What gets you into trouble is not what you don't know, it's what you know for sure, that just ain't so." Yogi Berra A lthough the advent of clinical practice guidelines and disease management strategies for patients with heart failure has resulted in dramatic overall improvements in patient care, the day-to-day management of individual patients with heart failure remains challenging. As one example, current heart failure practice guidelines recommend that doses of angiotensin-converting enzyme

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... nhibitors and ␤-blocker should be titrated to the levels used in clinical trials. Although this "one dose fits all" approach is entirely logical (and necessary) from the standpoint of clinical trial design, it is not necessarily logical in the management of individual heart failure patients, in whom body mass (and hence drug disposition) may range from morbidly obese to cachectic. The above example, which is emblematic of the types of problems that clinicians face when they try to adapt and individualize practice guidelines for their own patients, raises the broader question of how clinicians should individualize management strategies for heart failure. See p 1278 In the current issue of the Circulation, Anand and colleagues 1 report on changes in brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) levels in patients who were enrolled in the Valsartan Heart Failure Trial (Val-HeFT). The authors measured BNP and NE levels before randomization and during follow-up in approximately 4300 patients enrolled in the trial. As with other studies that have examined therapeutic responses in relation to levels of circulating neurohormones, Anand and colleagues 1 observed that the relative risk of having an event was significantly higher for those patients in whom the baseline BNP and NE levels were significantly elevated. The authors also found that BNP was a more sensitive predictor of morbidity and mortality than was NE. However, the salient finding in the study by Anand and colleagues 1 was that changes in BNP and NE levels tracked therapeutic outcomes. That is, morbidity and mortality were least in those patients with greatest decrease in BNP and NE levels, whereas the morbidity and mortality were greatest in those patients with the greatest percent increase in BNP and NE levels during the course of the trial. Thus, these data from a large scale well-designed clinical trial provide compelling evidence that changes in neurohormonal levels over time are associated with changes in morbidity and mortality in heart failure patients. One of the important issues raised by these findings is whether clinicians should use changes in levels of biomarkers, such as PNE and/or BNP, to guide heart failure management. Given the potential importance of this concept, it is useful to review the emerging role of biomarkers in treatment of patients with heart failure, as well as to discuss whether we now have sufficient information to use biochemical markers as a means to guide heart failure management.