Human leukocyte antigen-G is upregulated in heart failure patients: a potential novel biomarker

Immune activation and inflammation play critical roles in the development of heart failure (HF). Human leukocyte antigen-G (HLA-G) is a nonclassical, major histocompatibility complex class I (MHC-I) protein, upregulated in the context of transplantation, malignancy, and inflammation, and has been correlated with various clinical outcomes. We sought to evaluate the utility of plasma HLA-G in identifying patients with HF. We conducted a single-center, cross-sectional pilot study involving 82 patients diagnosed with HF and 10 healthy controls. Concentrations of circulating HLA-G and inflammatory markers were detected with specific enzyme-linked immunosorbent assay kits and quantified according to purified protein standards. The mean age of the patients was 49.1 ± 12.0 years and 62.2% were male. The median and interquartile range of HLA-G levels (U/ml) were significantly higher (p < 0.001) in HF patients (63, 36-98) compared with controls (28, 22-40). Moreover, HLA-G levels that were similarly (p = 0.766) upregulated across all New York Heart Association functional classes. There was no significant correlation between serum HLA-G and other biomarkers. In conclusion, HLA-G is upregulated in patients diagnosed with HF. Its marked elevation even in New York Heart Association class I patients might indicate that serum HLA-G is a more sensitive marker than other classical HF biomarkers.     

Burden of respiratory viruses in patients with acute respiratory failure

Respiratory viruses (RVs) are ubiquitous pathogens that represent a major cause of community‐acquired pneumonia and chronic pulmonary diseases exacerbations. However, their contribution to acute respiratory failure events requiring intensive care unit admission in the era of rapid multiplex molecular assay deserves further evaluation. This study investigated the burden of viral infections in non immunocompromised patients admitted to the intensive care unit for acute respiratory failure using a multiplex molecular assay. Patients were investigated for RVs using immunofluoresence testing and a commercial multiplex molecular assay, and for bacteria using conventional culture. Half the patients (34/70, 49%) had a documented RVs infection. No other pathogen was found in 24 (71%) patients. Viral infection was detected more frequently in patients with obstructive respiratory diseases (64% vs. 29%; P = 0.0075). Multiplex molecular assay should be considered as an usefull diagnostic tool in patients admitted to the intensive care unit with acute respiratory failure, especially those with acute exacerbations of chronic obstructive pulmonary disease and asthma. J. Med. Virol. 86:1198–1202, 2014. © 2013 Wiley Periodicals, Inc.

     

Heart rate dynamics during a treadmill cardiopulmonary exercise test in optimized beta-blocked heart failure patients

BACKGROUND: Calculating the maximum heart rate for age is one method to characterize the maximum effort of an individual. Although this method is commonly used, little is known about heart rate dynamics in optimized beta-blocked heart failure patients. AIM: The aim of this study was to evaluate heart rate dynamics (basal, peak and % heart rate increase) in optimized beta-blocked heart failure patients compared to sedentary, normal individuals (controls) during a treadmill cardiopulmonary exercise test. METHODS: Twenty-five heart failure patients (49+/-11 years, 76% male), with an average LVEF of 30+/-7%, and fourteen controls were included in the study. Patients with atrial fibrillation, a pacemaker or noncardiovascular functional limitations or whose drug therapy was not optimized were excluded. Optimization was considered to be 50 mg/day or more of carvedilol, with a basal heart rate between 50 to 60 bpm that was maintained for 3 months. RESULTS: Basal heart rate was lower in heart failure patients (57+/-3 bpm) compared to controls (89+/-14 bpm; p<0.0001). Similarly, the peak heart rate (% maximum predicted for age) was lower in HF patients (65.4+/-11.1%) compared to controls (98.6+/-2.2; p<0.0001). Maximum respiratory exchange ratio did not differ between the groups (1.2+/-0.5 for controls and 1.15+/-1 for heart failure patients; p=0.42). All controls reached the maximum heart rate for their age, while no patients in the heart failure group reached the maximum. Moreover, the % increase of heart rate from rest to peak exercise between heart failure (48+/-9%) and control (53+/-8%) was not different (p=0.157). CONCLUSION: No patient in the heart failure group reached the maximum heart rate for their age during a treadmill cardiopulmonary exercise test, despite the fact that the percentage increase of heart rate was similar to sedentary normal subjects. A heart rate increase in optimized beta-blocked heart failure patients during cardiopulmonary exercise test over 65% of the maximum age-adjusted value should be considered an effort near the maximum. This information may be useful in rehabilitation programs and ischemic tests, although further studies are required.     

