Stroke Recurrence in Patent Formen Ovale (PFO)

Abstract & Commentary

By John J. Caronna, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Caronna reports no financial relationships relevant to this field of study.

Synopsis: In this study, there is no correlation between the risk of recurrent stroke and the size of a PFO, the magnitude of the right-to-left shunt, or the presence of an atrial septal aneurysm.

Source: Serena J, Marti-Fàbregas J, Santamarina E, et al. Recurrent stroke and massive right-to-left shunt–Results from the prospective Spanish Multicenter (CODICIA) Study. Stroke 2008;39:3131-3136.

Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) have been identified as potential risk factors for stroke, particularly in patients with cryptogenic stroke. Some studies have demonstrated an association between the degree of right-to-left shunt (RLSh), the size of PFO, or the presence of ASA and the risk of stroke. Serena et al. prospectively examined the risk of recurrent stroke associated with PFO in a Spanish Multicenter Study. Four hundred and eighty-six patients at 17 hospitals with cryptogenic stroke were included. Patients were examined using contrast intracranial Doppler (c-TCD) at baseline, and the magnitude of the RLSh was quantified during a Valsalva maneuver. Transthoracic and/or transesophageal echocardiography (TEE), brain computed tomography (CT) scan, or brain magnetic resonance imaging (MRI) were performed. Functional outcome and stroke recurrence were determined initially at three months, and yearly thereafter. Massive RLSh was detected in 200 (41%). The mean followup was two years. Stroke recurrence was low (6%, n = 28) and similar in patients with massive RLSh (3%), with nonmassive RLSh (2%), and with no RLSh (5%) in both the younger group (< 55 years); p = NS and in the whole population (5% vs. 6% vs. 6%, respectively; p=NS). Regression analysis found no association between massive RLSh and recurrent stroke in either the whole population or in the younger population. The results were similar when concurrent ASA and massive RLSh were analyzed or when antithrombotic treatment and concomitant risk factors were included.

The authors conclude, based on their results, that neither massive RLSh nor massive RLSh with concurrent ASA is an independent risk factor for recurrent stroke in either the general or the younger stroke populations.

Because the risk of stroke recurrence was low and no significant differences were found between the use of antiplatelet and anticoagulant agents, these results do not offer justification for the use of anticoagulation in preference to antiplatelet drugs.


Although the association between RLSh due to PFO and cryptogenic stroke has been well established, there are few data and widely-varying results with regard to the relevance of PFO as a predictor of stroke recurrence.1,2 The CODICIA study was a multicenter, prospective, observational study of patients with first cryptogenic stroke conducted exclusively by neurologists. The main purpose of this study was to analyze the risk of stroke recurrence and the evaluation of medical treatment was a secondary objective. The CODICIA study confirmed the results of the PFO-ASA1 and the PICCS studies2 regarding the risk of stroke recurrence in patients with PFO. The recurrence rate was low and was similar in patients with or without RLSh and in those with both a PFO and ASA. No difference were found when the risk of stroke recurrence was analyzed relative to the magnitude of RLSh. As in other studies, the CODICIA study showed that c-TCD had a higher sensitivity than TEE in RLSh detection and quantification.3

The CODICIA study has certain limitations. TEE was not routinely performed, hence, the results as they relate to ASA must be interpreted with caution. In addition, because the study was not randomized, only cautious interpretation can be made concerning the efficacy of medical treatment. Nevertheless, the study indicates that given the low risk of stroke recurrence, especially in younger patients, the routine use of anticoagulation in patients with PFO is not warranted and the use of invasive treatment such as percutaneous PFO occlusion should be performed only within the framework of a randomized clinical trial.


1. Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001;345:1740-1746.

2. Homma S, Sacco RL, Di Tullio MR, et al. Effect of medical treatment in stroke patients with patent foramen ovale: Patent foramen ovale in Cryptogenic Stroke Study. Circulation 2002;105:2625-2631.

3. Jauss M, Zanette E. Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography. Cerebrovasc Dis 2000;10:490-496.