Congestive Heart Failure Group Research Articles

Gender differences across racial and ethnic groups in the quality of care for acute myocardial infarction and heart failure associated with comorbidities

This paper provides important insights on gender differences across racial and ethnic groups in a Medicare population in terms of the quality of care received for acute myocardial infarction (AMI) and congestive heart failure (CHF) in association with diabetes or hypertension/end-stage renal disease (ESRD). Both race/ethnicity and gender are associated with differences in the diagnostic evaluation and treatment of Medicare recipients with these conditions. In the AMI group, non-Hispanic Black and Hispanic patients of both genders were less likely to receive aspirin or beta-blockers than non-Hispanic Whites. These differences persisted for Hispanic women and men even when they presented with ESRD or diabetes. Rates for smoking cessation counseling were among the lowest among non-Hispanic Blacks and Hispanics with AMI-diabetes and non-Hispanic blacks with AMI-hypertension/ESRD. Gender comparisons within racial groups for the AMI and AMI-diabetes groups show that among non-Hispanic Whites, women were less likely to receive aspirin and beta-blockers. No gender differences were noted among non-Hispanic Black and Hispanic Medicare recipients. In the CHF group, Hispanics were the racial/ethnic group least likely to have an assessment of left ventricular function (LVF), even if they had diabetes and had lower rates of angiotensin-converting enzyme inhibitor therapy or even if they had combined CHF-hypertension/ESRD. Gender comparisons in both the CHF and CHF-hypertension/ESRD groups show that non-Hispanic White women were less likely to have an LVF assessment than non-Hispanic White men. Among all subjects, having comorbidities with AMI was not associated with higher markers of quality cardiovascular care. Closing the many gaps in cardiovascular care must target the specific needs of women and men across racial and ethnic groups.

Endothelial Activation, Dysfunction, and Damage in Congestive Heart Failure and the Relation to Brain Natriuretic Peptide and Outcomes

Congestive heart failure (CHF) is associated with marked endothelial dysfunction. We hypothesized that acute and chronic CHF may manifest different degrees of endothelial damage/dysfunction and activation, as reflected by different plasma endothelial markers, such as von Willebrand factor (vWF) and soluble thrombomodulin (both are indexes of endothelial damage/dysfunction) and soluble E-selectin (an index of endothelial activation). Second, we hypothesized a relation between endothelial markers and B-type natriuretic peptide (BNP, an index of cardiac function) in acute and chronic CHF that could be linked to prognosis. To test this hypothesis, we studied 35 patients with acute CHF, 40 patients with chronic CHF, and 32 healthy controls. The patients with CHF were followed up for the combined outcomes of cardiovascular death, nonfatal myocardial infarction, stroke, thromboembolism, and recurrent admissions to the hospital. vWF (p = 0.001), soluble thrombomodulin, E-selectin, and BNP (all p <0.0001) were higher in patients with acute and chronic CHF compared with controls. When the 2 CHF groups were compared, no significant differences were found in vWF or E-selectin (p = NS), but soluble thrombomodulin was significantly elevated in acute CHF (Tukey's post hoc test, p <0.05). Only high vWF was associated with a poorer outcome (log-rank test, p = 0.0188). None of the endothelial indexes correlated with plasma BNP. After a median follow-up of 18 months, only high (median or higher) vWF levels were predictive of adverse outcomes in the patients with CHF (log-rank statistic = 5.52, degree of freedom 1, p = 0.0188). In conclusion, despite similar ejection fractions, patients with acute and chronic CHF have different degrees of endothelial damage/dysfunction and activation, which may be related to differences in pathophysiology. High levels of vWF were associated with a worse short-term outcome. These endothelial markers were unrelated to plasma BNP levels and may imply a different release mechanism.

