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 II: Targeted Drug Therapy, Invasive Interventions, and Patient Disposition
Authors: Rob Rogers, MD, Department of Medicine/Division of Emergency Medicine, University of Maryland Hospital, Baltimore, MD; David J. Robinson, MD, MS, Director of Research, Division of Emergency Medicine, The University of Maryland 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.
As every emergency physician knows, congestive heart failure (CHF) is characterized by an extraordinary range of clinical presentations. Moreover, few conditions present with a more unstable triad of hemodynamic, respiratory, and metabolic parameters. In some cases, patients are very ill, unstable, and, frequently, are teetering on the cusp of precipitous clinical deterioration. In contrast, another subgroup may present with little more than mild dyspnea, fatigue, and limitations in physical exertion. Managing each of these populations requires a customized approach that can range from evaluation, titration, or addition of oral medication(s) used to improve cardiac function and CHF symptoms to, in cases of acute pulmonary edema, heat-of-battle, life-saving interventions with intravenous diuretics, morphine, oxygen, endotracheal intubation, and myocardial pump support.
Because of the diversity of presentations and the multiplicity of treatment and triage options in CHF, the emergency physician is faced with the challenge of managing some patients using a primary care model (i.e., making medication adjustments and evaluating suitability of the chronic treatment plan) and others from the perspective of an intensivist. Providing such a broad range of clinical services for a disease state as complicated as CHF is difficult at best, especially when the emergency department (ED) physician is seeing only a clinical snapshot of the patient at any point in time.
Complicating evaluation, stabilization, and disposition of patients with CHF is the fact that these individuals tend to be on complicated drug regimens—that may include digoxin, ACE inhibitors, diuretics, and beta-blockers—and, therefore, a thorough understanding of drug interactions, evidence-based trials, and drug-based treatment strategies for CHF is essential. The ED physician can play a critical role in improving outcomes by making refinements in the patient’s chronic drug regimen, and, especially, recognizing undertreatment in patients with CHF.
Part I of this two-part series outlined a systematic approach for evaluating and stabilizing patients with CHF. The authors emphasized the importance of identifying treatable conditions leading to left ventricular dysfunction, performing a detailed medication review to ensure that patients were receiving optimal therapy, and using adjunctive measures, when indicated, to stabilize respiratory status. In addition, the extensive differential diagnosis of CHF, which includes a diverse range of precipitating factors from acute myocardial infarction and drug-induced suppression of myocardial pump function to valvular insufficiency and inadequate medication therapy, requires the emergency physician to interpret an extended laboratory and radiographic data base in order to pinpoint inciting factors.
In this concluding part of our two-part series, the authors continue to focus on drug-based strategies for both chronic and acute management of CHF, including life-threatening manifestations such as pulmonary edema and cardiogenic shock. The role of revascularization, pump support, and inotropic enhancement is discussed in detail, with a special emphasis on improving outcomes through multi-modal interventions.
—The Editor
Drug Therapy for CHF: Acute vs. Chronic Interventions
Successful management of the patient who presents to the ED with CHF requires careful evaluation of the patient’s acute clinical status, prediction of the patient’s propensity for clinical deterioration, and meticulous management of the oral drug regimen. In the setting of severe, acute CHF, pharmacologic management in the ED will focus on maintaining oxygenation (with oxygen and airway control), normalizing blood pressure, and, usually, appropriate reduction of preload and afterload with such agents as diuretics and drugs that decrease peripheral vascular resistance. Other interventions may also be required.
In patients considered safe for discharge after ED evaluation and stabilization, the approach is markedly different. The ED physician will be required to review the medication regimen and determine whether CHF-ameliorating agents such as ACE inhibitors (ACEIs), beta-blockers, angiotensin II receptor blockers, oral diuretics, and/or digoxin require modification in dose, or whether some drugs should be deleted or added. Even if the patient with mild-to-moderate CHF is stabilized in the ED, the best clinical outcomes result when the patient’s current drug regimen, in consultation with the primary care physician or cardiologist, is refined to maximize the benefits of drug therapy.
Angiotensin II Receptor Blockers (ARBs). Although angiotensin II receptor blockers (ARBs) currently do not carry formal FDA approval for treatment of CHF, these drugs have been studied for their therapeutic efficacy in CHF, and clinicians concur that they are especially useful in patients intolerant to ACEIs. Angiotensin II, a potent vasoconstrictor, has been implicated as an important mediator of increased afterload in patients with heart failure.1 In addition, angiotensin II stimulates release of aldosterone, which increases salt and water retention and has growth-promoting effects in the myocardium and arterial wall. ARBs inhibit most of the effects of angiotensin II, whereas inhibition of the conversion of angiotensin I to angiotension II does not produce complete angiotensin II blockade, in large part, because angiotensin II still can be formed by other pathways during ACE inhibition. (See Table 1.)
| Table 1. Angiotensin II Receptor Antagonist5 |
| • Consider using in patients intolerant to ACEI
• Should not be a substitute in patients who have not been treated with ACEIs • Currently, these agents are not approved by the FDA for therapeutic use in CHF ______________________________________________________________ |
The Evaluation of Losartan in the Elderly (ELITE) trial evaluated 722 patients with class II-IV heart failure. Patients were randomized to receive losartan or captopril for 48 weeks. Rates of hospital admission for heart failure were the same in both groups; however, significantly fewer patients discontinued therapy due to side effects.2 A larger study, the ELITE II study, is in progress to compare effects on morbidity and mortality with losartan vs. captopril.
The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial studied 768 patients with either ischemic or nonischemic dilated cardiomyopathy and mild-to-moderate heart failure.3 Patients were randomized to candesartan (up to 16 mg/d), enalapril (up to 20 mg/d), or both in combination added to conventional therapy, such as digoxin and diuretics. At the midpoint of the trial, patients were randomly assigned to metoprolol or placebo. In the first phase of the trial, no significant differences were found among the three treatments, suggesting, on a preliminary basis, that ARBs are as effective as ACEIs in managing patients with mild-to-moderate CHF.
At present, despite studies supporting its efficacy in managing mild-to-moderate CHF, ARBs, which are widely used and approved for treatment of high blood pressure, do not carry FDA approval for therapeutic use in patients with CHF. Consequently, this class of drugs has been positioned by many practitioners as a substitute for or alternative therapy in patients with CHF who are intolerant of ACEIs. Additional trials, including ELITE II, valsartan-HeFT, and the CHARM trial, are underway to study the benefits of using this class of medications in heart failure. Preliminary studies report that valsartan is generally well-tolerated and effective for this condition.4
As a general rule, ARBs should be used as initial agents for treatment of CHF only in patients who are intolerant to ACEIs because of cough or angioedema, and who require angiotensin II suppression as part of their CHF treatment plan. Typically, they are not to be used as the initial class of choice in patients who have not had a previous trial with ACEIs, or in patients who are tolerating ACEIs without side effects.5 Reserving ARBs as back-up therapy, however, is subject to clinical judgment and may change with reports from ongoing trials and labeling changes regarding ARBs.
