Although patients with left ventricular dysfunction may present with low‐output syndrome and even cardiogenic shock, the majority are admitted with symptoms of congestion.1 The classic symptoms of congestive heart failure reflect fluid overload, that is, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema; these symptoms can be so dramatic that it is not surprising that patients seek hospitalization.2 Activation of the renin angiotensin system coupled with sympathetic hyperactivity results in marked sodium retention and increased filling pressures in the right and left ventricle that ultimately bring about these congestive symptoms of dyspnea and orthopnea.3 Increased filling pressure precedes admission to the hospital, and filling pressure falls during successful therapy.4, 5 Indeed, normalization of the left ventricular filling pressure much better predicts survival than improved cardiac output.6 However, despite the many advances in the evidence‐based armamentarium for heart failure, the one great deficiency in the evidence base is the lack of data on modalities that can reduce or normalize left ventricular filling pressures. This is not as unexpected as it seems because the symptoms of congestion are so dramatic and, until recently, the tools to mitigate were so few that randomized trials were difficult to conceive. However, the treatment paradigms for acute decompensated heart failure (ADHF) management are changing, and evidence‐based mortality trials for filling pressure reduction and congestion relief continue to evolve.710

DIURETICS

Mercurial diuretics were introduced in the 1920s as the mainstay of therapy for ADHF; the loop diuretics became the foundation of therapy in the 1960s.11, 12 In the Acute Decompensated Heart Failure National Registry database (ADHERE), 88% of patients received intravenous loop diuretics during their hospitalization.13 Loop diuretics act in the thick ascending limb of the loop of Henle to inhibit reabsorption of sodium and chloride by inhibiting the sodium, potassium, and chloride (Na⁺/K⁺/2Cl) pump. This blockade causes increased delivery of these solutes to the distal convoluted tubule and collecting duct, resulting in a shift in the balance of osmotic forces toward fluid secretion into the collecting system. Through this mechanism, loop diuretics increase natriuresis and diuresis (Figure 1).14

Figure 1

Less commonly used are the thiazide diuretics, which act on the distal convoluted tubule to block Na⁺, K⁺‐ATPase and thereby NaCl transport in the distal convoluted tubule.15 Thiazide diuretics are much less powerful than loop diuretics and are rarely used intravenously in the hospital. These do possess a synergistic effect when used with loop diuretics in that sodium reabsorption is blocked in 2 sections of the nephron.16 Extreme care must be taken to avoid overdiuresis, but this combination can be helpful to treat diuretic resistance.17

The third class of agents are the so‐called potassium‐sparing diuretics, which block sodium reuptake in the final portion of the nephron (the collecting ducts), resulting in an obligatory reuptake of potassium. These agents include the aldosterone receptor blocker spironolactone and eplerenone, which act primarily through competitive binding of receptors at the aldosterone‐dependent sodium‐potassium exchange site in the distal convoluted renal tubule. Although weak diuretics, they are the only class of diuretics shown to improve mortality in moderate to severe heart failure,18, 19 presumably by modulating the abnormal neurohormonal activation of the sympathetic nervous system and the renin‐angiotensin‐aldosterone axis.20 Unfortunately, severe hyperkalemia remains a significant side effect and can limit their use.21

Despite the obvious beneficial effects of loop diuretics in the treatment of ADHF, we lack key fundamental information about these most frequently used drugs. For example, what is the correct dose? Escalating the dose of diuretics has been associated with increased mortality in heart failure even when corrected for the severity of the illness.22, 23 Proposed explanations for the increased morality in patients with heart failure include activation of the renin‐angiotensin‐aldosterone system and sympathetic nervous system, decreases in the glomerular filtration rate (GFR) contributing to cardiorenal syndrome, and intravascular volume contraction and decreased left ventricular filling pressure worsening cardiac performance in patients without significant fluid retention.22, 23 It is now recognized that kidney dysfunction plays a vital role in the progress of patients with heart failure, and increases in serum creatinine or blood urea nitrogen are known predictors of mortality.24 Thus, larger doses of diuretics may result in unfavorable outcomes in heart failure patients because of adverse effects on renal function. In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), there was a clear increase in mortality with escalating loop diuretic doses, especially above 300 mg/day of furosemide (or an equivalent dose of another loop diuretic).25 Although patients with renal dysfunction may require higher doses, prudence would dictate using the lowest dose to gain a reasonable urine output.

How should loop diuretics be given: as a bolus or continuous infusion? Although diuretics have been typically given as a bolus, there are significant theoretical concerns about this method. Furosemide, for example, has a half‐life of approximately 2 hours; when it is given once or twice a day, a breaking phenomenon is seen in which the kidneys start to retain sodium and the effectiveness of the bolus is reduced.26 A Cochrane review has found evidence that a continuous infusion of diuretics produces more diuresis, although the same article suggests that more titration is needed to support this observation.27

Several loop diuretics are used clinically, including furosemide, torsemide, and bumetanide. Which one should be chosen? Furosemide is the least expensive and most widely used, but 2 animal models suggest more favorable cardiac effects (less fibrosis) with torsemide and even mortality benefit.28, 29 There are no comparable human data to guide the clinician, unfortunately. On a milligram per milligram basis, bumetanide produces more natriuresis than either torsemide or furosemide, but again, the clinical significance of this is not known.

VASODILATORS

ULTRAFILTRATION (UF)

UF removes water and nonprotein‐bound smallmolecular‐weight and mediummolecular‐weight solutes through the semipermeable membrane when hydrostatic pressure, generated by blood pressure or an external blood pump, exceeds oncotic pressure. The fluid removal rate can be adjusted between 100 and 500 mL/hour. The Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure (UNLOAD) trial randomized UF with intravenous diuretic therapy in patients with ADHF and showed that UF produced greater weight and fluid loss at 48 hours versus diuretics and reduced the 90‐day readmission rate for heart failure.51 There was no statistically significant difference noted between the overall mortality and serum creatinine between the 2 groups. Rogers et al52 found in a small, randomized trial that during a 48‐hour period, UF showed no significant difference in the renal hemodynamics (GFR and renal plasma flow in patients with ADHF) versus the standard treatment with intravenous diuretics. The Heart Failure Society of America treatment guidelines for the evaluation and management of patients with ADHF suggest that when congestion fails to improve in response to diuretic therapy, UF may be considered (strength of evidence = C).53

Perhaps the most vexing issue surrounding the use of diuretics, vasodilators, and UF is when to stop intravenous therapy in the hospitalized patient. There are no clear guidelines about this, and perhaps clinical experience is of paramount importance. Theoretically, vasodilator and fluid removal therapy should be continued until the patient is euvolemic, that is, has normal filling pressures (usually associated with normalization of the neck veins and loss of S3) with improvement in symptoms. This was clearly seen in the ESCAPE trial, in which use of either hemodynamic guidance or clinical evaluation of jugular venous pressure resulted in more normal filling pressures.5 This is an extremely important issue because continued fluid removal beyond the point at which the patient is euvolemic may result in renal dysfunction; the latter is a strong predictor of prolonged hospitalization and mortality.54, 55

Initial fluid removal can be rapid with either diuretics or UF, and filling pressures fall within minutes with nesiritide. This is beneficial to the patient as long as extracellular sodium and water reenter the vascular bed to maintain preload. Boyle and Sobotka56 emphasized the importance of this plasma refill rate and proposed monitoring the hematocrit as is done in dialysis to prevent excessive fluid removal. As can be seen in Figure 2, the plasma compartment is easily refilled when extracellular volume is increased in edematous patients early in their therapy. However, the plasma refill rate can fall precipitously when this compartment is depleted. Hence, clinicians must be ever alert to this transition period when continued fluid removal or vasodilator therapy results in depletion of vascular, not interstitial, volume with rapid declines in preload and cardiac output. Therefore, these therapies should be stopped when the patient becomes euvolemic, not later when the patient has become hypovolemic with the attendant problems. In the ESCAPE trial, the jugular venous pressure was the best indicator of a normal filling pressure,5, 54 although this is not an infallible guide. Our practice is to stop diuretics and vasodilators when edema has resolved and jugular venous pressure is below 8 cm. In addition, checking blood urea nitrogen and creatinine twice a day can give an early warning of hypovolemia when these rise 25% above baseline.57 Volume status should be carefully evaluated by changes in the physical examination, including postural blood pressure changes and increases in blood urea nitrogen and creatinine. When worsening renal function occurs, judicious fluid replacement with 500 to 1000 mL of normal saline given over 2 to 4 hours can quickly restore euvolemia and may improve renal function in the hypovolemic patient.

Figure 2

INVESTIGATIONAL THERAPIES

CONCLUSION

The goals in the management of ADHF are deceptively simple: improve symptoms by normalizing filling pressure and volume status efficiently without worsening renal function. Powerful tools, including diuretics, vasodilators, and UF, exist to accomplish these goals, but determining which tools to use in which patients and the precise manner in which to use the tools (alone or in combination and duration) remains more of an art than a science. The concept of euvolemia needs to be more carefully defined and conceptualized in a way that is useful for clinicians. Frequent monitoring of clinical signs, electrolytes, and renal function are our current best guides to assess volume status during therapy. Newer modalities hold promise that early detection of fluid overload may prevent hospitalization and reduce costs. Similarly, new pharmacologic therapies hold promise that their use may improve cardiac function and reduce renal abnormalities, thereby improving outcomes in patients with ADHF.

Although patients with left ventricular dysfunction may present with low‐output syndrome and even cardiogenic shock, the majority are admitted with symptoms of congestion.1 The classic symptoms of congestive heart failure reflect fluid overload, that is, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema; these symptoms can be so dramatic that it is not surprising that patients seek hospitalization.2 Activation of the renin angiotensin system coupled with sympathetic hyperactivity results in marked sodium retention and increased filling pressures in the right and left ventricle that ultimately bring about these congestive symptoms of dyspnea and orthopnea.3 Increased filling pressure precedes admission to the hospital, and filling pressure falls during successful therapy.4, 5 Indeed, normalization of the left ventricular filling pressure much better predicts survival than improved cardiac output.6 However, despite the many advances in the evidence‐based armamentarium for heart failure, the one great deficiency in the evidence base is the lack of data on modalities that can reduce or normalize left ventricular filling pressures. This is not as unexpected as it seems because the symptoms of congestion are so dramatic and, until recently, the tools to mitigate were so few that randomized trials were difficult to conceive. However, the treatment paradigms for acute decompensated heart failure (ADHF) management are changing, and evidence‐based mortality trials for filling pressure reduction and congestion relief continue to evolve.710

DIURETICS

Mercurial diuretics were introduced in the 1920s as the mainstay of therapy for ADHF; the loop diuretics became the foundation of therapy in the 1960s.11, 12 In the Acute Decompensated Heart Failure National Registry database (ADHERE), 88% of patients received intravenous loop diuretics during their hospitalization.13 Loop diuretics act in the thick ascending limb of the loop of Henle to inhibit reabsorption of sodium and chloride by inhibiting the sodium, potassium, and chloride (Na⁺/K⁺/2Cl) pump. This blockade causes increased delivery of these solutes to the distal convoluted tubule and collecting duct, resulting in a shift in the balance of osmotic forces toward fluid secretion into the collecting system. Through this mechanism, loop diuretics increase natriuresis and diuresis (Figure 1).14

Figure 1

Less commonly used are the thiazide diuretics, which act on the distal convoluted tubule to block Na⁺, K⁺‐ATPase and thereby NaCl transport in the distal convoluted tubule.15 Thiazide diuretics are much less powerful than loop diuretics and are rarely used intravenously in the hospital. These do possess a synergistic effect when used with loop diuretics in that sodium reabsorption is blocked in 2 sections of the nephron.16 Extreme care must be taken to avoid overdiuresis, but this combination can be helpful to treat diuretic resistance.17