Sleep–wake fluctuations and respiratory events during Cheyne–Stokes respiration in patients with heart failure

Fluctuations in sleep–wake state are thought to contribute to the respiratory instability of Cheyne–Stokes respiration in patients with heart failure by promoting the rhythmic occurrence of central apnea and ventilatory overshoot. There are no data, however, on the relationship between vigilance state and respiratory events. In this study we used a novel method to detect the occurrence of state transitions (time resolution: 0.25 s, minimum duration of state changes: 2 s) and to assess their time relationship with apnoeic events. We also evaluated whether end‐apnoeic arousals are associated with a ventilatory overshoot. A polysomnographic, daytime laboratory recording (25 min) was performed during Cheyne–Stokes respiration in 16 patients with heart failure. Automatic state classification included wakefulness and non‐rapid eye movement sleep stages 1–2. As a rule, wakefulness occurred during hyperpnoeic phases, and non‐rapid eye movement sleep occurred during apnoeic events. Ninety‐two percent of the observed central apneas (N = 272) were associated with a concurrent wakefulness → non‐rapid eye movement sleep → wakefulness transition. The delay between wakefulness → non‐rapid eye movement sleep transitions and apnea onset was ?0.3 [?3.1, 3.0] s [median (lower quartile, upper quartile); P = 0.99 testing the null hypothesis: median delay = 0], and the delay between non‐rapid eye movement sleep → wakefulness transitions and apnea termination was 0.2 [?0.5, 1.2] s (P = 0.7). A positive/negative delay indicates that the state transition occurred before/after the onset or termination of apnea. Non‐rapid eye movement sleep → wakefulness transitions synchronous with apnea termination were associated with a threefold increase in tidal volume and a twofold increase in ventilation (all P < 0.001), indicating ventilatory overshoot. These findings highlight that wakefulness → non‐rapid eye movement sleep → wakefulness transitions parallel apnoeic events during Cheyne–Stokes respiration in patients with heart failure. The relationships between state changes and respiratory events are consistent with the notion that state fluctuations promote ventilatory instability.     

Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs

In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.     

慢性心力衰竭患者血浆瘦素水平的变化

目的： 研究慢性心力衰竭（CHF）患者血浆瘦素（leptin）水平的变化。方法：应用放射免疫法测定了60例CHF患者和26例健康对照者的血浆瘦素水平，比较CHF组与对照组、CHF组不同心衰级别及不同病因亚组间的血浆瘦素水平。结果：CHF组患者血浆瘦素水平明显高于对照组（P＜0.01）；心功能Ⅳ级患者的血浆瘦素水平明显高于心功能Ⅲ级患者（P＜0.01）；CHF不同病因亚组间血浆瘦素水平无显著差异（P＞0.05）。结论：CHF患者血浆瘦素水平升高，并与心衰的严重程度相关，而与引起心衰的病因无关。     

Respiratory syncytial virus in critically ill adult patients with community-acquired respiratory failure: a prospective observational study

The incidence of respiratory syncytial virus (RSV) and influenza virus infection was determined during three RSV seasons in 158 adult patients consecutively admitted to the intensive care unit with community-acquired respiratory failure. Nasopharyngeal swabs were tested for the presence of RSV and influenza virus by real-time polymerase chain reaction. Six patients (4%) were positive for RSV and all recovered. This finding was in sharp contrast to influenza (23 (15%) patients, 4 (17%) deaths). In conclusion, even in the midst of the RSV season, RSV is an infrequent cause of respiratory failure in adults admitted to the intensive care unit.     

