Long-term Outcomes After Percutaneous Patent Foramen Ovale Closure (Severance PFO Registry)

Design: ambispective observational registry conducted at Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Part A (retrospective cohort): consecutive patients aged 19 years or older who underwent percutaneous PFO closure between 2010 and March 2026 and had at least one post-procedural agitated saline transthoracic echocardiography. Data are collected by direct review of electronic medical records, with the data cut-off set at the date of institutional review board approval. The requirement for informed consent is waived for this part.

The retrospective component comprises approximately 140 patients who underwent closure between 2010 and March 2026. A subgroup of these patients underwent two or more serial agitated saline transthoracic echocardiography examinations and is analyzed for the longitudinal trajectory of residual shunt.

Part B (prospective registry extension): patients aged 19 years or older who undergo percutaneous PFO closure after institutional review board approval and provide written informed consent. Follow-up visits are scheduled at 6, 12, 24, 48, 72, 96 and 119 months. Agitated saline transthoracic echocardiography is performed 6 months after closure and repeated at subsequent follow-up visits as clinically indicated.

Data collected: demographics and body mass index, smoking status, comorbidities (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, coronary artery disease, deep vein thrombosis, pulmonary embolism, hypercoagulable state), index event characteristics (stroke or transient ischemic attack type, TOAST classification, brain imaging, Risk of Paradoxical Embolism score), echocardiographic and anatomical variables (atrial septal aneurysm and excursion distance, septal hypermobility, PFO tunnel length, PFO opening size, Eustachian valve, Chiari network, left ventricular ejection fraction), procedural variables (device type and size, guidance modality, balloon sizing, procedure time, fluoroscopy time, procedural complications), antithrombotic therapy, serial agitated saline transthoracic echocardiography results, clinical events and modified Rankin Scale.

Agitated saline transthoracic echocardiography: 9 mL of normal saline mixed with 1 mL of air is agitated between two syringes and injected through an antecubital vein at rest and during the Valsalva maneuver. A study is positive when microbubbles appear in the left heart within three cardiac cycles after right atrial opacification. Shunt grade is assigned from the maximum number of microbubbles in the left heart within three cardiac cycles: small (1 to 10), moderate (11 to 30) or large (more than 30), in accordance with American Society of Echocardiography guidance. In patients with two or more serial examinations, the sequence of positive and negative results over time is recorded and the longitudinal pattern of residual shunt is classified.

Statistical analysis: continuous variables are summarized as mean with standard deviation or median with interquartile range, and categorical variables as frequency and percentage. Cumulative event rates are estimated by the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models are used to estimate hazard ratios with 95 percent confidence intervals. Predictors of residual shunt are examined by logistic regression. Analyses are performed with R version 4.0 or later, and a two-sided p value below 0.05 is considered statistically significant.

• Number of participants who die from any cause [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]
• Number of participants with device-related complications [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]
• Number of participants with new-onset atrial fibrillation [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]
• Number of participants with the composite of recurrent ischemic stroke or transient ischemic attack, all-cause death, or device-related complications [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]
• Longitudinal pattern of residual shunt on serial agitated saline transthoracic echocardiography [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]
• Time to spontaneous resolution of residual shunt [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]
• Predictors of residual right-to-left shunt on agitated saline transthoracic echocardiography [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]
• Functional status measured with the modified Rankin Scale [Срок оценки: From patent foramen ovale closure to the last follow-up: up to 16 years in the retrospective cohort and up to 119 months in the prospective cohort]