July 18th, 2013
BNP-Based Screening + Collaborative Care to Prevent Heart Failure?
John Ryan, MD and Kenneth McDonald, MD
CardioExchange’s John Ryan interviews Kenneth McDonald about the STOP-HF randomized trial, published in JAMA, of BNP-based screening versus usual primary care for preventing new-onset heart failure.
THE STUDY
Researchers randomized 1374 patients older than age 40 with at least one cardiovascular risk factor to receive usual primary care (control) or screening that involved brain-type natriuretic peptide (BNP) testing and, for patients with BNP levels ≥50 pg/mL, echocardiography and collaborative care by the patient’s PCP and a specialist cardiovascular center. The intervention group underwent significantly more cardiovascular investigations and received significantly more renin-angiotensin-aldosterone system (RAAS)–based therapy.
During a mean follow-up of 4.2 years, incidence of the primary endpoint — prevalence of asymptomatic LV systolic dysfunction with or without newly diagnosed heart failure — was significantly lower in the intervention group than the control group (5.3% vs. 8.7%), as was the incidence of asymptomatic LV systolic dysfunction alone (4.3% vs. 6.6%). New-onset heart failure was less common in the intervention group than in the control group (1.0% vs. 2.1%), but not significantly so.
THE INTERVIEW
Ryan: What mechanism do you think explains the difference in outcomes, especially given the small difference in RAAS-modifying therapy?
McDonald: Great question. It was probably multifactorial. RAAS-modifying therapy likely made a contribution, but the data also showed strongly that improved adherence, likely encouraged by BNP-based CV coaching, played a role in better LDL management. That was despite any recorded difference in therapy between the groups and, similarly, a strong trend toward a lower rate of heart failure (HF) in the intervention arm without any change in HF-modifying therapies.
Ryan: In the conclusion of the abstract, you report the combined endpoint instead of the primary endpoint. Could this give the false impression that there was a significant benefit in HF admissions?
McDonald: I don’t think so. The method of reporting the endpoint in the abstract was restricted by space. We wanted to remain faithful to the combined endpoint. It was an editorial decision, as I recall, to insert the data on asymptomatic LV systolic dysfunction as a stand-alone comment.
Ryan: What needs to be done before we consider adopting BNP-based screening, given the small size of the trial and the use of a surrogate endpoint as the primary outcome?
McDonald: Again, an important issue. We would like to see this interesting result confirmed by a large international trial.
Ryan: If the benefit is driven by changes in diastolic dysfunction, what does that mean? How does that relate to outcomes?
McDonald: We did see a signal when confining the analysis to new-onset HF and asymptomatic LV systolic dysfunction, but nonetheless the endpoint was dominated by asymptomatic LV diastolic dysfunction. However, the asymptomatic left ventricular diastolic dysfunction at the level that we defined is a secure independent predictor of outcome for heart failure and other CV events, most notably atrial fibrillation. I agree that we don’t yet know whether an intervention focused on asymptomatic LV diastolic dysfunction is effective. All that we can advocate for now is heightened attention to risk factors.
JOIN THE DISCUSSION
Do you think that BNP-based screening to prevent heart failure has promise? How does the present study affect your thinking?
3 Responses to “BNP-Based Screening + Collaborative Care to Prevent Heart Failure?”
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The “psycologic” meaning of this CV risk factor (especially for Heart Failure) is very strong for the patients: it is related directly to the stress of “his/her” heart (while LDL doesn’t link so much to it). In this manner you (doctor)can obtain from the patient more adherence to a modified lifestyle or other intervention therapies.
I have not read the article in full text, but judging from the abstract the Authors have assumed that BNP values of only ≥ 50 pg / ml are a sufficient indication for making an echocardiogram in asymptomatic individuals, provided they have risk factors( one or more) for cardiovascular disease. In contrast, I believe that this limit is too low and that it can generate a large number of ultrasound examinations negative for ventricular dysfunction. In Italy, according to Mannacio et al (1) the BNP level of 120 pg/ml was 91% sensitive and 85% specific, while 300 pg/ml was 80% sensitive and 91% specific for moderate or severe diastolic dysfunction ( within a cohort of patients with calcific aortic valve stenosis undergoing BNP assessment after surgical correction). Triggering a debate about this topic would be perhaps useful. In other words , it may be interesting to explore the cost-effectiveness of a screening program that includes a so frequent use of the echocardiogram for asymptomatic subjects. In this manner the very reliable negative predictive value of BNP would be not properly exploited , in my opinion. This in turn would result in a great number of unnecessary echocardiographic examinations. In this way, a very large number of cardiologists should be devoted to functions of echocardiographic assessment for screening purposes in apparently healthy individuals encumbered with one or more risk factors for CVD. However, in my opinion, a similarly accurate, but more cost-effective screening could be carried out using a BNP cut-off of 100 – 120 pg / ml.
1) Mannacio V, Antignano A, De Amicis V, Di Tommaso L, Giordano R, Iannelli G, Vosa C. B-type natriuretic peptide as a biochemical marker of left ventricular diastolic function: assessment in asymptomatic patients 1 year after valve replacement for aortic stenosis. Interact Cardiovasc Thorac Surg. 2013 May 8. [Epub ahead of print]
I’d like to congratulate Dr. McDonald and his colleagues for a very important and innovative study. Despite the obvious need for better early detection and prevention strategies for heart failure, and the consistent data linking biomarkers such as BNP/NT-proBNP and troponins with heart failure outcomes in the population, the field has been “stuck” because there has been very little information on what to do with the results of these tests. In part, this is because the type of study performed by McDonald et al is much harder to do than the observational studies performed to show the potential value of the biomarkers for risk assessment.
In my view, this study offers a way forward. The approach the investigators use is practical and acknowledges the limitations of these biomarkers–namely that they provide information that is not specific enough with regard to disease mechanisms to guide a uniform therapeutic response. Thus, the “gatekeeper” strategy, where the test is used to guide the intensity of monitoring and use of noninvasive imaging is a logical and well reasoned approach, both for the natiuretic peptides and cardiac troponins.
I completely agree that larger studies will be needed to assess the effectiveness and cost-effectiveness of this strategy, but at least a potential path forward has been defined. Well done!