Systolic Dysfunction Heart Failure Research Articles

Leukocyte Extracellular Vesicles Predict Progression of Systolic Dysfunction in Heart Failure with Mildly Reduced Ejection Fraction (LYCHEE) - A Prospective, Multicentre Cohort Study.

Risk stratification in heart failure with mildly-reduced ejection fraction (HFmrEF) remains challenging. We evaluated the predictive value of advanced glycation end products (AGEs) and plasma concentrations of extracellular vesicles (EVs) for the systolic and diastolic dysfunction progression in HFmrEF patients. Skin AGE accumulation was measured using AGE Reader. Plasma EV concentrations were measured using flow cytometry. Among 74 patients enrolled, 13 (18%) had systolic dysfunction progression and 5 (7%) had diastolic dysfunction progression during 6.5months follow-up. Leukocyte EVs concentrations were higher in patients with systolic dysfunction progression (p = 0.002) and predicted the progression with 75.0% sensitivity and 58.3% specificity, independent of other clinical variables (OR 4.72, 95% CI 0.99-22.31). Skin AGE levels and concentrations of other EV subtypes were not associated with systolic or diastolic dysfunction progression. Increased leukocyte EVs concentrations are associated with 4.7-fold higher odds of systolic dysfunction progression in HFmrEF patients.

Total 25-Hydroxyvitamin D Is an Independent Marker of Left Ventricular Ejection Fraction in Heart Failure with Reduced and Mildly Reduced Ejection Fraction.

Vitamin D emerged as an important prognostic biomarker in heart failure (HF), with currently highly debated therapeutic implications. Several trials on vitamin D supplementation in HF showed improvements in left ventricular (LV) remodeling and function and health-related quality of life (HRQoL), which did not translate into mid- to long-term beneficial effects regarding physical performance and mortality. We addressed total 25-hydroxyvitamin D (25(OH)D), serum albumin, and uric acid (UA) levels, focusing mainly on vitamin D deficiency, as potential markers of LV systolic dysfunction in HF with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Seventy patients with LVEF < 50% were comprehensively evaluated using ECG, echocardiography, lung ultrasound (LUS), blood sampling, and the six-minute walk test (6MWT). HRQoL was also assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Statistically significant positive correlations were found between LVEF, 25(OH)D, serum UA, and albumin, respectively (p = 0.008, p = 0.009, and p = 0.001). Serum UA (7.4 ± 2.4 vs. 5.7 ± 2.1, p = 0.005), NT-proBNP levels (1090.4 (675.2-2664.9) vs. 759.0 (260.3-1474.8), p = 0.034), and MLHFQ scores (21.0 (14.0-47.0) vs. 14.5 (4.5-25.5), p = 0.012) were significantly higher, whereas 25(OH)D concentrations (17.6 (15.1-28.2) vs. 22.7 (19.5-33.8), p = 0.010) were lower in subjects with severely reduced LVEF. Also, 25(OH)D was independently associated with LVEF in univariate and multiple regression analysis, maintaining its significance even after adjusting for confounders such as age, NT-proBNP, the presence of chronic coronary syndrome, hypertension, and anemia. According to our current findings, 25(OH)D is closely associated with LVEF, further supporting the need to establish correct vitamin D supplementation schemes and dietary interventions in HF. The changes in LVEF, 25(OH)D, serum UA, and albumin levels in HFrEF and HFmrEF indicate a similar pathophysiological background.

Hemodynamic force analysis is not ready for clinical trials on HFpEF

Hemodynamic force analysis has been proposed as a novel tool for early detection of subclinical systolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Here we investigated the ability of hemodynamic forces to discriminate between healthy subjects and heart failure patients with varying degrees of systolic dysfunction. We studied 34 controls, 16 HFpEF patients, and 25 heart failure patients with mid-range (HFmrEF) or reduced ejection fraction (HFrEF) using cardiac magnetic resonance with acquisition of cine images and 4D flow at 1.5 T. The Navier–Stokes equation was used to compute global left ventricular hemodynamic forces over the entire cardiac cycle. Forces were analyzed for systole, diastole, and the entire heartbeat, with and without normalization to left ventricular volume. Volume-normalized hemodynamic forces demonstrated significant positive correlation with EF (r2 = 0.47, p < 0.0001) and were found significantly lower in heart failure with reduced ejection fraction compared to controls (p < 0.0001 for systole and diastole). No difference was seen between controls and HFpEF (p > 0.34). Non-normalized forces displayed no differences between controls and HFpEF (p > 0.24 for all analyses) and did not correlate with EF (p = 0.36). Left ventricular hemodynamic force analysis, whether indexed to LV volumes or not, is not ready for clinical trials on HFpEF assessment.

