Climbing the Mountain of Acute Decompensated Heart Failure

Tolvaptan, an Oral Vasopressin V 2 Receptor Antagonist for Heart Failure?

For vaptans, as for life, balance is better.

Rafael Correo, de izquierdas, y Alvaro Noboa, magnate conservador, vencieron con un discurso clientelista en el pais mas inestable de America Latina.

Defining Hyponatraemia: A Call for Action

Renal dysfunction is a common and progressive complication of chronic heart failure, with a clinical course that typically fluctuates with the patient’s clinical status and treatment. Despite growing recognition of the frequent presentation of combined cardiac and renal dysfunction, or “cardiorenal syndrome,” its underlying pathophysiology is not well understood, and no consensus as to its appropriate management has been achieved. Because patients with heart failure are surviving longer and dying less frequently from primary arrhythmia, we expect that the cardiorenal syndrome will become more common. Against this background, the article by Wang and colleagues1 in the present issue of Circulation is particularly significant because it is the first prospective, controlled therapeutic trial in patients with this condition. To place the findings and implications of this study in context, we first briefly review what is currently known about the cardiorenal syndrome and its treatment options. See p 1620 In ambulatory heart failure patients, the presence of concomitant renal dysfunction consistently has been one of the strongest risk factors for mortality.2–4 This risk becomes evident even at serum creatinine clearance levels >1.3 mg/dL and estimated creatinine clearance values ≤60 to 70 mL/min. Furthermore, renal function is at least as powerful an adverse prognostic factor as most clinical variables, including ejection fraction and New York Heart Association function class. Although renal dysfunction predicts all-cause mortality, it is most predictive of death from progressive heart failure, which suggests that it is a manifestation of and/or exacerbating factor for left ventricular dysfunction.2 In the setting of hospitalization for decompensated heart failure, worsening renal function is even more important than baseline renal function for predicting adverse outcomes.5–8 Although any increase in creatinine is associated with poorer survival rates, longer hospitalization, and more frequent readmission, several studies have used a threshold of a …

Acute Kidney Function Declines in the Context of Decongestion in Acute Decompensated Heart Failure

Both diuretic response and hemoconcentration are indicators of decongestion and have individually been found to predict rehospitalization after admission for acute heart failure (HF). This study examines the value of combining diuretic response and hemoconcentration to better predict patients at low risk for rehospitalization after admission for acute HF. Diuretic response (defined as weight change per 40 mg of furosemide on day 4 after admission) and hemoconcentration (change in hemoglobin at discharge or day 7) were tested both individually and combined to predict the risk of HF and cardiovascular rehospitalization 60 days after hospitalization for acute HF. Analyses were performed in 1180 patients enrolled in the Placebo-Controlled Randomized Study of the Selective Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) trial and validated in 1776 patients enrolled in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Poor diuretic response was associated with low systolic blood pressure, high blood urea nitrogen, and history of coronary revascularization in both data sets (all P<0.05). Hemoconcentration was mainly associated with better renal function (P<0.05). Patients who displayed both favorable diuretic response and hemoconcentration had a markedly lower risk of rehospitalization for HF in PROTECT (multivariable HR, 0.41; 95% CI, 0.24 to 0.70; P<0.001) compared with all other patients. This finding was confirmed in EVEREST (multivariable HR, 0.52; 95% CI, 0.33 to 0.82; P=0.004) for patients with favorable diuretic response and hemoconcentration compared with all other patients. Combining 2 indicators of decongestion, hemoconcentration and diuretic response improves risk prediction for early rehospitalization after an admission for acute HF and may provide clinicians with an easily accessible tool to identify low-risk patients. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00354458 and NCT00071331.

Can saline repletion be the true TARGET for achieving fluid balance in acute heart failure?

Diuretics and vasodilators have been the cornerstone of heart failure (HF) therapy for decades. Although not shown to reduce mortality, diuretic and vasodilator therapy remain commonplace for treating acute decompensated HF, with diuretics being the mainstay of therapy for the removal of excess fluid in all patients with HF. This article discusses results of recent trials concerning diuretic or vasodilator therapy and HF, including the Diuretic Optimization Strategies Evaluation (DOSE) trial, the Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT), and the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST), as well as results from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial and the Preliminary Study of Relaxin in Acute Heart Failure (Pre-RELAX-AHF).