Effect of Congestive Heart Failure on Mexiletine Pharmacokinetics in a Japanese Population

The goal of this study was to evaluate the influence of congestive heart failure (CHF) on the clearance of mexiletine. The mexiletine clearance/bioavailability (CL/F) ratio was estimated in 584 inpatients receiving mexiletine therapy. The study population consisted of 210 patients with CHF [CHF group; 116 inpatients with New York Heart Association (NYHA) class I-II (group NYHA I-II) CHF and 94 inpatients with NYHA class III-IV (group NYHA III-IV) CHF] and 374 inpatients without CHF (Non-CHF group). Serum levels of mexiletine were determined by high performance liquid chromatography (HPLC). Mexiletine clearance was significantly lower in the CHF group when compared with the Non-CHF group (0.264+/-0.093 vs. 0.393+/-0.082 l/h/kg, mean+/-S.D., p<0.05). Further, the CL/F ratio was 50% lower in group NYHA III-IV when compared with the Non-CHF group, and the CL/F ratio tended to change in inverse proportion to NYHA class. CHF status significantly affects mexiletine clearance. Therefore, dose adjustments and careful monitoring are likely required in CHF patients receiving mexiletine.

Prognostic value of homocysteinemia in patients with congestive heart failure

Elevated plasma homocysteine levels are associated with increased risk of vascular disease and of congestive heart failure (CHF), with a relationship between homocysteine values and disease severity. Hyperhomocysteinemia is a risk factor for cardiac dysfunction. In this study, the predictive value of elevated homocysteine levels was investigated in the prognosis of ischemic and non-ischemic CHF. A total of 159 patients with CHF, 89 with non-ischemic and 70 with ischemic CHF (83% males, mean age 62 years, mean ejection fraction 27%), and 119 controls (79% males, mean age 59.8 years) had fasting blood samples taken to measure plasma homocysteine, vitamin B(12) and folate levels. Coronary angiography was performed for all patients. The mean duration of follow-up was 49.6+/-36.7 months. As in other studies, the mean level of homocysteinemia was significantly higher in the CHF group (15.80 micromol/L) than in the control group (10.90 micromol/L) (p=0.001) whatever the etiology (non-ischemic, 16.11+/-6.84 micromol/L; ischemic, 15.41+/-6.45 micromol/L). This result was observed without vitamin deficiency, but in patients, the mean creatinine value was moderately higher than in controls. We found a positive correlation between plasma homocysteine levels and New York Heart Association (NYHA) classification, creatinine and age. Moreover, hyperhomocysteinemia appears to be a powerful predictive factor of mortality in CHF patients (relative risk of death, 4.23; p=0.0003). In the follow-up of this study, 41.5% of patients with homocysteinemia >17 micromol/L died vs. 21.3% of patients with levels <17 micromol/L. In multivariate analysis, when homocysteine levels were adjusted for a second parameter (age, NYHA, creatinine, diabetes), the risk of death remained significant after each adjustment. Elevated homocysteine levels observed in CHF patients, whatever the etiology of their heart disease (ischemic or non-ischemic), were correlated with the severity of the disease. Hyperhomocysteinemia appears to be a predictive factor of mortality in CHF patients.

Usefulness of Korean Guideline for Grading Disability in Patient with Congestive Heart Failure

Background and Objectives:The increased prevalence of congestive heart failure (CHF) and disabled population with heart diseases has led, in 2000, to the establishment of Korean guidelines for grading disability in patients with CHF, but its usefulness has not been tested. The purpose of this study is to investigate the usefulness of the guidelines in grading disability and predicting the prognosis of patients with CHF. Subjects and Methods:Between January, 1999 and March, 2003, 546 consecutive CHF patients were enrolled. Of these 546 patients, only 240 completed one year of follow up before the severity of disability was graded. They were classified into either the disabled or non-disabled groups according to the Korean guidelines for grading disability. They were also subdivided into severe CHF or non severe groups. Severe CHF was defined as a status greater than New York Heart Association class III or to those requiring frequent hospitalization, i.e. more than twice. The mortality and frequency of severe CHF between the disabled and non-disabled groups were evaluated. Results: The prevalence of the disabled with CHF was 7.1% (17/240); one patient was graded in the severe disabled (grade 1), 4 in the moderate (grade 2) and 12 in the mild disabled (grade 3) groups. The mortality within the disabled group was higher than that in the non disabled group (8/17 vs. 1/223, 47.6% vs. 0.4%, p<0.001), but there was no difference according to the severity of disability (p=0.26). All survivors (9 patients) in the disabled group were classified with severe CHF, but 15 from 222 (6.8%) patients not classified in the disabled group also showed severe CHF stati. Half (8 patients, 50%) of the 16 whose total disability scores ranged between 15 and 19, 7 (21.2%) of the 33 with total scores between 10 and 14 were classified with severe CHF stati. Conclusion: The current Korean guidelines for grading of disability were able to relatively well predict the prognosis of CHF between the disabled and non disabled groups, but appeared too strict, in that some severe patients cannot be classified into the disabled group. Therefore, the current guidelines will either require modification following a large scaled study or the disability grades will have to be classified into more than 4 categories. (Korean Circulation J 2006;36:644-651)

