Tabla 1. Clinical characteristics of patent foramen ovale patients treated at Fleni.

Tabla 2. Clinical characteristics associated with recurrent stroke risk in patent foramen ovale pat...

Tabla 3. Closure devices used for percutaneous patent foramen ovale closure at Fleni.

Figura 1. Separated puncture sites.

Figura 2. Figures 2 and 3. Contrast injection into the left superior pulmonary vein to confirm corre...

Figura 3. Figures 4 and 5. Imágenes de ecocardiograma intra cardíaco mostrando aneurisma del tabiq...

Figura 4. Figure 6. Gentle tension maintained on the system during device release to prevent entangl...

Figura 5. Figures 9 and 10. Intracardiac echocardiography images showing a non-communicating tunnel ...

Tabla 4. RoPE score.

Introduction

The first description of patent foramen ovale (PFO) was made by Galen in the 16th century1. In 1951, in a review article, B. Johnson documented 41 cases of emboli lodged a PFO, establishing the passage of particulate material through it1 — a phenomenon subsequently confirmed by ultrasound-based studies2.

Following a period of conflicting scientific data comparing percutaneous PFO closure versus various medical therapies — including favorable, inconclusive, or unfavorable meta-analyses3-10 as well as randomized trials11, 12 —, in 2017 three studies showed that PFO closure, in a selected patient population, is superior to medical therapy for the secondary prevention of stroke13-15.

While PFO is associated with a variety of pathological conditions16, this report is limited to stroke patients in whom ICE-guided percutaneous PFO closure was attempted.

Material and methods

ICE was performed in 266 consecutive patients with embolic stroke of undetermined source (ESUS) and suspected PFO. Diagnosis was confirmed in 226 of them and ICE-guided percutaneous closure was attempted.

Their medical records were retrospectively reviewed to assess initial outcomes and in-hospital evolution.

Clinical characteristics are listed in Tables 1 and 2.

PFO diagnosis at our institution was established using ultrasound-based modalities combined with the Valsalva maneuver (VM) and agitated saline contrast injection, following a standardized protocol17.

Definitions

1) Procedural success: PFO closure with the device in correct position and absence of major complications during the procedure. 2) Clinical success: Procedural success plus absence of major in-hospital complications. 3) Major complications: Death from any cause; acute myocardial infarction; major or minor stroke; transient ischemic attack (TIA); arterial embolism in any location, or TIMI major bleeding18. 4) Minor complications: Any complication not meeting criteria for a major complication.

Closure technique

All patients underwent conscious sedation with local antisepsis and analgesia. Aspirin 100 mg was administered orally two hours before the procedure.

The first technical consideration is to avoid liberal intravenous fluid administration. While generous fluid loading is useful during percutaneous left atrial appendage closure to prevent appendage collapse, it is counterproductive in PFO closure: it increases left atrial (LA) pressure, which may shift the septum primum toward the interatrial septum, thus hindering passage through the PFO and potentially generating false-negative results on right-to-left shunt (RLS) assessment19-21. Our standard procedure is to administer 750–1000 mL of saline once the PFO has been crossed with the catheter in order to elevate LA pressure and prevent air entry during exchanges.

Percutaneous PFO closure begins with the placement of a 6-French (Fr) introducer and a 9-Fr, 35-cm-long introducer into the right femoral vein to facilitate passage of the ICE transducer from the femoral vein to the inferior vena cava. Placing the two femoral venipunctures at least one centimeter apart is essential to avoid creating a common channel, which would complicate post-procedural hemostasis (Figure 1). Following venous access, 5000 units of sodium heparin are administered.

To minimize procedural time, while the ICE system is being prepared and the transducer advanced to the right atrium (RA), an attempt is made under radiological guidance to cross the PFO into the LA using a multipurpose (MP) catheter and a 0.035-inch hydrophilic wire through the 6-Fr introducer. This attempt was successful in approximately 80% of cases; in the remaining patients, PFO crossing was attempted under ICE guidance. In select cases, a right coronary catheter and/or a straight 0.035-inch wire were required.

