Catestatin is useful in detecting patients with stage B heart failure

Screening patients with stage B heart failure(HF) may be one strategy for reducing human morbidity. To describe catestatin levels in different stages of HF and evaluate the diagnostic utility of catestatin for detecting stage B HF, we included 300 patients. Catestatin, BNP testing and echocardiogram were performed. Our studies showed catestatin decreased gradually from stage A to C. There was significant difference between stage A and B. Cutoff value for detecting stage B HF was 19.73?ng/ml for catestatin with 90% sensitivity and 50.9% specificity. These results may have implications in the new method to detect patients with stage B HF.     

Circulating stem cell vary with NYHA stage in heart failure patients

We have investigated the blood levels of sub-classes of stem cells (SCs) [mesenchymal stem cells (MSCs), haematopoietic stem cells (HSCs), endothelial progenitor cells/circulating endothelial cells (EPCs/CECs) and tissue-committed stem cells (TCSCs)] in heart failure (HF) patients at different stage of pathology and correlated it with plasmatic levels of proangiogenic cytokines. Peripheral blood level of SCs were analysed in 97 HF patients (24 in NYHA class I, 41 in class II, 17 in class III and 15 in class IV) and in 23 healthy controls. Plasmatic levels of PDGF-BB, bFGF, HGF, vascular endothelial growth factor (VEGF), SDF-1α, TNF-α and NTproBNP were also measured. Compared with healthy individuals, MSC, and in particular the sub-classes CD45⁻CD34⁻CD90⁺, CD45⁻CD34⁻CD105⁺ and CD45⁻CD34⁻CXCR4⁺ were significantly enhanced in NYHA class IV patients (16.8-, 6.4- and 2.7-fold, respectively). Level of CD45⁻CD34⁻CD90⁺CXCR4⁺cells progressively increased from class II to class IV (fold increases compared with controls: 8.5, 12 and 21.5, respectively). A significant involvement of CXCR4⁺ subpopulation of HSC (CD45⁺CD34⁺CD90⁺CXCR4⁺, 1.4 versus 13.3 cells/μl in controls and NYHA class III patients, respectively) and TCSC (CD45⁻CD34⁺CXCR4⁺, 1.5 cells/ μl in controls versus 12.4 and 28.6 cells/μl in NYHA classes II and IV, respectively) were also observed. All tested cytokines were enhanced in HF patients. In particular, for PDGF-BB and SDF-1α we studied specific ligand/receptors pairs. Interestingly, the first one positively correlated with TCSCs expressing PDGFR (r = 0.52, P = 0.001), whereas the second one correlated with TCSCs (r = 0.34, P = 0.005) and with MSCs CD90⁺ expressing CXCR4 (r = 0.39, P = 0.001). HF is characterized by the increase in the circulating levels of different MSC, HSC, EPC and TCSC subsets. Both the entity and kinetic of this process varied in distinct cell subsets. Specifically, differently from HSCs and EPCs/CECs, MSCs and TCSCs significantly increased with the progression of the disease, suggesting a possible distinct role of these cells in the pathophysiology of HF.     

Suppression of cerebral hemodynamics is associated with reduced functional capacity in patients with heart failure

This investigation elucidated the underlying mechanisms of functional impairments in patients with heart failure (HF) by simultaneously comparing cardiac-cerebral-muscle hemodynamic and ventilatory responses to exercise among HF patients with various functional capacities. One hundred one patients with HF [New York Heart Association HF functional class II (HF-II, n = 53) and functional class III (HF-III, n = 48) patients] and 71 normal subjects [older control (O-C, n = 39) and younger control (Y-C, n = 32) adults] performed an incremental exercise test using a bicycle ergometer. A recently developed noninvasive bioreactance device was adopted to measure cardiac hemodynamics, and near-infrared spectroscopy was employed to assess perfusions in the frontal cerebral lobe (Δ[THb](FC)) and vastus lateralis muscle (Δ[THb](VL)). The results demonstrated that the Y-C group had higher levels of cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise than the O-C group. Moreover, these cardiac/peripheral hemodynamic responses to exercise in HF-III group were smaller than those in both HF-II and O-C groups. Although the change of cardiac output caused by exercise was normalized, the amounts of blood distributed to frontal cerebral lobe and vastus lateralis muscle in the HF-III group significantly declined during exercise. The HF-III patients had lower oxygen-uptake efficiency slopes (OUES) and greater Ve-Vo(2) slopes than the HF-II patients and age-matched controls. However, neither hemodynamic nor ventilatory response to exercise differed significantly between the HF-II and O-C groups. Cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise were directly related to the OUES and Vo(2peak) and inversely related to the Ve-Vco(2) slope. Moreover, cardiac output or Δ[THb](FC) was an effect modifier, which modulated the correlation status between Δ[THb](VL) and Ve-Vco(2) slope. We concluded that the suppression of cerebral/muscle hemodynamics during exercise is associated with ventilatory abnormality, which reduces functional capacity in patients with HF.     