Does symptom‐limited cycle exercise cause low frequency diaphragm fatigue in patients with heart failure?

Reduced diaphragm contractility occurs in some healthy subjects when they exercise to exhaustion. This indicates low frequency fatigue, which may contribute to task failure. We hypothesised that patients with congestive heart failure (CHF) might be especially vulnerable to the development of low frequency diaphragm fatigue after exhaustive exercise. To study the effect of exhaustive incremental cycle exercise on diaphragm contractility in patients with CHF. 12 patients with CHF with an ejection fraction of 36.5 +/- 7.3% and 12 healthy age-matched control subjects performed an incremental cycle test to exhaustion. The unpotentiated twitch transdiaphragmatic pressure (twitch Pdi) in response to bilateral anterolateral magnetic phrenic nerve stimulation (BAMPS) was measured before and after exercise. Twitch Pdi at baseline was 20.2 +/- 6.7 cm H2O in the CHF group and 20.3 +/- .3 cm H2O in the controls (p = 0.957). 25 and 35 min post exercise the values were 19.9+/-5.4 and 20.0+/-5.1 cm H2O in the CHF group and 20.6 +/- 4.3 and 21.2 +/- 3.4 cm H2O in the control group; neither change was significant (F(2,27) = 0.007, p = 0.993; F(2,33) = 0.144, p = 0.866, respectively). When patients with CHF cycle to exhaustion, low frequency fatigue of the diaphragm does not occur, and this is unlikely to be an important factor limiting exercise capacity of such patients.

Diastolic Asynchrony Is More Frequent Than Systolic Asynchrony in Dilated Cardiomyopathy and Is Less Improved by Cardiac Resynchronization Therapy

To compare the incidence of diastolic and systolic asynchrony, assessed by tissue Doppler imaging (TDI), in patients with congestive heart failure (CHF) and severe left ventricular (LV) dysfunction, and to assess TDI changes induced by cardiac resynchronization therapy (CRT). Thirty percent of CRT candidates are nonresponders. Besides QRS width, the presence of echographic systolic asynchrony has been used to identify future responders. Little is known about diastolic asynchrony and its change after CRT. Tissue Doppler imaging was performed in 116 CHF patients (LV ejection fraction 26 +/- 8%). Systolic and diastolic asynchrony was calculated using TDI recordings of right ventricular and LV walls. The CHF group consisted of 116 patients. Diastolic asynchrony was more frequent than systolic, concerning both intraventricular (58% vs. 47%; p = 0.0004) and interventricular (72 vs. 45%; p < 0.0001) asynchrony. Systolic and diastolic asynchrony were both present in 41% patients, but one-third had isolated diastolic asynchrony. Although diastolic delays increased with QRS duration, 42% patients with narrow QRS presented with diastolic asynchrony. Conversely, 27% patients with large QRS had no diastolic asynchrony. Forty-two patients underwent CRT. Incidence of systolic intraventricular asynchrony decreased from 71% to 33% after CRT (p < 0.0001), but diastolic asynchrony decreased only from 81% to 55% (p < 0.0002). Cardiac resynchronization therapy induced new diastolic asynchrony in eight patients. Diastolic asynchrony is weakly correlated with QRS duration, is more frequent than systolic asynchrony, and may be observed alone. Diastolic asynchrony is less improved by CRT than systolic. Persistent diastolic asynchrony may explain some cases of lack of improvement after CRT despite good systolic resynchronization.