Positive affect dimensions and their association with inflammatory biomarkers in patients with chronic heart failure

Background

In cardiac patients positive affect has found to be associated with improved clinical outcomes, with reduced inflammation being one of the potential mechanisms responsible.

Methods

Positive affect was assessed using The Global Mood Scale (GMS), Positive and Negative Affect Schedule (PANAS), and Hospital Anxiety and Depression Scale (HADS) in patient with chronic heart failure (N = 210; 67 ± 9 years, 79% men). Markers of inflammation (TNFα, sTNFr1, sTNFr2, IL-6 and CRP) were measured and averaged at three consecutive time points.

Results

The positive affect dimensions of the GMS and PANAS were significantly associated with lower averaged levels of sTNFr2, TNFα and IL-6 (p < .1), even after adjustment for clinical and lifestyle confounders. Positive affect of the HADS was significantly associated with lower averaged levels of hsCRP (p < .1), but was no longer significant after correction for lifestyle confounders and depressive symptoms.

Conclusion

Positive affect is associated with reduced inflammation in patients with heart failure.     

免疫炎症机制在心力衰竭进展中的作用

心肾学说和心脏循环病理生理理论的建立,使心衰患者从利尿剂、血管扩张剂及正性肌力药物中获益。随着神经内分泌激素模式的建立,心衰的药物治疗发生了重大变革,血管紧张素转化酶抑制剂（ACEI）、β受体阻滞剂、醛固酮受体拮抗剂成为当今心衰的标准治疗措施。尽管拥有最先进的治疗措施,心衰的发病率和死亡率依然居高不下,心衰的重要致病机制并未完全阐明,因而研究心衰的致病机制显得尤为重要。     

Biological significance of miR-126 expression in atrial fibrillation and heart failure

We investigated the biological significance of microRNA-126 (miR-126) expression in patients with atrial fibrillation (AF) and/or heart failure (HF) to examine the possible mechanism of miR-126-dependent AF and development of HF. A total of 103 patients were divided into three groups: AF group (18 men and 17 women, mean age: 65.62±12.72 years), HF group (17 men and 15 women, mean age: 63.95±19.71 years), and HF-AF group (20 men and 16 women, mean age: 66.56±14.37 years). Quantitative real-time PCR was used to measure relative miR-126 expression as calculated by the 2−ΔΔCt method. miR-126 was frequently downregulated in the 3 patient groups compared with controls. This reduction was significantly lower in permanent and persistent AF patients than in those with paroxysmal AF (P<0.05, t-test). Moreover, miR-126 expression was markedly lower in the HF-AF group compared with the AF and HF groups. The 3 patient groups had higher N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, lower left ventricular ejection fraction (LVEF), larger left atrial diameter, and higher cardiothoracic ratio compared with controls. There were significant differences in NT-proBNP levels and LVEF among the AF, HF, and HF-AF groups. Pearson correlation analysis showed that relative miR-126 expression was positively associated with LVEF, logarithm of NT-proBNP, left atrial diameter, cardiothoracic ratio, and age in HF-AF patients. Multiple linear regression analysis showed that miR-126 expression was positively correlated with LVEF, but negatively correlated with the logarithm of NT-pro BNP and the cardiothoracic ratio (all P<0.05). Serum miR-126 levels could serve as a potential candidate biomarker for evaluating the severity of AF and HF. However, to confirm these results, future studies with a larger and diverse patient population are necessary.     

