B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope

BACKGROUND: The utility of B-type Natriuretic Peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin (hs-cTn) concentrations for diagnosis and risk-stratification of syncope is incompletely understood.

METHODS: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against the ones of clinical assessments, in patients >45years presenting with syncope to the emergency department (ED) in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by two physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic endpoint. The EGSYS, a syncope-specific diagnostic score, served as the diagnostic comparator. Death and MACE at 30 and 720 days were the prognostic endpoints. MACE were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding or valvular surgery. The ROSE, OESIL, San Fransisco Syncope Rule (SFSR) and Canadian Syncope Risk Score (CSRS) served as the prognostic comparators.

RESULTS: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope vs. other causes (p<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve (AUC), was 0.77-0.78 (95% confidence interval (CI) 0.74-0.81) for all four biomarkers, and superior to the one of EGSYS (AUC 0.68 [95%-CI 0.65-0.71], p<0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an AUC of 0.81 (p<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving pre-defined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ~30% of all patients. A total of 450 MACE occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for MACE was moderate-to-good (AUC 0.75-0.79), superior to ROSE, OESIL and SFSR, and inferior to the CSRS.

CONCLUSIONS: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in ED patients with syncope.

CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT01548352.