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  • 1区Q1影响因子: 22.3
    1. Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction.
    1. 心力衰竭患者的超声心动图特征,保存左心室喷射分数。
    作者:Shah Amil M , Cikes Maja , Prasad Narayana , Li Guichu , Getchevski Stoyan , Claggett Brian , Rizkala Adel , Lukashevich Ilya , O'Meara Eileen , Ryan John J , Shah Sanjiv J , Mullens Wilfred , Zile Michael R , Lam Carolyn S P , McMurray John J V , Solomon Scott D ,
    期刊:Journal of the American College of Cardiology
    日期:2019-12-10
    DOI :10.1016/j.jacc.2019.09.063
    BACKGROUND:The PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial tested the efficacy of sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Existing data on cardiac structure and function in patients with HFpEF suggest significant heterogeneity. OBJECTIVES:The aim of this study was to characterize cardiac structure and function, quantify their associations with clinical outcomes, and contextualize these findings with other HFpEF studies. METHODS:Echocardiography was performed in 1,097 of 4,822 PARAGON-HF patients within 6 months of enrollment. Associations with incident first heart failure hospitalization or cardiovascular death were assessed using Cox proportional hazards models adjusted for age, sex, region of enrollment, randomized treatment, N-terminal pro-brain natriuretic peptide, and clinical risk factors. RESULTS:Average age was 74 ± 8 years, 53% of patients were women, median N-terminal pro-brain natriuretic peptide level was 918 pg/ml (interquartile range: 485 to 1,578 pg/ml), 94% had hypertension, and 35% had atrial fibrillation. The mean left ventricular (LV) ejection fraction was 58.6 ± 9.8%, prevalence of LV hypertrophy was 21%, prevalence of left atrial enlargement was 83%, prevalence of elevated E/e' ratio was 53%, and prevalence of pulmonary hypertension was 31%. Heart failure hospitalization or cardiovascular death occurred in 288 patients at 2.8-year median follow-up. In fully adjusted models, higher LV mass index (hazard ratio [HR]: 1.05 per 10 g/m; 95% confidence interval [CI]: 1.00 to 1.10; p = 0.03), E/e' ratio (HR: 1.04 per unit; 95% CI: 1.02 to 1.06; p < 0.001), pulmonary artery systolic pressure (HR: 1.51 per 10 mm Hg; 95% CI: 1.29 to 1.76; p < 0.001), and right ventricular end-diastolic area (HR: 1.04 per cm; 95% CI: 1.01 to 1.07; p = 0.003) were each associated with this composite, while LV ejection fraction and left atrial size were not (p > 0.05 for all). Appreciable differences were observed in cardiac structure compared with other HFpEF clinical trials, despite similar E/e' ratio, pulmonary artery systolic pressure, and event rates. CONCLUSIONS:Diastolic dysfunction, left atrial enlargement, and pulmonary hypertension were common in PARAGON-HF. LV hypertrophy, elevated left- and right-sided pressures, and right ventricular enlargement were independently predictive of incident heart failure hospitalization or cardiovascular death. Echocardiographic differences among HFpEF trials despite similar clinical event rates highlight the heterogeneity of this syndrome. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
  • 2区Q2影响因子: 5.2
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    2. Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2.
    2. 向心力衰竭过渡期间葡萄糖代谢的改变:UCP-2的贡献。
    作者:Kutsche Hanna Sarah , Schreckenberg Rolf , Weber Martin , Hirschhäuser Christine , Rohrbach Susanne , Li Ling , Niemann Bernd , Schulz Rainer , Schlüter Klaus-Dieter
    期刊:Cells
    日期:2020-02-27
    DOI :10.3390/cells9030552
    The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes. We demonstrate that a downregulation of UCP-2 by siRNA in cardiomyocytes preserves contractile function in the presence of angiotensin II. Furthermore, silencing of UCP-2 was associated with an upregulation of glucose transporter type (Glut)-4, increased glucose uptake, and reduced intracellular lactate levels, indicating improvement of the oxidative glucose metabolism. To study this adaptation in vivo, spontaneously hypertensive rats served as a model for cardiac hypertrophy due to pressure overload. During compensatory hypertrophy, we found low UCP-2 levels with an upregulation of Glut-4, while the decompensatory state with impaired function was associated with an increase of UCP-2 and reduced Glut-4 expression. By blocking the aldosterone receptor with spironolactone, both cardiac function as well as UCP-2 and Glut-4 expression levels of the compensated phase could be preserved. Furthermore, we were able to confirm this by left ventricular (LV) biopsies of patients with end-stage heart failure. The results of this study show that UCP-2 seems to impact the cardiac glucose metabolism during the transition from hypertrophy to failure by affecting glucose uptake through Glut-4. We suggest that the failing heart could benefit from low UCP-2 levels by improving the efficiency of glucose oxidation. For this reason, UCP-2 inhibition might be a promising therapeutic strategy to prevent the development of heart failure.
  • 4区Q3影响因子: 1.9
    3. Prevention of heart failure with preserved ejection fraction (HFpEF): reexamining microRNA-21 inhibition in the era of oligonucleotide-based therapeutics.
    3. 保留射血分数(HFpEF)预防心力衰竭:在基于寡核苷酸的疗法时代重新审视microRNA-21抑制作用。
    作者:Ben-Nun David , Buja L Maximilian , Fuentes Francisco
    期刊:Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
    日期:2020-05-19
    DOI :10.1016/j.carpath.2020.107243
    Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of cases of heart failure, which is the most common cause of hospitalization in US patients over the age of 65. HFpEF pathogenesis is increasingly believed to be due to pathological hypertrophy and fibrosis of the myocardium that may be a result of systemic inflammation from comorbid conditions such as hypertension, diabetes mellitus, chronic obstructive pulmonary disease, anemia, chronic kidney disease and others. It is believed that oxidative stress triggers a process of pathological hypertrophy and fibrosis in cardiac endothelial cells, which leads to increased left ventricle filling pressures and, eventually, symptoms of heart failure. Numerous recent major clinical trials that have examined various therapies aimed at improving mortality in HFpEF have emerged empty-handed and thus the search for effective management strategies continues. Over the last several years, there have been many new developments in the field of antisense oligonucleotide-based therapeutics, which involves using noncoding nucleic acid particles such as microRNA and small interfering RNA to repress the expression of specific messenger RNA. In this article, we review the concept of using oligonucleotide-based therapeutics to prevent or treat HFpEF by targeting a specific microRNA that has been implicated in the pathogenesis of myocardial fibrosis and hypertrophy, microRNA-21 (miR-21). We review the various evidence that implicates miR-21 in the process of myocardial fibrosis and discuss recent attempts to use antimiR-21 compounds to prevent fibrosis. We also discuss proposed methods for screening patients at high risk for HFpEF for diastolic dysfunction in order to determine which patients.
  • 2区Q1影响因子: 5.5
    4. Genetic Variation in Sodium-glucose Cotransporter 2 and Heart Failure.
    4. 钠-葡萄糖协同转运蛋白2的遗传变异与心力衰竭。
    期刊:Clinical pharmacology and therapeutics
    日期:2021-02-01
    DOI :10.1002/cpt.2153
    Inhibition of sodium-glucose cotransporter 2 (SGLT2) represents an emerging pharmaceutical approach for the treatment of heart failure. The mechanisms by which SGLT2 inhibitors reduce the risk of heart failure are not well understood. The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the SLC5A2 gene, encoding SGLT2, and heart failure, and to assess potential mediators of this association. Regression and mediation analyses were conducted with individual participant data of the UK Biobank (n = 416,737) and validated in the cardiovascular high-risk cohort of the LUdwigshafen RIsk and Cardiovascular Health study (LURIC; n = 3316). Two intronic SNPs associated with SLC5A2 expression were included in a genetic score, which was associated with lower risk of heart failure in UK Biobank (odds ratio 0.97, 95% confidence interval, 0.95-0.99, P = 0.016). This association was also present in participants without type 2 diabetes or coronary artery disease (CAD). The associations of the genetic score with HbA1c, high-density lipoprotein cholesterol, uric acid, systolic blood pressure, waist circumference, and body composition mediated 35% of the effect of the score on heart failure risk. No associations of the genetic SGLT2 score with atherosclerotic cardiovascular disease outcomes or markers of volume status were observed, which was confirmed in the LURIC study. Variations in the gene encoding SGLT2 were associated with the risk of prevalent or incident heart failure. This association was mediated by several mechanisms and did not depend on the presence of type 2 diabetes or previous CAD events.
  • 3区Q2影响因子: 3.4
    5. Increased Prevalence of Diastolic Heart Failure in Patients with Rheumatoid Arthritis Correlates with Active Disease, but Not with Treatment Type.
    5. 类风湿关节炎患者舒张性心力衰竭的患病率增加与活动性疾病相关,但与治疗类型无关。
    作者:Schau Thomas , Gottwald Michael , Arbach Olga , Seifert Martin , Schöpp Maren , Neuß Michael , Butter Christian , Zänker Michael
    期刊:The Journal of rheumatology
    日期:2015-09-15
    DOI :10.3899/jrheum.141647
    OBJECTIVE:Although heart failure (HF) is a major cause of premature mortality, there is little information regarding its prevalence and associated risk factors in patients with rheumatoid arthritis (RA). In this study, we evaluated the prevalence of HF in a community-based RA cohort. Further, we investigated the effect of RA activity and present treatment on HF rate and cardiac structure. METHODS:A diagnostic workup for HF according to the European Society of Cardiology recommendations was performed in 157 patients with RA fulfilling the American College of Rheumatology/European League Against Rheumatism criteria (68% women, age 61 ± 13 yrs) from our outpatient clinic and in 77 age- and sex-matched controls. RESULTS:The prevalence of HF in patients with RA (24%) was unexpectedly high and differed significantly from the control sample (6%, p = 0.001). Diastolic HF was the dominant type (23% vs 6%), and clinical symptoms alone were of low diagnostic value. Active RA (28-joint Disease Activity Score ≥ 2.6: OR 3.4, 95% CI 1.3-9.8) was an independent risk factor of HF, as well as systemic inflammation (erythrocyte sedimentation rate > 16 mm/h: OR 5.4, 95% CI 2.1-16; C-reactive protein > 10 mg/l: OR 2.6, 95% CI 0.8-8.0) and RA duration > 10 years (OR 2.6, 95% CI 1.2-5.8). HF in RA was associated with concentric hypertrophy (48% vs 17%, p < 0.001) and reduced longitudinal strain (-17.2% vs -19.7%, p < 0.001). However, the prevalence of HF was equivalent between the treatment groups [conventional synthetic disease-modifying antirheumatic drugs (DMARD) 25%, tumor necrosis factor inhibitors 22%, other biological DMARD 27%]. CONCLUSION:Recognition of all diastolic HF in RA requires a complex diagnostic approach. Active rather than inactive RA places patients at a higher risk for HF, whereas influence of RA treatment on HF risk needs to be elucidated in further studies.
  • 2区Q1影响因子: 5.3
    6. Heart Failure With Midrange Ejection Fraction-What Is It, If Anything?
    6. 心力衰竭与中档弹射Fraction-What它,如果什么吗?
    作者:Boulet Jacinthe , Massie Emmanuelle , Rouleau Jean-Lucien
    期刊:The Canadian journal of cardiology
    日期:2020-12-02
    DOI :10.1016/j.cjca.2020.11.013
    The patient cohort with left ventricular ejection fractions (LVEFs) of 41%-49%, which has been defined as heart failure with midrange ejection fraction (HFmrEF), represent a significant proportion of the heart failure (HF) population. Despite the clear cutoffs established by different society guidelines, confusion remains regarding the exact significance of midrange LVEF within the HF syndrome. Patients with LVEF 41%-49% represent a heterogeneous group of patients sharing pathophysiologic mechanisms, biomarker profiles, comorbidities, and clinical characteristics with patients with preserved and reduced LVEF. In this clinical review, we discuss the underlying pathophysiologic mechanisms that culminate in the clinical syndrome of HF and contribute to the disparities observed between HFpEF, HFrEF, and HFmrEF. We highlight differences and similarities in clinical characteristics and imaging features between HFpEF and HFrEF in an effort to disentangle the heterogeneous group of patients with midrange LVEF, but ultimately we conclude that LVEF should be seen as simply one important element of a continuum throughout the HF syndrome, and that although is useful, it is an oversimplification, because HF syndrome is more of a continuum. The underlying pathophysiology, etiology, and comorbidities of patients presenting with HF is becoming ever more important as the limitations of a classification solely based on LVEF are being better recognised, and as patient-specific personalisation of care is becoming ever more important.
  • 3区Q1影响因子: 3.7
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    7. Heart failure in the last year: progress and perspective.
    7. 心力衰竭在去年:进步与观点。
    期刊:ESC heart failure
    日期:2020-12-05
    DOI :10.1002/ehf2.13124
    Research about heart failure (HF) has made major progress in the last years. We give here an update on the most recent findings. Landmark trials have established new treatments for HF with reduced ejection fraction. Sacubitril/valsartan was superior to enalapril in PARADIGM-HF trial, and its initiation during hospitalization for acute HF or early after discharge can now be considered. More recently, new therapeutic pathways have been developed. In the DAPA-HF and EMPEROR-Reduced trials, dapagliflozin and empagliflozin reduced the risk of the primary composite endpoint, compared with placebo [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.65-0.85; P < 0.001 and HR 0.75; 95% CI 0.65-0.86; P < 0.001, respectively]. Second, vericiguat, an oral soluble guanylate cyclase stimulator, reduced the composite endpoint of cardiovascular death or HF hospitalization vs. placebo (HR 0.90; 95% CI 0.82-0.98; P = 0.02). On the other hand, both the diagnosis and treatment of HF with preserved ejection fraction, as well as management of advanced HF and acute HF, remain challenging. A better phenotyping of patients with HF would be helpful for prognostic stratification and treatment selection. Further aspects, such as the use of devices, treatment of arrhythmias, and percutaneous treatment of valvular heart disease in patients with HF, are also discussed and reviewed in this article.
  • 8. Platelet-Derived Growth Factor in Heart Failure.
    8. 血小板衍生生长因子在心力衰竭。
    作者:Medamana John , Clark Richard A , Butler Javed
    期刊:Handbook of experimental pharmacology
    日期:2017-01-01
    DOI :10.1007/164_2016_80
    Defective vascular and cardiomyocyte function are implicated in the development and progression of both heart failure with reduced and preserved ejection fraction. Any treatment option that augments these myocardial processes may therefore be of significant value. The platelet-derived growth factor (PDGF) family is involved in a wide range of growth processes and plays a key role in both regulating angiogenesis and mesenchymal cell development. Thus, PDGF may serve as a potent therapy for heart failure. While numerous animal studies have demonstrated beneficial cardiovascular effects of growth factor therapy, promising laboratory data has not yet translated to effective therapies. In this review, we outline the biological role of PDGF and summarize previous studies that have focused on the cardiovascular effects of normal PDGF signaling, administration of PDGF, and the effects of PDGF on stem cell therapy.
  • 1区Q1影响因子: 11.9
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    9. Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction.
    9. 褪黑素可改善射血分数保留的心力衰竭小鼠模型的心脏功能。
    作者:Liu Yuan , Li Li-Na , Guo Sen , Zhao Xiao-Yan , Liu Yu-Zhou , Liang Cui , Tu Sheng , Wang Dan , Li Ling , Dong Jian-Zeng , Gao Lu , Yang Hai-Bo
    期刊:Redox biology
    日期:2018-07-11
    DOI :10.1016/j.redox.2018.07.007
    Melatonin has been shown to inhibit myocardial infarction-induced apoptosis, its function in heart failure with preserved ejection fraction (HFpEF) has not been investigated. This study aimed to investigate whether melatonin attenuates obesity-related HFpEF. Male mice were fed a high-fat diet (HFD) from weaning to 6 months of age to induce HFpEF. The mice were orally administered melatonin (50 mg/kg) by 3 weeks. Diastolic function was significantly improved by melatonin supplementation in mice fed an HFD. Melatonin attenuated obesity-induced myocardial oxidative stress and apoptosis and promoted the secretion of C1q/tumour necrosis factor-related protein 3 (CTRP3) by adipose tissue. And depletion of circulating CTRP3 largely abolished melatonin-mediated cardio-protection. Melatonin-mediated secretion of adipocyte-derived CTRP3 activated NF-E2-related factor 2 (Nrf2), which were largely abrogated by knocking down CTRP3 in adipocytes or Nrf2 in cardiomyocytes. Nrf2 activation was mediated by miR-200a, and a miR-200a antagomir offset the effects of melatonin-conditioned medium on Nrf2 expression. Our results indicate that melatonin can be used to treat and prevent obesity-related HFpEF.
  • 2区Q1影响因子: 3.6
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    10. Mouse Models of Heart Failure with Preserved or Reduced Ejection Fraction.
    10. 小鼠模型的心脏衰竭与保存或射血分数降低。
    作者:Noll Natalie A , Lal Hind , Merryman W David
    期刊:The American journal of pathology
    日期:2020-04-25
    DOI :10.1016/j.ajpath.2020.04.006
    Heart failure (HF) is a chronic, complex condition with increasing incidence worldwide, necessitating the development of novel therapeutic strategies. This has led to the current clinical strategies, which only treat symptoms of HF without addressing the underlying causes. Multiple animal models have been developed in an attempt to recreate the chronic HF phenotype that arises following a variety of myocardial injuries. Although significant strides have been made in HF research, an understanding of more specific mechanisms will require distinguishing models that resemble HF with preserved ejection fraction (HFpEF) from those with reduced ejection fraction (HFrEF). Therefore, current mouse models of HF need to be re-assessed to determine which of them most closely recapitulate the specific etiology of HF being studied. This will allow for the development of therapies targeted specifically at HFpEF or HFrEF. This review will summarize the commonly used mouse models of HF and discuss which aspect of human HF each model replicates, focusing on whether HFpEF or HFrEF is induced, to allow better investigation into pathophysiological mechanisms and treatment strategies.
  • 2区Q1影响因子: 4.1
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    11. A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II.
    11. 由于慢性输注低剂量降压药血管紧张素II而导致射血分数保留的心力衰竭小鼠模型。
    作者:Regan Jessica A , Mauro Adolfo Gabriele , Carbone Salvatore , Marchetti Carlo , Gill Rabia , Mezzaroma Eleonora , Valle Raleigh Juan , Salloum Fadi N , Van Tassell Benjamin W , Abbate Antonio , Toldo Stefano
    期刊:American journal of physiology. Heart and circulatory physiology
    日期:2015-07-17
    DOI :10.1152/ajpheart.00282.2015
    Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (ATII) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the ATII (0.2 mg·kg(-1)·day(-1)) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. ATII infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF.
  • 3区Q2影响因子: 2.9
    12. Effect of the peptides Relaxin, Neuregulin, Ghrelin and Glucagon-like peptide-1, on cardiomyocyte factors involved in the molecular mechanisms leading to diastolic dysfunction and/or heart failure with preserved ejection fraction.
    12. 效应的肽的松弛素,神经调节蛋白,生长素释放肽和胰高血糖素样肽-1,对涉及导致舒张功能障碍和/或与射血分数心脏衰竭的分子机制的心肌细胞因子。
    作者:Warbrick Ian , Rabkin Simon W
    期刊:Peptides
    日期:2018-05-25
    DOI :10.1016/j.peptides.2018.05.009
    Heart failure with preserved ejection fraction (HFpEF) represents an important cardiac condition because of its increasing prevalence, resistance to treatment and high associated morbidity and mortality. Two of the major mechanisms responsible for HFpEF are impaired cardiomyocyte sarcoplasmic reticulum (SR) Ca ATPase (SERCA2a), which is responsible for calcium reuptake into the SR, and cardiac fibroblasts/myofibroblasts that produce collagen or myocardial fibrosis. Phospholamban (PLB), in the SR and endoplasmic reticulum, is the primary regulator of SERCA2a in the heart and acts as a reversible inhibitor of SERCA2a. Glucagon-like peptide-1, a 30 amino acid peptide, improves diastolic function through increasing SERCA2a expression and activity as well as by decreasing phosphorylation of Ryanodine receptors. It also enhances collagen production through enhanced procollagen IalphaI/IIIalphaI, connective tissue growth factor, fibronectin, TGF-β3 as well as Interleukin -10, -1beta, and -6 gene expression. Relaxin-2, a two chain, 53 amino acid peptide, increases Ser16- and Thr17-phosphorylation levels of PLB, thereby relieving SERCA2a of its inhibition. H3 Relaxin inhibits TGF-β1-stimulated collagen deposition through H3 relaxin-induced increases in pSmad2. Neuregulin-1, an epidermal growth factor, induces nitric oxide and PI-3 kinase activation that enhance SERCA2 activity. Neuregulin-1 was associated with less myocardial macrophage infiltration and cytokine expression reducing collagen deposition. Ghrelin, a 28 amino acid peptide, improves SERCA2a function by inducing PLB phosphorylation. Ghrelin also reduces cardiac fibrosis. In summary, Glucagon-like peptide-1, Relaxin-2, Neuregulin-1, and Ghrelin each modify calcium dynamics, collagen expression, and myocardial fibrosis through attenuation of deleterious signaling cascades, and induction of adaptive pathways, representing potential therapeutic targets for HFpEF.
