Phase Of Chronic Heart Failure Research Articles

Assessment of congestion and clinical outcomes in patients with chronic heart failure using shear wave elasticity.

AimsThe relief of congestion is essential for the prevention of worsening heart failure (HF) resulting in hospitalizations. Assessment of the degree of organ congestion in the chronic phase of HF is important for determining therapeutic strategies. The aim of this study was to evaluate the efficacy of shear wave (SW) elasticity for assessing congestion and clinical outcomes in patients with chronic HF.Methods and resultsWe prospectively enrolled 345 consecutive patients with chronic HF who underwent SW elastography at outpatient clinic. Patients were divided into two groups according to the median value of SW elasticity: low group (SW elasticity <6.4 kPa, n = 176) and high group (SW elasticity ≥6.4 kPa, n = 169). The endpoint was cardiovascular death or hospitalization for HF. During the median follow‐up period of 19 months (range: 7–36 months), cardiovascular death or hospitalization for HF occurred in 4 patients of low group and 27 patients of high group. In high group, 8 patients died, and 19 patients were hospitalized for HF. In low group, 3 patients died, and 1 patient was hospitalized. Kaplan–Meier analysis showed that the event‐free survival rate was worse in high group than in low group (log‐rank test, P = 0.004). After adjusting for variables, high SW elasticity was independently related to cardiac events. In multivariate regression analysis, SW elasticity was correlated with left atrial volume index, early diastolic mitral inflow velocity to mitral annular velocity ratio, and inferior vena cava diameter.ConclusionsThe SW elasticity reflected haemodynamic congestion in patients with chronic HF, which was related to cardiac events.

Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy.

Cardiomyocyte hypertrophy is a compensatory phase of chronic heart failure that is induced by the activation of multiple signaling pathways. The extracellular signal-regulated protein kinase (ERK) signaling pathway is an important regulator of cardiomyocyte hypertrophy. In our previous study, it was demonstrated that phenylephrine (PE)-induced cardiomyocyte hypertrophy involves the hyperacetylation of histone H3K9ac by P300/CBP-associated factor (PCAF). However, the upstream signaling pathway has yet to be fully identified. In the present study, the role of the extracellular signal-regulated protein kinase (ERK)1/2 signaling pathway in PE-induced cardiomyocyte hypertrophy was investigated. The mice cardiomyocyte hypertrophy model was successfully established by treating cells with PE in vitro. The results showed that phospho-(p-)ERK1/2 interacted with PCAF and modified the pattern of histone H3K9ac acetylation. An ERK inhibitor (U0126) and/or a histone acetylase inhibitor (anacardic acid; AA) attenuated the overexpression of phospho-ERK1/2 and H3K9ac hyperacetylation by inhibiting the expression of PCAF in PE-induced cardiomyocyte hypertrophy. Moreover, U0126 and/or AA could attenuate the overexpression of several biomarker genes related to cardiac hypertrophy (myocyte enhancer factor 2C, atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain) and prevented cardiomyocyte hypertrophy. These results revealed a novel mechanism in that AA protects against PE-induced cardiomyocyte hypertrophy in mice via the ERK1/2 signaling pathway, and by modifying the acetylation of H3K9ac. These findings may assist in the development of novel methods for preventing and treating hypertrophic cardiomyopathy.

Redd1 protects against post‑infarction cardiac dysfunction by targeting apoptosis and autophagy.

