European Heart Journal Supplements

This Article Abstract FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Google Scholar Articles by Gheorghiade, M. Articles by Zannad, F. Search for Related Content PubMed Articles by Gheorghiade, M. Articles by Zannad, F. Social Bookmarking          What's this?

© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions{at}oupjournals.org

Modern management of acute heart failure syndromes

Mihai Gheorghiade^1,* and Faiez Zannad^2,3,4

¹Division of Cardiology, Northwestern University Feinberg School of Medicine, Galter 10-240, 201 E. Huron Street, Chicago, IL 60611, USA
²INSERM, Centre d'investigation clinique CIC-INSERM CHU, Hôpital Jeanne d'Arc, 54200 Dommartin les Toul, Nancy, France
³CHU, Département des Maladies Cardio-Vasculaires, Nancy, France
⁴Université Henri Poincaré, Nancy, France

^* Corresponding author. E-mail address: m-gheorghiade{at}northwestern.edu

	Abstract

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
Heart failure is an important and growing public health problem throughout the developed world. Clinical interest has recently focused on acute heart failure syndromes (AHFS), which make a major contribution to the substantial financial and humanistic burden of disease. Despite the undoubted clinical importance of AHFS, no universally accepted definition of the condition exists and the first treatment guidelines remain to be published. The prognosis for patients with AHFS remains poor. Many acute therapeutic interventions are yet to be validated in randomized controlled trials, although recent years have seen a number of large-scale studies and the introduction of several new treatment options. In contrast to AHFS, substantial progress has been made in developing management strategies for chronic heart failure, although use of well-established life-saving therapies remains suboptimal. A brief introduction to the current key issues in AHFS, which are discussed in more detail in this supplement, is provided in this paper.

Key Words: Acute disease • Congestive heart failure, classification/pathophysiology/mortality/therapy

	Introduction

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
Heart failure is a substantial and growing problem throughout the developed world—almost 1 million hospital admissions with a primary diagnosis of heart failure are recorded each year in the USA alone,¹ and as many as 30–60% of patients are re-admitted within 3–6 months of their initial discharge.² Chronic heart failure has long been recognized as an important public health problem, and substantial progress has been made in determining best practice and management strategies for this disease. Conversely, relatively little clinical attention has been focused on the major contribution of acute-stage disease to the social and financial burden of heart failure—for example, until the approval of nesiritide in 2001, no new therapies for acute heart failure had been approved by the US Food and Drug Administration for 14 years. This lack of activity is particularly striking when compared with other acute cardiac conditions with similar social and financial impact, such as acute myocardial infarction. However, several major initiatives have now been launched to redress this balance, including patient registries in Europe and the USA, development of the first treatment guidelines (soon to be published by the European Society of Cardiology), and a number of large-scale clinical trials of emergent therapies.

	Terminology

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
The classification of patients with acute heart failure is complex, and no universally accepted definition of the condition currently exists. Three subsets of patients can be distinguished: (i) the vast majority (>70%) of hospital admissions with a primary diagnosis of heart failure is due to worsening chronic heart failure,³ (ii) patients may also develop new-onset heart failure secondary to an acute cardiac injury such as myocardial infarction, and (iii) a third group of patients suffer from end-stage or refractory heart failure and do not respond well to therapy. Patient presentation may vary, encompassing worsening congestion, worsening chronic heart failure, pulmonary oedema, hypertensive crisis, or cardiogenic shock. This broad spectrum of aetiologies and presentations is referred to as acute heart failure syndromes (AHFS).

	Demographics

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
The recent increase in interest in AHFS has led to the initiation of several patient registries, which are already yielding important information about patient demographics. European initiatives include the EFICA (Epidémiologie Francaise de l'Insuffisance Cardiaque Aiguë)⁴ and EPICAL (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine)⁵ observational cohort studies and the EuroHeart Failure Survey covering 24 countries.⁶ The largest registry of AHFS patients worldwide is the ADHERE (Acute Decompensated Heart Failure National Registry) database in the USA.⁷ One observation that has been reinforced by such registries is the disparity between clinical trial patient cohorts and ‘real-life’ heart failure patient populations. For example, patients enrolled in heart failure trials are more often males and tend to be younger than those in hospital surveys (Table 1).⁸

View this table: [in this window] [in a new window]   Table 1 Age and sex of patients with AHFS: clinical trials compared with hospital surveys

 
The vast majority of individuals hospitalized with AHFS has signs and symptoms of congestion;⁹ only a small minority of patients (2% in ADHERE) presents with hypotension. Patients often have a prior history of heart failure: this was the case for 56% of patients in the EuroHeart Failure Survey⁶ and 75% in ADHERE.⁹ In both Europe and the USA, the incidence of cardiovascular disease and risk factors, including coronary artery disease, diabetes, atrial arrhythmias, and hyperlipidaemia, is high among patients hospitalized with heart failure.^6,9 A history of hypertension is particularly common, recorded in 72% of American and 53% of European patients.

