Response to Letter by Sharma et al and Leibeskind
We would like to thank Dr Sharman et al and Dr Liebeskind for their interest in our recent publication in which presence of a right-to-left shunt was associated with dramatic improvement after thrombolytic therapy in acute ischemic stroke patients. We demonstrated that tissue plasminogen activator (t-PA) thrombolysis was more effective in stroke patients with a right-to-left shunt than in patients without a right-to-left shunt. We believed that the action of t-PA is considered to be fibrin-dependent because of its favorable binding constant for fibrin-bound plasminogen and its activation of plasminogen in association with fibrin.1,2 Sharma et al proposed the possibility that high dose of t-PA through patent foramen ovale (PFO) could result in high rate of recanalization of occluded artery after t-PA infusion. They took interest in the relationship between size or function grading of PFO and dramatic clinical recovery. We were very interested in their suggestion and investigated size of PFO in our patients. Contrast transcranial Doppler demonstrated an right to left shunt in 17 (35.4%) patients. Of them, 13 patients were examined by transesophageal echocardiography to evaluate the PFO. The severity of shunt was assessed by transesophageal echocardiography using modified Lethen criteria, <10 (small), and >10 (large) microbubbles/3 seconds, respectively, with contrast echo.3 Three of 5 (60%) patients with large PFO had dramatic recovery, and 7 of 8 (88%) patients with small PFO had one. Therefore, there was no difference in rate of dramatic recovery between large and small PFO. However, the sample size is small. We should need more samples to elucidate Sharman’s hypothesis.
Liebeskind suggested that venous hemodaynamics enhanced collateral perfusion in patients with PFO, which induced the dramatic recovery after t-PA therapy. We read the comments with great interest. As Liebeskind mentioned, venous hemodaynamics might be affected by parallel cardiac preload. Therefore, we believe that patients with atrial fibrillation (AF) may have potential heart failure, and venous pressure is increased. In the present study, 24 patients with AF were enrolled. In fact, of them, 11 patients had brain natriuretic peptide >200 pg/mL, which indicates potential cardiac failure. However, patients with AF did not have more frequently dramatic recovery than those without AF (29.2% versus 58.3%; P=0.0417). Thus, we did not reach agreement that venous hemodaynamics enhanced collateral perfusion, which might induce the dramatic recovery after t-PA therapy. Off course, there is difference in venous hemodaynamics between patients with PFO and AF. Therefore, we should need a study to elucidate Liebeskind’s hypothesis.