Devices for Percutaneous Closure of PFO
Devices for Percutaneous Closure of PFO
Patent foramen ovale catheter closure was attempted in 660 patients (361 men, 299 women, mean age 49.3 ± 12.9 years, range: 18–84 years) between January 2001 and December 2004 (Figure 1). They fulfilled the criteria for PFO closure either by a history of cryptogenic ischaemic stroke (n = 381; 58%) and/or TIA (n = 336; 51%) and/or migraine (n = 50; 7.6%) and/or decompression illness (n = 3; 0.5%). One hundred and eighty subjects had a history of more than one ischaemic event (27%). Atrial septal aneurysms were present in 63 subjects (28%) in the Amplatzer group, in 95 (43%) in the Helex group, and in 82 (37%) in the CardioSEAL-STARflex group (P = 0.0062). Besides the differences found in regard to septal aneurysms before the procedure, there were no significant differences in baseline characteristics between the three groups. Coronary artery disease was defined as a history of myocardial infarction, coronary intervention, or coronary artery bypass grafting. The mean PFO diameters were 9.7 mm (2–21.2 mm; Amplatzer), 9.3 mm (2–25.7 mm; Helex), and 9.5 mm (2–19.5 mm; CardioSEAL). Device implantation for PFO closure was technically successful in all interventions. Most placement attempts were needed in the Helex group. In seven patients, the occluders were retrieved before release and exchanged for another Helex due to an unsatisfactory constitution. The longest procedural and fluoroscopic times were in the Helex group (33.5 ± 14.2 min; 6.6 ± 4.6 min), although these differed only slightly compared with the other groups (Amplatzer: 28.6 ± 13.2 min, 4.1 ± 3.4 min; CardioSEAL-STARflex: 31.4 ± 12.2 min, 4.9 ± 3.5 min). The mean hospital stay time was longest in the CardioSEAL-STARflex group (19.8 ± 8.8 h compared with 18.1 ± 5.4 h in the Amplatzer and 18.8 ± 9.3 h in the Helex group). Specifics regarding procedural complications have previously been described in detail. Briefly, one potential ischaemic event related to the procedure occurred with complete resolution (Helex group). This was most likely related to air embolism or thrombotic material on the device or delivery equipment. Likewise, as previously described, technical difficulties were uncommon with a slightly higher device embolization rate with the Helex device (3 embolizations vs. none with either of the other devices). Periprocedural cardiac tamponade occurred in two patients (one in the Helex and one in the Amplatzer group, respectively). In both cases, the suspected mechanism was accidental atrial perforation. Pericardiocentesis was successful in one and surgery was required in the second patient.
(Enlarge Image)
Figure 1.
Study flow chart. FU, follow-up; ICH, intracranial haemorrhage; SAH, subarachnoid haemorrhage.
No patients were lost to follow-up. The mean follow-up time was 59.2 ± 6.0 months and did not differ significantly between the three groups (Amplatzer: 59.4 ± 5.0 months; Helex: 59.1 ± 6.5 months; CardioSEAL-STARflex: 59.1 ± 6.5 months).
At 5-year follow-up, the highest complete closure rate was achieved with Amplatzer devices (n = 220; 100%) and the lowest with Helex occluders (n = 213; 96.8%). Complete closure after single device implantation was more common with the Amplatzer and with the CardioSEAL-STARflex than with the Helex occluder (Amplatzer vs. Helex vs. CardioSEAL-STARflex: n = 217 (98.6%) vs. n = 202 (91.8%) vs. n = 213 (96.8%; P = 0.0012). Likewise, implantation of a second device was most frequently required in patients who received a Helex occluder and least frequently in those treated with an Amplatzer device. Closure rates increased with follow-up duration. While complete defect closure was found in 608 patients 6 months after the intervention (92.1%; n = 211 Amplatzer, n = 189 Helex, n = 208 CardioSEAL-STARflex), at 5 years follow-up, PFO closure was achieved in 652 patients (98.8%; n = 220 Amplatzer, n = 213 Helex, n = 219 CardioSEAL-STARflex).