The third class of agents are the so‐called potassium‐sparing diuretics, which block sodium reuptake in the final portion of the nephron (the collecting ducts), resulting in an obligatory reuptake of potassium. These agents include the aldosterone receptor blocker spironolactone and eplerenone, which act primarily through competitive binding of receptors at the aldosterone‐dependent sodium‐potassium exchange site in the distal convoluted renal tubule. Although weak diuretics, they are the only class of diuretics shown to improve mortality in moderate to severe heart failure,18, 19 presumably by modulating the abnormal neurohormonal activation of the sympathetic nervous system and the renin‐angiotensin‐aldosterone axis.20 Unfortunately, severe hyperkalemia remains a significant side effect and can limit their use.21

Despite the obvious beneficial effects of loop diuretics in the treatment of ADHF, we lack key fundamental information about these most frequently used drugs. For example, what is the correct dose? Escalating the dose of diuretics has been associated with increased mortality in heart failure even when corrected for the severity of the illness.22, 23 Proposed explanations for the increased morality in patients with heart failure include activation of the renin‐angiotensin‐aldosterone system and sympathetic nervous system, decreases in the glomerular filtration rate (GFR) contributing to cardiorenal syndrome, and intravascular volume contraction and decreased left ventricular filling pressure worsening cardiac performance in patients without significant fluid retention.22, 23 It is now recognized that kidney dysfunction plays a vital role in the progress of patients with heart failure, and increases in serum creatinine or blood urea nitrogen are known predictors of mortality.24 Thus, larger doses of diuretics may result in unfavorable outcomes in heart failure patients because of adverse effects on renal function. In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), there was a clear increase in mortality with escalating loop diuretic doses, especially above 300 mg/day of furosemide (or an equivalent dose of another loop diuretic).25 Although patients with renal dysfunction may require higher doses, prudence would dictate using the lowest dose to gain a reasonable urine output.

How should loop diuretics be given: as a bolus or continuous infusion? Although diuretics have been typically given as a bolus, there are significant theoretical concerns about this method. Furosemide, for example, has a half‐life of approximately 2 hours; when it is given once or twice a day, a breaking phenomenon is seen in which the kidneys start to retain sodium and the effectiveness of the bolus is reduced.26 A Cochrane review has found evidence that a continuous infusion of diuretics produces more diuresis, although the same article suggests that more titration is needed to support this observation.27

Several loop diuretics are used clinically, including furosemide, torsemide, and bumetanide. Which one should be chosen? Furosemide is the least expensive and most widely used, but 2 animal models suggest more favorable cardiac effects (less fibrosis) with torsemide and even mortality benefit.28, 29 There are no comparable human data to guide the clinician, unfortunately. On a milligram per milligram basis, bumetanide produces more natriuresis than either torsemide or furosemide, but again, the clinical significance of this is not known.

VASODILATORS

ULTRAFILTRATION (UF)

UF removes water and nonprotein‐bound smallmolecular‐weight and mediummolecular‐weight solutes through the semipermeable membrane when hydrostatic pressure, generated by blood pressure or an external blood pump, exceeds oncotic pressure. The fluid removal rate can be adjusted between 100 and 500 mL/hour. The Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure (UNLOAD) trial randomized UF with intravenous diuretic therapy in patients with ADHF and showed that UF produced greater weight and fluid loss at 48 hours versus diuretics and reduced the 90‐day readmission rate for heart failure.51 There was no statistically significant difference noted between the overall mortality and serum creatinine between the 2 groups. Rogers et al52 found in a small, randomized trial that during a 48‐hour period, UF showed no significant difference in the renal hemodynamics (GFR and renal plasma flow in patients with ADHF) versus the standard treatment with intravenous diuretics. The Heart Failure Society of America treatment guidelines for the evaluation and management of patients with ADHF suggest that when congestion fails to improve in response to diuretic therapy, UF may be considered (strength of evidence = C).53

Perhaps the most vexing issue surrounding the use of diuretics, vasodilators, and UF is when to stop intravenous therapy in the hospitalized patient. There are no clear guidelines about this, and perhaps clinical experience is of paramount importance. Theoretically, vasodilator and fluid removal therapy should be continued until the patient is euvolemic, that is, has normal filling pressures (usually associated with normalization of the neck veins and loss of S3) with improvement in symptoms. This was clearly seen in the ESCAPE trial, in which use of either hemodynamic guidance or clinical evaluation of jugular venous pressure resulted in more normal filling pressures.5 This is an extremely important issue because continued fluid removal beyond the point at which the patient is euvolemic may result in renal dysfunction; the latter is a strong predictor of prolonged hospitalization and mortality.54, 55

Initial fluid removal can be rapid with either diuretics or UF, and filling pressures fall within minutes with nesiritide. This is beneficial to the patient as long as extracellular sodium and water reenter the vascular bed to maintain preload. Boyle and Sobotka56 emphasized the importance of this plasma refill rate and proposed monitoring the hematocrit as is done in dialysis to prevent excessive fluid removal. As can be seen in Figure 2, the plasma compartment is easily refilled when extracellular volume is increased in edematous patients early in their therapy. However, the plasma refill rate can fall precipitously when this compartment is depleted. Hence, clinicians must be ever alert to this transition period when continued fluid removal or vasodilator therapy results in depletion of vascular, not interstitial, volume with rapid declines in preload and cardiac output. Therefore, these therapies should be stopped when the patient becomes euvolemic, not later when the patient has become hypovolemic with the attendant problems. In the ESCAPE trial, the jugular venous pressure was the best indicator of a normal filling pressure,5, 54 although this is not an infallible guide. Our practice is to stop diuretics and vasodilators when edema has resolved and jugular venous pressure is below 8 cm. In addition, checking blood urea nitrogen and creatinine twice a day can give an early warning of hypovolemia when these rise 25% above baseline.57 Volume status should be carefully evaluated by changes in the physical examination, including postural blood pressure changes and increases in blood urea nitrogen and creatinine. When worsening renal function occurs, judicious fluid replacement with 500 to 1000 mL of normal saline given over 2 to 4 hours can quickly restore euvolemia and may improve renal function in the hypovolemic patient.

Figure 2

INVESTIGATIONAL THERAPIES

CONCLUSION

The goals in the management of ADHF are deceptively simple: improve symptoms by normalizing filling pressure and volume status efficiently without worsening renal function. Powerful tools, including diuretics, vasodilators, and UF, exist to accomplish these goals, but determining which tools to use in which patients and the precise manner in which to use the tools (alone or in combination and duration) remains more of an art than a science. The concept of euvolemia needs to be more carefully defined and conceptualized in a way that is useful for clinicians. Frequent monitoring of clinical signs, electrolytes, and renal function are our current best guides to assess volume status during therapy. Newer modalities hold promise that early detection of fluid overload may prevent hospitalization and reduce costs. Similarly, new pharmacologic therapies hold promise that their use may improve cardiac function and reduce renal abnormalities, thereby improving outcomes in patients with ADHF.

Although patients with left ventricular dysfunction may present with low‐output syndrome and even cardiogenic shock, the majority are admitted with symptoms of congestion.1 The classic symptoms of congestive heart failure reflect fluid overload, that is, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema; these symptoms can be so dramatic that it is not surprising that patients seek hospitalization.2 Activation of the renin angiotensin system coupled with sympathetic hyperactivity results in marked sodium retention and increased filling pressures in the right and left ventricle that ultimately bring about these congestive symptoms of dyspnea and orthopnea.3 Increased filling pressure precedes admission to the hospital, and filling pressure falls during successful therapy.4, 5 Indeed, normalization of the left ventricular filling pressure much better predicts survival than improved cardiac output.6 However, despite the many advances in the evidence‐based armamentarium for heart failure, the one great deficiency in the evidence base is the lack of data on modalities that can reduce or normalize left ventricular filling pressures. This is not as unexpected as it seems because the symptoms of congestion are so dramatic and, until recently, the tools to mitigate were so few that randomized trials were difficult to conceive. However, the treatment paradigms for acute decompensated heart failure (ADHF) management are changing, and evidence‐based mortality trials for filling pressure reduction and congestion relief continue to evolve.710

DIURETICS

Mercurial diuretics were introduced in the 1920s as the mainstay of therapy for ADHF; the loop diuretics became the foundation of therapy in the 1960s.11, 12 In the Acute Decompensated Heart Failure National Registry database (ADHERE), 88% of patients received intravenous loop diuretics during their hospitalization.13 Loop diuretics act in the thick ascending limb of the loop of Henle to inhibit reabsorption of sodium and chloride by inhibiting the sodium, potassium, and chloride (Na⁺/K⁺/2Cl) pump. This blockade causes increased delivery of these solutes to the distal convoluted tubule and collecting duct, resulting in a shift in the balance of osmotic forces toward fluid secretion into the collecting system. Through this mechanism, loop diuretics increase natriuresis and diuresis (Figure 1).14

Figure 1

Less commonly used are the thiazide diuretics, which act on the distal convoluted tubule to block Na⁺, K⁺‐ATPase and thereby NaCl transport in the distal convoluted tubule.15 Thiazide diuretics are much less powerful than loop diuretics and are rarely used intravenously in the hospital. These do possess a synergistic effect when used with loop diuretics in that sodium reabsorption is blocked in 2 sections of the nephron.16 Extreme care must be taken to avoid overdiuresis, but this combination can be helpful to treat diuretic resistance.17

The third class of agents are the so‐called potassium‐sparing diuretics, which block sodium reuptake in the final portion of the nephron (the collecting ducts), resulting in an obligatory reuptake of potassium. These agents include the aldosterone receptor blocker spironolactone and eplerenone, which act primarily through competitive binding of receptors at the aldosterone‐dependent sodium‐potassium exchange site in the distal convoluted renal tubule. Although weak diuretics, they are the only class of diuretics shown to improve mortality in moderate to severe heart failure,18, 19 presumably by modulating the abnormal neurohormonal activation of the sympathetic nervous system and the renin‐angiotensin‐aldosterone axis.20 Unfortunately, severe hyperkalemia remains a significant side effect and can limit their use.21

Despite the obvious beneficial effects of loop diuretics in the treatment of ADHF, we lack key fundamental information about these most frequently used drugs. For example, what is the correct dose? Escalating the dose of diuretics has been associated with increased mortality in heart failure even when corrected for the severity of the illness.22, 23 Proposed explanations for the increased morality in patients with heart failure include activation of the renin‐angiotensin‐aldosterone system and sympathetic nervous system, decreases in the glomerular filtration rate (GFR) contributing to cardiorenal syndrome, and intravascular volume contraction and decreased left ventricular filling pressure worsening cardiac performance in patients without significant fluid retention.22, 23 It is now recognized that kidney dysfunction plays a vital role in the progress of patients with heart failure, and increases in serum creatinine or blood urea nitrogen are known predictors of mortality.24 Thus, larger doses of diuretics may result in unfavorable outcomes in heart failure patients because of adverse effects on renal function. In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), there was a clear increase in mortality with escalating loop diuretic doses, especially above 300 mg/day of furosemide (or an equivalent dose of another loop diuretic).25 Although patients with renal dysfunction may require higher doses, prudence would dictate using the lowest dose to gain a reasonable urine output.

