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EXPEDITED REVIEW: EDITORIAL COMMENT

Transcatheter closure of atrial shunts

Focus on a lingering issue^*

^* Division of Cardiology, Mattel Children's Hospital and the David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California, USADr. Moore is a paid consultant for AGA Medical.

^* Reprint requests and correspondence: Dr. John W. Moore, Division of Cardiology, Mattel Children's Hospital at UCLA, B2-427, MDCC, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
jwmoore{at}mednet.ucla.edu

Along the way, it was discovered that the patent foramen ovale (PFO) might be occluded by similar devices employing techniques used for ASD occlusion (8). This observation placed us into the business of PFO closure with its much murkier indications. Although controversial, many studies have suggested that patients with PFO, especially younger patients with atrial septal aneurysm, have a higher risk of cryptogenic stroke than those with intact atrial septum (9–11). However, the evidence suggesting that transcatheter (or surgical) PFO closure to prevent stroke is more efficacious than medical therapy alone is at present inconclusive (12,13). Randomized controlled studies comparing device PFO closure and medical therapy are underway. In the meantime, device closure is being performed if medical therapy fails to prevent second events.

Particularly in stroke/PFO patients, but also in ASD patients, the issue of device-related thrombus is important. Obviously, if a device induces thrombus formation, it may be contraindicated. If the incidence is low, then the risks of device-related thrombosis and of subsequent embolic events need to be carefully evaluated. This is quite obvious, but it was buried in a pile of other issues when the primary focus was on ASD closure (7,14).

The original animal pathological studies of the Amplatzer and other devices showed that deposition of thrombus is part of a process that eventually leads to endothelization of devices (15,16). This observation in part led to the routine use of antiplatelet agents after device implantation. Paradoxically, routine definitive echocardiographic surveillance of devices during the most vulnerable period after implant was not incorporated into most ASD device studies (7,14). Only after some explanted ASD devices showed thrombus formation (17,18) and attention shifted to PFO closure for stroke prevention did routine post-implant transesophageal echocardiographic (TEE) surveillance come to the fore.

In this issue of the Journal, Krumsdorf et al. (19) report TEE follow-up of their 10-year 1,000-patient experiences with device closure of PFO and ASD. Their report focuses primarily on the important issues of device-related thrombosis and its consequences. Despite methodologic imperfections, the sheer volume of their experience commands our attention.

The report emphasizes PFO device closures (59% of the patients) in adult patients with previous embolic events. It also includes a substantial experience with ASD occlusion for hemodynamic indications in patients as young as 13 years. During the course of this study, the investigators implanted nine different devices, including large numbers of the following: 418 Amplatzer ASD and PFO devices; 169 CardioSEAL and StarFLEX devices (NMT Medical, Boston, Massachusetts); 161 Helex devices (W. L. Gore and Associates, Flagstaff, Arizona); and 127 PFO-Star devices (Applied Biometrics Inc., Burnsville, Minnesota).

In addition to regular transthoracic echocardiographic (TTE) follow-ups, the Krumsdorf et al. (19) protocol included routine TEE studies performed four weeks and six months after device implantation. The TEE studies were accomplished, on average, 71% of the scheduled times. If thrombus was present, additional TEE examinations were performed as indicated.

According to the researchers, regular follow-up TTE failed to identify patients with thrombus formation. Thrombus was identified by TEE evaluation in 15 of the 593 (2.5%) PFO patients and in 5 of the 407 (1.2%) ASD patients. Thrombus was most often located in the left atrium and directly contiguous with the device. Of these patients, 70% (14 of 20) were identified by the four-week TEE.

Highest on the list of factors associated with thrombus formation was the type of device. All 326 Amplatzer devices evaluated at four weeks were free of thrombus. In contrast, among 119 CardioSEAL and StarFLEX devices observed at four weeks, 7 (5.9%) had thrombus formation, and among 76 PFO-Star devices examined at four weeks, 5 (6.6%) had thrombus. The difference between Amplatzer and these alternative devices was significant (p < 0.05). The Helex device was examined in 122 patients at four weeks and one thrombus was found.

Other factors associated with thrombus formation were atrial fibrillation (n = 4) and persistent atrial septal aneurysm (n = 4). Factors not associated with thrombus included coagulation disorders, coronary disease and risk factors, patient age, gender, use of protamine during the implant procedure, type of medical prophylaxis post-implant, residual shunt post-implant, and device fracture.

In patients with thrombus identified, Krumsdorf et al. (19) employed medical therapy (most often warfarin) to dissolve the thrombus. They were successful in 85% of cases (17 of 20). Three patients required surgery to remove the thrombus (and device) and to perform surgical closure of their atrial shunts. Among patients with identified thrombus were four (20%) who suffered embolic events consisting of three minor strokes and one transient ischemic attack.

Krumsdorf et al. (19) offer a number of observations worthy of careful consideration. These observations impact on post-implant device surveillance, device selection, and perhaps also the indications for device implant.

The investigators recommend routine TEE surveillance of all devices 4 weeks, 6 months, and 12 months following implantation. Their observations demonstrate conclusively that TEE surveillance is necessary for the CardioSEAL, StarFLEX, and PFO-Star devices four weeks' post-implant. However, because no clots were detected by the four-week TEE on Amplatzer devices, routine TEE surveillance in patients with these devices should not be recommended. Further study of the Helex and the Buttoned devices (Custom Medical Devices, Amarillo, Texas) is necessary before guidelines regarding a four-week surveillance TEE can be proposed for these devices. Furthermore, Krumsdorf et al. (19) found only three clots in 903 TEE studies performed six months after device placement. Thus, their recommendation for TEE at 6 and 12 months in all patients may be excessive.

The researchers state that TTE was inadequate to detect device-related thrombus. However, large clots (such as those in Figure 1 of their report [19]) should be evident on TTE if acoustic windows are adequate. Experience in pediatric patients suggests that transthoracic surveillance of devices may be adequate for most children and for adults with adequate acoustic windows (7). Certainly, the risks of TEE surveillance (sedation, aspiration, esophageal tear, and so on) need to be considered when planning surveillance. We suggest that TTE be performed and reviewed before TEE. The TEE should be reserved for patients with inadequate acoustic windows, higher-risk devices, and/or higher-risk clinical situations.

Perhaps the report's most important observation is that thrombosis rates varied significantly with the devices. Although no clots were found on 326 Amplatzer devices four weeks after implantation, 5.9% of 119 CardioSEAL and StarFLEX devices and 6.6% of 76 PFO-Star devices had thrombus identified. These findings are consistent with our experience at University of California-Los Angeles and with other reports (20–22). Furthermore, although bioengineered devices are under development and may prove to be less thrombogenic than some current devices (23), in this regard the Amplatzer devices already set an exacting standard. The problem of device-related thrombosis may not be sufficient rationale for development of more biocompatible devices.

The Krumsdorf et al. (19) report includes data regarding neurological events in patients with demonstrated device-related thrombus. Unfortunately, the data are insufficient to draw conclusions regarding the efficacy of PFO device closure for prevention of cryptogenic stroke. Nevertheless, we believe that the investigators provide observations that can help guide our current practice: Their report offers reasonable assurance that the incidence of device thrombosis and related embolic events appear to be low enough on all current devices to justify continued use for ASD closure and continued study for PFO closure. Furthermore, routine TEE surveillance appears to be necessary after four weeks with some devices, but not for the Amplatzer devices. After the four-week examination, TEE surveillance should be individualized and TTE surveillance should be employed when acoustic windows are adequate.

	Footnotes

 
^* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.

	References

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