Inflammation and Atrial Electrical Remodelling in Patients With Embolic Strokes of Undetermined Source

doi:10.1016/j.hlc.2018.04.294

Heart, Lung and Circulation

Volume 28, Issue 6, June 2019, Pages 917-922

https://doi.org/10.1016/j.hlc.2018.04.294 Get rights and content

Background

About one third of ischaemic strokes are classified as embolic strokes of undetermined source (ESUS). A silent atrial fibrillation (AF) may play a pathogenic role in these strokes and P wave dispersion (PWD), representing an electrocardiographic (ECG) predictor for paroxysmal AF, thereby a potential marker of covert cardioembolism, was found to be increased in cryptogenic stroke. Furthermore, current evidence links AF to inflammation: inflammatory markers, such as high-sensitive C-reactive protein (hsCRP), have been related to the development and persistence of AF, possibly by promoting atrial remodelling. The aim of this study was to evaluate whether a relationship between PWD and hsCRP in patients with ESUS exists, in order to highlight a possible role for inflammation in the atrial electric remodelling, that predisposes to AF.

Methods

We enrolled 174 patients (91 males, 83 females; mean age 69 ± 13 years) with ESUS. All patients underwent neuroimaging examination, arterial ultrasound examination, echocardiography and ECG. P wave dispersion and hsCRP were measured in all subjects.

Results

A significant positive correlation was found between hsCRP and PWD (Spearman r: 0.35, p < 0.0001). In patients with high PWD (>40 msec; n = 102), hsCRP was three-fold higher than in patients with normal PWD (≤40 msec; n = 72)(1.57 ± 2.9 vs 0.42 ± 0.4 mg/dl, p = 0.0005).

Conclusions

Our results show increased hsCRP levels in cryptogenic stroke patients with high PWD. These findings provide support for the hypothesis that systemic inflammation plays a role in a fraction of patients with ESUS, by increasing AF risk via atrial electric remodelling.

Section snippets

Background

About one third of ischaemic strokes are classified as embolic strokes of undetermined source (ESUS) [1]. Many ESUS are suspected to arise from occult cardiac embolism; in this view, subclinical atrial fibrillation (AF) may play a pathogenic role in these strokes [2]. Recently, an updated model of thromboembolic stroke suggested the importance of systemic and atrial substrate in explaining the relationship between AF and stroke [3].

P wave dispersion (PWD), a well-known electrocardiographic

Methods

We enrolled 174 patients (91 males, 83 females; mean age 69 ± 13 years), admitted consecutively to the Stroke Unit Department of Siena University Hospital for ESUS.

All patients underwent neuroimaging examination (brain computerised tomography with angio-CT scan and/or brain magnetic resonance imaging), extracranial and transcranial arterial ultrasound examination, transthoracic echocardiography, 12-lead resting electrocardiogram (ECG) and 24-hour ECG monitoring. In patients with age <60 years (n =

Results

Descriptive statistics for the data are presented in Table 1. A significant positive correlation was found between CRP and PWD (Spearman r = 0.35, p < 0.0001) (Figure 1, A); furthermore, there was also a significant negative correlation between CRP and P min (Spearman r = −0.15, p = 0.04) (Figure 1, C). No correlation was found between CRP and P max (Spearman r = 0.13, p = 0.07) (Figure 1, B).

Out of 174 patients, PWD was high (>40 ms) in 102 subjects (58%); demographic characteristics of patients with

Discussion

The novel findings of our study are the following: PWD positively correlates with hsCRP levels and P min negatively correlates with hsCRP levels in patients with ESUS. In particular, in patients with high PWD (>40 ms), hsCRP levels are significantly higher than in patients with normal PWD.

In our previous study [7] we observed higher PWD values in strokes of unknown cause suggesting the hypothesis that PWD can be a marker of silent atrial fibrillation episodes occurrence [8], that may determine a

Conclusions

Our results show a positive correlation between CRP and PWD in ESUS, suggesting that the relationship between AF and stroke could be more complex than a simple cause and effect mechanism. Systemic inflammation could play a pathogenic role in atrial cardiopathy observed in this type of stroke, determining an impaired electrical atrial conduction with subsequent increase of PWD and possible increased risk of AF occurrence.

Acknowledgements

None.

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Inflammation, which is in our study represented by a higher level of IL-6, may have a possible role in the development of atrial cardiopathy, currently considered a potential pathogenic factor underlying CS even independently from the occurrence of atrial fibrillation together with the autonomic nervous system (ANS), which plays a well-known role in determining statistically significant and heterogeneous electrophysiological changes of atrial cardiomyocytes [39]. Systemic inflammation may play a role in a fraction of patients with CS by increasing AF risk via atrial electric remodeling [40] and also with the occurrence of paroxysmal silent AF [41]. After patients’ hospital admissions with the diagnosis of ischemic stroke, we had to eliminate basic causes of stroke using echocardiography, Holter ECG and blood tests, which took about 7 days.
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Original ArticleInflammation and Atrial Electrical Remodelling in Patients With Embolic Strokes of Undetermined Source

Background

Methods

Results

Conclusions

Section snippets

Background

Methods

Results

Discussion

Conclusions

Acknowledgements

Lancet Neurol

Int J Cardiol

Indian Pacing Electrophysiol J

J Stroke Cerebrovasc Dis

Embolic strokes of unknown source and cryptogenic stroke: implications in clinical practice

Front Neurol

Atrial fibrillation and mechanisms of stroke. Time for a new model

Stroke

How to identify patients at risk of silent atrial fibrillation after cryptogenic stroke: potential role of P wave dispersion

J Stroke

Inflammation as a risk factor for atrial fibrillation

Circulation

Original Article
Inflammation and Atrial Electrical Remodelling in Patients With Embolic Strokes of Undetermined Source