Overexpression of MCU vs. mito-ROS scavenging to attenuate proarrhythmic spontaneous Ca2+ release in diseased ventricular myocytes

Systolic dysfunction in heart failure and diabetic cardiomyopathy is associated with diminished Ca2+ transient amplitude and impaired mitochondrial function due to reduced mito-[Ca2+], in parallel with increased emission of mitochondrial reactive oxygen species (mito-ROS). Restoration of mito-[Ca2+] in diseased myocytes as a therapeutic approach remains contentious, as facilitation of mito-Ca2+ uptake has been shown to both protect against and exacerbate stress-induced Ca2+ dependent arrhythmia.

Mitochondrial Calcium Uniporter Overexpression Exacerbates Arrhythmogenic Calcium Mishandling in Diseased Rat Ventricular Myocytes

Systolic dysfunction in heart failure (HF) and diabetic cardiomyopathy (DCM) is associated with diminished Ca2+ transient amplitude and impaired mitochondrial function due to reduced mitochondrial [Ca2+]. Pharmacological or genetic facilitation of mito-Ca2+ uptake was shown to restore Ca2+ transient amplitude in DCM and HF, improving contractility. However, recent reports suggest that acute pharmacological enhancement of mito-Ca2+ uptake can exacerbate spontaneous Ca2+ release in myocytes from diseased animals, increasing propensity to stress-induced arrhythmias. To test whether chronic recovery of mito-[Ca2+] restores systolic Ca2+ release without adverse effects in diastole, we overexpressed mitochondrial Ca2+ uniporter (MCU) in ventricular myocytes (VMs) from rat hearts with hypertrophy induced by thoracic aortic banding (TAB). Measurement of mito-[Ca2+] using genetic probe mtRCamp1h revealed that mito-[Ca2+] in TAB VMs paced at 1 Hz under β-adrenergic stimulation is significantly lower than in Shams. Adenoviral MCU overexpression in TAB VMs restored mito-[Ca2+]. Confocal imaging of VMs loaded with fluorescent indicator Rhod-2 revealed that MCU overexpression in TAB VMs reversed the decrease in Ca2+ transient amplitude. Importantly, the decay of caffeine-induced Ca2+ transient in MCU-overexpressing TAB VMs was prolonged, indicative of decreased NCX activity. Moreover, MCU overexpression in TAB VMs was accompanied by a further increase in incidence of proarrhythmic spontaneous Ca2+ waves, suggesting exacerbation of RyR2 dysfunction. Experiments using genetic probe OMM-HyPer showed a 10-fold increase in mito-ROS emission in TAB VMs overexpressing MCU. Importantly, application of mito-ROS scavenger mitoTEMPO (20 µM, 10 min) restored Ca2+ transient amplitude, reduced spontaneous Ca2+ waves and restored mito-[Ca2+] in TAB VMs, rendering them normal. These findings suggest that restoration of mito-[Ca2+] in VMs from diseased hearts by MCU overexpression improves systolic Ca2+ release possibly via reduced NCX-mediated Ca2+ efflux, but exacerbates increased mito-ROS and RyR2 activity, increasing arrhythmic potential.

Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner

ABSTRACT Despite the existing association of gut dysbiosis and T cell inflammation in heart failure (HF), whether and how gut microbes contribute to T cell immune responses, cardiac fibrosis and dysfunction in HF remains largely unexplored. Our objective was to investigate whether gut dysbiosis is induced by cardiac pressure overload, and its effect in T cell activation, adverse cardiac remodeling, and cardiac dysfunction. We used 16S rRNA sequencing of fecal samples and discovered that cardiac pressure overload-induced by transverse aortic constriction (TAC) results in gut dysbiosis, characterized by a reduction of tryptophan and short-chain fatty acids producing bacteria in WT mice, but not in T cell-deficient mice (Tcra−/- ) mice. These changes did not result in T cell activation in the gut or gut barrier disruption. Strikingly, microbiota depletion in WT mice resulted in decreased heart T cell infiltration, decreased cardiac fibrosis, and protection from systolic dysfunction in response to TAC. Spontaneous reconstitution of the microbiota partially reversed these effects. We observed decreased cardiac expression of the Aryl hydrocarbon receptor (AhR) and enzymes associated with tryptophan metabolism in WT mice, but not in Tcra−/- mice, or in mice depleted of the microbiota. These findings demonstrate that cardiac pressure overload induced gut dysbiosis and T cell immune responses contribute to adverse cardiac remodeling, and identify the potential contribution of tryptophan metabolites and the AhR to protection from adverse cardiac remodeling and systolic dysfunction in HF.

Role of global longitudinal strain in assessment of left ventricular systolic function in patients with heart failure with preserved ejection fraction

ObjectivesTo detect systolic dysfunction in heart failure with preserved ejection fraction (HFpEF) patients by using global longitudinal strain (GLS). MethodsThis study included 46 heart failure patients: 24 with heart failure with reduced ejection fraction (HFrEF) and 22 with heart failure with preserved ejection fraction (HFpEF), and 20 patients with similar risk factor but no symptoms or signs of heart failure, matched for age and sex, as controls. All patients were screened by echocardiography. The ejection fraction of left ventricle was measured using Simpson’s method and the GLS of the left ventricle was measured by using two-dimensional speckle tracking. ResultsLeft ventricular ejection fraction (LVEF) was 61.90 ± 2.94% in the controls, 60.45 ± 7.4% in the HFpEF group (p = 0.421), and 32.75 ± 8.45% in the HFrEF group (p = 0.001). The value of left ventricle (LV) GLS (controls = −19.74 ± 1.12%, HFpEF = −15.03 ± 2.03%, HFrEF = −10.72 ± 1.99%, p = 0.0001) was significantly impaired in the HFpEF group despite normal LVEF. ConclusionThere is significant left ventricular systolic impairment detected by GLS despite preserved LVEF.

Characterization of left ventricle function in chronic TNF-mediated experimental arthritis

Background: Patients with Rheumatoid Arthritis (RA) have an increased risk for cardiovascular disorders. RA is often associated with left ventricle (LV) systolic dysfunction, however the contribution of chronic inflammatory burden on cardiac functional impairment is not completely understood. Recently, LV systolic dysfunction in heart failure is associated with the down regulation and impairment of neuregulin-1 (NRG1)/Receptor Tyrosine Kinase 2 and 4 (Erbb2 and Erbb4) pathway. Aim: To address potential cardiac dysfunction in association with the expression of inflammatory cytokines and chemokines as well as NRG1/Erbb in LV tissue samples in a chronic TNF-driven inflammatory, erosive arthritis model.

In Silico Analysis of Differential Gene Expression in Three Common Rat Models of Diastolic Dysfunction.

Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences. The top differentially expressed genes in the left ventricle of Dahl salt sensitive (Dahl/SS), spontaneous hypertensive heart failure (SHHF), and diabetes 1 induced HFpEF models were derived from published data in Gene Expression Omnibus and used for a comprehensive interpretation of the underlying pathophysiological context of each model. The diversity of the underlying transcriptomic of the heart of each model is clearly observed by the different panel of top regulated genes: the diabetic model has 20 genes in common with the Dahl/SS and 15 with the SHHF models. Advanced analytics performed in Ingenuity Pathway Analysis (IPA®) revealed that Dahl/SS heart tissue transcripts triggered by upstream regulators lead to dilated cardiomyopathy, hypertrophy of heart, arrhythmia, and failure of heart. In the heart of SHHF, a total of 26 genes were closely linked to cardiovascular disease including cardiotoxicity, pericarditis, ST-elevated myocardial infarction, and dilated cardiomyopathy. IPA Upstream Regulator analyses revealed that protection of cardiomyocytes is hampered by inhibition of the ERBB2 plasma membrane-bound receptor tyrosine kinases. Cardioprotective markers such as natriuretic peptide A (NPPA), heat shock 27 kDa protein 1 (HSPB1), and angiogenin (ANG) were upregulated in the diabetes 1 induced model; however, the model showed a different underlying mechanism with a majority of the regulated genes involved in metabolic disorders. In conclusion, our findings suggest that multiple mechanisms may contribute to diastolic dysfunction and HFpEF, and thus drug therapies may need to be guided more by phenotypic characteristics of the cardiac remodeling events than by the underlying molecular processes.

