The Clinical Challenge of Congestive Heart Failure: Optimizing Outcomes in the E
The Clinical Challenge of Congestive Heart Failure: Optimizing Outcomes in the Emergency Department and Outpatient Setting
Part I: Initial Assessment and Stabilization
Authors: David J. Robinson, MD, MS, Director of Research, Division of Emer- gency Medicine, The University of Maryland Medical Center, Baltimore, MD; Rob Rogers, MD, Division of Emergency Medicine, The University of Mary- land Medical Center, Baltimore, MD
Peer Reviewer: Jeremy Brown, MD, Department of Emergency Medicine, Beth- Israel Deaconess Medical Center; Instructor in Medicine, Harvard Medical School, Boston, MA.
From an emergency medicine perspective, the clinical presentation is well known: shortness of breath, weakness, fatigue, with or without ischemic symptoms, and a clinical severity profile that ranges from irritative symptoms to life-compromising pulmonary edema. Whether characterized by exercise intolerance, shortness of breath, peripheral edema, or pulmonary congestion, congestive heart failure (CHF) is one of the most important cardiovascular diseases amenable to emergency therapy. It effects approximately 1.5% of the U.S. adult population, causing a dramatic decline in quality of life and a shortened life expectancy among those who suffer from this condition.1
It is estimated that approximately 3 million people in the United States are afflicted with CHF. Because of the high morbidity, mortality, and cost associated with the disease, CHF is likely to remain a significant public health concern, with increasing emergency department (ED) encounters over time.
The most significant complication of ischemic cardiovascular disease, CHF is the most common hospital discharge diagnosis in patients older than age 65, and the fourth most, common discharge diagnosis overall. In the United States alone, more than 400,000 new cases of heart failure are diagnosed annually, and CHF is the only major cardiovascular disease for which the incidence is increasing. As might be expected, the prognosis for patients with CHF is poor. Data from large clinical trials indicate that patients with CHF have a five-year mortality rate of approximately 50% and that patients with the most severe symptoms (NYHA Classes III-IV) have approximately a 50% one-year mortality.2-5
The economic impact of CHF, where most cases emerge as a consequence of ischemic heart disease, also is significant. In the United States, annual expenditures for the diagnosis and treatment of CHF exceed $10 billion. Of this amount, approximately $230 million is spent on drug therapy and $7.5 billion on hospitalization. The remainder is spent on nursing home days ($1.9 billion) and physician office visits ($690 million). The average length of hospitalization for CHF is approximately nine days, at an average cost of more than $12,000. These patients frequently require recurrent hospitalizations, multiple visits to the ED, and many different medications to maintain their functional status.
Therefore, innovations in the medical management of CHF should be evaluated for their ability to ameliorate symptoms, prevent hospitalizations, reduce medical costs, and increase life span. Recent trials with angiotensin-converting-enzyme inhibitors (ACEIs) and beta-blockers have documented progress toward these goals.
More than ever before, the role of the emergency physician caring for patients with CHF has expanded to include drug-based interventions with intravenous and oral agents, among them are ACE inhibitors, beta-blockers, digoxin, diuretics, and oxygen. Fortunately, many patients who present to the ED with mild symptoms of heart failure, but without evidence of decompensation or acute, life-threatening complications (e.g., ischemia, hypoxia, hypotension, or arrhythmias) may be managed in the ED. However, almost without exception, stabilization and acute management of such patients will require pharmacotherapeutic intervention using medications that decrease preload, reduce afterload, and/or prevent ischemia. These medications frequently can be initiated and/or titrated in the ED, in consultation with the patient’s primary care physician or cardiologist. Consequently, familiarity with these drug classes is essential for optimizing patient outcomes.
With these issues in mind, this two-part series on CHF will review the current status of emergency evaluation, triage, and pharmacologic treatment of patients with CHF. The authors will review new strategies for acute management, identify approaches to subacute management, and review clinical trials demonstrating life prolongation and mortality reduction using medications approved for treatment of CHF.
— The Editor
Introduction
One of the most common disease entities encountered in the ED, congestive heart failure (CHF) encompasses a broad category of conditions that culminate in the heart’s inability to meet the metabolic and nutritional demands of the body. Heart failure can be characterized as a symptom complex that includes fatigue, shortness of breath and dyspnea on exertion, as well as other symptoms of congestion, and represents a clinically significant impairment in either the heart’s ability to pump, fill adequately, or both.2 As might be expected, CHF ranges in its severity from mild symptoms of volume overload to the severe symptoms of pulmonary edema and cardiogenic shock. Accordingly, it is essential that emergency physicians promptly intervene in patients with clinical decompensation, recognize medication side effects, be familiar with new trends in the treatment of heart failure, and develop a management plan that is customized for the patient’s presentation.
As the population in the United States ages, the prevalence of CHF predictably will increase over the next several years.6 In fact, it is estimated that the number of cases of heart failure will double over the next 40 years. Currently, CHF is the most common, "first-listed" diagnosis among hospitalized patients. From an emergency perspective, ED physicians must be capable of managing the increasing number of elderly patients with CHF who present to the ED not only with evidence of heart failure-mediated decompensation, but who are also taking new and experimental medications to treat this condition. Moreover, physicians must be aware of both typical and atypical presentations of CHF, they must remain current with the rapidly evolving therapeutic landscape in CHF, and they must be prepared for aggressive management modalities, including airway management and invasive hemodynamic monitoring.