How should loop diuretics be given: as a bolus or continuous infusion? Although diuretics have been typically given as a bolus, there are significant theoretical concerns about this method. Furosemide, for example, has a half‐life of approximately 2 hours; when it is given once or twice a day, a breaking phenomenon is seen in which the kidneys start to retain sodium and the effectiveness of the bolus is reduced.26 A Cochrane review has found evidence that a continuous infusion of diuretics produces more diuresis, although the same article suggests that more titration is needed to support this observation.27

Several loop diuretics are used clinically, including furosemide, torsemide, and bumetanide. Which one should be chosen? Furosemide is the least expensive and most widely used, but 2 animal models suggest more favorable cardiac effects (less fibrosis) with torsemide and even mortality benefit.28, 29 There are no comparable human data to guide the clinician, unfortunately. On a milligram per milligram basis, bumetanide produces more natriuresis than either torsemide or furosemide, but again, the clinical significance of this is not known.

VASODILATORS

ULTRAFILTRATION (UF)

UF removes water and nonprotein‐bound smallmolecular‐weight and mediummolecular‐weight solutes through the semipermeable membrane when hydrostatic pressure, generated by blood pressure or an external blood pump, exceeds oncotic pressure. The fluid removal rate can be adjusted between 100 and 500 mL/hour. The Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure (UNLOAD) trial randomized UF with intravenous diuretic therapy in patients with ADHF and showed that UF produced greater weight and fluid loss at 48 hours versus diuretics and reduced the 90‐day readmission rate for heart failure.51 There was no statistically significant difference noted between the overall mortality and serum creatinine between the 2 groups. Rogers et al52 found in a small, randomized trial that during a 48‐hour period, UF showed no significant difference in the renal hemodynamics (GFR and renal plasma flow in patients with ADHF) versus the standard treatment with intravenous diuretics. The Heart Failure Society of America treatment guidelines for the evaluation and management of patients with ADHF suggest that when congestion fails to improve in response to diuretic therapy, UF may be considered (strength of evidence = C).53

Perhaps the most vexing issue surrounding the use of diuretics, vasodilators, and UF is when to stop intravenous therapy in the hospitalized patient. There are no clear guidelines about this, and perhaps clinical experience is of paramount importance. Theoretically, vasodilator and fluid removal therapy should be continued until the patient is euvolemic, that is, has normal filling pressures (usually associated with normalization of the neck veins and loss of S3) with improvement in symptoms. This was clearly seen in the ESCAPE trial, in which use of either hemodynamic guidance or clinical evaluation of jugular venous pressure resulted in more normal filling pressures.5 This is an extremely important issue because continued fluid removal beyond the point at which the patient is euvolemic may result in renal dysfunction; the latter is a strong predictor of prolonged hospitalization and mortality.54, 55

Initial fluid removal can be rapid with either diuretics or UF, and filling pressures fall within minutes with nesiritide. This is beneficial to the patient as long as extracellular sodium and water reenter the vascular bed to maintain preload. Boyle and Sobotka56 emphasized the importance of this plasma refill rate and proposed monitoring the hematocrit as is done in dialysis to prevent excessive fluid removal. As can be seen in Figure 2, the plasma compartment is easily refilled when extracellular volume is increased in edematous patients early in their therapy. However, the plasma refill rate can fall precipitously when this compartment is depleted. Hence, clinicians must be ever alert to this transition period when continued fluid removal or vasodilator therapy results in depletion of vascular, not interstitial, volume with rapid declines in preload and cardiac output. Therefore, these therapies should be stopped when the patient becomes euvolemic, not later when the patient has become hypovolemic with the attendant problems. In the ESCAPE trial, the jugular venous pressure was the best indicator of a normal filling pressure,5, 54 although this is not an infallible guide. Our practice is to stop diuretics and vasodilators when edema has resolved and jugular venous pressure is below 8 cm. In addition, checking blood urea nitrogen and creatinine twice a day can give an early warning of hypovolemia when these rise 25% above baseline.57 Volume status should be carefully evaluated by changes in the physical examination, including postural blood pressure changes and increases in blood urea nitrogen and creatinine. When worsening renal function occurs, judicious fluid replacement with 500 to 1000 mL of normal saline given over 2 to 4 hours can quickly restore euvolemia and may improve renal function in the hypovolemic patient.

Figure 2

INVESTIGATIONAL THERAPIES

CONCLUSION

The goals in the management of ADHF are deceptively simple: improve symptoms by normalizing filling pressure and volume status efficiently without worsening renal function. Powerful tools, including diuretics, vasodilators, and UF, exist to accomplish these goals, but determining which tools to use in which patients and the precise manner in which to use the tools (alone or in combination and duration) remains more of an art than a science. The concept of euvolemia needs to be more carefully defined and conceptualized in a way that is useful for clinicians. Frequent monitoring of clinical signs, electrolytes, and renal function are our current best guides to assess volume status during therapy. Newer modalities hold promise that early detection of fluid overload may prevent hospitalization and reduce costs. Similarly, new pharmacologic therapies hold promise that their use may improve cardiac function and reduce renal abnormalities, thereby improving outcomes in patients with ADHF.

Acute decompensated heart failure (ADHF) is a common disorder that is frequently managed by hospitalists. This management is expected to expand over the next several years because of a continuing increase in the number of ADHF admissions coupled with a plateau or possible decline in the number of practicing cardiologists (Figure 1).114 In addition, 12% of fellowship training positions in cardiology were eliminated between 1995 and 2001, and the fact that the current number of training positions is inadequate to meet future demands is not recognized.15, 16 Given the severity of this disorder, the limited data from randomized, controlled clinical trials,17 and the limitations of current treatment, this management can be both challenging and rewarding. The goal of this special supplement of the Journal of Hospital Medicine is to assist hospitalists in this endeavor by summarizing the currently available data and treatment options and presenting a rational evidence‐based algorithm for the management of ADHF.

Figure 1

A multidisciplinary approach to heart failure has been shown to reduce cost, decrease length of stay, curtail readmissions, and improve compliance.1820 By leading and coordinating teams of physicians, pharmacists, nurses, nutritionists, physical therapists, and case managers and by developing and implementing indications for cardiology consultation, hospitalists can facilitate this multidisciplinary approach.21, 22 However, it is important to remember that hospitalists do not replace cardiologists, who remain a valuable and key component of this multidisciplinary team. Their input is vital in developing care pathways and criteria for consultation, and they, along with primary care physicians, will be the primary source of patient care following hospital discharge. Good communication between hospitalists and cardiologists is essential to optimize the care of patients with ADHF.

Maximizing the efficacy of ADHF care requires a thorough understanding of (1) the causes and potential treatments for the patient's acute decompensation, (2) the management of the patient's chronic heart failure, and (3) potential future therapies. Strategies to improve the continuum of heart failure care have been employed to help improve patient outcomes.23 For example, hospital‐based disease management programs have consistently been shown to optimize care and reduce rehospitalization rates in patients with heart failure.24 These programs involve a multidisciplinary, multifaceted approach to care in order to provide a continuum of care extending from hospitalization and into a patient's home environment.

Because of their practice location and experience, hospitalists are uniquely suited to influence acute inpatient care.25 They see patients in a variety of hospital settings and consequently tend to think of the entire system and not just an isolated component or patient.14 In addition, they have a vested interest in hospital quality improvement measures and are frequently involved in evaluating policies and procedures and developing and implementing clinical pathways, guidelines, and decision‐support tools.26 Data demonstrate that compliance is greater with evidence‐based guidelines and core performance measures when inpatient care is directed by a hospitalist.2730 Improved compliance with selected quality measures in patients with acute myocardial infarction and congestive heart failure has been observed when hospitals implement standardized admission and discharge orders.31, 32

Numerous transitions, such as outpatient to inpatient, intensive care unit to ward, and ward to home, occur during hospitalization, and these transitions are frequently associated with changes in the patient's medication regimen. During an acute illness, chronic medications may be held or discontinued, long‐acting medications may be changed to short‐acting ones to better titrate dose and achieve tighter control, and closed formularies may necessitate substituting 1 medication for another.33 A breakdown in communication during hospitalization‐associated transitions commonly affects medication regimens and can adversely impact patient care.3436 In a prospective evaluation, 53.6% [95% confidence interval (CI): 45.7%61.6%] of patients admitted to the hospital had at least 1 unintended discrepancy between their admission medication orders and their chronic outpatient regimen; 38.6% of these discrepancies were considered a potential threat to the patient.34 Likewise, 49% of patients being discharged from the hospital in another evaluation had an unexplained discrepancy between their preadmission and discharge medications.36 As a result, the Joint Commission on Accreditation of Healthcare Organizations now requires accredited facilities to perform medication reconciliation whenever a patient changes service, setting, provider, or level of care and new medication orders are written.37 This reconciliation is especially important in patients with heart failure, for whom polypharmacy is common and noncompliance with appropriate treatment regimens substantially increases readmission rates.3842

During these transition periods, hospitalists can play an important role in bridging the communication gap and providing this medication reconciliation.33 For example, actively involving hospitalists in all aspects of the reconciliation process at 1 institution resulted in a 4‐fold increase in consistency with preadmission medications.43 Similarly, because of the number of discharge summaries that they write, hospitalists are well suited to lead implementation of new policies and procedures to ensure compliance with recent changes in the Joint Commission on Accreditation of Healthcare Organizations requirements regarding these summaries.

In addition to playing an active role in acute patient management, hospitalists can substantially influence long‐term care and outcomes. Consequently, hospitalists must be well versed in the management of chronic heart failure. Patients are intensely focused on their illness during the hospitalization period, and this focus enhances opportunities for meaningful education and behavior modification. Numerous studies have demonstrated that adherence to long‐term therapy is improved when this therapy is initiated before or at hospital discharge.4446 In an evaluation of data from the Organized Program To Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure Registry (OPTIMIZE‐HF), the prescription of a ‐blocker at discharge was associated with a significant reduction in 60‐ to 90‐day mortality [hazard ratio (HR): 0.48; 95% CI: 0.30‐0.79], and prescription of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker at discharge was associated with a significant reduction in 60‐ to 90‐day mortality and/or rehospitalization (HR: 0.51; 95% CI: 0.34‐0.78).47 In the Cardiac Hospitalization Atherosclerosis Management Program (CHAMP), emphasizing initiation of chronic therapy prior to hospital discharge was associated with 3.0‐fold greater angiotensin‐converting enzyme inhibitor use and 3.2‐fold greater ‐blocker use at 1 year (both P < 0.01).46 Similarly, in patients surviving acute myocardial infarction, the strongest predictor of ‐blocker use at 30 days following discharge was receipt of a ‐blocker prescription at the time of discharge (HR: 15.8; 95% CI: 10.8‐23.3), and this beneficial effect was sustained for up to a year (Figure 2).44 Likewise, in patients with ADHF, the prevalence of ‐blocker therapy at 60 days was significantly increased when this therapy was initiated before discharge (91%) versus after discharge (73%; P < 0.001).45 This predischarge initiation of chronic therapy has been shown to reduce morbidity and mortality.

Figure 2

An awareness of new therapies for ADHF that are in late stages of clinical development can improve understanding of the complex pathophysiology of ADHF and enhance appropriate adaptation of these therapies once they become clinically available. These new therapies represent an attempt to improve on existing therapies, and consequently, they fall into the same 3 general categories as current therapies: diuretics, vasodilators, and inotropic agents.48, 49 Vasopressin receptor antagonists and adenosine receptor antagonists represent an attempt to stimulate aquaresis without inducing hyponatremia, hypokalemia, diminished glomerular filtration, or adverse neurohormonal activation;4854 endothelin receptor antagonists and newer natriuretic peptides represent an attempt to stimulate vasodilation and improve cardiac output without diminishing renal function;49, 55 and myosin activators and sodium‐potassium adenosine triphosphatase inhibitors represent an attempt to enhance contractility without inducing arrhythmogenicity or increasing mortality risk4859 (Table 1).

