Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

Canadian Cardiovascular Congress 2007

Quebec City, Quebec / October 20-24, 2007

Heart failure diagnosis is typically based on clinical evaluation, including history, physical examination, chest X-ray, and sometimes a left ventricular function assessment. However, various symptoms of heart failure, such as dyspnea, edema and fatigue, may mimic those of other illnesses. Greater speed and accuracy of heart failure diagnosis in primary and emergency care settings has the potential to expedite and improve both early and longer-term management of the condition.

Several studies have now determined that measurement of B-type or brain natriuretic peptide (BNP) and/or the aminoterminal fragment NT-proBNP are complementary to clinical evaluation in the diagnosis and management of heart failure. Released when cardiac myocytes are stretched excessively, these peptides reach elevated levels in the blood in the setting of heart failure and other conditions in which cardiac ventricles are under strain. Their release leads to decreases in cardiac output and blood volume.

Biomarker Measurement Recommended in Guidelines

In its current guidelines on heart failure (Arnold et al. Can J Cardiol 2006;22(1):23-45 and 2007;23(1):21-45), the CCS recommends that one of the two biomarkers should be measured “to help confirm or rule out...heart failure... in patients in whom the clinical diagnosis is in doubt.” Their measurement may also help establish prognosis in patients with confirmed heart failure (for example, the concentration of NTproBNP in the blood has been shown to be significantly related to New York Heart Association heart failure class) and help guide therapeutic decisions, although the evidence for these applications is considered less robust, comments Dr. Gordon Moe, Associate Professor of Medicine, University of Toronto, and Director, Heart Failure Program and Biomarker Laboratory, St. Michael’s Hospital, Toronto. “For diagnostic purposes...the data are strong. For someone in whom the diagnosis is obvious, I don’t think it’s helpful. That said, if the patient already has a history of heart failure, it’s a good prognostic marker, but the problem is we’re not sure how to deal with that information: we know the patients with higher measurements do not do well, but what to do about it? That’s still a dilemma. A third indication is following patients in terms of therapy. The data are not very clear-cut yet – that’s why we don’t give it a very strong recommendation – but that’s something to be considered, as well,” Dr. Moe suggests.

Clinicians measuring BNP or NT-proBNP as an adjunct to diagnosis can be guided by the cutpoints in the CCS guidelines, which emanate from the recent PRIDE study (Januzzi et al. Am J Cardiol 2005;95;948-54) and take into account the effect of age on NT-proBNP, Dr. Moe adds. For example, in patients aged between 50 and 75 years, heart failure is considered very likely if the patient’s NT-proBNP is >900 pg/mL, while the cutpoint is >1800 pg/mL in more elderly individuals.

IMPROVE-CHF Findings

Findings from the IMPROVE-CHF study (Improved Management of Congestive Heart Failure) (Circulation 2007; 115(24)3103-10) have contributed to the CCS recommendations on the use of BNP or NT-proBNP, notes Dr. Moe. In this study, investigators evaluated the clinical and economic value of adding NT-proBNP measurement to clinical assessment of patients presenting to emergency rooms with dyspnea of suspected cardiac origin. Five hundred patients (mean age approximately 70 years) were included in the analysis; about 35% had or reported a prior history of heart failure or left ventricular dysfunction. They were randomly allocated to NT-proBNP-guided care (n=246) or usual care (n=254). Physicians caring for the first group were given the NT-proBNP findings and information on their interpretation. “We also did a second NT-proBNP assay on patients who were admitted to hospital and those results were also given to the doctor [to guide management post-discharge],” Dr. Moe specified.

The IMPROVE-CHF results confirmed that NT-proBNP levels have strong predictive value in patients with dyspnea: they are significantly higher in patients with heart failure than in those without (median 3697 vs. 212 pg/mL, P<0.00001). The study’s key findings were that management guided by NT-proBNP measurement leads to time and resource savings in the first 60 days after the patient’s presentation. Notably, individuals whose biomarker levels were known spent 21% less time in the emergency room (5.6 vs. 6.3 hours, P=0.031) and underwent fewer tests for investigation of dyspnea. In the 60 days following their entry into the study, direct inpatient and outpatient medical costs for patients whose NT-proBNP levels were measured were 15% lower (US$5180 vs. $6129, P=0.0232). Over the same period, the number of patients who required rehospitalization for heart failure was 35% lower in the NT-proBNP group than in the usual care group. According to Dr. Moe, there are several possible reasons for this finding, including more targeted use of heart failure therapies in patients with a definitive diagnosis.

More Analysis on Outcomes

Dr. Moe and colleagues will present additional analysis from the IMPROVE-CHF study during the scientific sessions on Tuesday, October 23. In one paper (abstract 628), they indicate that the individuals whose therapy was guided by NT-proBNP had shorter length of both initial hospital stay (4.6 vs. 6.1 days, P=0.014) and subsequent hospital stays (1.3 vs. 2.5 days, P<0.004). They also had about 50% fewer readmissions (24 vs. 50, P=0.029). Dr. Moe comments, “Interestingly enough, NT-proBNP did not predict rehospitalization, which is in contrast to our previous studies. But then, our follow-up was only out to 60 days following randomization, so that may be too soon [to see an effect].” In this analysis, older age was the principal predictor of rehospitalization or death. Body mass index greater than 25-30 kg/m2 was predictive of fewer events, Dr. Moe adds.

In a separate presentation, Dr. Moe will describe the finding that anemia strongly predicted 60-day rehospitalization in the IMPROVE-CHF study. “This is observed consistently with the patient with chronic heart failure, but in acute heart failure it has not been reported before,” he remarks. There is a strong relationship between anemia and NT-proBNP, he states. “The higher the NT-proBNP, the lower the hemoglobin.”

Wider Role for Biomarkers?

Current evidence on BNP and NT-proBNP confirms their utility in differentiating heart failure from other conditions causing dyspnea and to some degree in guiding therapy. If the results of IMPROVE-CHF can be extrapolated to national health care, the use of NT-proBNP would mean savings of approximately $210 to 345 million annually. Unfortunately, Canadian hospitals and physicians have been slow to employ these biomarkers on a routine basis, remarks Dr. Moe. He adds that while the IMPROVE-CHF study focused on emergency room presentation, many elderly patients with dyspnea present to general or family physicians’ offices and that the test might prove highly useful in such primary care settings. “General practitioners see a lot of patients who have shortness of breath and in whom a diagnosis is unclear. This test could be extremely helpful.”

Please plan to attend:

Oral Sessions: Tuesday, October 23, 2007 (09:00-10:30) Room 302A-B, Level 3.

09:30 - 628. Provision of knowledge of NT-proB-type natriuretic peptide results improves hospitalization outcomes in patients with suspected acute heart failure. G Moe, Z Mariano, F Camacho.

09:45 - 629. Relationship between anemia and natriuretic peptide level in patients with suspected acute heart failure. G Moe, Z Mariano, F Camacho.