Stroke is the leading cause of death in Portugal, accounting for 9.9% of mortality nationwide (11235 deaths) in 2018, according to the latest available data from Statistics Portugal (INE). In 2018, an estimated 11388 potential years of life were lost due to cerebrovascular disease.1

In patients with cryptogenic stroke, one of the most frequently found abnormalities in the complementary investigation is patent foramen ovale (PFO).2 In the adult population, the prevalence of PFO is 20-25% and in patients who suffer a cryptogenic stroke, 40-50% have this anatomic variant.3

Right heart catheterization demonstrating a guidewire crossing the septum is the most accurate method for confirming the presence of PFO,4,5 but ultrasound technology has made available many non-invasive techniques for diagnosing a right-to-left shunt (RLS), such as transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) and transcranial Doppler ultrasound (TCD).6 TEE with bubble study is the most accepted standard noninvasive method for PFO diagnosis. It enables quantification of shunt size, documentation of anatomic characteristics and differentiation between PFO, atrial septal defect and pulmonary shunt.4,5 TCD is a more sensitive technique for shunt detection but less specific due to its inability to differentiate between cardiac and pulmonary shunting; it carries a sensitivity of 97% and specificity of 93% compared with TEE bubble study as the reference.7

Despite the efficacy of PFO occluder devices, their use has a rare potential risk of early and late complications including, in extreme cases, device dislodgement, atrial wall erosion, perforation, fracture, migration or embolization, infection, thrombosis, induction of arrhythmias and even death. Additionally, encumbrance of the interatrial septum by the prosthetic device may hinder future transseptal puncture and left-sided interventions such as left atrial appendage closure, arrhythmia ablation and mitral valve interventions. Finally, the risk of allergic reactions to nickel mesh cannot be excluded, and the need for prolonged dual antiplatelet therapy after the procedure may not be tolerated by all patients.8

Recently, a new percutaneous ‘deviceless’ system based on surgical suture-mediated PFO closure has been introduced in interventional practice, and shows a favorable efficacy and safety profile. The possible advantages of such a procedure are self-evident, notably avoidance of early and late complications related to the absence of a permanent implanted cardiac device. The complete and effective closure rates reported with this technique were similar to other device trials.8

The aim of the present study is to present the procedural details of the NobleStitch® technique and to report the baseline characteristics of patients who underwent the procedure in our center.

Atherosclerosis is by far the most frequent cause of brain ischemia; however, a significant number of ischemic strokes are due to cardioembolism, large vessel atherothromboembolism, small vessel occlusive disease or other less common mechanisms. The term cryptogenic stroke designates the category of ischemic stroke for which no probable cause is found despite a thorough diagnostic assessment and is defined in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification as a stroke of undetermined etiology.2 Patients presenting with this clinical picture should be screened for the presence or absence of a PFO. Recently, the European position paper on PFO stated that when a PFO is thought likely to be implicated in a cryptogenic embolism, it should be classified as PFO-related instead of cryptogenic stroke.10

In the presence of a PFO, certain anatomic characteristics are associated with a higher risk of embolism, such as the presence of an ASA (also termed a hypermobile septum primum). As is known, changes in right atrial volume and pressure lead to moments of patency of the foramen ovale. The presence of an ASA may open the PFO with every heartbeat, thereby increasing the potential for thrombus passage from the venous to the arterial system. A similar effect is exerted by a Eustachian valve (or a Chiari network), which can direct blood flow from the inferior vena cava to the foramen ovale.3

A meta-analysis of five randomized clinical trials (n=3440) showed that percutaneous PFO device closure plus long-term medical antithrombotic (primarily antiplatelet) therapy reduced the risk of recurrent stroke compared with long-term medical antithrombotic therapy (antiplatelet or anticoagulant) alone. However, this meta-analysis also found a significantly increased risk of atrial fibrillation (AF) in patients with devices, the risk being device-dependent (the great preponderance of AF events were transient episodes occurring within 4-6 weeks of device placement). Occurring in 3.2% of patients undergoing a device procedure, these generally self-limited, periprocedural AF events have less likelihood of serving as a new stroke source compared with AF events that occur later, and their clinical consequences are yet to be clarified.11,12 Observational studies have reported chest pain as an occasional side effect associated with device implantation, thought to be secondary to an enhanced inflammatory response, in some cases due to nickel allergy.8 An observational survey of approximately 14000 PFO device implants worldwide reported an incidence of 1 in 500 implantations resulting in surgical removal, most commonly due to severe and persistent chest pain, thought to be caused by allergy-induced formation of excessive scar tissue in 50% of cases.13

Percutaneous ‘deviceless’ systems were recently introduced with the purpose of overcoming most of the limitations of traditional PFO occluders. This new technique is potentially superior to traditional closure systems, particularly in terms of device-related complications such as dislodgement, fracture, embolization, migration, atrial wall erosion, heart perforation, infection, induction of atrial arrhythmias and major changes in atrial anatomy and function.8

The NobleStitch EL Italian Registry8 has shown that suture-mediated PFO closure is feasible in the majority of septal anatomies, with septal suture using this system being successfully carried out in 186 of 200 (96%) patients, and provides effective PFO closure comparable to traditional devices: at 206±130 days of follow-up, contrast TTE with the Valsalva maneuver revealed no RLS in 75% of patients and RLS grade ≤1 in 89%; significant RLS (grade 2 and 3) was present in 11%, and the technique's safety profile was good at medium-term follow-up.

Our experience is in line with this registry, indicating that suture-mediated PFO closure represents a valid, feasible and safe alternative to traditional umbrella-like devices. Although this technique requires an additional amount of contrast medium and radiation dose, the facts that general anesthesia or sedation and echocardiographic monitoring are not required during the procedure, and that it is a deviceless technique, largely compensate for these drawbacks. Another important point is that, in the event of failure, this technique does not preclude the possibility of implanting an umbrella-like device, if needed.

While it is essentially a fluoroscopically guided procedure that does not require echocardiographic monitoring, it is extremely important to perform an accurate preprocedural TEE assessment to optimally define the anatomical features of the PFO. All of our patients accepted for the procedure had a TEE assessment with good visualization of the interatrial septum, the PFO and adjacent structures.

A modified technique using a second NobleStitch® primum catheter has been described, which aims to increase the adhesion surface of the septa in order to maximize the success rate of the procedure, especially for very large tunnels and floppy aneurysms. Nevertheless, this alternative technique still needs to be tested in a larger number of cases and was not used in any of our patients.9

The majority of cases were performed recently, thereby precluding the accurate reporting of follow-up, which is why the aim of this paper was to document our initial experience with patient selection and with the technique itself. Experience with this new device is rapidly increasing in Europe and a clinical trial comparing PFO closure results with the NobleStitch EL® and with the FDA-approved Amplatzer PFO Occluder® device is currently underway (the NobleStitch EL STITCH trial).14 The results of this trial will allow a better understanding of the efficacy of this technique.

Our experience suggests that suture-mediated PFO closure represents a valid, feasible and safe alternative to traditional umbrella-like devices. It can be an option in the majority of PFO anatomies. However, the use of this technique as a first choice in PFO closure will require results of larger series and clinical trials.

The authors have no conflicts of interest to declare.