A proper echocardiographic assessment of PFO requires an adequate knowledge of anatomy and embryology of the heart [9, 10].

In embryonic life, the primitive atrium is a single cavity. The primary septum grows down from the supero-posterior wall of the atrium toward the endocardial cushions (Fig. 21.3(1), at the level of atrioventricular canal, thus limiting an area known as the primary foramen (ostium primum) (Fig. 21.3(2)). Meanwhile, the ostium primum progressively closes owing to the fusion of septum primum with endocardial cushions; multiple small perforations begin to develop and coalesce at the superior portion of the primary septum (Fig. 21.3(3)) to form a secondary communication between the two atria, known as the secondary foramen (ostium secundum). In the 12th week, an infolding of tissue, known as the secondary septum (septum secundum) (Fig. 21.3(4)), grows down along the right atrial side of the primary septum, progressively covering the ostium secundum (Fig. 21.3(5)), but leaving a free area inferiorly. As a result, a sort of canal (tunnel) guarantees a passage between the two atria, as required by the fetal circulation (Fig. 21.3(6)). After postnatal changes in pulmonary and systemic circulation, septum secundum forms a support against which the septum primum may press and fuse. This occurs in about 70 % of subjects, whereas in the remaining 30 %, the tunnel converts into a “flap-like” valve between the two atria that may open every time the right atrial pressure overcomes the left one.

The area where this “flap-like” valve is located is called the fossa ovalis, and the individual variability in morphology of all the structures participating in the formation of the fossa and of the PFO may result in several different anatomic variants: the fusion between the two septa may be irregular and more than one orifice may be detected; the degree of overlapping between the two septa (defined as tunnel, Fig. 21.4) is variable, and as a result, it is possible to have either very long or very short tunnel of the PFO; when septum primum is thin and redundant, it may be excessively mobile and creates a aneurysmal fossa ovalis (Fig. 21.5); the presence of abundant adipose tissue within the infolding septum secundum may result in a very thick and bulky septum (Fig. 21.6). Other important structures that may pose issues with the device delivery and placement are redundant Eustachian valve and the Chiari network, two embryonic remnants. Based on the anatomic features, we may therefore differentiate a simple from a complex PFO, where one or more of these characteristics are present (Table 21.1).

Preparation of patients for the intervention should start with a complete counseling to make them aware that PFO is thought to be the cause of their clinical event and that similar events may occur also in patients without PFO. Even though the closure of PFO removes a cause for cryptogenic stroke, the possible role of misdiagnosed atrial fibrillation should be mentioned. This aspect is particularly important because of the inconclusive results of the main randomized trials comparing percutaneous closure and medical treatment [11–13].

Other important aspects concern the exclusion of inherited or acquired thrombophilia, in order to give proper peri- and postprocedural antithrombotic therapy, and allergy to nickel (a very frequent issue in the general population) that is contained in most of the available prostheses [14].

Prior to the procedure, patients are usually treated with aspirin 100 mg and clopidogrel (loading dose 300 mg). An anticoagulant may be required tailored to the thrombotic risk in case of coagulation disorders, depending on the type of thrombophilia. Patients should also receive a single intravenous antibiotic dose within 1 h of percutaneous access, typically with cefazolin 2 g (or vancomycin in the presence of allergy to penicillin). Patients should receive intravenous normal saline at 1 mL/kg/h before and during the procedure to avoid left atrial hypovolemia, possibly with an air-eliminating filter in position. During procedure heparin 70 mg/kg is administered, soon after sheet insertion, to maintain ACT >250 s. Nasal cannula oxygen at 6 L/min is administered for hyperoxygenation, in case of an air embolus while catheterizing the left atrium.

