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. 2025 Mar 15;17(3):427.
doi: 10.3390/v17030427.

A New Approach to the Etiology of Syncope: Infection as a Cause

Branislav Milovanovic  1   2 , Nikola Markovic  1 , Masa Petrovic  1   2 , Vasko Zugic  1   2 , Milijana Ostojic  1 , Milica Dragicevic-Antonic  1 , Milovan Bojic  1   2
Affiliations

A New Approach to the Etiology of Syncope: Infection as a Cause

Branislav Milovanovic et al. Viruses. .

Abstract

Background/objectives: Syncope is a common clinical occurrence, with neurally mediated and orthostatic types accounting for about 75% of cases. The exact pathophysiological mechanisms remain unclear, with recent evidence suggesting autonomic nervous system damage and a potential infectious etiology. This study aimed to examine the role of infection in the development of syncope and orthostatic hypotension (OH).

Methods: The cross-sectional study included 806 patients from the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases "Dedinje". Patients were divided into three groups: unexplained recurrent syncope (n = 506), syncope with OH during the head-up tilt test (HUTT) (n = 235), and OH without a history of syncope (n = 62). All participants underwent the HUTT, and 495 underwent serological testing for various microorganisms. Data were analyzed using chi-squared tests and binary and multinomial logistic regression.

Results: The HUTT was positive in 90.6% of patients with syncope and OH, compared with 61.6% with syncope alone (p < 0.001). Serological testing revealed that 57.85% of syncope patients, 62.9% of syncope with OH patients, and 78% of OH patients had positive IgM antibodies to at least one microorganism. Multivariate analysis indicated that IgM antibodies to Coxsackievirus and Epstein-Barr virus were significant predictors of OH.

Conclusions: This study demonstrated a potential association between infections and syncope/OH. Further investigation into the role of infectious agents in autonomic dysfunction is warranted to clarify the underlying mechanisms of syncope and OH.

Keywords: autonomic dysfunction; head-up tilt test; neurocardiology; syncope.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Positive IgM antibodies for group 1.
Figure 2
Figure 2
Positive IgM antibodies for group 2.
Figure 3
Figure 3
Positive IgM antibodies for group 3.
See this image and copyright information in PMC

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