Epidemiology
CHF is a common clinical entity, and the number of deaths attributable to heart failure has markedly risen during the past several decades.1-4 These mortality and prevalence patterns are in stark contrast to the decrease in mortality from coronary disease and cerebrovascular disease over the same period. Put another way, many patients are surviving coronary events and hypertension only to develop CHF as their terminal event.7 Advances in the treatment of other chronic conditions, such as end-stage renal disease, also have indirectly led to the increasing incidence and prevalence of heart failure.6
As might be expected, CHF has made a substantial effect on health care costs and quality of life. It is estimated that approximately 75% of patients with heart failure are older than 65-70 years of age. As the leading cause of hospitalization in the geriatric age group, it is estimated that 8% of patients between the ages of 75 and 86 have heart failure.8,9 Currently, our country spends about $10 billion per year on the diagnosis and management of CHF. The presence of CHF more than doubles the age- and sex-adjusted risk of death from all causes.6 In the previous decade, the number of admissions for heart failure rose from 577,000 to 871,000.10 Moreover, those patients requiring hospitalization for CHF have an increased risk of mortality, a higher readmission rate, and a clinical course characterized by more precipitous functional decline.11 Consequently, although it is not yet clear whether outcomes can be affected by outpatient care, measures aimed at preventing hospital admission for CHF should be pursued aggressively, especially for low-risk patients. Finally, there are powerful clinical and cost incentives for developing improved prevention and treatment strategies for patients with CHF.6
Etiology
The etiology of CHF is diverse and ranges from ischemic heart disease and valvular dysfunction to myocarditis and infectious endocarditis. Broadly speaking, CHF can result from any disorder that decreases the ability of the ventricles to eject blood.7 Among the most common causes of CHF encountered by the ED physician are coronary artery disease, hypertension, and alcoholic cardiomyopathy. (See Table 1.) Valvular diseases such as aortic stenosis and mitral regurgitation, are also very common etiologies,15 which often coexist with ischemia-mediated causes, especially in the elderly. In addition, elderly patients appear to be at higher risk for acquiring iatrogenic heart failure, which may be caused by medication-related bradyarrhythmias, myocardial suppression, or other drug-related complications. Iatrogenic heart failure may occur even when coexistent heart disease is not apparent.11
| Table 1. Etiology of Congestive Heart Failure |
| • Coronary artery disease (acute, chronic)
• Hypertension • Valvular disease (aortic stenosis, mitral regurgitation) • Hyperthyroidism • Idiopathic dilated cardiomyopathy • Hypertrophic obstructive cardiomyopathy • Pericardial disease (constrictive pericarditis) • Post-partum cardiomyopathy • Myocardial toxins (alcohol, donarubicin, cocaine, sympathomimetics) • Infiltrative myocardial disease (amyloidosis, sarcoidosis, hemochromatosis) • Tachycardia-induced cardiomyopathy • High output failure (Paget’s disease, AV fistula) • Medications (calcium channel blockers, etc.) • Thiamine deficiency __________________________________________________________ |
From a practical perspective, coronary artery disease is the etiology of heart failure in about two-thirds of patients with left ventricular dysfunction. Accordingly, in both the ED and primary care setting, heart failure should be presumed to be of ischemic origin until proven otherwise.12 A common clinical entity that frequently is not recognized by the ED physician, diastolic heart failure is most often caused by chronic, uncontrolled hypertension, in which the ventricle is unable to relax and fill adequately for pumping blood to the periphery.7 Other etiologies the ED physician must consider in the differential diagnosis include hypertrophic cardiomyopathy, pericardial disease, and myocardial toxins, most notably, chemotherapeutic agents such as donarubicin, myocardium-suppressing calcium channel blockers, and alcohol, which is a significant myocardial toxin and can induce dilated cardiomyopathy in individuals who suffer from chronic alcohol abuse.13
Clinical Presentation
Although the clinical pathophysiology of CHF is complex, it is most clearly understood as a state in which the heart is not able to meet the metabolic requirements of the body. In broad terms, heart failure is a syndrome characterized by inadequate cardiac output and elevated left ventricular filling pressures.7 Moreover, it is clinically useful to characterize the signs and symptoms of CHF in terms of left vs. right heart failure. Left heart failure, regardless of the precipitating etiology, produces a constellation of signs and symptoms attributable to increased left ventricular filling pressures, which include dyspnea secondary to increased pulmonary capillary wedge pressure and fatigue associated with a decreased forward flow. Right heart failure, the most common cause of which is left ventricular failure, leads to lower extremity edema, ascites, congestive hepatomegaly, and jugular venous distension.14
Forward and backward symptoms refer to the predominant constellation of symptoms reported in any given patient with heart failure. For example, the major complaint in individuals with forward symptoms is fatigue, a consequence of inadequate ejection fraction. In contrast, backward symptoms are dominated by pulmonary congestion and include dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Elevated ventricular filling pressures lead to a symptom complex of dyspnea and fatigue. Although most cases of CHF are due to systolic dysfunction, a growing number of patients with heart failure maintain normal systolic function, but have a problem with left ventricular diastolic filling.
In approximately 80-90% of patients with CHF, clinical impairment is characterized by left ventricular systolic dysfunction, which is defined as an ejection fraction (EF) of less than 40%. As emphasized, diastolic heart failure is increasing in incidence and currently may account for as many as 40% of all inpatient hospitalizations for heart failure.15 Occult valvular disease and chronic ischemic heart disease also should be considered in patients with normal or preserved left ventricular function and signs of diastolic dysfunction. Specific disease states that induce diastolic heart failure include coronary ischemia, ventricular hypertrophy secondary to hypertension, infiltrative myocardial disease (such as amyloidosis), pericardial disease, hypertrophic cardiomyopathy, and aging.7
Drug Therapy in Congestive Heart Failure: The Neurohormonal Model
Targeted, outcome-effective drug therapy for CHF is based on a thorough understanding of the neurohormonal and hemodynamic models of cardiac decompensation. In fact, both acute and chronic drug-based therapy for CHF, including interventions or therapeutic modifications initiated in the ED, require selection of medications that affect the hormonal, compensatory responses to declining heart function, and that reduce cardiac workload in patients with impaired left ventricular function.
In the setting of clinically significant CHF, the failing myocardium activates several neurohormonal feedback loops that, over time, exacerbate the degree of cardiac decompensation and lead to progressive hemodynamic deterioration. In the setting of reduced pumping capacity, the heart initially attempts to maintain adequate systolic function by increasing heart rate and peripheral vascular resistance. These compensations are accomplished through activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system. Initially, these mechanisms are principally compensatory and can successfully maintain—and even, augment—cardiac output. Eventually, however, these compensatory mechanisms can lead to cardiac decompensation requiring drug therapy.