Post-infarction remodeling is accompanied and influenced by perturbations in the mammalian target of rapamycin (mTOR) signaling. Regulated in development and DNA damage response-1 (Redd1) has been reported to be involved in DNA repair and modulation of mTOR activity. However, little is known about the role of Redd1 in the heart. In the present study the potential contribution of Redd1 overex-pression to the chronic phase of heart failure after myocardial infarction (MI) was explored and the mechanisms underlying Redd1 actions were determined. Redd1 was downregulated in the mouse heart subjected to MI surgery. To determine the role of Redd1 in the process of MI, adeno-associated virus 9 mediated overexpression of Redd1 was used to enhance Redd1 content in cardiomyocytes. Redd1 overexpression improved left ventricular dysfunction and reduced the expansion index. Additionally, Redd1 overexpression resulted in suppressed myocardial apoptosis and improved autophagy. Furthermore, the studies revealed that Redd1 overexpression could inhibit the phosphorylation of mTOR and its downstream effectors P70/S6 kinase and 4EBP1. In conclusion, this study demonstrated that Redd1 overexpression protects against the development and persistence of heart failure post MI by reducing apoptosis and enhancing autophagy via the mTOR signaling pathway. The present study clearly demonstrated that Redd1 is a therapeutic target in the development of heart failure after MI.

Voluntary physical activity counteracts Chronic Heart Failure progression affecting both cardiac function and skeletal muscle in the transgenic Tgαq*44 mouse model.

Physical activity is emerging as an alternative nonpharmaceutical strategy to prevent and treat a variety of cardiovascular diseases due to its cardiac and skeletal muscle beneficial effects. Oxidative stress occurs in skeletal muscle of chronic heart failure (CHF) patients with possible impact on muscle function decline. We determined the effect of voluntary‐free wheel running (VFWR) in preventing protein damage in Tgαq*44 transgenic mice (Tg) characterized by a delayed CHF progression. In the early (6 months) and transition (12 months) phase of CHF, VFWR increased the daily mean distance covered by Tg mice eliminating the difference between Tg and WT present before exercise at 12 months of age (WT Pre‐EX 3.62 ± 1.66 vs. Tg Pre‐EX 1.51 ± 1.09 km, P < 0.005; WT Post‐EX 5.72 ± 3.42 vs. Tg Post‐EX 4.17 ± 1.8 km, P > 0.005). This effect was concomitant with an improvement of in vivo cardiac performance [(Cardiac Index (mL/min/cm2): 6 months, untrained‐Tg 0.167 ± 0.005 vs. trained‐Tg 0.21 ± 0.003, P < 0.005; 12 months, untrained‐Tg 0.1 ± 0.009 vs. trained‐Tg 0.133 ± 0.005, P < 0.005]. Such effects were associated with a skeletal muscle antioxidant response effective in preventing oxidative damage induced by CHF at the transition phase (untrained‐Tg 0.438 ± 0.25 vs. trained‐Tg 0.114 ± 0.010, P < 0.05) and with an increased expression of protein control markers (MuRF‐1, untrained‐Tg 1.12 ± 0.29 vs. trained‐Tg 14.14 ± 3.04, P < 0.0001; Atrogin‐1, untrained‐Tg 0.9 ± 0.38 vs. trained‐Tg 7.79 ± 2.03, P < 0.01; Cathepsin L, untrained‐Tg 0.91 ± 0.27 vs. trained‐Tg 2.14 ± 0.55, P < 0.01). At the end‐stage of CHF (14 months), trained‐Tg mice showed a worsening of physical performance (decrease in daily activity and weekly distance and time of activity) compared to trained age‐matched WT in association with oxidative protein damage of a similar level to that of untrained‐Tg mice (untrained‐Tg 0.62 ± 0.24 vs. trained‐Tg 0.64 ± 0.13, P > 0.05). Prolonged voluntary physical activity performed before the onset of CHF end‐stage, appears to be a useful tool to increase cardiac function and to reduce skeletal muscle oxidative damage counteracting physical activity decline.

Characteristics of Patients with Decreased Cognitive Function Undergoing Treatment for Acute Exacerbation of Chronic Heart Failure—Basic Survey for Standardization of Nursing to Prevent Discontinuation of Treatment