Finally, although major advancements in the medical therapy of heart failure patients have substantially improved outcomes,60 technological advances in mechanical devices,61 including automatic implantable cardioverter defibrillators, cardiac resynchronization therapy, and ventricular assist devices, as well as advances in the surgical treatment of heart failure,62 have also been used to support the failing heart. Heart failure patients being treated with mechanical devices, as well as those following cardiac transplant, require unique care. As more mechanical and surgical innovations emerge, nonpharmacologic therapy will continue to evolve as a cornerstone of the management strategy in heart failure patients. Hospitalists will need to rely on care pathways, criteria for consultation, and good communication with cardiologists to optimize the care of these patients. Hospitalists should work with their cardiology colleagues in their local institution to develop appropriate criteria for cardiology consultation, and everyone should be educated on these criteria.

The subsequent discussions in this supplement expand on these topics. First, I review the presentation and early recognition, risk stratification, and treatment of patients with ADHF and the role of the hospitalist in this assessment and treatment process. Next, Dr. Khan and Dr. Heywood review the role of diuretics, vasodilators, and ultrafiltration in the management of patients with volume overload and high filling pressures and conclude with a discussion of potential future pharmacologic treatment options, such as tolvaptan and rolofylline, and nonpharmacologic modalities, such as wireless hemodynamic monitoring through implanted devices. Finally, Dr. Michota and I discuss bridging the gap between evidence and practice in the management of patients with ADHF. We review the evidence‐based guidelines that are currently available; discuss the appropriate location for treatment based on the patient's initial history and physical, radiographic, and laboratory findings; provide a practical algorithm for this treatment; and discuss means to transition care from the inpatient setting to the outpatient setting in a manner that enhances compliance with long‐term therapy and reduces recidivism. Given the anticipated growth in ADHF and the need for hospitalists to manage this disease together with cardiologists and others, we believe that the provided information will be helpful in the management of ADHF.

Acute decompensated heart failure (ADHF) is a common disorder that is frequently managed by hospitalists. This management is expected to expand over the next several years because of a continuing increase in the number of ADHF admissions coupled with a plateau or possible decline in the number of practicing cardiologists (Figure 1).114 In addition, 12% of fellowship training positions in cardiology were eliminated between 1995 and 2001, and the fact that the current number of training positions is inadequate to meet future demands is not recognized.15, 16 Given the severity of this disorder, the limited data from randomized, controlled clinical trials,17 and the limitations of current treatment, this management can be both challenging and rewarding. The goal of this special supplement of the Journal of Hospital Medicine is to assist hospitalists in this endeavor by summarizing the currently available data and treatment options and presenting a rational evidence‐based algorithm for the management of ADHF.

Figure 1

A multidisciplinary approach to heart failure has been shown to reduce cost, decrease length of stay, curtail readmissions, and improve compliance.1820 By leading and coordinating teams of physicians, pharmacists, nurses, nutritionists, physical therapists, and case managers and by developing and implementing indications for cardiology consultation, hospitalists can facilitate this multidisciplinary approach.21, 22 However, it is important to remember that hospitalists do not replace cardiologists, who remain a valuable and key component of this multidisciplinary team. Their input is vital in developing care pathways and criteria for consultation, and they, along with primary care physicians, will be the primary source of patient care following hospital discharge. Good communication between hospitalists and cardiologists is essential to optimize the care of patients with ADHF.

Maximizing the efficacy of ADHF care requires a thorough understanding of (1) the causes and potential treatments for the patient's acute decompensation, (2) the management of the patient's chronic heart failure, and (3) potential future therapies. Strategies to improve the continuum of heart failure care have been employed to help improve patient outcomes.23 For example, hospital‐based disease management programs have consistently been shown to optimize care and reduce rehospitalization rates in patients with heart failure.24 These programs involve a multidisciplinary, multifaceted approach to care in order to provide a continuum of care extending from hospitalization and into a patient's home environment.

Because of their practice location and experience, hospitalists are uniquely suited to influence acute inpatient care.25 They see patients in a variety of hospital settings and consequently tend to think of the entire system and not just an isolated component or patient.14 In addition, they have a vested interest in hospital quality improvement measures and are frequently involved in evaluating policies and procedures and developing and implementing clinical pathways, guidelines, and decision‐support tools.26 Data demonstrate that compliance is greater with evidence‐based guidelines and core performance measures when inpatient care is directed by a hospitalist.2730 Improved compliance with selected quality measures in patients with acute myocardial infarction and congestive heart failure has been observed when hospitals implement standardized admission and discharge orders.31, 32

Numerous transitions, such as outpatient to inpatient, intensive care unit to ward, and ward to home, occur during hospitalization, and these transitions are frequently associated with changes in the patient's medication regimen. During an acute illness, chronic medications may be held or discontinued, long‐acting medications may be changed to short‐acting ones to better titrate dose and achieve tighter control, and closed formularies may necessitate substituting 1 medication for another.33 A breakdown in communication during hospitalization‐associated transitions commonly affects medication regimens and can adversely impact patient care.3436 In a prospective evaluation, 53.6% [95% confidence interval (CI): 45.7%61.6%] of patients admitted to the hospital had at least 1 unintended discrepancy between their admission medication orders and their chronic outpatient regimen; 38.6% of these discrepancies were considered a potential threat to the patient.34 Likewise, 49% of patients being discharged from the hospital in another evaluation had an unexplained discrepancy between their preadmission and discharge medications.36 As a result, the Joint Commission on Accreditation of Healthcare Organizations now requires accredited facilities to perform medication reconciliation whenever a patient changes service, setting, provider, or level of care and new medication orders are written.37 This reconciliation is especially important in patients with heart failure, for whom polypharmacy is common and noncompliance with appropriate treatment regimens substantially increases readmission rates.3842

During these transition periods, hospitalists can play an important role in bridging the communication gap and providing this medication reconciliation.33 For example, actively involving hospitalists in all aspects of the reconciliation process at 1 institution resulted in a 4‐fold increase in consistency with preadmission medications.43 Similarly, because of the number of discharge summaries that they write, hospitalists are well suited to lead implementation of new policies and procedures to ensure compliance with recent changes in the Joint Commission on Accreditation of Healthcare Organizations requirements regarding these summaries.

In addition to playing an active role in acute patient management, hospitalists can substantially influence long‐term care and outcomes. Consequently, hospitalists must be well versed in the management of chronic heart failure. Patients are intensely focused on their illness during the hospitalization period, and this focus enhances opportunities for meaningful education and behavior modification. Numerous studies have demonstrated that adherence to long‐term therapy is improved when this therapy is initiated before or at hospital discharge.4446 In an evaluation of data from the Organized Program To Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure Registry (OPTIMIZE‐HF), the prescription of a ‐blocker at discharge was associated with a significant reduction in 60‐ to 90‐day mortality [hazard ratio (HR): 0.48; 95% CI: 0.30‐0.79], and prescription of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker at discharge was associated with a significant reduction in 60‐ to 90‐day mortality and/or rehospitalization (HR: 0.51; 95% CI: 0.34‐0.78).47 In the Cardiac Hospitalization Atherosclerosis Management Program (CHAMP), emphasizing initiation of chronic therapy prior to hospital discharge was associated with 3.0‐fold greater angiotensin‐converting enzyme inhibitor use and 3.2‐fold greater ‐blocker use at 1 year (both P < 0.01).46 Similarly, in patients surviving acute myocardial infarction, the strongest predictor of ‐blocker use at 30 days following discharge was receipt of a ‐blocker prescription at the time of discharge (HR: 15.8; 95% CI: 10.8‐23.3), and this beneficial effect was sustained for up to a year (Figure 2).44 Likewise, in patients with ADHF, the prevalence of ‐blocker therapy at 60 days was significantly increased when this therapy was initiated before discharge (91%) versus after discharge (73%; P < 0.001).45 This predischarge initiation of chronic therapy has been shown to reduce morbidity and mortality.

Figure 2

An awareness of new therapies for ADHF that are in late stages of clinical development can improve understanding of the complex pathophysiology of ADHF and enhance appropriate adaptation of these therapies once they become clinically available. These new therapies represent an attempt to improve on existing therapies, and consequently, they fall into the same 3 general categories as current therapies: diuretics, vasodilators, and inotropic agents.48, 49 Vasopressin receptor antagonists and adenosine receptor antagonists represent an attempt to stimulate aquaresis without inducing hyponatremia, hypokalemia, diminished glomerular filtration, or adverse neurohormonal activation;4854 endothelin receptor antagonists and newer natriuretic peptides represent an attempt to stimulate vasodilation and improve cardiac output without diminishing renal function;49, 55 and myosin activators and sodium‐potassium adenosine triphosphatase inhibitors represent an attempt to enhance contractility without inducing arrhythmogenicity or increasing mortality risk4859 (Table 1).

Finally, although major advancements in the medical therapy of heart failure patients have substantially improved outcomes,60 technological advances in mechanical devices,61 including automatic implantable cardioverter defibrillators, cardiac resynchronization therapy, and ventricular assist devices, as well as advances in the surgical treatment of heart failure,62 have also been used to support the failing heart. Heart failure patients being treated with mechanical devices, as well as those following cardiac transplant, require unique care. As more mechanical and surgical innovations emerge, nonpharmacologic therapy will continue to evolve as a cornerstone of the management strategy in heart failure patients. Hospitalists will need to rely on care pathways, criteria for consultation, and good communication with cardiologists to optimize the care of these patients. Hospitalists should work with their cardiology colleagues in their local institution to develop appropriate criteria for cardiology consultation, and everyone should be educated on these criteria.

The subsequent discussions in this supplement expand on these topics. First, I review the presentation and early recognition, risk stratification, and treatment of patients with ADHF and the role of the hospitalist in this assessment and treatment process. Next, Dr. Khan and Dr. Heywood review the role of diuretics, vasodilators, and ultrafiltration in the management of patients with volume overload and high filling pressures and conclude with a discussion of potential future pharmacologic treatment options, such as tolvaptan and rolofylline, and nonpharmacologic modalities, such as wireless hemodynamic monitoring through implanted devices. Finally, Dr. Michota and I discuss bridging the gap between evidence and practice in the management of patients with ADHF. We review the evidence‐based guidelines that are currently available; discuss the appropriate location for treatment based on the patient's initial history and physical, radiographic, and laboratory findings; provide a practical algorithm for this treatment; and discuss means to transition care from the inpatient setting to the outpatient setting in a manner that enhances compliance with long‐term therapy and reduces recidivism. Given the anticipated growth in ADHF and the need for hospitalists to manage this disease together with cardiologists and others, we believe that the provided information will be helpful in the management of ADHF.

Acute decompensated heart failure (ADHF) is a common disorder that is frequently managed by hospitalists. This management is expected to expand over the next several years because of a continuing increase in the number of ADHF admissions coupled with a plateau or possible decline in the number of practicing cardiologists (Figure 1).114 In addition, 12% of fellowship training positions in cardiology were eliminated between 1995 and 2001, and the fact that the current number of training positions is inadequate to meet future demands is not recognized.15, 16 Given the severity of this disorder, the limited data from randomized, controlled clinical trials,17 and the limitations of current treatment, this management can be both challenging and rewarding. The goal of this special supplement of the Journal of Hospital Medicine is to assist hospitalists in this endeavor by summarizing the currently available data and treatment options and presenting a rational evidence‐based algorithm for the management of ADHF.

