ABSTRACT
It has been reported that high levels of calcium-phosphorus (Ca-P) product are an indicator of coronary calcification and mortality risk in patients undergoing chronic hemodialysis. In the present study, we aimed to evaluate the significance of Ca-P product to predict the prognosis of patients with heart failure (HF) and chronic kidney disease (CKD). We conducted a prospective observational study of 793 patients with decompensated HF and CKD, and measured the value of Ca-P product. The cut-off value was obtained from the survival classification and regression tree (CART) analysis to predict post-discharge all-cause mortality and/or worsening HF, and the patients were divided into 2 groups: a high group (Ca-P product > 28, n = 594) and a low group (Ca-P product ≤ 28, n = 199). We compared the patient baseline characteristics and post-discharge prognosis between the 2 groups. The age as well as the prevalence of male sex, ischemic etiology, and anemia were significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between the 2 groups. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (log-rank P = 0.001). In the multivariable Cox proportional hazard analysis, lower Ca-P product was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 0.981, P = 0.031). Lower Ca-P product predicts adverse prognosis in patients with HF and CKD.
Subject(s)
Heart Failure , Renal Insufficiency, Chronic , Humans , Calcium , Aftercare , Patient Discharge , Prognosis , Renal Insufficiency, Chronic/complications , PhosphorusABSTRACT
Objective The relationship between changes in the nutritional status after cardiac resynchronization therapy (CRT) and the prognosis has not been fully elucidated. We aimed to evaluate the changes in the nutritional status as assessed by the prognostic nutritional index (PNI) and their associations with the improvement in the cardiac function and subsequent clinical outcomes. Methods The study population consisted of 119 patients with a CRT-device. They were divided into 2 groups, based on whether their PNI had increased at 6 months after CRT-device implantation (positive ΔPNI group, n=73) or not (negative ΔPNI group, n=46). The left ventricular (LV) end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were measured before and six months after CRT-device implantation. We compared the changes in the cardiac function and prevalence of adverse events (re-hospitalization due to worsening heart failure or all cause death) between the two groups. Results In the positive ΔPNI group, the LVEDV (186±93 mL vs. 149±71 mL, p<0.05) and LVESV (134±75 mL vs. 98±62 mL, p<0.05) were significantly decreased 6 months after CRT-device implantation. In addition, the LVEF (31±11% vs. 37±12%, p<0.05) was significantly increased after CRT-device implantation. In the negative ΔPNI group, no significant changes were observed in any echocardiographic parameters. During a median follow-up period of 914 days, there were 67 (56.3%) adverse events. In the Kaplan-Meier analysis, the positive ΔPNI group was associated with a lower risk of adverse events than the negative ΔPNI group (50.6% vs. 65.2%, log-rank p=0.042). Conclusion Our results suggest that improvement in the cardiac function after CRT-device implantation is associated with increases in the PNI, resulting in favorable outcomes.
Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Heart Failure/therapy , Humans , Nutrition Assessment , Prognosis , Stroke Volume , Treatment OutcomeABSTRACT
BACKGROUND: Senescence is a major factor that increases oxidative stress in mitochondria, which contributes toward the pathogenesis of heart disease. However, the effect of antioxidant therapy on cardiac mitochondria in aged-cardiac performance remains elusive. OBJECTIVES: We postulated that the mitochondrial targeting of superoxide scavenging would have benefits in the aged heart. METHODS AND RESULTS: Generation of superoxide in the mitochondria and nicotinamide adenine dinucleotide phosphate oxidase activity increased in the heart of old mice compared with that in young mice. In old mice treated with a mitochondria-targeted antioxidant MitoTEMPO (180 µg/kg/day, 28 days) co-infusion using a subcutaneously implanted minipump, levels of superoxide in the mitochondria and nicotinamide adenine dinucleotide phosphate oxidase activity as well as hydrogen peroxide decreased markedly in cardiomyocytes. Treatment with MitoTEMPO in old mice improved the systolic and diastolic function assessed by echocardiography. Endothelium-dependent vasodilation in isolated coronary arteries and endothelial nitric-oxide synthase phosphorylation were impaired in old mice compared with that in young mice and were improved by MitoTEMPO treatment. Mitochondria from the old mice myocardium showed lower rates of complex I-dependent and II-dependent respiration compared with that from young mice. Supplementation of MitoTEMPO in old mice improved the respiration rates and efficiency of ATP generation in mitochondria to a level similar to that of young mice. CONCLUSION: Resolution of oxidative stress in mitochondria by MitoTEMPO in old mice restored cardiac function and the capacity of coronary vasodilation to the same magnitude observed in young mice. An antioxidant strategy targeting mitochondria could have a therapeutic benefit in heart disease with senescence.