	Pathophysiology

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
Four key factors contribute to the pathophysiology of AHFS: congestion, myocardial injury, renal dysfunction (cardiorenal syndrome), and comorbidities. This complexity must be borne in mind for successful patient management: all four aspects must be addressed if optimal therapy is to be achieved.

Congestion
Factors that can contribute to the development of an acute exacerbation of chronic heart failure include dietary indiscretion and poor compliance with medication. The effect of these alterations is to disrupt a previously stable clinical status, leading to a deterioration of haemodynamic function secondary to fluid overload or congestion. Haemodynamic abnormalities associated with AHFS are increased right and left ventricular filling pressures and decreased cardiac output. These haemodynamic alterations contribute to a progressive worsening of ventricular function, development of dyspnoea at rest, orthopnoea, fluid retention, and possible myocyte loss.

Myocardial injury
Although most attention has been focused on fluid overload and congestion, recent studies have found that myocardial injury may also be a common and important element of the pathophysiology of AHFS. Congestion may be secondary to a myocardial injury; conversely, the injury may be a result of increased left ventricular wall stress caused by high filling pressure. One study found that 60% of patients with acute cardiogenic pulmonary oedema and no myocardial infarction had elevated troponin T levels, which were predictive of poor long-term survival.¹⁰ Therefore, improving diastolic filling pressure, thus possibly minimizing myocardial injury, should be a major treatment goal for patients with AHFS. Failure to prevent or treat myocardial injury, resulting in a progressive worsening of baseline cardiac function with each hospitalization episode, may be a major contributor to the progression of heart failure and the high re-admission rates for patients with AHFS.

Renal dysfunction (cardiorenal syndrome)
It appears that even minor renal abnormalities contribute to the pathophysiology, and therefore prognosis, of AHFS.

Comorbidities
An important point to consider is that patients hospitalized with AHFS have a high incidence of comorbidities, including coronary artery disease, hypertension, uncontrolled diabetes, and atrial fibrillation, which may contribute to haemodynamic instability and congestion in AHFS.

	Prognosis/predictors of outcome

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
The prognosis for patients with heart failure is poor. Five year mortality rates as high as 25% have been reported—these rates are higher than for myocardial infarction or many types of cancer.¹¹ Although in-hospital mortality is relatively low in patients with worsening chronic heart failure, 60 day re-admission and mortality rates are as high as 40%.

A number of factors are associated with repeated rehospitalizations among patients with AHFS. Factors that are independently associated with exacerbations of heart failure include previous hospitalization, duration of symptoms >18 months, ischaemic aetiology, atrial fibrillation, high blood urea nitrogen, mild anaemia or hyponatraemia, persistent congestion, low systolic blood pressure, and poor exercise capacity at the time of discharge.^12–14 Presence of ischaemia and history of previous hospitalization are also predictive of recurrent hospitalization and 1 year mortality.^12,13 It is useful to recognize that, while some of these prognostic indicators are non-modifiable, appropriate action can be taken to redress others (such as hyponatraemia, anaemia, or congestion) during hospitalization.

Recent developments in heart failure prognostics include the use of biochemical markers to predict disease outcome. B-type natriuretic peptide (BNP) is produced by the myocardium in heart failure, as part of the body's compensatory response to the disease. Changes in levels of BNP may be predictive of early re-admission and mortality rates in patients hospitalized with heart failure.^15–17 In addition, the potential of cardiac troponin levels to predict outcome in patients with heart failure has been realized in recent years.^18,19 A combination of elevated cardiac troponin I and BNP is associated with a 12-fold increase in mortality risk.²⁰ Measurement of these and other biomarkers is likely to become an important future component of AHFS clinical management.

	Treatment targets

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
The key short-term treatment goal in patients with AHFS is to improve symptoms and haemodynamics, while preserving renal function and preventing—and protecting against—myocardial injury. Treatment of comorbidities is often a key part of the therapeutic strategy: effective management of cardiorenal syndrome is particularly important. No long-term deleterious effects should arise from acute therapy. In the longer-term, an important target is to implement life-saving therapies, including angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, and spironolactone.

