The Editors Roundtable: Acute Decompensated Heart Failure

Vincent E. Friedewald, MDa,*, Mihai Gheorghiade, MDb, Clyde W. Yancy, MDc, James B. Young, MDd, and William C. Roberts, MDe
Acknowledgment This CME activity is supported by an educational grant from Scios, Inc., Fremont, California. Disclosure Dr. Friedewald has no relevant nancial relationships to disclose. Dr. Gheorghiade has received honoraria for speaking from Otsuka, Rockville, Maryland; Medtronic, Minneapolis, Minnesota; and GlaxoSmithKline, Research Triangle Park, North Carolina. Dr. Roberts has received honoraria for speaking from AstraZeneca, Wilmington, Delaware; Merck, North Wales, Pennsylvania; Schering Plough, Kenilworth, New Jersey; Pzer, New York, New York; and Novartis, East Hanover, New Jersey. Dr. Yancy has received honoraria for speaking from GlaxoSmithKline, Research Triangle Park, North Carolina; Novartis, East Hanover, New Jersey; consulting fees and grant/research support from AstraZeneca, Wilmington, Delaware; GlaxoSmithKline, Research Triangle Park, North Carolina; Scios, Fremont, California; Nitromed, Lexington, Massachusetts; and Medtronic, Minneapolis, Minnesota. Dr. Young has received grant/research support from Abbott, Abbott Park, Illinois; Amgen, Thousand Oaks, California; AstraZeneca, Wilmington, Delaware; GlaxoSmithKline, Research Triangle Park, North Carolina; Guidant, St Paul, Minnesota; Medtronic, Minneapolis, Minnesota; Vasogen, Mississauga, Ontario, Canada; and has been a Consultant for Abbott, Abbott Park, Illinois; Acorn Cardiovascular, St. Paul, Minnesota; Amgen, Thousand Oaks, California; AstraZeneca, Wilmington, Delaware; Artesian Therapeutics, Gaithersburg, Maryland; Boehringer Ingelheim, Ingelheim, Germany; GlaxoSmithKline, Research Triangle Park, North Carolina; Guidant, St. Paul, Minnesota; Medtronic, Minneapolis, Minneapolis; Protemix, San DiAssistant Editor, American Journal of Cardiology; Clinical Professor, Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, Texas; Visiting Professor, University of Notre Dame, Notre Dame, Indiana; bProfessor of Medicine, Associate Chief of the Division of Cardiology, Chief of the Cardiology Clinical Service, and Director of the Telemetry Unit Northwestern University Feinberg School of Medicine, Chicago, Illinois; cMedical Director, Baylor Heart & Vascular Institute, Chief, Cardiothoracic Transplantation, Baylor University Medical Center, Dallas, Texas; dChairman, Division of Medicine, Professor, Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio; eEditor-in-Chief, American Journal of Cardiology; Director, Baylor Heart and Vascular Institute; Dean, A. Webb Roberts Center for Continuing Medical Education of Baylor Health Care System, Dallas, Texas. Manuscript received March 13, 2007; accepted March 13, 2007. *Corresponding author: Tel: 512-264-1611; fax: 512-264-7034. E-mail address: vfriedew@nd.edu (V. E. Friedewald). 0002-9149/07/$ see front matter 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2007.03.019
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ego, California; Scios, Freemont, California; Sunshine, Maumee, Ohio; Vasogen, Mississauga, Ontario, Canada; and World Heart, Oakland, California. Objectives: Upon completion of the activity, the physician should be able to: 1. Categorize patients according to type of ADHF. 2. Treat patients according to the type of ADHF and not treat all patients with ADHF the same. 3. Divide the treatment strategies into 3 phases during hospitalization. 4. Properly use decongesting and vasodilating agents in patients with ADHF. 5. Involve the patient as a key member of the management team. Introduction One million patients are hospitalized each year with acute decompensated heart failure (ADHF), and 20% of them are rehospitalized for this condition within 30 days of the initial admission.1 ADHF is the most common reason for hospital admission of patients 65 years of age, and 1/2 of ADHF patients 70 years of age are readmitted within 90 days. More than 50,000 patients die annually from ADHF, more than any single cancer.2 In the section Evaluation and Management of Patients with Acute Decompensated Heart Failure in the Heart Failure Society of America 2006 Comprehensive Heart Failure Practice Guideline,3 only 2 of 34 recommendations carried a level A strength of supporting evidence, highlighting the need for much more research about ADHF. In this Editors Roundtable, the faculty discusses best management strategies for patients with ADHF based on the limited knowledge base. Discussion Dr. Friedewald: What is acute decompensated heart failure (ADHF)? Dr. Yancy: ADHF applies to 2 groups of cardiac patients: (1) patients having symptoms of heart failure (HF) for the rst time, and (2) patients with exacerbated symptoms of established HF. Dr. Gheorghiade: I divide ADHF patients into 3 groups: (1) worsening chronic HF (70% of all cases of acute HF); (2) HF diagnosed for the rst time (25%), and (3) advanced or end-stage HFpatients who do not respond to treatment (5%). Dr. Yancy: Patients with ADHF are a heterogeneous group, and include many patients who do not have straightforward left ventricular systolic dysfunction with its classic signs and symptoms.