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands

Aims

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013–2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands.

Methods

In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%.

Conclusion

The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

     

Redox modulation of the inotropic response to dobutamine is impaired in patients with heart failure

It has been suggested that oxidative stress contributes to impaired left ventricular (LV) contractility in the setting of heart failure (HF). To test this hypothesis, we studied the effect of an antioxidant on contractility at rest and in response to dobutamine in 10 HF patients. We hypothesized that vitamin C would augment contractility in HF and that this effect would be of a greater magnitude in HF patients compared with patients with normal LV (NLV) function. Data from 10 patients with NLV function who participated in this study are included in this report and have been published elsewhere. A micromanometer-tipped catheter was introduced into the LV. In the experimental protocol, an infusion catheter was positioned in the left main coronary artery. The peak positive rate of change of LV pressure (LV +dP/dt) was measured in response to the intravenous infusion of dobutamine before and during the intracoronary infusion of vitamin C (96 mg/min). Vitamin C had no effect on basal LV +dP/dt in either HF or NLV groups. The infusion of vitamin C augmented the LV +dP/dt response to dobutamine by 22 +/- 4% in the NLV function group. In contrast, vitamin C had no effect on the inotropic response to dobutamine in the HF group. In the control protocol, without vitamin C, no differences were observed between responses to two sequential dobutamine infusions in either group (HF, n = 11; NLV, n = 9). Therefore, a positive effect of vitamin C on contractility was limited to patients with NLV function. The absence of this effect in HF patients may suggest that normal redox responsiveness is lost in this disease state.     

Nocturnal oxygen desaturation in patients with congestive heart failure

The aim of our study was to evaluate the modifications of the respiratory pattern during sleeping in patients with congestive heart failure (CHF) by a simple pulse-oxymetry. We studied 10 subjects (8M/2F), mean age 71.4 +/- 12.4 yrs, admitted to sub-intensive cardiological therapy unit, with diagnosis of CHF due to left ventricular insufficiency by ischemic, hypertensive or idiopathic cardiopathy, when in a stable clinical condition. All patients presented arterial blood gas values within normal limits. The ejection fraction of left ventricle showed a mean value of 30.4 +/- 8.2% (range 20%-45%). Nocturnal pulse-oxymetry was performed by pulse-oxymeter (PULSOX 7 Minolta) provided with a digital probe at a sliding speed 24 cm/h. Our data showed that all patients presented nocturnal desaturation episodes (mean oxygen desaturation index 15.7 +/- 18.4). In two patients, we found an "Overlap Syndrome" (obstructive sleep apnoea in presence of cardiopathy). In other patients pulse-oxymetry showed a typical sequence of "fall-rise" basal O2 saturation lasting from 36 to 72 seconds, collected in "wave trains" which were present from 14% to 70% of total sleep time compatible with periodic breathing. In conclusion, our study shows that patients affected by CHF, even if in stable condition and with a PaO2, within normal values, present more or less severe disturbances of nocturnal SaO2, with periodic and regular sequences of SaO2 fall-rise that may be referred to ventilatory troubles such as periodic breathing or Cheyne-Stokes breathing. In these patients the pulse-oxymetry may be considered an efficacious, simple, cheap and well tolerated method.     

Left ventricular pacing in patients with congestive heart failure

Cardiac resynchronisation therapy (CRT) using biventricular (BIV) pacing has proved its effectiveness to correct myocardial asynchrony and improve clinical status of patients with severe congestive heart failure (CHF) and widened QRS. Despite a different effect on left ventricular electrical dispersion, left univentricular (LV) pacing is able to achieve the same mechanical synchronisation as BIV pacing in experimental studies and in humans. This results in clinical benefits of LV pacing at mid-term follow-up, with significant improvement in functional class, quality of life and exercise tolerance at the same extent as those observed with BIV stimulation in non randomised studies. Furthermore these benefits are obtained at lesser costs and with conventional dual-chamber devices. However, LV pacing has to be compared to BIV pacing in randomised trials before being definitely considered as a cost-effective alternative to BIV pacing.     