Many treatment modalities exist for AHFS, including pharmacological, non-pharmacological, electrical, and surgical therapies. The management of heart failure can be divided into four distinct stages: (i) acute therapy during the first 24 h after hospital admission, (ii) management of the patient—who may already be stabilized or remain symptomatic—over the next few days, (iii) establishment of long-term medication before discharge from hospital, and (iv) ongoing outpatient or community-based management of chronic disease. Although significant progress has been made in validating evidence-based therapies for chronic heart failure, the use of most acute treatments remains empirical. There is a pressing need for clinical trials to define optimal treatment strategies, both during the first 24–48 h of hospitalization and over the next few days, particularly in those patients for whom acute therapy does not result in sufficient symptomatic and haemodynamic improvement.

	Acute therapies

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
Intravenous acute therapies for AHFS include diuretics, vasodilators (e.g. nitrovasodilators and nesiritide), and positive inotropes (e.g. dobutamine, dopamine, milrinone, and digoxin). Evidence for the use of these therapies is derived from two main sources: empirical data and randomized clinical trials. The use of some medications, including diuretics, nitroglycerin, dobutamine, dopamine, and digoxin, is still based mainly on empirical data. Several randomized trials have been carried out, particularly for more recently introduced therapies, but many of these have yielded equivocal or negative results.^{13,14,21–26}

Almost all patients with AHFS receive an intravenous diuretic. Despite their widespread use, there are no randomized, placebo-controlled trial data to support their efficacy and safety in AHFS. Furthermore, the use of high-dose diuretics has been associated with poor outcomes, particularly in patients with compromised renal function.^27–29 A recent analysis of ADHERE data found a significantly longer length of stay and intensive care unit length of stay, and slightly higher mortality, among patients with AHFS who were treated with intravenous diuretics compared with those who did not receive these drugs.³⁰

The beneficial effects of digoxin in patients with AHFS include increased cardiac index; decreased heart rate, left ventricular filling pressure, and right atrial pressure; and attenuation of neurohormonal abnormalities.³¹ In a randomized, placebo-controlled trial, chronic digoxin therapy was found to reduce the rate of hospitalization both overall and for worsening heart failure.³²

Vasodilators provide symptomatic improvement by decreasing pre-load and reducing cardiac filling pressures. However, nitrovasodilators are associated with the development of tachyphylaxis within 48 h, and long-term efficacy and safety data are lacking. A recently developed alternative is nesiritide, which provides a rapid and sustained reduction in pulmonary capillary wedge pressure, with no evidence of tachyphylaxis.²¹ Nesiritide has been available in the USA since 2001, and the latest data from ADHERE indicate that it is now more widely used than nitroglycerin.⁹

Positive inotropic agents are often used in the treatment of patients with AHFS, but again, few data on their efficacy and safety are available. Several studies have shown that dobutamine and milrinone are associated with increased risk of arrhythmias.^33,34 Furthermore, these agents do not reduce length of hospital stay and may in fact increase mortality, particularly in patients with ischaemic heart failure.^25,33–37 These therapies, therefore, should not be routinely used in patients with AHFS, but restricted to those individuals with low cardiac output.

Another relatively new agent for treatment of AHFS is the calcium-sensitizing inotropic agent levosimendan. This agent which has been shown to provide haemodynamic improvement in patients with AHFS^22,38 is not associated with arrhythmias but may be associated with improved mortality compared with dobutamine.²² Levosimendan may therefore represent a more acceptable alternative to positive inotropes in patients with low cardiac output.

	Implementation of life-saving therapies

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
The evidence-base for the utility of several long-term heart failure therapies, including ACE-I and beta-blockers, is extensive. Despite this, many patients who would benefit greatly from these life-saving drugs do not receive them. Initiating the use of such therapies in hospital is likely to increase uptake and compliance—a recent study found that in-hospital initiation of chronic beta-blockade was not only safe but also resulted in increased beta-blocker use at 60 days post-discharge.³⁹ However, the rate of prescription of chronic heart failure medications to patients discharged from hospital after an episode of AHFS is disappointingly low in both Europe and the USA.^9,40 This problem is currently being addressed by the OPTIMIZE-HF (Organized Program to Initiate Life-Saving Treatment in Hospitalized Patients with Heart Failure) programme, which aims to improve medical care and education of patients hospitalized with heart failure and initiate life-saving therapies before hospital discharge in eligible patients.³ By reducing the number and severity of acute exacerbations, enhanced management of chronic heart failure could not only improve quality and quantity of life for this large population, but would also be expected to make a substantial contribution to lowering the financial and social burden of AHFS.

