B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope
Authors: du Fay de Lavallaz Jeanne , Badertscher Patrick , Nestelberger Thomas , Zimmermann Tobias , Miró Òscar , Salgado Emilio , Christ Michael , Geigy Nicolas , Cullen Louise , Than Martin , Javier Martin-Sanchez F. , Di Somma Salvatore , Frank Peacock W. , Morawiec Beata , Walter Joan , Twerenbold Raphael , Puelacher Christian , Wussler Desiree , Boeddinghaus Jasper , Koechlin Luca , Strebel Ivo , Keller Dagmar I. , Lohrmann Jens , Michou Eleni , Kühne Michael , Reichlin Tobias , Mueller Christian ,   For the BASEL IX Investigators, Rubini Giménez Maria , Kozhuharov Nikola , Shrestha Samyut , Sazgary Lorraine , Freese Michael , Meissner Kathrin , Kulangara Caroline , Hartmann Beate , Coehlo Carine , Joray Lydia , Lopez-Ayala Pedro , Breidthardt Tobias , Bingisser Roland , Bustamante Mandrión José , Poepping Imke , Kawecki Damian , Muzyk Piotr , Nowalany-Kozielska Ewa , Greenslade Jaimi , Hawkins Tracey , Rentsch Katharina , von Eckardstein Arnold , Buser Andreas , Kloos Wanda , Steude Jana , Osswald Stefan 
Published: February 2019

Background:
The utility of BNP (B-type natriuretic peptide), NT-proBNP (N-terminal proBNP), and hs-cTn (high-sensitivity cardiac troponin) 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 those of clinical assessments, in patients >45-years old presenting with syncope to the emergency department 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 2 physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic end point. EGSYS (Evaluation of Guidelines in Syncope Study), a syncope-specific diagnostic score, served as the diagnostic comparator. Death and major adverse cardiac events at 30 and 720 days were the prognostic end points. Major adverse cardiac events 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. ROSE (Risk Stratification of Syncope in the Emergency Department), OESIL (Osservatorio Epidemiologico della Sincope nel Lazio), SFSR (San Fransisco Syncope Rule), and CSRS (Canadian Syncope Risk Score) 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 versus other causes (
P
<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve, was 0.77 to 0.78 (95% CI, 0.74–0.81) for all 4 biomarkers, and superior to EGSYS (area under the curve, 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 area under the curve of 0.81 (
P
<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving predefined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ≈30% of all patients. A total of 450 major adverse cardiac events occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for major adverse cardiac events was moderate-to-good (area under the curve, 0.75–0.79), superior to ROSE, OESIL, and SFSR, and inferior to CSRS.

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

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01548352.