Renin-Angiotensin II-Aldosterone System. The two most important systems activated by left ventricular dysfunction are the renin-angiotensin-aldosterone system and the sympathetic nervous system. Induction of renin release, production of angiotensin II, and release of norepinephrine lead to increased afterload, as well as salt and water retention, which leads to increased preload and afterload.15 Because of these neurohormonal responses, it is becoming widely accepted that definitive treatment of CHF should not be based exclusively on altering hemodynamic derangements caused by left ventricular dysfunction, but should also use pharmacotherapeutic approaches that inhibit and/or modulate pathways that lead to cardiac decompensation.
This neurohormonal model is supported by the observation that in heart failure, such hormonal regulators as angiotensin II and norepinephrine are elevated. Their end-organ effects include vasoconstriction accompanied by increased blood volume, heart rate, and myocardial contractility. The pathogenesis of CHF centers around the neurohormonal model.16 In this scheme, and initial insult to the myocardium, such as long-standing hypertension, acute myocardial infarction (AMI), or myocarditis, causes ventricular dysfunction, which then leads to cardiac remodeling and further reductions in EF and worsening of clinical symptoms such as arrhythmias and pump failure. Thus, the initial event damages functional myocytes and decreases the pumping ability of the heart.17 Myocardial remodeling is probably the most important mediator in the progression of heart failure and can be identified through changes in ventricular shape and dimension.
Sympathetic Nervous System. Increased sympathetic activity and plasma norepinephrine levels, both of which are elevated in chronic heart failure, over time, may exert deleterious effects on myocardial structure and function. Initially, activation of these systems restore and maintain cardiac output, but, over time, can lead to cardiac decompensation.16 In addition, mediators released when the renin-angiotensin-aldosterone system is activated can cause fibrosis and cardiac remodeling. It has been shown in animal models that stimulation of the beta-adrenergic receptors may induce myocyte apoptosis or programmed cell death. Activation of the sympathetic nervous system seems to play a central role in the development of myocyte necrosis and cardiac remodeling.18 Accordingly, drug-based therapies, such as beta-blockers, that block adrenergic pathways, have been found to be effective in the treatment of heart failure.
Clinical-Therapeutic Correlations. Other chemical mediators implicated in the neurohormonal cascade of CHF include renin, arginine vasopressin, atrial natriuretic peptide, and endothelin. In one study, combined use of clonidine and captopril (by inhibiting activated neurohormonal mechanisms) caused significant improvement in preload and afterload.19 Another model that has been invoked to explain clinical findings in patients with CHF is the cardiorenal model.20 This sequence is based on the pathophysiology of heart failure and decreased forward flow. According to this scheme, decreased renal blood flow—an almost universal phenomenon in chronic heart failure—activates a cascade of events that eventually leads to the production of renin, angiotensin I, angiotensin II, aldosterone, norepinephrine, and endothelin; all of which act together to increase blood pressure, produce salt and water retention, and possibly, cardiac toxicity, as described in the neurohormonal model of CHF.10 Drugs such as beta-blockers and ACE inhibitors target (inhibit) these critical pathways and prevent further deterioration.21,22
Diagnostic Challenges in Heart Failure
Patients who present to the ED with symptoms suggestive of CHF frequently suffer from other medical conditions that may confuse or mask the diagnosis, making it difficult to distinguish CHF from these other disease states. Perhaps, patients with chronic obstructive pulmonary disease (COPD) present the greatest diagnostic challenge since they frequently are elderly, have risk factors for heart disease, and present with such symptoms as shortness of breath, weakness, fatigue, and tachypnea. Other pulmonary processes also can present with symptoms compatible with heart failure, as can such conditions as obesity, coronary disease, and chronic conditions including sleep apnea. Symptoms such as exertional dyspnea and orthopnea may suggest almost any chronic pulmonary disease, including thromboembolic disease, pulmonary hypertension, and lower respiratory tract infection.23
A thorough and detailed search for a precipitant should be sought in every case of CHF to avoid missing a potentially life-threatening and/or reversible condition. In this regard, the diagnosis of thyrotoxicosis should be considered in the patient who has tachycardia, is hypertensive, and has no previous history of heart failure. In contrast, hypothyroidism should be considered in the myxedematous patient with a history of thyroid rugery. Reversible causes of CHF include arrhythmias, such as atrial fibrillation, valvular disease, and pericardial disease. Cardiac ischemia always requires strong consideration in the differential diagnosis, especially in the elderly or diabetic patient at risk for silent ischemia.
As a general rule, the physician should assume that coronary ischemia is the precipitant of heart failure until it is proven otherwise. One of the most common precipitants in patients receiving appropriate therapy for CHF is failure of patients to maintain fluid balance.24 In a recent study, 59% of admissions attributable to heart failure decompensation were due to excessive sodium retention which, in turn, lead to volume overload.25 As with many other illnesses, CHF seems to be triggered by a number of well-characterized, precipitating factors. These include anemia, thyrotoxicosis, pregnancy or the post-partum state, hypoxia, and ischemia. Early and aggressive management of these precipitants and comorbid conditions is essential and can have a favorable effect on morbidity and mortality. (See Table 2.)
| Table 2. Precipitants of Congestive Heart Failure49,50 |
| • Myocardial ischemia or infarction
• Atrial fibrillation—new onset or rapid ventricular response • Worsening valvular disease—mitral regurgitation • Pulmonary embolism • Hypoxia • Severe, uncontrolled hypertension • Thyroid disease • Pregnancy • Anemia • Infection • Tachycardia or bradycardia • Alcohol abuse • Medication or dietary noncompliance ______________________________________________ |
History and Physical Examination
Whenever possible, a detailed, comprehensive history should be performed on all patients presenting with signs and symptoms suggestive of CHF. In particular, patients should be evaluated for presence of coronary artery disease, hypertension, or valvular dysfunction. In addition, patients should be questioned regarding use of alcohol, chemotherapeutic agents such as donarubicin, negative inotropic agents, and symptoms suggestive of a recent viral syndrome. An assessment of conditions known to cause cardiac infiltrative disease, such as sarcoidosis and amyloidosis, should be sought in patients whose heart failure appears to be of unknown etiology. In all cases, a thorough differential diagnosis should be formulated, and such entities as pulmonary embolism, myocardial infarction (MI), and underlying pulmonary disease should be considered. It should be stressed that the findings of edema, rales, and dyspnea are nonspecific, and, in the patient with normal left ventricular function, these symptoms may reflect an alternative diagnosis.7
Patient’s with CHF can present with myriad complaints, including shortness of breath, dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, nocturia, and cough. Exertional dyspnea is extremely common in patients with heart failure. The most common symptoms, dyspnea and orthopnea, reflect elevated filling pressures and pulmonary congestion.24 Atypical presentations are quite common and include symptoms such chronic cough, fatigue, and insomnia. Patients can also present with ascites, right upper quadrant pain (from hepatic congestion), and weakness.