	Modern management of AHFS

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
As a result of the recent increased clinical and research interest in AHFS, the inaugural International Meeting on Acute Heart Failure Syndromes was held in Cannes, France on 1–2 May 2004. This meeting, co-chaired by us, brought together a multidisciplinary audience of clinicians and representatives from both the pharmaceutical industry and various regulatory bodies throughout Europe and beyond. The objectives of the meeting were to highlight the challenges posed by AHFS, to stimulate thoughts and discussion among all relevant parties, and to catalyse clinical change.

The first session of the meeting, Modern Management of Acute Heart Failure Syndromes, was chaired by John Burnett (Rochester, USA) and Alexandre Mebazaa (Paris, France) and supported by an unrestricted educational grant from GlaxoSmithKline. The session covered a range of topics, including the epidemiology and management of AHFS in both Europe and the USA, present and future therapy options, and the current and potential use of BNP as a treatment for heart failure. The articles in this supplement authored by the four speakers further explore these issues.

The Second International Meeting on Acute Heart Failure Syndromes will be held in Cannes on 1–3 April 2005.

	Acknowledgements

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 
Meeting session and publication were supported by an unrestricted educational grant from GlaxoSmithKline Ltd. M.G. has acted as a consultant to GlaxoSmithKline Ltd and Otsuka America Pharmaceutical Inc., and currently holds research grants from Scios Inc.

	References

Top Abstract Introduction Terminology Demographics Pathophysiology Prognosis/predictors of outcome Treatment targets Acute therapies Implementation of life-saving... Modern management of AHFS Acknowledgements References

 