Recent Trends in the Incidence, Treatment, and Prognosis of Patients With Heart Failure and Atrial Fibrillation (the Worcester Heart Failure Study)

Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: Results from efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan (EVEREST) program

Gender Does Not Affect Postdischarge Outcomes in Patients Hospitalized for Worsening Heart Failure With Reduced Ejection Fraction (from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan [EVEREST] Trial)

Acute decompensated heart failure (ADHF) is a common and highly morbid cardiovascular disorder. Most hospitalizations for ADHF are related to symptoms of congestion, and the vast majority of ADHF patients are treated with intravenous loop diuretics. Despite this nearly ubiquitous use, data supporting the safety and efficacy of loop diuretics in ADHF are limited, and controversy exists about the best way to use loop diuretics with regard to both dosing and means of administration (continuous infusion vs. intermittent boluses). We reviewed the data supporting the safety and efficacy of loop diuretics in patients with ADHF. A large body of observational literature suggests that loop diuretics, especially at higher doses, may be associated with increased mortality in patients with heart failure even after detailed adjustment for other measures of disease severity. Additionally, multiple small underpowered trials suggest that continuous infusion may be equivalent or superior to intermittent bolus dosing. In summary, there is a critical need to develop more robust data on the use of loop diuretics in ADHF. In that context, the NIH Heart Failure Clinical Research Network has begun the Diuretics Optimization Strategies Evaluation (DOSE) study, a multi-center, double-blind, randomized controlled trial that will enroll 300 patients with ADHF. The DOSE study will randomize patients using a 2 × 2 factorial design to low dose vs. high dose furosemide, and intermittent bolus vs. continuous infusion. Successful completion of the DOSE study will provide important data on the optimal clinical use of loop diuretics in ADHF.

Background: Myocardial injury (INJ) expressed by elevated high-sensitivity troponin (hs-Tn) is common in heart failure (HF), due to cardiovascular and non-cardiac conditions. The mechanisms of INJ in acute decompensated HF (ADHF) versus chronic HF (CHF) are still debated. This study’s purpose was to evaluate the determinants of elevated hs-TnT in ADHF and CHF. Methods: We retrospectively analyzed consecutive HF patients with hs-TnT measured on admission, hospitalized in a tertiary-care hospital. Rehospitalizations, acute coronary syndromes, embolisms, infections, autoimmunity and malignancy were excluded. Cut-off point for hs-TnT was 14 ng/L. Results: Our study included 488 HF patients, 56.55% with ADHF. Mean age was 72.52±10.09 years. 53.89% were females. 67.75% ADHF and 45.75% CHF patients had elevated hs-TnT. Median hs-TnT was higher in ADHF versus CHF (21.05[IQR 12.74-33.81] vs 13.20[IQR 7.93-23.25], p&lt;0.0001). In multivariable analysis in ADHF and CHF, log10NT-proBNP (HR=5.30, 95%CI 2.71–10.38, p&lt;0.001, respectively HR=5.49, 95%CI 1.71–17.57, p=0.004) and eGFR (HR=0.72, 95%CI 0.62–0.85, p&lt;0.001, respectively HR=0.71, 95%CI 0.55–0.93, p=0.014) were independent predictors for increased hs-TnT. Independent factors associated with elevated hs-TnT in ADHF were male sex (HR=2.52, 95%CI 1.31-4.87, p=0.006) and chronic pulmonary obstructive disease (COPD) (HR=10.57, 95%CI 1.26-88.40, p=0.029), while in CHF were age (HR=2.68, 95%CI 1.42-5.07, p=0.002) and previous stroke (HR=5.35, 95%CI 0.98-29.20, p=0.053). Conclusion: HF severity, expressed by NT-proBNP levels, and kidney disease progression, expressed by eGFR, were independent predictors associated with increased hs-TnT in both ADHF and CHF. Specific independent predictors were also indentified in ADHF (male sex, COPD) and CHF (age, history of stroke).

Atrial fibrillation (AF) is a common rhythm in patients with acute decompensated heart failure (ADHF). Registry and trial data1,2 indicate that 20% to 35% of patients with ADHF who are admitted to the hospital will be in AF at presentation. In about one third of these patients, the AF will be of recent onset. Despite the high frequency with which the combination of AF and ADHF is encountered, there are few published data that specifically address this problem. AF and worsening heart failure interact in a dangerous pattern. The adverse effects of AF in patients with heart failure may include loss of atrial transport, rapid and irregular ventricular rates, and toxic effects of antiarrhythmic drug therapy. Worsened heart failure, in turn, leads to increased atrial stretch and heightened sympathetic tone. These latter changes make the AF more resistant to treatment using either a rate-control or a rhythm-control strategy (Figure 1). Figure. Adverse interactions between AF and heart failure. AAD indicates antiarrhythmic drug. The immediate general goals of therapy in ADHF are to improve symptoms, restore oxygenation, improve organ perfusion, and limit cardiac and renal injury.3 In patients with sinus rhythm and ADHF, the appropriate use of vasodilators, oxygen, diuretics, positive inotropic agents, and mechanical devices to support ventilation or cardiac output forms the cornerstone of therapy. In patients who present with AF, however, additional treatment decisions are required. ### Initial Assessment The clinical history provides critical information that should be used to guide treatment. Five key questions that should be asked before starting therapy …