Figure 1

A multidisciplinary approach to heart failure has been shown to reduce cost, decrease length of stay, curtail readmissions, and improve compliance.1820 By leading and coordinating teams of physicians, pharmacists, nurses, nutritionists, physical therapists, and case managers and by developing and implementing indications for cardiology consultation, hospitalists can facilitate this multidisciplinary approach.21, 22 However, it is important to remember that hospitalists do not replace cardiologists, who remain a valuable and key component of this multidisciplinary team. Their input is vital in developing care pathways and criteria for consultation, and they, along with primary care physicians, will be the primary source of patient care following hospital discharge. Good communication between hospitalists and cardiologists is essential to optimize the care of patients with ADHF.

Maximizing the efficacy of ADHF care requires a thorough understanding of (1) the causes and potential treatments for the patient's acute decompensation, (2) the management of the patient's chronic heart failure, and (3) potential future therapies. Strategies to improve the continuum of heart failure care have been employed to help improve patient outcomes.23 For example, hospital‐based disease management programs have consistently been shown to optimize care and reduce rehospitalization rates in patients with heart failure.24 These programs involve a multidisciplinary, multifaceted approach to care in order to provide a continuum of care extending from hospitalization and into a patient's home environment.

Because of their practice location and experience, hospitalists are uniquely suited to influence acute inpatient care.25 They see patients in a variety of hospital settings and consequently tend to think of the entire system and not just an isolated component or patient.14 In addition, they have a vested interest in hospital quality improvement measures and are frequently involved in evaluating policies and procedures and developing and implementing clinical pathways, guidelines, and decision‐support tools.26 Data demonstrate that compliance is greater with evidence‐based guidelines and core performance measures when inpatient care is directed by a hospitalist.2730 Improved compliance with selected quality measures in patients with acute myocardial infarction and congestive heart failure has been observed when hospitals implement standardized admission and discharge orders.31, 32

Numerous transitions, such as outpatient to inpatient, intensive care unit to ward, and ward to home, occur during hospitalization, and these transitions are frequently associated with changes in the patient's medication regimen. During an acute illness, chronic medications may be held or discontinued, long‐acting medications may be changed to short‐acting ones to better titrate dose and achieve tighter control, and closed formularies may necessitate substituting 1 medication for another.33 A breakdown in communication during hospitalization‐associated transitions commonly affects medication regimens and can adversely impact patient care.3436 In a prospective evaluation, 53.6% [95% confidence interval (CI): 45.7%61.6%] of patients admitted to the hospital had at least 1 unintended discrepancy between their admission medication orders and their chronic outpatient regimen; 38.6% of these discrepancies were considered a potential threat to the patient.34 Likewise, 49% of patients being discharged from the hospital in another evaluation had an unexplained discrepancy between their preadmission and discharge medications.36 As a result, the Joint Commission on Accreditation of Healthcare Organizations now requires accredited facilities to perform medication reconciliation whenever a patient changes service, setting, provider, or level of care and new medication orders are written.37 This reconciliation is especially important in patients with heart failure, for whom polypharmacy is common and noncompliance with appropriate treatment regimens substantially increases readmission rates.3842

During these transition periods, hospitalists can play an important role in bridging the communication gap and providing this medication reconciliation.33 For example, actively involving hospitalists in all aspects of the reconciliation process at 1 institution resulted in a 4‐fold increase in consistency with preadmission medications.43 Similarly, because of the number of discharge summaries that they write, hospitalists are well suited to lead implementation of new policies and procedures to ensure compliance with recent changes in the Joint Commission on Accreditation of Healthcare Organizations requirements regarding these summaries.

In addition to playing an active role in acute patient management, hospitalists can substantially influence long‐term care and outcomes. Consequently, hospitalists must be well versed in the management of chronic heart failure. Patients are intensely focused on their illness during the hospitalization period, and this focus enhances opportunities for meaningful education and behavior modification. Numerous studies have demonstrated that adherence to long‐term therapy is improved when this therapy is initiated before or at hospital discharge.4446 In an evaluation of data from the Organized Program To Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure Registry (OPTIMIZE‐HF), the prescription of a ‐blocker at discharge was associated with a significant reduction in 60‐ to 90‐day mortality [hazard ratio (HR): 0.48; 95% CI: 0.30‐0.79], and prescription of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker at discharge was associated with a significant reduction in 60‐ to 90‐day mortality and/or rehospitalization (HR: 0.51; 95% CI: 0.34‐0.78).47 In the Cardiac Hospitalization Atherosclerosis Management Program (CHAMP), emphasizing initiation of chronic therapy prior to hospital discharge was associated with 3.0‐fold greater angiotensin‐converting enzyme inhibitor use and 3.2‐fold greater ‐blocker use at 1 year (both P < 0.01).46 Similarly, in patients surviving acute myocardial infarction, the strongest predictor of ‐blocker use at 30 days following discharge was receipt of a ‐blocker prescription at the time of discharge (HR: 15.8; 95% CI: 10.8‐23.3), and this beneficial effect was sustained for up to a year (Figure 2).44 Likewise, in patients with ADHF, the prevalence of ‐blocker therapy at 60 days was significantly increased when this therapy was initiated before discharge (91%) versus after discharge (73%; P < 0.001).45 This predischarge initiation of chronic therapy has been shown to reduce morbidity and mortality.

Figure 2

An awareness of new therapies for ADHF that are in late stages of clinical development can improve understanding of the complex pathophysiology of ADHF and enhance appropriate adaptation of these therapies once they become clinically available. These new therapies represent an attempt to improve on existing therapies, and consequently, they fall into the same 3 general categories as current therapies: diuretics, vasodilators, and inotropic agents.48, 49 Vasopressin receptor antagonists and adenosine receptor antagonists represent an attempt to stimulate aquaresis without inducing hyponatremia, hypokalemia, diminished glomerular filtration, or adverse neurohormonal activation;4854 endothelin receptor antagonists and newer natriuretic peptides represent an attempt to stimulate vasodilation and improve cardiac output without diminishing renal function;49, 55 and myosin activators and sodium‐potassium adenosine triphosphatase inhibitors represent an attempt to enhance contractility without inducing arrhythmogenicity or increasing mortality risk4859 (Table 1).

Finally, although major advancements in the medical therapy of heart failure patients have substantially improved outcomes,60 technological advances in mechanical devices,61 including automatic implantable cardioverter defibrillators, cardiac resynchronization therapy, and ventricular assist devices, as well as advances in the surgical treatment of heart failure,62 have also been used to support the failing heart. Heart failure patients being treated with mechanical devices, as well as those following cardiac transplant, require unique care. As more mechanical and surgical innovations emerge, nonpharmacologic therapy will continue to evolve as a cornerstone of the management strategy in heart failure patients. Hospitalists will need to rely on care pathways, criteria for consultation, and good communication with cardiologists to optimize the care of these patients. Hospitalists should work with their cardiology colleagues in their local institution to develop appropriate criteria for cardiology consultation, and everyone should be educated on these criteria.

The subsequent discussions in this supplement expand on these topics. First, I review the presentation and early recognition, risk stratification, and treatment of patients with ADHF and the role of the hospitalist in this assessment and treatment process. Next, Dr. Khan and Dr. Heywood review the role of diuretics, vasodilators, and ultrafiltration in the management of patients with volume overload and high filling pressures and conclude with a discussion of potential future pharmacologic treatment options, such as tolvaptan and rolofylline, and nonpharmacologic modalities, such as wireless hemodynamic monitoring through implanted devices. Finally, Dr. Michota and I discuss bridging the gap between evidence and practice in the management of patients with ADHF. We review the evidence‐based guidelines that are currently available; discuss the appropriate location for treatment based on the patient's initial history and physical, radiographic, and laboratory findings; provide a practical algorithm for this treatment; and discuss means to transition care from the inpatient setting to the outpatient setting in a manner that enhances compliance with long‐term therapy and reduces recidivism. Given the anticipated growth in ADHF and the need for hospitalists to manage this disease together with cardiologists and others, we believe that the provided information will be helpful in the management of ADHF.

Optimizing quality of care in patients with acute decompensated heart failure (ADHF) is crucial, given both the frequency and cost of hospitalization for this disorder. Several quality improvement strategies have been identified, including provider education; provider reminder systems and decision support; audit and feedback; patient education; organizational change; and financial incentives, regulation, and policy.1

To assist hospitalists in implementing these strategies, this article briefly reviews evidence‐based guidelines for the treatment of ADHF, presents a practical algorithm for patient assessment and treatment derived from these guidelines and personal experience, and discusses systems to enhance the ultimate transition of patient care from the inpatient to outpatient setting.

EVIDENCE‐BASED GUIDELINES

Evidence‐based guidelines are created in an attempt to promote optimal management of a condition or disorder based on expert analysis of all available relevant scientific data. Current guidelines for the assessment and treatment of ADHF have been developed by a national group purchasing organization,2 the European Society of Cardiology,3 the Heart Failure Society of America,4 and the American College of Emergency Physicians.5 Relevant components of these guidelines will be discussed in the patient assessment and treatment section below.

Publication of guidelines, in and of itself, however, is inadequate to ensure their acceptance and use.1 Data from the American Heart Association (AHA)/American Stroke Association (ASA) Get With The GuidelinesHeart Failure (GWTG‐HF) program continue to demonstrate a substantial gap between guideline recommendations and current care of patients with ADHF.6, 7 One way to promote systemwide adherence with published guidelines is to directly involve healthcare professionals in the implementation process. Consequently, development of local, hospital‐based procedures derived from national or international guidelines may be more effective than the simple dissemination of the guidelines themselves.1 Hospitalists have a unique insight into both patient care and the hospital setting and are frequently involved in evaluating hospital policies and procedures and implementing clinical pathways and guidelines.8 In addition, hospitalist care has been associated with greater compliance with disease‐specific guidelines compared to nonhospitalist care.9 As a result, hospitalists are uniquely suited to play a key role in the development of these procedures.

PATIENT ASSESSMENT AND TREATMENT

The differential diagnosis of any individual presenting to the emergency department (ED) with signs of systemic or pulmonary edema should include ADHF (Figure 1).25 These individuals require a rapid initial assessment to (1) establish the diagnosis, (2) determine the best location for subsequent treatment, and (3) institute the most appropriate initial therapy.

Figure 1

Treatment Algorithm

Treatment of ADHF should proceed along a logical care pathway governed by both clinical status and response to prior therapies (Figure 1). One must first consider whether there is evidence of respiratory failure or impending respiratory failure.20 If so, patients should receive immediate ventilatory support via continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or endotracheal intubation, depending on the degree of respiratory impairment.3, 5 In prospective controlled evaluations, patients with acute respiratory failure secondary to pulmonary edema who were randomized to treatment with CPAP demonstrated significant improvement in cardiopulmonary indices21, 22 and significant reductions in need for endotracheal intubation21 and short‐term mortality22 when compared with similar patients who received standard therapy without CPAP.