Effects of omapatrilat on cardiac nerve sprouting and structural remodeling in experimental congestive heart failure

Congestive heart failure (CHF) results in decreased cardiac sympathetic innervation. The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates cardiac neuronal remodeling in CHF. We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n = 8) or without (CHF group, n = 10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine cardiac structure and hemodynamic parameters. Myocardial nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls. In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group (P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high nerve counts. OMA treatment prevented heterogeneous reduction of nerve density. The left ventricular TH-positive nerve densities were 128 +/- 170 microm(2)/mm(2), 261 +/- 185 microm(2)/mm(2), and 503 +/- 328 microm(2)/mm(2) (P < .05), and the atrial GAP43-positive nerve densities were 1,683 +/- 1,365 microm(2)/mm(2), 305 +/- 368 microm(2)/mm(2), and 1,278 +/- 1,479 microm(2)/mm(2) (P < .05) for the control, CHF, and CHF+OMA groups, respectively. CHF results in heterogeneous cardiac denervation. Long-term OMA treatment prevented the reduction of nerve density and promoted beneficial cardiac structural remodeling.

Spironolactone improves carotid artery fibrosis and distensibility in rat post-ischaemic heart failure

Myocardial infarction causes neurohormonal activation involving aldosterone and angiotensin II (AngII). These hormones may increase arterial stiffness, an independent cardiovascular risk factor contributing to progression of congestive heart failure (CHF). This study aimed to determine the effect of aldosterone and AngII blockade on carotid artery distensibility and collagen density in adult Wistar rats with MI-induced CHF. Five groups were studied: Sham-operated, CHF, CHF + spironolactone, CHF + lisinopril, CHF + Spironolactone + Lisinopril. After echocardiography, in vitro isobaric carotid distensibility (echo-tracking technique) and collagen density were measured, and the incremental elastic modulus (Einc) calculated. In the CHF group, intra-ventricular pressure and cardiac weight were increased; carotid distensibility was reduced (CHF: 0.42 ± 0.30 per mmHg 3 versus sham: 1.75 ± 0.50 per mmHg 3; P < 0.001), and collagen content increased by 87% when compared to sham. All treatments reduced intra-ventricular pressure, carotid distensibility and fibrosis when compared to CHF but did not change cardiac weight. However, carotid distensibility and intra-ventricular pressure were not completely restored towards sham values and were significantly and inversely related. Spironolactone, which did not decrease significantly blood pressure, was the only drug reducing Einc independently of wall stress (WS). Thus, MI-induced CHF was associated with carotid artery remodeling. This vascular change, which may contribute to maintain cardiac hypertrophy and CHF, is largely prevented by AngII and aldosterone blockade. Only spironolactone reduced the stiffness of carotid wall material independently of blood pressure and WS.

PTEN/PI3K pathways are involved in the signal transduction of myocardial remodeling in patients with congestive heart failure