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Dr. Roberts: Are patients with cor pulmonale included in the denition of ADHF? Dr. Yancy: Yes, because cor pulmonale is driven by left ventricular dysfunction. Patients with ADHF often have other co-morbid conditions, including chronic lung disease, renal insufciency, diabetes mellitus, atrial dysrhythmias, and anemia. Dr. Georghiade: About 40% of patients with ADHF have diabetes mellitus; 50% have systemic arterial hypertension; and 30% have renal insufciency. Dr. Young: My criteria for ADHF include anyone going to an urgent care center with symptoms due to HF or complications of HF, such as an arrhythmia or syncope. Dr. Roberts: What about sudden weight gain? Dr. Young: I would not call that acute decompensated HF, just worsening HF. Patients with chronic HF have weight uctuations of 5 pounds per week, and symptoms uctuate accordingly. Weight gain itself, however, does not inevitably lead to a need for urgent care. Dr. Friedewald: My concern about your denition of ADHF is some other factors often determine whether a patient seeks urgent care, such as lack of health insurance or convenient transportation. Dr. Roberts: I agree that a denition should not depend on where patients go after symptoms appear. They can have acute decompensation and remain at home. Dr. Young: The natural history of ADHF is that a bad event will eventually happen and, when it does, the patient either seeks treatment or dies. Dr. Yancy: Many European experts believe ADHF involves only patients with pulmonary edema. In North America, however, we allow a number of different ways for ADHF to be manifest. Dr. Gheorghiade: Such heterogeneity, however, makes it difcult to do studies on these patients. We need a clearer denition of ADHF. Pulmonary edema, hypertension, and right-sided HF are all clinical presentations. We should not confuse clinical presentation with a denition of ADHF. ADHF classication is often done in retrospect, because it is very difcult to classify patients when they are rst admitted. At the time of admission the clinical picture encompasses several different processes hypertension, right-sided HF, and pulmonary edema. Other parameters, like the ejection fraction, are needed to classify the patient, and they are not known when the patient is seen for the rst time. It usually takes 24 hours before the HF patient can be classied properly. It is important to distinguish between classication, which can be done later, and mode of presentation. Dr. Roberts: No one has mentioned etiology in the denition of ADHF. Dr. Gheorghiade: Initially, the etiology is not important, because a high left ventricular lling pressure is the main reason a patient with ADHF comes to the hospital. The immediate therapeutic goal is to reduce the lling pressure, regardless of whether the etiology is acute myocardial infarction or acute aortic regurgitation. Dr. Roberts: Mitral stenosis is immediately correctible. Dr. Gheorghiade: Yes, but the initial goal is to reduce

congestion. As soon as the patient is stable, etiology becomes very important, because it guides to denitive therapy. Regardless of whether the patient has hypertension or aortic valve stenosis, most deaths are due to a high lling pressure, not to a low cardiac output. The immediate therapeutic goal in ADHF is to safely improve the left ventricular lling pressure. Dr. Young: Heart failure is the umbrella under which are acute, decompensated, ischemic, valvular, rightsided, left-sided, and so on. Dr. Roberts: The common denominator of ADHF is sudden elevation of the left ventricular end-diastolic pressure? Dr. Young: Yes. Dr. Gheorghiade: Elevation of left ventricular end-diastolic pressure, however, does not have to be sudden. It can be gradual. Dr. Roberts: Untreated, however, it eventually reaches a level where the symptoms are intolerable, and the result is ADHF. Dr. Gheorghiade: That is correct. Dr. Friedewald: What are the demographics of ADHF? Dr. Gheorghiade: The mean patient age is 75 years. Forty to 50% of patients have preserved left ventricular systolic function; 70% have a history of systemic hypertension, 60% have documented coronary arterial disease; 45% are post-myocardial infarction; 30% have a history of atrial brillation; 40% have diabetes mellitus; and 30% have chronic obstructive pulmonary disease. Secondary mitral regurgitation is common. Although ADHF is a complex entity, the patient comes to the emergency department for a single reason: the left ventricular lling pressure is high, causing breathlessness. Thus, the immediate treatment end point is to eliminate dyspnea. The other abnormalities can be treated later. About 50% of patients with ADHF present to the hospital with reactive hypertension, which is an intermittent form of hypertension. These patients may be normotensive 6 hours later. Dr. Roberts: You said that 40% of patients with ADHF have diabetes mellitus, which adults essentially do not get unless they are overweight. Is that not correct? Dr. Yancy: Yes. Patients with HF and an increased body mass index do better than persons of normal weight. Dr. Roberts: That is also true for patients with acute myocardial infarction. Dr. Friedewald: Would you expand on reactive hypertension in patients with ADHF? Dr. Gheorghiade: Among 200,000 patients in The Acute Decompensated Heart Failure National Registry (ADHERE) and other registries, 50% were hypertensive at the time of their initial presentation. Many of the hypertensive patients, however, were normotensive prior to admission; after admission, their pressures were often easy to control and were frequently normal within 6 to 24 hours. The reason for this arterial systolic pressure reactivity is activation of neurohormones due to the high left ventricular lling pressure. Thus, this population should not be confused with patients who have a history of hypertension, because the 2 are distinctly different pathophysiological conditions. The blood pressure cannot increase unless there is adequate left ventricular function, so blood pressure in a

