Percutaneous and Non-fluoroscopic Procedure for Atrial Septal Defect Closure, Patent Foramen Ovale Closure and Transcatheter Edge-to-edge Repair

Structural heart diseases (SHDs) encompass a broad spectrum of cardiovascular conditions requiring percutaneous interventional management across diverse patient populations and include both congenital heart diseases (CHDs), such as atrial septal defect (ASD) and patent foramen ovale (PFO), and acquired valvular diseases, such as mitral regurgitation (MR). Collectively, these conditions present significant clinical challenges.^1,2 ASD has a global prevalence of 1.64%, and accounts for 6–10% of all CHDs, whereas PFO occurs in approximately 25% of adults.^3,4 In addition, acquired valvular diseases, such as MR, affect up to 9.3% of individuals aged >75 years, reflecting the growing burden of SHD in ageing populations.²

Traditional surgical treatment for ASD involves open-heart repair under cardiopulmonary bypass. Although effective, this procedure is highly invasive, entails prolonged postoperative recovery and is associated with higher complication risks.^5,6 In recent years, percutaneous ASD closure has developed rapidly. Due to its advantages of minimal invasiveness, fewer complications and faster recovery, it has gradually replaced traditional thoracotomy and become the preferred treatment for ASD.⁷ Similarly, PFO closure involves the placement of an occluder device at the site of the PFO to seal the interatrial channel, thereby preventing paradoxical embolism by eliminating right-to-left atrial shunting across the PFO.⁴ This procedure can be performed under guidance by fluoroscopy, transoesophageal echocardiography (TOE), intracardiac echocardiography or transthoracic echocardiography (TTE).⁸ Transcatheter edge-to-edge repair (TEER) for MR offers advantages such as minimal invasiveness and repeatability.^9,10 Performed via the femoral vein (or transapical approach) under TOE and fluoroscopic guidance, TEER involves clipping the anterior and posterior leaflets together at the regurgitation zone to reduce the severity of MR.^11,12 These percutaneous interventions have transformed the treatment paradigm for their respective conditions, offering minimally invasive alternatives to traditional surgical approaches.

Despite their advantages, conventional percutaneous approaches, including ASD closure, PFO closure and TEER, have significant limitations related to the need for radiation exposure and the use of contrast agents. Fluoroscopic guidance, although enabling precise device positioning, exposes patients to ionising radiation, with long-term malignancy risks.¹³ In addition, contrast agents pose risks of allergic reactions and contrast-induced nephropathy.^14,15 The incidence of allergic reactions with current iodine-based contrast agents is approximately 0.6%, and approximately 12% of children undergoing interventional treatment for CHD experience contrast-induced nephropathy.^16–18 These safety concerns particularly limit treatment options for vulnerable populations, including pregnant women, patients with renal insufficiency and those with contrast allergies.

Growing awareness of radiation-associated risks has driven the development of radiation dose-reduction technologies.^19,20 It has been reported that radiation exposure during percutaneous coronary interventions decreased significantly (by 36%) between 2008 and 2018 in Germany.²¹ However, physicians and patients remain exposed to low-dose fluoroscopy, further stimulating substantial interest in radiation-free cardiac interventions. At a high-volume medical centre in Italy, the proportion of zero-fluoroscopy procedures increased from 8.5% in 2017 to 22.9% in 2021, fully demonstrating this developmental trend.²²

Percutaneous and non-fluoroscopic (PAN) procedures use echocardiographic guidance as an alternative to conventional fluoroscopy.²³ This eliminates radiation exposure while maintaining procedural efficacy, potentially expanding treatment access to vulnerable populations and resource-limited settings. By enabling radiation-free SHD treatment, the PAN technique represents a significant advance in minimally invasive cardiac intervention.³

This review examines the current clinical applications for and evidence of the use of PAN procedures in ASD closure, PFO closure and TEER, evaluating the efficacy and safety of the procedures, as well as implementation considerations.

Percutaneous and Non-fluoroscopic Procedure

Implementation of the PAN procedure follows a comprehensive, systematic framework designed to ensure procedural safety and efficacy across varying complexities. The overall approach can be structured into four sequential phases: patient selection, preoperative assessment, intraoperative team coordination and postoperative evaluation Figure 1).