Subject(s)
Aging/metabolism , Antioxidants/pharmacology , Coronary Vessels/drug effects , Mitochondria, Heart/drug effects , Myocytes, Cardiac/drug effects , Organophosphorus Compounds/pharmacology , Oxidative Stress/drug effects , Piperidines/pharmacology , Adenosine Triphosphate/metabolism , Age Factors , Animals , Antioxidants/administration & dosage , Cell Respiration/drug effects , Coronary Vessels/metabolism , Hydrogen Peroxide/metabolism , Infusions, Subcutaneous , Male , Mice, Inbred C57BL , Mitochondria, Heart/metabolism , Myocytes, Cardiac/metabolism , NADPH Oxidases/metabolism , Nitric Oxide Synthase Type III/metabolism , Organophosphorus Compounds/administration & dosage , Phosphorylation , Piperidines/administration & dosage , Superoxides/metabolism , Vasodilation/drug effects , Ventricular Function, Left/drug effectsABSTRACT
BACKGROUND: Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODSâANDâRESULTS: In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60â for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS: Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.
Subject(s)
Diabetic Cardiomyopathies/therapy , Heart Failure/therapy , Hot Temperature , Steam Bath , Aged , Aged, 80 and over , Chronic Disease , Diabetic Cardiomyopathies/blood , Female , Heart Failure/blood , Heart Failure/etiology , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Prospective StudiesABSTRACT
Several studies have demonstrated that oral intake of n-3 polyunsaturated fatty acids, specifically eicosapentaenoic acid (EPA), prevents ventricular tachyarrhythmias (VT) with ischemic heart disease, but the underlying mechanisms still remain unclear. Thus, we examined the relation between the serum EPA/arachidonic acid (AA) ratio and electrophysiological properties in patients with ischemic heart disease. The study subjects consisted of 57 patients (46 males, mean age, 66 ± 13 years) with ischemic heart disease. T-wave alternans (TWA) and heart rate variability were assessed by 24hour Holter ECG, and left ventricular ejection fraction (LVEF) was determined by echocardiography. Fasting blood samples were collected, and the serum EPA/AA ratio was determined. Based on a median value of the serum EPA/AA ratio, all subjects were divided into two groups: serum EPA/AA ratio below 0.33 (Group-L, n = 28) or not (Group-H, n = 29). We compared these parameters between the two groups. LVEF was not different between the two groups. The maximum value of TWA was significantly higher in Group-L than in Group-H (69.5 ± 22.8 µV versus 48.7 ± 12.0 µV, P = 0.007). In addition, VT defined as above 3 beats was observed in 7 cases (25%) in Group-L, but there were no cases of VT in Group-H (P = 0.004). However, low-frequency (LF) component, high-frequency (HF) component, LF to HF ratio, and standard deviation of all R-R intervals were not different between the two groups. These results suggest that a low EPA/AA ratio may induce cardiac electrical instability, but not autonomic nervous imbalance, associated with VT in patients with ischemic heart disease.