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way indicates cardiac reserve in patients with ADHF. Patients with peak systolic blood pressures of 120 mm Hg at the time of admission have a poor prognosis because their ventricles are unable to appropriately respond to increased sympathetic tone. Dr. Yancy: Few patients with ADHF have low blood pressure or shock. In The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), the patients with lower blood pressure and cardiac outputs on admission did not respond well to therapy. Dr. Young: In both The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) and the ADHERE registries (50,000 and 100,000 patients, respectively), 50% had preserved left ventricular systolic function. Dr. Gheorghiade: Most physicians treating ADHF focus on improving the cardiac output, although cardiac output is usually normal or high in these patients, and it is not the major problem. The treatment goal should be to reduce the pulmonary arterial wedge pressure, which, of course, corresponds with the left ventricular end-diastolic pressure (the lling pressure). Dr. Roberts: If we could prevent systemic hypertension, would we also prevent most cases of HF? Dr. Yancy: In the Systolic Hypertension in the Elderly Project, among patients with coronary heart disease and systolic hypertension, concomitant administration of a thiazide diuretic plus a blocker led to an 80% reduction in subsequent HF. It is likely that treating hypertension to goal (blood pressure at least 140/90 mm Hg) would reduce the incidence of HF by 50%. There are no prospective trials, however, designed to prevent HF. Dr. Roberts: Perhaps lipid-lowering or antihypertensive therapy will prove to be the best anti-HF therapy. Dr. Yancy: Statin therapy also may have a stabilizing effect in ADHF, possibly because of its anti-inammatory effect. Dr. Young: The data on the favorable effect of statins is impressive in HF cohorts, even when not prescribed for elevated lipids. Coupled with antihypertensive therapy, this may be the direction we need to go to prevent symptomatic left ventricular diastolic dysfunction. Dr. Roberts: Do you include statins in the treatment of patients with idiopathic dilated cardiomyopathy? Dr. Yancy: Yes, I do sometimes. Dr. Gheorghiade: Heart failure may be a consequence of hypertension, coronary arterial disease, atrial brillation, and diabetes mellitus, and all of them, of course, are treatment targets in ADHF, in addition to lowering the left ventricular lling pressure. Dr. Roberts: Patients with increased left ventricular end-diastolic pressures who have normal-sized left ventricles and thick left ventricular walls are not the same as patients with comparable end-diastolic pressures, but who have dilated left ventricular cavities and relatively thin walls, are they? Dr. Gheorghiade: No, because the left ventricular enddiastolic pressure is a function of the left atrium contracting against a stiff left ventricle. Dr. Yancy: We call a left ventricular ejection fraction

40% heart failure with preserved systolic function. A left ventricle with an ejection fraction of 45% looks pretty sick, a ventricle with an ejection fraction of 55% looks better, and a ventricle with an ejection fraction of 70% looks great. We should differentiate, however, between patients with symptomatic pulmonary congestion in the presence of a normal-sized left ventricular chamber versus patients with symptomatic congestion and a dilated left ventricular cavity. Dr. Gheorghiade: I agree, but it is unusual for patients to have preserved left ventricular systolic function and high lling pressures, unless they have an inltrative cardiomyopathy (amyloidosis, for example) or systemic hypertension. Dr. Roberts: Are you talking about left ventricular walls that are much thicker than normal versus those ventricular walls that are not thickened? Dr. Gheorghiade: Primary left ventricular diastolic dysfunction is a rare cause of HF. Few patients with left ventricular hypertrophic cardiomyopathy develop HF. Dr. Roberts: You said 40 to 45% of patients with HF had left ventricular diastolic failure. Dr. Gheorghiade: Yes, but I said diastolic, not primary diastolic HF. There is a difference. The ventricular wall may be thick, but it is not primary thickening. I distinguish between primary diastolic dysfunction and secondary diastolic dysfunction. Patients with myocardial ischemia and patients with systemic hypertension both have secondary diastolic dysfunction. Thus, there are many patients with diastolic HF, but it is not a primary form of diastolic HF. They have thicker ventricles, but there is not always a good correlation between ventricular thickness and the presence of diastolic HF. Dr. Young: This is both a structural and a mechanical phenomenon, complicated by the reality that patients with left ventricular systolic dysfunction have varying degrees of diastolic dysfunction. Dr. Roberts: But not the reverse. Dr. Young: That is correct. The one profound driver in the process is afterload increasewhich, by denition, is hypertension. Because only recently has the importance of diastolic HF been recognized, therapies primarily focusing on diastolic HF have not been designed. Dr. Roberts: What are the most common signs or symptoms of diastolic HF? Dr. Gheorghiade: Of patients with ADHF, 70% edema; 70% rales; 40%, a systolic precordial murmur; 40% dyspnea at rest; and 30% have jugular venous distention. Dr. Yancy: Both the European regulatory body and the Food and Drug Administration state that the sine qua non of ADHF is dyspnea. Dr. Friedewald: What is the natural history of ADHF? Dr. Yancy: The death rate for the hospitalized patient with ADHF is low, but in some select, very well-dened groups, it is as high as 20%. Even with optimal care, however, the 30-day risk of death is 10%. At 1 year from the indexed hospitalization, the risk of death is about 30%. The death rate at 1 year for ambulatory class III HF patients is about 10%. The risk of rehospitalization is 50%. There is something about hospitalization that changes the natural history, but we do not know what that is.

