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Objectives: We sought to define the characteristics of fluid retention after thiazolidinedione (TZD) initiation in patients with established heart failure (HF).Background: Fluid retention associated with the use of TZD is commonly attributed to exacerbation of HF, which has led to the proscription of these potentially useful agents in patients with chronic HF.Methods: We examined 111 consecutive diabetic patients with chronic systolic HF who were treated with TZD from January 1999 to June 2001. A retrospective chart review was performed to determine the incidence of fluid retention in this cohort. Physical signs of fluid retention were compared between TZD users and an age- and gender-matched control group of diabetic, non-TZD users with chronic HF who had fluid retention. Baseline clinical and echocardiographic data were compared between TZD users with and without fluid retention.Results: Nineteen TZD users (17.1%) developed fluid retention, which reversed after drug withdrawal and presented predominantly as peripheral and not central edema. Comparing patients in the upper and lower tertiles of weight gain, more female patients and insulin users developed TZD-related fluid retention. However, there were no differences in the baseline New York Heart Association functional class or echocardiographic severity of cardiac dysfunction.Conclusions: Although fluid retention after treatment with TZD in diabetic patients with chronic systolic HF occurs, the mechanism is undefined. Fluid retention related to TZD tends to be peripheral and is usually reversible after drug withdrawal. No direct association between the risk of fluid retention and the baseline degree of severity of HF was observed. [ABSTRACT FROM AUTHOR]

Clinical trials have demonstrated new, safe, efficacious ways to use these cardiovascular agents: Beta-blockers are now first-line treatment for heart failure, and the HOPE trial showed that ACE inhibitors reduce morbidity and mortality in patients at high risk of cardiac events. [ABSTRACT FROM AUTHOR]

Clinical trials have demonstrated new, safe, efficacious ways to use these cardiovascular agents: Beta-blockers are now first-line treatment for heart failure, and the HOPE trial showed that AGE inhibitors reduce morbidity and mortality in patients at high risk of cardiac events. [ABSTRACT FROM AUTHOR]

Expanded options in heart failure therapy have raised practical questions. The major drugs--ACE inhibitors, diuretics, and digoxin--have been joined by carvedilol and possibly other beta-blockers. How are they and other drugs integrated into a unified treatment plan? [ABSTRACT FROM AUTHOR]

1 Labetalol at a dose of 800 to 1600 mg daily inhibited isoprenaline- induced tachycardia and phenylephrine-induced elevation in arterial pressure in hypertensive subjects. The beta-adrenoreceptor effect was four times more potent than the alpha-adrenoreceptor effect. 2 Isoprenaline-induced tachycardia was more effectively blocked than isoprenaline-induced inotropism, thereby raising the possibility of a subselective effect on cardiac beta-adrenoceptors. 3 Labetalol reduced blood pressure in hypertensive subjects with no change in cardiac output in the supine or upright position and with marked inhibition of the heart rate and blood pressure response to treadmill exercise. 4 Labetalol administered in single doses to patients with stable, treated congestive heart failure impaired blood pressure support during exercise. 5 The unique adrenoceptor and haemodynamic effects of labetalol make it a potentially attractive drug for management of hypertension and other cardiovascular disorders. [ABSTRACT FROM AUTHOR]

Plasma B-type natriuretic peptide (BNP) assays have become widely used to diagnose and manage patients with heart failure. However, differences in assay characteristics may have important implications when BNP is used as a screening test for heart failure at a specific cutoff value. We performed a prospective comparison of 2 commercially available assays--one that is a laboratory-based, microparticle enzyme immunoassay (MEIA) that uses EDTA plasma specimens and one that is a point-of-care (POC), single-use fluorescence immunoassay that uses EDTA--anticoagulated whole blood or plasma specimens-in patients with heart failure and healthy controls. Despite the overall concordance between different SNP assays for the diagnosis of heart failure, their sensitivities may differ when compared at the approved diagnostic cutoff value of 100 pg/mL. At this cutoff value, the MEIA on AxSYM demonstrated greater sensitivity than POC Triage BNP assay in minimally symptomatic patients with heart failure. Therefore, for screening purposes, cutoff values for plasma BNP or N-terminal pro-BNP levels should be specific for each assay to optimize test performance. These findings suggest that there is a relationship between the decision statistics used in screening for left ventricular dysfunction and the type of diagnostic assay used. [ABSTRACT FROM AUTHOR]

The advent of neurohormonal blockade in heart failure (HF) has been an overwhelming success, but current evidence points to a ceiling effect as newer neurohormonal targets are exploited in an incremental manner. This has lead us to question whether the neurohormonal model of HF can be sustained by simply stacking multiple neurohormonal or cytokine blockers together as treatment. A unifying theme in some of these disparate trials relates to either a lack of efficacy or, more importantly, adversity resulting in regression of already achieved benefits. It is our contention that the available evidence has uncovered the remarkable complexity of interaction within the context of the neurohormonal construct. As we stand at a crossroad in HF and begin to fervently pursue non-neurohormonal therapeutic targets, we must also direct attention at navigating the multifaceted labyrinth of the neurohormonal model that has led to the current imbroglio. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to determine the prognostic significance of estimated creatinine clearance (CrCl) in relation to 6-min walk distance in ambulatory patients with congestive heart failure (HF).Background: Although measurement of renal function is integral to the management of chronic congestive HF, its prognostic implications are not well described and have not been formally evaluated relative to measures of functional capacity.Methods: We analyzed outcomes of the 585 participants of the 6-min walk substudy of the Digitalis Investigation Group (DIG) trial. The CrCl was estimated using the Cockcroft-Gault equation. Predictors of all-cause mortality were identified using semiparametric Cox proportional hazards regression and completely parametric hazard analyses.Results: Most subjects (85%) were New York Heart Association functional class II and III. Mean age was 65 (+/-12) years and mean ejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a median of 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrCl was 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21% (86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the top quartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to 2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses, independent predictors of mortality were estimated CrCl (adjusted HR [quartile 1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m [adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization for worsening HF, and need for diuretic treatment. Parametric (hazard) analysis confirmed consistent effects of estimated CrCl on mortality in several subgroups including that of patients with EF >45%.Conclusion: In ambulatory patients with congestive HF, estimated CrCl predicts all-cause mortality independently of established prognostic variables. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate modern surgical outcomes in patients with stable heart failure undergoing elective major noncardiac surgery and to compare the experience of patients with heart failure who have reduced vs preserved left ventricular ejection fraction (EF). PATIENTS AND METHODS: We retrospectively studied 557 consecutive patients with heart failure (192 EF less than or equal to 40% and 365 EF greater than 40%) and 10,583 controls who underwent systematic evaluation by hospitalists in a preoperative clinic before having major elective noncardiac surgery between January 1, 2003, and March 31, 2006. We examined outcomes in the entire cohort and in propensity-matched case-control groups. RESULTS: Unadjusted 1-month postoperative mortality in patients with both types of heart failure vs controls was 1.3% vs 0.4% (P equals .009), but this difference was not significant in propensity-matched groups (P equals .09). Unadjusted differences in mean hospital length of stay among heart failure patients vs controls (5.7 vs 4.3 days; P less than .001) and 1-month readmission (17.8% vs 8.5%; P less than .001) were also markedly attenuated in propensity-matched groups. Crude 1-year hazard ratios for mortality were 1.71 (95% confidence interval [CI], 1.5-2.0) for both types of heart failure, 2.1 (95% CI, 1.7-2.6) in patients with heart failure who had EF less than or equal to 40%, and 1.4 (95% CI, 1.2-1.8) in those who had EF greater than 40% (P less than .01 for all 3 comparisons); however, the differences were not significant in propensity-matched groups (P equals .43). CONCLUSION: Patients with clinically stable heart failure did not have high perioperative mortality rates in association with elective major noncardiac surgery, but they were more likely than patients without heart failure to have longer hospital stays, were more likely to require hospital readmission, and had a substantial long-term mortality rate. [ABSTRACT FROM AUTHOR]

The benefits of aldosterone receptor antagonists (spironolactone and eplerenone) for patients with heart failure were shown in 2 recent randomized controlled trials. Some of the proposed mechanisms of action of aldosterone antagonists are (1) inhibition of myocardial and vascular remodeling, (2) blood pressure reduction, (3) decreased collagen deposition, (4) decreased myocardial stiffness, (5) prevention of hypokalemia and arrhythmia, (6) modulation of nitric oxide synthesis, and (7) immunomodulation. Like many hormone receptors, the aldosterone receptor can be either nuclear or membrane bound. Most of the activities of the aldosterone receptor are subserved by the nuclear receptors and often lead to alterations in gene transcription. Although these agents are well tolerated in carefully selected patient populations that meet the inclusion criteria of large clinical trials, their use in unselected elderly patients with heart failure and multiple comorbidities has been associated with a significant risk of hyperkalemia and renal failure. Although no convincing data exist to predict which individual patients will respond to aldosterone inhibition, patients with more severe heart failure and those with acute myocardial infarction with concomitant heart failure or left ventricular dysfunction are most likely to respond. Theoretically, aldosterone receptor antagonists may also be beneficial in patients with more mild to moderate systolic heart failure or even in those with diastolic heart failure, although direct evidence is still lacking. [ABSTRACT FROM AUTHOR]