  • 1区Q1影响因子: 8.4
    13. Endothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse Model.
    13. 内皮细胞衰老有助于心力衰竭随着老龄小鼠模型射血分数。
    作者:Gevaert Andreas B , Shakeri Hadis , Leloup Arthur J , Van Hove Cor E , De Meyer Guido R Y , Vrints Christiaan J , Lemmens Katrien , Van Craenenbroeck Emeline M
    期刊:Circulation. Heart failure
    日期:2017-06-01
    DOI :10.1161/CIRCHEARTFAILURE.116.003806
    BACKGROUND:Because of global aging, the prevalence of heart failure with preserved ejection fraction (HFpEF) continues to rise. Although HFpEF pathophysiology remains incompletely understood, endothelial inflammation is stated to play a central role. Cellular senescence is a process of cellular growth arrest linked with aging and inflammation. We used mice with accelerated aging to investigate the role of cellular senescence in HFpEF development. METHODS AND RESULTS:Senescence-accelerated mice (SAM, n=18) and control mice with normal senescence (n=15) were fed normal chow or a high-fat, high-salt diet (WD). Vascular and cardiac function was assessed at 8, 16, and 24 weeks of age. At 24 weeks, both SAM on WD (SAM-WD) and SAM on regular diet displayed endothelial dysfunction, as evidenced by impaired acetylcholine-induced relaxation of aortic segments and reduced basal nitric oxide. At week 24, SAM-WD had developed HFpEF, characterized by diastolic dysfunction, left ventricular hypertrophy, left atrial dilatation, and interstitial fibrosis. Also, exercise capacity was reduced and lung weight increased. Cardiovascular inflammation and senescence were assessed by immunohistochemical and immunofluorescence staining of hearts and aortas. SAM-WD showed increased endothelial inflammation (intercellular adhesion molecule 1 expression) and increased endothelial senescence (acetyl-p53/CD31 costaining). The latter correlated with diastolic function and intercellular adhesion molecule 1 expression. CONCLUSIONS:SAM develop endothelial dysfunction. Adding a high-salt, high-fat diet accelerates endothelial senescence and instigates endothelial inflammation. This coincides with hemodynamic and structural changes typical of HFpEF. Targeting endothelial senescence could be a new therapeutic avenue in HFpEF.
  • 1区Q1影响因子: 12.9
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    14. Heart failure with preserved ejection fraction: present status and future directions.
    14. 射血分数保留的心力衰竭:现状和未来方向。
    期刊:Experimental & molecular medicine
    日期:2019-12-19
    DOI :10.1038/s12276-019-0323-2
    The clinical importance of heart failure with preserved ejection fraction (HFpEF) has recently become apparent. HFpEF refers to heart failure (HF) symptoms with normal or near-normal cardiac function on echocardiography. Common clinical features of HFpEF include diastolic dysfunction, reduced compliance, and ventricular hypokinesia. HFpEF differs from the better-known HF with reduced ejection fraction (HFrEF). Despite having a "preserved ejection fraction," patients with HFpEF have symptoms such as shortness of breath, excessive tiredness, and limited exercise capability. Furthermore, the mortality rate and cumulative survival rate are as severe in HFpEF as they are in HFrEF. While beta-blockers and renin-angiotensin-aldosterone system modulators can improve the survival rate in HFrEF, no known therapeutic agents show similar effectiveness in HFpEF. Researchers have examined molecular events in the development of HFpEF using small and middle-sized animal models. This review discusses HFpEF with regard to etiology and clinical features and introduces the use of mouse and other animal models of human HFpEF.
  • 2区Q1影响因子: 7.4
    15. Hypoxia-inducible factor 1-alpha (HIF-1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction.
    15. 缺氧诱导因子1-α(HIF-1α),其介导和肥胖射血分数心脏衰竭之间的关系的一个因素。
    作者:Warbrick Ian , Rabkin Simon W
    期刊:Obesity reviews : an official journal of the International Association for the Study of Obesity
    日期:2019-03-03
    DOI :10.1111/obr.12828
    Heart failure with preserved ejection fraction (HFpEF), a common condition with an increased mortality, is strongly associated with obesity and the metabolic syndrome. The latter two conditions are associated with increased epicardial fat that can extend into the heart. This review advances the proposition that hypoxia-inhibitory factor-1α (HIF-1α) maybe a key factor producing HFpEF. HIF-1α, a highly conserved transcription factor that plays a key role in tissue response to hypoxia, is increased in adipose tissue in obesity. Increased HIF-1α expression leads to expression of a potent profibrotic transcriptional programme involving collagen I, III, IV, TIMP, and lysyl oxidase. The net effect is the formation of collagen fibres leading to fibrosis. HIF-1α is also responsible for recruiting M1 macrophages that mediate obesity-associated inflammation, releasing IL-6, MCP-1, TNF-α, and IL-1β with increased expression of thrombospondin, pro α2 (I) collagen, transforming growth factor β, NADPH oxidase, and connective tissue growth factor. These factors can accelerate cardiac fibrosis and impair cardiac diastolic function. Inhibition of HIF-1α expression in adipose tissue of mice fed a high-fat diet suppressed fibrosis and reduces inflammation in adipose tissue. Delineation of the role played by HIF-1α in obesity-associated HFpEF may lead to new potential therapies.
  • 16. [Effect of sacubitril/valsartan on cardiac function in heart failure rabbits with preserved ejection fraction].
