Patent foramen ovale closure by using transesophageal echocardiography for cryptogenic stroke: single center experience in 132 consecutive patients

Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke, arterial desaturation, decompression illness, and migraine [1]. Percutaneous PFO closure is an option for patients with a cryptogenic stroke caused by the paradoxical embolism through the PFO [2]. Among patients with PFO and cryptogenic stroke, closure has reduced recurrent stroke and has a statistically significant effect on the composite of stroke, transient ischemic attack (TIA), and death in adjusted analyses [3]. Percutaneous closure is the preferred treatment, because it results in a smaller wound and a lower rate of postprocedural complications than open heart surgery [4, 5]. In most hospitals, the percutaneous procedures are performed using plain fluoroscopy in the catheter room. This procedure has some disadvantages, including the following: the inevitable radiation damage to patients and operators; the adverse effects of contrast agents on kidneys; and high cost. Moreover, when serious complications occur, e.g., occlude falling off or iatrogenic injury leading to cardiac tamponade, thoracotomy or extracorporeal circulation cannot be immediately performed [6‐8]. To avoid the abovementioned disadvantages, transesophageal echocardiography (TEE) with clear sound window is used for patients. We proposed a TEE-guided transcatheter PFO closure approach.

Since the beginning of our program of the percutaneous closure of PFO, we used a simplified and economical TEE-only guided approach that is feasible, safe, and effective. We retrospectively reviewed cases in our hospital to evaluate this approach.

The foramen ovale is a potential door capable of opening from the right to left atrium. Approximately 20 to 25% of the population has PFO. In young stroke patients, the prevalence reached 45% [11]. Patients with PFO are several times more likely to have stroke, migraine, peripheral arterial embolism, decompression sickness, and other risks than the normal population. The pathogenicity of PFO attracted the attention of numerous experts and scholars, and PFO closure has been explored to prevent recurrent stroke events, treat migraine, and platypnea-orthodeoxia [12]. Although the efficacy of PFO closure for cryptogenic stroke has been controversial, numerous experimental studies showed that PFO closure is superior to medical therapy in terms of preventing further stroke. Several recent meta-analyses found that PFO closure showed a marked benefit in preventing recurrent stroke/TIA with increased incidence of atrial fibrillation, and patients with moderate-to-large shunts or aged less than 60 years old had benefitted from interventional closure. Guidelines must be updated to reflect this procedure [13‐15].

In most centers, fluoroscopy-guided approach has been generally used for the percutaneous closure of PFO, and TEE is only used for pre- or intra-procedural evaluation. However, X-rays emitted by fluoroscopy negatively affect the health of patients and operators. The contrast agents used in the process of digital subtraction angiography may also adversely affect the health of patients. The TEE-only guided occlusion of several simple congenital heart diseases, such as atrial septal defect (ASD), ventricular septal defect, and patent ductus arteriosus, is safe and effective [16‐18]. PFO occlusion is similar to ASD occlusion, but PFO occlusion has its particularity. The main difficulty of PFO occlusion is how the catheter passes through the PFO channel. TEE feasibly provides guidance throughout the entire PFO closure procedure. TEE can clearly show the location of the catheter and guide the catheter through PFO to establish the path during the occlusion process. Accurately understanding the morphology of PFO in patients to improve the success rate of procedures and reduce complications is necessary for operators. Meanwhile, echocardiography is better than radiation guidance in assessing anatomy and hemodynamics [19]. TEE can observe the following in detail: the sizes of inlet and outlet of PFO, the tunnel length of PFO, the thickness of secondary septum, whether interatrial septal aneurysm was combined and its sizes, and whether abnormal eustachian valve and other abnormalities exist. TEE can also be used to monitor the whole process of occluder release, especially when determining whether or not the occluder was correctly placed, finding whether residual shunts exist, whether it affected the heart valves or coronary sinus, and whether aortic erosion occurs. The use of TEE also allowed for occluder replacement if the occluder was incorrectly positioned. After completely releasing the occluder, TEE was also applied to reevaluate the effect of the occlusion. The main advantages of this type of approach is the avoidance of X-ray radiation and contrast agent application. Moreover, incision is not necessary. All of our procedures were performed in the operating room, and the disinfected areas included the chest and groin to avoid delay in transfer or re-anesthesia of the patients in the event of severe complications (detachment of occluder or pericardial tamponade) due to operational failure. The procedure can be immediately converted to thoracotomy. In our procedures, the patients usually need general anesthesia with endotracheal intubation, which is a fly in the ointment. Professor Pan XB from Fuwai hospital in Beijing had successfully performed the ASD closure for some patients by only using TTE [8]. We may perform PFO closure for some suitable patients whose pictures are sufficiently clear by only using TTE under local anesthesia. However, TTE cannot provide a picture as clear as that produced by TEE and can be highly inaccurate in overweight, barrel-chested patients [7].