Prognostic impact of diastolic dysfunction in systolic heart failure-A cross-project analysis from the German Competence Network Heart Failure.

We investigated the modifying role and prognostic importance of diastolic dysfunction (DD) in patients with heart failure and systolic dysfunction (SD). The echocardiographic evaluation of diastolic function in patients with SD provides further prognostic information. From the German Competence Network Heart Failure, 1046 heart failure patients with reduced left ventricular ejection fraction (LVEF; <50%) were echocardiographically studied and followed for a median of 5 years. SD was subdivided into nonsevere (LVEF 36%-49%) and severe (LVEF ≤35%); DD was subdivided into nonsevere (E/E' <15) and severe (E/E' ≥15). In general, severe SD was associated with higher hazard ratios (HRs; 2-fold to 3.5-fold) for all endpoints (all-cause death, cardiac death, cardiovascular hospitalization, duration of hospitalization). Patients with severe SD had a 2.5-fold risk of death (95% confidence interval [CI]: 1.84-3.47, P < 0.001), and patients with severe DD showed a 1.8-fold risk (95% CI: 1.17-2.61, P = 0.004). Furthermore, we observed a strong interaction of SD and DD: concomitant severe DD in patients with moderate SD increased risk substantially (HR: 1.73, 95% CI: 1.16-2.6, P = 0.007); by contrast, in patients with severe SD, additional presence of severe DD added little or no risk (HR for interaction: 0.5-1.2). In heart failure patients with reduced LVEF, the evaluation of diastolic function provides additional prognostic information. Although severe SD generally increased the risk for all endpoints, the degree of DD and its impact as a prognostic marker for overall and cardiovascular mortality appeared of particular relevance in subjects with nonsevere SD.

LCZ696: The Next Step in Improving RAS Inhibition?

LCZ696 is a single molecule which combines the angiotensin receptor blocker valsartan with the neprilysn inhibitor sacubitril (AHU377). In the recently published PARADIGM-HF trial, LCZ696 proved superior to enalapril in reducing overall mortality, heart failure hospitalizations, and other endpoints in patients with systolic dysfunction heart failure. Increases in counter-regulatory natriuretic peptides which oppose sodium retention, vasoconstriction, and the deleterious structural changes which follow neurohormonal activation are thought to account for these improved outcomes. In two large hypertension studies, LCZ696 has proved to be a potent, effective antihypertensive agent with tolerability similar to valsartan and placebo and potency comparable to amlodipine. Although several have occurred in the heart failure population, there have been no cases of angioedema noted in the hypertension trials, although few black patients-a group at high risk for its occurrence-have been studied. Whether LCZ696 will displace angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) as preferred renin-angiotensin system (RAS) blocking agents in hypertension will require demonstration of improved long-term outcomes compared with currently preferred first-line drugs. In this regard, experience has shown that it is difficult to extrapolate results achieved in heart failure to the treatment of hypertension, a condition in which neurohormonal activation is less critical in determining long-term prognosis. It will be particularly important to demonstrate renal protection with LCZ696 in patients with diabetes, proteinuria, and hypertension-the only therapeutic area other than heart failure in which RAS blockade has proved essential for optimal endpoint reduction. Superiority over available RAS blockers in terms of 'vascular protection' in high-risk populations represents another path to acceptance of LCZ696 as a preferred agent in cardiovascular medicine.

Prevalence and prognostic significance of right ventricular systolic dysfunction in heart failure with preserved ejection fraction. Insights from a cardiac magnetic resonance imaging study

Background Cardiac magnetic resonance imaging (CMR) is the goldstandard technique for the assessment of right ventricular function. Recent data indicate that right ventricular ejection fraction (RVEF) <45% by CMR is a strong predictor of outcome in patients with dilated cardiomyopathy. However, the prognostic significance of RVEF in heart failure with preserved ejection fraction (HFpEF) is unknown.

