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Ross T. Tsuyuki, BSc(Pharm), PharmD, MSc; Robert S. McKelvie, MD, PhD; J. Malcolm O. Arnold, MD; Álvaro Avezum, Jr, MD; Antônio C. P. Barretto, MD; Antonio C. C. Carvalho, MD; Debra L. Isaac, MD; Allan D. Kitching, MD, MSc; Leopoldo S. Piegas, MD, PhD; Koon K. Teo, MB, PhD; Salim Yusuf, DPhil, FRCPC

Arch Intern Med. 2001;161:2337-2342.

Background  Few studies have prospectively and systematically explored the factors that acutely precipitate exacerbation of congestive heart failure (CHF) in patients with left ventricular dysfunction. Knowledge of such factors is important in designing measures to prevent deterioration of clinical status. The objective of this study was to prospectively describe the precipitants associated with exacerbation of CHF status in patients enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study.

Methods  We conducted a 2-stage, multicenter, randomized trial in 768 patients with CHF who had an ejection fraction of less than 40%. Patients were randomly assigned to receive enalapril maleate, candesartan cilexetil, or both for 17 weeks, followed by randomization to receive metoprolol succinate or placebo for 26 weeks. Investigators systematically documented information on clinical presentation, management, and factors associated with the exacerbation for any episode of acute CHF during follow-up.

Results  A total of 323 episodes of worsening of CHF occurred in 180 patients during 43 weeks of follow-up; 143 patients required hospitalization, and 5 died. Factors implicated in worsening of CHF status included noncompliance with salt restriction (22%); other noncardiac causes (20%), notably pulmonary infectious processes; study medications (15%); use of antiarrhythmic agents in the past 48 hours (15%); arrhythmias (13%); calcium channel blockers (13%); and inappropriate reductions in CHF therapy (10%).

Conclusions  A variety of factors, many of which are avoidable, are associated with exacerbation of CHF. Attention to these factors and patient education are important in the prevention of CHF deterioration.

From the Division of Cardiology, University of Alberta, Edmonton (Dr Tsuyuki); the Division of Cardiology, McMaster University, Hamilton, Ontario (Drs McKelvie, Kitching, Teo, and Yusuf); the Division of Cardiology, University of Western Ontario, London (Dr Arnold); the Dante Pazzanese Cardiology Institute (Drs Avezum and Piegas), the Heart Institute, University of São Paulo Medical School Hospital (Dr Barretto), and the Paulista School of Medicine, Federal University of São Paulo (Dr Carvalho), São Paulo, Brazil; and the Division of Cardiology, University of Calgary, Calgary, Alberta (Dr Isaac).

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