TNFα in patients with congestive heart failure

Abstract. It is now generally accepted that chronically extensive stimulation of the cytokine system—and of TNF in particular—is detrimental to the heart and to peripheral tissue and that such stimulation may contribute to the pathogenesis of congestive heart failure of various causes. During the past decade, basic and clinical research has provided growing evidence for the role of systemic and local inammatory responses that, however, have so far failed to translate into new treatments for patients. The present paper represents an attempt to critically review the general concepts that lie behind the dichotomy existing between an impressive bulk of biologic research showing the role of TNF as a pathogen in congestive heart failure and the difculties in translating this evidence into patients treatment.     

Is Chagas cardiomyopathy an independent risk factor for patients with heart failure?

Some studies showed increased mortality in chagasic patients but most of these studies did not perform statistical adjustments to socioeconomic variables. The main objective of this study was to investigate if there is an independent association between Chagas etiology and mortality in patients with heart failure and moderate to severe left ventricle systolic dysfunction. Stratified analysis by the variables associated to chagasic etiology and multivariate analysis through logistic regression were performed to evaluate the relationship between Chagas cardiomyopathy and one-year mortality. Among 417 patients initially evaluated, 191 had the inclusion criteria. The mortality was higher in patients with Chagas cardiomyopathy than in the patients with other etiologies (log rank test; p = 0.036). At one-year follow-up, the mortality in chagasic patients was 21.6% versus 10.6% in the remaining (relative risk = 2.03; 95% CI = 0.98–4.2; p = 0.05). At logistic regression, educational level was identified as a confounder variable of the association between Chagas cardiomyopathy and one-year mortality. This association was no more statistically significant after adjustment for educational level (odds ratio = 1.67; 95% CI = 0.63–4.41). In this study, Chagas cardiomyopathy was a marker of worse prognosis, but was not independently associated to increased one-year mortality in outpatients with heart failure and moderate to severe systolic dysfunction.     

Is specialty care associated with improved survival of patients with congestive heart failure?

Background Implementation of the complex treatment strategies that have been shown to improve survival of patients with congestive heart failure (CHF) may require certain expertise. We wanted to examine the association between pattern of outpatient care and survival of patients with CHF. Methods In a retrospective cohort study conducted with national Veterans Health Administration (VHA) databases, we examined the association between the pattern of outpatient care and survival in 11,661 patients discharged from VA hospitals between October 1, 1991, and September 30, 1992, with the primary diagnosis of CHF (cohort 1). Patients were divided into 4 groups, on the basis of their pattern of outpatient care over a 12-month period after discharge: 1) general medicine clinic visits only (GM-only); 2) cardiology clinic visits only (CARD-only); 3) general medicine and cardiology (MIXED) clinic visits; and 4) neither general medicine nor cardiology clinic visits (no-GM/CARD). We used the Cox proportional hazards model to evaluate 1-year survival, controlling for clinical and demographic factors. Consistency of our results was examined by performing identical analysis on a cohort of patients discharged from VHA hospitals between October 1, 1994, and September 30, 1995 (cohort 2, n = 10,141). Results The overall 1-year mortality rate was 23% in the primary cohort. The unadjusted mortality rate was highest for patients in the no-GM/CARD follow up (29%) and lowest for patients in the MIXED group (19%). By use of the MIXED group as reference and adjusting for important clinical and demographic factors, the risk of death (risk ratio [95% CI]) was 1.12 (0.94-1.34) in the CARD-only group, 1.26 (1.15-1.38) in the GM-only group, and 1.48 (1.28-1.72) in the no-GM/CARD group. Cohort-2 results were consistent with cohort 1 for most covariates, and significant survival differences were again found between GM-only and the MIXED group (1.25 [1.14-1.37]). Conclusions We found an improved survival associated with cardiologist care and a mixture of general practitioner and cardiologist care compared with general practitioner care. The pattern of outpatient care may therefore be important for the survival of patients with CHF. (Am Heart J 2003;145:300-9.)     

How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure?

