Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association We combed through both guidelines and summarized 3 recommendations covering use of biomarkers in ambulatory care Summary Recommendation Created by Jill E. Allen, PharmD, BCPS, and Geraldine Gardner, DO, FACC, FACP
1 Serum biomarkers have multiple roles in heart failure (HF). In addition to providing clinicians with important information about disease severity, they assist in HF prevention, diagnosis, and prognosis. Their role in the management of drug therapy is also evolving. A HF guideline update from the ACC/AHA/HFSA and an AHA Scientific Statement provide recommendations about the use of biomarkers in HF. This summary focuses on use of biomarkers in ambulatory care. Refer to the guideline and statement for additional recommendations related to use during hospitalization. Key biomarkers used in ambulatory care management of HF are summarized in Table 1. Table 1. Key Biomarkers for Ambulatory Care Management of HF* Biomarker Function / Source Applications BNP, NT-proBNP Hemodynamic load Correlates with LVED wall stress Predicts mortality, HF events sst2 Myocardial fibrosis Correlates with LVEDP Predicts mortality, hospitalization Incremental prognostic value over natriuretic peptides Gal-3 Myocardial fibrosis Predicts mortality, hospitalization Incremental prognostic value over natriuretic peptides * Adapted from AHA Scientific Statement and ACC/AHA/HFSA guideline Abbreviations: B-type natriuretic peptide (BNP); gelatinase-associated lipocain-3 (GAL-3); heart failure (HF); left ventricular end diastolic (LVED) N-terminal pro B-type natriuretic peptide (NT-proBNP); soluble suppressor of tumorgenicity 2 (sst2l). I. Role of biomarkers to screen high-risk patients for HF Recommendation: Screening patients at high risk for HF with BNP or NT-proBNP followed by team-based care and optimization of guideline-directed management and therapy (GDMT) by a cardiovascular specialist has utility to prevent left ventricular dysfunction or new-onset HF. [Class of Recommendation (COR) IIa; Level of Evidence (LOE) B-R] Details: Cough suppression exercises may include education, identifying cough triggers, cough suppression techniques, improving laryngeal hygiene and hydration, breathing exercises, and counseling. Cough suppression techniques use strategies such as pursed lip breathing, swallowing, and sipping water. A bundle of cough suppression exercises given over 3 to 4 outpatient sessions has been shown to improve refractory chronic cough. Cough suppression exercises are usually delivered by specialist teams including speech and language therapists or physical therapists. Clinicians with expertise in cough suppression exercises may be lacking in some settings. Comments: Evaluate patients with shortness of breath for HF. Start with a history and physical exam. BNP or NT-proBNP are simple lab tests that you should be able to use in your setting. I usually reserve these for acute phase HF. Keep in mind that sst2 and Gal3 may not be available nor covered by the patient s insurance. You may also want to consider a 2-view chest x-ray, which is inexpensive. If the above tests come back with an abnormal result, perform an echocardiogram to confirm the result.
