What are the next steps in managing a 45-year-old male with elevated NT-proBNP levels?

From the Guidelines

The next steps in managing a 45-year-old male with an NT-proBNP level of 177 should focus on determining the underlying cause and establishing appropriate treatment, starting with a comprehensive cardiac evaluation, including a detailed medical history, physical examination, electrocardiogram (ECG), and echocardiogram to assess cardiac structure and function, as elevated NT-proBNP levels often indicate heart failure but can also result from other conditions such as renal dysfunction, pulmonary hypertension, or acute coronary syndrome 1. Given the NT-proBNP level of 177, which is below the suggested partition value of 800 pg/mL for the diagnosis of HFpEF, but still elevated, it is essential to consider other factors that may influence NT-proBNP levels, such as obesity, sex, age, and comorbid conditions like pulmonary disease, renal dysfunction, and atrial fibrillation 1.

Key Considerations

• A thorough diagnostic workup is necessary to guide appropriate management, including laboratory tests such as complete blood count, comprehensive metabolic panel, lipid profile, thyroid function tests, and hemoglobin A1c to identify contributing factors.
• If heart failure is confirmed, treatment typically begins with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), along with a beta-blocker, titrating doses upward as tolerated, and considering the addition of a diuretic for volume overload.
• Lifestyle modifications are crucial, including sodium restriction, moderate exercise, smoking cessation, and limiting alcohol consumption.

Diagnostic Approach

• The patient should undergo measurement of serum natriuretic peptide with subsequent echocardiography, and specialist evaluation is indicated if these levels are elevated, as suggested by the National Institute for Health and Clinical Excellence guideline 1.
• Echocardiography and specialist evaluation should be available within 2 weeks of presentation if patients have a history of myocardial infarction or high serum natriuretic peptide levels and no later than 6 weeks after presentation if the serum natriuretic peptide levels are increased but not high.

Management

• The patient's management plan should prioritize determining the underlying cause of the elevated NT-proBNP level and establishing appropriate treatment, with a focus on lifestyle modifications and pharmacologic therapy as needed, to improve outcomes and reduce the risk of cardiac events 1.
• The implementation of optimal postoperative treatment could be guided by the serial monitoring of BNP levels, and the use of a postoperative rise in BtNP levels as a marker of a myocardium at risk of failure, aiming to develop treatment algorithms similar to those for ACS 1.

From the FDA Drug Label

In a 7-day valsartan-controlled study in patients with reduced ejection fraction (HFrEF), administration of sacubitril and valsartan resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan In a 21-day study in HFrEF patients, sacubitril and valsartan significantly increased urine ANP and cGMP and plasma cGMP, and decreased plasma NT-proBNP, aldosterone and endothelin-1. In PARADIGM-HF, sacubitril and valsartan decreased plasma NT-proBNP (not a neprilysin substrate) and increased plasma BNP (a neprilysin substrate) and urine cGMP compared with enalapril In PARAMOUNT, a randomized, double-blind, 36-week study in patients with heart failure with LVEF greater than or equal to 45% comparing 97/103 mg of sacubitril and valsartan (n=149) to 160 mg of valsartan (n =152) twice-daily, sacubitril and valsartan decreased NT-proBNP by 17% while valsartan increased NT-proBNP by 8% at Week 12 (p = 0. 005). In PARAGON-HF, sacubitril and valsartan decreased NT-proBNP by 24% (Week 16) and 19% (Week 48) compared to 6% and 3% reductions on valsartan, respectively.

The next steps in managing a 45-year-old male with elevated NT-proBNP levels may include:

• Further evaluation to determine the underlying cause of the elevated NT-proBNP levels
• Consideration of sacubitril and valsartan as a potential treatment option, given its ability to decrease NT-proBNP levels in patients with heart failure 2
• Monitoring of NT-proBNP levels to assess response to treatment and adjust the management plan as needed
• Assessment of left ventricular ejection fraction (LVEF) to determine if the patient has heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), as this may influence treatment decisions.

From the Research

Next Steps in Managing Elevated NT-proBNP Levels

The patient, a 45-year-old male, presents with an NT-proBNP level of 177. To manage this condition, the following steps can be considered:

• Evaluate the patient's medical history and perform a physical examination to identify potential causes of elevated NT-proBNP levels, such as heart failure, heart muscle disease, valve disease, rhythm abnormalities, pulmonary hypertension, or cytotoxic injury to the heart 3
• Consider ordering additional diagnostic tests, such as echocardiography, electrocardiography, or chest radiography, to assess cardiac function and structure
• Measure BNP levels, if applicable, but note that BNP concentrations may rise with neprilysin inhibition, whereas NT-proBNP is not a substrate of neprilysin inhibition and may be a more reliable marker in certain situations 4

Prognostic Implications

Elevated NT-proBNP levels are associated with an increased risk of adverse outcomes, including mortality. Studies have shown that:

• NT-proBNP values ≥ 1800 pg/ml are associated with in-hospital mortality in very elderly patients without an admission diagnosis of heart failure 5
• NT-proBNP levels above 6000 pg/ml identify patients with advanced heart failure who are at higher risk of death within 90 days after hospital discharge 6
• High NT-proBNP levels are strong predictors of outcome in elderly heart failure patients, with mortality rates of 21% after 3 months, 35% after 1 year, and 40% after 2 years 7

Monitoring and Treatment

Regular monitoring of NT-proBNP levels and adjustment of treatment as needed may be beneficial in managing patients with elevated NT-proBNP levels. Additionally, consideration of underlying cardiac involvement and appropriate treatment may improve outcomes in hospitalized very elderly patients 5