Clinical characteristics and outcomes of heart failure with preserved ejection fraction: Lessons from epidemiological studies

SummaryRecent epidemiological studies have demonstrated that nearly half of all patients with heart failure (HF) have preserved left ventricular ejection fraction (HFPEF). Compared to those with reduced EF, patients with HFPEF are older, more likely to be women, less likely to have coronary artery disease, and more likely to have hypertension and atrial fibrillation. Patients with HFPEF receive different pharmacological as well as nonpharmacological treatments from those with reduced EF. Morbidity and mortality in patients with HFPEF are largely similar to those with reduced EF. Although much information has recently been obtained about the clinical characteristics, medications, and outcomes of HFPEF by large-scale clinical and epidemiological studies, effective management strategies need to be established for this type of HF

The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes

A failing heart shows severe energy insufficiency, and it is presumed that this energy shortage plays a critical role in the development of cardiac dysfunction. However, little is known about the mechanisms that cause energy metabolic alterations in the failing heart. Here, we show that the novel RING-finger protein 207 (RNF207), which is specifically expressed in the heart, plays a role in cardiac energy metabolism. Depletion of RNF207 in neonatal rat cardiomyocytes (NRCs) leads to a reduced cellular concentration of adenosine triphosphate (ATP) and mitochondrial dysfunction. Consistent with this result, we observed here that the expression of RNF207 was significantly reduced in mice with common cardiac diseases including heart failure. Intriguingly, proteomic approaches revealed that RNF207 interacts with the voltage-dependent anion channel (VDAC), which is considered to be a key regulator of mitochondria function, as an RNF207-interacting protein. Our findings indicate that RNF207 is involved in ATP production by cardiomyocytes, suggesting that RNF207 plays an important role in the development of heart failure

Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

<p>Abstract</p> <p>Background</p> <p>The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM) have not been defined completely. We have shown in conscious dogs with DM that: <it>1</it>) baseline coronary blood flow (CBF) was significantly decreased, <it>2</it>) endothelium-dependent (ACh) coronary vasodilation was impaired, and <it>3</it>) reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes.</p> <p>Methods</p> <p>Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv) over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4).</p> <p>Results</p> <p>The array data revealed that 797 genes were differentially expressed (P < 0.01; fold change of at least ±2). 150 genes were expressed at significantly greater levels in diabetic dogs and 647 were significantly reduced. There was no change in eNOS mRNA. There was up regulation of some components of the NADPH oxidase subunits (gp91 by 2.2 fold, P < 0.03), and down-regulation of SOD1 (3 fold, P < 0.001) and decrease (4 - 40 fold) in a large number of genes encoding mitochondrial enzymes. In addition, there was down-regulation of Ca²⁺cycling genes (ryanodine receptor; SERCA2 Calcium ATPase), structural proteins (actin alpha). Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase), which were markedly down regulated.</p> <p>Conclusion</p> <p>our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.</p

Cross-disease communication between cancer and heart failure provides a rational approach to prevention and treatment of both diseases

Accumulating clinical data have demonstrated a clear positive association between cancer and cardiac disorders, particularly chronic heart failure (CHF). These two diseases can be mutual drivers of each other, and hence frequently co-occur in patients. The immune system is the core mechanism that eliminates transformed cells from our bodies. However, immune cells often play distinct or even conflicting roles in cancer and CHF. Moreover, CHF alters the properties of immune cells, particularly those of regulatory T cells. Our previous study showed that the oxidative phosphorylation capacity of peripheral blood mononuclear cells is impaired in CHF, leading to the increased production of reactive oxygen species. Therefore, the co-occurrence of cancer and CHF becomes a serious problem, affecting the treatment of both diseases, and consequently negatively affecting patient survival rates. To date, few methods have been identified that effectively treat both diseases at the same time. Mitochondria activity may change in immune cells during their activation and exhaustion, and in CHF. Mitochondria activity is also largely affected in myocardia in CHF. We here focus on the mitochondrial abnormalities of immune cells in cancer and CHF, and discuss possible ways to treat cancer and CHF at the same time by targeting mitochondrial abnormalities. Many cancer cells are inevitably produced daily in our bodies, mostly owing to enzymatic nucleotide errors of DNA replication and repair. Therefore, the possibility of ways to prevent cancer by preventing the onset of heart failure will also be discussed

Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease. It also causes skeletal muscle dysfunction, which is responsible for reduced exercise capacity commonly seen in heart failure. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac and skeletal muscle dysfunction in heart failure and diabetes mellitus. Based on the findings in animal models, this review discusses the role of oxidative stress that may be involved in the development and progression of cardiac and skeletal dysfunction associated with diabetes

Clinical Characteristics and Outcome of Hospitalized Patients With Heart Failure in Japan

Background :Heart failure (HF), defined as a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood, is a leading cause of mortality and hospitalization for adults older than 65 years in the industrialized countries. The characteristics and outcome of patients with HF have been described by several epidemiological studies and large scale clinical trials, performed mainly in the United States and Europe. Very little information is available on this issue in Japan. Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) is designed to prospectively study the characteristics, treatment, and outcomes of a broad sample of patients hospitalized with HF at teaching hospitals throughout Japan between January 2004 to June 2005 and the outcomes, including death and hospital readmission, will be followed through 2006 (mean follow-up at least 1 year). Participating cardiologists identify patients admitted for worsening of HF symptoms. Demographics, medical history, severity, treatment, and outcome data are collected and entered into a database via secure web browser technology. As of June 2005, baseline data for 2,676 patients with HF have been registered from 164 participating hospitals. Conclusions: The JCARE-CARD will provide important insights into the management of patients with HF in routine clinical practice in Japan, thus providing the framework for improved management strategies for these patients. (Circ J 2006; 70: 1617 - 1623