The technique for percutaneous closure of PFO borrowed that used for ASD, but skills in the use of different devices are also required, because several different prostheses have been over the years. The two main approaches currently favored by the operators consist of an echo-guided or a fluoroscopy-guided procedures [15]. Debate continues about whether echocardiographic guidance is required for PFO closure, as opposed to fluoroscopic guidance alone. The former is carried out using either transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE), and when TEE is performed, the presence of both the echocardiographer and the anesthetist (to reduce patient discomfort during the procedure) is required. Conversely, the latter approach has the advantage of completely avoiding the need for the anesthetist during the procedure even though a complete study of PFO morphology with TEE is mandatory before the intervention. However, it cannot be excluded that, during the procedure, the operator may need TEE to perform a transseptal puncture rather than manage possible prosthetic mismatches or misunderstood complications. So, this kind of approach should be limited to expert operators and is advisable in the treatment of simple PFO.

The procedure is carried out through a systemic venous approach. The femoral site is the more suitable because it allows to trace the direction of blood flow as it is in the fetal circulation that is also at the basis of pathophysiology of PFO-related diseases. For this reason, it is usually preferred over all other attempted approaches: internal jugular [16], axillary [17], or hepatic vein [18]. After local anesthesia of the groin, a regular 0.035-in. J-tip guidewire is introduced through a puncture needle, followed by a 6-Fr sheath insertion. Owing to the anatomy of PFO (with a vertically angled tunnel directed from the inferior border of the fossa ovalis in the right atrium to the superior left atrium), the simple advancement of the 0.035-in. J-tipped guidewire will readily pass through the PFO into the left atrium in about half of the cases. If not, a curved catheter (multipurpose shape, curve 1 or 2) placed at the level of the diaphragm will direct the wire medially toward the PFO. If the PFO still cannot be passed, it may be negotiated with the catheter alone or, if that fails, with a straight wire or a PCI guidewire. A typical situation for this would be a PFO that consists only of a small hole in one of the corners of the initial foramen (Fig. 21.7). In this case, it would be necessary to guide the wire to a sharp turn once it has entered the PFO tunnel. Occasionally, it may be necessary to learn more about anatomy before passing the PFO displaying the fossa ovalis injecting contrast medium, withdrawing a MP catheter previously positioned in the superior vena cava toward the interatrial septum in the direction where the PFO is suspected to be (in the left anterior oblique projection). In other cases, especially when the procedure is performed with fluoroscopic guidance, right atrial angiography may be performed with a pigtail catheter in the left anterior/oblique (40/40°) projection, to see the PFO and potential atrial septal aneurysm. In small PFOs, hand injection contrast angiography through the catheter can help identify the entry point. In cases with difficult advancement of the guidewire into the left atrium, a JR4, hockey stick, or XB 3.5 guide catheters may be used. Should there be fenestrations within the PFO that prohibit advancement of the catheter, a 4- or 5-F catheter may be used. When PFO is located in a very eccentric position and delivery of a large size prosthesis is required (as in cases with wide septal aneurysm), a transseptal puncture may be performed in the middle of the fossa ovalis to allow central positioning of the prosthesis. When the assessment of tunnel length or foramen width is important in the choice of device, gentle balloon sizing of the PFO may be performed. The sizing balloon catheters are usually mounted on a shaft in an “over-the-wire” system and advanced across the PFO, inflated gently until they assume a “dog bone” configuration. Radiopaque markers on the shaft may help in the measurement of the foramen/tunnel size. Another technique to assess compressible tunnel is to inflate a balloon-tipped pulmonary capillary wedge catheter within the left atrium, withdrawing the balloon against the septum, and perform a hand injection of contrast medium through the guiding catheter in the right atrium. Once the catheter is in the left atrium, the guidewire is advanced into one of the pulmonary veins (usually the left superior one). It is mandatory to exclude that the guidewire is into the left appendage to prevent atrial perforation. So the proper position may be confirmed by hemodynamic measurement of left atrial pressure, by fluoroscopy (the catheter is typically “outside” of the heart shadow), or by echocardiography. The catheter is then advanced into the correspondent pulmonary vein and exchanged over a 260-cm, 0.035-in. extra-stiff guidewire to support the positioning of the guide catheter through the PFO. After choosing the proper device (type and size), the delivery system is advanced in the left atrium. Each device has its own preparation and delivery technique, but a common mandatory step during the preparation is to check for the complete elimination of air bubbles from the system. After which the device is advanced, through the guide catheter, to the left atrium and pushed out of the sheath up to the middle waist so that the left disk can fully form. The sheath and the pusher are then pulled back, as a single unit, until the left disk gets stopped at the septum. From there on, only the sheath will be pulled back while gently advancing on the pusher cable. The entire set is pushed against the septum to put the right disk into its proper place (Fig. 21.8). Device stability was controlled by means of the Minnesota maneuver, pushing and pulling the device toward both atria before deployment. Depending on which approach is chosen, echo or contrast hand injection through the sheath next to the right atrial disk is used to confirm that the device is positioned correctly. At fluoroscopy, in the left anterior oblique projection, the two disks are seen in profile. The distance between the two disks superiorly reflects the thickness of the septum secundum. After device delivery, the guide catheter may be retrieved, and 10-min manual compression of the femoral vein is enough to achieve a complete hemostasis at the puncture site.