It is common for elderly patients to present in atypical fashion, which may include absence of dyspnea or orthopnea. The geriatric group—much like diabetics—is more likely to develop silent ischemia and MI as a precipitant of CHF. Consequently, all older patients who present to the ED with new onset or exacerbation of CHF require a work-up to determine whether coronary ischemia, either acute, unstable, or progressive, is the cause for myocardial pump dysfunction. Older patients in particular may present a diagnostic dilemma for emergency physicians because they may lack typical signs, symptoms, and physical findings.26 For example, older patients may be less likely to report exertional dyspnea secondary to their sedentary lifestyle. Decreased exercise tolerance, fatigue, and unexplained confusion in the elderly may also be among the primary complaints in patients with CHF.23 Pulmonary disease may complicate the diagnosis.27 Older patients may also present to the ED with occult cardiogenic shock or ileus as the initial manifestation of heart failure.28
Physical Examination. One of the principal functions of the physical examination is to identify subtle signs and symptoms—lid lag, goiter, medication use, murmurs, abnormal heart rhythms—that suggest a treatable underlying disease. Patients with CHF may present with a wide range of findings, including resting tachycardia, jugular venous distension, a third heart sound, rales, lower extremity edema, a laterally displaced apical impulse, or they may present with only shortness of breath and weakness. Poor capillary refill, cool extremities, or an altered level of consciousness may also be present.23 A third heart sound is considered to be one of the most reliable indicators of CHF. However, it is important to remember that some patients with severe systolic dysfunction who are currently taking digoxin and diuretics may lack a third heart sound, cardiomegaly, on chest x-ray, or edema.29 Consequently, CHF cannot be excluded in patients who have a normal-sized heart on chest x-ray and absence of extremity edema or pulmonary rales.2
Pulmonary rales frequently are absent on physical examination, although, when present, they are strongly suggestive of cardiac decompensation.24 Physical exam findings are not a sensitive indicator of heart failure.30 Physical exam findings suggesting an alternate diagnosis, such as barrel-chest and diminished air movement, should be sought out to narrow the differential diagnosis. It should be stressed that wheezing may be secondary to bronchial wall edema and may be a manifestation of cardiac asthma, especially in patients with no history of COPD or asthma.
Assessment in the ED. Because the physical examination is not predictably sensitive or specific for the diagnosis of CHF, adjunctive diagnostic and radiographic procedures usually are required to establish the diagnosis, suggest a course for initial stabilization, generate a definitive treatment plan, and guide the triage decision. Every patient with symptoms suggestive of CHF should have a 12-lead ECG and should be placed on a cardiac monitor. Arrhythmias such as atrial fibrillation or signs of ischemia can give important clues to precipitants and comorbid conditions, such as left ventricular hypertrophy (LVH). Older patients with electrocardiographic evidence of LVH tend to have a higher incidence of new CHF and develop it earlier compared to patients without evidence of LVH.31 A chest x-ray should be performed to identify pleural effusions, pneumothorax, pulmonary edema, or infiltrates.
Pulmonary edema secondary to left ventricular dysfunction initially begins as cephalization of pulmonary blood flow and proceeds to form the classic "bat wing" pattern. Patients in whom a diagnosis of cardiac ischemia or infarction is suspected should have cardiac enzymes drawn. A complete blood count, electrolytes, and digoxin level, if applicable, also are mandatory. Patients with suspected hyperthyroidism should have thyroid function studies drawn. Echocardiography has revolutionized the evaluation of cardiac disease and can be used in the ED to evaluate for the presence of pericardial effusion, tamponade, valvular regurgitation, or wall motion abnormalities. If an acute process such as a ruptured aortic valve from endocarditis or acute cardiac tamponade in a dialysis patient is suspected, echocardiography should not be delayed.
Patient Stabilization
Rapid, efficient assessment of patients with heart failure should always take priority so that appropriate interventions can be made expeditiously based on objective clinical data. Without exception, patients should be placed on a cardiac monitor, they should have a pulse oximeter attached, and intravenous access should be established. Patients should also be placed on oxygen to maintain adequate oxygen saturation. In patients with severe symptoms (i.e. individuals with acute heart failure and pulmonary edema) other measures such as continuous positive airway pressure (CPAP) and endotracheal intubation (ETI) may be employed when indicated in order to assure adequate oxygenation and ventilation.
Non-invasive ventilation (NIV) is defined as the administration of ventilatory support by noninvasive means, most commonly by face mask. In contrast, ETI is not a benign procedure and may be complicated by misplacement of the ET tube as well as increased sympathetic drive, which has the potential for exacerbating cardiac ischemia in susceptible patients. Moreover, ETI can increase intracranial pressure; the procedure is uncomfortable and prevents speaking and eating. Given these limitations, the use of NIV by way of CPAP or with BiPAP has gained growing popularity over the last few years. Supporting the patient’s airway with NIV provides a valuable adjunct and may prevent more invasive interventions such as ETI. Nocturnal nasal CPAP (N-PAP) has been shown to eliminate recurrent episodes of severe cardiopulmonary disease, including pulmonary edema.32
Despite growing interest in assessing the benefits and risks of noninvasive ventilatory techniques for patients with CHF, COPD, and asthma, it should be stressed that there currently is considerable controversy surrounding the use of noninvasive ventilation in the ED. Its precise role for patients with CHF and ventilatory failure requires more evaluation before definitive recommendations can be made. At present, these ventilatory approaches are used most commonly for exacerbations of COPD and asthma, although they are being used more frequently in patients with CHF exacerbations, including those complicated by pulmonary edema.33
In this regard, one important study concluded that CPAP therapy delivered by face mask for the treatment of pulmonary edema is safe and effective.34 In fact, there is a growing number of trials that suggest CPAP carries a favorable benefit-to-risk ratio. A trend toward lower mortality rates is has been reported with the use of CPAP, and this technique, when used, appears to decrease the rate of intubations.35 NIV appears to alleviate respiratory fatigue by significantly decreasing the work of breathing, which is a salutary effect in patients with fluid overload and pulmonary edema.