To investigate the roles of PTEN (phosphatase and tensin homologue deleted on chromosome ten)/PI3K (phosphatidylinositol 3 kinase) signal transduction pathways in myocardium remodeling in patients with congestive heart failure (CHF). A small amount of papillary muscle tissue was collected during mitral valve displacement from 39 patients of mitral valve disease with CHF, 12 cases with grade II, 15 cases with grade III, and 12 cases with grade IV cardiac function. 30 cases of healthy persons and 8 cases of heart donors who died of accident were included as controls. Pathological examination was conducted. Immunoprecitipation was used to assay the protein expression and phosphorylation of PTEN, PI3K and Akt (protein kinase B), and protein expression of alpha-skeletal-actin in myocardial tissues. Typical myocardial remodeling was shown in the myocardial tissues from the valvular heart disease patients with CHF. Hypertrophy was dominant in the myocardial tissues at early stagy of CHF, the myocardial tissues in the end stage of CHF was characterized by disordered alignment of myocytes, discontinuity and dissolving of cardiac fiber, destroyed subcellular organs, and hyperplasia of interstitial tissue. The protein expression of PTEN [absorbance value (A) ratio of PTEN and beta-actin] in control group was 3.29 +/- 0.11, grade II cardiac function was 2.56 +/- 0.19, grade III was 1.52 +/- 0.35, grade IV was 0.91 +/- 0.10, PTEN protein expressions in CHF groups were lower than that of control group and negatively correlated to the levels of cardiac function (P < 0.05 or 0.01). On the contrary, The phosphorylation of PI3K (PI3K/beta-actin) in control group was 0.21 +/- 0.04, grade II cardiac function was 0.52 +/- 0.09, grade III was 1.12 +/- 0.29, grade IV was 1.62 +/- 0.54; The phosphorylation of Akt (Akt/beta-actin) in control group was 0.75 +/- 0.13, grade II cardiac function was 1.21 +/- 0.34, grade III was 2.45 +/- 0.71, grade IV was 3.55 +/- 0.80; The protein expression of alpha-skeletal-actin (alpha-skeletal-actin/beta-actin) in control group was 0.20 +/- 0.03, grade II cardiac function was 0.41 +/- 0.04, grade III was 0.82 +/- 0.09, grade IV was 1.56 +/- 0.11, their expressions in CHF groups were higher than that of control group and positively correlated to the levels of cardiac function (P < 0.05 or 0.01). Both the PTEN and PI3K signal pathways are involved in the pathogenesis of myocardial remodeling in CHF patients with valvular heart disease, which play an important role in the pathogenesis of myocardial hypertrophy. PTEN may play a negative regulation role in the process of myocardial remodeling.

Diagnostic value of plasma concentration of pro-brain natriuretic peptide in congestive heart failure in pediatric patients with ventricular septal defects

The value of plasma brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) can reflect cardiac function and therefore can be used for diagnosing congestive heart failure (CHF) and evaluating cardiac function. There are few reports, however, on the value of BNP and NT-proBNP in pediatric cases of congenital heart defect. The aim of this study was to assess the value of plasma NT-proBNP in the diagnosis of CHF and evaluation of cardiac function in pediatric patients with ventricular septal defect (VSD). Fifty-one patients with VSD aged from 2 months to 2 years old (mean 7.9 months) were enrolled. According to the modified Ross Score, the patients were divided into three groups, no CHF group (20 patients), mild CHF group (18 patients) and moderate to severe CHF group (13 patients). Fifteen age-matched normal children were used as controls. Plasma NT-proBNP was measured using enzyme immunoassay. All patients had complete echocardiographic study, including measurement of left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic wall stress (LVSEWS), heart rate corrected mean velocity of circumferential fiber shortening (mVcFc), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and contractility index (Con). The correlation between plasma NT-proBNP level and modified Ross Score and echocardiographic cardiac functional indexes was determined. The sensitivity, specificity and ROC curve of plasma NT-proBNP for diagnosing CHF was studied. Plasma NT-proBNP was positively correlated with modified Ross Score (r = 0.75, P < 0.01). Plasma NT-proBNP concentration in moderate to severe CHF group (2061 +/- 908) fmol/ml was significantly higher than that of mild CHF group (810 +/- 335) fmol/ml, and Plasma NT-proBNP concentration in mild CHF group was higher than that in no CHF group (309 +/- 68) fmol/ml. 97.14% of normal controls and subjects in no CHF group had their plasma NT-proBNP below 400 fmol/ml. 83.3% of children in mild CHF group had their plasma NT-proBNP between (400-1400) fmol/ml while in moderate and severe CHF group 84.6% of children had their plasma NT-proBNP beyond 1400 fmol/ml. Plasma NT-proBNP was also positively correlated with LVEDVI and LVSEWS. There was no correlation among mVcFc, LVEF, LVFS, Con and plasma NT-proBNP concentration. Using plasma NT-proBNP concentration > or = 400 fmol/ml as cut-point for diagnosing CHF, the sensitivity was 89.3%, the specificity was 91.2%, and the area under the ROC curve was 0.944. Plasma NT-proBNP level could be used to assess cardiac function and diagnose CHF in pediatric patients with VSD.