    16. [Sacubitril / Valsartan对保存射血分数的心力衰竭兔心功能的影响]。
    作者:Gao S Y , Yao D H , Li J F , Xie Q M , Jiang S C
    期刊:Zhonghua xin xue guan bing za zhi
    日期:2019-11-24
    DOI :10.3760/cma.j.issn.0253-3758.2019.11.007
    To investigate the effect of sacubitril/valsartan on cardiac function in heart failure rabbits with preserved ejection fraction. Forty-five healthy adult male New Zealand rabbits were divided into sham operation group (12) and model group (33) by random number table method. HFpEF model was constructed by abdominal aortic constriction in model group. In sham operation group, 1 rabbit died due to anesthesia accident, and 1 rabbit in model group died of acute left heart failure. At 8 weeks of modeling, 3 rabbits were excluded due to the failure to establish the successful model. At the 8th week of modeling, 2 rabbits in sham operation group were selected and sacrificed by random number table method, and 3 rabbits in model group were selected and sacrificed for myocardial histological examination. Then, 9 rabbits in sham operation group and 26 rabbits in model group entered the subsequent experiment. The model group was randomly divided into untreated group (8), valsartan intervention group (9), and sacubitril/valsartan intervention group (9), respectively, drugs were applied per gavage. The feeding and exercise activity of rabbits in each group were evaluated by simple cardiac function classification at baseline, 4 and 8 weeks post intervention. Echocardiography was used to detect interventricular septal thickness at diastole(IVSd), interventricular septal thickness at systolic(IVSs), left ventricular posterior wall of diastolic(LVPWd), left ventricular internal diameter at diastolic(LVIDd), left ventricular internal diameter at systolic(LVIDs), and calculate the left ventricular ejection fraction(LVEF), mitral valve's early diastolic flow velocity(E)/late mitral diastolic maximum flow rate ratio(A) and heart rate at baseline, 4 and 8 weeks post intervention. Serum N terminal B-type natriuretic peptide (NT-proBNP) and angiotensin (Ang)Ⅱ and soluble matrix lysin 2(sST2) content was determined by ELISA at baseline, 4 and 8 weeks post intervention. Eight weeks after intervention, the hearts of rabbits were taken and weighed, and heart mass index (HMI) and left ventricular mass index (LVMI) were calculated. (1) Evaluation results of cardiac function: there were 2, 5, and 2 rabbits with cardiac function grade Ⅰ,Ⅱ and Ⅲ before the drug intervention, and 4, 4, and 1 rabbits with respective cardiac function grade after 8 weeks of intervention in valsartan group (0.05). There were 2, 4, and 3 rabbits with heart function gradeⅠ,Ⅱ and Ⅲ before the drug intervention, and 7, 2, and 0 rabbits with respective heart function grade after 8 weeks of intervention in sacubitril/valsartan group(0.05). (2) Echocardiographic results: at 8 weeks after drug intervention, IVSd and IVSs of rabbits in untreated group were significantly higher than those in sham operation group, and the ratio of E/A was significantly lower than that in sham operation group(all 0.01). IVSs of the valsartan group was significantly higher than that of sham operation group, and the ratio of E/A was significantly lower than that of sham operation group(all 0.01). The E/A ratio in the sacubitril/valsartan group was significantly lower than that in sham operation group(0.01). IVSd and IVSs in valsartan group were significantly lower than those in untreated group(all 0.05), and IVSd in sacubitril/valsartan group was significantly lower than that in untreated group(0.01). The IVSd, IVSs, LVPWd, LVIDd, LVIDs, LVEF, E/A ratios were similar between sacubitril/valsartan group and valsartan group(all 0.05). There was no significant difference in heart rate between the groups(0.05). (3) Serum NT-proBNP, Ang Ⅱ and sST2 levels: 4 weeks after drug intervention, untreated group, valsartan group, and sacubitril/valsartan group's serum NT-proBNP levels were significantly higher than that of sham operation group(all 0.01); serum NT-proBNP was significantly lower in sacubitril/valsartan group than that in untreated group(0.01). Four weeks after intervention, serum AngⅡ levels were significantly higher in untreated group, valsartan group, sacubitril/valsartan group than in sham group(all 0.01), but there was no statistically significant difference between the modeling groups(0.05). Four weeks after drug intervention, the serum sST2 contents in untreated group, valsartan group, and sacubitril/valsartan group were significantly higher than in sham operation group(all 0.01), and which was significantly lower in valsartan group and sacubitril/valsartan group than in untreated group(all 0.01), which were significantly lower in sacubitril/valsartan group than in valsartan group(0.01). Eight weeks after drug intervention, serum NT-proBNP levels were significantly higher in untreated group, valsartan group, and sacubitril/valsartan group than in sham operation group(all 0.01), which were significantly lower in valsartan group and sacubitril/valsartan group than in untreated group(all 0.01), which were significantly lower in valsartan group than in sacubitril/valsartan group(0.01). Eight weeks after drug intervention, Ang Ⅱ levels were significantly higher in valsartan group and sacubitril/valsartan group than in untreated group(all 0.01), which tended to be higher in untreated group and valsartan group, tended to be lower in sacubitril/valsartan compared to value at 4 weeks(all 0.05). Eight weeks after drug intervention, serum sST2 was significantly higher in untreated group and valsartan group than in sham operation group(all 0.01), which tended to be higher in sacubitril/valsartan group compared to sham operation group(0.05), which were significantly lower in valsartan group and sacubitril/valsartan group than in untreated group(all 0.01), which was significantly lower in sacubitril/valsartan group than in valsartan group(0.01). (4) Comparison of whole-heart mass, left ventricular mass, HMI and LVMI: 8 weeks after drug intervention, the whole-heart mass, left ventricular mass, HMI and LVMI were significantly higher in untreated group than in sham operation group(all 0.01), and the above indexes were also significantly higher in valsartan group than in sham operation group(all 0.05), tended to be lower in valsartan group compared to untreated group (all 0.05). HMI and LVMI were lower in sacubitril/valsartan group than in untreated group(all 0.05). All the above indexes tended to be lower in sacubitril/valsartan group than in valsartan group(all 0.05). Sacubitril/valsartan is superior to valsartan alone on improving cardiac function in HFpEF rabbits.
  • 2区Q1影响因子: 4.1
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    17. Characterization of a mouse model of obesity-related fibrotic cardiomyopathy that recapitulates features of human heart failure with preserved ejection fraction.
    17. 肥胖相关性纤维化性心肌病的小鼠模型的特征,该模型通过保留射血分数来概括人类心力衰竭的特征。
    期刊:American journal of physiology. Heart and circulatory physiology
    日期:2018-07-13
    DOI :10.1152/ajpheart.00238.2018
    Heart failure with preserved ejection fraction (HFpEF) is caused, or exacerbated by, a wide range of extracardiac conditions. Diabetes, obesity, and metabolic dysfunction are associated with a unique HFpEF phenotype, characterized by inflammation, cardiac fibrosis, and microvascular dysfunction. Development of new therapies for HFpEF is hampered by the absence of reliable animal models. The leptin-resistant db/ db mouse has been extensively studied as a model of diabetes-associated cardiomyopathy; however, data on the functional and morphological alterations in db/ db hearts are conflicting. In the present study, we report a systematic characterization of the cardiac phenotype in db/ db mice, focusing on the time course of functional and histopathological alterations and on the identification of sex-specific cellular events. Although both male and female db/ db mice developed severe obesity, increased adiposity, and hyperglycemia, female mice had more impressive weight gain and exhibited a modest but significant increase in blood pressure. db/ db mice had hypertrophic ventricular remodeling and diastolic dysfunction with preserved ejection fraction; the increase in left ventricular mass was accentuated in female mice. Histological analysis showed that both male and female db/ db mice had cardiomyocyte hypertrophy and interstitial fibrosis, associated with marked thickening of the perimysial collagen, and expansion of the periarteriolar collagen network, in the absence of replacement fibrosis. In vivo and in vitro experiments showed that fibrotic changes in db/ db hearts were associated with increased collagen synthesis by cardiac fibroblasts, in the absence of periostin, α-smooth muscle actin, or fibroblast activation protein overexpression. Male db/ db mice exhibited microvascular rarefaction. In conclusion, the db/ db mouse model recapitulates functional and histological features of human HFpEF associated with metabolic dysfunction. Development of fibrosis in db/ db hearts, in the absence of myofibroblast conversion, suggests that metabolic dysfunction may activate an alternative profibrotic pathway associated with accentuated extracellular matrix protein synthesis. NEW & NOTEWORTHY We provide a systematic analysis of the sex-specific functional and structural myocardial alterations in db/ db mice. Obese diabetic C57BL6J db/ db mice exhibit diastolic dysfunction with preserved ejection fraction, associated with cardiomyocyte hypertrophy, interstitial/perivascular fibrosis, and microvascular rarefaction, thus recapitulating aspects of human obesity-related heart failure with preserved ejection fraction. Myocardial fibrosis in db/ db mice is associated with a matrix-producing fibroblast phenotype, in the absence of myofibroblast conversion, suggesting an alternative mechanism of activation.
  • 1区Q1影响因子: 13.8
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    18. Macrophages in Heart Failure with Reduced versus Preserved Ejection Fraction.