During follow-up, 24 patients (3.6%) underwent a second intervention for closure of relevant residual shunts. Three of these patients suffered from recurrent cerebral ischaemia prior to the second implantation. In the Amplatzer group, a second device was implanted in two patients. In the first patient, a second Amplatzer occluder was implanted 7 months after the index procedure. In the second patient, a Premere occluder (St Jude Medical, St Paul, MN, USA) was implanted after 25 months. One patient who had been treated with a CardiaStar-occluder prior to randomization and implantation of an Amplatzer occluder underwent explantation of the Amplatzer occluder and operative defect closure due to a severe persistent shunt 12 months after implantation and low likelihood of complete closure with a third device. In the CardioSEAL-STARflex group, seven patients required a second device. In one case, TEE examination at 6 months follow-up showed an atrial septum with multiple fenestrations. These may have been unrecognized at first implantation. A second STARflex device was implanted. The other six residual shunts were closed using Premere in three patients (after 15, 23, and 25 months), Amplatzer in one (after 13 months), and CardioSEAL-STARflex devices in two patients (after 12 and 30 months). In the Helex group, 15 patients underwent a second procedure for residual shunt closure: 1 Premere occluder was implanted after 9 months, 1 Helex device after 16 months, and 11 Amplatzer devices between 1 week and 55 months after the initial procedure. One of these Amplatzer devices was implanted because a TEE at 6 months follow-up revealed a severe shunt due to late device embolization (to the aortic bifurcation). In this case, the transthoracic echocardiography before discharge as well as the TEE 30 days after the intervention showed the device well positioned. Late device embolizations are very rare and there are only few case reports available. In two patients, implantation of an Amplatzer device was attempted but technically not possible. Of these patients, one underwent surgical defect closure for a large residual shunt 19 months after the implantation.
The combined primary endpoint of TIA, stroke, cerebral death, or paradoxical embolism occurred in 25 patients (3.8%) within 5 years of follow-up (Table 2): 10 TIAs (1.5%), 12 strokes (1.8%), 3 cases of cerebral death (0.5%), and no paradoxical embolism. In the Amplatzer group, there were significantly fewer events (1.4%; 2 strokes, 1 cerebral death; P = 0.042) than in the CardioSEAL-STARflex group (5.9%; 6 TIAs, 6 strokes, 1 cerebral death) or in the Helex group (4.1%; 4 TIAs, 4 strokes, 1 cerebral death). Survival analysis using the log-rank test demonstrated superiority of the Amplatzer device compared with the CardioSEAL-STARflex (P = 0.01) regarding the occurrence of primary endpoint events. Compared with the Helex device, there was a trend to better results with the Amplatzer device (P = 0.079). All of the affected patients were examined by neurologists within the context of their endpoint event, and a hospital discharge letter was available for each of these cases.
Regarding the stroke and death rate (3.8% taking all groups into account), there was no significant difference between the three groups (P = 0.5827). Likewise, there was no significant difference in the stroke and vascular death rates (2.7% taking all groups into account) between the groups (P = 0.1081). The respective hazards are shown in Figure 2.
(Enlarge Image)
Figure 2.
Cumulative hazards and numbers at risk for (A) the primary endpoint, (B) stroke and death, (C) stroke and vascular death, and (D) any neurological event or necessity of operative intervention.
Two patients in the Amplatzer group suffered from minor strokes at 5 and 19 months after implantation. In both patients, TEE at 1 month follow-up visit excluded residual shunts or thrombus formation on the occluder surface. In addition, one patient died as a consequence of intracranial haemorrhage 4 years after the intervention (no antiplatelet or anticoagulation therapy at this time).
