Prohormones in the Early Diagnosis of Cardiac Syncope

J Am Heart Assoc. 2017 Dec 14;6(12):e006592. doi: 10.1161/JAHA.117.006592.

Abstract

Background: The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin.

Methods and results: We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1-year follow-up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes (P<0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76-0.84), 0.69 (95% CI, 0.64-0.74), 0.58 (95% CI, 0.52-0.63), and 0.68 (95% CI, 0.63-0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82-0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87-0.93), which was significantly higher than for the ED probability alone (P=0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of <77 pmol/L and an ED probability of <20% had a sensitivity and a negative predictive value of 99%.

Conclusions: The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01548352.

Keywords: arrhythmia; biomarker; diagnosis; syncope (fainting).

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / blood*
  • Aged
  • Atrial Natriuretic Factor / blood*
  • Biomarkers / blood
  • Early Diagnosis*
  • Emergency Service, Hospital
  • Endothelin-1 / blood*
  • Female
  • Follow-Up Studies
  • Glycopeptides / blood*
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Prospective Studies
  • Protein Precursors / blood*
  • Syncope / blood
  • Syncope / diagnosis*
  • Syncope / physiopathology

Substances

  • Biomarkers
  • C-terminal proendothelin-1
  • Endothelin-1
  • Glycopeptides
  • Peptide Fragments
  • Protein Precursors
  • copeptins
  • midregional pro-atrial natriuretic peptide, human
  • proadrenomedullin
  • Adrenomedullin
  • Atrial Natriuretic Factor

Associated data

  • ClinicalTrials.gov/NCT01548352