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Dr. Roberts: Are you saying that patients should not come to the hospital? Dr. Yancy: No, we assume it would even be worse without hospitalization. Dr. Friedewald: Is etiology a factor in prognosis? Dr. Gheorghiade: Yes. Data from OPTIMIZE show that myocardial ischemia carries a far worse prognosis than primary cardiomyopathy. The mortality curve in patients with class IV HF is linear between mortality and time. Patients hospitalized for HF resemble the post-myocardial infarction curve, with a very high event rate in the rst 60 days, followed by a relatively at curve. Dr. Gheorghiade: Etiology is the key to proper management, but not for assessing prognosis. Dr. Yancy: The precipitating cause must be addressed in a patient with ADHF. Chronic HF trials have shown no difference in outcomes with blockers or angiotensinconverting enzyme (ACE) inhibitors or any other evidencebased therapy as a function of the etiology of left ventricular dysfunction. Thus, therapy for HF is stratied according to left ventricular function, not etiology. Dr. Roberts: Many of these studies, however, do not include patients with severe aortic stenosis, mitral stenosis, coarctation of the aorta, and other such correctable conditions. It would be terrible to miss such a diagnosis. Dr. Yancy: That is correct. Dr. Roberts: It appears that HF specialists are the cardiac oncologists of heart disease, because you are focused on longevity. Longevity, however, is not the orientation of the average cardiologist. Dr. Gheorghiade: About 80% of patients with HF are not seen by a cardiologist. There are studies suggesting that cardiologists are no better in managing HF than are general internists. Dr. Young: In response to Dr. Roberts assertion that HF specialists are cardiac oncologists, I am reminded of a patient I saw this morning who was referred for inoperable 3-vessel coronary arterial disease. He had well-compensated class I HF. He had been told by his physician that he was going to die and that he might need a heart transplant. How long is he going to live? Although the overall prognosis for such patients is not good, there are categories of HF patients who do well for decades, a fact that is sometimes lost in the descriptions of high morbidity and high mortality. Such negative attitudes on the part of physicians cause many patients with HF to go through a lot of unnecessary psychological angst. Dr. Gheorghiade: I am reminded of a patient, a physician, who was diagnosed years ago with end-stage HF. Today, he has a normal-sized heart. I see such patients nearly every day. Many patients with proper medical therapy of their HFI call them chemical, rather than mechanical transplants have sufcient myocardial viability, such that their ejection fraction can be normalized over time. Dr. Yancy: You are correct. HF specialists tend to think in 1-year and 5-year mortality constructs, much the sameas Dr. Roberts pointed outas oncologists. Dr. Gheorghiade: But there is a huge difference. The oncologist does not have truly life-saving therapy, whereas HF specialists do.

