1. Low adrenomedullin and endothelin-1 predict cardioinhibitory response during vasovagal reflex in adults above 40 years of age
Viktor Hamrefors 1,2, David Nilsson 1, Olle Melander 1,2, Richard Sutton 3, and Artur Fedorowski 1,4
1 Department of Clinical Sciences, Lund University, Malmö, Sweden
2 Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
3 National Heart and Lung Institute, Imperial College, Hammersmith Hospital Campus, London, UK
4 Department of Cardiology, Skåne University Hospital, Malmö, Sweden
CONCLUSIONS
In patients aged 40 years or more with vasovagal syncope, lower age and lower levels of adrenomedullin (MR-pro- ADM) and endothelin-1 (CT-proET1) are associated with tilt-induced asystole.
BACKGROUND
Cardioinhibitory (CI) vasovagal syncope (VVS) may respond to pacemaker therapy in older adults which prompted the hypothesis that there may be neuroendocrine differences between CI and non-CI VVS. We aimed to relate patient characteristics and resting plasma-levels of four neuroendocrine biomarkers to different forms of VVS.
METHODS
One-hundred-and-fifty-nine patients, years, with unexplained syncope provided blood samples (supine) followed by head-up tilt testing (HUT). Patients were classified as negative HUT, non-CI, non-asystolic CI, and asystolic VVS. Plasma C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1 (CT-proET-1), mid-regional-proadrenomedullin-peptide (MR-proADM), and pro-atrial-natriuretic-peptide (MR-proANP) were related to diagnosis and compared with a population-cohort (Malmö-Preventive-Project; n=5416).
RESULTS
One-hundred-and-ten patients had VVS (80 non-CI, 11 non-asystolic CI and 19 asystolic CI VVS) and 49 had negative HUT. Patients with asystolic VVS were younger (55±14) compared with negative HUT (67±14, p=0.002) and non-CI VVS (65±12, p=0.010). Lower MR-pro-ADM (Odds ratio [OR] per 1 Standard Deviation [SD]: 2.40, 95%CI, ; p=0.011) and lower CT-pro-ET1 (OR per 1 SD: 1.66, 95%CI, ; p=0.041) were associated with asystolic VVS. MR-pro-ADM and CT-pro-ET1-levels did not differ between negative HUT and the population control-group. Patients aged < 65 years (median) with plasma MR-pro-ADM < 0.46 pm/l plus CT-pro-ET1 < 47.7 pm/l (lowest quartiles) had an OR of 10.0 (2.5– 38.9; p=0.001) for asystolic VVS compared with older patients with higher levels of these markers.
FIGURES
Levels of CT-proET1 and MR-proADM according to diagnosis. Please note that by design outliers are not displayed.
NoDx = no diagnosis; VVS=Vasovagal syncope; VASIS=Vasovagal Syncope Investigators; non-CI=non-cardioinhibitory.
Corresponding author: Viktor Hamrefors; Conflicts of interest: AF and OM are listed as co-inventors on a patent application “Biomarkers for the diagnosis, prognosis, assessment and therapy stratification of syncope” (PCT/EP2013/001081) for the use of BRAHMS CT-proAVP, CT-proET-1, MR-pro-ADM and MR-proANP for diagnosis of syncope. RS is a consultant to Medtronic Inc., member of Abbott Speakers’ Bureau and stockholder in Boston Scientific Inc., Edwards Lifesciences, Shire PLC, AstraZeneca PLC and Roche SA.