The purpose of this study is to clarify the characteristics of patients with decreased cognitive function undergoing treatment for acute exacerbation phase of chronic heart failure as a basic survey with a view to the standardization of nursing to prevent discontinuation of treatment of patients with declining cognitive function in the acute exacerbation phase of chronic heart failure. As the first stage of the research, using the interview guide created based on the background of discontinuation of treatment and symptomatic monitoring from 33 target literature sources, seven certified chronic heart failure nurses and 15 certified dementia nurses were given semi-structured interviews. Data obtained from the interviews was analyzed by qualitative induction. As a result, we obtained opinions/views on 8 situations namely, “cognitive function at hospitalization”, “characteristics at hospitalization, “characteristics when receiving examinations, procedures or treatment”, “characteristics of course of treatment”, “characteristics related to difficulties in grasping the symptoms of chronic heart failure and indices of deterioration”, “characteristics when using diuretics”, “characteristics concerning compliance with dietary restrictions” and “support required for discharge from hospital” concerning patients with declining cognitive function. In the future, it is necessary to prepare nursing protocols incorporating these contents for standardization of nursing.

Abstract 118: Adipose Inflammation Is Critically Involved in the Progression of Heart Failure During Pressure Overload

Several clinical studies have shown that insulin resistance is prevalent among patients with impaired cardiac function and that systemic insulin resistance is the risk factor for the development of heart failure; however, underlying mechanisms have not been fully elucidated. We have previously reported that increased p53 level in adipose tissue is crucially involved in adipose inflammation and insulin resistance during pressure overload. Here we show that . Pressure overload increased sympathetic activity and promoted lipolysis in adipose tissue. Accelerated lipolysis resulted in increases of reactive oxygen species and DNA damage, leading to up-regulation of adipose p53. This up-regulation activated the NF-kappaB pathway and induced adipose inflammation and insulin resistance. Genetic disruption of adipose p53 markedly attenuated adipose inflammation and metabolic abnormalities associated with heart failure. We also observed that cardiac function and survival in the chronic phase of heart failure were significantly better in adipose tissue p53-deficient mice than control littermates. Pharmacological inhibition of adipose p53 after imposing pressure overload also improved cardiac dysfunction as well as insulin resistance in the chronic phase of heart failure. These results suggest that inhibition of adipose inflammation is a potential target for treating metabolic abnormalities and systolic dysfunction in patients with heart failure.

Prevention of Left Ventricular Remodelling after Acute Myocardial Infarction: An Update

Left ventricular remodelling is a progressive process, which starts immediately after acute myocardial infarction and evolves in the chronic phase of heart failure. It is characterized by left ventricular chamber dilatation and increased wall stress, which results in alteration of the contractile properties of the non-infarct zone and impairment of the systolic and diastolic performances of the left ventricle. Neurohormonal activation and increased sympathetic stimulation are among the factors that have been linked to the development and progression of left ventricular dysfunction after acute myocardial infarction. The present review will address recent insights from new patents and experimental studies of drugs, which ought to prevent left ventricular remodelling. Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers and Beta-Blockers have been proven effective in modulating the process of remodelling and in reducing the occurrence of adverse events. However, in most of the trials high risk patients have been excluded, and uncertainty still exists regarding a number of clinically relevant questions. Data from experimental studies have identified new targets for interventions to prevent reverse left ventricular remodelling, i.e. stem cell transfer, activation of cardiac and leukocyte-dependent oxidant stress pathways, inflammatory pathway activation, matrix-metalloproteinase activation.

Papillary muscle dyssynchrony: what is the optimal cut-off value?

We appreciate the useful comments by Cabrera-Bueno et al. underscoring the importance of mitral regurgitation (MR) in patients with dilated cardiomyopathy (DCM). Cardiac resynchronization therapy (CRT) improves functional MR during the acute and chronic phase of heart failure by improving the coordination of the left ventricular segments and papillary muscle contractions.1,2. However, MR volumes of the patients with minimal papillary muscle dyssynchrony did not improve following CRT.2 The best echocardiographic cut-off value to predict significant papillary muscle dyssynchrony, which in turn, would help patient selection for CRT is still unknown. The papillary muscles usually get closer to each …

The detrended fluctuation analysis of acute-phase heart-rate variability in acute coronary syndromes — A pilot study

