidad, por lo que se requieren nuevos fármacos y estudios clínicos que mejoren las perspectivas anestésicas y el abordaje terapéutico.

Abstract: Heart failure with preserved ejection fraction (HFPEF) is frequent and challenging to manage in the adult population during the perioperative period. It is a complex clinical syndrome with structural and functional cardiac abnormalities with left ventricular preserved ejection fraction (LVPEF) ≥ 50%. Biomarkers, echocardiography, cardiac catheterization, and other noninvasive methods confirm the diagnosis. Currently, there is no specific effective management compared to failure with reduced LVPEF. Aim: To prepare a literature review of HFpEF and its anesthetic implications. Methods: A non-systematic literature review was carried out in the following databases: Pubmed/Medline, LILACS, ScienceDirect. Results: HFpEF is a common entity with a prevalence between 36.9 % and more than 50 % of all patients. The pathophysiology includes diastolic alterations of the cardiac cycle, including relaxation and ventricular compliance phases. From the anesthetic point of view, sinus rhythm should be maintained in arrhythmias, chronotropic response controlled, pulmonary congestion avoided, etiologies/comorbidities specifically managed, ventricular filling pressures preserved, and hemodynamic stability achieved. Conclusion: Patients with HFPEF represent an anesthetic challenge. Management includes specific treatment of etiologies, comorbidities, and phenotypes. Unlike heart failure with reduced ejection fraction, there are no therapies that reduce mortality, so new drugs and clinical studies are required to improve anesthetic prospects and therapeutic management.

Resumo: Introdução: A falência cardíaca de ejecção preservada é frequente e de difícil abordagem perio-peratória na população adulta. É uma síndrome clínica complexa com alterações estruturais e funcionais cardíacas de ejeção do ventrículo esquerdo preservada (FEVI) ≥ 50 %. Os biomarcadores, a ecocardiografia, o cateterismo cardíaco e outros métodos não invasivos confirmam o diagnóstico. Atualmente, não há manejo específico efetivo comparado à da falência com FEVI reduzida. Objetivo: Elaborar uma revisão da literatura sobre falência cardíaca com fração de ejeção preservada e suas implicações anestésicas. Métodos: Foi realizada uma revisão não sistemática da literatura nas bases de dados: PubMed/Medline, LILACS, ScienceDirect. Resultados: A falência cardíaca com fração de ejeção preservada é uma entidade comum com uma prevalência entre 36,9 % e mais de 50 % do total de pacientes. A fisiopatologia inclui alterações diastólicas do ciclo cardíaco incluindo as fases de relaxamento e de complacência ventricular. Do ponto de vista anestésico, deve-se manter o ritmo sinusal em arritmias, controlar a resposta cro-notrópica, evitar congestão pulmonar, lidar em específico com as etiologias-comorbidades, conservar pressões de fibrilação ventricular e atingir estabilidade hemodinâmica. Conclusão: Os pacientes com essa síndrome representam um desafio anestésico. O manejo inclui tratamento específico das etiologias, comorbidades e fenótipos. À diferença da falência cardíaca com fração de ejeção reduzida, não existem terapias que diminuam a mortalidade; portanto, são exigidos novos fármacos e estudos clínicos que melhorem as perspectivas anestésicas e a abordagem terapêutica.

Clinical profile of patients presenting with heart failure with preserved ejection fraction

Background: Evaluate the clinical profile of patients presenting with heart failure having normal or preserved ejection fraction and to determine the prevalence of comorbid illnesses in these patients.Methods: The study was carried out on patients that presented with heart failure at the Vadilal Sarabhai hospital, Ahmedabad between September 2014-2016. Heart failure patients with normal ejection fraction (>50%) were selected. Socio-demographic, vital signs, data of 2D Echocardiography and Tissue Doppler study were collected. The patients were classified as per the Echocardiographic study into four categories. Different laboratory parameters were compared in patients with respect to (a) grade of Hypertension (b), grade of anemia (c), HbA1c levels. Statistical analysis was done using the SPSS software v20. Mann-Whitney and Kruskal-Wallis tests were performed to compare the means between different study groups.Results: Out of the 70 patients, a majority (47%) belonged to the Grade 2 (pseudo-normalized) group of diastolic dysfunctions with most of them having only dyspnea and pedal edema (33%). 58.6% patients required intensive care for at least one day. Regarding co-morbidities 27 (38.6%) had hypertension, 34 (48.6%) were diabetic and 49(70%) had anemia. Patients with higher grade of dysfunction had higher HbA1c (p=0.023) and worsening anemia (p=0.003).Conclusions: Authors concluded that it is of prime importance to find, prevent and treat the comorbidities along with targeted therapies for HFpEF. Further evaluation can be done for clinical applicability of different markers including HbA1c and U.ACR for renal dysfunction in HFpEF.