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Marker identified for risk of post-operative atrial fibrillation

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(Vienna, 07 June 2018) A cross-disciplinary study conducted by three MedUni Vienna departments showed, for the first time, that a specific lymphocyte population is associated with the occurrence of atrial fibrillation after elective cardiac surgery. This facilitates the prediction of individual risk and, together with the associated personalised pharmacotherapeutic strategy, represents a further step towards precision medicine.

With more than 4.5 million people affected in Europe alone, atrial fibrillation is the commonest form of cardiac arrhythmia encountered in everyday clinical practice. Atrial fibrillation is associated with an enhanced risk of thromboembolic events and triggers more than a quarter of all ischaemic insults. A particular form of atrial fibrillation is "post-operative atrial fibrillation", which occurs with a frequency (incidence) of around 45% following cardiac surgeries and is associated with a much poorer long-term prognosis. It is therefore important to identify high-risk patients in a stable condition prior to a heart operation and to take antiarrhythmic countermeasures in good time, thereby preventing the onset of atrial fibrillation.

Autoimmune reaction a possible trigger for atrial fibrillation
Preoperative flow cytometry of patient bloods showed that people with a higher proportion of so-called CD4+CD28null T lymphocytes had a much higher risk of developing atrial fibrillation after a heart operation. These specific T cells are the principal actors in autoimmune diseases such as rheumatoid arthritis or multiple sclerosis. Due to the loss of the CD28 (=CD28null) surface receptor, this cell population loses its potential to regulate and suppress its inflammatory activity and becomes aggressive towards healthy body tissue, resulting in an excessive auto-aggressive response.

These immune cells also occur in the heart and coronary vessels. The researchers are working on the assumption that, as a result of long-standing inflammatory processes along the heart tissue, the proportion of this lymphocyte subgroup increases. In response to an acute inflammatory stimulus, such as that associated with cardiac surgery, the CD4+CD28null T lymphocytes unleash their inflammatory potential and their auto-aggressive activity against vital heart muscle tissue.
From a purely hypothetical point of view, it is assumed that the consequent induction of apoptosis and necrosis leads to the formation of multiple micro-scars along the atrial myocardium, which encourage the development of circular electrical excitation, thereby resulting in the onset of atrial fibrillation.

Precision medicine prior to cardiac surgery: statin therapy reduces risk
Based on the anti-inflammatory potential of statins, it was shown that patients already on statin treatment preoperatively had a significantly lower proportion of CD4+CD28null T lymphocytes. It was also shown that preoperative statin therapy was associated with a significantly lower probability of developing post-operative atrial fibrillation.

The findings of this study represent a significant contribution towards personalised medicine. Firstly, preoperative measurement of this specific lymphocyte subgroup can indicate the risk of post-operative atrial fibrillation and consequently identify high-risk patients, who will potentially benefit from more intensive antiarrhythmic therapy. Secondly, it was shown that this lymphocyte population can be suppressed by preoperative administration of statins and that statins significantly reduce the probability of atrial fibrillation.

The study (AFAN study) was conducted as part of an extensive collaboration between the Department of Medicine II, Division of Cardiology, together with the Department of Surgery, Division of Cardiac Surgery (collaboration partners: Günther Laufer and Tatjana Fleck) and the Department of Anesthesia, Critical Care and Pain Medicine, Division of Cardiothoracic Vascular Surgery (collaboration partner: Barbara Steinlechner). The project leader was Patrick Sulzgruber (Department of Medicine II, Cardiology) supervised by Alexander Niessner (Department of Medicine II, Cardiology).

Service: Scientific Reports
Patrick Sulzgruber, Barbara Thaler, Lorenz Koller, Johanna Baumgartner, Arnold Pilz, Matthias Steininger, Sebastian Schnaubelt, Tatjana Fleck, Günther Laufer, Barbara Steinlechner, Max-Paul Winter, Georg Goliasch, Johann Wojta and Alexander Niessner "CD4+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery" Scientific Reports (2018).