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Hypersplenism: an independent risk factor for myocardial remodeling in chronic heart failure patients.

ABSTRACT: BACKGROUND:During the progression of chronic heart failure (CHF), decreased cardiac functioning is often associated with congestion in the inferior vena vein, which in turn induces splenomegaly and subsequent hypersplenism. Hypersplenism has been shown to exacerbate endothelial dysfunction and adverse cardiac remodeling in HF mice. However, it is unknown whether this effect also occurs in CHF patients with hypersplenism. Here, we compared different patterns of myocardial remodeling between patients with and without hypersplenism. METHODS:33 CHF patients with hypersplenism were selected and carefully examined. Clinical data and baseline hemogram measurements were included in the evaluation. Another 35 CHF patients were randomly chosen as controls. All patients received formal HF treatment to ameliorate their symptoms and to preserve heart structure and functioning. Peripheral blood-derived endothelial progenitor cells (EPCs) were cultured, and the experimenters were blinded to the patients' clinical characteristics. The biological properties of the cells were then compared. The groups were also compared in terms of the free plasma hemoglobin and heme levels, endothelial adhesion molecule expression, left ventricular ejection fraction (LvEF) and cardiovascular events (re-PCI, re-myocardial infarction, stent thrombosis, stroke and death due to cardiovascular or vascular causes). RESULTS:The free plasma hemoglobin and heme levels were significantly higher in the CHF patients with hypersplenism compared with the controls (P<0.001). Additionally, the CHF patients with hypersplenism had increased levels of VCAM-1, ICAM-1, P-selectin and E-selectin (P<0.001). Echocardiography revealed a significant reduction in the LVEF in these patients compared with the controls at the 24(th) month (P=0.013). During a mean follow-up period of 24±1 months, cardiovascular events were observed in 16 patients in the CHF with hypersplenism group and 9 patients in the control group. Univariate Kaplan-Meier analysis further revealed a significant difference between the groups (P=0.021). The mRNA levels of endothelial NO synthase enzyme (eNOS) in EPCs from the CHF patients with hypersplenism were significantly lower than those in the control subjects (P<0.001). We also observed decreased proliferation potential of EPCs from the CHF patients with hypersplenism (P<0.001). Further, a significant increase in TUNEL(+) EPCs was observed in the CHF patients with hypersplenism after 6 h of stimulated ischemia compared with the control subjects (P<0.001). CONCLUSIONS:CHF patients with hypersplenism are susceptible to myocardial remodeling. Increased oxidative stress and endothelial dysfunction caused by excess free plasma hemoglobin and heme may partially explain this causality.

SUBMITTER: Tang Y

PROVIDER: S-EPMC4483994 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Hypersplenism: an independent risk factor for myocardial remodeling in chronic heart failure patients.

Tang Yong Y Lu Wenbin W Zhang Ziwei Z Zuo Pengfei P Ma Genshan G

International journal of clinical and experimental medicine 20150415 4

<h4>Background</h4>During the progression of chronic heart failure (CHF), decreased cardiac functioning is often associated with congestion in the inferior vena vein, which in turn induces splenomegaly and subsequent hypersplenism. Hypersplenism has been shown to exacerbate endothelial dysfunction and adverse cardiac remodeling in HF mice. However, it is unknown whether this effect also occurs in CHF patients with hypersplenism. Here, we compared different patterns of myocardial remodeling betwe ...[more]

PMID: 26131093

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Project description:BackgroundGiven high on-treatment mortality in heart failure (HF), identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues. Circulating extracellular RNAs (ex-RNAs) regulate important biological processes and are emerging as biomarkers of disease, but less is known about their role in the acute setting, particularly in the setting of HF.MethodsWe examined the ex-RNA profiles of 296 acute coronary syndrome (ACS) survivors enrolled in the Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education Cohort. We measured 374 ex-RNAs selected a priori, based on previous findings from a large population study. We employed a two-step, mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes (left ventricular [LV] ejection fraction, LV mass, LV end-diastolic volume, left atrial [LA] dimension, and LA volume index) then tested relations of these ex-RNAs with prevalent HF (N=31, 10.5%). We performed further bioinformatics analysis of microRNA (miRNAs) predicted targets' genes ontology categories and molecular pathways.ResultsWe identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF. Of these 44 exRNAs, miR-29-3p, miR-584-5p, and miR-1247-5p were also associated with prevalent HF. The three microRNAs were implicated in the regulation p53 and transforming growth factor-β signaling pathways and predicted to be involved in cardiac fibrosis and cell death; miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation.ConclusionsAmong ACS survivors, we observed that miR-29-3p, miR-584-5p, and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF.Relevance for patientsmiR-29c-3p, miR-584-5p, and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF.

Project description:ImportanceMortality is high among patients heart failure (HF) who are receiving treatment, and therefore identifying new pathways rooted in preclinical cardiac remodeling phenotypes may afford novel biomarkers and therapeutic avenues. Circulating extracellular RNAs (ex-RNAs) are an emerging class of biomarkers with target-organ epigenetic effects relevant to myocardial biology, although large human investigations remain limited.ObjectiveTo measure the association of highly expressed circulating ex-RNAs with left ventricular remodeling and incident HF in a community-based cohort.Design, setting, and participantsThis is a prospective observational cohort study of individuals who were included in the eighth examination of the Framingham Offspring Cohort (2005-2008). Collected data include measurements of the left ventricle via electrocardiography, determination of circulating ex-RNAs in plasma, and incidence of heart failure. Data analysis was completed from December 2016 to June 2018.ExposuresA total of 398 circulating ex-RNA molecules in plasma were measured by reverse transcription polymerase chain reaction; disease ontology analysis was also performed.Main outcomes and measuresEchocardiographic indices of left ventricular (LV) remodeling and incident heart failure.ResultsA total of 2763 participants of the Framingham Heart Study with measured ex-RNAs (mean [SD] age, 66.3 [9.0] years; 1499 [54.3%] female) were included in this study. Of this sample, 2429 to 2432 individuals had echocardiographic measures recorded (depending on the measurement). A total of 2681 individuals had HF status determined, of whom 116 (4.3%) experienced HF (median [interquartile range] follow-up, 7.7 [6.6-8.6] years). We identified 12 ex-RNAs associated with LV mass and at least 1 other echocardiographic phenotype (LV end-diastolic volume or left atrial dimension). Of these 12 ex-RNAs, 3 micro RNAs (miR-17, miR-20a, and miR-106b) were associated with a 15% reduction in long-term incident HF per 2-fold increase in circulating level during the follow-up period, after adjustments for age, sex, established HF risk factors, and prevalent or interim myocardial infarction. These 3 RNAs shared sequence homology and targeted a shared group of messenger RNAs that specified pathways relevant to HF (eg, transforming growth factor-? signaling, growth/cell cycle, and apoptosis), and shared a disease association with hypertension in disease ontology analysis.Conclusions and relevanceThis study identifies a group of circulating, noncoding RNAs associated with echocardiographic phenotypes, long-term incident HF, and pathways relevant to myocardial remodeling in a large community-based sample. Further investigations into the functional biology of these ex-RNAs are warranted for surveillance for HF prevention.

Project description:(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR-). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (-9.7 ± 5.2% vs. -7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined.

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Hypersplenism: an independent risk factor for myocardial remodeling in chronic heart failure patients.

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Hypersplenism: an independent risk factor for myocardial remodeling in chronic heart failure patients.

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