The present study showed that acute ischemic stroke severity altered the effect of chronic AF on the outcome of thrombolytic therapy.
We observed that severe stroke patients with chronic AF (baseline NIHSS score > 14) may be more prone to developing poor outcomes than those with lower scores. To our knowledge, this is the first study to identify stroke patients with chronic AF according to stroke severity and evaluate the significance of this distinction with respect to outcomes after thrombolytic treatment. Baseline NIHSS thresholds may be used to evaluate treatment strategies for stroke patients with chronic AF.
Although international guidelines suggest thrombolysis treatment as a first-line treatment for eligible patients when administered within 4.5 hours after the onset of stroke, only one in 3 patients treated by thrombolysis achieves a significant benefit [13, 14]. It is still controversial whether acute ischemic stroke patients with chronic AF should receive rtPA therapy. Raymond and colleagues found that patients with chronic AF have worse stroke outcomes than do patients without AF, and the risk of poor outcomes was greater in patients with a longer duration of AF, but those investigators were not able to perform additional subgroup analyses to identify high-risk patients because of the small sample size.
The characteristics of blood clots in patients with chronic AF are still controversial. Stroke patients with chronic AF may have old, large emboli that are resistant to being dissolved with alteplase after reaching intracranial vessels. Our study found that moderate stroke patients treated by thrombolysis may achieve favorable outcomes, but severe stroke patients may not gain any obvious benefit. The reason may be that the emboli of moderate stroke patients split into small fragments after reaching intracranial vessels; these patients would thus achieve significant benefit from alteplase treatment. On the other hand, old, large emboli, which are unlikely to dissolve, may cause a sudden occlusion of large cerebral arteries and may lead to severe stroke with a high NIHSS score. Accordingly, severe stroke patients with AF are resistant to rtPA therapy.
Whether the characteristics of blood clots and their response to rtPA treatment are affected by the chronicity of AF awaits further investigation. Postmortem pathological examination showed that cerebral arteries are mostly occluded by red thrombi in patients with cardioembolic stroke [15, 16]. Red thrombi contain some fibrin and erythrocytes which were found more vulnerable to tPA than other thrombi, with a resultant easier to recanalize.However, the chronicity of AF may affect the characteristics of the culprit clots and their resistance to rtPA treatment, and the components of the embolus may be organized and calcified. Several studies have shown that clots associated with AF are more resistant to dissolution with rtPA [17, 18].
Our study has several limitations. First, this study was a single-center study, and the current study findings should be confirmed by a multicenter study. Second, the composition of the emboli, which is significant for the identification of pathophysiological changes, was unclear in chronic AF patients. Finally, this study was merely observational, and further studies are required to elaborate on the pathophysiological effects of thrombolysis on thrombi in patients with chronic AF.