N-Terminal Pro-B-Type Natriuretic Peptide in Risk Stratification of Heart Failure Patients With Implantable Cardioverter-Defibrillator

Abstract

Background: The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) is well-established. However, whether it could facilitate the risk stratification of HF patients with implantable cardioverter-defibrillator (ICD) is still unclear.

Objective: To determine the associations between baseline NT-proBNP and outcomes of all-cause mortality and first appropriate shock due to sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in ICD recipients.

Methods and results: N-terminal pro-B-type natriuretic peptide was measured before ICD implant in 500 patients (mean age 60.2 ± 12.0 years; 415 (83.0%) men; 231 (46.2%) Non-ischemic dilated cardiomyopathy (DCM); 136 (27.2%) primary prevention). The median NT-proBNP was 854.3 pg/ml (interquartile range [IQR]: 402.0 to 1,817.8 pg/ml). We categorized NT-proBNP levels into quartiles and used a restricted cubic spline to evaluate its nonlinear association with outcomes. The incidence rates of mortality and first appropriate shock were 5.6 and 9.1%, respectively. After adjusting for confounding factors, multivariable Cox regression showed a rise in NT-proBNP was associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the hazard ratios (HRs) with 95% CI across increasing quartiles were 1.77 (0.71, 4.43), 3.98 (1.71, 9.25), and 5.90 (2.43, 14.30) for NT-proBNP (p for trend < 0.001). A restricted cubic spline demonstrated a similar pattern with an inflection point found at 3,231.4 pg/ml, beyond which the increase in NT-proBNP was not associated with increased mortality (p for nonlinearity < 0.001). Fine-Gray regression was used to evaluate the association between NT-proBNP and first appropriate shock accounting for the competing risk of death. In the unadjusted, partial, and fully adjusted analysis, however, no significant association could be found regardless of NT-proBNP as a categorical variable or log-transformed continuous variable (all p > 0.05). No nonlinearity was found, either (p = 0.666). Interactions between NT-proBNP and predefined factors were not found (all p > 0.1).

Conclusion: In HF patients with ICD, the rise in NT-proBNP is independently associated with increased mortality until it reaches the inflection point. However, its association with the first appropriate shock was not found. Patients with higher NT-proBNP levels might derive less benefit from ICD implant.

Keywords: N-terminal pro-B-type natriuretic peptide; all-cause mortality; appropriate defibrillator shock; heart failure; implantable cardioverter-defibrillator; restricted cubic spline.

Figure 1

Flowchart on patient inclusion and exclusion.

Figure 2

Outcomes in heart failure (HF) with implantable cardioverter-defibrillator (ICD) according to N-terminal pro-brain natriuretic peptide (NT–proBNP) quartiles.

Figure 3

Survival curves for all-cause mortality (A) and cumulative incidence curves for first appropriate shock (B) according to NT-proBNP quartiles (Q1–Q4). NT-proBNP quartiles were defined as Q1, NT-proBNP ≤ 401.9 pg/ml; Q2, NT-proBNP 402.0 ≤ 854.2 pg/ml; Q3, NT-proBNP 854.3 ≤ 1,817.7 pg/ml; Q4, NT-proBNP ≥ 1,817.8 pg/ml.

Figure 4

Distributions of NT-proBNP in the overall population and adjusted hazard ratios (HRs) of all-cause mortality according to NT-proBNP levels. This plot demonstrates the nonlinear relationship between baseline NT-proBNP levels and the risk of all-cause mortality. A single inflection point was found at 3,231.4 pg/ml. Increases in NT-proBNP from 0 to 3,231.4 pg/ml were associated with a rapid increase in mortality risk but further increases in NT-proBNP >3,231.4 pg/mL were not associated with an increased risk (p for nonlinearity < 0.001). The dotted line indicates the corresponding 95% CIs. The 25th percentile of NT-proBNP (402.0 pg/ml) was set as a reference. A density plot is also drawn to show the distribution of NT-proBNP.