In fact, some trials are beginning to suggest additional benefits from combined use of ACEIs and ARBs. For example, the addition of the angiotensin II receptor blocker, losartan, to existing ACEI therapy appears to produce additional decreases in afterload with few side effects.6 The Randomized Angiotensin Receptor Antagonist-Angiotensin-Converting Enzyme Inhibitor Study (RAAS) currently in progress will examine the possible advantages of combining an ACEI with an ARB. Another investigation, the Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan (OPTIMAAL) trial, is an ongoing multicenter, double-blinded, randomized, parallel, captopril-controlled trial investigating the use of losartan in patients sustaining a myocardial infarction.7,8
Spironolactone (Aldactone). In the past few years, there has been renewed interest in the aldosterone antagonist, spironolactone. Currently, it is thought that patients may not achieve maximal suppression by taking ACEIs or ARBs and that the addition of spironolactone may contribute additional aldosterone suppression that may be useful in CHF management. Aldosterone not only promotes potassium loss, it also causes ventricular fibrosis and sodium retention, and it is speculated that by using an aldosterone antagonist such as spironolactone, sodium retention and myocardial fibrosis may be decreased.
To examine these issues, the RALES study evaluated the use of spironolactone in patients with CHF. Focusing primarily on all-cause mortality, the study enrolled 1600 patients with class III-IV heart failure who were already on ACEIs and diuretics and then had spironolactone added to their regimen. The study was terminated prematurely after demonstrating a significant benefit in the aldactone arm of the study.5 It should be stressed that hyperkalemia can occur with spironolactone, and this adverse consequence of drug therapy is more likely to occur in patients already taking ACEIs. Based on this study, spironolactone is reserved primarily as adjunctive therapy in patients with stage IV heart failure; additional trials are needed to clarify its effectiveness for class II-III failure. Although spironolactone is not formally approved for use in heart failure, it can be used in selected patients, especially those who are refractory to other therapies.
Calcium Channel Blockers. Calcium channel blockers (CCBs) induce arterial dilatation in the coronary and systemic vascular beds. The rationale for using these agents in CHF has been to improve cardiac performance by decreasing myocardial ischemia and afterload. The role of CCBs in CHF has undergone intensified investigation over the past decade. Numerous CCBs have been studied in this regard, among them verapamil (Calan, Covera, Isoptin), diltiazem (Cardizem, Dilacor, Tiazac), and nifedipine (Adalat, Procardia XL). Newer agents, including amlodipine (Norvase) and felodipine (Plendil), also have been evaluated in recent clinical trials. Although small, clinically significant benefits have been demonstrated in several randomized trials, CCBs do not carry formal approval for use as therapeutic agents to improve symptoms or outcomes in patients with CHF.5
In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE-1), 1153 patients with class III-IV ischemic or nonischemic cardiomyopathy were randomized to placebo vs. amlodipine (up to 10 mg/d), which was added to conventional therapy. Amlodipine had no effect on the combined risk of death and hospitalization for cardiovascular events. Amlodipine did, however, decrease all-cause mortality, and it was found to lower the risk of death by 45% in patients with nonischemic cardiomyopathy; it had no adverse outcome on survival. This benefit was found only in the nonischemic myocardiopathic subgroup of the study. More data will need to be generated before a firm conclusion can be reached.9
What is known is that amlodipine is safe for use in patients with CHF who require CCB treatment for such other indications as hypertension or angina, especially when beta-blockers or nitrates have not been effective.10 The possible benefits of amlodipine in patients with non-ischemic CHF currently is being evaluated in the PRAISE-2 Trial, which should shed more conclusive evidence on the value of adding amlodipine to triple drug therapy (ACEIs, digoxin, and diuretics) in patients whose LV dysfunction is non-ischemic in nature. Currently, however, amlodipine appears as if it can be used safely in patients with all stages of CHF, if they require calcium blocker therapy for clinical reasons.11 (See Table 2.)
| Table 2. Calcium Channel Blockers with Available, Long-Term Safety Data |
| (not indicated for treatment of CHF)
• Amlodipine—start at 2.5 mg/d and titrate to 10 mg/d over weeks to months
|
Felodipine, another dihydropyridine, has been evaluated in patients with stable Class II-III heart failure, but not Class IV. Felodipine was evaluated in the third Vasodilator Heart Failure Trial (V-HeFT III). In this trial, 450 patients with mild-to-moderate ischemic or nonischemic cardiomyopathy were randomized to sustained-release felodipine (10 mg/d) vs. placebo. Each was added to conventional therapy. Felodipine had no effect on exercise tolerance or all-cause mortality.12 An absence of deleterious effects with CCB therapy also was shown in the Survival and Ventricular Enlargement Trial (SAVE), in which the incidence of all-cause mortality, cardiovascular death, severe heart failure, and recurrent myocardial infarction was evaluated in 940 patients taking CCBs and 1180 patients not taking CCBs 24 hours before randomization to placebo vs. captopril. The use of CCB in this study did not lead to clinical deterioration or improvement with respect to further cardiac events.13
Of the clinically available CCBs, only amlodipine and felodipine have long-term safety trials to support their permissive, but not therapeutic, use in patients with CHF. There is substantial evidence that they do not adversely affect outcome in patients with CHF. Based on labeling and clinical trials, amlodipine is the preferred CCB because it has been evaluated for safe use in all classes of CHF, including NYHA functional class IV, whereas felodipine has not. (See Table 2.) The results of further studies such as PRAISE-2 are needed to clarify whether CCBs will become part of the armamentarium for treatment of heart failure.
Digoxin. Digitalis has remained an adjunct for the treatment of chronic CHF for more than 200 years and remains one of the most commonly prescribed drugs in the world. Despite its widespread use for treating patients with CHF, there are no conclusive data confirming its ability to reduce mortality and prolong life in patients with CHF. To clarify this issues, The National Heart, Lung, and Blood Institute, in conjunction with The Department of Veteran’s Affairs, conducted a large clinical trial—the Digitalis Investigation Group (DIG) study—to investigate the benefits of digoxin in heart failure.
The DIG study was a randomized, double-blinded, collaborative, international trial of approximately 8,000 patients with CHF. The largest portion of the trial involved 6,800 patients with class I-IV heart failure with an ejection fraction (EF) less than 45%; 84% of the patients had class II and III heart failure. The primary end point was mortality, with the secondary end points including death from cardiovascular causes, death from worsening heart failure, hospitalization for worsening heart failure, and hospitalization for other causes. Ninety-five percent of the patients were taking an ACEI, 82% were being treated with diuretics, and 44% had been treated previously with digoxin. Patients were randomly assigned to placebo or digoxin and were followed for two years.
Importantly, digoxin had no effect on all-cause mortality, which was 35% for both groups. However, digoxin did reduce the risk of hospitalization over the study period; specifically, patients receiving digoxin had a 26.8% chance of hospitalization whereas patients taking placebo had a 34.7% chance of hospitalization.14 These salutary effects related to reduced hospitalization rates are significant, but because digoxin did not demonstrate improved survival rates in CHF (as do ACEIs), this agent should not be used as exclusive, first-line treatment for CHF. It may be added to a regimen of ACEIs and diuretics if symptoms of heart failure persist despite treatment with these agents, and it may be considered early in the natural history of atrial fibrillation, especially when ventricular rate control is required in the setting of CHF or left atrial enlargement secondary to increased left ventricular end diastolic pressures.
Although life prolongation and mortality-reduction data is lacking, patients with severe CHF may derive unique benefits from digoxin because studies do show this agent can increase exercise tolerance, improve symptoms of CHF, and decrease the risk of hospitalization. The importance of these clinical benefits should not be underestimated. However, digoxin should be used with caution in patients with renal insufficiency and in patients currently taking amiodarone. In addition, digoxin levels should be measured in all patients presenting to the ED with cardiac symptoms, rhythm abnormalities, deterioration in CHF, or unexplained clinical findings suggestive of possible drug toxicity.
Data from two other trials, the Randomized Assessment of Digoxin on Inhibitors of the Angiotensin-Converting Enzyme (RADIANCE) trial and the Prospective Randomized Study of Ventricular Failure and the Efficacy of Digoxin (PROVED) trial, also suggest benefits from chronic digoxin therapy in patients with class III-IV heart failure and increased heart size on chest x-ray.15 Once again, however, it should be stressed that digoxin’s primary role consists of add-on therapy to patients already on ACEIs and diuretics who require additional symptomatic relief, improvements in left ventricular function, or quality-of-life (i.e., functional class upgrades) enhancement in the setting of moderate-to-advanced heart failure. (See Table 3.) In this patient population, during consultation with the patient, the emergency physician may need to reinforce a preexisting regimen containing ACEIs and diuretic with the addition of digoxin to the regimen.
| Table 3. Digoxin Dosing |
| • Start at 0.125 mg/d if renal function impaired. May need qod dosing.
• 0.250 mg/d with near normal renal function • Careful dosing in the elderly, impaired renal function, and patients taking Amiodarone (may need dose reduction) • Toxicity exacerbated by hypokalemia. • Frequent drug levels. _________________________________________________________ |
Diuretics. In the setting of CHF, diuretics induce peripheral vasodilation, reduce cardiac filling pressures, and prevent fluid retention.16,17 Diuretics have been proven to be useful for symptomatic improvement in patients with heart failure, especially in those individuals with evidence of congestion, including dyspnea on exertion, edema, and orthopnea. In severe CHF, the most commonly used agents are loop diuretics, including furosemide (Lasix), torsemide (Demadex), and bumetanide (Bumex). In mild-to-moderate CHF, hydrochlorothiazide diuretics continue to play a pivotal role in symptom control. Furosemide is used most often for treatment of acute exacerbations and long-term maintenance therapy in patients with severely compromised left ventricular dysfunction. As a general rule, diuretics should be prescribed for the overwhelming majority of patients with heart failure who have symptoms of volume overload. Typically, these agents should be used in conjunction with ACEIs, which, unlike diuretics, prolong long-term survival in the patient with CHF.
Diuretics are effective for controlling edema and volume overload symptoms,18 and, therefore, addition of these agents to a chronic regimen may be required in the ED in patients with worsening CHF symptoms. As such, the main goal of diuretic therapy is to alleviate signs and symptoms of fluid overload, which are assessed clinically by evaluating patients for the presence of jugular venous distension and peripheral edema. Therapy with diuretics should be continued until these signs and symptoms are well controlled. In patients with severe LV pump dysfunction, alleviation of fluid overload, pulmonary congestion, and edema may require aggressive diuretic therapy, even to the point of producing pre-renal azotemia, with significantly elevated BUN and creatinine levels. As long as the patient is asymptomatic and diuresis is controlling symptoms of overload, some degree of prerenal azotemia is permissible.5
Diuretic therapy can be titrated until there is evidence of orthostatic hypotension, acceptable azotemia, and/or reduction of jugular venous distension.15 (See Table 4.) Potential side effects of administration of diuretics may include: a) electrolyte abnormalities, especially potassium depletion, which may be a more pronounced loss if more than one diuretic is necessary for control (follow electrolytes vigilantly in patients on digoxin therapy); b) activation of the neurohormonal cascade, which is known to be deleterious in patients with heart failure; and c) pre-renal azotemia and hypotension, which are usually secondary to overdiuresis or progression of heart failure associated with decreased renal perfusion. This may produce a contraction alkalosis, accompanied by hypokalemia, and elevated serum bicarbonate concentration.
| Table 4. Diuretic Therapy in Congestive Heart Failure |
| Loop Diuretics |
• Furosemide (Lasix)—20-200 mg daily or bid |
| Long-acting Thiazide Diuretics |
• Metalazone 2.5-10.0 mg qd bid_____________________________________________ |
Although many controlled trials have been performed to evaluate the benefits of diuretic therapy in patients with CHF, none has conclusively shown long-term morbidity and mortality advantages. Therapy is generally initiated with a once-daily dose of a loop or thiazide diuretic, beginning at lower doses and titrating until signs and symptoms of volume overload are controlled.19 In some patients, a second diuretic agent with a second site of action (e.g., a proximal tubule diuretic [thiazide] may be added to a loop [furosemide] diuretic, or a distal tubule diuretic [spironolactone] may be added to a loop or proximal tuble agent) may be added to provide better diuresis. This strategy may be necessary in patients with a decreased glomerular filtration rate and who, therefore, have decreased delivery of loop diuretics to their site of action.20
It should be stressed that resistance to diuresis may also be seen in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs).5 In fact, worsening symptoms of CHF, increasing peripheral edema, poorly controlled hypertension, azotemia, and/or hyperkalemia may be seen as a consequence of NSAID therapy in patients with CHF; these findings may require discontinuation of NSAID therapy. Some patients with relatively resistant edema may require twice daily dosing of their diuretic. When daily doses of furosemide exceed 80 mg, a bid dosing schedule can be used. Diuretic therapy should be accompanied by a dietary program characterized by avoidance of excessive sodium intake. Potassium levels and renal function should be measured frequently in patients taking diuretics to avoid precipitating renal insufficiency and hypokalemia-mediated cardiac arryhthymias.19
Hydralazine and Isordil. Combination treatment with hydralazine and Isordil has remained an attractive alternative for afterload reduction, especially in patients intolerant to conventional afterload reduction with ACEIs. This combination of drugs should not be used in the treatment of heart failure in patients who have not first been given a trial with ACEIs. Although there is currently little evidence to support the use of either drug alone as therapy for CHF, two large trials have evaluated the long-term effects of combination hydralazine and Isordil. (See Table 5.)
| Table 5. Recommended Dosages of Hydralazine and Isordil |
| • Hydralazine—start at 10 mg po qid, target dose 75-100 mg/d, max 300 mg/d
• Isordil—start 10 mg po tid, target 40 mg tid (Recommended is a nitrate free interval pm-am)
|
In the first trial, the Vasodilator Heart Failure Trial (V-HeFT I), combination hydralazine and Isordil significantly improved EF and decreased mortality by 25-30% compared to prazosin. In the second trial, V-HeFT II, the vasodilator combination increased EF and exercise tolerance more than did the ACEI, enalapril. In other studies, combination therapy has been shown in some studies to work as well as ACE inhibition. There is no data showing additional benefits that may accrue from adding combination therapy to patients already on an ACEI or beta-blocker.5,10
Inotropic Support
Inotropic support of patients with CHF remains an important treatment option for patients with severe CHF, although its efficacy and safety in patients with class II-III heart failure is less well established. Parenterally administered positive inotropic therapy increases cardiac output and decreases symptoms of congestion. Despite the potential advantages of these agents in decompensated heart failure, some of these agents have been associated with an increased mortality rate in clinical trials, perhaps, in part, because inotropic agents are known to increase myocardial oxygen demand and may activate neurohormonal mechanisms.5
Parenteral inotropic agents can be administered continuously to patients admitted to the hospital with exacerbations of heart failure. These agents can be administered in the hospital or continuously at home with an infusion pump. Home inotropic therapy was shown in one study to reduce hospital admission length of stay and improve functional heart failure classes (I-IV).21 In some patients, positive inotropic therapy may be necessary as a therapeutic bridge to transplantation.22 Long-term outpatient use of positive inotropic agents has been discouraged due to reported increased mortality rates in some trials and lack of consensus on what agent should be used. For example, The Vesnarinone Evaluation of Survival Trial (VEST) found an increased mortality with the use of 60 mg/d of vesnarinone.15,23 Another trial evaluating intravenous dobutamine was terminated because of an increased mortality rate.
Two different types of positive inotropes have been advocated for use in congestive heart failure: beta-adrenergic agonists such as dobutamine and phosphodiesterase inhibitors such as milrinone.5 Both classes of agents work by increasing myocardial contractility. The American College of Cardiology and the American Heart Association recommend the use of dobutamine and milrinone for patients with refractory congestive heart failure requiring hospital admission or in patients with severe refractory heart failure at home. In other words, these drugs should only be used in patients who have failed to respond to maximal therapy with established and or/approved strategies such as ACEIs, diuretics, digoxin, and other agents.
When indicated, patients seen and admitted to the hospital through the ED can be started on these inotropic agents if their clinical condition has been refractory to other agents. It is recommended that dobutamine be started at a low dose (2-5 mcg/kg/min) to avoid arryhthymias, tachycardia, and exacerbation of myocardial ischemia. Milrinone may also be used; it should be started using a loading dose of 50 mcm/kg followed by a continuous infusion of 0.375-0.75 mcm/kg/min. Patients who respond to dobutamine may be transitioned to a chronic long-term basis at home.
In summary, there are few data demonstrating the safety and efficacy of using inotropic therapy in decompensated heart failure. The Outcome of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure trial (OPTIME CHF) is a multicenter, randomized, placebo-controlled trial that is ongoing and will evaluate patients with heart failure. Currently, recommendations of the American College of Cardiology and the American Heart Association are to administer inotropic agents only to patients with severe or refractory heart failure. Positive inotropic therapy should be used with caution in patients with coronary artery disease and ischemic cardiomyopathy.
Anticoagulation in CHF
Oral anticoagulation with warfarin (Coumadin) for managing patients with CHF is controversial. The argument for anticoagulation stems from the observation that patients with severely depressed left ventricular function (EF < 35%) appear to be at higher risk for thromboembolic events. In particular, there does appear to be a propensity to form thromboemboli following large anterior wall myocardial infarction that is accompanied by a severely depressed EF. Accordingly, some experts recommend warfarin anticoagulation in individuals who have sustained a large, anterior wall myocardial infarction (AWMI) and have documentation of low EF. It is known that patients who have sustained a large anterior myocardial infarction benefit from warfarin anticoagulation.24
The use of warfarin in the setting of CHF in the absence of a history of recent AWMI is much more controversial. It is speculated that patients with dilated cardiomyopathy and reduced EF are more prone to intracardiac thrombus and emboli because of dilated ventricular chambers, atrial fibrillation, and the presence of wall motion abnormalities.24,25 However, given that there are conflicting studies regarding the use of anticoagulation in congestive heart failure (dilated cardiomyopathy), it is unclear at this time which patients would best be served with warfarin vs. aspirin therapy.5
Several clinical trials in heart failure help shed some light on this difficult topic. In a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial, patients with left ventricular dysfunction who were on warfarin had improved survival and reduced mortality.26 However, patients in this study were not randomized to warfarin. An unexpected finding from this trial was that women were at a higher risk of thromboembolic events compared to men. Furthermore, a 10% reduction in EF in women was associated with an approximately 53% increased risk of thromboembolic disease. This effect was not observed in men.
The Survival and Ventricular Enlargement (SAVE) trial showed that patients with an EF less than 28% had a nearly two-fold increase in relative risk of stroke compared to patients with an EF greater than 28%. Based on data from the V-HeFT trials, there appears to be no difference in rate of thromboembolic event in patients with nonischemic cardiomyopathy compared to ischemic cardiomyopathy. The problem with these studies is that none corrects for well-known risks for thromboembolic disease, such as that seen with atrial fibrillation. The V-HeFT studies do not show a benefit of anticoagulation, while the SAVE trial had an 80% risk reduction of stroke in patients who received warfarin anticoagulation. Aspirin reduced the risk by 56%. It is important to note that anticoagulation therapy was not randomized or controlled. These trials consistently show a benefit of aspirin therapy in preventing thromboembolic disease in patients with dilated cardiomyopathy.26 Complications of anticoagulation therapy are obvious and include serious intracranial hemorrhage and gastrointestinal bleeding.
Based on these studies, it seems reasonable to initiate warfarin anticoagulation in patients who have severe CHF (EF < 30%) that is accompanied by atrial fibrillation, previous TIA or thromboembolic events, a history of a left ventricular thrombus, or recent AWMI. Unless this constellation of risk factors and clinical findings are present, it seems prudent to opt for daily aspirin therapy (325 mg/d), since studies show benefits using this agent. Patients who take warfarin for the triad of CHF, low EF, and post-anterior MI should be carefully followed in anticoagulation clinics. Such drugs as trimethoprim-sulfa and fluoroquinolones can interfere with warfarin metabolism and potentiate the effects of warfarin. In summary, additional studies are needed before warfarin can be recommended routinely for most patients with CHF.
Severe CHF and Acute Pulmonary Edema: Emergency Intervention
Because of the increasing prevalence of CHF, ED physicians can expect to encounter more and more patients with decompensated CHF, pulmonary edema, and cardiogenic shock.27 It is well documented that CHF can occur suddenly in patients as a consequence of acute coronary ischemia, myocardial infarction, arrhythmia, bacterial endocarditis, and, for a variety of reasons, in patients with chronically compensated heart failure.28 If pharmacologic measures are instituted early in the patient’s ED course, however, these usually are treatable conditions, and endotracheal intubation and other invasive procedures usually can be avoided. Moreover, early identification and aggressive management may prevent progression of mild, decompensated heart failure to overt pulmonary edema.
Etiology. Conditions that most commonly lead to the development of pulmonary edema (i.e., cardiogenic pulmonary edema) include myocardial ischemia, fluid excess and volume overload, medication noncompliance, arrhythmias such as atrial fibrillation, and hypertensive crisis. If myocardial infarction or ischemia is suspected, it is important to differentiate right ventricular from left ventricular dysfunction, because therapy for each entity is different. Left heart failure secondary to left ventricular ischemia or infarction may require aggressive diuresis and afterload reduction, whereas, right ventricular failure may require intravenous fluids to increase preload. Establishing whether the presentation is secondary to myocardial ischemia/infarction is a top priority since emergent reperfusion therapy, as well as other mortality-reducing interventions, may salvage myocardium and improve survival.29
Presentation. Typically, patients with pulmonary edema present in extremis with tachypnea, anxiety, shortness of breath, and diaphoresis, and may have classic "pink, frothy" sputum. Patients may also present with jugular venous distension, peripheral edema, hepatojugular reflex, and ascites. Many individuals with pulmonary edema will be hypertensive secondary to a hypercatacholaminergic state, or, alternatively, they may be hypotensive if cardiogenic shock is present. As with any other critical illness, airway management should always take precedence. This includes assuring adequate oxygenation and ventilation.
Medical Management. Management of the patient with pulmonary edema is complex and requires multi-modal drug therapy and frequent reassessments of the patient’s clinical status. Patients should be placed in the upright position, placed on a monitor and pulse oximeter, and supplemental oxygen should be administered. An arterial blood gas is essential for guiding respiratory management. A Foley catheter should be inserted to follow urinary output and response to diuretic therapy. Medical management will focus around four essential principles and strategies: 1) Oxygen administration and proper airway management; 2) diuresis; 3) preload reduction and; 4) afterload reduction. (See Tables 6 and 7.)
| Table 6. Treatment of Pulmonary Edema26 |
| • Oxygen therapy
• Nitroglycerin, IV or other route (can administer sublingual or spray while IV access being obtained) • Intravenous diuretic • Morphine sulfate • Cardiovascular support medications—including Dobutamine, Dopamine, Nitroprusside • Thrombolytic therapy or revascularization for AMI • Airway management—invasive and noninvasive • Correction of underlying etiology—valve repair, etc. ____________________________________________________________________________ |
| Table 7. Treatment Modalities of Acute Heart Failure/Pulmonary Edema, Medication Dosages |
| • Lasix 20-80 mg IV (patients already on outpatient dose may require more) or,
• Bumex 0.5-1 mg IV (1 mg of Bumex is roughly equivalent to 40 mg Lasix) or, • Demadex 5-20 mg IV • Tridil start at 10-20 mcg/min and titrate to BP (use with caution if inferior/right ventricular infarction suspected) • Sublingual Nitroglycerin 0.4 mg • Nitroglycerin Spray • Captopril: Captopril 25 mg SL, IV Vasotec (more studies needed before routine clinical practice) • Morphine Sulfate 2-4 mg IV. Avoid if inferior wall MI suspected or if hypotensive or presence of tenuous airway ______________________________________________________________________________________ |
Morphine. Anxiety and preload reduction can be accomplished by administering morphine sulfate at a dose of 2-4 mg IV, titrating up to 10 mg IV as required; blood pressure, mental status, and respiratory status should be monitored vigilantly. Morphine sulfate probably also decreases plasma catecholamine levels, thereby reducing afterload and decreasing risk of fatal arrhythmias. Blood pressure must be monitored carefully, especially in the setting of suspected inferior wall infarction, in patients with severely depressed left ventricular function, and in patients who have a tenuous airway or altered mental status.
Diuretics. Diuretics remain one of the most important and rapidly effective treatment modalities for management of cardiogenic pulmonary edema. Furosemide (Lasix), the most commonly used diuretic, also acts as a venodilator, which may have an additive effect in conjunction with other modalities that reduce preload. Furosemide produces rapid venodilation and, as a result, decreases left and right ventricular pressures.30 Depending on the patient’s clinical condition, state of hydration, and previous use of diuretics, an initial dose of 20-80 mg IV is administered. It should be stressed, however, that in patients with moderate to severe reduction in EF, only a small portion of the diuretic reaches its site of action in the renal tubules.20
Controversy in the literature continues over the relative efficacy of intravenous bolus furosemide vs. continuous infusion. One study found that continuous infusion was superior to bolus administration in patients with refractory congestive heart failure; however, other studies conclude that bolus furosemide is equally effective for achieving maximal diuresis.31,32
Nitroglycerin. Nitroglycerin remains a foundation of medical management. Some patients who present in acute pulmonary edema may require redistribution of, rather than reduction in, circulating volume, and this is rapidly accomplished with nitrates.33 As a general rule, nitroglycerin is administered in sublingual, spray, paste, or intravenous form. The sublingual or spray route of administration may suffice while venous access is being obtained. Once intravascular access is established, intravenous nitroglycerin (Tridil) is the preferred route of administration for lowering preload and increasing venous capacitance.
Nitroglycerin should be administered as an initial IV dose of 10-20 mcg/min and titrated to maintain arterial systolic pressure higher than 100 mmHg. It is the treatment of choice for patients with coronary disease and concomitant hypertension or pulmonary edema. In one study, intravenous nitrate therapy given in the prehospital setting was shown to improve short-term prognosis in patients with acute pulmonary edema.34 Alternatively, intravenous afterload reduction with nitroprusside can be used for patients with little to no response to nitrates, in patients with acute aortic or mitral regurgitation, and in those with severe hypertension as a precipitating factor in pulmonary edema.29
ACE Inhibitors. Another approach that has gained favor in recent years is the administration of sublingual or intravenous ACEI therapy. ACEI therapy, specifically with captopril, or IV enalapril (Vasotec), decreases afterload and improves left ventricular function. In one study, sublingual captopril added to conventional therapy of oxygen, morphine, diuretics, and nitroglycerin produced more rapid clinical improvement. Furthermore, intravenous captopril has been shown to be effective in CHF by improving cardiac wall motion and left ventricular function.35
Accordingly, a combined approach of diuresis, preload, and afterload reduction is favored in most critically ill patients.28 Patients with severe cardiogenic pulmonary edema may also benefit from intra-aortic ballon counterpulsation (IABCP). Placement of a pulmonary artery catheter should be considered in patients not responding to intensive medical therapy and those with worsening clinical parameters. Echocardiography should be performed immediately in most patients if it is available, unless an obvious etiology or precipitant has been identified. Such precipitating conditions as a ruptured chordae tendinae, endocarditis, or aortic dissection may be more clearly defined by echocardiography.29,36
Cardiogenic Shock Drug Therapy and Adjunctive Treatment Strategies
Cardiogenic shock represents a life-threatening—and frequently terminal—condition of the heart failure spectrum. Cardiogenic shock is defined as hypotension in the presence of pulmonary edema secondary to severe left ventricular systolic dysfunction accompanied by the inability of the heart to meet the metabolic demands of the body. Treatment often requires invasive hemodynamic monitoring by means of a Swan-Ganz catheter and insertion of an intra-arterial line for blood pressure monitoring.