In the Helex group, one patient had a TIA (inability to extend the left hand) 30 min after implantation. In this patient, Valsalva manoeuvre immediately after the intervention did not show a residual shunt; hence, the most likely mechanism was air embolism or device- or delivery system-associated thrombus formation undetected by TEE. In addition, three TIAs were reported at 4, 33, and 54 months after the procedures. A mild residual shunt was present in one of these patients at follow-up examinations. A stroke occurred in four patients (at 1, 36, 45, and 56 months). In only one of these patients, a residual shunt was present. One patient in the Helex group died from subarachnoid haemorrhage 13 months after device implantation (no antiplatelet or anticoagulation therapy at this time).
In the CardioSEAL-STARflex device group, there were six cases of TIA. In one, the TIA occurred within 3 days after the intervention in a patient with large residual shunt after device implantation. Two patients experienced amaurosis fugax 4 and 18 months after the intervention, and three patients reported TIAs between the 4- and 5-year follow-up visits. Neither of these patients had a residual shunt. There were six cases of ischaemic stroke. One minor stroke occurred within 30 days after device implantation. In this patient, TEE at the end of the procedure excluded residual shunting. One patient was hospitalized after echocardiographic detection of right and left atrial thrombus formation on the occluder 2 months after PFO closure. During the hospital stay, a major ischaemic stroke occurred despite anticoagulation. To prevent further embolic events, operative extraction of the intraatrial thrombi was performed. The occluder was removed and the atrial septal defect was closed using a pericardial patch. Four additional strokes have been reported: two within the first year, one after 4 years, and one 5 years after the intervention. A residual shunt could not be detected in any of the affected patients. However, two of the patients had meanwhile developed atrial fibrillation. One patient died due to massive cerebral haemorrhage 3 months after PFO closure (taking dual antiplatelet therapy consisting of aspirin and clopidogrel).
Within 5 years of implantation, 12 patients (11 in the CardioSEAL-STARflex group, 1 in the Helex group) developed a device-associated thrombus. Thrombus formation was significantly more common in the CardioSEAL-STARflex group than in the other groups (P < 0.0001). All were seen within 3 months after implantation and 10 resolved after anticoagulation (9 in the CardioSEAL-STARflex group, 1 in the Helex group). Two patients in the CardioSEAL-STARflex group needed operative thrombectomy of large atrial thrombi. Throughout follow-up, no thrombi were observed in the Amplatzer group.
Using these results, we performed an additional endpoint analysis comparing the three groups for a combination of recurrent neurological events and complications requiring surgery. Taking all groups into account, there were 25 neurological events (3.8%; 3 in the Amplatzer group, 9 in the Helex group, 13 in the CardioSEAL-STARflex group) and 6 complications requiring surgery (0.9%; 2 in the Amplatzer group, 1 in the Helex group, 3 in the CardioSEAL-STARflex group) with no significant difference between the three devices (P = 0.4025). The respective hazards are shown in Figure 2.
At 5 years follow-up, 40 patients had presented with the new onset of atrial fibrillation (27 in the CardioSEAL-STARflex group, 5 in the Helex group, and 8 in the Amplatzer group). The incidence of atrial fibrillation was significantly higher in the CardioSEAL-STARflex group than in the other groups (P < 0.0001). Atrial fibrillation was most often detected within 1 month after device implantation (n = 18; 4 in the Amplatzer group, 2 in the Helex group, and 12 in the CardioSEAL-STARflex group). In five of these patients, atrial fibrillation began during implantation (one in the Helex group, four in the CardioSEAL-STARflex group). In 25 cases (17 CardioSEAL-STARflex, 3 Helex, and 5 Amplatzer), atrial fibrillation was paroxysmal and sinus rhythm could be maintained with medical therapy.
There were 10 deaths (1.5%) of non-neurological cause at last follow-up. In the Amplatzer group, one patient died in a car accident 2 months and two patients due to cancer 28 and 35 months after implantation. In the Helex group, there were four deaths. Two patients died within 6 months of follow-up, one after 3 months secondary to bilateral pneumonia following an acute myocardial infarction requiring prolonged intensive care, and one of unknown cause. Two patients died of cancer after 30 and 47 months, respectively. In the CardioSEAL-STARflex group, two patients died as a consequence of a myocardial infarction 10 and 25 months after the intervention and one patient due to sudden cardiac death 11 months after the intervention.