Remember that patient involvement with daily weights and lower sodium diets can be a cost-effective way to treat the patient who is not in acute phase without ordering serial BNP values. II. Role of biomarkers for HF diagnosis 2 Recommendation: Measuring BNP or NT-proBNP can help diagnose or exclude HF in patients presenting with dyspnea. [COR I; LOE A] Details: This recommendation applies to ambulatory patients with new-onset dyspnea and evaluation of acute dyspnea in the emergency department (ED). The greatest utility of natriuretic peptide levels in the ED may be for ruling out HF. Although a high natriuretic peptide level supports the diagnosis of HF, other cardiac and non-cardiac conditions can cause high natriuretic peptide levels (see Table 2). Alternatively, obesity can lower them. Comments: Right ventricular failure and renal failure are associated with elevated BNP values. Further workup is indicated if an echocardiogram shows elevated pulmonary/right ventricular pressures. Table 2. Key Biomarkers for Ambulatory Care Management of HF* Cardiac Acute coronary syndrome Right ventricular dysfunction Heart muscle disease, including LVH Valvular heart disease Pericardial disease Atrial fibrillation Myocarditis Cardiac surgery Cardioversion Myocardial damage from toxins (eg, cancer chemotherapy) Non-Cardiac Anemia Renal failure Obstructive sleep apnea Old age Pulmonary hypertension Pulmonary embolism Critical illness Sepsis Severe burns Severe pneumonia *Adapted from ACC/AHA/HFSA guideline and AHA Scientific Statement III. The role of biomarkers for HF prognosis or risk stratification Recommendation: In chronic New York Heart Association A class II-IV HF, measuring BNP or NT-proBNP levels can help establish disease severity or prognosis. [COR I; LOE A] Other biomarkers may provide additive risk stratification. [COR IIb; LOE B-NR] These may include sst2, GAL-3, and others. Details: Based on evolving evidence, a combination of biomarkers may be helpful. Biomarkers for cardiac fibrosis (eg, sst2, GAL-3) have additive prognostic value to natriuretic peptides. Advantages of sst2 over natriuretic peptides include that it is not affected by old age, renal function, or obesity. Comments: The ACC/AHA/HFSA guideline notes that there are insufficient data to make recommendations about serial monitoring of natriuretic peptides or use of natriuretic peptide levels to guide drug therapy. Some patients will have chronically elevated BNP values over time. Clinical history and physical exam are the most important guides to help treat such individuals. Those with HF should adhere
3 to daily weight monitoring, which is more helpful for the clinician to assess fluid status versus serial BNP values, which may not add value but will likely add cost. As to which natriuretic peptide to monitor, the guideline notes that BNP and NT-proBNP generally perform in a similar fashion. One exception is their use in patients treated with the angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril-valsartan (Entresto). While BNP is a substrate of neprilysin, NT-proBNP is not. Consequently, sacubitril-valsartan increases BNP levels while lowering NT-proBNP levels. In the PARADIGM-HF study, patients who had significant lowering of NT-proBNP levels had a significantly lower risk of cardiovascular death or HF hospitalization. The AHA scientific statement advises that it is too early to use NT-proBNP response as a surrogate to guide treatment with sacubitril-valsartan. See this Evidence & Advice post for more about the role of biomarkers for heart failure including the primary care clinician s role in managing patients with chronically elevated BNP.
4 ACC/AHA/HFSA Class of Recommendation (COR) and Level of Evidence (LOE) Guide Strength of Recommendation I: Strong benefit Benefit >>> Risk IIa: Moderate benefit Benefit >> Risk IIa: Moderate benefit Benefit >> Risk III: No benefit Benefit = Risk III: Harm Risk > Benefit Quality of Evidence A: High from multiple randomized clinical trials/meta-analyses B-R: Moderate from randomized clinical trials/meta-analyses B-NR: Moderate from non-randomized studies C-LD: Limited data C-EO: Consensus of expert opinion About the authors Dr Allen is a drug information consultant and medical writer at Pin Oak Associates, which she founded in 1995. Dr Gardner is Lead, Cardiology Section, Providence Medical Group, Everett, WA. References Chow SL, Maisel AS, et al. Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement from the American Heart Association. Circulation 2017; 135 (22): e1054-e1091. Huelsmann M, Neuhold S, et al. PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease): A Prospective Randomized Controlled Trial. J Am Coll Cardiol 2013; 62 (15): 1365-1372. Ledwidge M, Gallagher J, et al. Natriuretic Peptide-Based Screening and Collaborative Care for Heart Failure: The STOP-HF Randomized Trial. JAMA 2013; 310 (1): 66-74. Packer M, McMurray JJ, et al. Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure. Circulation 2015; 131 (1): 54-61. Yancy CW, Jessup M, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017. Zile MR, Claggett BL, et al. Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. J Am Coll Cardiol 2016; 68 (22): 2425-2436.