BACKGROUND: Treatment with spironolactone (SPL) is beneficial in patients with severe congestive heart failure (CHF). In the Randomized Aldactone Evaluation Study SPL was well tolerated, particularly with regard to renal function and serum K(+) levels. Our aim was to investigate whether the reported low frequency of adverse effects during SPL treatment in a heart failure study population could be confirmed in an unselected heart failure outpatient cohort and to identify potential predictors of harmful effects. METHODS AND RESULTS: We investigated 125 consecutive patients with CHF recruited from our heart failure clinic. Inclusion criteria were LVEF (left ventricular ejection fraction) 5,0, 5.5, 6.0, or 6.5 mmol/L, respectively, and (2) rise in serum creatinine to 120%, 150%, and 200% of baseline, respectively. Mean age was 72.9 years (range 46.5 to 90.6 years); 27% were women. The New York Heart Association class distribution was: I, 6%; II, 44%; III, 46%; and IV, 4%. Mean LVEF was 29+/-5%. Other medication included angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in 86% and beta-blockers in 39%. At baseline, serum creatinine levels were 117.6+/-6.5 (mean+/-standard deviation; micromol/L, normal <130) and serum K(+) was 4.2+/-0.3 mmol/L. The mean follow-up period was 11 months, and the cumulative observation period was 73 SPL treatment years. Mean peak serum-creatinine was 167.6 micromol/L+/-11.9 (45% increase from baseline) and mean peak serum K(+) was 5.0+/-0.4 mmol/L (21% increase from baseline). Sixty patients were already on SPL when admitted to the CHF clinic. The remainder were initiated on SPL. During the follow-up period 36% of the patients developed hyperkalemia (>5 mmol/L), with 10% having serum K(+) >6 mmol/L. An increase in serum creatinine of >20% was seen in 55%, and in 24% an increase of >50% was found. These alterations in serum creatinine and serum K(+) were not significantly more frequent in patients treated with angiotensin-converting enzyme inhibitors or beta-blockers or different doses of SPL. CONCLUSION: SPL adverse effects (impaired renal function, increase in serum K(+)) are much more prevalent in our elderly CHF patient population than previously reported. The recommendations from our study are that (1) particular caution is mandated in elderly patients with an LVEF <20%, (2) potassium supplementation should be discontinued, (3) changes in body weight should raise concern, and (4) a dose-adjustment of the concomitant conventional diuretic regime should be considered. Care should be given to the frequent monitoring of electrolytes and renal parameters.     

Should vitamin D status be assessed in patients with congestive heart failure?

For decades the vitamin D biological system has been considered almost exclusively as the master integrator of calcium-phosphate homeostasis and bone metabolism. More recently, the discovery that many human tissues and cells, which do not directly participate in mineral ion homeostasis, express the vitamin D receptor (VDR) and are able to convert the circulating pro-hormone 25-hydroxyvitamin D in its active form, 1,25-dihydroxyvitamin D, has provided new insights into the biological function of this peculiar endocrine system. Several reports have highlighted a variety of human diseases possibly related to vitamin D insufficiency or deficiency (respectively defined as 25-hydroxyvitamin D serum levels lower than 30 or lower than 20 ng/ml). In particular, experimental and observational studies, including those published in this journal issue, support the concept that vitamin D deficiency is involved in the pathogenesis of congestive heart failure, a disabling condition affecting over 15 million of patients worldwide. Considering that circulating levels of 25-hydroxyvitamin D represent the accepted clinical indicator of individual vitamin D status, the measurement of this pro-hormone can be regarded as an appropriate and cost-effective screening tool in patients with chronic heart failure.     

Is rhythm control superior to rate control in patients with atrial fibrillation and congestive heart failure?

In 1,009 patients with atrial fibrillation and congestive heart failure, the 2-year mortality rate was 31% in patients treated with rate control (n = 505) versus 29% in patients treated with rhythm control (n = 504). After adjusting for differences in baseline characteristics and medications, no significant difference in mortality was found between the 2 groups.     

Is hydrotherapy an appropriate form of exercise for elderly patients with biventricular systolic heart failure?

Hydrotherapy (exercise in warm water) is considered to be a safe and beneficial method to use in the rehabilitation of stable heart failure patients, but there is little information on the effect of the increased venous return and enhanced preload in elderly patients with biventricular heart failure. We present a case report of an elderly man who was recruited to participate in a hydrotherapy study. We compared echocardiographic data during warm water immersion with land measurements, and observed increases in stroke volume from 32 mL (land) to 42 mL (water), left ventricular ejection fraction from 22 to 24%, left ventricular systolic velocity from 4.8 to 5.0 cm/s and left atrioventricular plane displacement from 2.1 to 2.2 mm. In opposite, right ventricular systolic velocity decreases from 11.2 to 8.4 cm/s and right atrioventricular plane displacement from 8.1 to 4.7 mm. The tricuspid pressure gradient rose from 18 mmHg on land to 50 mmHg during warm water immersion. Thus, although left ventricular systolic function was relatively unaffected during warm water immersion, we observed a decrease in right ventricular function with an augmented right ventricular pressure. We recommend further investigation to observe the cardiac effect of warm water immersion on patients with biventricular systolic heart failure and at risk of elevated right ventricular pressure.     

Is there a role for calcium channel blockers in congestive heart failure?

Over the past several decades, we have made great strides in understanding the pathophysiology of heart failure and have developed new therapeutic targets based on utilizing several different models in clinical trials. Currently, standard therapy involves angiotensin-converting enzyme inhibitors and β-blockers. In an effort to further reduce mortality, investigators focused on other vasodilators (calcium channel blockers) that might prove to be advantageous when added to standard therapy. Largescale trials showed that the calcium channel blockers did not have a specific role in mortality reduction, but the third-generation dihydropyridine calcium channel blockers were safe to use in patients with heart failure.     

Platelet activation in patients with congestive heart failure: do we have enough evidence to consider clopidogrel?

Our understanding of the pathogenesis of congestive heart failure (CHF) has improved remarkably in recent years. However, despite better knowledge and novel pharmaceutical strategies, this disease is still one of the most brutal killers in the Western world. The pathophysiology of CHF is complex, and much of our comprehension revolves strictly around the neurohormonal and mechanical mechanisms involved. It has been suggested that CHF is associated with altered hemostasis, but whether a prothrombotic state contributes to the pathogenesis and progression of the disease is still not well known. The purpose of this review article is to discuss our current knowledge of platelet activation in patients with CHF and the potential role of antiplatelet agents in preventing these hemostatic abnormalities. Clopidogrel is an established medication that reduces the incidence of stroke, myocardial ischemia, or vascular death. It is currently the drug of choice in the prophylaxis of subacute stent thrombosis and postischemic stroke treatment. Promising results of the most resent trials (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events [CAPRIE] and Clopidogrel in Unstable angina to prevent Recurrent Events [CURE]) may expand future indications of this ADP receptor antagonist for prevention of thrombotic complications in the CHF population. Currently conducted clinical trials (Warfarin and Antiplatelet Therapy in Chronic Heart Failure [WATCH] and Plavix Use for Treatment of Congestive Heart Failure [PLUTO-CHF] should clarify the role of clopidogrel in these patients. (Am Heart J 2003;145:397-403.)     

Is depression a problem in patients with chronic heart failure?

Depression is a common psychiatric disorder, characterized by a persistent lowering of mood, loss of interest in routine activities and diminished ability to experience pleasure. There are several depression classification systems and diagnostic tools based on clinical symptoms, i.e. the International Classification of Diseases (ICD-10), the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the Hamilton Depression Rating Scale, the Montgomery-Asberg Scale and Beck's Depression Inventory. Depression frequently occurs in patients with heart failure, as similar pathophysiological mechanisms of neurohormonal activation, arrhythmia, inflammation and hypercoagulation are present in both these diseases. Prognosis in patients with depression is also affected by insufficient cooperation between a patient and his doctor as regards the lifestyle and medication intake of a patient. Depression is usually accompanied by remission and relapse periods which might be related to the current heart failure status of a patient and despite intensive medical treatment they may recur. Depression is often difficult to diagnose or even left undiagnosed and thus untreated, because its symptoms: fatigue, apathy and decreased exercise tolerance, are common in the general population. Furthermore, safety and efficacy of antidepressant therapy in patients with cardiovascular diseases are not well established. Evidence from clinical trials evaluating the influence of depression behavioral and pharmacological treatment on morbidity and mortality in patients with heart failure is also limited. Taking into account that depression affects prognosis in patients with variety of disorders and common pathological mechanisms present both in depression and heart failure, screening tests for depression should be considered not only in patients with diagnosed heart failure but also those at risk of heart failure development.     

Neurohormonal activation in congestive heart failure: does it normalize after heart transplantation?

INTRODUCTION AND OBJECTIVE: In patients with congestive heart failure, neurohormonal activation plays an important role in disease progression and prognosis. The aim of this study was to document the evolution of neurohormonal activation after heart transplantation. PATIENTS AND METHOD: Thirty-seven patients on the waiting list for heart transplantation were included in the study. Plasma levels of angiotensin II, aldosterone, endothelin, atrial natriuretic peptide and adrenomedullin were measured before heart transplantation and again 1, 4, 9 and 12 months afterwards. Plasma levels of norepinephrine and renin were measured before and 1 month after heart transplantation. RESULTS: The levels of angiotensin II, norepinephrine and renin showed a nonsignificant trend towards reduction. The levels of aldosterone were unchanged, and an increase in endothelin levels was seen 9 and 12 months after transplantation. Plasma levels of atrial natriuretic peptide and adrenomedullin were significantly lower 1, 4, 9 and 12 months after heart transplantation compared to pretransplant levels. CONCLUSIONS: During the first several months after heart transplantation there were no significant reductions in plasma levels of angiotensin II, aldosterone and endothelin, and there were significant reductions soon after surgery in peptides with a predominantly vasodilator effect (atrial natriuretic peptide and adrenomedullin). This unfavorable neurohormonal profile may contribute to the development of posttransplant complications such as edema, arterial hypertension and endothelial dysfunction.