Multiple etiologies can produce cardiogenic shock, among them: acute myocardial ischemia and infarction; aortic dissection; acute aortic regurgitation and insufficiency; pericardial tamponade; and right-ventricular infarction. Cardiogenic shock is caused most often by myocardial infarction, in which the ischemic insult has been severe enough to make at least 40% of the myocardium nonfunctional. Occurring in approximately 7.5-8% of all myocardial infarctions,37 the presence of cardiogenic shock should be suspected in individuals with low systolic blood pressure (< 90 mmHg), altered mental status, oliguria, clammy or cyanotic skin in the setting of coronary artery disease, or suspected ischemia or infarction. Elderly patients with congestive heart failure and shock often do not present with classical findings.
Emergency physicians should have a high index of suspicion of cardiogenic shock, which usually occurs by four mechanisms: 1) left ventricular systolic dysfunction; 2) mechanical complications including ruptured ventricular aneurysm and acute mitral regurgitation from ischemic papillary muscle; 3) right ventricular infarction; and 4) drug effects and hypovolemia. Therapy for cardiogenic shock will require several different approaches including use of positive inotropic agents for blood pressure and tissue perfusion support, use of IABCP, and urgent revascularization by PTCA, thrombolysis, or CABG. In the cardiogenic shock and acute MI, emergency revascularization is the mainstay of therapy.
IABCP has been available for the treatment of cardiogenic shock since 1970. It is generally considered a bridging device until definitive revascularization with CABG, PTCA, and/or thrombolytics can be implemented. No studies to date have shown a definite mortality benefit from IABCP. However, this approach seems to be most effective when used in conjunction with revascularization. IABCP works primarily by "unloading" the heart during systole and augmenting coronary and cerebral flow during diastole.
Revascularization remains an attractive approach for the patient in cardiogenic shock secondary to myocardial infarction and treatable lesions in the coronary artery tree. Cardiogenic shock is the leading cause of death in patients hospitalized for myocardial infarction, with many nonrandomized studies suggesting that revascularization reduces mortality.38 The first randomized study evaluating revascularization using CABG or PTCA, the Should we emergently revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) study, is currently in progress. This multicenter, randomized, unblinded study will evaluate the possible benefits of emergent revascularization for cardiogenic shock associated with acute MI. Patients are being randomized to two revascularization strategies: emergency PTCA or CABG vs. initial stabilization to include thrombolytic therapy and/or IABP followed by delayed revascularization.37
Revascularization with PTCA or CABG has a number of potential benefits that include reversal of myocardial ischemia associated with the shock state. Studies suggest that the benefit of coronary angioplasty in cardiogenic shock is observational, however, and are subject to selection bias. Moreover, some studies have shown no benefit from PTCA for cardiogenic shock. Until the SHOCK study generates definitive data and other studies address other aspects of this issue, it is unclear which approach is best.5
Thrombolytic therapy for acute myocardial infarction associated with cardiogenic shock also is controversial. It is thought by some experts that thrombolytic therapy may be less effective in patients with cardiogenic shock due to myocardial infarction. Data from the Gruppo Italiano per lo Studio della Sopravvivenza nell’ Infarto Miocardico (GISSI-I Trial) suggest that hospital mortality rates for patients with class IV heart failure were high. There were no significant differences between control patients and those treated with streptokinase (69.9% vs 70.1%, respectively). Although there are no randomized trials showing benefit of angioplasty (PTCA), the GISSI-I trial concluded that PTCA should be considered preferable to thrombolysis in this patient subgroup.
If PTCA is not available, a non-fibrin specific lytic agent, such as streptokinase, should be used.39 Data from the APSAC Intervention Mortality Study (AIMS) trial showed an approximate 35% reduction in mortality at one month in hypotensive patients treated with lytic therapy. It also showed a 50% reduction in mortality at one year in this same patient population.37 Pooled data from European thrombolytic trials have shown a statistically significant benefit of lytic therapy in patients with both a heart rate greater than 100 and a systolic blood pressure less than 100.37 Conclusions drawn are that thrombolytic therapy both prevents the development of cardiogenic shock and may benefit patients who present in cardiogenic shock. Three placebo-controlled trials of thrombolysis have studied the development of cardiogenic shock after thrombolytic therapy. These include AIMS, Anglo-Scandinavian Study of Early Thrombolysis (ASSET), and the German Anisoylated Plasminogen Streptokinase Activator Complex (APSAC) trial. All three of these trials showed a reduction in the incidence of cardiogenic shock to less than 4% of the population studied.
The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial showed that t-PA was the most successful lytic agent for reducing the incidence of cardiogenic shock, and, therefore, t-PA should be considered the drug of choice in patients suitable for thrombolytic therapy. Furthermore, early prehospital thrombolysis has been shown to significantly reduce frequency of CHF symptoms post myocardial infarction.10 However, in one study, thrombolytic therapy for acute myocardial infarction (AMI) improved prognosis and prolonged life but increased the prevalence of CHF in the older population.40 Predictors of the development of congestive heart failure include: 1) large anterior wall MI; 2) increased age; 3) diabetes; and 4) presence of rales on admission to the hospital.41
Drug therapy for cardiogenic shock consists of parenteral administration of positive inotropic agents to increase cardiac output and reduce pulmonary wedge pressure. (See Table 8.) Agents used include dopamine, dobutamine, and norepinephrine. In patients with severe hypotension (less than 80 systolic), dobutamine should be avoided as it can cause vasodilation and further drops in mean arterial pressure because of its effect on peripheral beta-adrenergic receptors.29 Invasive hemodynamic monitoring using a pulmonary artery catheter (Swan-Ganz) and echocardiography may be necessary in many cases. In cases where shock persists despite dopamine doses in excess of 15 mcg/kg/min, IABP counterpulsation can be used as an adjunctive measure. Alternatively, norepinephrine can be added to dopamine if IABP is not readily available.
| Table 8. Inotropic Agents Used in the Treatment of Cardiogenic Shock Dosages and Precautions |
| • Dopamine—start at 2-5 mcg/kg/min and titrate upward
• Dobutamine—start at 2-3 mcg/kg/min and titrate upward • Norepinephrine—start at 2-4 mcg/min and titrate upward _______________________________________________________________________________ |
Disposition
The decision to admit or discharge the patient with CHF from the ED should be made as early as possible in the patient’s course. (See Table 9.) Clearly, patients with arrhythmias (e.g., rapid atrial fibrillation, unstable ventricular rhythms, symptomatic bradycardia), evolving ischemia, infarction, syncope, evidence of shock, and/or hypoxia should be admitted for more intensive management and are not disposition dilemmas. Some hemodynamically stable patients with mild decompensation can be treated in the ED with diuresis and other measures—usually augmentation or modification of their anti-CHF drug regimen—and discharged with close follow-up with their physician. (See Tables 10 and 11.)