Once potential respiratory issues have been addressed, the next items for consideration are circulation and perfusion. Patients with low cardiac output and hypotension (cardiogenic shock) are at risk for developing critical end‐organ dysfunction. In these patients, insertion of a pulmonary artery catheter may aid in assessment of hemodynamic status and response to therapy.4 Patients with low cardiac output and low filling pressures should receive IV fluid loading.3 In contrast, for patients with low cardiac output and high filling pressures, inotropic agents should be considered.3, 4 Also, these patients may require IV vasodilators and/or IV diuretics to treat pulmonary edema once blood pressure (BP) and cardiac output have been stabilized.2, 3, 20

For patients with ADHF who present with symptoms of congestion, but not respiratory failure or cardiogenic shock, the initial therapeutic decision is governed by their BP. Approximately 50% of patients with ADHF will have an SBP > 140 mm Hg.12, 23 These patients tend to be older and to have diastolic rather than systolic dysfunction.12, 20, 23 Symptoms typically have been present for only a short period of time (2448 hours) and are more often due to maldistribution of fluid producing pulmonary edema than total body fluid overload. Consequently, initial treatment should focus on aggressive BP control to relieve this edema. Sublingual or topical nitrates are recommended as a first step, and initial diuretic use should be minimal to avoid intravascular volume depletion leading to renal dysfunction.20 In contrast, patients presenting with SBP between 90 mm Hg and 140 mm Hg are more likely to have some degree of systolic dysfunction, leading to a gradual worsening of their heart failure symptoms and total body fluid overload over a period of weeks.20 These patients require aggressive diuresis. Although the efficacy of IV loop diuretics has not been established in randomized, controlled clinical trials, observational experience demonstrates that they can effectively reduce filling pressures, relieve volume overload, and decrease symptoms of congestion.4 They are currently the mainstay of therapy for ADHF secondary to fluid retention, and their use is recommended in all 4 guidelines.25

This initial therapeutic choice, however, is only the starting point, and it is important not to stop at this stage. No single definitive therapy for ADHF exists, and not all patients will respond to initial treatment. Optimal management requires early recognition and addressing of both an inadequate response to therapy and any adverse affects induced by this therapy. Frequent reevaluations are an essential component of treating patients with ADHF. For example, the timeline in one of the guidelines calls for assessing the patient's response at 2 and 4 hours after initiation of IV therapy and adjusting treatment as indicated based on these assessments (Figure 2).2

Figure 2

If the patient has an adequate response to initial therapy, defined as SBP <140 mm Hg, stable renal function, and urine output >500 mL over 2 hours (>250 mL if serum creatinine >2.5 mg/dL), this therapy can continue unchanged, and focus shifts to long‐term management issues.2, 4, 14 However, if the response is inadequate, it is important to identify and treat the cause of this inadequate response.

Inadequate urine output secondary to diuretic resistance is common in patients with ADHF, especially in those on long‐term diuretic therapy.3 Despite a 90% prevalence of IV diuretic use in ADHERE, 70% of patients either gained weight or lost fewer than 5 pounds during hospitalization, and 42% were discharged with unresolved symptoms.24 Clearly, diuretic therapy did not produce the desired effect in many of these patients. This inadequate response to loop diuretics is a direct result of their pharmacologic properties, especially as they relate to patients with heart failure. The physiologic effects of loop diuretics are directly related to their concentration in the lumen of the nephron. This concentration depends on both the patient's renal function and the dose and half‐life of the administered diuretic.25 Comorbid renal dysfunction is common in patients with ADHF.26 In addition, even in the absence of this dysfunction, the short half‐life of loop diuretics limits the amount of time that their luminal concentration is in the effective range, and rebound sodium retention can occur whenever the diuretic concentration is below this range.25 Furthermore, the dose‐response curve of loop diuretics is S‐shaped. As a result, a threshold concentration exists beyond which no further augmentation in urine output occurs; ie, there is a maximum physiologic response that is reduced in patients with heart failure.25 Guideline recommendations for patients with diuretic resistance attempt to address these physiologic and pharmacologic limitations. These recommendations include fluid restriction to decrease the overall volume of diuresis necessary, increasing diuretic dose or instituting continuous infusion loop diuretic therapy to increase the amount of time during which the luminal concentration is within the effective range, sequential diuretic blockade to take advantage of the different mechanisms of action of the various diuretic classes to affect different components of the nephron, bypassing the kidney through the use of ultrafiltration, and when these are inadequate, adding a vasodilator in an attempt to augment cardiac output and renal perfusion.3, 4, 24, 25, 2729

Addition of an IV vasodilator is the primary means of addressing an inadequate response typified by hypertension, worsening renal function, and/or persistent symptoms, rather than diuretic resistance. Approximately 25% of patients with ADHF receive IV vasoactive therapy, including nitroglycerin, nesiritide, milrinone, or dobutamine, although predominantly vasodilators, at some point during their hospitalization.11, 12 These agents improve hemodynamics and reduce symptoms of ADHF.5, 3032 Their use, in combination with low‐dose diuretics, has been shown to be more efficacious than high‐dose diuretics alone.3, 27 Adding a vasodilator may reduce adverse, diuretic‐induced, neurohormonal activation. In an animal model, combining nesiritide with IV furosemide significantly attenuated the rise in plasma aldosterone produced by IV furosemide alone,33 and this finding has been subsequently confirmed in patients with heart failure.34 Finally, vasodilators have proven to be a safer alternative than inotropes in patients with ADHF. In an analysis of data from ADHERE, covariate‐adjusted and propensity‐adjusted mortality risk was >50% lower for patients receiving nitroglycerin or nesiritide compared with those receiving dobutamine,11 and in an analysis of data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, which evaluated patients with advanced heart failure, the risk‐adjusted mortality hazard ratio (HR) was significantly increased for inotropes (HR: 2.14; 95% confidence interval [CI]: 1.104.15) but not for vasodilators in the absence of inotropes (HR: 1.39; 95% CI: 0.643.00).35

TRANSITION OF CARE

Lastly, optimal management of ADHF requires successful transition of care from an inpatient to an outpatient setting. Recidivism is both common and costly. Approximately 2% of patients with ADHF are readmitted within 2 days, 20% within 1 month, and 50% within 6 months of hospital discharge.40 Frequently, these readmissions are caused by nonadherence to the therapeutic regimen following discharge.41 In an evaluation of patients hospitalized for ADHF at a large urban medical center, noncompliance with prescribed diet and/or drugs was the most common precipitating factor for admission (64% of patients), followed by uncontrolled hypertension (44%), cardiac arrhythmia (29%), environmental factors (19%), and inadequate therapy (17%).42 Similarly, in a prospective evaluation of elderly patients hospitalized for ADHF, 53% of readmissions occurring within 90 days of discharge were deemed to be preventable, with the most common contributing factors being noncompliance with medications and/or diet (33%), inadequate discharge planning (15%), inadequate follow‐up (20%), insufficient support system (21%), and failure to seek medical attention promptly when symptoms recurred (20%).43 Consequently, patient education and arrangement for appropriate follow‐up are crucial components of successfully transitioning care to an outpatient setting.

Effective patient education is time‐consuming. Patients must be taught when, how, and why to take their medication. They need to understand their dietary guidelines and the reasons for these guidelines. They need to know how to use daily weigh‐ins as a means of monitoring their fluid status and what to do in response to a change in weight or symptoms. Finally, they need to be cognizant of what constitutes appropriate exercise and the need for this exercise.4447 To enhance understanding and retention, this information should be presented to the patient over the course of the hospitalization. Comprehension should be tested continually and education repeated until appropriate understanding is ensured. Patient education provided in a rushed or perfunctory manner at the moment of discharge is unlikely to be retained or effective.38, 39

Ideally, the patient should be referred to a comprehensive heart failure disease management program for postdischarge care. Numerous evaluations have established the effectiveness of these programs in enhancing use of appropriate medications, improving functional status, reducing readmissions and mortality, and decreasing costs.4454 For example, in separate evaluations, the prevalences of appropriate vasodilator use (93% vs. 61%; P < .001),51 ‐blocker use (71% vs. 40%; P < .001),50 and ACE inhibitor use (84% vs. 59%; P < .001)52 were significantly greater for disease management program participants compared with nonparticipants. In addition, participation in a disease management program was associated with a 52% reduction in the risk of hospitalization for cardiovascular causes (P < .001) and a 72% reduction in ED visits (P < .01) in 1 evaluation,45 a 36% reduction (95% CI: 16.7%50.9%) in the risk of heart failure admission or death in another,53 and a 67% reduction (95% CI: 41%82%) in the adjusted risk of death in yet another evaluation.52 Unfortunately, recent data indicate that these programs must be ongoing to sustain these benefits. In a prospective evaluation, patients with heart failure were randomized to either standard care or a multidisciplinary disease management program for 6 months followed by standard care.55, 56 Significantly fewer patients in the disease management group required readmission to the hospital (HR: 0.55; 95% CI: 0.350.88) during the 6‐month period in which they actively participated in the disease management program.56 However, by the end of follow‐up (mean 2.8 years), there was no significant difference between treatment groups in all‐cause mortality (HR: 1.09; 95% CI: 0.691.72) or the composite endpoint of death, ED visit, or hospitalization (HR: 1.01; 95% CI: 0.751.37).55

CONCLUSION

A gap between evidence‐based guidelines and current management of patients with ADHF exists. Multiple strategies to bridge this gap in patient management can be employed. Patients with ADHF require rapid assessment to determine appropriate treatment location and initial therapy. Clinical status should guide treatment selection. Once effective acute therapy has been established, strategies to improve long‐term outcomes should be implemented. These strategies include ensuring that care complies with established core performance measures, providing patient education in a manner suited to ensure comprehension and retention, and arranging for appropriate outpatient follow‐up, ideally in a comprehensive heart failure disease management program. Increasing the awareness of the gap between evidence‐based guidelines and current management, as well as strategies to bridge this gap, is crucial to improving the outcomes of patients with ADHF.

Optimizing quality of care in patients with acute decompensated heart failure (ADHF) is crucial, given both the frequency and cost of hospitalization for this disorder. Several quality improvement strategies have been identified, including provider education; provider reminder systems and decision support; audit and feedback; patient education; organizational change; and financial incentives, regulation, and policy.1

To assist hospitalists in implementing these strategies, this article briefly reviews evidence‐based guidelines for the treatment of ADHF, presents a practical algorithm for patient assessment and treatment derived from these guidelines and personal experience, and discusses systems to enhance the ultimate transition of patient care from the inpatient to outpatient setting.

EVIDENCE‐BASED GUIDELINES

Evidence‐based guidelines are created in an attempt to promote optimal management of a condition or disorder based on expert analysis of all available relevant scientific data. Current guidelines for the assessment and treatment of ADHF have been developed by a national group purchasing organization,2 the European Society of Cardiology,3 the Heart Failure Society of America,4 and the American College of Emergency Physicians.5 Relevant components of these guidelines will be discussed in the patient assessment and treatment section below.

Publication of guidelines, in and of itself, however, is inadequate to ensure their acceptance and use.1 Data from the American Heart Association (AHA)/American Stroke Association (ASA) Get With The GuidelinesHeart Failure (GWTG‐HF) program continue to demonstrate a substantial gap between guideline recommendations and current care of patients with ADHF.6, 7 One way to promote systemwide adherence with published guidelines is to directly involve healthcare professionals in the implementation process. Consequently, development of local, hospital‐based procedures derived from national or international guidelines may be more effective than the simple dissemination of the guidelines themselves.1 Hospitalists have a unique insight into both patient care and the hospital setting and are frequently involved in evaluating hospital policies and procedures and implementing clinical pathways and guidelines.8 In addition, hospitalist care has been associated with greater compliance with disease‐specific guidelines compared to nonhospitalist care.9 As a result, hospitalists are uniquely suited to play a key role in the development of these procedures.

PATIENT ASSESSMENT AND TREATMENT

The differential diagnosis of any individual presenting to the emergency department (ED) with signs of systemic or pulmonary edema should include ADHF (Figure 1).25 These individuals require a rapid initial assessment to (1) establish the diagnosis, (2) determine the best location for subsequent treatment, and (3) institute the most appropriate initial therapy.