Moreover, NIV can be used as a temporizing measure while other therapeutic pharmacotherapeutic measures are undertaken, such as diuresis and preload reduction.36 NIV increases alveolar recruitment, improves oxygenation, and decreases intrapulmonary shunting. Potential complications of NIV include gastric distension, pulmonary aspiration, and barotrauma.34 Use of NIV requires a cooperative patient and should only be performed in appropriate clinical situations since NIV does not provide a definitive airway and should not be used if severe respiratory deterioration is anticipated. In a randomized, prospective trial of BiPAP vs. CPAP in pulmonary edema, one study found that BiPAP improves ventilation and vital signs more rapidly than CPAP.37
Despite the reported clinical utility of NIV, unfortunately, there is a lack of randomized, controlled trials that can provide definitive conclusions regarding its safety and efficacy in patients with respiratory compromise in the clinical setting of acute CHF. At least one report that NIV may worsen ischemia and increase the risk of MI in patients with pulmonary edema further clouds the issue.33 Additionally, the use of NIV in some studies was found to actually increase the in-hospital mortality rate when used in patients with respiratory distress that is linked to multiple etiologies, including cardiogenic pulmonary edema.32 Clearly, further studies are needed on the efficacy and safety of NIV before the administration of CPAP (NIV) can be routinely recommended in this patient population.35
Finally, other measures to improve gas exchange are currently under investigation, including the use of inhaled nitric oxide. Use of conventional vasodilators improve pulmonary hypertension and congestion but lead to a mismatch in ventilation-perfusion and actually worsen gas exchange in patients with CHF. However, recent studies suggest that the use of inhaled nitric oxide may decrease ventilation-perfusion mismatches and improve gas exchange.1,38
Drug-Based Management of Chronic Heart Failure: Initiation, Evaluation, and Titration of Oral Agents in the ED
From the emergency perspective, medical management of patients with CHF can include any one or more of the following interventions or assessments: 1) administering medications to treat hemodynamic derangements; 2) evaluating and ruling out such precipitants to CHF as coronary ischemia, thyrotoxicosis, infection, and anemia; 3) aggressive airway and respiratory management to treat hypoxia; 4) controlling a compromised airway; and 5) generating a disposition based on the stability of the patient.
Fortunately, many patients who present to the ED with mild symptoms of heart failure but without evidence of decompensation or acute, life-threatening complications (e.g., among them, ischemia, hypoxia, hypotension, or arrhythmias) may be managed in the ED. Almost without exception, stabilization and acute management of such patients will require pharmacotherapeutic intervention using medications that decrease preload, reduce afterload, and/or prevent ischemia. These medications frequently can be initiated and/or titrated in the ED, in consultation with the patient’s primary care physician or cardiologist.
Measures to reduce volume overload, decrease afterload, improve left ventricular function, and inhibit the neurohormonal cascade associated with heart failure include administration of diuretics, ACE inhibitors, inotropic agents, and beta-blockers. It is mandatory that changes to drug dosages or the decision to add a medication to an existing regimen be discussed with the patient’s primary care physician or cardiologist if possible. Many of these medications should only be added or have their dose increased in stable, euvolemic patients with no evidence of significant cardiac decompensation. Close follow-up after discharge from the ED should be arranged.
Beta-Blockers. Increasingly, beta-blockers have emerged as foundation drugs for the treatment of CHF, which means this class now has a dual role for management of chronic CHF and for use as cardioprotective agent following AMI. The emergency physician must be aware that the presence of CHF, even in the setting of MI, no longer represents an absolute contraindication to beta-blocker use, and that clinical judgement should dictate which patients might benefit from low-dose, gradual titration of a beta-blocker in this setting.
Numerous studies published in the last few years have validated the use of beta-blockers for the management of chronic CHF. The benefits of beta-blockers to prevent recurrent MI has been well established. Despite their effectiveness as cardioprotective agents, this medication class is underused in post-MI patients, with one study indicating that only 35-65% of eligible patients currently enrolled in managed care plans are currently receiving beta-blockers following their MI. This is unfortunate, because post-MI studies in the pre-thrombolytic era, as well as recent studies in the setting of thrombolysis, continue to show a benefit for beta-blockers.
Overall, studies with atenolol and propranolol show a 27% reduction in recurrent MI over a two-year period, if beta-blockers are started at the time of AMI and continued on an oral basis thereafter. Beta-blockers are useful for suppressing silent myocardial ischemia, they have a modest anti-arrhythmic effect, and when used carefully, especially, in low doses with incremental titration, also appear to be beneficial in heart failure and may prevent adverse remodeling of the left ventricle, as well as improve survival. Beta-blockers improve survival post-MI especially in patients with large MIs and LV dysfunction, but the mechanism for these salutary effects has not been established.
Two recent studies from Yale and the University of Maryland have again demonstrated the value of beta-blockers after MI. The Yale study evaluated more than 45,000 cases of AMI in patients 65 years of age or older. In this retrospective cohort study, half of the patients were given a beta-blocker at discharge. Beta-blocker use was associated with a 14% lower risk of mortality at one year post discharge. The Maryland study was also a retrospective study of more than 200,000 patients with MI. Thirty-four percent of these patients were given beta-blockers, and various subgroups were analyzed, including those with CHF, COPD, renal insufficiency, and diabetes. Mortality was lower in every subgroup of patients treated with beta-blockers compared with untreated patients. In otherwise healthy patients with no complications or comorbid conditions, mortality was reduced by 40% in the beta-blocker group. Both studies concluded that beta-blockers are underused post MI, especially in the elderly and in subgroups of patients who might not be considered candidates for beta blockade because of pre-existing conditions.