PFO is closely associated with migraines, but the underlying mechanism of PFO-induced migraine remains unclear. One hypothesis states that some specific metabolites such as serotonin and endothelial vasoconstrictor peptide, or subclinical emboli that enter the cerebral circulation system through PFO cause the migraine [20, 21]. A clinical meta-analysis shows that patients with PFO are 2.5 times more likely to suffer from migraines and 3.4 times more likely to suffer from migraines with aura [22]. The 25% incidence of PFO in the general population increased to 50% in the migraine population. Whether or not the PFO closure is effective in treating migraines remains controversial. Several randomized studies have failed to confirm that the improvement in migraine is due to the closure of the foramen ovale. Some retrospective and observational studies have reported the high rates of migraine relief (ranging from 50 to 80%) after PFO closure [2, 12]. In the present study, migraine relief was reported in 73.7% among the 57 patients after the closure procedure. The proportion of patients with a score of more than 60 before the closure procedure was as high as 57.9%, whereas a score of more than 60 indicated that headache significantly affected the family, work, study, or social activities of the patients, and their quality of life has significantly decreased. Twelve months after occlusion, nearly 50% of the patients scored 15 points lower than the preoperative scores, and the total score was less than 50 points, thereby indicating that migraine symptoms disappeared or significantly decreased in most patients.

PFO occlusion showed good efficacy despite the lack of randomized control group. All PFOs (100%) were successfully closed using the cardi-O-fix PFO occluder. During long-term follow-up of 27.0 ± 9.1 months, recurrent stroke was not encountered, and severe complications were not detected. Paroxysmal atrial fibrillation occurred in only four (3%) patients after the procedure. However, although no blood flow signal between the atriums was observed by echocardiography after PFO closure, the residual right-left shunt in 39 (31.1%), 21 (15.9%), and 10 (7.6%) of 132 patients who underwent reexamination of foaming test at 3, 6, and 12, months after the procedure was observed, respectively. The high incidence of residual shunt in the follow-up period of this study may be due to the use of c-TTE for assessing RLS. In some other trials c-TEE was used for follow-up. TEE is a semi-traumatic and painful examination for patients, and completing Valsalva maneuver successfully during the process was difficult for some of them. Thus, the residual shunt may have been underestimated. In addition, the patient with a large residual RLS, as demonstrated by the c-TTE at 12 months of follow-up, was the one who had received transseptal puncture during the closure procedure. We assumed that the application of transseptal puncture may have contributed to the large residual shunt. Transseptal puncture technique may be an effective option for facilitating device closure after the failure of conventional approach, but an increased incidence of residual shunt was observed with this technique [23]. Comparative studies between Cardi-O-fix PFO occluder and other type of occluders have been rarely conducted. Perhaps the lack of effectiveness of the device was also a factor affecting the high rate of residual shunt. Moreover, other reasons for residual shunt after occlusion exists. Atrial-level shunt is not the sole source of paradoxical emboli. Pulmonary arteriovenous malformations, venous abnormalities, including persistent left-sided superior vena cava to the left atrium, or an unroofed coronary sinus may also cause paradoxical embolization. Positive results on bubble testing after PFO closure are not uncommon; important anatomic lesions may coexist and remain a potential risk factor for recurrent paradoxical embolization [24]. In the present study, the possibility of pulmonary vascular malformations in the four (3.1%) patients with a moderate-to-large residual RLS at 12 months of follow-up was ruled out by computed tomographic pulmonary angiography. The four patients were asked to take aspirin (3–5 mg/kg body weight) orally to prevent the recurrence of CS and to undergo a review c-TTE with Valsalva maneuver annually. If residual RLS drops to a small shunt, the aspirin treatment can be discontinued. If residual RLS does not reduce and neurology embolism event recurs, then secondary percutaneous intervention or surgical closure is recommended.

In summary, TEE-only guided PFO closure allowed the avoidance of the use of X-rays and contrast agents and provided a safe, feasible, and effective method for the closure of PFO. The percutaneous transcatheter closure of PFO was performed successfully in all patients. According to the 12-month c-TTE follow-up study, more than 90% of patients did not have residual shunt. Mean long-term follow-up for > 2 years did not show recurrence of stroke. More than 70% of patients with migraine experience felt relieved after the closure procedure.