    18. 心力衰竭中巨噬细胞的射血分数减少与保留射血分数的关系。
    作者:DeBerge Matthew , Shah Sanjiv J , Wilsbacher Lisa , Thorp Edward B
    期刊:Trends in molecular medicine
    日期:2019-02-05
    DOI :10.1016/j.molmed.2019.01.002
    There is a growing number of individuals living with heart failure (HF) with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Long-term prognosis remains poor in both cases, especially in HFpEF, which is rising in incidence and lacks effective therapeutics. In both HFrEF and HFpEF, there is evidence that elevated inflammatory biomarkers, implicating innate immune cells such as macrophages, are associated with worsened clinical outcomes. Macrophage subsets are active in both inflammatory and reparative processes, yet our understanding of the causative roles for these cells in HF development and progression is incomplete. Here, we discuss recent findings interrogating the role of macrophages in inflammation and its resolution in the context of HF, with a specific focus on HFrEF versus HFpEF.
  • 3区Q1影响因子: 5.3
    19. Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure: A Meta-Analysis of Randomized Clinical Trials.
    19. 心力衰竭中的钠-葡萄糖共转运蛋白2抑制剂:一项随机临床试验的荟萃分析。
    作者:Kumar Kris , Kheiri Babikir , Simpson Timothy F , Osman Mohammed , Rahmouni Hind
    期刊:The American journal of medicine
    日期:2020-05-07
    DOI :10.1016/j.amjmed.2020.04.006
    BACKGROUND:We aimed to conduct this study with the goal of further clarifying the role of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with preexisting heart failure with reduced ejection fraction with or without diabetes and to leverage increased sample size and power to evaluate clinically important secondary safety and efficacy outcomes. METHODS:This meta-analysis was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was a composite of cardiovascular death or heart failure hospitalization. Secondary outcomes included the individual components of the primary outcome; major adverse cardiovascular events (defined as a composite of cardiovascular death, myocardial infarction, stroke), any death, myocardial infarction, or stroke, along with adverse events such as volume depletion, acute kidney injury, adverse events leading to drug discontinuation, amputation, and severe hypoglycemia. Other outcomes included the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score and changes in N-terminal pro-hormone BNP (NT-proBNP). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for dichotomous variables and weighted difference (MD) and 95% CI for continuous variables. RESULTS:Compared with placebo, SGLT2i use was associated with a significant reduction of cardiovascular death or heart failure hospitalization (HR = 0.74; 95% CI = 0.66-0.82; P <0.01), heart failure hospitalization (HR = 0.69; 95% CI = 0.57-0.84; P <0.01), cardiovascular death (HR = 0.79; 95% CI = 0.68-0.92; P <0.01), and any death (HR = 0.80; 95% CI = 0.70-0.92; P <0.01). CONCLUSIONS:SGLT2i was associated with a decreased risk of clinically relevant cardiovascular death, heart failure hospitalization, and heart failure symptoms with similar rates of adverse events.
  • 1区Q1影响因子: 8.3
    20. Allicin improves the function of cardiac microvascular endothelial cells by increasing PECAM-1 in rats with cardiac hypertrophy.
    20. 大蒜素提高通过与心脏肥大的大鼠增加PECAM-1的心脏微血管内皮细胞的功能。
    作者:Shi Pilong , Cao Yonggang , Gao Jingquan , Fu Bowen , Ren Jing , Ba Lina , Song Chao , Qi Hanping , Huang Wei , Guan Xueying , Sun Hongli
    期刊:Phytomedicine : international journal of phytotherapy and phytopharmacology
    日期:2018-10-19
    DOI :10.1016/j.phymed.2018.10.021
    OBJECTIVE:Cardiac microvascular damage is significantly associated with the development of cardiac hypertrophy (CH). Researchers found that allicin could inhibit CH, but the relationship between cardiac microvessel and the inhibition of allicin on CH has not been reported. We aimed to investigate the effect of allicin on the function of cardiac microvascular endothelial cells (CMECs) in CH rat. MATERIALS AND METHODS:The hemodynamic parameters were measured by BL-420F biological function experimental system and the indicators of the ventricular structure and function were measured by echocardiographic system. MTT assay was performed to assess the cell viability. Nitrite detection was performed to detect nitric oxide content. The morphology and molecular characteristics were detected by electron micrographs, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), western blot. Wound healing experiment, analysis of tube formation and shear adaptation were performed to assess CMECs migration ability, angiogenesis and shear-responsiveness respectively. RESULT:Our findings have identified that microvascular density was decreased by observing the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in CH rats. Interestingly, allicin improved the distribution and expression of PECAM-1. Meanwhile, allicin enhanced the migration and angiogenesis ability of CMECs, activated PECAM-1-PI3K-AKT-eNOS signaling pathway, however, the role of allicin was disappear after PECAM-1 was silenced. Allicin decreased the expression of caspase-3 and receptor interacting protein 3 (RIP3), inhibited necroptosis, and increased the levels of Angiopoietin-2 (Ang-2) and platelet-derived growth factor receptor-β (PDGFR-β). Under 10 dyn/cm condition, allicin advanced the modification ability of CMECs's shear-adaptation by activating PECAM-1. CONCLUSION:Allicin provided cardioprotection for CH rats by improving the function of CMECs through increasing the expression of PECAM-1.
  • 1区Q1影响因子: 10.8
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    21. Epicardial fat in heart failure patients with mid-range and preserved ejection fraction.
    21. 心外膜脂肪在心脏衰竭患者的中档和射血分数。
    作者:van Woerden Gijs , Gorter Thomas M , Westenbrink B Daan , Willems Tineke P , van Veldhuisen Dirk J , Rienstra Michiel
    期刊:European journal of heart failure
    日期:2018-08-01
    DOI :10.1002/ejhf.1283
    AIMS:Adipose tissue and inflammation may play a role in the pathophysiology of patients with heart failure (HF) with mildly reduced or preserved ejection fraction. We therefore investigated epicardial fat in patients with HF with preserved (HFpEF) and mid-range ejection fraction (HFmrEF), and related this to co-morbidities, plasma biomarkers and cardiac structure. METHODS AND RESULTS:A total of 64 HF patients with left ventricular ejection fraction >40% and 20 controls underwent routine cardiac magnetic resonance examination. Epicardial fat volume was quantified on short-axis cine stacks covering the entire epicardium and was related to clinical correlates, biomarkers associated with inflammation and myocardial injury, and cardiac function and contractility on cardiac magnetic resonance. HF patients and controls were of comparable age, sex and body mass index. Total epicardial fat volume was significantly higher in HF patients compared to controls (107 mL/m vs. 77 mL/m , P <0.0001). HF patients with atrial fibrillation and/or type 2 diabetes mellitus had more epicardial fat than HF patients without these co-morbidities (116 vs. 100 mL/m , P =0.03, and 120 vs. 97 mL/m , P =0.001, respectively). Creatine kinase-MB, troponin T and glycated haemoglobin in patients with HF were positively correlated with epicardial fat volume (R =0.37, P =0.006; R =0.35, P =0.01; and R =0.42, P =0.002, respectively). CONCLUSION:Heart failure patients had more epicardial fat compared to controls, despite similar body mass index. Epicardial fat volume was associated with the presence of atrial fibrillation and type 2 diabetes mellitus and with biomarkers related to myocardial injury. The clinical implications of these findings are unclear, but warrant further investigation.
  • 3区Q2影响因子: 3.1
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    22. Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure.
    22. 炎症细胞因子和趋化因子作为心力衰竭的治疗靶标。
    作者:Hanna Anis , Frangogiannis Nikolaos G
    期刊:Cardiovascular drugs and therapy
    日期:2020-09-09
    DOI :10.1007/s10557-020-07071-0
    Heart failure exhibits remarkable pathophysiologic heterogeneity. A large body of evidence suggests that regardless of the underlying etiology, heart failure is associated with induction of cytokines and chemokines that may contribute to the pathogenesis of adverse remodeling, and systolic and diastolic dysfunction. The pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 have been extensively implicated in the pathogenesis of heart failure. Inflammatory cytokines modulate phenotype and function of all myocardial cells, suppressing contractile function in cardiomyocytes, inducing inflammatory activation in macrophages, stimulating microvascular inflammation and dysfunction, and promoting a matrix-degrading phenotype in fibroblasts. Moreover, cytokine-induced growth factor synthesis may exert chronic fibrogenic actions contributing to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In addition to their role in adverse cardiac remodeling, some inflammatory cytokines may also exert protective actions on cardiomyocytes under conditions of stress. Chemokines, such as CCL2, are also upregulated in failing hearts and may stimulate recruitment of pro-inflammatory leukocytes, promoting myocardial injury, fibrotic remodeling, and dysfunction. Although experimental evidence suggests that cytokine and chemokine targeting may hold therapeutic promise in heart failure, clinical translation remains challenging. This review manuscript summarizes our knowledge on the role of TNF-α, IL-1, IL-6, and CCL2 in the pathogenesis of heart failure, and discusses the promises and challenges of targeted anti-cytokine therapy. Dissection of protective and maladaptive cellular actions of cytokines in the failing heart, and identification of patient subsets with overactive or dysregulated myocardial inflammatory responses are required for design of successful therapeutic approaches.
  • 4区Q3影响因子: 1.6
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    23. Irisin: linking metabolism with heart failure.
    23. Irisin:将新陈代谢与心力衰竭联系起来。
    作者:Li Jiamin , Xie Susu , Guo Lei , Jiang Jun , Chen Han
    期刊:American journal of translational research
    日期:2020-10-15
    The heart is an organ with extremely high energy expenditure, and cardiac performance is consistent with its metabolic level. Under pathological situations, the heart adjusts its metabolic pattern through mitochondrial regulation and substrate selection to maintain energy homeostasis. Heart failure is associated with impaired cardiac energy production, transduction or utilization. Reduced exercise tolerance, skeletal muscle dystrophy and even cardiac cachexia are commonly found in patients with advanced heart failure. Irisin is a newly identified myokine and is mainly secreted by skeletal muscles after exercise. Irisin regulates metabolism and plays essential roles in the development of metabolic diseases. The heart is another abundant source of irisin synthesis and secretion other than skeletal muscle. However, the functions of irisin in the heart have not been completely elucidated. This review introduces the current understanding of the physiological role of irisin, alteration of irisin levels in heart failure, possible mechanisms of irisin in metabolic remodeling and cardiac hypertrophy, and perspectives of irisin serving as a novel target in the management of heart failure.
  • 1区Q1影响因子: 10.8
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    24. Epidemiology of heart failure.
    24. 心力衰竭的流行病学。
    作者:Groenewegen Amy , Rutten Frans H , Mosterd Arend , Hoes Arno W
    期刊:European journal of heart failure
    日期:2020-06-01
    DOI :10.1002/ejhf.1858
    The heart failure syndrome has first been described as an emerging epidemic about 25 years ago. Today, because of a growing and ageing population, the total number of heart failure patients still continues to rise. However, the case mix of heart failure seems to be evolving. Incidence has stabilized and may even be decreasing in some populations, but alarming opposite trends have been observed in the relatively young, possibly related to an increase in obesity. In addition, a clear transition towards heart failure with a preserved ejection fraction has occurred. Although this transition is partially artificial, due to improved recognition of heart failure as a disorder affecting the entire left ventricular ejection fraction spectrum, links can be made with the growing burden of obesity-related diseases and with the ageing of the population. Similarly, evidence suggests that the number of patients with heart failure may be on the rise in low-income countries struggling under the double burden of communicable diseases and conditions associated with a Western-type lifestyle. These findings, together with the observation that the mortality rate of heart failure is declining less rapidly than previously, indicate we have not reached the end of the epidemic yet. In this review, the evolving epidemiology of heart failure is put into perspective, to discern major trends and project future directions.
  • 3区Q1影响因子: 5.3
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    25. Risk Factors for Heart Failure in the Community: Differences by Age and Ejection Fraction.
    25. 心力衰竭的危险因素:年龄和射血分数的差异。
    期刊:The American journal of medicine
    日期:2019-11-17
    DOI :10.1016/j.amjmed.2019.10.030
    BACKGROUND:Differences in comorbid conditions in patients with heart failure compared with population controls, and whether differences exist by type of heart failure or age, have not been well documented. METHODS:The prevalence of 17 chronic conditions were obtained in 2643 patients with incident heart failure from 2000 to 2013 and controls matched 1:1 on sex and age from Olmsted County, Minnesota. Logistic regression determined associations of each condition with heart failure. RESULTS:Among 2643 matched pairs (mean age 76.2 years, 45.6% men), the comorbidities with the largest attributable risk of heart failure were arrhythmia (48.7%), hypertension (28.4%), and coronary artery disease (33.9%); together these explained 73.0% of heart failure. Similar associations were observed for patients with reduced and preserved ejection fraction, with the exception of hypertension. The risk of heart failure attributable to hypertension was 2-fold higher in patients with heart failure with preserved ejection fraction (38.7%) than in patients with heart failure with reduced ejection fraction (17.8%). Hypertension, coronary artery disease, arrhythmia, and diabetes were more strongly associated with heart failure in younger (≤75 years) compared to older (>75 years) persons. CONCLUSIONS:Patients with heart failure have a higher prevalence of many chronic conditions than controls. Similar associations were observed in patients with reduced and preserved ejection fraction, with the exception of hypertension, which was more strongly associated with heart failure with preserved ejection fraction. Finally, some cardiometabolic risk factors were more strongly associated with heart failure in younger persons, highlighting the importance of optimizing prevention and treatment of risk factors and, in particular, cardiometabolic risk factors.
  • 3区Q2影响因子: 2.6
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    26. Interleukin-16 promotes cardiac fibrosis and myocardial stiffening in heart failure with preserved ejection fraction.