Sacubitril/Valsartan is useful and safe in elderly people with heart failure and reduced ejection fraction. Data from a real-word cohort

BackgroundHF elderly patients are underrepresented in Sacubitril/Valsartan HF trials, and the effect of S/V in real-life patients with advanced age is unknown. The aim of this study was to evaluate the use and safety of S/V in a real-word cohort of elderly patients.MethodsWe performed a prospective registry of patients who started S/V in clinical practice. We compared baseline characteristics, adverse events during follow-up and causes of S/V withdrawal according to age.ResultsA total of 427 patients started treatment with S/V: 222 (52.0%) < 70 years old, 140 (32.8%) between 70 and 79 and 65 (15.2%) ≥ 80. During a mean follow-up of 7.0 ± 0.1 months S/V was well tolerated, with no age-related differences in adverse events (26.8%, 25.9%, 23.1% respectively; p = 0.83). Symptomatic hypotension tended to be more frequent in the elderly (19.8%, 25.6%, 33.3% respectively; p = 0.17). The withdrawal of S/V was more frequent in younger patients (14.4%, 10.0%, 4.6% respectively; p = 0.05) and related to poor prognosis (HR 13.51, 95% CI 3.22–56.13, p < 0.001).ConclusionsSacubitril/Valsartan is useful and safe in elderly people with HF-rEF in real-life clinical practice, and withdrawal is associated to poor prognosis. The doses achieved are lower in elderly people.     

Alveolar fluid reabsorption is increased in rats with compensated heart failure

Alveolar fluid reabsorption (AFR) is important in keeping the air spaces free of edema. This process is accomplished via active transport of Na(+) across the alveolo-capillary barrier mostly by apical Na(+) channels and basolateral Na(+)-K(+)-ATPases. Recently, we have reported that acute elevation of left atrial pressures is associated with decreased AFR in isolated rat lungs. However, the effect of chronic elevation of pulmonary capillary pressure, such as seen in patients with congestive heart failure (CHF), on AFR is unknown. CHF was induced by creating an aorto-caval fistula (ACF) in Sprague-Dawley male rats. Seven days after the placement of the fistula, AFR was studied in the isolated perfused rat lung model. AFR in control rats was 0.49 +/- 0.02 ml/h (all values are means +/- SE) and increased by approximately 40% (0.69 +/- 0.03 ml/h) in rats with chronic CHF (P < 0.001). The albumin flux from the pulmonary circulation into the air spaces did not increase in the experimental groups, indicating that lung permeability for large solutes was not increased. Na(+)-K(+)-ATPase activity and protein abundance at the plasma membrane of distal alveolar epithelial tissue were significantly increased in CHF rats compared with controls. These changes were associated with increased plasma norepinephrine levels in CHF rats compared with controls. We provide evidence that in a rat model of chronic compensated CHF, AFR is increased, possibly due to increased endogenous norepinephrine upregulating active sodium transport and protecting against alveolar flooding.     

Factors associated with elevated plasma phenylalanine in patients with heart failure

Amino Acids - Elevated phenylalanine has been observed in patients with advanced heart failure (HF) and in community cohorts at risk of HF, and has been shown to have prognostic value. This study...     

Proteomics of epicardial adipose tissue in patients with heart failure

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot closely linked to the pathogenesis of heart failure (HF). But the molecular signatures related to the mechanism of HF have not been systematically explored. Here, we present comprehensive proteomic analysis of EAT in HF patients and non‐HF patients as controls. A total of 771 proteins were identified in liquid chromatography‐tandem mass spectrometry experiments. Amongst them, 17 increased in abundance in HF and seven decreased. They were involved in HF‐related processes including inflammation and oxidative stress response and lipid metabolism. Of these proteins, serine proteinase inhibitor A3 (Serpina3) levels in EAT were highly up‐regulated in HF, with HF/non‐HF ratio of 4.63 (P = .0047). Gene expression of Serpina3 via quantitative polymerase chain reaction was significantly increased in the HF group. ELISA analysis confirmed a significant increase in circulating plasma Serpina3 levels in the HF group (P = .004). In summary, for the first time, we describe that parts of EAT proteome may be reactive and work as modulators of HF. Our profiling provides a comprehensive basis for linking EAT with pathogenesis of HF. Understanding the role of EAT may offer new insights into the treatment of HF.     

Increased endothelin-1 production in patients with chronic heart failure

Endothelin-1 (ET-1) concentrations are elevated in patients with congestive heart failure (CHF), although the cause of this increase remains uncertain. We hypothesized that abnormalities in ET-1 production, clearance, or a combination of these may be the cause of elevated ET-1 concentrations in chronic CHF. The kinetics of clearance of ET-1 were measured with (125)I-labeled ET-1 in eight patients with CHF and five age-matched normal individuals. In both normal subjects and the CHF group, the kinetics of ET-1 clearance were best described by a three-compartment model. The steady-state volume of distribution of ET-1 was significantly greater in the CHF group compared with normal subjects (25.2 +/- 3.9 vs. 13.8 +/- 2.1 l/kg; P < 0.05). The total clearance rate from plasma was greater in the CHF group (0.119 +/- 0.018 vs. 0.047 +/- 0.013 l.kg(-1).min(-1); P = 0.05). The total body production rate of ET-1 was also significantly higher in patients with CHF (0.21 +/- 0.03. vs. 0.06 +/- 0.02 ng.kg(-1).min(-1); P < 0.05). It appears that increased ET-1 production rather than decreased clearance is the cause of elevated ET-1 concentrations in patients with chronic CHF.