Subject(s)
Arachidonic Acid/blood , Eicosapentaenoic Acid/blood , Myocardial Ischemia , Tachycardia, Ventricular , Aged , Electrocardiography, Ambulatory/methods , Electrophysiologic Techniques, Cardiac/methods , Electrophysiological Phenomena , Female , Glucans , Humans , Japan , Male , Middle Aged , Myocardial Ischemia/blood , Myocardial Ischemia/complications , Myocardial Ischemia/diagnosis , Myocardial Ischemia/physiopathology , Predictive Value of Tests , Risk Assessment/methods , Risk Factors , Statistics as Topic , Tachycardia, Ventricular/blood , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/physiopathologyABSTRACT
BACKGROUND: Serum heart-type fatty acid-binding protein (H-FABP) has been widely used as a marker of cardiac myocyte injury. This study was carried out to examine the relationships of H-FABP levels with age, gender, and other physiologic characteristics in a large population of community-dwelling residents. METHODS AND RESULTS: Serum H-FABP levels were measured in 2,099 subjects who received an annual health check-up (age 40-87 years). The relationships between H-FABP and blood pressure, laboratory data, electrocardiogram (ECG) findings, and lifestyle factors were cross-sectionally analyzed. Mean H-FABP values were significantly higher in men than in women. Serum H-FABP levels were increased with aging significantly. Both the multivariate regression and multiple logistic regression analyses indicated that serum H-FABP levels were independently affected by age, body mass index, creatinine clearance, and ECG abnormality score. CONCLUSION: Serum H-FABP levels were affected by age, gender, obesity, renal function, and ECG abnormality in a large group of volunteers. These effects should be taken into account in determining appropriate reference values for H-FABP. In addition, high serum H-FABP levels may represent latent cardiac injury and have important clinical implications.
Subject(s)
Fatty Acid-Binding Proteins/blood , Heart Diseases/blood , Heart Diseases/physiopathology , Myocytes, Cardiac/metabolism , Adult , Age Factors , Aged , Aged, 80 and over , Asian People , Body Mass Index , Creatinine/blood , Cross-Sectional Studies , Electrocardiography , Fatty Acid Binding Protein 3 , Female , Heart Diseases/epidemiology , Humans , Japan , Kidney/metabolism , Kidney/physiopathology , Male , Middle Aged , Molecular Epidemiology , National Health Programs , Obesity/blood , Obesity/epidemiology , Obesity/physiopathology , Sex FactorsABSTRACT
Despite a variety of biological roles for nitric oxide (NO) in the cardiovascular system, little is known about whether NO is involved in cardiac hypertrophy. We hypothesized that NO production following a sustained increase in shear stress by volume-overload modifies the level of cardiac hypertrophy independent of hemodynamic changes. Volume-overload was induced by shunt formation between the left common carotid artery and the external jugular vein in 21 rabbits. These shunt rabbits were randomly assigned to 3 groups: shunt with no treatment (n = 8), shunt treated with a low dose of N(G)-nitro-L-arginine methyl ester (L-NAME. 0.5 g/L in drinking water, n=8), and shunt with a high dose of L-NAME (1.5 g/L, n = 5). Eight sham operated rabbits were used as controls. Treatments were started immediately after operation and were continued for 6 weeks. Chronic volume-overload by shunt formation caused left ventricular dilatation and arterial enlargement proximal to the fistula. The relative wall thickness of the left ventricle was decreased, indicating eccentric cardiac hypertrophy. L-NAME elevated mean arterial blood pressure (P < 0.01) and reduced the increment of cardiac output (P < 0.05). L-NAME attenuated ventricular weight (P < 0.01) ventricular cavity dilatation (P < 0.01). and arterial enlargement (P < 0.05). The re-capitulation of atrial natriuretic factor mRNA in the hypertrophied left ventricular myocardium by volume-overload was attenuated with L-NAME. In this model with chronic volume-overload, NO plays a pivotal role in the progression of cardiovascular remodeling by regulating the loading conditions of the heart.