Patent foramen ovale (PFO) occluder devices are commonly used in clinical practice to prevent recurrent cryptogenic strokes and treat migraines [1, 2]. These devices, which are often composed of nickel-containing alloys, have demonstrated long-term efficacy in reducing the risk of thromboembolic events [3]. However, complications related to device implantation, such as device migration, incomplete endothelialization, and nickel hypersensitivity, have been increasingly reported [4, 5]. Nickel allergy, in particular, is a significant concern due to the widespread use of nickel in medical devices. The prevalence of nickel allergy in the general population is high, yet its incidence following PFO or atrial septal defect (ASD) occluder is not well documented [6]. Despite these challenges, the exact pathophysiology behind nickel hypersensitivity in intracardiac devices remains unclear, prompting further investigation into the role of nickel allergy in device-related complications [7, 8].

Nickel hypersensitivity reactions can manifest with a broad range of symptoms, including chest pain, migraines, palpitations, and dyspnea, often appearing weeks to years after device implantation. In patients with pre-existing nickel sensitivity, the body’s immune response can lead to chronic inflammation, which can result in persistent symptoms that do not resolve with conventional medical management [9]. Nickel ions (Ni²⁺) leached from occluders act as haptens that bind to host proteins (e.g., toll-like receptor 4/TLR4), triggering innate immune activation via the NF-$\kappa$B pathway [10]. This promotes dendritic cell maturation and antigen presentation, activating nickel-specific CD4⁺/CD8⁺ T-cells [11]. Sustained inflammation results in mast cell degranulation (histamine, tryptase release $\to$ chest pain, rash), macrophage recruitment (IL-1$\beta$, TNF-$\alpha$ release $\to$ endothelial dysfunction) [4], and impaired endothelialization due to matrix metalloproteinase (MMP)-mediated tissue remodeling. These processes establish a prothrombotic milieu, facilitating microthrombi formation on incompletely endothelialized struts [12]. Microemboli can then traverse residual shunts, potentially triggering migraines or systemic inflammation [9]. In such cases, device explantation has been shown to significantly improve patient outcomes, particularly in individuals who have not responded to pharmacological interventions such as corticosteroids and antiplatelet therapy. Several case reports and studies have documented the complete resolution of symptoms following device removal, reinforcing the importance of recognizing nickel hypersensitivity as a potential cause of device failure [13, 14].

Despite the growing awareness of nickel hypersensitivity in patients with implanted PFO/ASD occluder devices, there are no standardized guidelines for preoperative allergy screening or the management of nickel-related complications. Current diagnostic approaches rely on skin patch testing, which can identify patients at risk of developing hypersensitivity reactions before or after device implantation [15]. Additionally, the decision to remove the device often depends on the severity of symptoms and the patient’s overall quality of life (QoL) post-implantation. The present study aims to retrospectively analyze the outcomes of patients who underwent totally endoscopic removal of PFO/ASD occluder devices due to nickel hypersensitivity, focusing on symptom resolution and the safety of the minimally invasive surgical approach.

Of 110 patients initially referred for endoscopic explantation evaluation, 95 (86.4%) comprised the final study cohort after application of exclusion criteria (Fig. 1). The screening process excluded 15 patients: 8 (7.3%) for insufficient medical optimization or asymptomatic status, 2 (1.8%) for device thrombosis, 2 (1.8%) for significant residual shunt, and 3 (2.7%) for contraindications to endoscopic approach (1 with autoimmune disease, 1 with prior right thoracic surgery, 1 with BMI $>$35 kg/m²).

All 95 patients in the final cohort successfully underwent totally endoscopic device removal without conversion to open procedure (100% technical success rate). The cohort of 95 patients had a median age of 32.6 years, with a notable female predominance (89.5%). Among the patients, the most commonly used devices were from LifeTech Scientific Corporation accounting for 34.7%, while AGA Amplatzer devices were used in 10.5% of cases. Cardiovascular comorbidities, such as coronary artery disease (2.1%), hyperlipidemia (5.3%), and hypertension (5.3%), were relatively uncommon. Psychiatric conditions were also infrequent, with 7.4% of patients diagnosed with anxiety and 5.3% with depression. Autoimmune and thyroid conditions were rare. Notably, metal allergies were highly prevalent, with 47.4% of patients reporting allergies to common items like belt buckles or earring studs, indicating a potential link between metal sensitivity and device-related complications.

The primary indication for device placement was a history of stroke or TIA (47.4%), followed by refractory headaches or migraines (36.8%). ASD accounted for 10.5% of cases, and 5.3% of patients were asymptomatic. The high prevalence of neurological conditions, particularly migraines and stroke, reflects their established association with PFO. Importantly, patients with documented allergy histories, particularly metal allergies, may have experienced complications that led to the need for device removal, suggesting a possible influence of allergies on long-term device success (Table 1).

After device placement, 84.2% of the patients reported experiencing pain, with specific symptoms varying widely. Headaches or migraines were prevalent in 47.4% of patients, while chest pain affected 21.1%. Neurological symptoms were reported in 42.1% of the cohort, such as dizziness or vertigo (21.1%) and blurred vision (21.1%). Cardiovascular issues were common, such as palpitations (15.8%), breathlessness on exertion (21.1%), and arrhythmias or tachycardia (15.8%). Fatigue affected 31.6% of patients, and gastrointestinal symptoms, skin rash, and depression were reported by 10.5% of patients each. Notably, the majority of symptoms (84.2%) occurred immediately post-operatively, while 10.5% experienced symptoms within the first month, and 5.3% had symptoms that appeared more than one month after surgery (Table 2).

3.1 Nickel Allergy Testing

Fig. 2 demonstrates the outcomes of nickel allergy patch testing in patients with implanted PFO/ASD occluder devices. In the left image, a clear positive reaction (indicated by the red arrow) is visible, showing localized inflammation at the nickel test site. The right image presents the testing process, where various allergens are applied on the patient’s back using patches. Positive reactions to nickel were commonly observed in patients who experienced postoperative complications, reinforcing the connection between nickel hypersensitivity and the need for device explantation.

Fig. 2.

Patch testing for nickel allergy in patients with PFO/ASD occluder devices. The images depict the results of patch testing, with positive reactions indicated by the red arrows. The left image shows a skin reaction with inflammation at the test site, while the right image displays the test setup, including various allergens applied via patches. The positive reaction suggests nickel hypersensitivity, a key factor in postoperative complications and device explantation decisions.

3.2 Intraoperative Findings and Surgical Procedure

Fig. 3 illustrates the critical steps in the totally endoscopic removal of a PFO occluder device, highlighting both the technical aspects and intraoperative findings. Upon exposure of the right atrium, the device is delicately separated from the septal tissue, after that, the residual septal defect is inspected for any structural abnormalities or incomplete healing. The procedure is completed with direct suturing of the septal defect or using tissue patch. The totally endoscopic approach, as demonstrated in these images, was efficient and resulted in a clear operative field, allowing for a successful and complication-free surgery.

Fig. 3.

Intraoperative images of totally endoscopic removal of a PFO occluder device. The sequence illustrates (A) initial exposure of the heart and surrounding structures, (B) identification and isolation of the PFO occluder device, (C) device removal and (D) inspection of the residual defect, (E) preparation for septal repair, and (F) completion of the repair with direct suturing.

All 95 patients undergoing PFO or ASD occluder removal were treated with a totally endoscopic surgical approach, without the need for thoracotomy or sternotomy. Residual septal defects after devices removal were sutured directly in 96.8% patients, and only 3 patients (3.2%) requiring a tissue patch. Nickel allergy testing was performed in all patients, with a majority (89.5%) testing positive, suggesting a strong correlation between nickel sensitivity and device-related complications. The mean CPB time was 71.2 minutes, while cross-clamp time averaged 34.6 minutes. Intraoperative blood loss was minimal, averaging 36.8 mL, and ventilation time postoperatively averaged 4.7 hours. There were no cases of reoperation for bleeding or in-hospital deaths, reflecting a favorable safety profile. The tricuspid valve was inspected intraoperatively and found to be functionally normal, thus requiring no repair. There was no iatrogenic damage to the valve. Chest drainage volume was low, averaging 17.5 mL, with an average chest drainage weaning time of 10.9 hours. Only 2 patients (2.1%) developed postoperative AF, further indicating a low complication rate (Table 3). Fig. 4 depicts the explanted PFO occluder device in multiple orientations. The images clearly show the device’s structural integrity post-explantation, with visible tissue remnants and signs of complete endothelialization.

Fig. 4.

Explanted PFO occluder device, displaying post-removal condition. The figure shows multiple views of the device, including top-down and side perspectives.

Table 3. Perioperative data of patients received PFO/ASD occluder removal.

Characteristic		Result
Surgical approach
	Totally endoscopic	95 (100)
	Thoracotomy/sternotomy	0
Residual septal defects
	Directly repair	92 (96.8)
	Tissue Patch	3 (3.2)
Nickel allergy testing
	Patch positive	85 (89.5)
	Patch negative	10 (10.5)
CPB time, median (IQR), min		71.2 (50–128)
Cross Clamp time, median (IQR), min		34.6 (14–76)
Blood loss, mean (SD), mL		36.8 (21.6)
Ventilation time, mean (SD), h		4.7 (1.8)
Reoperation for bleeding, n (%)		0
In hospital death (%)		0
Chest drainage volume, mean (SD), mL		17.5 (19.3)
Chest drainage weaning time, mean (SD), h		10.9 (1.8)
Postoperative AF, n (%)		2 (2.1)

Values are presented as median (range) or n (%). PFO, Patent Foramen Ovale; ASD, Atrial Septal Defect; CPB, Cardiopulmonary Bypass; SD, Standard Deviation; AF, Atrial Fibrillation.

3.3 Postoperative Findings and Surgical Scarring

Fig. 5 shows the postoperative incisions following a totally endoscopic PFO occluder device removal. The red arrows indicate small thoracoscopic entry sites used during the surgery, while the white arrow highlights the primary incision through which the occluder device was removed. The image reveals minimal scarring and localized bruising, demonstrating the effectiveness of the endoscopic approach.

Fig. 5.

Postoperative thoracoscopic incisions following totally endoscopic removal of a PFO occluder device. The red arrows highlight small thoracoscopic entry points, while the white arrow indicates the primary incision for device removal. Minimal scarring is visible, demonstrating the less invasive nature of the procedure. The image illustrates the favorable cosmetic outcome and limited surgical trauma associated with the endoscopic approach.

QoL ratings among the 95 patients markedly improved following PFO/ASD occluder removal (Table 4). Preoperatively, most patients reported poor QoL (55.8%, n = 53), with only 7.4% (n = 7) rating it as good. By 3 days post-surgery, a substantial improvement was observed: 52.6% (n = 50) reported good QoL, and poor ratings decreased sharply to 5.3% (n = 5). At 1-month follow-up, good QoL further increased to 76.8% (n = 73), while poor ratings persisted in only 2 patients (2.1%). The most dramatic improvement occurred at 6 months post-surgery, with 95.8% (n = 91) reporting good QoL, and only 2 patients each categorized as fair (2.1%) or poor (2.1%) (Fig. 6). Sensitivity analyses confirmed the robustness of these findings. Linear mixed models of continuous SF-36 scores showed a significant time effect (p 0.001). A binary model for achieving “Good” QoL yielded similarly increasing odds over time (6-month OR = 42.10, 95% CI: 19.21–92.28). A complete-case analysis (n = 91) produced nearly identical results, indicating that missing data did not influence the conclusions.

Fig. 6.

Longitudinal quality of life improvement following endoscopic PFO/ASD occluder removal. Stacked percentage bar chart showing the distribution of Quality of Life ratings (Poor, Fair, Good) at four time points among 95 patients. Percentages are labeled within each segment. Adjusted odds ratios (OR) from GEE ordinal regression model are displayed above each bar, demonstrating significant improvement over time (all p 0.0001). The proportion of patients reporting “Good” QoL increased from 7.4% preoperatively to 95.8% at 6 months post-surgery.

Table 4. Quality of life ratings over time with adjusted odds ratios from GEE ordinal regression (n = 95).

Follow-up timepoint	Quality of life rating, n (%)			Adjusted OR* (95% CI)	p-value†
	Poor	Fair	Good
Pre-surgery	53 (55.8)	35 (36.8)	7 (7.4)	1.00 (Ref)
3-day post-surgery	5 (5.3)	40 (42.1)	50 (52.6)	8.21 (4.12–16.35)	0.0001*
1-month post-surgery	2 (2.1)	20 (21.1)	73 (76.8)	15.47 (7.89–30.35)	0.0001*
6-month post-surgery	2 (2.1)	2 (2.1)	91 (95.8)	35.92 (16.84–76.61)	0.0001*

GEE, generalized estimating equations; OR, Odds Ratio; CI, Confidence Interval, *Adjusted for age, sex, indication, device brand, implant-to-explant interval, and nickel allergy status. †p-values adjusted for multiple comparisons (Bonferroni correction; $\alpha$ = 0.0167). Proportional Odds Assumption: Score test p = 0.12, assumption upheld. Sensitivity Analyses: Linear mixed model for continuous SF-36 scores showed consistent improvement over time (p 0.001). Binary logistic GEE (Good vs. Not Good) yielded similar ORs and significance. Complete-case analysis (n = 91) did not alter conclusions.