    26. Interleukin-16促进心肌纤维化和心肌僵硬在射血分数保留的心脏衰竭。
    作者:Tamaki Shunsuke , Mano Toshiaki , Sakata Yasushi , Ohtani Tomohito , Takeda Yasuharu , Kamimura Daisuke , Omori Yosuke , Tsukamoto Yasumasa , Ikeya Yukitoshi , Kawai Mari , Kumanogoh Atsushi , Hagihara Keisuke , Ishii Ryohei , Higashimori Mitsuru , Kaneko Makoto , Hasuwa Hidetoshi , Miwa Takeshi , Yamamoto Kazuhiro , Komuro Issei
    期刊:PloS one
    日期:2013-07-19
    DOI :10.1371/journal.pone.0068893
    BACKGROUND:Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosis, a crucial factor in HFpEF; however, inflammatory mechanisms and mediators involved in the development of HFpEF remain unclear. Therefore, we sought to identify novel inflammatory mediators involved in this process. METHODS AND RESULTS:An analysis by multiplex-bead array assay revealed that serum interleukin-16 (IL-16) levels were specifically elevated in patients with HFpEF compared with HFrEF and controls. This was confirmed by enzyme-linked immunosorbent assay in HFpEF patients and controls, and serum IL-16 levels showed a significant association with indices of LV diastolic dysfunction. Serum IL-16 levels were also elevated in a rat model of HFpEF and positively correlated with LV end-diastolic pressure, lung weight and LV myocardial stiffness constant. The cardiac expression of IL-16 was upregulated in the HFpEF rat model. Enhanced cardiac expression of IL-16 in transgenic mice induced cardiac fibrosis and LV myocardial stiffening accompanied by increased macrophage infiltration. Treatment with anti-IL-16 neutralizing antibody ameliorated cardiac fibrosis in the mouse model of angiotensin II-induced hypertension. CONCLUSION:Our data indicate that IL-16 is a mediator of LV myocardial fibrosis and stiffening in HFpEF, and that the blockade of IL-16 could be a possible therapeutic option for HFpEF.
  • 2区Q1影响因子: 8.2
    27. Drugs That Ameliorate Epicardial Adipose Tissue Inflammation May Have Discordant Effects in Heart Failure With a Preserved Ejection Fraction as Compared With a Reduced Ejection Fraction.
    27. 保留射血分数与降低射血分数相比,可改善心外膜脂肪组织炎症的药物可能对心力衰竭产生不同的影响。
    作者:Packer Milton
    期刊:Journal of cardiac failure
    日期:2019-09-18
    DOI :10.1016/j.cardfail.2019.09.002
    Heart failure with a preserved ejection fraction (HFpEF) and heart failure with a reduced ejection fraction (HFrEF) have distinctive pathophysiologies, and thus, therapeutic approaches to the 2 disorders should differ. Neurohormonal activation drives the progression of HFrEF, and neurohormonal antagonists are highly effective in HFrEF, but not in HFpEF. Conversely, a broad range of chronic systemic inflammatory or metabolic disorders cause an expansion and inflammation of epicardial adipose tissue; the secretion of adipocytokines may lead to microvascular dysfunction and fibrosis of the underlying myocardium, which (if the left atrium is affected) may lead to atrial fibrillation (AF) and (if the left ventricle is affected) may lead to HFpEF. Anti-inflammatory drugs (such as statins and anticytokine agents) can ameliorate epicardial adipose tissue dysfunction. Statins appear to ameliorate the development of atrial myopathy (both experimentally and clinically), and in randomized controlled trials, they reduce the incidence of new-onset and recurrent AF and decrease the risk of heart failure with the features of HFpEF; yet, they have no benefits in HFrEF. Similarly, anticytokine agents appear to prevent heart failure in patients with or prone to HFpEF, but adversely affect HFrEF. Several antihyperglycemic agents also reduce epicardial fat mass and inflammation, but this benefit may be offset by additional actions to cause sodium retention and neurohormonal activation. Thiazolidinediones have favorable effects on experimental AF and HFpEF, but their antinatriuretic actions negate these benefits, and they worsen the clinical course of HFrEF. Glucagon-like peptide-1 receptor agonists also ameliorate AF and HFpEF in laboratory models, but their positive inotropic and chronotropic effects may be deleterious in HFrEF. By contrast, metformin and sodium-glucose cotransporter 2 inhibitors alleviate epicardial adipose tissue dysfunction and may reduce the risk of AF and HFpEF; yet, they may have additional actions to promote cardiomyocyte survival that are useful in HFrEF. The concordance of the benefits of anti-inflammatory and antihyperglycemic drugs on AF and HFpEF (but not on HFrEF) supports the paradigm that epicardial adipose tissue is a central pathogenetic mechanism and therapeutic target for both AF and HFpEF in patients with chronic systemic inflammatory or metabolic diseases.
  • 2区Q1影响因子: 4.4
    28. Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning.
    28. 使用机器学习技术识别保留射血分数的心力衰竭中新的表型。
    作者:Hedman Åsa K , Hage Camilla , Sharma Anil , Brosnan Mary Julia , Buckbinder Leonard , Gan Li-Ming , Shah Sanjiv J , Linde Cecilia M , Donal Erwan , Daubert Jean-Claude , Mälarstig Anders , Ziemek Daniel , Lund Lars
    期刊:Heart (British Cardiac Society)
    日期:2020-01-07
    DOI :10.1136/heartjnl-2019-315481
    OBJECTIVE:Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups ('phenogroups') based on clinical and echocardiogram data using machine learning, and to compare clinical characteristics, proteomics and outcomes across the phenogroups. METHODS:We applied model-based clustering to 32 echocardiogram and 11 clinical and laboratory variables collected in stable condition from 320 HFpEF outpatients in the Karolinska-Rennes cohort study (56% female, median 78 years (IQR: 71-83)). Baseline proteomics and the composite end point of all-cause mortality or heart failure (HF) hospitalisation were used in secondary analyses. RESULTS:We identified six phenogroups, for which significant differences in the prevalence of concomitant atrial fibrillation (AF), anaemia and kidney disease were observed (p<0.05). Fifteen out of 86 plasma proteins differed between phenogroups (false discovery rate, FDR<0.05), including biomarkers of HF, AF and kidney function. The composite end point was significantly different between phenogroups (log-rank p<0.001), at short-term (100 days), mid-term (18 months) and longer-term follow-up (1000 days). Phenogroup 2 was older, with poorer diastolic and right ventricular function and higher burden of risk factors as AF (85%), hypertension (83%) and chronic obstructive pulmonary disease (30%). In this group a third experienced the primary outcome to 100 days, and two-thirds to 18 months (HR (95% CI) versus phenogroups 1, 3, 4, 5, 6: 1.5 (0.8-2.9); 5.7 (2.6-12.8); 2.9 (1.5-5.6); 2.7 (1.6-4.6); 2.1 (1.2-3.9)). CONCLUSIONS:Using machine learning we identified distinct HFpEF phenogroups with differential characteristics and outcomes, as well as differential levels of inflammatory and cardiovascular proteins.
  • 1区Q1影响因子: 5.3
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    29. Heart Rate-Induced Myocardial Ca Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction.
    29. 保留射血分数的心力衰竭患者的心率诱导心肌钙保留和左心室容积减少。
    作者:Silverman Daniel N , Rambod Mehdi , Lustgarten Daniel L , Lobel Robert , LeWinter Martin M , Meyer Markus
    期刊:Journal of the American Heart Association
    日期:2020-08-28
    DOI :10.1161/JAHA.120.017215
    Background Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca overload caused by increased myocardial Na levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension. Methods and Results In 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left-sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end-diastolic pressure in both groups (controls -4.3±4.1 mm Hg versus patients with HFpEF -8.5±6.0 mm Hg, =0.08). Pacing also reduced LV end-diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls -15%±14% versus patients with HFpEF -32%±11%, =0.009). Coronary venous [Ca] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na] did not change. Conclusions Higher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca retention.
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