Dr. Roberts: What life-saving therapies are you referring to? Dr. Gheorghiade: Beta blockers, ACE inhibitors, aldosterone-blocking agents, cardiac resynchronization therapy, intracardiac debrillators, perhaps statins. Although HF is a condition with a bad prognosis, we have remedies. The problem is that there is a huge gap between what we can do and what is being done. Dr. Yancy: This is true with chronic HF, where we have greatly improved therapies, but treating patients with ADHF is far less successful. Dr. Gheorghiade: It is essential to identify the precipitating cause of ADHF for patients to improve. If the precipitating cause is not delineated and treated, the patient will not improve. Atrial brillation, infection, diabetes mellitus, anemia, all must be treated. Unfortunately, this is not being done nearly enough. I have seen patients with a hemoglobin of 5 mg/dl who were treated with diuretics; they will not improve until the anemia is corrected. The same is true for controlling the heart rate in atrial brillation. The precipitating cause is key to successful treatment of patients with ADHF. Dr. Friedewald: I am concerned that so few HF patients are seen by cardiologists. I would argue that every patient with HF should be evaluated at least once by a cardiologist. Dr. Gheorghiade: With 1 million annual hospitalizations for HF in the USA that desire is not possible. Dr. Yancy: Outcomes for patients with HF are determined more by factors, such as renal function, systemic blood pressure, and hemoglobin, than by etiology. Every patient with heart failure should have a practitioner who has a HF focus, even if that person is a nurse practitioner. Dr. Roberts: What is your general workup for a patient with rst-time ADHF? Dr. Gheorghiade: I recommend a full right and leftsided cardiac catheterization, including coronary angiography and left ventriculography. Dr. Yancy: The guidelines recommend cardiac catheterization in patients with HF and angina pectoris. No more than 5% of patients admitted to the hospital with ADHF undergo cardiac catheterization. Dr. Roberts: What laboratory tests do you do routinely perform? Dr. Gheorghiade: Tests are renal function and target organ function, electrolytes, Doppler echocardiogram, chest radiograph, and perhaps the brain naturetic peptide (BNP). Dr. Roberts: Why perhaps the BNP? Dr. Yancy: The role of BNP is unresolved. It is most useful when there is diagnostic ambiguity, whether dyspnea, for example, is due to pulmonary or cardiac disease. When the likelihood of lung disease is high, the BNP does not have much diagnostic value. The BNP, however, can provide unique prognostic information. Thus, while the role of serial BNP measurements is unresolved, BNP does have value in cases of diagnostic ambiguity and for determining prognosis. Dr. Friedewald: How do you assess the mortality risk in a patient with ADHF? Dr. Yancy: In ADHERE, 3 measurements indicated a 22% inpatient risk of death: blood urea nitrogen 37 mg/dl, systolic blood pressure 115 mm Hg, and creatinine 2.75

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mg/dl. When the blood urea nitrogen was 37 mg/dl and the systolic blood pressure was 115 mm Hg, the risk of inpatient death was only 2%. Dr. Gheorghiade: The systolic blood pressure at the time of admission is a major predictor of risk: when it is 120 mm Hg, the in-hospital mortality is 7%, the postdischarge mortality is 14%, and the readmission rate is 30%, compared to an in-hospital mortality of 1% and a postdischarge mortality of 5% when the systolic blood pressure is 115 mm Hg. Systolic blood pressure is an indicator of left ventricular systolic function. Thus, when the systolic blood pressure is high, e.g., 190 mm Hg, the ejection fraction is probably well preserved. A patient with a systolic blood pressure of 120 mm Hg at admission is likely in trouble and too often that patient is treated the same as a patient with a higher systolic blood pressure. The systolic blood pressure is not only a good prognostic indicator, but when it is low, it indicates that maximal therapy from the outset blockers, ACE inhibitors, aldosterone antagonists, is warranted. Dr. Roberts: How do you manage the blood pressure in a patient who was previously hypertensive and is admitted with ADHF with a low systolic blood pressure? Dr. Gheorghiade: That patient has a terrible prognosis. Trials have taught us that it is extremely important not to lower the blood pressure further. To do so can signicantly decrease the coronary perfusion pressure. It is extremely important in such patients to improve cardiac function without decreasing coronary perfusion, because the myocardium is likely ischemic and there is increased neurohormonal activity that adds to the myocardial ischemia. Dr. Roberts: Do you try at all to increase the blood pressure? Dr. Yancy: Even though marginal or low blood pressure is a risk of poor outcome, it is a terribly inappropriate target for therapy, because the only way to increase the blood pressure is with vasoconstrictors and inotropes. Given that blood pressure is a product of cardiac output and peripheral arterial resistance, increasing the cardiac output by reducing resistance using vasodilators and other strategies is a more physiologic way to normalize and elevate the blood pressure. Fluctuations in blood pressure during ADHF may increase near-term event rates. Protecting the patient from hypotension is probably a better therapeutic target than actually raising the blood pressure. Dr. Young: It is better for the HF patient to have a lower blood pressure and a slower heart rate, as long as the patient is walking, talking, and urinating. What is most important is perfusion and organ function. Dr. Friedewald: Does the initial blood glucose have prognostic value? Dr. Gheorghiade: In both OPTIMIZE and in ESCAPE, there was no short-term difference in outcomes between patients with and without diabetes mellitus. These trials, however, only looked at short-term differences. Dr. Yancy: What about hyponatremia and anemia? Dr. Young: The patients serum sodium level should be normalized. Whether to treat anemia is highly controversial, even though patients with anemia have worse short-term and long-term outcomes than those without anemia.