The present study demonstrates that totally endoscopic removal of PFO/ASD occluder devices is a safe and effective treatment for patients with severe, device-related complications, particularly those associated with nickel hypersensitivity. The primary findings indicate that device explantation significantly improves clinical symptoms, with 95.8% of patients reporting good QoL at six months postoperatively. Additionally, the totally endoscopic approach was associated with minimal perioperative complications, no conversions to thoracotomy, and excellent cosmetic outcomes, reinforcing its safety and efficacy. The findings underscore the need for careful patient selection and monitoring for nickel hypersensitivity in individuals undergoing PFO/ASD device implantation.

Our findings are consistent with previous studies that have highlighted the positive outcomes of device removal in patients experiencing complications associated with nickel hypersensitivity. Similar to the results reported by Sharma et al. [9] who found significant symptom relief in 58 patients following the removal of atrial septal occluders, our study showed a high rate of symptom resolution. Likewise, Fernandes et al. [22] reported complete migraine resolution in a 16-year-old patient following device explantation due to nickel allergy, a result that aligns with the improvements observed in our cohort. However, our study differs from prior research in terms of the surgical approach. While previous studies have primarily focused on open thoracotomy for device removal, such as in the case series by Verma and Tobis [23], we employed a totally endoscopic approach, which resulted in minimal scarring and faster recovery times. This minimally invasive method demonstrated similar efficacy in symptom resolution without the need for more invasive surgical techniques. Furthermore, our study highlights the importance of preoperative nickel allergy testing, as 89.5% of patients with positive tests showed substantial improvement post-explantation, which reinforces the findings of Apostolos et al. [6] on the role of nickel allergy in device-related complications. Besides, the 10.5% nickel-negative patients also exhibited improvement post-explantation, which may attributed to removal of endothelial dysfunction profiles, confirming device removal as a universal solution for refractory complications. The combination of our surgical approach and focus on allergy testing makes our study unique compared to prior literature.

The finding that a substantial majority of patients in this cohort presenting for occluder removal had a documented allergy—most commonly metal hypersensitivity—is striking but consistent with a growing body of evidence. This high prevalence is not representative of the general population receiving cardiac occluders but is instead a profound example of selection bias. This cohort does not consist of random post-operative patients; it is a highly specific group whose devices have failed, often due to intolerable adverse symptoms that prompted surgical intervention. Therefore, the 80%+ figure likely reflects the key etiological role of hypersensitivity reactions in driving device failure and explantation, rather than the incidence of allergy in all implanted patients.

Supplementary Table 1 highlight various cases and studies concerning patients who underwent device explantation due to complications related to PFO or ASD occlusion devices. A recurrent theme across several studies is the resolution of symptoms, such as migraines, chest pain, and systemic hypersensitivity, following the removal of the devices. In the case of Fernandes et al. [22], a 16-year-old male experienced complete relief from migraines post-explantation after six years, with incomplete endothelialization identified as a contributing factor [22]. Other studies, such as Spina et al. [24] and Wertman et al. [4], also underscore the link between nickel hypersensitivity and adverse outcomes, recommending preoperative allergy screening. Studies like Rodés-Cabau et al. [1] showed that dual antiplatelet therapy could reduce migraines in patients with ASD occlusion devices. Finally, Sadasivan Nair et al. [14] and Verma and Tobis [23] highlight that nickel allergies are a significant reason for explantation, with complete symptom resolution post-device removal in most cases. These findings underscore the importance of preoperative assessments and monitoring for nickel allergies to avoid long-term complications.