Results
Patent foramen ovale catheter closure was attempted in 660 patients (361 men, 299 women, mean age 49.3 ± 12.9 years, range: 18–84 years) between January 2001 and December 2004 (Figure 1). They fulfilled the criteria for PFO closure either by a history of cryptogenic ischaemic stroke (n = 381; 58%) and/or TIA (n = 336; 51%) and/or migraine (n = 50; 7.6%) and/or decompression illness (n = 3; 0.5%). One hundred and eighty subjects had a history of more than one ischaemic event (27%). Atrial septal aneurysms were present in 63 subjects (28%) in the Amplatzer group, in 95 (43%) in the Helex group, and in 82 (37%) in the CardioSEAL-STARflex group (P = 0.0062). Besides the differences found in regard to septal aneurysms before the procedure, there were no significant differences in baseline characteristics between the three groups. Coronary artery disease was defined as a history of myocardial infarction, coronary intervention, or coronary artery bypass grafting. The mean PFO diameters were 9.7 mm (2–21.2 mm; Amplatzer), 9.3 mm (2–25.7 mm; Helex), and 9.5 mm (2–19.5 mm; CardioSEAL). Device implantation for PFO closure was technically successful in all interventions. Most placement attempts were needed in the Helex group. In seven patients, the occluders were retrieved before release and exchanged for another Helex due to an unsatisfactory constitution. The longest procedural and fluoroscopic times were in the Helex group (33.5 ± 14.2 min; 6.6 ± 4.6 min), although these differed only slightly compared with the other groups (Amplatzer: 28.6 ± 13.2 min, 4.1 ± 3.4 min; CardioSEAL-STARflex: 31.4 ± 12.2 min, 4.9 ± 3.5 min). The mean hospital stay time was longest in the CardioSEAL-STARflex group (19.8 ± 8.8 h compared with 18.1 ± 5.4 h in the Amplatzer and 18.8 ± 9.3 h in the Helex group). Specifics regarding procedural complications have previously been described in detail. Briefly, one potential ischaemic event related to the procedure occurred with complete resolution (Helex group). This was most likely related to air embolism or thrombotic material on the device or delivery equipment. Likewise, as previously described, technical difficulties were uncommon with a slightly higher device embolization rate with the Helex device (3 embolizations vs. none with either of the other devices). Periprocedural cardiac tamponade occurred in two patients (one in the Helex and one in the Amplatzer group, respectively). In both cases, the suspected mechanism was accidental atrial perforation. Pericardiocentesis was successful in one and surgery was required in the second patient.
(Enlarge Image)
Figure 1.
Study flow chart. FU, follow-up; ICH, intracranial haemorrhage; SAH, subarachnoid haemorrhage.
No patients were lost to follow-up. The mean follow-up time was 59.2 ± 6.0 months and did not differ significantly between the three groups (Amplatzer: 59.4 ± 5.0 months; Helex: 59.1 ± 6.5 months; CardioSEAL-STARflex: 59.1 ± 6.5 months).
At 5-year follow-up, the highest complete closure rate was achieved with Amplatzer devices (n = 220; 100%) and the lowest with Helex occluders (n = 213; 96.8%). Complete closure after single device implantation was more common with the Amplatzer and with the CardioSEAL-STARflex than with the Helex occluder (Amplatzer vs. Helex vs. CardioSEAL-STARflex: n = 217 (98.6%) vs. n = 202 (91.8%) vs. n = 213 (96.8%; P = 0.0012). Likewise, implantation of a second device was most frequently required in patients who received a Helex occluder and least frequently in those treated with an Amplatzer device. Closure rates increased with follow-up duration. While complete defect closure was found in 608 patients 6 months after the intervention (92.1%; n = 211 Amplatzer, n = 189 Helex, n = 208 CardioSEAL-STARflex), at 5 years follow-up, PFO closure was achieved in 652 patients (98.8%; n = 220 Amplatzer, n = 213 Helex, n = 219 CardioSEAL-STARflex).
During follow-up, 24 patients (3.6%) underwent a second intervention for closure of relevant residual shunts. Three of these patients suffered from recurrent cerebral ischaemia prior to the second implantation. In the Amplatzer group, a second device was implanted in two patients. In the first patient, a second Amplatzer occluder was implanted 7 months after the index procedure. In the second patient, a Premere occluder (St Jude Medical, St Paul, MN, USA) was implanted after 25 months. One patient who had been treated with a CardiaStar-occluder prior to randomization and implantation of an Amplatzer occluder underwent explantation of the Amplatzer occluder and operative defect closure due to a severe persistent shunt 12 months after implantation and low likelihood of complete closure with a third device. In the CardioSEAL-STARflex group, seven patients required a second device. In one case, TEE examination at 6 months follow-up showed an atrial septum with multiple fenestrations. These may have been unrecognized at first implantation. A second STARflex device was implanted. The other six residual shunts were closed using Premere in three patients (after 15, 23, and 25 months), Amplatzer in one (after 13 months), and CardioSEAL-STARflex devices in two patients (after 12 and 30 months). In the Helex group, 15 patients underwent a second procedure for residual shunt closure: 1 Premere occluder was implanted after 9 months, 1 Helex device after 16 months, and 11 Amplatzer devices between 1 week and 55 months after the initial procedure. One of these Amplatzer devices was implanted because a TEE at 6 months follow-up revealed a severe shunt due to late device embolization (to the aortic bifurcation). In this case, the transthoracic echocardiography before discharge as well as the TEE 30 days after the intervention showed the device well positioned. Late device embolizations are very rare and there are only few case reports available. In two patients, implantation of an Amplatzer device was attempted but technically not possible. Of these patients, one underwent surgical defect closure for a large residual shunt 19 months after the implantation.
The combined primary endpoint of TIA, stroke, cerebral death, or paradoxical embolism occurred in 25 patients (3.8%) within 5 years of follow-up (Table 2): 10 TIAs (1.5%), 12 strokes (1.8%), 3 cases of cerebral death (0.5%), and no paradoxical embolism. In the Amplatzer group, there were significantly fewer events (1.4%; 2 strokes, 1 cerebral death; P = 0.042) than in the CardioSEAL-STARflex group (5.9%; 6 TIAs, 6 strokes, 1 cerebral death) or in the Helex group (4.1%; 4 TIAs, 4 strokes, 1 cerebral death). Survival analysis using the log-rank test demonstrated superiority of the Amplatzer device compared with the CardioSEAL-STARflex (P = 0.01) regarding the occurrence of primary endpoint events. Compared with the Helex device, there was a trend to better results with the Amplatzer device (P = 0.079). All of the affected patients were examined by neurologists within the context of their endpoint event, and a hospital discharge letter was available for each of these cases.
Regarding the stroke and death rate (3.8% taking all groups into account), there was no significant difference between the three groups (P = 0.5827). Likewise, there was no significant difference in the stroke and vascular death rates (2.7% taking all groups into account) between the groups (P = 0.1081). The respective hazards are shown in Figure 2.
(Enlarge Image)
Figure 2.
Cumulative hazards and numbers at risk for (A) the primary endpoint, (B) stroke and death, (C) stroke and vascular death, and (D) any neurological event or necessity of operative intervention.
Two patients in the Amplatzer group suffered from minor strokes at 5 and 19 months after implantation. In both patients, TEE at 1 month follow-up visit excluded residual shunts or thrombus formation on the occluder surface. In addition, one patient died as a consequence of intracranial haemorrhage 4 years after the intervention (no antiplatelet or anticoagulation therapy at this time).
In the Helex group, one patient had a TIA (inability to extend the left hand) 30 min after implantation. In this patient, Valsalva manoeuvre immediately after the intervention did not show a residual shunt; hence, the most likely mechanism was air embolism or device- or delivery system-associated thrombus formation undetected by TEE. In addition, three TIAs were reported at 4, 33, and 54 months after the procedures. A mild residual shunt was present in one of these patients at follow-up examinations. A stroke occurred in four patients (at 1, 36, 45, and 56 months). In only one of these patients, a residual shunt was present. One patient in the Helex group died from subarachnoid haemorrhage 13 months after device implantation (no antiplatelet or anticoagulation therapy at this time).