Once the MP catheter reaches the LA, the wire is directed preferentially into the left superior pulmonary vein. The MP catheter is then advanced over the wire into this vein until distal positioning is achieved, and a contrast injection is administered to confirm correct placement (Figures 2 and 3).

Anatomical assessment via ICE is then performed, beginning with the home view and transitioning to the bicaval view; the short-axis view at the level of the aortic valve was rarely necessary. Key anatomical features assessed include PFO size and morphology; tunnel length and configuration; presence of a hypermobile septum or atrial septal aneurysm (ASA) (Figures 4 and 5); Chiari network and/or persistent Eustachian valve; and septum secundum hypertrophy, among other less critical findings. These anatomical data are used for device size selection.

It is important to emphasize that only the MP catheter is left in the pulmonary vein during ICE assessment; intracavitary wires are avoided due to thrombogenic risk.

Once the device is selected, it is thoroughly flushed by submerging it in saline until all air bubbles are eliminated. The delivery sheath and dilator are similarly purged.

After completing all preparatory steps, a 0.035-inch extra-support J-tipped wire is placed through the catheter into the pulmonary vein. The MP catheter and 6-Fr introducer are then removed, leaving the wire in place. The delivery sheath and dilator are advanced over the wire into the LA.

Once the LA is entered, the dilator and wire are removed, always under a continuous saline flush, while asking the patient to perform brief cough maneuvers to prevent air entry. This step is monitored radiologically to confirm that the sheath remains within the LA.

The delivery system is then connected to the sheath and the device is advanced, confirming adequate attachment to the system by gently advancing and retracting it within the distal third of the sheath. The left atrial disc is subsequently deployed and approximated to the interatrial septum under combined radiological and ICE guidance. Once correct positioning is confirmed, the right atrial disc is released. Final adjustments are made under ICE and fluoroscopic guidance, and the device is released while maintaining gentle tension on the delivery wire to prevent entanglement (Figures 6, 7, and 8).

In 40 of the ESUS patients studied, ICE did not detect a PFO. In these patients, an MP catheter was positioned at the fossa ovalis and agitated saline contrast was injected during the Valsalva maneuver. If no bubble passage or RLS was detected on Doppler imaging, the procedure was concluded. In a small subset of these patients, pulmonary angiography was subsequently performed.

Transseptal puncture was not attempted in any of these 40 patients.

In some cases, ICE revealed a tunnel that did not connect both atria — an image consistent with an ultimately non-existing PFO (Figures 9 and 10). This finding has also been reported by other investigators1.

At procedure completion, the ICE transducer and delivery sheath are withdrawn; the introducers are removed, and anticoagulation is reversed with protamine sulfate, in that order. After achieving hemostasis by manual compression of the access sites, a compression dressing is applied. Before the patient is rolled out of the cath lab, clopidogrel 75 mg is administered.

A transthoracic echocardiogram is performed the following day to confirm device position and, most importantly, to exclude pericardial effusion.

Patient is discharged with an indication of aspirin 100 mg/day and rosuvastatin 40 mg/day indefinitely, and pantoprazole 20 mg/day and clopidogrel 75 mg/day for 6 months to minimize the risk of recurrent post-closure events22.

Results

From November 21, 2016, to August 25, 2025, ICE was performed in 266 patients with ESUS and suspected PFO. PFO was confirmed in 226 cases (84.9%), in whom ICE-guided percutaneous closure was indicated.

Clinical characteristics of these patients are listed in Tables 1 and 2.

In all 226 patients, both procedural and clinical success rates were 100%. There were no major complications, and minor complications were experienced by 7.5% of patients.

