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Left Ventricular Ejection Fraction Assessment in Older Adults: An Adjunct to Natriuretic Peptide Testing to Identify Risk of New-Onset Heart Failure and Cardiovascular Death?
Study Questions:
Does the assessment of left ventricular ejection fraction (LVEF) aid in heart failure (HF) and cardiovascular mortality risk assessment above that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in older adults?
Methods:
Serum NT-proBNP levels and LVEF were assessed in 4,137 adults ≥65 years without HF symptoms enrolled into the Cardiovascular Health Study. LVEF was assessed by echocardiogram at baseline and 5 years after enrollment. Patients were categorized as having normal (LVEF ≥55%), borderline (≥45% to <55%), or subnormal (<45%) systolic function. Patients had an abnormal NT-proBNP if the level was ≥190 pg/ml (sample 70th percentile). The primary outcomes of interest were incident HF and cardiovascular mortality during the period of follow-up, assessed using Cox modeling (hazard ratio [95% confidence interval] provided). Areas (AUC) under the receiver operating characteristic curves were compared for LVEF and BNP risk stratification.
Results:
The mean ± standard deviation patient age was 72.7 ± 5.5 years, 59% were female, and 13% were African American. At baseline, LVEF was subnormal in 2.6% of patients, borderline in 5.1%, and normal in 92%. Median [25th, 75th] NT-proBNP levels were 111 [56, 219] and 29.5% had a level ≥190 pg/ml. Over a median 10.7 years of follow-up, 1,112 (27%) patients developed new HF symptoms, and 893 (22%) died of cardiovascular causes. The risk of HF was 2.95 [2.6-3.3] and 2.4 [2.0, 2.9] higher for those with NT-proBNP ≥190 pg/ml and LVEF <55%, respectively. Compared with patients who had a normal LVEF and NT-proBNP at baseline, the adjusted risk of new-onset HF was 1.3 [0.92, 1.7] for those (n = 135) with a low NT-proBNP and LVEF <55%, 2.1 [1.8, 2.4] for those (n = 1,037) with high NT-proBNP and LVEF ≥55%, and 2.7 [2.1, 3.4] for those (n = 162) with high NT-proBNP and LVEF <55%. Likewise, compared with patients who had a normal LVEF and NT-proBNP at baseline, the adjusted risk of death was 1.7 [1.2, 2.3] for those with a low NT-proBNP and LVEF <55%, 1.9 [1.6, 2.3] for those with high NT-proBNP and LVEF ≥55%, and 3.0 [2.3, 3.8] for those with high NT-proBNP and LVEF <55%. Overall, the AUCs for predicting HF development-based LVEF, NT-proBNP, and LVEF plus NT-proBNP were 0.679, 0.719, and 0.723, respectively (p = 0.14 for addition of LVEF to NT-proBNP). For mortality, corresponding AUCs were 0.726, 0.759, and 0.761, respectively (p = 0.25 for addition of LVEF to NT-proBNP). Among patients whose NT-proBNP increased ≥25% from baseline to ≥190 pg/ml on follow-up, an LVEF <55% was also associated with increased risk of cardiovascular death. However, an abnormal LVEF again failed to improve risk stratification for either endpoint.
Conclusions:
The authors concluded that LVEF assessment added to NT-proBNP does not routinely improve HF prognostication in older adults.
Perspective:
Predicting HF development and mortality risk can be challenging. In this observational cohort study, an abnormal LVEF in asymptomatic older adults was associated with a worse outcome. However, echocardiography did not improve prognostication above that of patient demographics and baseline or follow-up NT-proBNP levels. The authors argue that LVEF likely adds little accuracy to NT-proBNP risk assessment because an incident decline in LVEF is not common (8% of older adults) and absolute LVEF percentage may not have a strong influence on HF symptom development or survival. However, foregoing echocardiography in asymptomatic patients with abnormal BNPs may prevent introduction of interventions with proven mortality benefit (evidenced-based medications or ICD therapy) in systolic HF that would not be necessarily indicated in patients with diastolic HF and normal LVEF.
Keywords: Follow-Up Studies, Area Under Curve, Demography, Systole, Natriuretic Peptides, Biomarkers, Cardiology, Heart Failure, Peptide Fragments, Stroke Volume, Ventricular Function, Confidence Intervals, ROC Curve, Diastole, Risk Assessment, United States, Echocardiography
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