Figure 1

Treatment Algorithm

Treatment of ADHF should proceed along a logical care pathway governed by both clinical status and response to prior therapies (Figure 1). One must first consider whether there is evidence of respiratory failure or impending respiratory failure.20 If so, patients should receive immediate ventilatory support via continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or endotracheal intubation, depending on the degree of respiratory impairment.3, 5 In prospective controlled evaluations, patients with acute respiratory failure secondary to pulmonary edema who were randomized to treatment with CPAP demonstrated significant improvement in cardiopulmonary indices21, 22 and significant reductions in need for endotracheal intubation21 and short‐term mortality22 when compared with similar patients who received standard therapy without CPAP.

Once potential respiratory issues have been addressed, the next items for consideration are circulation and perfusion. Patients with low cardiac output and hypotension (cardiogenic shock) are at risk for developing critical end‐organ dysfunction. In these patients, insertion of a pulmonary artery catheter may aid in assessment of hemodynamic status and response to therapy.4 Patients with low cardiac output and low filling pressures should receive IV fluid loading.3 In contrast, for patients with low cardiac output and high filling pressures, inotropic agents should be considered.3, 4 Also, these patients may require IV vasodilators and/or IV diuretics to treat pulmonary edema once blood pressure (BP) and cardiac output have been stabilized.2, 3, 20

For patients with ADHF who present with symptoms of congestion, but not respiratory failure or cardiogenic shock, the initial therapeutic decision is governed by their BP. Approximately 50% of patients with ADHF will have an SBP > 140 mm Hg.12, 23 These patients tend to be older and to have diastolic rather than systolic dysfunction.12, 20, 23 Symptoms typically have been present for only a short period of time (2448 hours) and are more often due to maldistribution of fluid producing pulmonary edema than total body fluid overload. Consequently, initial treatment should focus on aggressive BP control to relieve this edema. Sublingual or topical nitrates are recommended as a first step, and initial diuretic use should be minimal to avoid intravascular volume depletion leading to renal dysfunction.20 In contrast, patients presenting with SBP between 90 mm Hg and 140 mm Hg are more likely to have some degree of systolic dysfunction, leading to a gradual worsening of their heart failure symptoms and total body fluid overload over a period of weeks.20 These patients require aggressive diuresis. Although the efficacy of IV loop diuretics has not been established in randomized, controlled clinical trials, observational experience demonstrates that they can effectively reduce filling pressures, relieve volume overload, and decrease symptoms of congestion.4 They are currently the mainstay of therapy for ADHF secondary to fluid retention, and their use is recommended in all 4 guidelines.25

This initial therapeutic choice, however, is only the starting point, and it is important not to stop at this stage. No single definitive therapy for ADHF exists, and not all patients will respond to initial treatment. Optimal management requires early recognition and addressing of both an inadequate response to therapy and any adverse affects induced by this therapy. Frequent reevaluations are an essential component of treating patients with ADHF. For example, the timeline in one of the guidelines calls for assessing the patient's response at 2 and 4 hours after initiation of IV therapy and adjusting treatment as indicated based on these assessments (Figure 2).2

Figure 2

If the patient has an adequate response to initial therapy, defined as SBP <140 mm Hg, stable renal function, and urine output >500 mL over 2 hours (>250 mL if serum creatinine >2.5 mg/dL), this therapy can continue unchanged, and focus shifts to long‐term management issues.2, 4, 14 However, if the response is inadequate, it is important to identify and treat the cause of this inadequate response.

Inadequate urine output secondary to diuretic resistance is common in patients with ADHF, especially in those on long‐term diuretic therapy.3 Despite a 90% prevalence of IV diuretic use in ADHERE, 70% of patients either gained weight or lost fewer than 5 pounds during hospitalization, and 42% were discharged with unresolved symptoms.24 Clearly, diuretic therapy did not produce the desired effect in many of these patients. This inadequate response to loop diuretics is a direct result of their pharmacologic properties, especially as they relate to patients with heart failure. The physiologic effects of loop diuretics are directly related to their concentration in the lumen of the nephron. This concentration depends on both the patient's renal function and the dose and half‐life of the administered diuretic.25 Comorbid renal dysfunction is common in patients with ADHF.26 In addition, even in the absence of this dysfunction, the short half‐life of loop diuretics limits the amount of time that their luminal concentration is in the effective range, and rebound sodium retention can occur whenever the diuretic concentration is below this range.25 Furthermore, the dose‐response curve of loop diuretics is S‐shaped. As a result, a threshold concentration exists beyond which no further augmentation in urine output occurs; ie, there is a maximum physiologic response that is reduced in patients with heart failure.25 Guideline recommendations for patients with diuretic resistance attempt to address these physiologic and pharmacologic limitations. These recommendations include fluid restriction to decrease the overall volume of diuresis necessary, increasing diuretic dose or instituting continuous infusion loop diuretic therapy to increase the amount of time during which the luminal concentration is within the effective range, sequential diuretic blockade to take advantage of the different mechanisms of action of the various diuretic classes to affect different components of the nephron, bypassing the kidney through the use of ultrafiltration, and when these are inadequate, adding a vasodilator in an attempt to augment cardiac output and renal perfusion.3, 4, 24, 25, 2729

Addition of an IV vasodilator is the primary means of addressing an inadequate response typified by hypertension, worsening renal function, and/or persistent symptoms, rather than diuretic resistance. Approximately 25% of patients with ADHF receive IV vasoactive therapy, including nitroglycerin, nesiritide, milrinone, or dobutamine, although predominantly vasodilators, at some point during their hospitalization.11, 12 These agents improve hemodynamics and reduce symptoms of ADHF.5, 3032 Their use, in combination with low‐dose diuretics, has been shown to be more efficacious than high‐dose diuretics alone.3, 27 Adding a vasodilator may reduce adverse, diuretic‐induced, neurohormonal activation. In an animal model, combining nesiritide with IV furosemide significantly attenuated the rise in plasma aldosterone produced by IV furosemide alone,33 and this finding has been subsequently confirmed in patients with heart failure.34 Finally, vasodilators have proven to be a safer alternative than inotropes in patients with ADHF. In an analysis of data from ADHERE, covariate‐adjusted and propensity‐adjusted mortality risk was >50% lower for patients receiving nitroglycerin or nesiritide compared with those receiving dobutamine,11 and in an analysis of data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, which evaluated patients with advanced heart failure, the risk‐adjusted mortality hazard ratio (HR) was significantly increased for inotropes (HR: 2.14; 95% confidence interval [CI]: 1.104.15) but not for vasodilators in the absence of inotropes (HR: 1.39; 95% CI: 0.643.00).35

TRANSITION OF CARE

Lastly, optimal management of ADHF requires successful transition of care from an inpatient to an outpatient setting. Recidivism is both common and costly. Approximately 2% of patients with ADHF are readmitted within 2 days, 20% within 1 month, and 50% within 6 months of hospital discharge.40 Frequently, these readmissions are caused by nonadherence to the therapeutic regimen following discharge.41 In an evaluation of patients hospitalized for ADHF at a large urban medical center, noncompliance with prescribed diet and/or drugs was the most common precipitating factor for admission (64% of patients), followed by uncontrolled hypertension (44%), cardiac arrhythmia (29%), environmental factors (19%), and inadequate therapy (17%).42 Similarly, in a prospective evaluation of elderly patients hospitalized for ADHF, 53% of readmissions occurring within 90 days of discharge were deemed to be preventable, with the most common contributing factors being noncompliance with medications and/or diet (33%), inadequate discharge planning (15%), inadequate follow‐up (20%), insufficient support system (21%), and failure to seek medical attention promptly when symptoms recurred (20%).43 Consequently, patient education and arrangement for appropriate follow‐up are crucial components of successfully transitioning care to an outpatient setting.

Effective patient education is time‐consuming. Patients must be taught when, how, and why to take their medication. They need to understand their dietary guidelines and the reasons for these guidelines. They need to know how to use daily weigh‐ins as a means of monitoring their fluid status and what to do in response to a change in weight or symptoms. Finally, they need to be cognizant of what constitutes appropriate exercise and the need for this exercise.4447 To enhance understanding and retention, this information should be presented to the patient over the course of the hospitalization. Comprehension should be tested continually and education repeated until appropriate understanding is ensured. Patient education provided in a rushed or perfunctory manner at the moment of discharge is unlikely to be retained or effective.38, 39

Ideally, the patient should be referred to a comprehensive heart failure disease management program for postdischarge care. Numerous evaluations have established the effectiveness of these programs in enhancing use of appropriate medications, improving functional status, reducing readmissions and mortality, and decreasing costs.4454 For example, in separate evaluations, the prevalences of appropriate vasodilator use (93% vs. 61%; P < .001),51 ‐blocker use (71% vs. 40%; P < .001),50 and ACE inhibitor use (84% vs. 59%; P < .001)52 were significantly greater for disease management program participants compared with nonparticipants. In addition, participation in a disease management program was associated with a 52% reduction in the risk of hospitalization for cardiovascular causes (P < .001) and a 72% reduction in ED visits (P < .01) in 1 evaluation,45 a 36% reduction (95% CI: 16.7%50.9%) in the risk of heart failure admission or death in another,53 and a 67% reduction (95% CI: 41%82%) in the adjusted risk of death in yet another evaluation.52 Unfortunately, recent data indicate that these programs must be ongoing to sustain these benefits. In a prospective evaluation, patients with heart failure were randomized to either standard care or a multidisciplinary disease management program for 6 months followed by standard care.55, 56 Significantly fewer patients in the disease management group required readmission to the hospital (HR: 0.55; 95% CI: 0.350.88) during the 6‐month period in which they actively participated in the disease management program.56 However, by the end of follow‐up (mean 2.8 years), there was no significant difference between treatment groups in all‐cause mortality (HR: 1.09; 95% CI: 0.691.72) or the composite endpoint of death, ED visit, or hospitalization (HR: 1.01; 95% CI: 0.751.37).55

CONCLUSION

A gap between evidence‐based guidelines and current management of patients with ADHF exists. Multiple strategies to bridge this gap in patient management can be employed. Patients with ADHF require rapid assessment to determine appropriate treatment location and initial therapy. Clinical status should guide treatment selection. Once effective acute therapy has been established, strategies to improve long‐term outcomes should be implemented. These strategies include ensuring that care complies with established core performance measures, providing patient education in a manner suited to ensure comprehension and retention, and arranging for appropriate outpatient follow‐up, ideally in a comprehensive heart failure disease management program. Increasing the awareness of the gap between evidence‐based guidelines and current management, as well as strategies to bridge this gap, is crucial to improving the outcomes of patients with ADHF.

Optimizing quality of care in patients with acute decompensated heart failure (ADHF) is crucial, given both the frequency and cost of hospitalization for this disorder. Several quality improvement strategies have been identified, including provider education; provider reminder systems and decision support; audit and feedback; patient education; organizational change; and financial incentives, regulation, and policy.1

To assist hospitalists in implementing these strategies, this article briefly reviews evidence‐based guidelines for the treatment of ADHF, presents a practical algorithm for patient assessment and treatment derived from these guidelines and personal experience, and discusses systems to enhance the ultimate transition of patient care from the inpatient to outpatient setting.

EVIDENCE‐BASED GUIDELINES

Evidence‐based guidelines are created in an attempt to promote optimal management of a condition or disorder based on expert analysis of all available relevant scientific data. Current guidelines for the assessment and treatment of ADHF have been developed by a national group purchasing organization,2 the European Society of Cardiology,3 the Heart Failure Society of America,4 and the American College of Emergency Physicians.5 Relevant components of these guidelines will be discussed in the patient assessment and treatment section below.