Plasma soluble HLA-G levels in a cohort of heart failure patients exposed to chemicals

Heart failure (HF) is a syndrome caused by structural and/or functional cardiac abnormalities, resulting in a reduced cardiac output and/or elevated intracardiac pressures. Several studies reported a crucial role of immune activation and inflammation in the chronic heart failure (HF) pathogenesis, suggesting that pro-inflammatory and anti-inflammatory mediators could be predictive markers of the HF development and/or progression. Human Leukocyte Antigen-G (HLA-G), a tolerogenic and anti-inflammatory class I non-classical major histocompatibility complex molecule, was reported to be upregulated in patients diagnosed with HF, suggesting a tentative to regulate the inflammatory condition. We evaluated soluble (s)HLA-G plasmatic levels in patients with stable chronic heart failure at baseline visit and after 6 and 12 months. The 14 bp Insertion/Deletion polymorphisms of the HLA-G gene was also analyzed. We showed that in HF subjects, sHLA-G levels were higher in NYHA class II and III subjects (mild-severe symptoms) (6.11 ± 1.15 ng/ml; 8.25 ± 2.27 ng/ml, respectively) in comparison with NYHA class I subjects (no symptoms) (2.35 ± 0.43 ng/ml) (I vs II: p = 0.0156; I vs III: p = 0.0122). Moreover, the exposure to chemicals seems to affect sHLA-G levels, with higher sHLA-G levels in exposed patients (3.36 ± 5.12 ng/ml) in comparison with unexposed subjects (2.01 ± 2.84 ng/ml). The HLA-G 3′UTR 14 bp INS/DEL polymorphism correlated with sHLA-G, with the 14 bp INS/INS genotype associated with higher sHLA-G levels during the 12 months follow-up in unexposed subjects (p = 0.008). In conclusion, these results support a correlation between sHLA-G levels, genetics and HF disease in presence of work chemical exposition.     

肺炎伴心衰患儿血清中内皮素及内源性洋地黄样因子水平变化分析

目的探讨肺炎和肺炎并发心力衰竭(肺炎心衰),患儿血清内皮素和内源性洋地黄样因子水平变化。方法采用放射免疫分析法测定患儿内皮素和内源性洋地黄样因子。结果肺炎及肺炎心衰患儿内皮素和内源性洋地黄样因子有明显改变。结论内皮素及内源性洋地黄样因子与肺循环、缺氧有关。     

Impact of chronic obstructive pulmonary disease on linear and nonlinear dynamics of heart rate variability in patients with heart failure

The objective of this study was to investigate the impact of chronic obstructive pulmonary disease (COPD)-heart failure (HF) coexistence on linear and nonlinear dynamics of heart rate variability (HRV). Forty-one patients (14 with COPD-HF and 27 HF) were enrolled and underwent pulmonary function and echocardiography evaluation to confirm the clinical diagnosis. Heart rate (HR) and R-R intervals (iRR) were collected during active postural maneuver (APM) [supine (10 min) to orthostasis (10 min)], respiratory sinus arrhythmia maneuver (RSA-M) (4 min), and analysis of frequency domain, time domain, and nonlinear HRV. We found expected autonomic response during orthostatic changes with reduction of mean iRR, root mean square of successive differences between heart beats (RMSSD), RR tri index, and high-frequency [HF (nu)] and an increased mean HR, low-frequency [LF (nu)], and LF/HF (nu) compared with supine only in HF patients (P<0.05). Patients with COPD-HF coexistence did not respond to postural change. In addition, in the orthostatic position, higher HF nu and lower LF nu and LF/HF (nu) were observed in COPD-HF compared with HF patients. HF patients showed an opposite response during RSA-M, with increased sympathetic modulation (LF nu) and reduced parasympathetic modulation (HF nu) (P<0.05) compared with COPD-HF patients. COPD-HF directly influenced cardiac autonomic modulation during active postural change and controlled breathing, demonstrating an autonomic imbalance during sympathetic and parasympathetic maneuvers compared with isolated HF.     

Circulating endothelial cells in patients with heart failure and left ventricular dysfunction

Introduction and Aims: Acute and chronic heart failure may manifest different degrees of endothelial damage and angiogenesis. Circulating endothelial cells (CEC) have been identified as marker of vascular damage. The aim of our study was to evaluate the evolution of the CEC at different stages of patients with heart failure. We also investigated a potential correlation between CEC and markers of vascular damage and angiogenesis. Methods: We studied 32 heart failure patients at hospital admission (acute phase) and at revision after 3 months (stable phase) and 32 controls. Circulating markers of endothelial damage (CEC; von Willebrand factor, vWF and soluble E-selectin, sEsel) and angiogenesis (vascular endothelial growth factor, VEGF and thrombospondin-1) were quantified. Results: Levels of CEC, vWF, sEsel and VEGF are significantly higher in heart failure patients than in controls. Levels of CEC (36.9 ± 15.3 vs. 21.5 ± 10.0 cells/ml; p< 0.001), vWF (325 ± 101 vs. 231 ± 82%; p< 0.001) and VEGF (26.3 ± 15.2 vs. 21.9 ± 11.9 ng/ml; p< 0.001) are significantly higher in the acute phase than in the stable phase of heart failure. CEC levels correlate with vWF and VEGF. Results show than 100% of patients in acute phase and 37.5% in stable phase have levels of CEC higher than the 99th percentile of the distribution of controls (16 cells/ml). Therefore, increases in CEC represent a relative risk of 9.5 for heart failure patients suffering from acute phase. Conclusions: CEC, in addition to being elevated in heart failure, correlate with vWF levels, providing further support for CEC as markers of endothelial damage. Levels of CEC are associated with the acute phase of heart failure and could be used as a marker of the worsening in heart failure.     

Effects of an educational intervention on heart failure knowledge,self-care behaviors,and health-related quality of life of patients with heart failure: Exploring the role of depression

ObjectivesTo test effects of an educational intervention on patient-reported outcomes among rural heart failure (HF) patients and to examine whether effects differed between patients with and without depression.MethodsPatients (N = 614) were randomized to usual care (UC) or 1 of 2 intervention groups. Both intervention groups received face-to-face education, followed by either 2 phone calls (LITE) or biweekly calls until they demonstrated content competency (PLUS). Follow-up lasted 24 months. Statistical analyses included linear mixed models and subgroup analyses by depression status.ResultsBoth intervention groups showed improvement in HF knowledge at 3 months (LITE–UC, p = 0.003; PLUS–UC, p < 0.001). Improvement lasted 24 months only in the PLUS group. Compared to UC, both intervention groups exhibited better self-care at 3 months (LITE–UC, p < 0.001; PLUS–UC, p < 0.001) and 12 months (LITE–UC, p = 0.001; PLUS–UC, p = 0.002). There were no differences in health-related quality of life (HRQOL) among groups. In subgroup analyses, similar effects were found among non-depressed, but not among depressed patients.ConclusionThe educational intervention improved HF knowledge and self-care, but not HRQOL. No intervention effects were observed in patients with depressive symptoms.Practice ImplicationsThe simple educational intervention is promising to improve HF knowledge and self-care. Additional strategies are needed for depressed patients.     

New therapeutic options for patients with heart failure with reduced ejection fraction and acute decompensated heart failure

BackgroundPatients with acute decompensated heart failure (ADHF) are at severe risk of death and rehospitalization. Several clinical studies have been designed to evaluate the efficacy and safety of new molecules administered before discharge or shortly after ADHF. The aim of this article is to summarize current knowledge on recently published findings on treatment of patients with heart failure with reduced ejection fraction (HFrEF) and ADHF.MethodsWe performed a thorough search for literature pertaining to our review via the PubMed database.ResultsIn this review, we summarize original papers concerning the efficacy and safety of new molecules in patients with HFrEF and ADHF.ConclusionsPeri-discharge initiation of treatment with new molecules is possible and safe for patients with HFrEF and ADHF. New molecules, if administered before discharge or shortly after, reduce the risk of cardiovascular death or worsening heart failure within the vulnerable phase, and are also nephroprotective.     

Surfactant protein B intron 4 variation in German patients with COPD and acute respiratory failure

Chronic obstructive pulmonary disease (COPD) is a major health problem. Genetic factors that contribute to the disease have been postulated. The pulmonary surfactant protein B (SP-B), which is essential for normal lung function, is considered as a candidate gene for COPD in this case-control study. We studied the SP-B intron 4 size variants in 346 individuals. This group consisted of 118 patients with chronic bronchitis or COPD, including 24 patients with acute respiratory failure (ARF) in COPD, 118 matched controls without pulmonary disease and 110 healthy individuals (population control). The frequency of intron 4 variants was similar in either control group (10.9%, 14.4%, respectively), with a small increase in the COPD group (18.6%). This increase was due to a high increase of intron 4 variants in the ARF subgroup (37.5%, p = 0.003, OR 4.9, 95% CI: 1.76-13.6). The data indicate that SP-B intron 4 variants may associate with increased risk of ARF in COPD and may be used as a marker of susceptibility in this disease subgroup.     

Current strategies for preventing renal dysfunction in patients with heart failure: a heart failure stage approach

Renal dysfunction is common during episodes of acute decompensated heart failure, and historical data indicate that the mean creatinine level at admission has risen in recent decades. Different mechanisms underlying this change over time have been proposed, such as demographic changes, hemodynamic and neurohumoral derangements and medical interventions. In this setting, various strategies have been proposed for the prevention of renal dysfunction with heterogeneous results. In the present article, we review and discuss the main aspects of renal dysfunction prevention according to the different stages of heart failure.     

Heart failure: a model of cardiac and skeletal muscle energetic failure

Chronic heart failure (CHF), the new epidemic in cardiology, is characterized by energetic failure of both cardiac and skeletal muscles. The failing heart wastes energy due to anatomical changes that include cavity enlargement, altered geometry, tachycardia, mitral insufficiency and abnormal loading, while skeletal muscle undergoes atrophy. Cardiac and skeletal muscles also have altered high-energy phosphate production and handling in CHF. Nevertheless, there are differences in the phenotype of myocardial and skeletal muscle myopathy in CHF: cardiomyocytes have a lower mitochondrial oxidative capacity, abnormal substrate utilisation and intracellular signalling but a maintained oxidative profile; in skeletal muscle, by contrast, mitochondrial failure is less clear, and there is altered microvascular reactivity, fibre type shifts and abnormalities in the enzymatic systems involved in energy distribution. Underlying these phenotypic abnormalities are changes in gene regulation in both cardiac and skeletal muscle cells. Here, we review the latest advances in cardiac and skeletal muscle energetic research and argue that energetic failure could be taken as a unifying mechanism leading to contractile failure, ultimately resulting in skeletal muscle energetic failure, exertional fatigue and death.     

The reliability of continuous measurement of mixed venous oxygen saturation during exercise in patients with chronic heart failure

Continuous assessment of mixed venous oxygen saturation (cSvO₂) during exercise using a fiber optic pulmonary artery catheter can provide valuable information on the physiological determinants of the exercise capacity in patients with chronic heart failure (CHF). Since its accuracy is not well established during exercise, this study evaluated the reliability of a fiber optic pulmonary artery catheter for measuring SvO₂ during exercise in CHF patients. Ten patients with stable CHF performed steady-state exercise tests at 30 and 80% of the ventilatory threshold and consequently a symptom-limited incremental exercise test. During the tests, SvO₂ was monitored continuously using a fiber optic pulmonary artery catheter (CCOmbo, Edwards Lifesciences, Irvine, CA, USA) and by oximetric analysis of mixed venous blood samples obtained at rest (n = 26), steady state (n = 17) and peak exercise (n = 8). There was a significant correlation between oximetrically determined SvO₂ and cSvO₂ values (r = 0.97). The bias between both methods was 0.6% with limits of agreement from −8 to 9%. The limits of agreement for SvO₂ values <30% (n = 16) were slightly wider than for SvO₂ values >30% (n = 35) (from −10 to 12% and from −7 to 8%, respectively). In conclusion, continuous measurement of SvO₂ during exercise using a fiber optic pulmonary catheter is reliable in patients with CHF, with somewhat less accurate measurements of SvO₂ below 30%.