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

Abstract

BackgroundThe 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.ObjectiveTo 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 resultsN-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).ConclusionIn 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.

Role of N-terminal pro-B type natriuretic peptide as a predictor of poor outcomes in patients with HFrEF receiving primary prevention implantable cardioverter-defibrillator therapy: a systematic review and dose–response meta-analysis

“…Conclusively, after detailed consideration, nine studies were chosen for final inclusion, with a total of 5117 participants incorporated in this meta-analysis (figure 1). 11–18 26 The participant in this research had a mean age of 62.4 years, whereas 76.4% of the participants were men. Amid the overall patients, the aetiology of 48.5% patients was ischaemic and the mean duration of follow-up was 3.6 years.…”

“…In patients with HF with ICD, greater NT-pro BNP levels were generally linked with all-cause mortality (HR=2.12 (95% CI=1.53 to 2.93); p<0.001), but with considerable heterogeneity (I 2 =78.1%, p<0.001 for heterogeneity) (figure 2A). Succeeding a leave-one-out analysis, however, revealed that two studies14 15 markedly increased heterogeneity within the included studies. Following the withdrawal of the aforementioned studies, heterogeneity fell substantially (I 2 =0%, p=0.587 for heterogeneity), and the pooled effect size remained statistically significant (HR=1.57 (95% CI=1.40 to 1.76); p<0.001).…”

“…However, a large cohort study conducted by Deng et al suggests that HF aetiology (ICM and NICM) had no effect on the significant correlation between NT-pro BNP and appropriate ICD shock in patients with HF based on their multivariate analysis. 15 Unfortunately, since the majority of our included studies recruited the whole HF population, subgroup analysis was not possible in this meta-analysis. 11 13–18 …”

“…However, a large cohort study conducted by Deng et al suggests that HF aetiology (ICM and NICM) had no effect on the significant correlation between NT-pro BNP and appropriate ICD shock in patients with HF based on their multivariate analysis. 15 Unfortunately, since the majority of our included studies recruited the whole HF population, subgroup analysis was not possible in this meta-analysis. 11 13-18 In regard to addressing the aforementioned dispute, Mirelis et al conducted a cohort study in which they demonstrated that the combination of late gadolinium enhancement from cardiac magnetic resonance (CMR) and positive genotype was useful in predicting SCD risk in patients with NICM and thus capable of stratifying the most qualified patients who benefit the most from primary prevention ICD therapy in this population.…”

“…Accordingly, several cohort studies have shown that measuring NT-pro BNP is effective in predicting the likelihood of appropriate ICD shock and all-cause mortality in primary prevention candidates, despite the ambiguous relationship between these two entities. [11][12][13][14][15][16][17][18] Thus, this meta-analysis aims to evaluate the association between NT-pro BNP along with appropriate ICD shock and allcause mortality in patients with HFrEF who received ICD implantation as primary prevention of SCD.…”