Muscle metaboreflex is blunted with reduced vascular resistance response of nonexercised limb in patients with chronic heart failure

Background Exercise-mediated muscle metaboreflex (MMR) activates the sympathetic nervous system afferently and may play an important role in the reduction in blood flow in nonexercised limb, thus enhancing exercised skeletal muscle blood flow (ie, normal regional blood flow redistribution during exercise). However, few data are available to describe the relationship between MMR and peripheral vascular control during exercise in congestive heart failure (CHF). The aim of this study was to determine whether MMR is impaired in CHF, and, if so, whether MMR is related to clinical severity of CHF and to changes in nonexercised limb vascular resistance in CHF. Methods and results Eleven CHF patients and 9 healthy age- and gender-matched controls were examined. All subjects performed a rhythmic handgrip exercise test at 50% of maximal voluntary contraction for 3 minutes on 2 occasions with and without postexercise upper arm regional circulatory occlusion (RCO/non-RCO). Changes in systolic blood pressure were measured and plotted against protocol time for both RCO and non-RCO. The area under each curve was estimated, and the calculating difference in the area between RCO and non-RCO was regarded as MMR. In addition, changes in calf vascular resistance were measured continuously by plethysmography after the handgrip test and the area differences between the RCO and non-RCO data was taken to represent MMR-provoked resistance changes in the nonexercised limb. During the handgrip exercise, systolic blood pressure increased similarly on the 2 occasions for both groups. MMR was significantly lower in CHF patients than in controls (68.2 ± 23.1 versus 160.4 ± 29.6 arbitrary units; P < .05). Decrease in MMR activity was related to clinical severity of CHF (controls, 160.4 ± 29.6; New York Heart Association class II, 87.6 ± 29.8; New York Heart Association class III, 34.3 ± 34.8 arbitrary units; P < .05). The increase in calf vascular resistance between RCO and non-RCO protocols in the control group was significant (+146.5 ± 38.0 arbitrary units; P < .05), whereas the difference in the CHF group was not significant (−72.9 ± 126.9 arbitrary units; not significant). Conclusions Exercise-induced MMR control in mild to moderate CHF is impaired in association with a blunted increase in nonexercised limb vascular resistance. This suggests that blunted MMR activity impairs regional blood flow redistribution and may contribute in part to exercise intolerance in this disorder.

Increased expression of tumor necrosis factor‐α converting enzyme and tumor necrosis factor‐α in peripheral blood mononuclear cells in patients with advanced congestive heart failure

Tumor necrosis factor-alpha converting enzyme (TACE) has recently been identified as a metalloproteinase-disintegrin, which converts pro-tumor necrosis factor-alpha (TNF-alpha) to the mature form, and is an important mediator in the pathogenesis of CHF. In order to establish the importance of TACE in the regulation of TNF-alpha synthesis in peripheral blood mononuclear cells (PBMC), we analyzed mRNAs and protein-positive cells of both TACE and TNF-alpha in PBMC obtained from patients with congestive heart failure (CHF). PBMC were obtained from 46 patients with CHF and 22 controls. PBMC were activated by phorbol 12-myristate 13-acetate and ionomycin and assessed for TACE and TNF-alpha mRNAs by real-time RT-PCR, intracellular TACE and TNF-alpha levels by flow cytometry, and TNF-alpha secretion by supernatant ELISA. Levels of TACE and TNF-alpha mRNAs, intracellular TACE and TNF-alpha, and supernatant TNF-alpha were higher in CHF than in controls (P<0.001). There was a positive correlation between TACE and TNF-alpha levels in CHF patients (mRNA: r=0.60, P<0.001, intracellular protein levels: r=0.76, P<0.001). When the CHF group was divided into two subgroups by NYHA functional class (I and II vs. III and IV), levels of TACE and TNF-alpha were significantly higher in severe CHF patients (NYHA III or IV) than in mild CHF patients (NYHA I or II) (mRNA: P<0.001; intracellular protein levels: P<0.001). These results demonstrate that in patients with CHF, and especially those with severe CHF, TACE expression in PBMC increases with TNF-alpha expression. These observations suggest that TACE in PBMC is an important regulator of TNF-alpha maturation, meaning that TACE may be a potential target for the inhibition of cellular TNF-alpha production in CHF.

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.

Contribution of Vascular NAD(P)H Oxidase to Endothelial Dysfunction in Heart Failure and the Therapeutic Effects of HMG-CoA Reductase Inhibitor

The vascular NAD(P)H oxidase-derived superoxide anion (O(2)-) plays a crucial role in the pathological progression of hypertension and atherosclerosis, and HMG-CoA reductase inhibitors (statins) have vascular antioxidant effects. However, it is unclear whether the vascular NAD(P)H oxidase is involved in the endothelial dysfunction of congestive heart failure (CHF) and whether HMG-CoA reductase inhibitors (statins) exert their vasoprotective effects in CHF. The present study examined both the involvement of vascular NAD(P)H oxidase in endothelial dysfunction in dogs with tachycardia-induced CHF and the therapeutic effect of a statin (pitavastatin). Femoral blood flow (FBF) responses to acetylcholine was significantly impaired in the CHF group, but were improved by pitavastatin. Vascular O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression were significantly elevated in CHF compared with the normal group. The elevated O(2)-production in the CHF group was suppressed by the NAD(P)H oxidase inhibitor, apocynin, to the normal level. In contrast, neither the gene expression nor the activity of endothelial nitric oxide synthase (eNOS) differed significantly between the normal and CHF groups. However, pitavastatin significantly suppressed O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression and increased eNOS expression and activity compared with the CHF group. The activated vascular NAD(P)H oxidase contributes to endothelial dysfunction in CHF, which was partly improved by pitavastatin via its inhibition of NAD(P)H oxidase.

Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation.

In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHF. The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein-cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.

Multiscale entropy analysis: a new measure of complexity loss in heart failure

Heart failure may lead to loss of complexity in physiologic dynamics. However, conventional entropy measures yield contradictory results. We applied a recently developed method, multiscale entropy (MSE) that quantifies the regularity of physiologic signals over multiple time scales. We tested the hypothesis that the rate at which entropy varies with time scale can discriminate between healthy and different classes of con- gestive heart failure (CHF) subjects. Material and Methods: We analyzed long-term Holter re- cordings from two group of subjects: 72 records from healthy subjects aged 5512 years and 43 from patients with CHF aged 5416. The CHF group included 12 subjects in NYHA classes I-II, and 31 subjects in classes III-IV. We calculated an entropy measure (SampEn) that applies to physiologic time series plotted as a function of time scale. Next, we computed the rate of change of entropy for scales smaller and larger than approximately 5 seconds and developed clustering criteria for the different groups. Results and Conclusions: Healthy and CHF subjects have different MSE curve profiles. Further, heart rate dynamics with CHF have significantly lower multiscale entropy values com- pared with healthy subjects. A 2-dimensional scatter plot based on the rate of variation of entropy with time scale showed robust separation of healthy and all CHF classes. These findings are consistent with the basic concept of information loss in cardio- vascular regulatory mechanisms in CHF and may be useful in clinical assessment.

Evaluation of dietary patterns in dogs with cardiac disease.