1. American Heart Association. Heart Disease and Stroke Statistics – 2004 Update. Dallas, TX: American Heart Association; 2003.
2. Krumholz HM, Parent EM, Tu N et al. Readmission after hospitalization for congestive heart failure among Medicare beneficiaries. Arch Intern Med 1997;157:99–104.[Abstract]
3. Klein L, Gheorghiade M. Therapeutic strategies for patients hospitalized with worsening heart failure. Ital Heart J 2003;4:71–74.[Medline]
4. Zannad F, Cohen Solal A, Desnos M et al. Clinical and etiological features, management and outcomes of acute heart failure: the EFICA cohort study. Eur Heart J 2002;4(Suppl.):579.
5. Zannad F, Briancon S, Juilliere Y et al. Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL Study. Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine. J Am Coll Cardiol 1999;33:734–742.[Abstract/Free Full Text]
6. Cleland JG, Swedberg K, Follath F et al. The EuroHeart Failure Survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J 2003;24:442–463.[Abstract/Free Full Text]
7. Fonarow GC. The Acute Decompensated Heart Failure National Registry (ADHERE): opportunities to improve care of patients hospitalized with acute decompensated heart failure. Rev Cardiovasc Med 2003;4(Suppl. 7):S21–S30.
8. McMurray J. Heart failure: we need more trials in typical patients. Eur Heart J 2000;21:699–700.[Free Full Text]
9. The ADHERE Registry. First Quarter 2004 National Benchmark Report. Fremont, CA: Scios Inc.; 2004.
10. Perna ER, Macin SM, Parras JI et al. Cardiac troponin T levels are associated with poor short- and long-term prognosis in patients with acute cardiogenic pulmonary edema. Am Heart J 2002;143:814–820.[CrossRef][ISI][Medline]
11. Stewart S, MacIntyre K, Hole DJ et al. More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 2001;3:315–322.[CrossRef][ISI][Medline]
12. Opasich C, Rapezzi C, Lucci D et al. Precipitating factors and decision-making processes of short-term worsening heart failure despite "optimal" treatment (from the IN-CHF Registry). Am J Cardiol 2001;88:382–387.[CrossRef][ISI][Medline]
13. Cuffe MS, Califf RM, Adams KF Jr et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 2002;287:1541–1547.[Abstract/Free Full Text]
14. Gheorghiade M, Gattis WA, O'Connor CM et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 2004;291:1963–1971.[Abstract/Free Full Text]
15. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med 1999;341:577–585.[Free Full Text]
16. Cheng V, Kazanagra R, Garcia A et al. A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. J Am Coll Cardiol 2001;37:386–391.[Abstract/Free Full Text]
17. Colucci WS, Elkayam U, Horton DP et al. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. N Engl J Med 2000;343:246–253.[Abstract/Free Full Text]
18. Del Carlo CH, O'Connor CM. Cardiac troponins in congestive heart failure. Am Heart J 1999;138:646–653.[CrossRef][ISI][Medline]
19. Ishii J, Nomura M, Nakamura Y et al. Risk stratification using a combination of cardiac troponin T and brain natriuretic peptide in patients hospitalized for worsening chronic heart failure. Am J Cardiol 2002;89:691–695.[CrossRef][ISI][Medline]
20. Horwich TB, Patel J, MacLellan WR et al. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003;108:833–838.[Abstract/Free Full Text]
21. VMAC Investigators. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002;287:1531–1540.[Abstract/Free Full Text]
22. Follath F, Cleland JG, Just H et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002;360:196–202.[CrossRef][ISI][Medline]
23. Kaluski E, Kobrin I, Zimlichman R et al. RITZ-5: randomized intravenous TeZosentan (an endothelin-A/B antagonist) for the treatment of pulmonary edema: a prospective, multicenter, double-blind, placebo-controlled study. J Am Coll Cardiol 2003;41:204–210.[Abstract/Free Full Text]
24. O'Connor CM, Gattis WA, Adams KF, Jr et al. Tezosentan in patients with acute heart failure and acute coronary syndromes: results of the Randomized Intravenous TeZosentan Study (RITZ-4). J Am Coll Cardiol 2003;41:1452–1457.[Abstract/Free Full Text]
25. Felker GM, Benza RL, Chandler AB et al. Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. J Am Coll Cardiol 2003;41:997–1003.[Abstract/Free Full Text]
26. Torre-Amione G, Young JB, Colucci WS et al. Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 2003;42:140–147.[Abstract/Free Full Text]
27. Francis GS, Siegel RM, Goldsmith SR et al. Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis. Ann Intern Med 1985;103:1–6.
28. Northridge D. Frusemide or nitrates for acute heart failure? Lancet 1996;347:667–668.[CrossRef][ISI][Medline]
29. Mehta RL, Pascual MT, Soroko S et al. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA 2002;288:2547–2553.[Abstract/Free Full Text]
30. Emerman C, De Marco T, Costanzo MR et al. Impact of intravenous diuretics on the outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. In 8th Annual Scientific Meeting of the Heart Failure Society of America; September 12–15 2004; Toronto, Canada.
31. Gheorghiade M, Hall V, Lakier JB et al. Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure. J Am Coll Cardiol 1989;13:134–142.[Abstract]
32. 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.
33. Burger AJ, Horton DP, LeJemtel T et al. Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT study. Am Heart J 2002;144:1102–1108.[CrossRef][ISI][Medline]
34. Siostrzonek P, Koreny M, Delle-Karth G et al. Milrinone therapy in catecholamine-dependent critically ill patients with heart failure. Acta Anaesthesiol Scand 2000;44:403–409.[CrossRef][ISI][Medline]
35. Burger AJ, Elkayam U, Neibaur MT et al. Comparison of the occurrence of ventricular arrhythmias in patients with acutely decompensated congestive heart failure receiving dobutamine versus nesiritide therapy. Am J Cardiol 2001;88:35–39.[ISI][Medline]
36. Silver MA, Horton DP, Ghali JK et al. Effect of nesiritide versus dobutamine on short-term outcomes in the treatment of patients with acutely decompensated heart failure. J Am Coll Cardiol 2002;39:798–803.[Abstract/Free Full Text]
37. Gheorghiade M, Gattis WA, Klein L. OPTIME in CHF trial: rethinking the use of inotropes in the management of worsening chronic heart failure resulting in hospitalization. Eur J Heart Fail 2003;5:9–12.[CrossRef][ISI][Medline]
38. Slawsky MT, Colucci WS, Gottlieb SS et al. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation 2000;102:2222–2227.[Abstract/Free Full Text]
39. Gattis WA, O'Connor CM, Gallup DS et al. Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial. J Am Coll Cardiol 2004;43:1534–1541.[Abstract/Free Full Text]
40. Komajda M, Follath F, Swedberg K et al. The EuroHeart Failure Survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J 2003;24:464–474.[Abstract/Free Full Text]
41. Nieminen MS, Akkila J, Hasenfuss G et al. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol 2000;36:1903–1912.[Abstract/Free Full Text]

CiteULike    Connotea    Del.icio.us    What's this?

This Article Abstract FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Google Scholar Articles by Gheorghiade, M. Articles by Zannad, F. Search for Related Content PubMed Articles by Gheorghiade, M. Articles by Zannad, F. Social Bookmarking          What's this?

Online ISSN 1554-2815 - Print ISSN 1520-765X

Copyright © 2008 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics