Congestive Heart Failure: Critical Clinical Issues in Cardiogenic Shock, Hemodia
Congestive Heart Failure: Critical Clinical Issues in Cardiogenic Shock, Hemodialysis, and Maintenance Drug Therapy (Part II)
Author: J. Michael Albrich, MD, FACEP, FACP, Assistant Clinical Professor of Medicine, Oregon Health Sciences University; Clinical Medical Director, Department of Emergency Medicine, Legacy Good Samaritan Hospital, Portland, OR.
Peer Reviewers: William J. Brady, MD, FACEP, Assistant Professor, Department of Emergency Medicine, University of Virginia; Clinical Director, Department of Emergency Medicine, University of Virginia Health Sciences Center, Charlottesville, VA.
Frank Ruiz, MD, Assistant Professor of Surgery, University of California-San Francisco; Department of Emergency Services, San Francisco General Hospital, San Francisco, CA.
The first part of this two-part series on congestive heart failure (CHF) presented a systematic approach to evaluating and treating patients with severe, life-threatening CHF and pulmonary edema. Assessment strategies, disposition considerations, and pharmacotherapeutic interventions in the emergency setting were discussed in detail.
The second part of this comprehensive review addresses clinical challenges in specific subgroups of patients, including those with cardiogenic shock, as well as patients on hemodialysis. Although cardiogenic shock once carried a dismal mortality, the death rate associated with this condition can be reduced in individual patients when left ventricular dysfunction is the result of acute coronary occlusion.
Similarly, clinical outcomes in dialysis patients with CHF can be improved if stabilization is followed by immediate dialysis when indicated. In this regard, stabilization requires aggressive treatment of hyperkalemia, prompt reduction of afterload and preload, and carefully titrated drug therapy.
Finally, the ED physician frequently encounters patients with urgent, but non-life-threatening manifestations of chronic CHF. Because most of these patients are taking multiple medications, including digoxin, diuretics, ACE inhibitorsas well as angiotensin II receptor antagonists, beta blockers, and/or calcium channel blockersthe emergency practitioner must be aware of the downsides, side effects, and potential benefits of these medications.
With these issues in mind, Part II of our series presents special treatment issues that pertain to the management of the high risk subgroups, and an overview of pharmacotherapeutic intervention for patients with mild to moderate congestive heart failure.
The Editor
Cardiogenic Shock: Drug Therapy
Cardiogenic shock has a mortality rate of 85%.1 Rapid evaluation and simultaneous treatment are required to improve outcomes. About 10-15% of patients suffering acute myocardial infarction (AMI) are volume-depleted. Therefore, if the hypotensive patient in congestive heart failure (CHF) is not obviously volume overloaded (moist rales with portable chest x-ray evidence of pulmonary edema), fluid challenge (in carefully monitored boluses of 250 cc) may be life-saving. The presence of jugulovenous distention (JVD) can be misleading in the absence of signs of volume overload; both pericardial tamponade and right ventricular infarction may present with JVD and may respond to fluid challenge with clinical improvement.
Successful fluid management in the face of cardiogenic shock requires close observation and further clinical information from Doppler echocardiography (structural) and pulmonary artery wedge pressure (hemodynamic) monitoring in the intensive care unit. Expeditious diagnostic evaluation (Doppler or angiography) of the causes of cardiogenic shock will reduce the high mortality rate associated with this syndrome. (See Table 1.) In this era of percutaneous transcoronary angioplasty (PTCA), it is possible to reduce mortality of cardiogenic shock due to coronary occlusion (acute myocardial infarction) from 85% to 45-50%, if the infarct-related artery can be opened without delay.2
Inotropic Agents for Persistent Hypotension
Norephinephrine 2-20 mcg/min IV
In patients with low blood pressure or those who are progressing toward shock, dobutamine at 2-3 mcg/kg/min or dopamine at 2-5 mcg/kg/min may improve clinical status. Dobutamine may have some advantage in this group, as it acts directly on the ventricle, whereas dopamine acts through endogenous neuronal norepinephrine.3
In patients who are severely hypotensive (£ 70 mmHg), in clinical shock, or both and are volume overloaded or have received saline administration, moderate (4-5 mcg/kg/min) doses of dopamine may improve cardiac output without causing systemic vasoconstriction.
Increasing the dose to 15-20 mcg/kg/min may be required for persistent hypotension, but this dose is associated with arrhythmia and systemic vasoconstriction. If high-dose dopamine fails, consider intra-aortic balloon counterpulsation, where available, to support circulation as a bridge to transplantation. In the absence of intra-aortic counterpulsation balloon, inttravenous (IV) norepinepherine may increase blood pressure to temporarily acceptable levels (³ 80 mmHg). This is understood to be a desperate maneuver.
Nonpharmacologic Therapies. Rotating Tourniquets. Currently, rotating tourniquets are not thought to effectively reduce preload from the extremities.4
Dialysis and Phlebotomy. Dialysis is the definitive method for removal of volume overload in renal failure. Phlebotomy may be necessary when heart failure complicates polycythemia to avoid hyper viscosity syndrome during diuresis.
CHF is present in about 31% of patients who begin dialysis, and it will develop in another 25%.5 The two-year survival of dialysis patients with recurrent CHF is only 33% compared with 80% in patients without CHF.6 Acute CHF/pulmonary edema in dialysis patients is most often due to volume overload that is amenable to dialysis. ED treatment, therefore, is directed at stabilizing these patients until dialysis is available. Volume overload is most often associated with hypertension. In the absence of a history of low blood pressure (usually, in end-stage CHF), the finding of normal blood pressure or hypotension in pulmonary edema should alert the physician to the possibility of hyperkalemia, AMI, or pneumonia with sepsis. Certainly, the other causes of shock must also be considered, including pericardial tamponade, and hypovolemic, spinal, or anaphylactic shock.
Treatment of hyperkalemia in dialysis patients has recently undergone change. Bicarbonate, used for decades to treat hyperkalemia, has been shown to be ineffective in reducing the potassium levels in these patients.7,8 Salbutamol, both nebulized and IV, has been shown to reduce potassium in children.9 Nebulized albuterol and insulin/glucose have also been shown to reduce potassium in adults.8 (See Table 2.) These are effective temporizing measures until dialysis is available. Calcium should be avoided in dialysis patients with hyperkalemia who are taking digoxin, as it can exacerbate digoxin toxicity. In fact, hyperkalemia is a recognized consequence of digoxin excess.10 Digoxin levels should be measured in any dialysis patient on digoxin who presents with hyperkalemia.
Sacchetti et al have presented a descriptive analysis of the ED management of pulmonary edema in dialysis patients.11 They found that effective treatment consisted of preload reduction with nitrates and afterload reduction with captopril, nifedipine, and, in severe cases, nitroprusside. (See Table 3.) The treatment of pulmonary edema in dialysis patients differs slightly from treatment of cardiogenic pulmonary edema in patients without renal insufficiency. In dialysis patients, loop diuretics are not used, and nifedipine, as well as captopril, may be used with patients who are hypertensive.
Mild to Moderate CHF: Pharmacological Adjustments in the ED
Overview. The emergency physician frequently sees patients with a variety of urgent but not emergent medical problems associated with CHF. Pharmacologic management of CHF in these patients requires different agents and has different goals than those discussed above in the management of pulmonary edema and acute severe failure. In acute CHF, relief of symptoms by rapid vasodilation and diuresis is paramount, whereas, long-term therapy attempts to increase survival, improve exercise tolerance, reduce heart size, and avoid fluid retention. The major pharmacologic classes used to treat heart failure are:
• The vasodilators: the angiotensin converting enzyme inhibitors (ACEIs), the angiotensin II receptor blocker, losartan, and hydralazine and isosorbide dinitrate.
• The diuretics: thiazides, loop diuretics, and the potassium-sparing diruetics
A variety of other drugs are currently experimental or have failed to improve or have even reduced survival.
• Beta blockers: currently the most promising agents based on recent trials.12-14
• Calcium channel blockers: first generation (diltiazem, nifedipine, verapamil) exacerbate heart failure; second generation (felodipine, amlodipine) appear to have less negative inotropic effects.
• Inotropic agents: milrinone, amrinone, vesnarinone.
• Other: anticoagulants, antiarrhythmic agents.
The Vasodilators. The use of vasodilators for treatment of heart failure is based on observations over decades that arteriorlar and venous vasoconstriction by a variety of endogenous substances raises afterload impeding cardiac output and collapses venous capacitance vessel increasing preload.15 Randomized, controlled trials discussed below have established the central role of vasodilator therapy in the treatment of systolic left ventricular heart failure, in particular, the angiotensin-converting enzyme inhibitors (ACEIs) and the combination of hydralazine and isosorbide dinitrate. ACEIs block conversion of angiotensin I to angiotensin II, which simulates adrenergic system (norepinepherine) and production of aldosterone. Angiotensin II directly and indirectly produces peripheral vasoconstriction and fluid retention. Hydralazine is an arterial vasodilator and nitroglycerin dilates arterial and venous vessels.
Systolic and combined systolic and diastolic left heart failure causes the vast majority of clinical heart failure studied in these trials. Pure diastolic heart failure with preserved systolic function is unusual and has not been adequately studied with ACEIs.1 The current approach is to reduce filling pressure with nitrates and diuretics.
In the first Veterans Administration Cooperative Study of the effect of vasodilators in heart failure (V-HeFT I), 642 male patients who were already taking digoxin and diuretics were randomized to additional medication: placebo prazosin or hydralazine, and isosorbide dinitrate (ISDN).16 At the end of two years, the hydralazine and ISDN group enjoyed a 34% reduction in mortality over placebo and prazosin. Placebo and prazosin were not statistically different. The hydralazine and ISDN group improved ejection fraction significantly more than the other treatment arms. Prazosin, an arterial vasodilator, had no effect on the venous vessels and caused a tachyphylaxis that increased cardiac work. Thus, combined hydralazine and ISDN was the first vasodilator therapy to reduce mortality and improve cardiac output.
In the following year, the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) randomized 253 NYHA class IV patients (30% female) already taking digoxin, diuretics, and, in 45%, ISDN, to the ACEI enalapril vs. placebo.17 The mean dose of enalapril was 18 mg and the starting dose that caused the least hypotension was 2.5 mg. At the end of six months, the morality reduction was 40% and, at the conclusion of the study, death was reduced by 27%. The difference in mortality between treatment arms was entirely due to lack of progression of heart failure. Significant improvement in NYHA functional class was observed over the placebo group. Patients taking the vasodilator ISDN also enjoyed improved survival. Consequently, the ACEI benefit was in addition to ISDN.
In 1991, the second Veterans Administration vasodilator trial, V-HeFT II, reported the comparison of combination hydralazine and ISDN and enalapril in 804 men who were predominantly in NYHA class II and III.18 After two years, the mortality in the enalapril group was 18% and in the hydralazine/ISDN group, 25%. Enalapril reduced mortality an additional 28%, which was due almost entirely to the prevention of sudden death in the less severe classes of heart failure (NYHA I and II). The combination of hydralazine and ISDN improved ejection fraction and peak oxygen consumption more than enalapril. The mortality of both groups was more than 40% at four years of treatment. Enalapril conferred a greater survival advantage than hydralazine and ISDN; both regimens delayed but did not prevent death due to heart failure.
Since heart failure is so common and costly, it was postulated by the SOLVD (Studies of Left Ventricular Dysfunction) investigators that even a moderately effective agent might have a large impact on mortality and the rate of hospitalization.
In the first trial, these investigators randomized 2569 symptomatic patients with ejection fraction no higher than 0.35 (NYHA II-III) to enalapril or placebo19 and followed them for a mean of 41 months. The dose ranged from 2.5-20 mg. They found a 16% mortality reduction and 26% reduction in the end point, death or hospitalization. Most of the mortality reduction was due to lack of progression of heart failure. In a second study, the SOLVD investigators randomized 2117 asymptomatic patients with reduced ejection fraction, less than or equal to 0.35, to the same treatments, enalapril or placebo.20 After a mean of 37 months, there was a trend toward mortality reduction for the enalapril group, but it was not significant. Enalapril did reduce the end points, death or development of overt heart failure, by 29% and death or hospitalization for heart failure by 20%.
The most common initial insult leading to CHF is AMI. Since enalapril clearly offered survival benefits and improved left ventricular dysfunction in chronic heart failure, it and other ACEIs may reduce the mortality and impede the adverse effects of remodeling that occurs after myocardial infarction. Several trials confirmed that mortality is decreased when an ACEI is begun as little as three days after myocardial infarction in patients with or without symptoms.21,22 Two "mega trials", GISSI-3 and ISIS-4, have shown that lisinopril and captopril, respectively, started within 24 hours of AMI, will show significant mortality reduction at six weeks.23,24 It is important to note that the mortality benefits seen in all of the above trials were obtained at certain target doses given in Table 4. The mortality benefit of lower doses is uncertain.
Initiation of ACEI therapy with the lowest doses provides the greatest safety. Particular caution is needed in the presence of hyponatremia that suggests a highly stimulated renin-angiotensin system that is a poor prognostic sign in heart failure.25
In a recent study of 6800 patients, enalapril and other ACEIs demonstrated similar rates of adverse reaction.26 Adverse reactions included: hypotension (15%), fatigue (6%), cough (5%), azotemia (3.8%), hyperkalemia (1%), and angioedema (0.4%).
Patients who are hypotensive, hyperkalemic, in renal failure (creatine > 3.0), or who develop cough or angioedema should not receive ACEIs.
Losartan. Recently, the angiotensin receptor site AT1 inhibitor losartan has been introduced as an antihypertensive. ACEIs inhibit the conversion of angiotensin I to angiotensin II. In the process, bradykinin builds up that is associated with cough. Direct inhibition of the receptor site is not associated with bradykinin build-up. This drug is particularly useful in patients who are unable to tolerate ACEIs due to cough.27 Recently, the ELITE (Evaluation of Losartan in the Elderly) study compared losartan to captopril in 722 CHF patients over a 12-month period.28 Losartan had fewer patients discontinue therapy due to adverse reactions (12% vs 21%), lower all-cause mortality (4.8% vs 8.7%, a 46% reduction, P = 0.035) and lower rates of hospital admission for any reason (22% vs 30%). Symptom improvement and admissions for decompensated CHF were similar for the two drugs. These dramatic findings await the confirmation of a larger ELITE trial in progress.
Isosorbide and Hydralazine. In heart-failure patients unable to tolerate ACEIs or losartan, the combination of hydralazine and ISDN therapy still provides a survival advantage over digoxin and diuretics alone. The starting and target doses are given in Table 5.
Diuretics. Diuretics play a central role in the management of salt and water retention and the symptoms of chronic heart failure.29 In particular, they provide symptomatic relief of dyspnea, fatigue, and edema. No large, randomized controlled trials demonstrate their effectiveness on survival in heart failure. Diuretics stimulate the renin-aldosterone-angiotensin system and its chronic deleterious effects, but, when used in combination with ACEIs, this can be mitigated and functional survival prolonged. Most diuretics cause potassium loss. This can be mitigated by ACEIs, potassium supplementation, or combined use with a potassium-sparing diuretic. Combination of more than one class of diuretic may be the most effective method of maintaining diuresis in the face of faltering renal function. Failure of furosemide to produce a diuresis may be overcome by the addition of metolazone to furosemide.30
Aggressive diuresis of patients with cor pulmonale is to be avoided as these patients rely on high central venous and right heart pressures in the face of pulmonary hypertension to maintain adequate left atrial filling pressure and cardiac output.31 Volume overloaded cor pulmonale patients are diuresed gently with careful attention to blood pressure.
Commonly used diuretics and doses appear in Table 6.
Adverse reactions to diuretics include:
• overdiuresis (fatigue, dizziness, hypotension, falls, reduced cardiac output);
• underdiuresis (symptoms of heart failure);
• hypokalemia (arrhythmia, digoxin toxicity, myalgias, and weakness);
• hyperkalemia (potassium-sparing duretics in combination with potassium supplements and ACEIs);
• hypomagnesemia (prevents correction of hypokalemia until magnesium deficiency is corrected);
Digoxin. Treatment of heart-failure patients in normal sinus rhythm has been controversial. Recently, one study evaluated 178 patients on chronic digoxin, diuretic, and ACEI therapy for NYHA II-III heart failure with ejection fractions of less than 0.35.32 Half were randomized to continued digoxin at dosages unlikely to cause toxicity, and half received placebo for 12 weeks. Twenty-three of the placebo patients and four of the digoxin patients had to be withdrawn from the study due to worsening heart failure. Thus, withdrawal of digoxin in stable heart failure patients increases risk of developing symptomatic heart failure six-fold. A large trial (6800 patients) of digoxin in heart failure by the Digoxin Investigation Group was recently completed. Digoxin therapy had no effect on mortality but reduced hospitalization by 6% compared to the control group.33
Beta blockers. Chronic adrenergic stimulation is associated with heart failure and is known to have significant detrimental effects on the myocardium. For this reason, beta-adrenergic blockade has been an attractive therapeutic approach.34 Small trials have suggested improved myocardial function and reduced symptoms with beta blockers. Typically, the beta-blocker is started at a low dose (e.g., metoprolog 5 mg) and increased slowly to avoid exacerbation of CHF.12 The largest trial to date of the beta blocker carvedilol suggests reduced mortality and hospitalization in patients already taking an ACEI, digoxin, and a diuretic.13 However, due to an early run-in feature of the trial wherein all patients received the trial drug and some deaths occurred (and were not counted in the trial results), the benefits of carvedilol in an unselected population of heart-failure patients remains uncertain.14 The BEST (Beta Blocker Evaluation Survival Trial) currently in progress should define the role for these agents in heart failure.35 Currently, the use of beta blockers for treatment of CHF is investigational and has no place in the management of decompensated CHF.