Dr. Roberts: How do you dene anemia in these patients? Dr. Young: A hemoglobin 12 mg/dl. Dr. Roberts: How do you treat hyponatremia? Dr. Young: By a variety of measures, and all focusing on limiting the amount of free water intake versus salt intake, and, if possible, lowering the doses of diuretics. In anemic patients. thiazide-based diuretics also should be avoided. Dr. Gheorghiade: In OPTIMIZE-HF, 25% of the patients had hyponatremia. In ESCAPE, 25% of patients also had hyponatremia, both at admission and at discharge. Thus, hyponatremia is common, and it is not properly treated. The most intriguing aspect of ESCAPE was that, although patients with hyponatremia had the best clinical and hemodynamic response to therapy, compared to patients with normal serum sodium levels, their post-discharge mortality was 3 times higher. Hyponatremia is an independent and major predictor of prognosis. Hyponatremia also indicates the presence of a unique form of HF. Dr. Yancy: Hyponatremia also correlates with the extent of neurohormonal activation in patients with ADHF. I would argue that treating hyponatremia has not been shown to be benecial and, until we have done so, it is not necessarily a target of therapy. Dr. Friedewald: Are results of tests for renal function improved by successful treatment of ADHF? Dr. Yancy: That is not known. Dr. Friedewald: Which specic agents improve morbidity and mortality in ADHF? Dr. Yancy: The therapeutic target in ADHF is primarily hemodynamic, the same as in patients with chronic HF. Currently, in patients with ADHF, the target of therapy is also hemodynamic, but good results with this strategy have not been seen. Dr. Gheorghiade: Treatment of ADHF can be separated into 3 different phases: (1) early management for improving hemodynamics; (2) in-hospital management for eliminating residual symptoms; and (3) predischarge management for implementing life-saving therapies. Dr. Young: The goal is to make the patient feel better, to protect the patient from end-organ damage especially the cardiorenal syndromeand to set the stage for getting the patient out of the hospital, which primarily requires decongestion. Dr. Yancy: Given that ADHF is a heterogeneous disease process with multiple patient phenotypes, is lowering mortality an appropriate target? Will a single therapeutic strategy for a patient population this diverse lower mortality? Dr. Young: ADHF cannot be viewed with the same mindset as patients with acute myocardial infarction, for example. Treatment of the latter is straight forward and much the same for all patients. Treating patients with HF is far more complex. While I believe that reduction in acute hospital mortality for ADHF is a laudable goal, that reduction is not going to be achieved with any 1 specic intervention. Rather, it will require a combination of therapies related to the 3 goals I mentioned earlier and the 3 treatment phases Dr. Georghiade outlined.

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Dr. Gheorghiade: Improved survival is not the issue; rather, the issue is not increasing mortality with our treatment. Dr. Yancy: I agree. Dr. Gheorghiade: One dilemma with ADHF is that many therapies that improve hemodynamicssuch as dobutaminealso kill myocardial cells. Dr. Yancy: I agree that seeking a single intervention targeted towards lowering mortality is unrealistic. What is more relevant is relieving symptoms and lowering morbidity while increasing mortality. Dr. Gheorghiade: The HF guidelines are based more on opinion than facts, which we lack. The guidelines urge improving the pulmonary arterial wedge pressure with a combination of vasodilators and diuretics, but not excessive diuresis. We should not rely solely on diuretic therapy to relieve congestion. Dr. Yancy: The guidelines do, however, emphasize decongesting the patient. Dr. Gheorghiade: By using combination therapy, not single therapy. Dr. Young: The HF therapy is made more complex by the need also to treat co-morbidities such as anemia, myocardial ischemia, hypertension, diabetes mellitus, and hyperglycemia. Dr. Yancy: Decongestion with diuretics is an appropriate rst step. Is the second step the administration of highbolus diuretic therapy, continuous diuretic infusion, or vasodilators combined with standard diuretic therapy? Dr. Young: I come back to the underlying co-morbidities. I would treat a patient admitted with ADHF and long-standing hypertension and left ventricular systolic and diastolic dysfunction immediately with both vasodilators and diuretics, relying more on the vasodilators to lower the left ventricular end-diastolic pressure rather than being aggressive with diuretics. Diuretic use has changed with time. It is rare for me to see a patient who needs to be admitted to the hospital that I do not start on a continuous diuretic infusion. If a patient is sufciently volume overloaded to be admitted to the hospital, guessing the doses of intermittent, pulsed diuretics is much more problematic than guessing the dose of continuous infusion. Dr. Gheorghiade: For some patients, diuretics are second-line therapy. Hypertensive patients even those with reactive hypertensionare often older, and they may have redistribution of body uids rather than being total body uid overloaded. Dr. Friedewald: Do you not give these patients both a vasodilator and a diuretic? Dr. Gheorghiade: Yes. Most of the time, I use the combination, but not always. There should not be anything routine. About 50% of these patients are hypertensive, and the goal in these patients is to reduce the blood pressure, not reduce uid overload. In other patients, the pulmonary arterial wedge pressure may be the only target. In patients who are hypertensive, there are 2 targets for therapy: simultaneous reduction of both the blood pressure and the pulmonary arterial wedge pressure. Dr. Friedewald: Does everyone agree that patients with ADHF should rst be decongested?

Dr. Gheorghiade: Yes, but how to achieve that should be determined by how the patient presents. Dr. Young: How often do you not give diuretics to patients admitted with ADHF? Dr. Gheorghiade: I usually use diuretics, but I do not rely solely on them, as happens too often. Dr. Young: How often do you see acute pulmonary edema with a normal total body volume? Dr. Gheorghiade: This occurs in about 5% of patients with ADHF. Dr. Young: Do you give diuretics to those patients? Dr. Gheorghiade: No. Dr. Young: Most physicians do not think that way. Most give all patients with pulmonary edema an intravenous bolus of diuretics. Dr. Gheorghiade: The problem is mainly the quantity of diuretics given. According to ESCAPE, the deleterious effects of diuretics were not so much related to the diuretic, but to the amount given. Dr. Yancy: What is the role of inotropes? Dr. Young: I use them only for patients in shock or near-shock. Dr. Gheorghiade: I use inotropes for patients in the low cardiac output state. There is no other choice. Most physicians in the USA unfortunately use inotropes in patients with normal cardiac output. Dr. Friedewald: What is the role of vasodilatorsnitroprusside, nitroglycerin, and nesiritide? Dr. Yancy: In patients with symptoms at rest in the absence of hypotension, 1 of 3 vasodilators should be used: nitroprusside, nitroglycerin, or nesiritide. Nitroprusside has an excellent prole, helping to normalize blood pressure and to relieve concomitant pulmonary congestion by reducing both preload and afterload. Nitroglycerin relieves pulmonary congestion in patients with ADHF by reducing preload. Dr. Gheorghiade: Nesiritide is an excellent choice both for hypertensive and normotensive patients. Unfortunately, nesiritide is too often used as rescue therapy in patients who do not respond to other therapies. These patients are frequently hypotensive and have impaired renal function. Although nesiritide is an excellent drug for ADHF patients with normal or elevated blood pressure, it is often used in patients who are most likely to have adverse effects from this drug. Dr. Roberts: How do you administer nitroglycerin for ADHF? Dr. Yancy: Topically, intravenously or sublingually. Dr. Young: Nitrates are excellent drugs in ADHF when used correctly. These patients must be carefully monitored, watching for tachyphylaxis, and titrating the drug over time. Vasodilators should not be used in the hypotensive patients. At presentation, patients with ADHF may be hypertensive or normotensive or hypotensive, and each needs to be addressed differently with respect to the vasodilator/diuretic combination. I make such decisions very early in the course of ADHF. Dr. Gheorghiade: Nitroprusside requires invasive monitoring, because it can rapidly lower the arterial blood pressure to zero. Dr. Friedewald: What about oxygen?

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Dr. Yancy: Oxygen is the only pure pulmonary vasodilator we have. It will overcome any other inuence, and decongest the pulmonary circulation. Dr. Friedewald: Lets discuss future therapies, starting with aquaretic therapy. Dr. Gheorghiade: Aquaretic therapy, or vasopressin antagonism, is safe, can be added to diuretic therapy, and signicantly reduces body weight, without adverse effects on the heart rate, blood pressure, renal function, or serum potassium, and generally normalizes the serum sodium. Theoretically, it can be used with or without a diuretic. Dr. Yancy: Acute administration of natriuretic peptides improves congestion and relieves dyspnea, but perhaps not more effectively than nitroglycerin. Natriuretic peptides, however, may have adverse effects on renal function and increased risk of death 30 days after administration. These questions are being resolved by a very large multicenter international trial in ADHF involving 7,000 patients. The planning stages are underway for this trial, called Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF). Dr. Friedewald: What about devices? Dr. Young: Mechanical removal of uid has been around a long time. Venoveno ultraltration devices to remove uid are miniaturized, efcient, and easy to use. The UNLOAD trial and several other trials will give us greater insight into their usefulness. I believe that mechanical uid removal devices are going to be a good option in the future. Dr. Roberts: I understand that the average patient in the USA with an acute coronary event has a body mass index of about 29, which I suspect is the same as patients with ADHF. How would signicant weight loss affect the longevity of ADHF patients? Dr. Young: I believe it would be very effective. Dr. Gheorghiade: The problem is that chronic HF patients are malnourished, even including some who are overweight. Dr. Roberts: Malnourished from a protein standpoint? Dr. Gheorghiade: Yes. The heart requires a lot of protein to function properly. We are currently studying the potential role of essential amino acid supplements and other therapies to improve nutrition in HF patients. Dr. Friedewald: How should future trials of ADHF be conducted? Dr. Gheorghiade: Thus far, ADHF trials have involved patients who are not stratied. There are different populations of patients with ADHF, including those with various blood pressures, serum sodium levels, geographical differences (different continents), and each of these different patient types needs to be stratied for proper investigation. We are currently putting together a large trial that straties patients admitted with acute HF into 2 groups: those treated with standard care, and those treated with maximal aggression. Dr. Friedewald: Is it difcult to nd funding for such trials? Dr. Young: It is a horrible problem. Support is mostly from industry.