Accurate and precise knowledge of the anatomy of the atrial septum and the nearby structures is essential for the effectiveness and safe performance of PFO closure. Therefore, irrespective of the planned procedural approach, a systematic and comprehensive approach to TEE should be performed in all patients before undergoing percutaneous closure of PFO [19]. The goal of this examination is the meaningful understanding of atrial anatomy, of all the atrial structures that may be relevant for device selection and deployment. A proper checklist for evaluation should be carried out on all patients, as follows:

When TEE is used along with fluoroscopy during the procedure, it may be useful to guide the crossing of PFO (especially when transseptal puncture is required), the positioning of the device, the post-closure monitoring of the relationship between the prosthesis and the adjacent structures, and the monitoring for possible complications [20]. The recent introduction of 3D echo technology allowed a better understanding of PFO morphology [21]. In particular, by using real-time 3D TEE imaging, it is possible to measure the size the of left and right atrial PFO opening and of tunnel length included in between the two openings [22]. 3D TTE is a promising modality to provide comprehensible en face imaging of ASD because of its noninvasiveness, low cost, portability, and wide availability [23].

A valid alternative to TEE is the use of intracardiac echocardiography (ICE) that allows to perform the procedure without sedation and without the need for an expert echocardiographer during the intervention [24, 25]. Currently available ICE systems are the AcuNav catheter (Siemens Medical Systems), the ViewFlex catheter (St Jude Medical), and the Ultra ICE (Boston Scientific). Table 21.2 shows the main technical characteristics of each system. Each catheter requires a specific ultrasound console for the visualization of the images, which is generally compatible with other devices from the same manufacturer. When using ICE, femoral, jugular, or subclavian accesses are possible. However, the femoral is the preferred access for most of the physicians because of its strategic position on the table. To avoid vascular complications, the catheter should be carefully advanced from the groin toward the heart under continuous fluoroscopic guidance because of its stiffness. The use of a long sheath (30 cm) is strongly recommended to protect vessels until below the heart. In the phased array technology devices, once the catheter is positioned in the right atrium, its manual advancement, clockwise rotation, and posterior flexion allow a complete visualization of all the main structures of the heart, thus enabling performance of all steps necessary for PFO closure, including possible transseptal puncture. The main disadvantages of ICE when compared to TEE are that it requires a second femoral vein puncture and adds significant odds and costs to the procedure [26].

In the majority of cases, device selection is based on TEE images. Although some operators only perform transthoracic echocardiography and/or transcranial Doppler studies before bringing the patient to the cardiac catheterization laboratory, a transesophageal echocardiogram should be considered critical in selecting devices and technical strategies likely for success in advance of the procedure [27].