Heart failure is one of the fastest growing CV conditions in Canada. Over 750,000 Canadians have it, another 100,000 develop heart failure each year, and almost 50% die within five years of diagnosis. The majority of these patients are ambulatory, meaning that the initial suspicion and diagnosis of heart failure rests with their family physician. But the diagnosis of heart failure can be difficult through history and examination alone, especially in elderly patients with non-specific dyspnea and other comorbidities. That's where the natriuretic peptides (NPs) come in.

Certain biomarkers can revolutionize the diagnosis and treatment of common CV conditions. Think of LDL-cholesterol for predicting and reducing risk of atherosclerotic CVD, or troponin levels for diagnosis and management of acute coronary syndromes. Similarly, NPs have revolutionized the diagnosis and prognosis of heart failure. And with wider availability of NP testing and provincial coverage, now is a good time for primary care physicians to become familiarized with when and how to use NPs for the diagnosis of heart failure.

What are natriuretic peptides?

NPs are proteins secreted by the myocardium in response to volume or pressure overload. BNP, or brain NP, is biologically active causes natriuresis, diuresis and vasodilation, improving myocardial relaxation and reducing myocardial fibrosis. BNP also opposes activated renin-angiotensin-aldosterone and sympathetic nervous systems. NT-pro-BNP is released from the same molecule that makes BNP but is biologically inert. However, both BNP and NT-pro-BNP provide comparable accuracy in the diagnosis and prognosis of heart failure.

When should I consider ordering an NP level?

NP testing is recommended in patients with risk factors for heart failure and in those in whom the diagnosis of heart failure remains uncertain. In addition, NP levels can be used to predict prognosis and disease severity, and also to potentially guide heart failure therapy, although the latter remains controversial. NPs can also be useful to rule out heart failure in a patient who presents with dyspnea of unclear etiology.

How do I interpret NP levels?

Traditionally, NP levels are reported as pg/mL. NP levels are higher in patients presenting with acute heart failure, such as those in the emergency room, vs those with chronic heart failure. But for today's discussion, let's focus on ambulatory patients, the kind seen in family practices. In these patients, a BNP level or < 50 pg/mL or an NT-pro-BNP level of < 125 pg/mL can be used to effectively rule out heart failure. In patients with suspected heart failure whose NP levels are higher than these thresholds, further investigation including echocardiography, as well as specialist consultation, should be considered. Remember that NP levels should be treated as a continuous variable, so that the higher the value, the higher the likelihood of heart failure. And most importantly, NP levels do not differentiate between heart failure with reduced or preserved ejection fraction.

What else other than heart failure can affect NP levels?

NP levels can sometimes be falsely low, especially in patients with obesity, but still are predictive of heart failure diagnosis and severity. Therefore, we suggest using NP cut-points that are lowered by 50% in these patients. NP levels are also falsely low in patients with flash pulmonary edema, or those with severe mitral valve disease, though these conditions are uncommonly encountered in primary care.

NP levels can be artificially high in women and in the elderly, although the mechanisms for this are poorly understood. They are also higher in patients with chronic kidney disease, a factor that should be kept in mind since CKD not uncommonly coexists with heart failure.

Should I order BNP, NT-pro-BNP, or both? 

Both BNP and NT-pro-BNP provide similar accuracy in helping to diagnosis heart failure and in assessing disease activity. Therefore, we suggest you become familiar with one or the other and its cut-points, and order that test as your routine NP in the appropriate clinical situations. The one proviso is for patients being treated with a neprilysin inhibitor (sacubitril/valsartan). In these patients, it is recommended to preferentially use NT-pro-BNP rather than BNP for heart failure diagnosis and prognosis. Finally, NP tests can be performed in the non-fasting state.

I think my patient might have heart failure, and their NP level is above the threshold you mentioned. What do I do now?

If your patient has suspected heart failure, and their NP level is high, you have more work to do. Assuming you have already checked their other relevant labwork (CBC, electrolytes, HbA1c, renal and thyroid function), these patients warrant an ECG and an echocardiogram. If the additional testing further convinces you of the heart failure diagnosis, it is time to act. This means optimizing treatment of underlying risk factors (hypertension, diabetes), and initiating heart failure treatment. That would include diuretics for symptom management, and then evidence-based treatments depending on whether the patient has preserved or reduced ejection fraction. And of course, always consider specialist assessment as needed for your heart failure patients.

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The development of this blog was overseen by the Canadian Collaborative Research Network.  There was no outside funding provided for the development of this article.