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The likelihood of recurrent embolic events after percutaneous closure of patent foramen ovale (PFO) is low and unrelated to a residual shunt in the vast majority of cases, according to results of a single-center retrospective study published online June 27, 2013, ahead of print in Catheterization and Cardiovascular Interventions. According to the authors, ongoing randomized trials will be required to answer whether PFO closure reduces the risk of recurrent events. 

Investigators led by Horst Sievert, MD, of CardioVascular Center Frankfurt (Frankfurt, Germany), analyzed follow-up data from 1,930 patients who underwent percutaneous PFO closure for secondary prevention of paradoxical embolic events at their institution between August 1994 and May 2009.

Before PFO closure, patients experienced at least 1 embolic event, and 28% had recurrent events including strokes, TIAs, or peripheral embolic events, for an annual preprocedural recurrence rate of 22.4%.

Low Recurrence Rate After PFO Closure

Over a mean follow-up of 39 ± 30.7 months, 63 events were reported in 55 patients, including 25 ischemic strokes, 36 TIAs, and 2 peripheral embolic events, for an annual recurrence rate of the composite primary endpoint of 1% per year.

None of the recurrent events were classified as ‘likely due to paradoxical embolism,’ meaning a residual shunt existed and all other possible causes had been ruled out.

Among the strokes, 2 cases were considered “possibly due to paradoxical embolism” because a residual shunt was present and in 1 instance another potential cause had not been ruled out, while in the second instance a potential cause was identified (nondevice-related valvular endocarditis). However, the great majority of strokes (23 of 25) were deemed “definitely not due to paradoxical embolism” because a residual shunt was excluded.

Among the TIAs, 5 of 36 events were considered possibly due to a residual shunt, although other potential causes were identified in all 5 patients. But again, the preponderance of TIAs (31 of 36) were unrelated to paradoxical embolism because a residual shunt was excluded by transesophageal echocardiography (TEE). The most common potential causes identified were:

• Atherosclerosis (30.5%)
• Cryptogenic stroke (19.4%)
• Cardio-embolism due to A-fib (13.8%)
• Carotid stenosis (5.5%)
• Meningioma (5.5%)

Of 2 peripheral embolic events, both were considered possibly related to paradoxical embolism due to the presence of a residual shunt, although both patients had concomitant A-fib.

Overall, 9 events were deemed potentially due to paradoxical embolism, for an annual rate of 0.14%. 

Recurrence-free survival was 98.8% (95% CI 95.7-100%) at 1 year, 97.1% (95% CI 93.9-100%) at 3 years, and 95% (95% CI 91.9-98.5%) at 5 years.

In multivariable analysis, event-free survival was associated with:

• Total number of events before PFO closure (HR 1.4; 95% CI 1.2-1.7)
• Age (HR 1.03; 95% CI 1.01-1.06)
• New-onset A-fib (HR 2.3; 95% CI 1.1-5.0)
• Thrombus formation (HR 6.8; 95% CI 2.4-19.3)
• Diabetes (HR 2.4; 95% CI 1.1-5.2)
• Use of the Sideris device (HR 5.5; 95% CI 1.6-18.6) 

Importantly, although recurrent events were more common in patients with vs. without a residual shunt (3% vs. 1%), this association was not shown on multivariable analysis (HR 1.7; 95% CI 0.8-3.6; P = 0.16). However, among patents with residual shunts, having a small shunt compared with a moderate or large shunt tended to decrease the rate of recurrent events (1% vs. 4.5%; P = 0.13).

Don’t Dismiss Residual Shunting Altogether

The authors observe that the current results, together with similar findings from the randomized CLOSURE I trial comparing PFO closure with medical therapy, “suggest that most recurrent events are unrelated to the PFO, the device, or incomplete closure.”

However, it would be premature to conclude that residual shunting plays no role in recurrent events, they say, “given the very small shunt magnitude in the majority of patients with a residual shunt” in the current study. Moderate or large shunts may cause embolic events either via paradoxical embolism or association with other conditions that may trigger stroke, such as A-fib.

Moreover, Dr. Sievert and colleagues caution, the substantial reduction in annual rate of recurrent events after PFO closure “cannot be discounted.” Therefore, they conclude, “careful patient selection is of paramount importance when evaluating the merits of PFO closure.”

Study Details

Device implantation was technically successful in all patients (34 required a second attempt), with complete PFO closure on TEE 1 month or later after the procedures. A small residual shunt remained in 5.5% of patients, and a moderate to large shunt in 2.5%. Subsequently, 68 patients underwent percutaneous closure of a residual shunt, and 8 had surgery due to a residual shunt (n = 3), thrombus formation (n = 3), or pericardial tamponade (n = 2).

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