Publication of guidelines, in and of itself, however, is inadequate to ensure their acceptance and use.1 Data from the American Heart Association (AHA)/American Stroke Association (ASA) Get With The GuidelinesHeart Failure (GWTG‐HF) program continue to demonstrate a substantial gap between guideline recommendations and current care of patients with ADHF.6, 7 One way to promote systemwide adherence with published guidelines is to directly involve healthcare professionals in the implementation process. Consequently, development of local, hospital‐based procedures derived from national or international guidelines may be more effective than the simple dissemination of the guidelines themselves.1 Hospitalists have a unique insight into both patient care and the hospital setting and are frequently involved in evaluating hospital policies and procedures and implementing clinical pathways and guidelines.8 In addition, hospitalist care has been associated with greater compliance with disease‐specific guidelines compared to nonhospitalist care.9 As a result, hospitalists are uniquely suited to play a key role in the development of these procedures.

PATIENT ASSESSMENT AND TREATMENT

The differential diagnosis of any individual presenting to the emergency department (ED) with signs of systemic or pulmonary edema should include ADHF (Figure 1).25 These individuals require a rapid initial assessment to (1) establish the diagnosis, (2) determine the best location for subsequent treatment, and (3) institute the most appropriate initial therapy.

Figure 1

Treatment Algorithm

Treatment of ADHF should proceed along a logical care pathway governed by both clinical status and response to prior therapies (Figure 1). One must first consider whether there is evidence of respiratory failure or impending respiratory failure.20 If so, patients should receive immediate ventilatory support via continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or endotracheal intubation, depending on the degree of respiratory impairment.3, 5 In prospective controlled evaluations, patients with acute respiratory failure secondary to pulmonary edema who were randomized to treatment with CPAP demonstrated significant improvement in cardiopulmonary indices21, 22 and significant reductions in need for endotracheal intubation21 and short‐term mortality22 when compared with similar patients who received standard therapy without CPAP.

Once potential respiratory issues have been addressed, the next items for consideration are circulation and perfusion. Patients with low cardiac output and hypotension (cardiogenic shock) are at risk for developing critical end‐organ dysfunction. In these patients, insertion of a pulmonary artery catheter may aid in assessment of hemodynamic status and response to therapy.4 Patients with low cardiac output and low filling pressures should receive IV fluid loading.3 In contrast, for patients with low cardiac output and high filling pressures, inotropic agents should be considered.3, 4 Also, these patients may require IV vasodilators and/or IV diuretics to treat pulmonary edema once blood pressure (BP) and cardiac output have been stabilized.2, 3, 20

For patients with ADHF who present with symptoms of congestion, but not respiratory failure or cardiogenic shock, the initial therapeutic decision is governed by their BP. Approximately 50% of patients with ADHF will have an SBP > 140 mm Hg.12, 23 These patients tend to be older and to have diastolic rather than systolic dysfunction.12, 20, 23 Symptoms typically have been present for only a short period of time (2448 hours) and are more often due to maldistribution of fluid producing pulmonary edema than total body fluid overload. Consequently, initial treatment should focus on aggressive BP control to relieve this edema. Sublingual or topical nitrates are recommended as a first step, and initial diuretic use should be minimal to avoid intravascular volume depletion leading to renal dysfunction.20 In contrast, patients presenting with SBP between 90 mm Hg and 140 mm Hg are more likely to have some degree of systolic dysfunction, leading to a gradual worsening of their heart failure symptoms and total body fluid overload over a period of weeks.20 These patients require aggressive diuresis. Although the efficacy of IV loop diuretics has not been established in randomized, controlled clinical trials, observational experience demonstrates that they can effectively reduce filling pressures, relieve volume overload, and decrease symptoms of congestion.4 They are currently the mainstay of therapy for ADHF secondary to fluid retention, and their use is recommended in all 4 guidelines.25

This initial therapeutic choice, however, is only the starting point, and it is important not to stop at this stage. No single definitive therapy for ADHF exists, and not all patients will respond to initial treatment. Optimal management requires early recognition and addressing of both an inadequate response to therapy and any adverse affects induced by this therapy. Frequent reevaluations are an essential component of treating patients with ADHF. For example, the timeline in one of the guidelines calls for assessing the patient's response at 2 and 4 hours after initiation of IV therapy and adjusting treatment as indicated based on these assessments (Figure 2).2

Figure 2

If the patient has an adequate response to initial therapy, defined as SBP <140 mm Hg, stable renal function, and urine output >500 mL over 2 hours (>250 mL if serum creatinine >2.5 mg/dL), this therapy can continue unchanged, and focus shifts to long‐term management issues.2, 4, 14 However, if the response is inadequate, it is important to identify and treat the cause of this inadequate response.

Inadequate urine output secondary to diuretic resistance is common in patients with ADHF, especially in those on long‐term diuretic therapy.3 Despite a 90% prevalence of IV diuretic use in ADHERE, 70% of patients either gained weight or lost fewer than 5 pounds during hospitalization, and 42% were discharged with unresolved symptoms.24 Clearly, diuretic therapy did not produce the desired effect in many of these patients. This inadequate response to loop diuretics is a direct result of their pharmacologic properties, especially as they relate to patients with heart failure. The physiologic effects of loop diuretics are directly related to their concentration in the lumen of the nephron. This concentration depends on both the patient's renal function and the dose and half‐life of the administered diuretic.25 Comorbid renal dysfunction is common in patients with ADHF.26 In addition, even in the absence of this dysfunction, the short half‐life of loop diuretics limits the amount of time that their luminal concentration is in the effective range, and rebound sodium retention can occur whenever the diuretic concentration is below this range.25 Furthermore, the dose‐response curve of loop diuretics is S‐shaped. As a result, a threshold concentration exists beyond which no further augmentation in urine output occurs; ie, there is a maximum physiologic response that is reduced in patients with heart failure.25 Guideline recommendations for patients with diuretic resistance attempt to address these physiologic and pharmacologic limitations. These recommendations include fluid restriction to decrease the overall volume of diuresis necessary, increasing diuretic dose or instituting continuous infusion loop diuretic therapy to increase the amount of time during which the luminal concentration is within the effective range, sequential diuretic blockade to take advantage of the different mechanisms of action of the various diuretic classes to affect different components of the nephron, bypassing the kidney through the use of ultrafiltration, and when these are inadequate, adding a vasodilator in an attempt to augment cardiac output and renal perfusion.3, 4, 24, 25, 2729

Addition of an IV vasodilator is the primary means of addressing an inadequate response typified by hypertension, worsening renal function, and/or persistent symptoms, rather than diuretic resistance. Approximately 25% of patients with ADHF receive IV vasoactive therapy, including nitroglycerin, nesiritide, milrinone, or dobutamine, although predominantly vasodilators, at some point during their hospitalization.11, 12 These agents improve hemodynamics and reduce symptoms of ADHF.5, 3032 Their use, in combination with low‐dose diuretics, has been shown to be more efficacious than high‐dose diuretics alone.3, 27 Adding a vasodilator may reduce adverse, diuretic‐induced, neurohormonal activation. In an animal model, combining nesiritide with IV furosemide significantly attenuated the rise in plasma aldosterone produced by IV furosemide alone,33 and this finding has been subsequently confirmed in patients with heart failure.34 Finally, vasodilators have proven to be a safer alternative than inotropes in patients with ADHF. In an analysis of data from ADHERE, covariate‐adjusted and propensity‐adjusted mortality risk was >50% lower for patients receiving nitroglycerin or nesiritide compared with those receiving dobutamine,11 and in an analysis of data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, which evaluated patients with advanced heart failure, the risk‐adjusted mortality hazard ratio (HR) was significantly increased for inotropes (HR: 2.14; 95% confidence interval [CI]: 1.104.15) but not for vasodilators in the absence of inotropes (HR: 1.39; 95% CI: 0.643.00).35

TRANSITION OF CARE

Lastly, optimal management of ADHF requires successful transition of care from an inpatient to an outpatient setting. Recidivism is both common and costly. Approximately 2% of patients with ADHF are readmitted within 2 days, 20% within 1 month, and 50% within 6 months of hospital discharge.40 Frequently, these readmissions are caused by nonadherence to the therapeutic regimen following discharge.41 In an evaluation of patients hospitalized for ADHF at a large urban medical center, noncompliance with prescribed diet and/or drugs was the most common precipitating factor for admission (64% of patients), followed by uncontrolled hypertension (44%), cardiac arrhythmia (29%), environmental factors (19%), and inadequate therapy (17%).42 Similarly, in a prospective evaluation of elderly patients hospitalized for ADHF, 53% of readmissions occurring within 90 days of discharge were deemed to be preventable, with the most common contributing factors being noncompliance with medications and/or diet (33%), inadequate discharge planning (15%), inadequate follow‐up (20%), insufficient support system (21%), and failure to seek medical attention promptly when symptoms recurred (20%).43 Consequently, patient education and arrangement for appropriate follow‐up are crucial components of successfully transitioning care to an outpatient setting.

Effective patient education is time‐consuming. Patients must be taught when, how, and why to take their medication. They need to understand their dietary guidelines and the reasons for these guidelines. They need to know how to use daily weigh‐ins as a means of monitoring their fluid status and what to do in response to a change in weight or symptoms. Finally, they need to be cognizant of what constitutes appropriate exercise and the need for this exercise.4447 To enhance understanding and retention, this information should be presented to the patient over the course of the hospitalization. Comprehension should be tested continually and education repeated until appropriate understanding is ensured. Patient education provided in a rushed or perfunctory manner at the moment of discharge is unlikely to be retained or effective.38, 39

Ideally, the patient should be referred to a comprehensive heart failure disease management program for postdischarge care. Numerous evaluations have established the effectiveness of these programs in enhancing use of appropriate medications, improving functional status, reducing readmissions and mortality, and decreasing costs.4454 For example, in separate evaluations, the prevalences of appropriate vasodilator use (93% vs. 61%; P < .001),51 ‐blocker use (71% vs. 40%; P < .001),50 and ACE inhibitor use (84% vs. 59%; P < .001)52 were significantly greater for disease management program participants compared with nonparticipants. In addition, participation in a disease management program was associated with a 52% reduction in the risk of hospitalization for cardiovascular causes (P < .001) and a 72% reduction in ED visits (P < .01) in 1 evaluation,45 a 36% reduction (95% CI: 16.7%50.9%) in the risk of heart failure admission or death in another,53 and a 67% reduction (95% CI: 41%82%) in the adjusted risk of death in yet another evaluation.52 Unfortunately, recent data indicate that these programs must be ongoing to sustain these benefits. In a prospective evaluation, patients with heart failure were randomized to either standard care or a multidisciplinary disease management program for 6 months followed by standard care.55, 56 Significantly fewer patients in the disease management group required readmission to the hospital (HR: 0.55; 95% CI: 0.350.88) during the 6‐month period in which they actively participated in the disease management program.56 However, by the end of follow‐up (mean 2.8 years), there was no significant difference between treatment groups in all‐cause mortality (HR: 1.09; 95% CI: 0.691.72) or the composite endpoint of death, ED visit, or hospitalization (HR: 1.01; 95% CI: 0.751.37).55

CONCLUSION

A gap between evidence‐based guidelines and current management of patients with ADHF exists. Multiple strategies to bridge this gap in patient management can be employed. Patients with ADHF require rapid assessment to determine appropriate treatment location and initial therapy. Clinical status should guide treatment selection. Once effective acute therapy has been established, strategies to improve long‐term outcomes should be implemented. These strategies include ensuring that care complies with established core performance measures, providing patient education in a manner suited to ensure comprehension and retention, and arranging for appropriate outpatient follow‐up, ideally in a comprehensive heart failure disease management program. Increasing the awareness of the gap between evidence‐based guidelines and current management, as well as strategies to bridge this gap, is crucial to improving the outcomes of patients with ADHF.