Heart-rate variability (HRV) analyzed by detrended fluctuation analysis (DFA), which resulted in a short-term fractal exponent — alpha, has prognostic implication in chronic phase of heart failure and survivors of myocardial infarction. We adopted DFA to study the acute-phase HRV in acute coronary syndromes (ACS) by recruiting 30 age- and co-morbidity-matched adults in acute-stress simulation in comparison with 33 consecutive ACS patients. The 30 volunteers got stepwise elevated alpha with increased intensity of exercise (0.95 ± 0.050 to 1.07 ± 0.084 to 1.20 ± 0.083, p < 0.05). The alpha of 33 ACS patients correlated with the complexity of post-MI course (1.004 ± 0.0080 in non-complicated vs. 1.216 ± 0.058 in complicated p < 0.05). No significance existed in categories of age, ACS type, numbers of diseased vessel, infarct-related artery or Killip classification. The increased alpha value of DFA may imply unresolved cardiac stress which demands further attention.

Does an endocrinal phase of chronic heart failure exist?

Does an endocrinal phase of chronic heart failure exist?

Influence of venous function on exercise tolerance in chronic heart failure.

The clinical phase of chronic heart failure (HF) includes a marked decline in exercise tolerance, in part due to impaired skeletal muscle blood flow delivery. Interestingly, the role of the venous system on exercise tolerance in patients with HF has not received much attention, despite evidence of changes in venous structure and function. The purpose of this study was to examine the relationship between forearm arterial and venous function, and exercise tolerance in patients with HF and age-matched controls. Vascular function and exercise tolerance was examined in 20 patients with HF (age 59 +/- 13 years) and 10 control subjects (age 51 +/- 16 years). Nondominant forearm arterial inflow, vascular resistance, venous capacitance, and venous outflow were evaluated at rest and after 5 minutes of upper arm occlusion, using strain gauge plethysmography. Exercise tolerance was measured as the maximum walking distance achieved on a 6-minute walking test. Maximum walking distance (HF: 178 +/- 65 m; controls: 562 +/- 136 m, P=.0001), and forearm vascular function after occlusion were significantly different between groups (forearm arterial inflow: HF 15.3 +/- 6; controls 22 +/- 6.7; forearm venous capacitance: HF 1.4 +/- 0.5; controls 2.0 +/- 0.4; forearm venous outflow: HF 24.5 +/- 9.4; controls: 33 +/- 10 mL x 100 mL tissue(-1) x min(-1); and forearm vascular resistance: HF 7.8 +/- 3; controls 4.6 +/- 1.4 U). Correlation analysis revealed significant associations between all forearm vascular measurements after occlusion and maximum walking distance. These data confirm previous studies indicating the importance of arterial reactivity on exercise tolerance in patients with HF. Additionally, the results suggest the importance of venous function as a contributing factor to exercise performance.

Left Ventricular Dilatation After Myocardial Infarction

Left ventricular (LV) dilatation after myocardial infarction (MI) is a major predictor of prognosis and identifies which patients will develop heart failure. Left ventricular dilatation or remodeling starts immediately after MI and progresses in the chronic phase of heart failure. Factors influencing remodeling, such as infarct size and neurohumoral activation, including the sympathetic and renin-angiotensin system, are discussed. Remodeling can be affected by reduction of infarct size and inhibition of neurohumoral activation. The effect of thrombolysis, β-blockade, and angiotensin-converting enzyme (ACE) inhibition in the acute phase after MI and in the chronic phase of heart failure on remodeling are discussed. On the basis of beneficial effects of ACE inhibition and β-blockade in acute MI and in chronic heart failure, a treatment strategy is proposed in which both ACE inhibition and β-blockade are started early after MI. Depending on infarct size and ventricular function, continued treatment in the chronic phase of heart failure must be considered.

Left ventricular dilatation after myocardial infarction: ACE inhibitors, beta-blockers, or both?