Dr. Friedewald: Lets discuss disease management. Dr. Yancy: Disease management in ADHF carries some good news. There are indicators of quality that have been promulgated across all hospitals in this country. Using these indicators, we recently demonstrated that certain therapeutic strategies, such as the use of ACE inhibitors and blockers, appear to modify 60- to 90-day outcomes. Such clinical trials have repetitively shown that best practices make a difference in outcomes. When a HF patient is hospitalized, an excellent opportunity arises to place that patient on the right drugs and into the right follow-up schemes. Dr. Friedewald: How do you determine the optimal time to discharge a patient with ADHF from the hospital? Dr. Gheorghiade: This is a very important issue. Guidelines do not tell us when patients are ready for discharge. Although congestion is the main reason for admission, 50% of these patients do not lose weight during hospitalization. When they go home, they go home with the same amount of uid, which has shifted from the lungs, where you can still hear it with the stethoscope and see it on chest x-ray, to other portions of the body. Dr. Yancy: I agree that we do not have a good barometer for discharge. Dr. Gheorghiade: There are things we could do better: watching the patient climb a ight of stairs, perform a BNP, and determine if a patient can lie fully reclined. These are simple tasks, but they are not being done. Dr. Yancy: I discharge the patient when the presenting symptoms are gone, there is improvement in the background medical therapy, and there is a well-dened plan of care for the future. Dr. Gheorghiade: I rely on how patients feel. I perform an orthopnea test to be certain that patients can lay at for 1 minute, and I ask them to climb 1 ight of stairs. If they pass these tests, and they have no signs of congestion, I discharge them. Dr. Young: I make certain the patient feels better compared to symptoms at admission, is ambulating, and is decongested. I will send a patient home with a small amount of peripheral edema. It is more important to see improvement than total resolution. And a long-term treatment plan is essential. Dr. Roberts: Can we train more physicians to specialize in treating patients with HF? Dr. Yancy: As immediate past chair of the membership committee of the Heart Failure Society of America, my charge for 3 years was to try to nd ways to get more professionals involved in treatment of patients with HF. Although there are people who are interested in specializing in HF, there is a disconnect between the way we train people and the way people are hired. Physicians are typically hired according to what they can do procedurally, but we train people according to what they need to know cognitively. This needs to be changed, and the Heart Failure Society of America is raising the awareness of the value of the cognitive input of HF specialists. It is our hope that we can achieve certication of HF management as a recognized subspecialty. Revenue and other such resources, however, drive a lot of this sort of behavior in our society, so if we can add value to the

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designation as a HF physician, more people will be interested in pursuing this subspecialty. Dr. Young: A good HF clinician must have a good understanding of renal pathophysiology, pulmonary pathophysiology, hemodynamics and heart transplantation. There are a lot of exciting aspects of this specialty. Reimbursement issues, however, hamper these efforts. Unless we create more systems to deal with the reimbursement issues, HF specialists will continue to struggle and inadequate numbers will enter the subspecialty. Dr. Gheorghiade: The most important member of the HF team is the patient. The physician sees these patients once every 2 months, and the patients are with themselves 24 hours a day, 7 days a week. So the patient is a very important component, because therapy for HF is chronic. When patients do not take their medicines and/or fail to do other proper things, outcomes are bad. The patient is the major part of the HF management team. Dr. Friedewald: Thank you. Needs Assessment: The need for this activity for cardiologists and other healthcare specialists in cardiovascular medicine is based on the following premises: 1. Acute decompensated heart failure (ADHF) is a common cause of morbidity and mortality. 2. ADHF is associated with many co-morbid conditions. 3. ADHF is a complex, multidimensional condition demanding knowledge of cardiac, pulmonary, hemodynamic, and renal function. 4. Knowledge about ADHF is not as advanced as our understanding of other cardiovascular conditions, such as chronic congestive heart failure and acute myocardial infarction.

5. There is a need for more physicians to be trained in treating patients with ADHF. Target Audience: This activity is designed for cardiologists and all other health care specialists caring for patients with acute and chronic coronary heart disease. CME Credit: The A. Webb Roberts Center for Continuing Medical Education of Baylor Health Care System, Dallas, designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity. The A. Webb Roberts Center for Continuing Medical Education for Baylor Health Care System, Dallas, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. CME Instructions: After reading this article, go online at www.AJConline.org to register, complete a post-test with a minimum score of 80%, complete an evaluation, and print a certicate. Combination of Media: Print and Internet Computer Requirements: Windows 2000, Pentium 3 or greater, 512 ram, 80 gigabytes storage Estimated Time to Complete: 1 hour Release Date: June 2007 Termination Date: June 2008
1. American Heart Association. Heart Disease and Stroke Statistics. Available at: http://circ.aha.journals.org/cgi/reprint/113/6/e85. 2. American Cancer Society. Cancer Statistics 2005. Available at: http:// int-caonline.amcancersoc.org/cgi/content/full/55. 3. Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Cardiac Failure 2006;12:10 38.