ArticlesTreatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations
Introduction
Treatment of systolic heart failure has advanced considerably in the past 20 years, due largely to a growing understanding of the pathophysiological role of neurohormonal factors.1, 2 Landmark trials established angiotensin-converting-enzyme (ACE) inhibitors as cornerstone therapy3, 4 and showed reductions in mortality and morbidity with spironolactone5 and β-blockers.6, 7 In addition, an intensive multidisciplinary approach to follow-up reduces hospital readmission.8, 9
Even with intensive treatment, mortality and morbidity are high.3, 4, 5, 6 Questions remain as to how proven therapies, such as ACE inhibitors, should be implemented and what doses are best.10, 11, 12, 13 Furthermore, it is not clear whether diuretic doses should be as low as possible to limit hypotension and renal impairment or as high as tolerable to reduce cardiac loading.
Current treatment strategies ignore plasma neurohormone concentrations, yet they are independent markers of cardiac status and prognosis in cardiac disease including heart failure.14, 15, 16 To date, brain natriuretic peptide (BNP), and particularly its aminoterminal portion (N-BNP), appears to be the most powerful neurohormonal predictor of left-ventricular function and prognosis.17, 18, 19, 20 BNP and N-BNP are secreted primarily from the left ventricle in response to changes in left-ventricular wall stretch.21 Concentrations of BNP and N-BNP are related to left-ventricular filling pressures22 and wall stress.23 BNP concentrations accurately discriminate between decompensated heart failure and other causes of breathlessness that lead to hospital admission.24 BNP concentrations fall after treatment with loop diuretic and ACE inhibitors, reflecting a reduction in left-ventricular filling pressure.22 Pilot data have shown that vasodilator treatment can be titrated to reduce BNP concentrations towards the normal range.25
We hypothesised that titration of treatment to reduce plasma N-BNP concentrations in patients with systolic heart failure would prove superior to treatment with empirical trial-based therapy dictated by clinical acumen.
Section snippets
Patients
Patients aged 35–85 were recruited after hospital admission with decompensated heart failure or from a specialist cardiology outpatient clinic. All had impaired left-ventricular systolic function (left-ventricular ejection fraction <40% on 2-dimensional echocardiography), established symptomatic heart failure (New York Heart Association [NYHA] class II–IV), and were treated with ACE inhibitors, loop diuretic with or without digoxin.
Patients were excluded by recent acute coronary syndrome
Baseline variables
Between Feb 1, 1998, and Jan 31, 1999, 69 patients were recruited of whom 33 were randomised to the BNP group and 36 to the clinical group. There were no withdrawals from the trial, which ended on July 31, 1999, with median follow-up of 9·7 months in the BNP group and 9·5 months in the clinical group (p=0·78) and complete 6 month follow-up on all patients. The groups were matched for demographic and clinical features, left-ventricular function, and functional status (table 2).
N-BNP concentrations
In the BNP group,
Discussion
Drug treatment of established heart failure is increasingly complex yet objective practical guidelines for management of individual patients are lacking. We surmised that pharmacotherapy guided by plasma N-BNP concentrations would prove more effective than usual clinical practice. First, our study shows that circulating N-BNP concentrations can be reduced by intensification of drug therapy in heart failure. Mean plasma N-BNP concentrations for patients for the BNP group declined to well within
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