G. Michael Felker, MD, MHS, FACC

1. What is acute decompensated heart failure? Isn’t it just a worsening of chronic heart failure?

    Acute decompensated heart failure (ADHF) is a clinical syndrome of worsening signs or symptoms of heart failure requiring hospitalization or other unscheduled medical care. For many years, ADHF was viewed as simply an exacerbation of chronic heart failure as a result of volume overload, with few implications beyond a short-term need to intensify diuretic therapy (a similar paradigm to exacerbations of chronic asthma). Recent decades have seen an explosion of research into the epidemiology, pathophysiology, outcomes, and treatment of ADHF. Multiple lines of evidence now support the concept that ADHF is a unique clinical syndrome with its own epidemiology and underlying mechanisms and a need for specific therapies. ADHF is not just a worsening of chronic heart failure, any more than an acute myocardial infarction (MI) is just a worsening of chronic angina.

    Outcomes data from a variety of studies now support the concept that hospitalization for ADHF can often signal a dramatic change in the natural history of the heart failure syndrome. Rates of rehospitalization or death are as high as 50% within 6 months of the initial ADHF event, which is a much higher event rate than is seen with acute MI.

2. Are there clinically important subcategories of ADHF?

    There is great interest in developing a framework for understanding ADHF that would assist in stratifying patients, guiding therapy, and developing new treatments, similar to the basic framework developed for acute coronary syndromes (i.e., ST segment elevation myocardial infarction [STEMI], non–ST segment elevation myocardial infarction [NSTEMI], and unstable angina). Although this area is rapidly evolving, a few general clinical phenotypes of ADHF have emerged.

3. What is the role of biomarkers like B-type natriuretic peptides (BNPs) in the diagnosis of ADHF?

    Although the clinical symptoms (dyspnea, paroxysmal nocturnal dyspnea [PND], orthopnea, fatigue) and signs (elevated jugular venous pressure, pulmonary rales, edema) of ADHF are well known, the diagnosis can often be challenging in patients presenting to acute care settings. This is especially true in the elderly and patients with significant comorbid conditions such as chronic obstructive pulmonary disease (COPD). The development of natriuretic peptides as a diagnostic tool has been a major advance in ADHF diagnosis. The clinically available natriuretic peptides for ADHF diagnosis include BNP and its biologically inert amino-terminal fragment, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Despite some subtle differences between these two biomarkers, they provide similar diagnostic information when used in patients presenting to the emergency department with unexplained dyspnea, although the range of values is significantly different (in general, NT-proBNP levels are approximately 5 to 10 times greater than BNP levels in the same patient). The landmark Breathing Not Properly Study measured BNP levels in 1586 patients presenting to the emergency department with unexplained dyspnea. In this study, treating physicians were blinded to BNP values and a panel of cardiologists adjudicated whether hospitalizations were due to ADHF or other causes (based on all clinical data other than the BNP values). As shown in Figure 22-1, a cutoff of 100 pg/mL of BNP had a positive predictive value of 79% and a negative predictive value of 89% for the diagnosis of ADHF. The area under the receiver operating characteristic (ROC) curve was 0.91, suggesting a very high degree of accuracy for establishing the diagnosis of ADHF. Subsequent studies have demonstrated similar findings for NT-proBNP, although optimal diagnostic cutoffs are different (450 pg/mL for patients younger than 50 years and 900 pg/mL for patients older than 50 years). The use of natriuretic peptide has now become the standard of care in the diagnosis of patients with dyspnea presenting to acute care settings, and has a class I indication (“should be done”) in clinical practice guidelines.

4. What features suggest patients who are particularly high risk?

    Analysis of large datasets from both clinical trials and registries of ADHF patients have identified a few features that consistently suggest a high risk of short-term morbidity and mortality in patients hospitalized with ADHF (Box 22-1). Across studies, the most consistent of these are blood urea nitrogen (BUN), serum creatinine, SBP, and hyponatremia. Interestingly, BUN has consistently proved to be a stronger predictor of outcomes than creatinine (Fig. 22-2). One potential explanation of this finding is that BUN may integrate both renal function and hemodynamic information. Unlike the situation in many other cardiovascular conditions, higher blood pressure has consistently been associated with lower risk. Hyponatremia appears to be associated with lower output and greater neurohormonal activation, and risk appears to be increased with even mild forms of hyponatremia. A variety of biomarkers also appear to have strong prognostic implications in ADHF, in particular the natriuretic peptides (BNP or NT-proBNP) and troponin.

5. What are the goals of therapy in ADHF?

    Specific therapies for ADHF should be assessed in the context of the overall goals of therapy. A summary of suggested goals of therapy based on current guidelines from the Heart Failure Society of America (HFSA) and European Society of Cardiology (ESC) are shown in Box 22-2.

6. How should we give diuretics in ADHF?

    Because most episodes of ADHF are associated with some degree of congestion or volume overload, intravenous (IV) loop diuretics remain a cornerstone of ADHF therapy. Because many symptoms in ADHF (in particular dyspnea) appear to be closely related to elevated ventricular filling pressures, reduction of filing pressures in order to improve acute symptoms is a major goal of therapy. Recently, however, observational data from a variety of sources have led to questions about the appropriate use of diuretics in patients with ADHF. Studies of patients with both chronic heart failure and ADHF have shown that higher diuretic use is associated with a higher incidence of adverse events (especially worsening renal function) and mortality. Interpreting this type of data is highly problematic because of the issue of confounding by indication (i.e., patients who need higher diuretic doses are typically sicker, and thus it is impossible to determine if higher doses of diuretics are simply a marker of greater disease severity or whether they directly contribute to worsening outcomes). Controversy also exists regarding whether continuous infusion (as opposed to intermittent bolus administration) may be a safer and more efficacious way of administering IV diuretics in ADHF. These questions have been recently addressed by a National Institutes of Health (NIH)–sponsored randomized clinical trial (the Diuretic Optimization Strategies Evaluation [DOSE]).