Left ventricular (LV) dilatation after myocardial infarction (MI) is a major predictor of prognosis and identifies which patients will develop heart failure. Left ventricular dilatation or remodeling starts immediately after MI and progresses in the chronic phase of heart failure. Factors influencing remodeling, such as infarct size and neurohumoral activation, including the sympathetic and renin-angiotensin system, are discussed. Remodeling can be affected by reduction of infarct size and inhibition of neurohumoral activation. The effect of thrombolysis, beta-blockade, and angiotensin-converting enzyme (ACE) inhibition in the acute phase after MI and in the chronic phase of heart failure on remodeling are discussed. On the basis of beneficial effects of ACE inhibition and beta-blockade in acute MI and in chronic heart failure, a treatment strategy is proposed in which both ACE inhibition and beta-blockade are started early after MI. Depending on infarct size and ventricular function, continued treatment in the chronic phase of heart failure must be considered.

Decreased gene expression of neuronal nitric oxide synthase in hypothalamus and brainstem of rats in heart failure

Nitric oxide may act at autonomic sites in the brain to regulate sympathetic outflow. Our goal was to determine whether gene expression of the neuronal isoform of nitric oxide synthase (nNOS) is altered in discrete autonomic brain regions of rats in the chronic phase of heart failure compared to sham-operated control rats. Experiments were performed in rats 4 to 5 weeks after left coronary artery ligation. Histological data indicated that there was a 39% outer and a 45% inner infarct of the left ventricular myocardium in the heart failure group. The myocardium in sham-operated rats showed no observable damage. Total RNA was purified from microdissected brain tissue blocks containing hypothalamus, dorsal pons, dorsal medulla, rostral ventrolateral medulla, and caudal ventrolateral medulla. Changes in nNOS mRNA were semiquantified in each region using reverse transcription-polymerase chain reactions in which known concentrations of deletion mutant of the gene were coamplified as an internal standard. Compared with controls, significant decreases in nNOS mRNA levels were found in hypothalamus (19%), dorsal pons (43%) and dorsal medulla (34%) of rats with heart failure. There were no statistically significant differences in nNOS mRNA levels in rostral or caudal ventrolateral medulla between the control and heart failure groups. Concomitant with the changes nNOS gene expression in central sites, the plasma concentration of norepinephrine was significantly elevated in rats with heart failure compared to sham-operated control rats. Our results show that heart failure is associated with decreases in nNOS gene expression in at least three regions of the brain and with increased sympathetic outflow to the periphery. The decreased NO production that is likely associated with the decreases in nNOS gene expression may lead to the increased sympathetic drive seen in chronic heart failure.

Decreased gene expression of neuronal nitric oxide synthase in hypothalamus and brainstem of rats in heart failure

Nitric oxide may act at autonomic sites in the brain to regulate sympathetic outflow. Our goal was to determine whether gene expression of the neuronal isoform of nitric oxide synthase (nNOS) is altered in discrete autonomic brain regions of rats in the chronic phase of heart failure compared to sham-operated control rats. Experiments were performed in rats 4 to 5 weeks after left coronary artery ligation. Histological data indicated that there was a 39% outer and a 45% inner infarct of the left ventricular myocardium in the heart failure group. The myocardium in sham-operated rats showed no observable damage. Total RNA was purified from microdissected brain tissue blocks containing hypothalamus, dorsal pons, dorsal medulla, rostral ventrolateral medulla, and caudal ventrolateral medulla. Changes in nNOS mRNA were semiquantified in each region using reverse transcription-polymerase chain reactions in which known concentrations of deletion mutant of the gene were coamplified as an internal standard. Compared with controls, significant decreases in nNOS mRNA levels were found in hypothalamus (19%), dorsal pons (43%) and dorsal medulla (34%) of rats with heart failure. There were no statistically significant differences in nNOS mRNA levels in rostral or caudal ventrolateral medulla between the control and heart failure groups. Concomitant with the changes nNOS gene expression in central sites, the plasma concentration of norepinephrine was significantly elevated in rats with heart failure compared to sham-operated control rats. Our results show that heart failure is associated with decreases in nNOS gene expression in at least three regions of the brain and with increased sympathetic outflow to the periphery. The decreased NO production that is likely associated with the decreases in nNOS gene expression may lead to the increased sympathetic drive seen in chronic heart failure.