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

INTRODUCTION: Several studies have demonstrated that combining left ventricular ejection fraction and New York Heart Association functional class is insufficient for predicting risk of appropriate implantable cardioverter-defibrillator (ICD) shock in primary prevention candidates. Hence, our aim was to assess the relationship between N-terminal pro-B type natriuretic peptide (NT-pro BNP) along with appropriate ICD shock and all-cause mortality in order to improve the stratification process of patients with heart failure with reduced ejection fraction (HFrEF) being considered for primary preventive ICD therapy. METHODS: A systematic literature search from several databases was conducted up until 9 June 2022. Studies were eligible if they investigated the relationship of NT-pro BNP with all-cause mortality and appropriate ICD shock. RESULTS: This meta-analysis comprised nine studies with a total of 5117 participants. Our study revealed that high levels of NT-pro BNP were associated with all-cause mortality (HR=2.12 (95% CI=1.53 to 2.93); p<0.001, I(2)=78.1%, p<0.001 for heterogeneity) and appropriate ICD shock (HR=1.71 (95% CI=1.18 to 2.49); p<0.001, I(2)=43.4%, p=0.102 for heterogeneity). The adjusted HR for all-cause mortality and appropriate ICD shock increased by approximately 3% and 5%, respectively per 100 pg/mL increment pursuant to concentration–response model (P(non-linearity) <0.001). The curves became steeper after NT-pro BNP reached its inflection point (3000 pg/mL). CONCLUSION: A positive concentration-dependent association between elevated NT-pro BNP levels along with the risk of all-cause mortality and appropriate ICD shock was found in patients with HFrEF with ICD. PROSPERO REGISTRATION NUMBER: CRD42022339285.