With this framework, procedural execution relies on three fundamental technical considerations:

• the key anatomical structure detection method uses stable vascular landmarks, such as the entrance of the inferior vena cava and the aortic isthmus, to create stable imaging planes for reliable device tracking and improved positioning accuracy;
• the working length marking method prevents sheath overinsertion and cardiac perforation through precise distance measurement and catheter marking; and
• the effective echo view method ensures optimal echocardiographic visualisation with device trajectory tracking (>1 cm) for precise tip positioning.

The technical execution of these procedures follows a three-step approach. Step 1 involves establishment of the vascular pathway with selection of the appropriate access route based on patient-specific anatomical considerations. Step 2 encompasses comprehensive premeasurement, marking, verification and assembly procedures to ensure precise insertion and delivery system preparation. Step 3 consists of the controlled release of occluder or clip devices under continuous echocardiographic guidance, with real-time assessment of device positioning and function.²³ This systematic framework provides institutions with reproducible technical protocols, supporting consistent application of radiation-free interventions for SHD.

Patient Selection and Preoperative Assessment

Selection of Patients for Atrial Septal Defect Closure

ASD closure is primarily indicated for patients aged ≥2 years or weighing >10 kg Table 1). For patients weighing <10 kg or those with femoral venous access limitations, the jugular approach may be selected as an alternative.²⁴ The defect should be centrally located, ≥5 mm in diameter, and with right heart volume overload. Essential anatomical criteria include adequate septal rims: ≥5 mm from the coronary sinus, superior/inferior vena cava, and pulmonary veins; and ≥7 mm from the atrioventricular valve.²⁴ The total atrial septal diameter must exceed the diameter of the selected occluder. Contraindications include ostium primum or sinus venosus defects, severe pulmonary hypertension with right-to-left shunt, active endocarditis, bleeding disorders and complex malformations requiring surgery Table 1).^3,24

Selection of Patients for Patent Foramen Ovale Closure

PFO closure is primarily indicated for patients aged >16 years with unexplained stroke or transient ischaemic attack after comprehensive evaluation has excluded other embolic sources Table 1). Ideal candidates include those with PFO-related cerebral events accompanied by deep venous thrombosis or pulmonary embolism who are not suitable for anticoagulation therapy, or patients experiencing recurrent events despite optimal medical therapy.^3,4 Contraindications include identifiable cerebral embolic sources, contraindications to anticoagulation therapy, active thrombotic disease, systemic infection, combined pulmonary hypertension with the PFO serving as a special channel and recent massive cerebral infarction Table 1).³

Selection of Patients for Transcatheter Edge-to-edge Repair

The selection of patients for TEER requires adherence to established guideline recommendations. Primary candidates include those with severe degenerative MR (grade ≥3+) at high surgical risk, as well as those with secondary MR who remain symptomatic despite optimal guideline-directed medical therapy Table 1).^11,12 Essential eligibility criteria include left ventricular ejection fraction 20–50% and anatomical suitability confirmed by comprehensive echocardiographic assessment.¹² Contraindications include an inability to tolerate anticoagulation therapy, active mitral valve endocarditis, rheumatic mitral valve disease and the presence of intracardiac or venous thrombosis Table 1).¹¹

Preoperative Echocardiographic Assessment

Comprehensive echocardiographic evaluation forms the foundation for the PAN procedure, providing anatomical and haemodynamic information essential for procedural planning and intraoperative guidance. Preoperative evaluation requires integration of TTE and TOE findings. TTE serves as the primary screening tool, whereas TOE provides detailed anatomical characterisation and serves as the preferred intraoperative guidance modality for complex cases.

Assessment of Atrial Septal Defect

Echocardiographic evaluation focuses on defect characterisation, including precise measurement of defect diameter and assessment of the surrounding structures. Key measurements include distances from the defect to the atrioventricular valves, coronary sinus and vena cavae. Evaluation of right heart dimensions and function assesses the haemodynamic significance of the shunt. Additional assessment includes exclusion of anomalous pulmonary venous drainage and measurement of total atrial septal length to ensure adequate space for occluder deployment. The quality of acoustic windows, particularly parasternal and subcostal views, determines the feasibility of TTE guidance.²⁵

Assessment of Patent Foramen Ovale

PFO evaluation requires specialised techniques, including contrast echocardiography to demonstrate and quantify right-to-left shunting. Detailed anatomical assessment focuses on PFO tunnel characteristics, including length (reflecting septal overlap) and width, which are critical determinants of occluder selection and procedural success.²⁶ The assessment should include evaluation of associated atrial septal aneurysm and measurement of the degree of septal mobility, because these factors influence procedural complexity and device selection.³

Assessment Prior to Transcatheter Edge-to-edge Repair

Critical parameters in the assessment of patients for TEER are leaflet mobility, regurgitation jet location, anterior and posterior leaflet lengths, and grasping zone evaluation for calcification or structural abnormalities.¹² 3D echocardiographic reconstruction provides optimal visualisation for procedural planning.¹¹

Imaging Window Assessment

Adequate echocardiographic windows are a prerequisite for the success of the PAN procedure. For ASD and PFO procedures, evaluation focuses on the quality of the TTE parasternal four-chamber, short-axis and subcostal views.^27,28 Patients with suboptimal transthoracic windows due to body habitus, chest wall deformity or pulmonary disease require TOE guidance.²³ The TEER procedure typically requires TOE guidance due to procedural complexity and the need for detailed anatomical visualisation.^29,30 However, experienced centres may use TTE guidance in patients with optimal acoustic windows and favourable anatomy.²³

Technical Requirements for Ultrasound Equipment

Table 2 presents the minimum frame rate requirements to ensure real-time visualisation of moving structures during device deployment. For both ASD/PFO closure and TEER procedures, 2D imaging must achieve ≥30 frames per second to adequately track catheter and device movement. Colour Doppler flow imaging requires ≥15 frames per second to assess blood flow patterns and detect residual shunts or regurgitation during and after device deployment. Adequate penetration depth is crucial for visualising cardiac structures in different patient populations. For adult patients undergoing ASD or PFO closure, TTE penetration must reach 10–30 cm, whereas in paediatric applications 5–15 cm is required. TEER procedures demand adequate probe penetration depths, with adult TTE requiring 30 cm, paediatric TTE requiring 16 cm, and TOE requiring 20 cm to adequately visualise complex mitral valve anatomy.

Table 2 also summarises frequency ranges optimised for different patient populations and anatomical targets. Adult ASD/PFO procedures use 1.5–4.5 MHz for adequate penetration, whereas procedures in paediatric populations use higher frequencies (3.0–8.0 MHz) for improved resolution. TEER procedures require broader frequency ranges (2.0–8.0 MHz) to accommodate the complex imaging demands of valvular interventions. Although ASD and PFO closure can be effectively performed with standard 2D and M-mode imaging, TEER procedures require advanced capabilities, including 3D en face zoom mode), full-volume imaging and multiplanar reconstruction.²³ These enhanced imaging modalities provide the comprehensive anatomical assessment required for precise leaflet capture and clip positioning.

Operator Qualifications and Multidisciplinary Team Approach

Operators must demonstrate competency in echocardiographic guidance, including proficiency in both TTE and TOE, with expertise in real-time imaging during interventional procedures. Essential skills include familiarity with procedure-specific echocardiographic views and competence in manipulating echo-guided instruments and devices.^23,31 A structured learning pathway is recommended for operator training, beginning with ASD closure, followed by PFO closure. Advanced procedures, such as TEER, should only be undertaken after completing a minimum of 100 foundational cases to ensure technical proficiency and safety standards.²³

Beyond individual operator expertise, the PAN procedure requires coordination among experienced echocardiographers, interventional cardiologists and cardiac surgeons. This collaborative approach ensures accurate preoperative assessment, appropriate patient selection and optimal procedural outcomes while maintaining patient safety throughout the intervention. Essential preoperative preparation requirements for ASD closure, PFO closure and TEER are outlined in Supplementary Table 1.

Percutaneous and Non-fluoroscopic Procedures

Atrial Septal Defect Closure

The choice of echocardiographic guidance modality depends primarily on the quality of the patient’s acoustic window and procedural complexity. TTE guidance is preferred for patients with adequate acoustic windows, offering straightforward operation without endotracheal intubation while eliminating radiation exposure. TOE guidance is reserved for complex cases, including patients with suboptimal rim characteristics, large defects or anatomical proximity to vena cavae.²⁷ Although TTE provides excellent procedural visualisation in suitable patients, image quality limitations in patients with increased chest wall thickness may compromise catheter visualisation and procedural success.³² TOE offers superior image resolution because the probe is positioned adjacent to the left atrial posterior wall, placing the interatrial septum within optimal imaging range.²⁷ However, TOE necessitates general anaesthesia with endotracheal intubation, increasing procedural complexity and associated risks.

Echocardiography-guided Percutaneous Atrial Septal Defect Closure via a Femoral Vein Approach

The femoral venous approach represents the primary access route for most ASD closures. Procedural success depends on accurate measurement of working length, defined as the distance from the third intercostal space at the right mid-clavicular line to the right femoral venous puncture site (or the left if right femoral vein puncture fails). This measurement serves as a critical safety parameter, preventing excessive catheter advancement and cardiac perforation.

Technical Considerations

Measure the distance and mark it on the catheter and guidewire during the procedure. Puncture the femoral vein, insert an arterial sheath and administer heparin 80 U/kg.³ A 6-Fr multipurpose catheter and a super-stiff guidewire are delivered through the arterial sheath, with the guidewire tip extending 2–4 cm beyond the catheter.²⁷ If there is obvious resistance, the catheter and guidewire should be withdrawn back into the arterial sheath, the catheter stabilised, the guidewire advanced again and catheter delivery attempted again.²⁷

Under ultrasound guidance, the catheter and guidewire shadows can be visualised within the inferior vena cava during advancement. Once the catheter and guidewire reach the working distance inside the body, the guidewire should be withdrawn and the catheter gently rotated clockwise. The catheter can be positioned using the apical four-chamber view. The catheter direction should be adjusted under TTE to advance it through the ASD into the left atrium. A small amount of normal saline can be injected through the catheter to confirm its position. The guidewire is inserted through the catheter to a depth that does not exceed 5–7 cm than the working length. The guidewire is retained, the catheter is withdrawn and the insertion depth is marked. After removal of the arterial sheath, the delivery sheath is advanced over the super-stiff guidewire into the left atrium, ensuring the insertion depth matches the previously recorded catheter depth. While the guidewire and the inner core of the delivery sheath are being withdrawn, the outer sheath is gently advanced to maintain the sheath tip’s position in the left atrium.

Under TTE monitoring, the catheter of the ASD closed system should be filled with normal saline to avoid sucking in air due to negative pressure during the procedure. After successful occluder placement, its position and morphology are verified in the aortic short-axis, apical four-chamber and subxiphoid views to ensure no interference with surrounding structures before release. The long sheath is withdrawn, the puncture site is sutured, compression is applied for haemostasis and the puncture site is secured with a pressure bandage.

Echocardiography-guided Percutaneous Atrial Septal Defect Closure via a Jugular Vein Approach

For patients weighing <10 kg or those with femoral venous approach limitations (e.g. congenital absence of the inferior vena cava, post-inferior vena cava filter implantation), the jugular vein approach may be selected.²⁴

Technical Considerations

Technical principles for the jugular vein approach remain similar to the femoral approach, with working length measured from the jugular puncture site to the third intercostal space. Increased attention to vascular access management is required due to the proximity of critical neck structures and the increased risk of complications in the confined operative space. General anaesthesia with endotracheal intubation is mandatory for airway protection and procedural safety. The jugular vein approach maintains similar device deployment principles as the femoral vein route, with particular emphasis on avoiding complications related to cervical vascular access.

Patent Foramen Ovale Closure

PFO anatomy presents unique technical challenges due to its characteristically small and irregular tunnel morphology.²⁸ This constrained anatomical space demands enhanced precision in device positioning compared with ASD closure. The procedural approach, postoperative management and potential complications mirror those of percutaneous ASD closure.³

Technical Considerations

PFO closure using femoral venous access follows identical procedural techniques as described for ASD closure, including working length determination, catheter advancement and device deployment protocols.³³ The fundamental distinction lies in the enhanced precision requirements necessitated by the smaller, irregular tunnel anatomy. Preoperative TOE assessment becomes critical for accurate measurement of tunnel dimensions and evaluation of septal overlap characteristics.²⁶ Operators must precisely identify both tunnel entrance and exit points under continuous ultrasound guidance, ensuring accurate occluder positioning across the entire communication length.

Device selection differs from that in ASD closure, focusing on tunnel length and width rather than defect diameter.^8,26 Successful deployment requires complete expansion of both atrial discs with optimal septal apposition to achieve complete tunnel sealing.³³ Release criteria emphasise complete tunnel occlusion rather than specific waist diameter matching, verified through intraoperative contrast echocardiography demonstrating elimination of right-to-left bubble passage.³³

The constrained working space within PFO tunnels limits flexibility in catheter manipulation, requiring refined operative techniques and enhanced operator experience compared with ASD closure. The enhanced precision requirements position PFO closure as moderately complex within the PAN procedure spectrum. Procedural success depends on understanding the unique anatomical characteristics of PFO tunnels and adapting deployment techniques accordingly.³⁴

Transcatheter Edge-to-edge Repair

TEER using the PAN procedure represents a technically demanding procedure in radiation-free interventional cardiology. Unlike ASD and PFO closures, TEER requires comprehensive TOE guidance throughout the procedure due to the complexity of mitral valve anatomy and the precision demands of leaflet capture. Patient positioning involves standard supine placement with sterile preparation, typically using general anaesthesia with endotracheal intubation.

The support system positioned at 80 cm from the right sternal border at the third intercostal space provides a consistent reference framework, with comprehensive TOE re-evaluation of mitral valve pathology preceding intervention. Initial working distance measurement from the right mid-clavicular line at the third intercostal space to the puncture site establishes critical safety parameters for catheter positioning while minimising the risk of cardiac perforation.³⁵

Technical Considerations

PAN-guided TEER relies primarily on TOE for real-time spatial anatomical guidance, providing superior visualisation compared with conventional fluoroscopic approaches. The enhanced soft tissue contrast and dynamic imaging capabilities of TOE enable precise assessment of leaflet mobility, characterisation of the regurgitation jet and real-time monitoring of device positioning. For patients with exceptional acoustic windows, experienced centres may use TTE guidance as an alternative imaging modality, although TOE remains the preferred approach for optimal procedural outcomes.³⁶

Successful transseptal access is a fundamental prerequisite for TEER success, requiring optimal puncture site selection based on three anatomical criteria: central fossa ovalis positioning, posterior location relative to the aortic root and appropriate 4–5 cm distance from the mitral valve plane. The ultrasound-guided puncture technique involves identification of optimal septal ‘tenting’ under continuous imaging surveillance, with specialised ultrasound-compatible guidewires providing enhanced visibility for precise positioning. The systematic approach to steerable guide catheter insertion includes initial catheter straightening for vascular traversal, followed by neutral positioning upon entry into the right atrium. Dilator advancement proceeds under continuous ultrasound monitoring to prevent contact with the left atrial wall and associated tissue injury, maintaining anticoagulation protocols, with an activated clotting time >250 seconds throughout the procedure.

Advancement of the mitral clip delivery system proceeds under comprehensive TOE guidance, with alignment markers ensuring proper positioning and an adequate distance from atrial walls and valvular structures. Steering manoeuvres create appropriate angulation while avoiding contact with anatomical landmarks such as the coumadin ridge. Multiplanar ultrasound visualisation is used for precise leaflet capture, with bicommissural and X-plane imaging ensuring a perpendicular valve plane approach. 3D TOE reconstruction provides optimal clip orientation using an en face surgical perspective for identification of the target region. After successful leaflet grasping, the characteristic ‘bouncing sign’ is typically seen, namely rhythmic clip movement synchronised with motion of the captured leaflet; this serves as a reliable indicator of adequate tissue engagement prior to final clip release.³⁰

Prerelease assessment includes testing of clip arm stability and verification of the removability of the connection line. Comprehensive TOE evaluation encompasses assessment of leaflet insertion depth, clip mobility and residual pathology, as well as quantification of the reduction in MR. Multiple clip procedures require additional consideration to preserve previously deployed device stability, with systematic catheter withdrawal under TOE guidance and rigorous air evacuation protocols preventing embolic complications.³⁶

The technical complexity of PAN-guided TEER significantly exceeds that of ASD closure and PFO closure, requiring extensive experience in both interventional cardiology and advanced echocardiographic techniques.³⁷ Success depends on mastering the integration of complex anatomical assessment, precise device manipulation and comprehensive imaging guidance within a radiation-free procedural environment.

Clinical Outcomes

Atrial Septal Defect Closure

Percutaneous ASD closure under echocardiography-only guidance demonstrates excellent feasibility and technical maturity in clinical practice. Early studies from Chinese centres reported procedural success rates of 92–96.5%.^25,38 Continuous technical improvements and accumulated experience have led to significantly enhanced success rates of 98–100% in recent studies.^39–43 This progression establishes the technique as a reliable alternative to conventional fluoroscopic approaches, with success rates now consistently matching or exceeding traditional methods across multiple clinical centres.

International experiences corroborate these findings across diverse healthcare systems. A German single-centre retrospective study of 330 patients achieved 98.2% procedural success under TOE guidance.⁴⁴ Iranian centres reported 94% success rates using transthoracic guidance alone.⁴⁵ An Indonesian study evaluating oval-shaped ASDs achieved zero-fluoroscopy procedures in 88.7% of cases (63/71), with fluoroscopic assistance or conversion due to technical difficulties required in 11.2% of procedures. Notably, the procedural success rate across all 63 patients who successfully underwent zero-fluoroscopy closure was 100%.⁴⁶ A comprehensive meta-analysis of eight international studies encompassing 1,229 patients showed a 98% success rate (95% CI [96–100%]) for non-fluoroscopic approaches.⁴⁷ These international validations support the global applicability of the PAN procedure across diverse patient populations and healthcare infrastructures, as detailed in Table 3.

Clinical evidence establishes an excellent safety profile for echocardiography-guided ASD closure, with minimal procedural complications reported across diverse patient populations.^40,43 Long-term follow-up results demonstrate sustained efficacy and durability, with patients experiencing minimal residual shunts, the absence of device embolisation or displacement and occasional trace residual shunts resolving spontaneously during extended follow-up periods.^42,43,48 Studies in pregnant patients provide particularly compelling safety evidence, demonstrating the absence of serious procedural complications, with no haemorrhagic events (including abnormal vaginal bleeding, retroplacental haematoma or placental abruption), confirming technique safety in this vulnerable population.^48,49

The PAN procedure demonstrates significant advantages in terms of operational efficiency and healthcare resource usage compared with conventional methods. Comparative studies reveal consistently shorter operative times and hospital stays in echocardiography-guided percutaneous ASD occlusion procedures compared with traditional fluoroscopic approaches.^42,50 Outpatient procedure studies have reported similar results, showing markedly reduced procedural duration.^41,51 Furthermore, the outpatient procedures were shown to have significant healthcare economic advantages, with medical costs reduced by more than 30% compared with concurrent inpatient procedures.⁴¹ Within echocardiography-guided approaches, comparative studies of different vascular routes show that the jugular vein approach results in shortened hospitalisation duration and reduced medical expenses compared with the femoral vein approach.⁴¹ Collectively, these findings demonstrate substantial clinical and economic benefits of the PAN procedure.

The PAN technique demonstrates broad applicability across diverse and complex patient populations, extending treatment options to previously challenging cases. Paediatric patients with concurrent systemic malformations, including pectus excavatum, pectus carinatum or scoliosis, undergo safe and effective closure procedures.^40,42 Complex anatomical variants, including fenestrated or multiple ASDs, benefit from real-time echocardiographic monitoring, improving closure success rates and reducing the incidence of residual shunting.⁴⁰ These expanded applications, combined with the safety of the technique in pregnancy, demonstrate the versatility and safety advantages of radiation-free approaches in populations where conventional fluoroscopic methods present increased risks.⁴⁸

Patent Foramen Ovale Closure

Percutaneous PFO closure under TTE guidance demonstrates excellent feasibility and achieves high procedural success rates in clinical practice. A large-scale study that included 403 patients reported a success rate of 95.04%, with procedural termination occurring in only 20 patients due to an inability to advance the sheath Table 3).²⁸

Subsequent investigations by Yang et al. demonstrated 100% procedural success rates in 35 patients, with completion of percutaneous PFO closure under TTE guidance in all patients Table 3).³³ Among these 35 patients, additional TOE assistance was required in five due to poor acoustic windows, although notably without the need for endotracheal intubation. Operational efficiency studies confirm good procedural performance, with a mean operative time of 20–25 minutes.^28,33

The learning curve characteristics of PFO closure under echocardiographic guidance demonstrate manageable progression with accumulated experience. Studies indicate that operative time gradually decreases with case accumulation, stabilising after approximately 50 cases.³⁴ Success rates improve from 80% to 92% during the learning process Table 3), importantly demonstrating that the technique maintains high safety and efficacy even during the learning phase.³⁴ This learning curve profile supports the implementation of systematic training and progressive skill development in centres adopting PAN techniques.

Clinical safety profiles demonstrate acceptable complication rates with successful conservative management of reported adverse events. Serious complications include pericardial effusion (incidence ~3.23%) and coronary air embolism (incidence ~0.99%), all of which improved after symptomatic treatment.²⁸ Other studies report lower complication rates with only minor complications (e.g. trace residual shunts and small amounts of pericardial effusion), all of which resolved spontaneously or improved with conservative treatment.^28,33 No serious complications, including device embolisation, displacement or peripheral vascular injury, have been observed across reported studies.

Clinical efficacy extends beyond procedural success to include significant symptom improvement and durable prevention of recurrent events. Studies demonstrate substantial improvement in PFO-related migraine symptoms after closure.²⁸ Follow-up results confirm technique durability and safety, with short-term follow-up showing no device-related complications within 3 months after the procedure and no recurrence of neurological events in stroke patients.^28,33 Medium-term follow-up demonstrates maintained device position and morphology, with no serious complications, confirming the long-term safety and efficacy of echocardiography-guided PFO closure techniques.⁴

Transcatheter Edge-to-edge Repair

Although evidence for echocardiography-guided TEER remains relatively limited compared with the use of the PAN technique for ASD and PFO closure, existing studies demonstrate promising technical feasibility and procedural success. Many clinical studies have consistently demonstrated high procedural success rates, with complete technical success and appropriate device deployment achieved in all cases under TOE guidance Table 3).^35,36,52,53 These preliminary results establish the technical viability of radiation-free TEER.

Immediate efficacy and safety profiles demonstrate encouraging early outcomes with acceptable risk profiles. Studies consistently show significant improvement in MR severity, with most patients achieving mild or trace regurgitation immediately after the procedure.^35,36 The complete elimination of radiation exposure offers significant advantages for special populations and healthcare personnel, addressing long-standing concerns regarding the effects of cumulative radiation exposure in complex valve interventions.^36,52,53 Procedural complications remain within acceptable ranges, with echocardiography-only guidance maintaining safety standards comparable to conventional fluoroscopic approaches.

Technological integration represents an emerging frontier in PAN-guided TEER, with innovative combinations enhancing procedural capabilities and expanding access potential. The PAN procedure was successfully combined with robot-assisted technology to perform remote surgery, with 100% procedural success rates reported, demonstrating the feasibility of spatial separation between the operator and patient.^36,52–54 This integration of robotic assistance with radiation-free guidance opens new possibilities for complex valve interventions in resource-limited settings and enables specialised expertise to reach broader patient populations through remote surgical capabilities.

Medium-term follow-up results indicate sustained efficacy, although longer-term studies remain necessary for comprehensive evaluation. In the medium term, patients maintained mild or trace MR with significantly improved cardiac function compared with their preprocedural status.^35,36 These preliminary findings indicate that the PAN technique has significant potential for TEER, marking notable progress in minimally invasive valvular interventions. However, the limited scope of current evidence necessitates larger long-term follow-up studies to further validate efficacy and to define the role of echocardiography-guided TEER within the broader spectrum of mitral valve interventions.

Discussion

The PAN procedure represents a paradigm shift in interventional cardiology, offering radiation-free alternatives across a spectrum of structural heart interventions.³ The three echocardiography-guided percutaneous interventions demonstrate a graduated complexity hierarchy that facilitates systematic implementation: ASD closure has the most mature evidence base with established protocols; PFO closure offers moderate complexity with evolving indications; and TEER is a challenging application requiring advanced expertise. This progression creates a natural pathway for institutional adoption and the development of operator training. Successful adoption requires systematic institutional commitment extending beyond technical training to include quality assurance programs, outcome monitoring systems and the development of multidisciplinary teams.^3,24 Centres considering the PAN approach should implement graduated training programs beginning with ASD closure before progressing to more complex percutaneous interventions.

The elimination of ionising radiation represents the fundamental advantage of the PAN procedure, addressing critical safety concerns for patients, healthcare personnel and institutional radiation protection programs. Beyond safety benefits, this radiation-free approach reduces infrastructure requirements by eliminating dependence on expensive fluoroscopic equipment, potentially expanding interventional capabilities to resource-limited settings.^23,25 Consequently, the PAN procedure has gained recognition from the UN and was incorporated into a UN global sustainable development initiative in 2023 aimed at enhancing accessibility to cardiovascular disease treatment in developing countries.³¹

Current evidence demonstrates that these procedures reduce procedure times, shorten hospital stays and eliminate radiation protection requirements, providing substantial healthcare system benefits. Furthermore, the feasibility of performing these interventions in outpatient settings enhances cost-effectiveness while improving patient satisfaction and the efficiency of resource utilisation.^41,51

Despite the demonstrated advantages, the PAN procedure faces some implementation challenges that limit its widespread adoption. The dependence on image quality represents the primary technical limitation, with procedural success directly related to adequate echocardiographic visualisation.^8,12,25 Patients with suboptimal acoustic windows due to body habitus, chest wall deformities or pulmonary disease may require TOE guidance under tracheal intubation.^8,55 For operators, the learning curves for this innovative medical procedure vary according to the complexity of the percutaneous intervention. Some studies have reported that PFO closure required approximately 50 cases for proficiency.³⁴ Others have reported that TEER has the steepest learning curve due to the technical complexity of navigating clip devices through intricate cardiac delivery systems.^36,37 The primary challenge involves transitioning from fluoroscopic to echocardiographic guidance, requiring operators to develop advanced imaging interpretation skills and spatial awareness for complex anatomical navigation.^33,34 In addition, maintenance of operator proficiency requires adequate case volumes, which may be challenging in smaller centres with limited SHD referrals.

Future technological developments may address current PAN procedure limitations and expand clinical applications. Advanced ultrasound technologies, including enhanced imaging algorithms and procedure-specific device optimisation, may improve the quality of visualisation and procedural success rates in challenging patients. The integration of artificial intelligence for real-time image enhancement and automated anatomical recognition may reduce operator learning curves and improve procedural consistency. In addition, the development of specialised instruments designed specifically for echocardiography-guided intervention may enhance procedural precision and broaden the spectrum of treatable conditions.^31,56

Adoption of the PAN procedure has important socioeconomic significance. By reducing dependence on equipment, shortening hospital stays and decreasing costs, this technique improves the efficiency of healthcare resource usage. Advances in robot-assisted technology may enhance procedural precision and safety, while developments in remote connectivity could expand access to specialised medical resources in underserved regions.

Conclusion

The PAN procedure performed for ASD closure, PFO closure and TEER represents an important advance in the treatment of SHD. The use of the PAN technique for ASD closure has the strongest evidence base, with international validation from multiple centres confirming safety and efficacy. Although the use of the PAN technique for PFO closure and TEER shows promising feasibility based on current studies, further international experience is needed to establish comprehensive evidence. The elimination of radiation exposure provides particular benefits for vulnerable populations, including paediatric and pregnant patients, while potentially expanding access to structural heart interventions in resource-limited settings. With growing clinical experience and improved infrastructure support, this technique is expected to play an increasingly important role in the minimally invasive treatment of cardiovascular diseases.

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