    Using a 2 × 2 factorial design, DOSE randomized 308 patients to either high (2.5 × chronic oral dose given IV) or low (1 × chronic oral dose given IV) dosages of diuretics, and also to either continuous infusion or every-12-hour IV bolus. With regard to route of administration, there was no significant difference in either efficacy or safety when diuretics were given as intermittent boluses or as continuous infusion. With regard to dosing, there was a general trend towards greater decongestion and improved symptoms with higher-dose diuretics (although the study did not meet its nominal primary efficacy endpoint of patient global assessment with a P value = 0.06). This suggestion of improved efficacy did appear to come at a cost of more episodes of renal dysfunction in the higher-dose arm, but these changes were transient and did not appear to have any impact on post-discharge clinical outcomes. Taken as a whole, the results from DOSE appear to generally support an aggressive approach to decongestion of volume overloaded patients with ADHF, although renal function, electrolytes, and volume status need to be carefully monitored.

7. What about using vasodilators such as nesiritide?

    Nesiritide, a recombinant form of human BNP, is a vasodilator with similar hemodynamic effects to other parenteral vasodilators, such as nitroglycerin and sodium nitroprusside. Nesiritide was approved for ADHF therapy based on its ability to speed the resolution of symptoms in patients with ADHF in the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) study. Subsequently, several retrospective meta-analyses have suggested the possibility that nesiritide therapy could be associated with adverse effects on renal function or even increased mortality. This led to substantial controversy about the appropriate role of nesiritide in ADHF management. The ASCEND-HF study was a large international randomized controlled trial designed to assess the impact of nesiritide on symptoms, renal function, and 30-day clinical outcomes. ASCEND-HF randomized 7141 patients with ADHF within 24 hours of initial IV treatment for heart failure. This study showed statistically significant (but clinically very modest) improvements in dyspnea with nesiritide at both 6 and 24 hours from randomization. There was no significant difference in either death or the composite of death or heart failure hospitalization at 30 days. Overall, the ASCEND-HF results do not support the routine use of nesiritide in patients with ADHF.

8. What is the role of inotropes like dobutamine or milrinone in patients with ADHF?

    Inotropic drugs, which increase cardiac contractility, are theoretically appealing as a therapy for ADHF. Despite this theoretical appeal, however, available data clearly demonstrate that such agents are not indicated for the vast majority of ADHF patients. In the OPTIME-CHF study, a large randomized trial of IV milrinone therapy in ADHF, randomization to milrinone did not shorten length of stay or improve other clinical outcomes, and it was associated with significantly higher rates of arrhythmias and hypotension than was the placebo. These data suggest that the routine use of inotropes is not indicated in ADHF management. Importantly, OPTIME-CHF specifically excluded patients with shock or other apparent indications for inotropes. As noted earlier, the vast majority of ADHF patients do not have evidence of end-organ hypoperfusion or shock. In the subset of patients with cardiogenic shock or severe end-organ dysfunction, inotropic therapy may still be indicated as a method of achieving short-term stabilization until more definitive long-term therapy (such are revascularization, cardiac transplantation, or mechanical cardiac support) can be employed.

9. What is the role for invasive hemodynamic monitoring in patients with ADHF?

    The routine use of invasive hemodynamic monitoring (such as with pulmonary artery catheters) is not indicated in patients with ADHF. This recommendation is based primarily on the results of the ESCAPE study, which demonstrated no advantage in terms of days alive and free from hospitalization when patients hospitalized with advanced heart failure were randomized to pulmonary artery catheter-guided therapy versus usual care. Invasive hemodynamic monitoring may be indicated to guide therapy in selected patients who are refractory to initial therapy, particularly those with hypotension or worsening renal function.

10. What is cardiorenal syndrome in ADHF?

    Worsening renal function during hospitalization for ADHF represents a major clinical challenge. Often termed cardiorenal syndrome (CRS), this clinical syndrome is characterized by persistent volume overload accompanied by worsening of renal function. Development of CRS, as defined by an increase in serum creatinine of 0.3 mg/dL or more from admission, occurs in as many as one-third of patients hospitalized with ADHF. Development of CRS is associated with higher mortality and increased length of stay in patients with ADHF. Although the underlying mechanisms of CRS remain ill defined, data suggest that higher diuretic doses, preexisting renal disease, and diabetes mellitus are associated with an increased risk. The optimal therapeutic strategy for patients with ADHF and CRS remains unknown. A variety of clinical approaches (hemodynamically guided therapy, inotropes, temporarily holding diuretics, etc.) have all been used with varying results, and there are no large outcomes studies to guide management of these challenging patients. Ultrafiltration therapy, which results in the removal of both free water and sodium, is currently being studied as an approach to CRS in an NIH-sponsored, randomized clinical trial that has recently completed enrollment.

11. How should we determine when to discharge patients?

    The decision of when to discharge a patient with ADHF from the hospital is often based on clinical judgment rather than objective criteria. Criteria that should be met before consideration of hospital discharge have been published in the HFSA guidelines (Box 22-3). Most patients should have follow-up scheduled within 7 to 10 days of discharge, and high-risk patients should be considered for earlier follow-up (by phone or in person) or referral to a comprehensive disease management program. Early adjustment of diuretics may be required as patients make the transition from the hospital environment (with IV diuretics and controlled low-sodium diet) to home.

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