| Table 9. Clinical Pearls in the Management of Congestive Heart Failure48 |
| • Avoid NSAIDs in patients with congestive heart failure if possible
• Never assume that lack of rales or x-ray evidence of edema means left-sided failure is not present • Elderly patients can and often do present atypically without classic signs and symptoms such as increasing dyspnea, orthopnea, and PND. • Patients presenting with heart failure are ischemic or infarcting until proven otherwise • Avoid aggressive diuresis if inferior/right ventricular infarction suspected • Avoid nitroglycerin if inferior/right ventricular infarction suspected • If patients are not on what is deemed appropriate therapy, find out why and discuss management issues with their primary care physician to prevent ED visits and hospitalizations. This is especially true for ACE inhibitors • Watch for hyperkalemia in patients on ACEI, Aldactone, and patients being heparinized, receiving Bactrim, NSAIDs. • Patients receiving beta-blocker therapy may need dose reduction or discontinuance if clinically significant decompensation develops. Decompensation on beta-blocker therapy many times warrants a temporary increase in diuretic dose • Always ascertain history of high sodium intake or medication noncompliance • Consider thromboembolic disease in patients who present with a history of a large myocardial infarction and reduced ejection fraction • Some patients with heart failure may need to have pre-renal indices (BUN 50, creatinine 3.0) in order to prevent congestive symptoms • The precipitant for heart failure should be diligently pursued
|
| Table 10. Admission Criteria Chart11,28 |
| Hypoxia (oxygen saturation < 90%)
Myocardial ischemia Poor social support Comorbid conditions such as COPD, anemia, hyperthyroidism Tachycardia Patients on numerous medications needing in-hospital titration Pulmonary edema or respiratory distress Comorbid medical problems (renal failure, pneumonia) Anasarca Syncope or hypotension
|
| Table 11. Patient Discharge Criteria11 |
| Stable fluid balance
Relatively free from congestion—orthopnea, edema, ascites Stable blood pressure Heart rate > 50 and < 100 No evidence of angina of unstable pattern No symptomatic arrhythmias Able to perform activities of daily living Stable renal function, generally Cr < 2.5 and BUN < 50 Stable serum sodium, generally > 133 Worsening anemia not present
|
The ED physician should consider admitting symptomatic patients who have made numerous visits to their physician or clinic with similar complaints and in patients renal insufficiency. Evidence of congestion and hypoperfusion, development of ascites or anasarca, and decompensated heart failure coexisting with other renal or pulmonary diseases should warrant urgent hospitalization. Immediate hospitalization also should be considered in patients with pulmonary edema, evidence of arterial desaturation, tachycardia, hypotension, and changed mental status. Patients who take multiple medications and have severe class IV heart failure may need hospital admission for refinement and reinforcement of their drug regimen with agents known to be effective in CHF.
A large percentage of patients who are deemed to be at low risk for complications can be admitted to a general medical bed. In fact, one study suggests that a significant number of patients with heart failure exacerbations are at low risk for complications and do not need acute care hospitalization. These patients can potentially be treated at home with medication adjustment and with follow-up care delivered under the auspices of home health nursing. Low-risk patients in this study were defined as individuals with mild-to-moderate decompensation of chronic CHF or mild heart failure presenting for the first time.42
Another cost-effective strategy is intensive home-care surveillance of patients. This has been shown to prevent hospitalization and improve morbidity rates in older patients with severe heart failure.43 Close telephone monitoring from heart failure experts can also prevent hospitalization in patients with severe disease.11 In an important study, hospitalization for heart failure was significantly related to preventable factors, such as sodium retention.44 Patient self-monitoring of weight, dyspnea, and edema plays an important role in the prevention of recurrent admission.
Accordingly, patient education in the ED is essential in patients seen for CHF. Patients who are referred to a multidisciplinary heart failure team have been shown to have lower hospitalization rates. In fact, patients with chronic heart failure are probably best served by these specialized teams.10 For example, patients who are not on appropriate, outcome-maximizing medical therapy should have should be seen by specialized providers. ACEIs, which are considered an essential ingredient in the CHF treatment cocktail,45 are underused in this population. Consideration should also be given to adding digoxin to the medical regimen of eligible patients since it has been shown to decrease the risk of hospitalization.46 Noncompliance with medications or diet should be discussed with the patient, family members, and, in some cases, case managers, in order to prevent recurrent hospital admissions.29
Summary
CHF is a common clinical entity, the prevalence of which can be expected to increase as our society ages.47 Hence, emergency physicians must be prepared to meet the challenge of managing an increasing number of patients afflicted with this disorder. Important advances and studies in pharmacologic therapy have intensified treatment strategies. ED physicians must remain up-to-date not only with current treatments for heart failure, but also with strategies for decreasing morbidity and mortality and decreasing hospitalization rates for this condition. In conclusion, the care of the patient with heart failure is complex, and should be multidisciplinary, involving emergency physicians, primary care physicians, cardiologists, and specialized "heart failure teams."
References
1. Newby, Goonfield, Flapan, et al. Regulation of peripheral vascular tone in patients with heart failure: Contribution of angiotensin II. Heart 1998;80:134-140.
2. Pit B, Konstam. Overview of angiotensin II-receptor antagonists. Am J Cardiol 1998;8:475-495.
3. Tsuyuki, Yusef, Rouleau, et al. Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists, and beta blockers in patients with congestive heart failure: Design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study. Can J Cardiol 1997;13:1166-1174.
4. Ander, Jaggi, Rivers, et al. Undetected cardiogenic shock in patients with congestive heart failure presenting to the emergency department. Am J Cardiol 1998;82:888-891.
5. Packer, Cohn. Consensus recommendations for the management of chronic heart failure. Am J Cardiol 1999;83:1A-38A.
6. Hamroff G, Blaufarb, Mancini, et al. Angiotensin II-receptor blockade further reduces afterload in patients maximally treated with angiotensin-converting enzyme inhibitors for heart failure. J Cardiovasc Pharmacol 1997;30:533-536.
7. O’Connor CM, Gattis, Swedberg, et al. Current and novel pharmacologic approaches in advanced heart failure. Am Heart J 1998;135:S249-S263.
8. Kupari, et al. Congestive heart failure in old age: Prevalence, mechanisms and 4-Year progress in the Helsinki Aging Study. J Int Med 1997;241:387-394.
9. O’Connor, Carson, Miller, et al. Effect of amlodopine on mode of death among patients with advanced heart failure in the PRAISE trial. Am J Cardiol 1998;82:881-887.
10. Stevenson LW, Massie, Francis, et al. Optimizing therapy for complex or refractory heart failure: A management algorithm. Am Heart J 1998;135:S293-S309.
11. Shah NB, Der, Ruggerio, et al. Prevention of hospitalizations for heart failure with an interactive home monitoring program. Am Heart J 1998;135:373-378.
12. Levin. Evidence-based contemporary heart failure management. Resid Staff Physician 1999;2:59-67
13. Hager WD, Davis, Riba, et al. Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: The SAVE study experience. Am Heart J 1998;135:406-413.
14. Hobbs RE. Digoxin’s effect on mortality and hospitalization in heart failure: Implications of the DIG study. Cleve Clin J Med 1997;64:234-237.
15. Gheorghiade, Cody, Francis, et al. Current medical therapy for advanced heart failure. Am Heart J 1998;135:S231-S248.
16. Cody, Kubo, Pickworth, et al. Diuretic treatment for the sodium retention of congestive heart failure. Arch Intern Med 1994;154:1905-1914.
