Response by du Fay de Lavallaz et al to Letter Regarding Article, “B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope”

We thank Dr Nguyen et al for their critical review of our manuscript "B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope." 1 As correctly highlighted by Nguyen et al, further biomarkers or prohormones such as copeptin, pro-endothelin-1, and proadrenomedullin were collected as originally planned during study design and have already been evaluated in a previous publication. 2s noted by Nguyen et al, the etiologies underlying cardiac syncope are heterogenous, ranging from arrhythmias to structural and valvular heart disease.Structural heart diseases, such as myocardial infarction or valvular diseases, as well as tachyarrhythmias or pulmonary embolism, all lead to changes in intracardiac volumes and filling pressures.Numerous studies have shown that natriuretic peptides are reliable surrogates for these changes in hemodynamic stress, mediated by volume or pressure overload. 3As highlighted in our analysis, bradyarrhythmias seem to be less correlated to natriuretic peptide concentrations than tachyarrhythmias, but previous research suggested that loss of atrioventricular synchrony during the bradycardic event could lead to an increased wall tension, therefore increasing these biomarkers' circulating concentrations. 4he establishment of an exact diagnosis in syncope patients is challenging and other studies tended to focus on prognostic endpoints.To the best of our knowledge, a single other study 5 also focused on the diagnostic endpoint of cardiac syncope, which were defined by using the work-up available during the index event only.BASEL IX (Basel Syncope Evaluation Study) goes beyond the initial patient evaluation by incorporating all relevant cardiovascular findings and events detected during the first year of follow-up.Our stringent methodology moreover requires 2 fully trained physicians to agree on the exact syncope etiology, which further bolster the validity of our diagnostic evaluation.A systematic diagnostic work-up encompassing, for instance, an electrophysiologic study or a loop recorder implantation in all participants goes beyond the observational design of our study.We do, however, agree that further well-structured, possibly controlled, and randomized studies are required to definitively highlight the importance of biomarkers in the diagnostic evaluation of patients presenting with syncope.