Minor complications were distributed as follows. 1) 4 cases of arrhythmia: three episodes of atrial fibrillation (AF) in the cath lab (1.3%) — two self-terminating and one requiring pharmacological cardioversion — and one episode of atrial tachycardia (0.4%) at 24 hours after implantation requiring pharmacological reversion. 2) 5 cases of minor bleeding (2.2%) consistent with mild, persistent oozing at the access site that resolved with prolonged manual compression. These events occurred early in the study and were eliminated by separating the two femoral punctures by a greater distance. 3) 7 cases of blistering (3.0%) in the dorsolumbar region secondary caused by a reaction to the adhesive compression dressing. 4) 1 case of rupture and embolization (0.4%) of a fragment from the 6-Fr introducer, successfully retrieved from the RA using a snare. 5) 1 case of non-suppurative phlebitis (0.4%) in the right upper limb secondary to vein puncturing at the site.

The implanted closure devices are detailed in Table 3.

A total of 226 closure devices of 8 different types were used across the 226 treated patients. Device-related severe adverse events (SAEs) consisted exclusively of the arrhythmias described above; none were associated with clinical events.

All patients were discharged the day after the percutaneous closure, with the exception of the five patients who experienced persistent access-site bleeding, who required a mean hospitalization of 4 days.

Discussion

This cohort of ESUS patients with PFO is notable for several features: patients were predominantly middle aged, had high RoPE scores (Figure 11), and had a lower prevalence of conventional cardiovascular risk factors compared to other stroke populations — such as those with chronic AF or atherosclerotic cervicocephalic disease. AF was present in only 0.5% of these patients; hypertension, dyslipidemia, and diabetes were present in 17%, 15%, and 2.5% of cases, respectively. Conversely, clinical features associated with a risk of stroke recurrence were prevalent in a high number of cases, either in isolation or in combination within the same individual. Among them, the most notable included thrombophilia in 3% of cases; prior pharmacological or mechanical thrombolytic therapy for stroke in 13.5% of patients; history of miscarriage in 15% of subjects; current oral contraceptive use in 20% of patients; prior stroke or TIA in 24% of cases; and hypermobile interatrial septum or ASA detected on ICE in 41% of subjects.

A particularly concerning finding was that 4.5% of patients suffered a new stroke while awaiting PFO closure; in all these cases a PFO was confirmed by ICE.

As noted, pulmonary angiography was performed in a small number of patients in whom ICE had excluded PFO; four cases of pulmonary fistula were identified. Pulmonary angiography was reserved exclusively for patients with high clinical suspicion of pulmonary fistula — such as those with dorsal bruits, characteristic chest X-ray findings, Rendu-Osler-Weber disease, etc. In all other cases, further evaluation for this condition was pursued with CT angiography.

The incidence of device-related SAEs was 2%, consisting exclusively of three episodes of AF and one episode of atrial tachycardia. There were no cases of device dislodgement or embolization.

The overall results were a 100-% procedural success rate; 100-% clinical success rate; 0% for major complications; 7.5% for minor complications, and a 2-% rate for device-related SAEs.

These outcomes are considered to reflect multiple contributing factors, most notably device selection optimization and accurate implantation resulting from ICE use, the standardized closure technique employed, and the characteristics of the most frequently used devices.

The primary motivation for presenting this analysis is to share our experience with ICE-guided PFO closure and to highlight the most relevant findings from our series.

Conclusion

This analysis shows that, with a refined, ICE-guided technique, percutaneous PFO closure can be performed successfully in our setting with a high procedural success rate and a low complication profile. Patients with ESUS and PFO exhibit distinct clinical characteristics.

Abbreviations

ASA: Atrial septal aneurysm

ESUS: Embolic stroke of undetermined source

Fr: French (introducer diameter measurement unit)

ICE: Intracardiac echocardiography

LA: Left atrium

MP: Multipurpose catheter

PFO: Patent foramen ovale

RA: Right atrium

RLS: Right-to-left shunt

SAEs: [Device-related] severe adverse events

TIA: Transient ischemic attack

VM: Valsalva maneuver

after percutaneous closure of patent foramen ovale. Catheter Cardiovasc Interv. 2013;82:541-546.

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