Evaluation of Left Atrial Two-Dimensional Strain in Patients with Systolic Heart Failure using Velocity Vector Imaging

were obtained from apical views. Results: A significant differences in LA volume index (LAVI) and strain were found in patients with systolic heart failure (SHF) versus normal subjects (23.8 ± 4.1 versus 57.8 ± 19.7 ml/m 2 , P < 0.001 and 39.6 ± 10.6 versus 8.2 ± 5.3%, P < 0.001). Multivariate analysis of separate walls revealed significant inverse relationship between LA size and volume with total and regional (2-ch view) 2D strains of LA. Significant inverse relationship were also detected between pulmonary artery systolic pressure and both total LA strain (22 ± 8 versus 42 ± 10 mmHg, r = -0.4, P < 0.001) and LA strain in 2-chamber (r = -0.5, P < 0.001). A cutoff value of total average LA strain (≥ 23.28%) can differentiate normal and abnormal LA function with a sensitivity of 93% and specificity of 100% and a cutoff value of total LA strain (in average) of 17.2% can differentiate mild and moderate and severe diastolic dysfunction with a sensitivity of 100% and a specificity of 97%. Conclusions: LA strain seems to be a better determinant for diagnosis of abnormal LA function and the degree of diastolic dysfunction in SHF.

Prognostic value of right ventricular systolic dysfunction in heart failure with preserved ejection fraction

Prognostic value of right ventricular systolic dysfunction in heart failure with preserved ejection fraction

Gender and Other Disparities in Referral to Specialized Heart Failure Clinics Following Emergency Department Visits

Persons with heart failure (HF) at high risk for adverse events should be followed by specialized HF clinics, since follow-up by specialized HF clinics improves outcomes for HF patients. The objective was to determine whether there were disparities for gender and other factors associated with referral of patients to specialized HF clinics. In this prospective cohort study, patients with a confirmed primary diagnosis of HF were recruited by nurses at 8 hospital emergency departments (ED) in Québec, Canada. They were interviewed by telephone at 6 weeks post ED discharge and subsequently at 3 months and 6 months. Pertinent clinical variables were extracted from medical charts by trained nurses. Bivariate analysis and multiple logistic regression were used to identify whether gender and other potential factors were associated with referral to the HF clinic. We enrolled 549 patients (mean age 75.5±11.0 years; 51% males). By 6 months after their ED visit for HF, 37.6% of the cohort were referred to specialized HF clinics. Men were more likely to be referred (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.12, 3.74). Other factors associated with referral were younger age (OR 0.95; 95% CI 0.92, 0.98), and systolic dysfunction HF (left ventricle ejection fraction <40%) (OR 3.08; 95% CI 1.77, 5.46). There are disparities in referral with respect to gender, age, and type of HF. These disparities in referral need to be addressed.

Predictors of Right Ventricular Systolic Dysfunction in Compensated and Decompensated Heart Failure

Current understanding of the mechanisms of right ventricular (RV) systolic dysfunction in heart failure (HF) is limited. The authors analyzed a limited access dataset from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) provided by the National Heart, Lung, and Blood Institute (NHLBI). RV systolic function was measured by echocardiography at baseline and at 3-month follow-up using fractional area change. Univariate and multivariate analysis was performed with linear regression. Of 433 patients enrolled in the ESCAPE trial, 190 had RV systolic function measured at baseline (decompensated HF) and 147 had it measured at 3-month follow-up. On both occasions, parameters of congestion were associated with RV systolic function. Interestingly, lower hematocrit level was also associated with better RV systolic function. In multivariate analysis, only wedge pressure remained a statistically significant predictor of RV dysfunction. In summary, cardiac diastolic pressures and corresponding echocardiographic parameters, as well as hematocrit level, predicted RV systolic function in both compensated and decompensated systolic HF.