17. Morrison RT, et al. Edema and principles of diuretic use. Med Clin N Am 1997;81:689-704.
18. Haim, Shotan, Boyko, et al. Effects of beta-blocker therapy in patients with coronary disease in New York Heart Association Classes II and III. Am J Cardiol 1998;81:1455-1460.
19. Cohn JN. The management of chronic heart failure. N Engl J Med 1996;335:490-498.
20. Brater. Diuretic therapy. N Engl J Med 1998;339:387-395.
21. Harjai, Mehra, Ventura, et al. Home inotropic therapy in advanced heart failure—Cost analysis and clinical outcomes. Chest 1997;112:1298-1303.
22. Leier, Binkley. Parenteral inotropic support for advanced congestive heart failure. Prog Cardiovasc Dis 1998;41:207-224.
23. Scherrer-Crosbie, Cocca-Spofford, et al. Effect of vesnarinone on cardiac function in patients with severe congestive heart failure. Am Heart J 1998;136:769-777.
24. Koniaris LS, Goldhaber. Anticoagulation in dilated cardiomyopathy. J Am Coll Cardiol 1998;31:745-748.
25. Garg, Gheorghiade, Syed. Antiplatelet and anticoagulation therapy in the prevention of thromboemboli in chronic heart failure. Prog Cardiovasc Dis 1998;41:225-236.
26. Al-Khadra AS, Salem, et al. Warfarin anticoagulation and survival: A cohort analysis from the studies of left ventricular dysfunction. J Am Coll Cardiol 1998;31:749-753.
27. Fromm, Varon, Gibbs. Congestive heart failure and pulmonary edema for the emergency physician. J Emerg Med 1995;13:71-87.
28. Levin. Acute congestive heart failure—The need for aggressive therapy. Postgrad Med 1997;101:97-100
29. Guidelines for the Evaluation and Management of Heart Failure-Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Circulation 1995;92:2764-2784.
30. Pickkers, Dormans, Smits, et al. Direct vasoactivity of furosemide. Lancet 1996;347:1338-1339.
31. Aeser, Gullestad, et al. Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure. Scand J Clin Lab Invest 1997;57:361-367.
32. Pivac, Rumboldt, Sardelic, et al. Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure. Int J Pharmacologic Res 1998;18:121-128.
33. Gammage M. Commentary—Treatment of acute pulmonary edema: Diuresis or vasodilatation? Lancet 1998;351:382-383.
34. Bertini G, Giglioli, et al. Intravenous nitrates in the prehospital management of acute pulmonary edema. Ann Emerg Med 1997;30:493-499.
35. Arcidiacono, Asmundo, et al. Left ventricular performance after intravenous infusion of captopril in patients with congestive heart failure. Minerva Cardioangiol 1995;43:481-484.
36. Sacchetti AD, Harris. Acute cardiogenic pulmonary edema—What’s the latest in emergency treatment? Postgrad Med 1998;103:145-147,153-154,160-162.
37. Barry, Sarembock. Cardiogenic shock: Therapy and prevention. Clin Cardiol 1998;21:72-80.
38. Hochman, Sleeper, Godfrey, et al. Should we emergently revascularize occluded coronaries for cardiogenic shock: An international randomized trial of emergency PTCA/CABG-trial design. Am Heart J 1999;137:313-321.
39. White, Van de Werf, et al. Thrombolysis for acute myocardial infarction. Circulation 1998;97:1632-1646.
40. Gotsman, Admon, Zahger, et al. Thrombolysis in acute myocardial infarction improves prognosis and prolongs life but will increase the prevalence of heart failure in the geriatric population. Int J Cardiol 1998;65:S29-S35.
41. O’Connor CM, Hathaway, Bates, et al. Clinical characteristics and long-term outcome of patients in whom congestive heart failure develops after thrombolytic therapy for acute myocardial infarction: Development of a predictive model. Am Heart J 1997;133: 663-673.
42. Butler, Hanumanthu, Chomsky, et al. Frequency of low-risk hospital admissions for heart failure. Am J Cardiol 1998;81:41-44.
43. Kornowski. Intensive home-care surveillance prevents hospitalization and improves morbidity rates among elderly patients with severe congestive heart failure. Am Heart J 1995;129:762-766.
44. Bennett, Huster, Baker, et al. Characterization of the precipitants of hospitalization for heart failure decompensation. Am J Crit Care 1998;7:168-174.
45. Lowe, Candlish, Henry, et al. Management and outcomes of congestive heart failure: A prospective study of hospitalized patients. Med J Australia 1998;168:115-118.
46. Mark DB. Economics of treating heart failure. Am J Cardiol 1997;80:33H-38H.
47. Uretsky BF, Pina, Quigg, et al. Beyond drug therapy: Nonpharmacalogic care of the patient with advanced heart failure. Am Heart J 1998;135:S264-S284.
48. Feenstra, Grobbee, Mosterd, et al. Adverse cardiovascular effects of NSAIDs in patients with congestive heart failure. Drug Safety 1997;17:166-180.
Physician’s CME Questions
It should be stressed that hyperkalemia can occur with spironolactone, and this adverse consequence of drug therapy is more likely to occur in patients already taking which of the following drug(s)?
A. Diuretics
B. Digoxin
C. ACEIs
D. Isordil
E. None of the above.
In the PRAISE-1 study, amlodipine decreased all-cause mortality and was found to lower the risk of death by what percentage in patients with nonischemic cardiomyopathy?
A. 25%
B. 33%
C. 40%
D. 45%
E. None of the above.
According to the article, digoxin levels should be measured in all patients presenting to the ED with which of the following?
A. Cardiac symptoms
B. Rhythm abnormalities
C. Deterioration in CHF
D. Unexplained clinical findings suggestive of possible drug toxicity
E. All of the above.
Diuretics have been proven to be useful for symptomatic improvement in patients with heart failure, especially in those individuals with evidence of congestion, including:
A. Dyspnea on exertion.
B. Edema.
C. Orthopnea.
D. B and C
E. A, B, and C
Potential side effects of administration of diuretics may include which of the following?
A. Electrolyte abnormalities, especially potassium depletion, which may be a more pronounced loss if more than one diuretic is necessary for control (follow electrolytes vigilantly in patients on digoxin therapy).
B. Activation of the neurohormonal cascade, which is known to be deleterious in patients with heart failure.
C. Pre-renal azotemia and hypotension, which are usually secondary to overdiuresis or progression of heart failure associated with decreased renal perfusion.
D. All of the above.
Beta-adrenergic agonsists and phosphodiesterase inhibitors work by:
A. decreasing myocardial contractility.
B increasing myocardial contractility.
C. neither decreasing nor increasing myocardial contractility.
D. maintaining myocardial contractility.
E. None of the above
At what dose is it recommended to start dobutamine?
A. 1 mcg/kg/min
B. 2-5 mcg/kg/min
C. 6-8 mcg/kg/min
D. 9-11 mcg/kg/min
E. None of the above
Conditions that most commonly lead to the development of pulmonary edema include which of the following?
A. Myocardial ischemia
B. Fluid excess and volume overload
C. Medication noncompliance
D. Arrhythmias
E. All of the above
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