Thiamine. Thiamine deficiency occurs in 20% or more patients with CHF on long-term loop diuretic therapy.36 The fraction maybe higher in patients who drink alcohol. Shimon studied 30 patients with long-term furosemide therapy treated with 200 mg IV thiamine or placebo for one week.37 The thiamine-treated patients showed improvement in ejection fraction by 14%, diuresis by 35%, and sodium excretion by 40%. All 30 patients were subsequently treated with oral thiamine for seven weeks; 27 patients finished the study. At completion, the average ejection fraction had increased 22% (from 27% to 33%). With little risk from thiamine therapy, these results suggest that thiamine replacement for at least a seven-week period may benefit CHF patients on loop diuretics. Longer-term studies are needed to define morbidity and efficacy of these supraphysiologic doses of thiamine.
Calcium channel blockers. First generation. Verapamil, nifedipine, and diltiazem should be avoided because of their negative inotropic effects that exacerbate heart failure.38
Second generationAmlodipine. PRAISE investigators compared amlodipine and placebo in patients receiving standard drug therapy and found no increased mortality and a trend toward improvement in nonischemic dilated cardiomyopathy.39 Patients had ejection fraction less than 30%. Demonstration of significant benefit for nonischemic cardiomyopathy awaits a larger trial that is in progress.
Felodipine. A major study found no benefit in the treatment of CHF.40
Anticoagulants. Anticoagulants used prophylactically have not been shown to reduce the already low rate of deep venous thrombosis or stroke in heart failure patients in normal sinus rhythm.41 However, in a retrospective review of the SOLVD trial patients, multivariate analysis found that there was a 24% reduction in sudden death in patients taking antiplatelet agents and a 32% reduction in sudden death for patients taking coumadin.42 Because of the risks of coumadin therapy, it should be reserved for well-defined indications such as atrial fibrillation and proven DVT pending prospective trials confirming efficacy in CHF. Aspirin is indicated for ischemic cardiomyopathy and is sufficiently low risk to be taken by all CHF patients.
Inotropic Agents. Oral inotropic agents have had uniformly disappointing survival results. Milrinone is the prototype of this class.43 Vesnarinone has had equivocal results and is currently under study.44 Short-term inotropic support with dobutamine has been used in the outpatient setting.
Medications to Avoid. Non-steroidal anti-inflammatory drugs (NSAIDs) aggravate heart failure by interfering with prostaglandin metabolism and promoting fluid retention. Antiarrhythmics have not been shown to prolong survival in heart failure and may be harmful.45
Mild-to-moderate exacerbations of CHF may be treated and observed in the ED and discharged after communication with the private physician, but only if the patient responds to therapy. Oxygenation must be adequate as measured by O2 saturation at rest and after mild exercise in patients who are discharged. Observation units within the ED may assist the evaluation and disposition of CHF patients. Mild-to-moderate exacerbations of heart failure that respond poorly to therapy or are complicated by other factors (e.g., diabetes, possible acute myocardial ischemia, or rhythm abnormalities) should be admitted and observed.