The endoscopic method used in our cohort resulted in shorter recovery times, minimal postoperative complications, and excellent cosmetic outcomes. Unlike traditional open thoracotomy, which has been the standard in cases requiring PFO or ASD device explantation [23]. Furthermore, the high success rate of direct septal repair (96.8%) without the need for extensive patch repair emphasizes the effectiveness of the endoscopic technique in managing residual septal defects, a finding that has not been as prominently addressed in prior studies. The minimal blood loss (36.8 mL) and low incidence of postoperative AF (2.1%) in our study further highlight the safety profile of this technique compared to previous reports where complications such as arrhythmia were more prevalent following device explantation using traditional methods [9]. Additionally, the emphasis on preoperative nickel allergy testing, with 89.5% of patients showing positive results, supports the growing recognition of the importance of allergy screening in device-related procedures [6]. This comprehensive combination of a minimally invasive approach and targeted preoperative assessments makes our study unique and highlights the potential for improving patient outcomes in future cases.

One limitation of our study is its retrospective design, which may introduce selection bias and limit the generalizability of the results. While our retrospective design precludes definitive causal attribution, the temporal association between device implantation and symptom onset provides compelling evidence: 84.2% (80/95) of patients developed symptoms within 24 hours post-procedure (Table 2), corresponding precisely to the 12–72 hour activation window of Type IV nickel hypersensitivity reactions. This acute manifestation pattern—distinct from endothelialization failure (typically $>$4 weeks)—strongly implicates immune-mediated mechanisms rather than mechanical complications. Additionally, the relatively small sample size of 95 patients may not fully capture the broader population of individuals with PFO/ASD occluder devices, especially those with nickel hypersensitivity. While our cohort represents the largest reported series of totally endoscopic PFO/ASD device explantations, we acknowledge that rare indications inherently limit sample size. The lack of a control group for comparison with non-allergic patients further limits the strength of our conclusions. Moreover, long-term follow-up data beyond six months were not available, preventing an assessment of the durability of symptom relief and long-term complications. While our study confirmed nickel allergy via patch testing, we lacked micro-level analysis of explanted devices (e.g., SEM quantification of corrosion or microthrombi). Future work will include these analyses to quantify surface degradation and its clinical correlations. Lastly, while nickel hypersensitivity was identified in the majority of patients, the specific pathophysiological mechanisms linking nickel allergy to device-related symptoms remain unclear, requiring further research.

In conclusion, the totally endoscopic removal of PFO/ASD occluder devices offers a promising, minimally invasive option for patients experiencing complications related to nickel hypersensitivity or device intolerance. This approach is not only associated with favorable cosmetic outcomes and reduced surgical trauma but also provides significant symptom relief. However, the current understanding of nickel hypersensitivity and its long-term impact on intracardiac devices remains limited. Future studies should focus on developing standardized screening protocols for nickel allergy prior to device implantation and exploring the long-term safety and effectiveness of endoscopic explantation procedures. Additionally, more extensive research is needed to elucidate the pathophysiological mechanisms linking nickel exposure to device-related complications, which could inform both preoperative assessments and post-implantation monitoring strategies. Multicenter, prospective trials with larger, more diverse populations will be crucial to improving the management and treatment outcomes for patients requiring PFO/ASD occluder.

The datasets generated and analyzed during the current study are not publicly available due to privacy and confidentiality concerns but are available from the corresponding author on reasonable request. Access to the data may be granted for research purposes following approval by the institutional review board and adherence to applicable data protection regulations.

HS contributed to the conception and design of the work; acquired, analyzed, and interpreted the patient data; and drafted the manuscript. MR Contributed to the design of the work; acquired data (surgical procedures); analyzed and interpreted the intraoperative and outcomes data; and critically revised the manuscript for important intellectual content. DL contributed to the acquisition and analysis of the data, including statistical analysis; and critically revised the manuscript. SJ contributed to the design of the work, supervised the surgical procedures and data acquisition, and critically revised the manuscript. NC contributed to the conception of the work, the analysis and interpretation of follow-up data, and the revision of the manuscript. LZ contributed to the conception and design of the work; coordinated the study and supervised data acquisition; interpreted the results; critically revised the manuscript for important intellectual content; served as the corresponding author and finalized the manuscript; and ensured adherence to ethical standards. All authors provided final approval of the version to be published and agree to be accountable for all aspects of the work.

This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board of The First Medical Center of Chinese PLA General Hospital (No. S2025-492-01). Given the retrospective nature of the study, the requirement for informed consent was waived. All patient data were anonymized to ensure privacy and confidentiality. The ethical guidelines of the hospital were strictly followed throughout the research process.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/HSF49911.