Page 13 - Journal of Structural Heart Disease Volume 3, Issue 5

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Original Scienti c Article
present with cryptogenic stroke [9]. A case-controlled study also showed that anti-phospholipid antibodies are strongly associated with PFO and atrial septal an- eurysms [10]. Therefore, autoimmune diseases with various hypercoagulable factors may increase the risk of stroke. However, the PFO in Cryptogenic Stroke Study and Anti-Phospholipid Antibodies and Stroke Study (PICSS-APASS) post-hoc retrospective analysis did not show an increased risk of stroke in patients with anti-phospholipid antibodies and PFO [11].
Our retrospective observational study shows that PFO or ASD closure can be safely performed in pa- tients with thrombotic disorders or prothrombotic states using the Amplatzer or Gore Helex device. Only 1 thrombotic event occurred on an Amplatzer device (1.4%) for PFO closure, but this was in the presence of new onset atrial brillation. This patient also had hyperhomocysteinemia and experienced recurrent stroke 8 years after closure.
There were no cases of thrombosis observed on Gore Helex devices, which suggests that the e-PTFE device may not be thrombogenic even in throm- bophilic patients. In this higher-risk patient popu- lation, there was no procedural mortality, systemic infection, endocarditis on the implanted device, or erosion with a mean follow-up of 43.5 ± 34.7 months. Thus, septal closure in this thrombophilic patient population may be safely performed with a low risk of recurrent thrombotic events using either Amplatzer or Gore Helex devices.
Of the thrombophilic conditions, most were due to estrogen-containing medications, which are known to increase thrombosis [12]. A higher than expect- ed number (n = 79 out of 104; 76%) of patients who had a stroke, TIA, or peripheral arterial embolus were females, of whom 51 (65%) were receiving OCP or HRT. These observations suggest that estrogen com- pounds predispose to paradoxical embolism in the presence of a septal defect. These ndings are con- sistent with those of our previous study showing a higher rate of PFO in post-menopausal women with a stroke who were using HRT [13]. Stopping OCP or HRT may have led to the low rate of recurrent stroke following septal closure, but this was not a random- ized trial of medical therapy (without OCP) versus de- vice closure. It is not known what the recurrent stroke rate would be in women who stop taking hormone
therapy but do not get their PFO closed. This raises the question whether enrolling women who were on OCPs at the time of the event but subsequently stopped taking OCPs might bias the population of PFO closure for cryptogenic stroke trials to a lower risk group and thus produce lower subsequent events.
The Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Stan- dard of Care Treatment (RESPECT) trial [14] showed a 10-year event rate point estimate for annualized re- current stroke in the intention-to-treat cohort of 0.57 per 100 patient- years (closure group) versus 1.05 per 100 patient-years in the medical group. Patients with mild forms of thrombophilia were included in the RE- SPECT trial, but the investigators did not capture the frequency of OCP/HRT use at the time of the initial stroke. Thus, this large randomized trial did not show whether the lower than expected frequency of re- current stroke was partly due to stopping hormone therapy at entry into the trial. The RESPECT trial also demonstrates that a longer-term follow-up is neces- sary, as the risk of recurrent stroke in the medically treated group continued to be constant at about 1% per year for the 10 years of observation. It is hypoth- esized that this yearly risk of recurrent stroke might continue in the medically treated group for the rest of the patients’ lives.
This was a retrospective observational study of a complex patient population in a tertiary care center, which may limit its generalizability. The procedures were performed in a single center by experienced op- erators who routinely perform PFO or ASD closures. Nevertheless, this study provides useful data on the management of such complex patients, as most are excluded from randomized clinical trials. Thus, scant information is available about device implantation in patients with thrombophilia.
In conclusion, in this group of patients with throm- bophilic conditions, PFO or ASD closure may be safely performed using an Amplatzer or Gore Helex device without a high risk of developing thrombus on the device. Moreover, 66% of women with thrombophilia who presented with cryptogenic stroke, TIA, or pe- ripheral arterial embolism were receiving OCP or HRT, which is a form of thrombophilia that can be reversed by medication cessation. The high frequency of this transient and reversible form of thrombophilia may
Kar, S. et al.
Septal Defect Closure in Thrombophilia