The ED may become the site of contact between frequently returning elderly heart failure patients and multidisciplinary intervention teams. Such teams have been shown to reduce readmission and cost.46 Patients with new-onset left heart failure should be admitted to the hospital for evaluation. Pulmonary edema has a high cardiovascular complication rate, and, therefore, these patients should be admitted to the intensive care unit.47 Pulmonary edema associated with volume overload in dialysis patients that responds to dialysis need not be admitted. The prognosis of decompensated CHF presenting to the ED has a poor six-month prognosis independent of subsequent hospital treatment.48
Instructions that should be provided to the patient who is discharged home include:
• encourage exercise appropriate to clinical state;
• encourage patient to construct written advance directives.
Managed care organizations may require consultation with the patient’s primary care provider before referral in non-emergent presentation. Complex or life-threatening complications of heart failure should be referred to a cardiologist or other appropriate on-call subspecialty consultant without delay.
The treatment of CHF in special subgroups of patients, such as those with cardiogenic shock and renal dialysis, requires customized approaches in order to maximize clinical outcomes. In addition, a number of medications have been shown to prolong life in patients with CHF, and emergency physicians must be familiar with their use.
References
1. Committee of Evaluation and Management of Heart Failure. Guidelines for the evaluation and management of heart failure: Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 1995;92:2764-2784.
2. Bengston JR, Kaplan AJ, Pieper KS, et al. Prognosis in cardiogenic shock after acute myocardial infarction in the interventional era. J Am Coll Cardiol 1992; 20:1482-1489.
3. Anderson FL, Port JD, Reid BB, et al. Effect of therapeutic dopamine administration on myocardial catecholamine and neuropeptide Y concentrations in the failing ventricles of patients with idiopathic dilated cardiomyopathy. J Cardiovasc Pharmacol 1992;20;800-6.
4. Francis GS. Rotating tourniquets for acute cardiogenic pulmonary edema. JAMA 1995; 274:1192.
5. Harnett JD, Foley RN, Kent GM, et al. Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis, and risk factors. Kidney Int 1995;47:884-890.
6. Parfrey PS, Harnett JD, Barre PE. The natural history of myocardial disease in dialysis patients. J Am Soc Nephol 1991;2:2-12.
7. Kim HJ. Combined effect of bicarbonate and insulin with glucose in acute therapy of hyperkalemia in end-stage renal disease patients. Nephron 1996;72:476-482.
8. Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol. Am J Kidney Dis 1996; 28:508-514.
9. McClure RJ, Prasad VK, Brocklebank JT. Treatment of hyperkalaemia using intravenous and nebulised salbutamol. Arch Dis Child 1994;70:126-128.
10. Fenton F, Smally AJ, Laut J. Hyperkalemia and digoxin toxicity in a patient with kidney failure. Ann Emerg Med 1996; 28:440-441.
11. Sacchetti AO, McCabe J, Torres M, et al. ED management of acute congestive heart failure in renal dialysis patients. Am J Emerg Med 1993;11:644-647.
12. Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group. Lancet 1993;342:1441-1446.
13. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 1996;334:1349-1355.
14. Pfeffer MA, Stevenson LW. Beta-adrenergic blockers and survival in heart failure. N Engl J Med 1996;334:1396-1397.
15. Cohn JN, Franciosa JA. Vasodilator therapy of cardiac failure. N Engl J Med 1977;297:27-31,254-258.
16. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration cooperative study. N Engl J Med 1986;314:1547-1552.
17. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429-1435.
18. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;325:303-310.
19. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302.
20. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. [Published erratum appears in N Engl J Med 1992;327:1768.] N Engl J Med 1992;327:685-691.
21. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821-828.
22. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE investigators. N Engl J Med 1992;327:669-677.
23. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. GISSI-3: Effects of lisinopril and transdermal glyceryl trinitrate singly and together on six-week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343:1115-1122.
24. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: A randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995;345:669-685.
25. Brophy JM, Deslauriers G, Rouleau JL. Long-term prognosis of patients presenting to the emergency room with decompensated congestive heart failure. Can J Cardiol 1994;10:543-547.
26. Kostis JB, Shelton B, Gosselin G, et al. Adverse effects of enalapril in the Studies of Lelft Ventricular Dysfunction (SOLVD). SOLVD Investigators. Am Heart J 1996;131:350-355.
27. Crozier I, Ikram H, Awan N, et al. Losartan in heart failure. Hemodynamic effects and tolerability. Losartan Hemodynamic Study Group. Circulation 1995; 91:691-697.
28. Pitt B, Segal R, Martinez FA, et al. Randomized trial of losartan versus captopril in patients over 65 with heart failure. Evaluation of Losartan in the Elderly Study, ELITE. Lancet 1997;349:747-752.
29. Taylor SH. Refocus on diuretics in the treatment of heart failure. Eur Heart J 1995;16 Suppl F:7-15.
30. Kiyingi A, Field MJ, Pawsey CC, et al. Metolazone in treatment of severe refractory congestive cardiac failure. Lancet 1990;335:29-31.
31. Vandiviere HM. Pulmonary hypertension and cor pulmonale. South Med J 1993;86:2S7-10.
32. Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med 1993;329:1-7.
33. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-533.
34. Sackner-Bernstein JD, Mancini DM. Rationale for treatment of patients with chronic heart failure with adrenergic blockade. JAMA 1995;274:1462-1467.
35. Design of the Beta-Blocker Evaluation Survival Trial (BEST). The BEST Steering Committee. Am J Cardiol 1995;75:1220-1223.
36. Brady JA, Rock CL, Horneffer MR. Thiamin status, diuretic medications, and the management of congestive heart failure. J Am Diet Assoc 1995;95:541-44.
37. Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med 1995;98:485-490.
38. Piepho RW. Calcium antagonist use in congestive heart failure; still a bridge too far? J Clin Pharmacol 1995;35:443-453.
39. Packer M, O’Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med 1996;335:1107-1114.
40. Littler WA, Sheridan DJ. Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group. Br Heart J 1995;73:428-433.
41. Cioffi G, Pozzoli M, Forni G, et al. Systemic thromboembolism in chronic heart failure. A prospective study in 406 patients. Eur Heart J 1996; 17:1381-9.
42. Dries DL, Domanski MJ, Waclawiw MA, et al. Effect of antithrombotic therapy on risk of sudden coronary death in patients with congestive heart failure. Am J Cardiol 1997;79:909-913.
43. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group . N Engl J Med 1991;325:1468-1475.
44. Cohn JN. The management of chronic heart failure. N Engl J Med 1996;335:490-498.
45. Visser FC, Visser CA. Current controversies with ACE inhibitor treatment in heart failure. Cardiology 1996;87 (Suppl 1):23-28.
46. Rich MW, Beckham V, Wittenberg C, et al. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995;333:1190-1195.
47. Katz MH, Nicholson BW, Singer DE, et al. The triage decision in pulmonary edema. J Gen Intern Med 1988; 3:533-539.
48. Brophy JM, Deslauriers G, Boucher B, et al. The hospital course and short-term prognosis of patients presenting to the emergency room with decompensated congestive heart failure. Can J Cardiol 1993;9:219-224.
Physician CME Questions
25. The two-year survival rate of dialysis patients with CHF is:
A. 80%
B. 33%
C. 2%
26. In treatment of hyperkalemia in dialysis patients:
A. bicarbonate has been shown to be ineffective.
B. salbutamol has been shown to reduce potassium in children.
C. albuterol and insulin/glucose have been shown to reduce potassium levels in adults.
27. In the Cooperative North Scandinavian Enalapril Survival Study, enalapril reduced mortality:
A. 40%.
B. 60%.
C. 20%.
28. Which of the following was shown to reduce mortality at six weeks in the GISSI-3 and ISIS-4 "mega-trials?"
A. Verapamil and ramipril
B. Lisinopril and captopril.
C. Enalapril and captopril.
29. Which of the following can mitigate potassium loss experienced with use of diuretics?
A. Use in combination with ACEIs
B. Potassium supplementation
C. Use in combination with a potassium-sparing diuretic
D. All of the above
30. The recommended dosage for dobutamine in treatment of persistent hypotension in CHF is:
A. 15-20 mcg/kg/min
B. 2-5 mcg/kg/min
C. 4-10 mcg/kg/min
31. Which of the following should be avoided in CHF patients due to inotropic effects?
A. Calcium channel blockers
B, ACE inhibitors
C. Thiamine
32. Which of the following patients does not need to be admitted to the hospital?
A. Patients with new-onset left heart failure
B. Patients with pulmonary edema
C. Patients with pulmonary edema associated with volume overload that responds to dialysis.
D. None of the above.
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