Ryanodine Receptor S2808 Phosphorylation in Heart Failure

In this issue of Circulation Research , Zhang et al1 provide direct and clear evidence that phosphorylation of S2808 in the cardiac ryanodine receptors (RyR2) has no impact on either normal cardiac function, sympathetic stimulation of the heart, or progression of heart failure (HF) after myocardial infarction (MI). They used mice in which the S2808 site was rendered nonphosphorylatable in S2808A knock-in mice, and the results directly contradict results published by the group of A.R. Marks.2–4 This has been a highly controversial area. This new study compels me to assess this pathway in a balanced way, but recognizing that my opinions are influenced by work that my group has done in this area. My goal here is not to microdissect each controversial piece of data in dozens of relevant papers (see recent reviews and tables5,6), but rather to provide my informed opinion about key aspects of this issue in a balanced manner. Let us first consider the model that importantly raised the issue of SR Ca leak as a potential pathophysiological cardiac effect in HF. Article, see p 831 In 2000 the Marks group published an exciting and seminal paper that has fueled intensive research over the past 11 years.7 They proposed that in HF, PKA hyperphosphorylates RyR2-S2808, causing FKBP12.6 dissociation from RyR2, which directly enhances SR Ca leak/depletion and systolic dysfunction in HF (Figure). Tenets later added to this core model were a down-regulation of phosphatases associated with the RyR2 in HF (which would facilitate the PKA-dependent RyR2 hyperphosphorylation) and that this diastolic SR Ca leak could also contribute to triggered arrhythmias. An extensive series of papers by the same group since then have provided highly consistent and compelling support for this working hypothesis, extending the impact of this intriguing PKA/RyR-S2808/FKBP12.6/RyR …

Renal Dysfunction Is a Stronger Determinant of Systemic Neutrophil Gelatinase–Associated Lipocalin Levels Than Myocardial Dysfunction in Systolic Heart Failure

Background Neutrophil gelatinase–associated lipocalin (NGAL) is released by renal tubular cells in response to inflammation and injury. Recent studies have demonstrated that NGAL is up-regulated in cardiomyocytes within the failing myocardium. However, the overall relationship between systemic NGAL levels and myocardial structure and performance has not been established. Methods and Results We measured systemic NGAL levels in 130 subjects with chronic systolic heart failure (HF) and comprehensive echocardiographic evaluation, as well as 69 subjects with acute decompensated systolic HF and hemodynamic evaluation. In the chronic HF cohort, higher plasma NGAL levels were modestly associated with increasing age ( r = 0.18; P = .035), higher New York Heart Association functional class (rank sums: P = .022) and impaired renal function (eGFR: r = −0.53; P < .0001; cystatin C: r = 0.60; P < .0001). Plasma NGAL levels were modestly associated with indices of diastolic dysfunction (mitral E/Ea: r = 0.27; P = .002; LAVi: r = 0.25; P = .011; tricuspid E/Ea: r = 0.20; P = .029), but not after adjustment for renal function ( P > .10 for all). In Cox proportional hazards analysis, plasma NGAL predicted cardiac death or transplantation after adjustment for age, gender, left ventricular ejection fraction, and mitral E/Ea (hazard ratio 1.68, 95% confidence interval 1.08–2.57; P = .022), but not after adjustment for renal function ( P = .83). In the acute HF cohort, we did not observe any relationship between NGAL and hemodynamic indices, but NGAL strongly correlated with renal function. Conclusions Systemic NGAL levels are largely determined by underlying impairment of renal rather than myocardial function. Our findings did not support any prognostic significance or relationship between systemic NGAL levels and indices of cardiac structure and function after adjustment for underlying renal function.

Adiponectin and Myocardial Performance in Chronic Systolic Heart Failure: Potential Role in Compensation for Endothelial Dysfunction

Background: Plasma adiponectin levels are elevated in patients with chronic systolic heart failure (HF) and associated with adverse outcomes. In contrast, low adiponectin levels are related to endothelial dysfunction in non-HF setting. Herein, we examine the relationship between adiponectin and endothelial dysfunction in systolic HF. Methods: In 139 patients with HF (left ventricular [LV] ejection fraction ≤35%, NYHA functional class II-IV), we measured plasma adiponectin and asymmetric dimetharginine (ADMA, surrogate of endothelial dysfunction) levels and performed comprehensive echocardiography with assessment of cardiac structure and performance.

Mineralocorticoid receptors, corticosteroids and the heart: where do we stand?

Mineralocorticoid receptors, corticosteroids and the heart: where do we stand?