Several studies have shown that depression is an important predictor of morbidity and mortality in patients with ischaemic heart failure. We have investigated whether clinically recognised depression is linked to mortality in patients with non-ischaemic heart failure due to dilated cardiomyopathy (DCM) in the Royal Brompton Hospital (RBH), a tertiary cardiac centre located in London, UK. We retrospectively examined a cohort of 396 consecutive adult patients with DCM who satisfied our inclusion and exclusion criteria identified from an echocardiographic database and the hospital medical records. Mean age was 53"15 years. In all, 83 patients (21%) were clinically depressed, the majority of which (60%) were taking antidepressant therapy. After a follow-up period of 48 months, 83 (21%) patients died, 15 (4%) underwent cardiac transplantation and 130 (33%) were readmitted; 29 (35%) of the deaths and 40 (31%) of the readmissions were among clinically depressed patients. After 5 years, clinically depressed patients had significantly higher mortality and readmission rates than non-depressed; 36 vs. 16% (hazards ratio for death, 3.0; 95% CI, 1.4-6.4; Ps0.004), and 87 vs. 74% (hazards ratio for readmission, 0.25; 95% CI, 0.07-0.90; Ps 0.03), respectively. The risk of depression was greatly increased in the presence of other recognised adverse clinical variables at baseline. Depression increases the risk of death and readmission in patients with heart failure secondary to non-ischaemic DCM. The risk associated with depression appears to be greatest among patients with milder disease, those with a shorter duration of symptoms and those demonstrating a lower systolic or diastolic blood pressure, renal impairment, or a restrictive left ventricular physiology on echocardiography. Interventions targeted at reducing depression warrant further study as a possible way to improve quality of life andyor outcome in patients with heart failure.

Renal hydrogen ion excretion increases with chronic acid loads and decreases with alkali loads. We examined the mechanism of adaptation by analyzing vacuolar proton-translocating adenosine triphosphatase (H' ATPase) 31-kD subunit protein and mRNA levels, and immunocytochemical distribution in kidneys from rats subjected to acid or alkali loads for 1,3,5,7, and 14 d. Acid-and alkali-loaded rats exhibited adaptive responses in acid excretion, but showed no significant changes in H' ATPase protein or mRNA levels in either cortex or medulla. In contrast, there were profound adaptive changes in the immunocytochemical distribution of H' ATPase in collecting duct intercalated cells. In the medulla, H' ATPase staining in acidloaded rats shifted from cytoplasmic vesicles to plasma membrane, whereas in alkali-loaded rats, cytoplasmic vesicle staining was enhanced, and staining of plasma membrane disappeared. In the cortical collecting tubule, acid loading increased the number of intercalated cells showing enhanced apical H' ATPase staining and decreased the number of cells with basolateral or poorly polarized apical staining. The results indicate that both medulla and cortex participate in the adaptive response to acid and alkali loading by changing the steady-state distribution of H' ATPase, employing mechanisms that do not necessitate postulating interconversion of intercalated cells with opposing polarities. (J. Clin. Invest. 1991. 88:126-136.)

No abstract

The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity.

BACKGROUND: Chronic heart failure is a major cause of morbidity and mortality world-wide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear. OBJECTIVES: To assess the harms and benefits of diuretics for chronic heart failure SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Issue 2 2004), MEDLINE 1966-2004, EMBASE 1980-2004 and HERDIN database. We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Only double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were entered into the Review Manager 4.2 computer software, and analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi-square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model. MAIN RESULTS: We included 14 trials (525 participants), 7 were placebo-controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo-controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95% CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control (91 participants), diuretics improved exercise capacity in participants with CHF, difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001. AUTHORS' CONCLUSIONS: The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity