Transcatheter Patent Foramen Ovale Closure Guided Only by Transesophageal Echocardiography Without fluoroscopy

Background Standby of transesophageal echocardiography (TEE) is necessary for any PFO closure in case of some cases with complicated anatomy of patent foramen ovale (PFO). The safety and effectiveness of Transcatheter PFO closure guided only by TEE navigation without fluoroscopy is unclear. Methods From 2017.06 to 2019.11, we included 38 patients who were recommended for PFO closure by the department of neurology at our hospital. The procedure was performed in a regular operating room by TEE navigation without fluoroscopy. Follow-up was given at 1st month, 3rd month, 6th month, 1st year and 2nd year after operation for each patient. Results All 38 patients were successfully performed PFO-closure guided by TEE. Procedural and intrahospital survival was 100%. Survival after a mean follow-up of 17.1±1.6months was 100%. "Catheter in sheath” technique was adopted in 16 cases. After the procedure, all 28 migraines with aura alleviated at different degree. All 10 patients suffering from pre-operational cryptogenic stroke survived and showed no evidence for recurrence of stroke (fatal or non-fatal), peripheral embolism or transient ischemic attack during follow-up. No serious adverse events in the PFO closure procedure and during the follow-up period. First clinical experiences showed that percutaneous TEE guided PFO closure is safe and


Introduction
Patent foramen ovale (PFO), a remnant of fetal anatomy, is associated with neurological events (such as cryptogenic stroke, transient ischemic attack [1], migraine with aura [2] among other clinical manifestations) because the permanent or temporary open statue of foramen ovale may allow blood from the right atrium to communicate directly with the blood in left atrium. This communication may cause "paradoxical emboli", where thrombi originating from a vein pass through the foramen ovale into the systemic arterial circulation, causing cerebral or other systemic thromboembolic infarction [3]. The prevalence of PFO is approximately 25% [4] in the adult population. If patients with neurological events benefit from PFO closure is discussed controversially. Some studies showed that patients with cryptogenic stroke have a decreased risk of recurrent stroke and patients [5] suffering from migraine with aura experience a remission of migraine [6] after PFO closure. Interventional PFO closure is usually performed using fluoroscopy and transesophageal echocardiography (TEE) guidance. Some experienced interventional cardiologists even perform PFO closure using fluoroscopy navigation only [7,8]. However, standby of TEE is necessary for any PFO closure in case of some cases with complicated anatomy of PFO. As standard interventional PFO closure is fluoroscopy-guided, we evaluated interventional PFO closure guided by TEE only with considerable experience in atrial septal defect closure [9] , our center performed PFO-closure in patients following the recommendation of a neurologist recommendation of closure.

Patient selection and Methods
From 2017.06 to 2019.11, we included 38 patients who were recommended for PFO closure by the department of neurology at our hospital. 26 females and 12 males suffered from migraine with aura or cryptogenic stroke in the presence of a PFO. Age ranged from 9 to 57 years with a mean age of 36.2 ± 14.4 years. The patients who were recommended for PFO closure were enrolled by the criteria: For migraine with aura, the patients were diagnosed by neurologists according to the criteria of the International Headache Society (2nd edition) [10]. For cryptogenic stroke or transient ischemic attack (TIA), the patients were diagnosed by neurologists with clinical and/or radiologically evidence.
For confirmation of a PFO, the patients were first screened by transcranial ultrasound for a right-to-left shunt. Next, patients were sent to transthoracic echocardiography (TTE) for advanced PFO evaluation: 1. confirmation of PFO; 2. ≥medium right-to-left shunt was detected (Right-to-left shunting, RLS, was detected with or without the Valsalva maneuver and > 10 microbubbles were detected in left atrium [11]).
Exclusive criteria: patients with psychiatric, neurodegenerative, inflammatory, infective diseases, pregnancy or contraindication to antiplatelet therapy were excluded. More patients baseline characters are described in Table 1.

Procedure
The procedure was performed in a regular operating room by TEE navigation without fluoroscopy. All patients with supine position were TEE re-evaluated before the procedure.
The main purpose was to reassure the PFO and provide device selection basis. When the re-evaluation confirmed the procedure, patients were given general anesthesia and  Procedural details -PFO closure  Table 2.  Table 3.

Safety and adverse events
There were no serious adverse events in the PFO closure procedure, reported by other reaserchers [15,16], including device-related (transient atrial fibrillation, general fatigue or syncope) and related to the implant procedure (access site bleeding, retroperitoneal hematoma or another bleeding), and unrelated events. During follow-up, there was no device-related side effect.

Discussion
PFO is the most common congenital heart defect. It has been historically associated with several pathological conditions, with varying strength of evidence, most importantly with stroke but also with other diseases like platypnea-orthodeoxia, decompression illness, systemic and coronary embolization, obstructive sleep apnoea, migraine headache with aura and pulmonary embolism [17]. With a PFO large proportion in the general population, it is quite difficult to make a strong link between PFO and some specific pathological condition. Therefore, preventive PFO closure for some disease like that mentioned above is a subject of great controversy. Therefore, numerous clinical trials investigate the effect of PFO closure to prevent neurological events. Among these, three ongoing clinical trials (PRIMA [17] , PREMIUM [6] and EASTFORM [18] ) focus on migraine. Even though patients suffering from migraine with aura did benefit from PFO closure in the PREMIUM trial, the PFO closure is still needed more trial to prove its therapy value for migraine. Maybe the PRIMA trial, an ongoing trial, could give us the answer. In our study, we enrolled migraine with aura patients based on the PREMIUM trial selection process with a favorable outcome.
For cryptogenic stroke patients, PFO closure has been studied intensely including CLOSURE I [19], PC [20], RESPECT [21], CLOSE [22] and Gore REDUCE [23] Based on all the above 5 RCTs, we can conclude PFO-closure devices decrease the risk of recurrent stroke compared with medical therapy in patients with cryptogenic stroke [16]. Some study [24] reported stroke may re-attack after PFO-closure and 6-months antiplatelet or anticoagulation therapy. This may relate with a too big device which was difficult covered by new endocardial tissue in the 6-months regular antiplatelet therapy period. So longer antiplatelet or anticoagulation therapy may be recommended for the PFO-closure with the big device. In our study, none of the patients with cryptogenic stroke suffered from a stroke during follow-up. Although the follow-up time is not very long and the cases number is limited, our good results still can to some extent prove PFO-closure is an effective prevention for recurrent stroke after cryptogenic stroke.
In 1992, TEE had been considered as the most helpful tool of screening PFO in patients with stroke who are less than 45 years of age and in those without clinical evidence of heart disease [25]. TEE is crucial for PFO and PFO closure for years [26]. With the great application of guiding of simple congenital heart disease for transthoracic intervention in China [27,28], TEE has been reconsidered changing its role from diagnosis to therapy guiding for structural heart disease. Even in the publication focusing on fluoroscopy for PFO closure [7,8] TEE has been confirmed as helpful in complex anatomy. Low complication rates of PFO closure are required to justify its therapeutic role in the prevention of neurological events. Despite the device-related complications, procedurerelated complications, including atrial fibrillation, hematomas, or transient hypotension [16,29] Figure 1 1A: a wire guide a delivery sheath from Inferior vena cava to superior vena cava; 1B: the loading sheath is trying to pass PFO; 1C: the delivery sheath has passed the PFO and wire is out; 1D: the PFO closure device is delivered to the left atrium; 1E: the left disc of the device is released; 1F: the right disc of the device is released and the device is fixed.

Figure 2
The schematic of "catheter in sheath" technique A 5 Fr MPA 2 diagnostic catheter is advanced in the delivery sheath, then the double joint of this combination makes the wire have multiple angles to get through PFO.