Stroke Risk from Pacemaker Leads in Patients with PFO
Abstract & Commentary
By Michael H. Crawford, MD, Editor
Source: DeSimone CV, et al. Stroke or transient ischemic attack in patients with transvenous pacemaker or defibrillator and echocardiographically detected patent foramen ovale. Circulation 2013;128:1433-1441.
Pacemaker or defibrillator leads have been shown to have attached thrombi in up to one-third of cases and asymptomatic pulmonary emboli have been documented in up to 20% of patients. Thus, concern has arisen that right heart endocardial leads in patients with a patent foramen ovale (PFO) may lead to cerebral embolic events. These investigators from the Mayo Clinic in Rochester, MN, performed a retrospective analysis of 6075 patients seen in the last decade who had an endocardial lead placed in the right heart. The primary outcome assessed was a diagnosis of stroke or transient ischemic attack (TIA) consistent with a cardioembolic source. Patients were excluded who had obvious carotid, intracranial, or aortic sources and intracranial hemorrhage; who lacked adequate data to define the timing of any cerebral events; or who had an inadequate echo evaluation for PFO. Their policy during the sampling time was to perform a comprehensive echo evaluation in everyone getting an endocardial lead. The average follow-up after device implantation was 4.7 years. A definite PFO was found in 364 of these patients (6%). The two groups were similar in baseline characteristics. In the PFO group, 8.2% had a cerebral event vs 2% in the no PFO group (P < 0.0001). About two-thirds of the events were strokes for a rate of 5.2% vs 1.4%, repectively. The difference in the rate of events widened over time. The hazard ratio of having a PFO was 3.49 (95% CI, 2.33-5.25, P < 0.0001) and was similar after adjustment for known stroke risk factors and anticoagulant or aspirin use (3.3). The all-cause mortality rate was similar in the two groups. The authors concluded that the presence of a PFO on routine echo in patients undergoing endocardial lead placement increased the risk of cerebral embolic events and perhaps should encourage the use of anticoagulants, PFO closure, and epicardial lead placement in these patients.
Commentary
Just when we thought PFO closure to prevent cryptogenic stroke was dead, this paper comes along and reopens the issue. Despite the attractiveness of the PFO theory of cryptogenic stroke and migraine causation, these relationships have been hard to prove. General population studies of PFO subjects have found no consistent association with stroke or migraines. The CLOSURE I trial randomized PFO patients after cryptogenic stroke to closure vs anticoagulant or antiplatelet therapy and found no difference in recurrent stroke.1 However, they excluded patients with endocardial leads and most of the strokes observed were non-embolic, so the study was underpowered for embolic stroke. Endocardial lead patients are different in that these devices are nidi for thrombi and they often lie in proximity to the atrial septum. In this study, the stroke event curves didn’t separate for 6 months suggesting that it takes time for lead thrombi to form or that it takes time for small emboli to raise the pulmonary pressures and increase the likelihood of right to left shunting. Lead-induced tricuspid regurgitation may take time to develop and cause increased elevated right atrial pressure. The lack of an observed mortality difference may be because the cerebral events are usually small. Thus, in these specific patients, the association between PFO and stroke/TIA may hold.
There are several limitations to this study. Retrospective studies are subject to various biases and causality cannot be definitively proven. Also, the specific role of anticoagulant and antiplatelet therapy in this study could not be determined and may have influenced the results. Transesophageal echocardiography (TEE) was done in about one-third of patients and may have biased the study toward stroke patients who are more likely to get TEE. Also, TEE increases the sensitivity of PFO detection. In those who got TEE, the PFO rate was 14% vs 6% in the study overall. Given that pathologic and other studies have found PFOs in up to 25% of normal individuals, this study seems insensitive, which may have biased it toward larger PFO patients who are more likely to have paradoxical emboli. This study used routine clinical echoes and we don’t know how many used contrast or Valsalva. Finally, no right ventricular pressure data were reported.
For all these reasons, this study is hypothesis-generating. However, the results make us pause again. Should we view endocardial lead patients differently? Should they all have TEEs to detect PFOs? If PFOs are detected should they all take antiplatelet or anticoagulant agents? Should those with especially large PFOs or higher right atrial pressures have their PFO closed or epicardial leads used? Do we need to survey endocardial lead patients periodically to assess for the development of large thrombi? None of these questions can be answered by this study, but the issues are real because the consequences of stroke can be devastating.
REFERENCE
1. Furlan AJ, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012;366:991-999.