In the CardioSEAL-STARflex device group, there were six cases of TIA. In one, the TIA occurred within 3 days after the intervention in a patient with large residual shunt after device implantation. Two patients experienced amaurosis fugax 4 and 18 months after the intervention, and three patients reported TIAs between the 4- and 5-year follow-up visits. Neither of these patients had a residual shunt. There were six cases of ischaemic stroke. One minor stroke occurred within 30 days after device implantation. In this patient, TEE at the end of the procedure excluded residual shunting. One patient was hospitalized after echocardiographic detection of right and left atrial thrombus formation on the occluder 2 months after PFO closure. During the hospital stay, a major ischaemic stroke occurred despite anticoagulation. To prevent further embolic events, operative extraction of the intraatrial thrombi was performed. The occluder was removed and the atrial septal defect was closed using a pericardial patch. Four additional strokes have been reported: two within the first year, one after 4 years, and one 5 years after the intervention. A residual shunt could not be detected in any of the affected patients. However, two of the patients had meanwhile developed atrial fibrillation. One patient died due to massive cerebral haemorrhage 3 months after PFO closure (taking dual antiplatelet therapy consisting of aspirin and clopidogrel).
Within 5 years of implantation, 12 patients (11 in the CardioSEAL-STARflex group, 1 in the Helex group) developed a device-associated thrombus. Thrombus formation was significantly more common in the CardioSEAL-STARflex group than in the other groups (P < 0.0001). All were seen within 3 months after implantation and 10 resolved after anticoagulation (9 in the CardioSEAL-STARflex group, 1 in the Helex group). Two patients in the CardioSEAL-STARflex group needed operative thrombectomy of large atrial thrombi. Throughout follow-up, no thrombi were observed in the Amplatzer group.
Using these results, we performed an additional endpoint analysis comparing the three groups for a combination of recurrent neurological events and complications requiring surgery. Taking all groups into account, there were 25 neurological events (3.8%; 3 in the Amplatzer group, 9 in the Helex group, 13 in the CardioSEAL-STARflex group) and 6 complications requiring surgery (0.9%; 2 in the Amplatzer group, 1 in the Helex group, 3 in the CardioSEAL-STARflex group) with no significant difference between the three devices (P = 0.4025). The respective hazards are shown in Figure 2.
At 5 years follow-up, 40 patients had presented with the new onset of atrial fibrillation (27 in the CardioSEAL-STARflex group, 5 in the Helex group, and 8 in the Amplatzer group). The incidence of atrial fibrillation was significantly higher in the CardioSEAL-STARflex group than in the other groups (P < 0.0001). Atrial fibrillation was most often detected within 1 month after device implantation (n = 18; 4 in the Amplatzer group, 2 in the Helex group, and 12 in the CardioSEAL-STARflex group). In five of these patients, atrial fibrillation began during implantation (one in the Helex group, four in the CardioSEAL-STARflex group). In 25 cases (17 CardioSEAL-STARflex, 3 Helex, and 5 Amplatzer), atrial fibrillation was paroxysmal and sinus rhythm could be maintained with medical therapy.
There were 10 deaths (1.5%) of non-neurological cause at last follow-up. In the Amplatzer group, one patient died in a car accident 2 months and two patients due to cancer 28 and 35 months after implantation. In the Helex group, there were four deaths. Two patients died within 6 months of follow-up, one after 3 months secondary to bilateral pneumonia following an acute myocardial infarction requiring prolonged intensive care, and one of unknown cause. Two patients died of cancer after 30 and 47 months, respectively. In the CardioSEAL-STARflex group, two patients died as a consequence of a myocardial infarction 10 and 25 months after the intervention and one patient due to sudden cardiac death 11 months after the intervention.