To determine the dietary patterns and intake of nutrients of concern in dogs with cardiac disease. Prospective study. 82 dogs with dilated cardiomyopathy (DCM) or chronic valvular disease. Owners of dogs were contacted and given a standardized telephone questionnaire regarding diet and a 24-hour food recall to determine daily intake of calories, protein, fat, sodium, potassium, and magnesium. Among the 82 dogs, 71% had no congestive heart failure (CHF), and 29% had CHF or a history of CHF. Sixty-one percent of dogs had concurrent diseases. Anorexia was or had been evident in 34% of dogs and was significantly more common in the CHF group and in dogs with DCM. Most dogs (92%) received some treats and table food, with a median percentage of daily calories from treats of 19% (range, 0% to 100%). Most owners (57%) that administered pills used human or pet foods for pill administration. Most dogs ate more than the Association of American Feed Control Officials (AAFCO) minimum values for fat and protein. Daily sodium intake varied from 14 to 384 mg/100 kcal, compared with the AAFCO minimum of 17 mg/100 kcal. A median of 25% of total daily sodium came from treats and table food (range, 0% to 100%). Dogs with CHF ate significantly more sodium, compared with dogs with no CHF. Dietary intake for dogs with cardiac disease is highly variable and often not optimal.

Prediction of heart failure post myocardial infarction: comparison of ejection fraction, transmitral filling parameters, and the index of myocardial performance.

Following an acute myocardial infarction (MI), the development of congestive heart failure (CHF) has been associated with a reduced ejection fraction (EF), pseudonormal or restrictive diastolic filling, and an increased index of myocardial performance (IMP). To determine the comparative predictive value of EF, transmitral filling parameters, and IMP for the development of CHF following a first MI. A retrospective analysis of consecutive echocardiographic and Doppler studies in patients admitted for their first acute MI from the years 1988 through 1992. We studied 109 patients following their first MI with two-dimensional and Doppler within 24 hours of MI. We divided patients into those who developed CHF within 15 days (43 patients) and without CHF (66 patients). Patients who developed CHF had greater LV dilatation, lower EF (27.7%+/- 10.2% vs 45.6%+/- 13.2%, P < 0.001), higher E/A, shorter deceleration times (DCT; 157 +/- 69 msec vs 248 +/- 105 msec, P < 0.001), and increased IMP. Utilizing multiple logistic regression, EF (strongest predictor), DCT, and IMP were predictive of CHF. Nineteen patients in the no CHF group developed late CHF and had lower EFs (30.5%+/- 13.1% vs 50.5%+/- 9.8%, P < 0.001), higher E/A and shorter DCTs (161 +/- 39 msec vs 283 +/- 103 msec, P < 0.001). EF, DCT, and E/A were predictive of late CHF in patients without initial CHF. For patients admitted with a first MI, the EF, DCT, and to a lesser extent IMP predicted who would ultimately develop CHF. An EF < 40% or a DCT < 200 msec correctly predicted CHF in 60 of 62 patients. We conclude that the early and ultimate development of CHF following a first MI were associated with an moderately reduced EF < 40%, pseudonormal diastolic filling indices, and an increased IMP.

Effect of congestive heart failure on humoral and ex vivo cellular immune responses to influenza vaccination in older adults

This study examined the effect of congestive heart failure (CHF) on immune responses to influenza vaccination (2000–2001 preparation) in three groups of older adults including healthy, Class II and Class III/IV CHF. Serum antibody titers measured by hemagglutination inhibition (HI), and interferon-γ (IFN-γ), interleukin-10 (IL-10) and granzyme B (GrzB) levels in ex vivo virus-activated mononuclear cell cultures showed significant responses from pre-vaccination to 4 and 12 weeks post-vaccination (P<0.01). There was a trend for lower GrzB and higher IFN-γ and IL-10 levels in healthy versus CHF groups (P<0.06) for all viral strains at 4 weeks. HI titers did not differ between groups. In the regression model, Grz B levels were significantly predicted by the IFN-γ:IL-10 ratio and performance on the 6min Walk Test; age and CHF dropped out of the model. In conclusion, CHF in older adults predicts GrzB responses to influenza vaccination due to cytokine and physical ability differences.