It is possible that the beta-blocker carvedilol, a non-selective beta-blocker with alpha-one mediated vasodilator properties as well as antioxidant activity, may play an important role not only for its approved indications (i.e., for hypertension and mild CHF) but also as a post-MI cardioprotective agent. A British study evaluated the role of carvedilol in AMI, in which the drug was intravenously administered to patients, after which subjects were converted to oral therapy. The six-month end points consisted of all major cardiovascular events. Results of the study demonstrated a significant (42%) reduction in serious cardiac events in the carvedilol group. Of the 30% of patients who had an EF less than 30% associated with their MI, at three months the group randomized to carvedilol treatment had a smaller chamber size, a trend toward increased EF, and improved wall motion score. Adverse cardiac events, including reinfarction, unstable angina, and need for urgent revascularization, were also reduced in this group, confirming that not only did post-MI patients with CHF on carvedilol not suffer adverse events from the drug but also achieved a significant remodeling benefit.
Of special note is the fact that about two-thirds of these MI patients received thrombolytic therapy, suggesting, but not proving conclusively, that improved survival benefits with beta-blockers such as carvedilol extend to patients who undergo clot lysis. Further studies are likely to be forthcoming. However, it appears as if carvedilol is safe to use after AMI with or without associated heart failure. But whether this agent is different than other beta-blockers with established track records in long-term cardio-protection cannot be answered from this small trial. Moreover, whether the remodeling benefits demonstrated in this study can be extended to other beta-blockers cannot be answered at the present time. Although the jury remains out on whether, or to what degree, carvedilol may be safer and more effective than other beta-blockers, it does appear to be an appropriate addition to the cardioprotective cocktail for patients with MI and associated heart failure.
Beta-blockers exert their salutary effects on CHF by inhibiting the neurohormonal cascade as mediated by the sympathetic nervous system and the renin-angiotensin-aldosterone system.20 Cardiac adrenergic drive, a catecholaminergic state that has a direct depressant effect on cardiac myocytes, is increased in the failing myocardium, which leads to significant progression of left ventricular dysfunction.12,39
A plethora of well-designed, randomized studies have shown that beta-blockers not only improve symptoms of CHF, they improve left ventricular function and reverse altered hemodynamics. Long-term treatment of heart failure with beta-blockers can produce significant benefits.40,41 In more than 20 studies evaluating more than 10,000 patients using beta-blockers in the setting of CHF, beta-blockers have been shown to increase EF and decrease the combined risk of death and hospitalization of CHF. Patients with class II-III heart failure of ischemic etiology on beta-blockers have been found to have an approximately 38% reduction in all-cause mortality, accompanied by a reduction of severity of symptoms linked to heart failure.3,12 One meta-analysis demonstrated a 30% reduction in the mortality rate in patients on beta-blockers.40
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II) confirmed significant clinical benefits using the beta blocker, bisoprolol (a beta-1 selective adrenoceptor blocker) in patients with stable heart failure patients (class II & III) who did not have clinical evidence of severe class IV symptoms and recent instability. The CIBIS-II study showed a 32% reduction in all-cause mortality, a 45% reduction in sudden death, a 30% reduction in hospitalization for CHF, and a 15% reduction in all-cause hospitalization.42 The Metoprolol in Dilated Cardiomyopathy (MDC) Trial , the first major placebo-controlled trial of a beta-blocker in heart failure, showed a 34% reduction in mortality. A three-year follow-up of the MDC trial continues to show a significant reduction in mortality.43
Future trials currently in progress are investigating what type of beta blocker (i.e., selective, non-selective, or vasodilating) will show the most significant effect in CHF, or whether clinical outcomes are equivalent. These trials include the Carvedilol or Metoprolol European Trial (COMET) and CIBIS-II. The COMET will compare the effects of carvedilol vs. metoprolol on all-cause mortality.44 Currently, carvedilol, a beta 1, 2 and alpha 1-adrenergic antagonist and a vasodilator, is the only approved beta-blocker for treatment of CHF, although there are ongoing trials designed to evaluate such beta-blockers as metoprolol and bucindolol.45 Carvedilol, in particular, has been shown to increase both left and right ventricular function in patients with systolic dysfunction.46 Two trials, the PRECISE (Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise) and the MOCHA (Multicenter Oral Carvedilol Heart Failure Assessment study) trials have shown that beta-blocker therapy with carvedilol in patients with heart failure significantly reduces the risk of death and of hospitalizations.7,12,16
The PRECISE trial evaluated 278 patients with ischemic or nonischemic cardiomyopathy. Patients were randomized to placebo or carvedilol at a dose of 50-100 mg/d, which was added to diuretic and other therapies. In this study, carvedilol produced a 39% reduction in combined risk of death or all cause hospitalization and a 46% reduction in risk of hospitalization for CHF and other cardiovascular reasons.12,47
As a rule, beta-blockers should not be used in the setting of acute pulmonary edema or decompensated heart failure, because there is a risk of inducing rapid deterioration. Concern that beta-blockers may lead to acute deterioration in patients with significantly depressed EFs has been a deterrent to their routine use in the ED in the setting of CHF. Accordingly, they are currently contraindicated in patients with hypervolemia and significant clinical signs of decompensation because of their negative inotropic effect. Typically, beta-blockers are most prudently initiated in the hemodynamically stable patient who has been deemed euvolemic and at low risk of decompensation.
It should be stressed that clinical trials evaluating beta-blockers have been performed only in stable patients, excluding patients with brittle or acute, severe CHF. Moreover, because ACE inhbitors constitute primary therapy for treatment of CHF, beta-blockers should be considered add-on or adjunctive therapy in patients already being treated with ACE inhibitors. In summary, more data is needed before this class can be recommended for routine use in patients with any significant degree of deterioration.12 The COPERNICUS trial, the results of which will not be available until 2001, will evaluate the use of beta-blockers in this patient group. At present, in the ED, beta-blockers should not be used in the patient with decompensated CHF (stage IV NYHA functional class) inasmuch as there is no evidence to support their use in this unstable patient population.
Beta-blockers can be used safely in patients with stable, CHF and these agents do not prevent patients from deriving benefit from physical training.48 Most patients with class II-III CHF should be started on a beta-blocker unless they are unable to tolerate it or have the appearance of side effects. Side effects include hypotension and fluid retention, as well as worsening heart failure, bradycardia, and heart block. Patients with asthma, underlying heart block, or bradycardia should not receive beta-blocker therapy.12 As with most medication classes, beta-blockers should be started at very low doses and titrated up. Carvedilol, one of the drugs approved for use in heart failure, is generally started at 3.125 mg bid and titrated up slowly over weeks to 6.25 mg bid, 12.5 mg bid, 25 mg bid, and so forth. Diuretics may need to be titrated if decompensation and congestive symptoms increase before beta-blocker therapy is stabilized at a steady dose. (See Tables 3 and 4.)
| Table 3. Carvedilol, Metoprolol, and Bisoprolol—Dosages and Side Effects |
Carvedilol—start at 3.125 mg bid and titrate up slowly, reduce or discontinue if patient decompensates Metoprolol—start at 12.5 mg bid Bisoprolol—start at 1.25 mg qdCaution should be exercised in patients with clinical decompensation until further data are available. Do not start beta-blocker therapy unless patient is near euvolemic. ______________________________________________________________ |
| Table 4. Beta-Blockers’ Effect on CHF— Mortality Benefit39,60 |
| • Increase ejection fraction
• Decrease all-cause mortality • Decrease mortality secondary to heart failure • Prevent fatal arrhythmias • Prevent ischemia _____________________________________________________ |
ACE Inhibitors. ACE inhibitors (ACEIs) continue to be workhorse drugs for management of CHF. These agents exert their clinical effects by inhibiting the enzyme responsible for the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor.12 As a general rule, all patients with CHF should be prescribed an ACEI unless this class is contraindicated in the patient or the drug is poorly tolerated. Elderly patients with CHF not treated with an ACEI have an increased mortality rate compared to those on placebo.4
Numerous trials, including the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), the Veteran’s Administration Cooperative Vasodilator-Heart Failure Trial (V-HeFT I), the Studies of Left Ventricular Dysfunction (SOLVD), and the Survival and Ventricular Enlargement Trial (SAVE), have confirmed that ACEIs significantly reduce morbidity and mortality in CHF.51 The Randomized Evaluation of Strategies for Left Ventricular Dysfunction Study (RESOLVD) is a trial evaluating the combination neurohormonal blockade regimen using an angiotensin II antagonist (eandesartan), an ACEI (enalapril), and a beta-blocker (metoprolol) in patients with heart failure. Although results from this study are not currently available, they will be used to design a large scale mortality trial and will aid in the understanding of the importance of neurohormonal blockade in CHF.52,53
Several studies are also in progress that will investigate the use of ACEIs in the progression of atherosclerotic disease. They include the Heart Outcome Prevention Evaluation (HOPE), the Study of Evaluate Carotid Ultrasound with Ramipril and Vitamin E (SECURE), the Quinapril Ischemic Event Trial (QUIET), and the Simvastatin and Enalapril Coronary Atherosclerosis Trial (SCAT).
Not only do ACEIs help improve symptoms of CHF, including fatigue and improving exercise tolerance, they also significantly decrease morbidity and mortality associated with the post-infarction state.50 Several trials have confirmed the benefit of ACEIs in patients who have sustained a MI. In addition, however, ACEI therapy is associated with improved left ventricular function in patients sustaining myocardial damage during infarction and numerous studies have shown that ACEIs confer a substantial survival benefit to patients with CHF following MI.54 The Survival and Ventricular Enlargement (SAVE) trial randomized 2231 patients with a recent MI and EF less than 40% to placebo vs. captopril (target dose 150 mg/d). Treatment with the ACEI decreased mortality by 19% and subsequent risk of developing moderate to severe heart failure by 22%. Other studies that have shown similar benefits with ACEI therapy in CHF include the Acute Infarction Ramipril Efficacy (AIRE) trial, the Trandolapril Cardiac Evaluation (TRACE) study, Studies of Left Ventricular Dysfunction (SOLVD) trial, and Fosinopril in Acute Myocardial Infarction Study (FAMIS). In most trials evaluating ACEIs in heart failure, dyspnea is relieved and exercise tolerance is improved.12,55
It should be stressed that despite proven benefits, this class of drugs is commonly underprescribed, especially in the elderly population, and therefore, ED physicians evaluating patients with CHF in the ED should ensure that eligible patients have not been denied the benefits of ACEIs. Moreover, older patients may be on lower than optimal doses, which places them at a higher risk for future clinical deterioration.56 Some physicians are reluctant to use ACEIs because of their side effects, which include cough, worsening renal function, hyperkalemia, hypotension, and the risk of angioedema.50,15 These must be weighed against the potential benefits in the individual patient.
Currently, five ACEIs are approved for the use in patients with CHF: They include: captopril, enalapril, lisinopril, quinapril, and fosinopril. ACEIs should be started at a very low dose and titrated up gradually over several weeks to achieve clinical end points (i.e., relief of fatigue, shortness of breath, and weakness) while avoiding side effects. Renal function should be followed very carefully, especially during initial titration, to avoid precipitating hyperkalemia and/or renal insufficiency. Renal function should be checked within 1-2 weeks of initiating therapy. Close monitoring of renal function and electrolytes should occur on a regular basis. (See Table 5.)
| Table 5. ACE Inhibitors and Dosage |
| Drugs and dosages approved for treatment of heart failure |
| • Captopril (Capoten)—start 6.25-12.5 mg po tid, usual dose 50-100 mg tid
• Enalapril (Vasotec)—start 2.5 mg po qd/bid, usual 2.5-10 mg tid • Lisinopril (Prinivil, Zestril)—start 5 mg po qd, usual 5-20 mg/d • Quinapril (Accupril)—start 5 mg po bid, usual 20-40 mg/d • Fosinopril (Monopril)—start 10 mg po qd, usual 20-40 mg/d • Ramipril (Altace) approved for use post-infarction—start 2.5 mg po bid, usual 10 mg/d (BUN, Creatinine, and Potassium should be checked within 1-2 weeks starting therapy)
|
The Assessment of Treatment with Lisinopril and Survival (ATLAS) study established what dose (higher vs lower) of lisinopril, would be more beneficial in reducing hospitalization and mortality. Approximately 3500 patients from 287 centers in 19 different countries with class III and IV (and some hospitalized class II patients) heart failure were investigated. All-cause mortality and hospitalization was significantly lower in patients randomized to the higher dose of lisinopril. Importantly, there was no major difference in the side effect profile.15 This study, however, did not show dramatic difference in all-cause mortality, although it did demonstrate a decrease in death, all-cause hospitalizations, and hospitalizations for heart failure in patients taking the higher dose lisinopril. A similar study, the NETWORK study, which evaluated enalapril dosing, did not show a significant benefit of high vs. low-dose enalapril. It seems reasonable to prescribe the highest dose of an ACEI tolerable until long-term, randomized trial results are available.57 The ongoing ACHIEVE trial will investigate 10,500 patients with respect to high- vs. low-dose quinapril.
Even at target dosages, some patients will not respond as well, especially if they are taking NSAIDS or ASA. A subgroup analysis of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II study) found evidence to suggest a significant interaction of the between the ACEI, enalapril, with aspirin. In this study, the favorable hemodynamic effects of enalapril were much less pronounced in patients taking aspirin compared to patients not taking aspirin.58 Further ongoing studies are now being conducted to clarify this important issue.
The overall results from multiple trials suggest that emergency physicians should make every effort to use ACEIs at the dose proven in clinical trials unless impeded by side effects or poor patient tolerance. CHF readmission rates seem to be lower if patients are maintained on higher doses of ACEIs.59
References
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17. Kurrelmeyer, Karla, et al. Cardiac remodeling as a consequence and cause of progressive heart failure. Clin Cardiol 1998;21(supp I):I14-I19.
18. Colucci WS. The effects of norepinephrine on myocardial biology: Implications for therapy of heart failure. Clin Cardiol 1998;21(supp I):I20-I24.
19. Manolis, Olympios, et al. Combined sympathetic suppression and angiotensin-converting enzyme inhibition in congestive heart failure. Hypertension 1997;29:525-530.
20. Pepper, Lee. Sympathetic activation in heart failure and its treatment with beta blockade. Arch Intern Med 1999;159:225-234.
21. Mazayev, Fomina, Sulimov, et al. Valsartan in heart failure patients Previously untreated with an ACE inhibitor. Int J Cardiol 1998;65:239-246.
22. Levin. Evidence-based contemporary heart failure management. Resid Staff Physician 1999.
23. Bales, Sorrentino. Causes of congestive heart failure—Prompt diagnosis may affect prognosis. Postgrad Med 1997;101:44-49,54-56.
24. Stevenson LW, et al. Optimizing therapy for complex or refractory heart failure: A management algorithm. Am Heart J 1998;135:S293-S309.
25. Bennett, Huster, Baker, et al. Characterization of the precipitants of hospitalization for heart failure decompensation. Am J Crit Care 1998;7:168-174.
26. Aronow, Tresch. The clinical diagnosis of heart failure in older patients. J Am Geriatr Soc 1997;45:1252-1257.
27. Emmet. Nonspecific and atypical presentation of disease in the older patient. Geriatrics 1998;53:50-60.
28. Minezaki, Okubo, Kamiishi, et al. Ileus, A clinical sign of congestive heart failure. J Am Geriatr Soc 1999;47:258-259.
29. Al-Khadra, Salem, et al. Antiplatelet agents and survival: A cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) Trial. J Am Coll Cardiol 1998;31:419-425.
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31. Aronow, Ahn. Association of electrocardiographic left ventricular hypertrophy with the incidence of new congestive heart failure. J Am Geriatr Soc 1998;46:1280-1281.
32. Wood, Lewis, Von Harz, et al. The use of noninvasive positive pressure ventilation in the emergency department: Results of a randomized clinical trail. Chest 1998;113:1139-1346.
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34. Kelly, Georgakas, Bau, et al. Experience with the Use of Continuous Positive Airway Pressure (CPAP) therapy in the emergency management of acute severe cardiogenic pulmonary edema. Aust N Z J Med 1997;27: 319-322.
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38. Koelling, Kirmse, Di Salvo, et al. Inhaled nitric oxide improves exercise capacity in patients with severe heart failure and right ventricular dysfunction. Am J Cardiol 1998;81:1494-1497.
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48. Demopoulos, Yeh, et al. Nonselective beta-adrenergic blockade with carvedilol does not hinder the benefits of exercise training in patients with congestive heart failure. Circulation 1997;95:1764-1767.
49. O’Connor, Carson, Miller, et al. Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Am J Cardiol 1998;82:881-887.
50. Rich, Brooks, et al. Temporal trends in pharmacotherapy for congestive heart failure at an academic medical center. Am Heart J 1998;135:367-372.
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Physician CME Questions
Data from large clinical trials indicate that patients with CHF have a five-year mortality rate of:
A. approximately 50%.
B. 25%.
C. 10%.
D. 75%.
It is estimated that approximately 75% of patients with heart failure are:
A. 80 years of age or older.
B. older than ages 65-70.
C. in the 55-60 year age group.
D. none of the above.
The most common causes of of CHF encountered by the emergency physician include:
A. hypertension.
B. alcoholic cardiomyopathy.
C. coronary artery disease.
D. all of the above.
Specific disease states that induce diastolic heart failure include:
A. infiltrative myocardial disease.
B. pericardial disease.
C. hypertrophic cardiomyopathy.
D. coronary ischemia.
E. all of the above.
What diagnosis should be considered in a patient who presents with tachycardia, is hypertensive, and has no previous history of heart failure?
A. Hypothyroidism
B. Upper respiratory tract infection.
C. Thyrotoxicosis
D. None of the above.
Which of the following is not a sensitive indicator for heart failure?
A. Cardiac monitor
B. Physical findings
C. 12-lead EKG
D. Chest x-ray.
A study indicated that what percent of eligible patients currently enrolled in managed care plans were receiving beta-blockers following their MI?
A. 35-65%
B. 15%
C. 80-90%
D. 5%
In the PRECISE study, carvedilol produced what percent reduction in combined risk of death or all-cause hospitalization?
A. 12%
B. 58%
C. 76%
D. 39%
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