ADVERTISEMENT
Fluoroscopy-Only Guided Transcatheter Patent Foramen Ovale Closure: The Importance of Pre-Procedural Echocardiography
© 2024 HMP Global. All Rights Reserved.
Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of the Journal of Invasive Cardiology or HMP Global, their employees, and affiliates.
Abstract
Objectives. Percutaneous closure of a patent foramen ovale (PFO) to prevent recurrent paradoxical thromboembolic events has become the standard of care. However, it remains uncertain if transesophageal echocardiography (TOE) guidance improves procedural success with an existing comprehensive pre-procedural TOE. The aim of the study was to compare the effectiveness of percutaneous PFO closure guided by fluoroscopy (FS) only vs TOE plus FS.
Methods. Consecutive patients undergoing percutaneous PFO closure between February 2017 and April 2023 were analyzed. Based on pre-procedural echocardiography, patients were scheduled either for an FS-only or TOE/FS-guided procedure. The primary-endpoint was effective PFO-closure (residual-shunt grade 0/1 at 6-month follow-up). The secondary-endpoints included procedural safety/efficacy and major adverse cardiovascular events during hospital stay and at the 6-month follow-up.
Results. Two hundred-three patients (mean age 51.8 ± 12.5 years, 39.4% women, Risk of Paradoxical Embolism score = 7 [IQR = 6-7]) underwent PFO closure with FS-only guidance (88 patients, 43.3%) or TOE/FS guidance (115 patients, 56.7%). The main indications for PFO closure were cryptogenic stroke (179 patients, 88.2%) and peripheral embolism (13 patients, 6.4%). At baseline, a right-to-left shunt of grade 2 or higher was present in 199 patients (98%). The procedure time in the FS group was shorter (13 minutes in the FS group vs 16.5 minutes in the TOE/FS group, P = .002). The immediate procedural success was 99.5%. At 6 months, effective closure was achieved in 195 patients (96.1% [FS group: 97.7% vs TOE/FS group 97.8%, P = .29]). The rates of atrial fibrillation and recurrent thromboembolic events were not different among the procedural strategies (3.9% [P = .47] and 0.5% [P = .43]).
Conclusions. After comprehensive pre-procedural echocardiography workup, PFO closure with FS guidance only seems equally safe and effective as TOE/FS guidance. A standardized pre-procedural echocardiography protocol facilitates procedural planning with excellent echocardiographic and clinical outcomes.
Introduction
A solid body of evidence indicates that in patients with a history of cryptogenic stroke, percutaneous patent foramen ovale (PFO) closure with self-expanding, double-disc occluders is superior to medical therapy for the prevention of recurrent events.1-4 Percutaneous PFO closure is usually performed under conscious sedation or general anesthesia and guided by transesophageal echocardiography (TOE) or intracardiac echocardiography. Reports on procedural results using only fluoroscopy (FS) guidance for percutaneous PFO closure are scarce and show heterogenous results. While some authors suggest similar efficacy and safety with the use of FS only,5,6 others report higher rates of residual shunts and higher rates of repeat percutaneous intervention with FS guidance only as compared to additional TOE guidance.7 The requirements for pre-procedural echocardiography, allowing a well-founded decision for FS-only or TOE/FS-guided PFO closure, are not well defined.
Overall, it remains uncertain whether pre-procedural planning and subsequent procedural strategy has an impact on outcomes after percutaneous PFO-closure. The present report compares results of an FS-only vs TOE/FS implantation strategy, which was chosen based on the availability, quality, and findings of a comprehensive echocardiography protocol.
Methods
Patients and study design. This investigator-initiated, single-center study included consecutive patients undergoing transcatheter PFO closure using self-expanding, double-disc occluders at the Heart Center Lucerne (Switzerland) between February 2017 and April 2023. Patients gave general consent for the use and publication of their clinical data. The study was conducted in accordance with the Declaration of Helsinki,8 the principles of Good Clinical Practice, the Human Research Act (HRA), and the Human Research Ordinance (HRO).9 The Swiss Ethics Committee (PAL-Registry ID: 2022-02034) approved the study. Treatment followed the standard of care at the Heart Center Lucerne and were not influenced by the registry’s protocol. PFO closure was performed under either FS guidance (FS group) or TOE-plus-FS-guidance (TOE/FS group).
Prior to the procedure, patients underwent a comprehensive workup, which included an accurate clinical history, transthoracic echocardiography (TTE), TOE, Holter electrocardiogram (ECG) monitoring (for 1 to 7 days), and thrombophilia screening, as well as brain magnetic resonance (MR) or computed tomography (CT) scan in patients with stroke. Six-month follow-up included clinical and echocardiographic data.
The primary endpoint was effective PFO closure, defined as a residual shunt grade 0 or 1, as assessed by contrast echocardiogram at the 6-month follow-up. Secondary endpoints were procedural safety/efficacy and major adverse cardiovascular events during hospital stay and at 6-month follow-up. Clinical endpoints included mortality, stroke, bleeding, vascular complications, acute kidney injury, and other complications related to transcatheter PFO closure.
Echocardiography. All patients underwent TTE and TOE before PFO closure, and TTE (plus TOE at the physician’s discretion) 6 months after the procedure to assess procedural efficacy. Agitated saline, at rest and after Valsalva maneuver, was used to semi-quantitatively assess the right-to-left-shunt (RLS). RLS was graded according to the number of microbubbles detected in the left atrium after shunting from the right atrium. A still frame was identified during the first 3 cardiac cycles of contrast entering the right atrium and the RLS was then graded as follows: Grade 0 = no bubbles; Grade 1 (small RLS) = 5 bubbles or less seen in the left heart; Grade 2 (moderate RLS) = obvious shunt with 6 to 20 bubbles seen in the left heart; and Grade 3 (large RLS) = more than 20 bubbles with partial or complete opacification of the left heart.2 The maximal RLS grade was used for the analysis.
Requirements for FS-only strategy. Depending on the quality and the completeness of the pre-procedural TTE and TOE, the patients were either scheduled for an FS procedure or a TOE/FS procedure. For an FS-only strategy, the following needed to be confirmed (Figure 1):
TTE:
- Focused right ventricular (RV)-view with measurement of indexed end-diastolic RV area. Values less than 11.5 cm2/m2 for females and less than 12.6 cm2/m2 for males were considered normal and suggestive of PFO rather than an atrial septal defect (ASD).10
- Color-Doppler assessment of the inter-atrial septum (IAS), ideally in a subcostal view. Absence of a color jet perpendicular to the IAS was considered suggestive of a PFO rather than an ASD.
- A comprehensive bubble study, including 2 or more attempts at rest as well as after Valsalva maneuver, recording at least 10 cardiac cycles each, confirming RLS.
TOE:
- Thorough assessment of the IAS to exclude ASD type 2 as well as sinus venosus type defects, performed by rotating the probe in the cranial as well as the caudal portion, thereby sweeping the color-Doppler plane through the entirety of the IAS, using a Nyquist limit of less than 50 cm/s.
- Detection and recording of all observed color-Doppler jets at the level of the IAS. A jet perpendicular to the IAS was regarded as suggestive for an ASD. A jet parallel to the IAS, between the septum primum and the septum secundum, was regarded as compatible with a PFO.
- A TOE bubble test, exhibiting bubbles crossing the IAS through the PFO channel. If bulging of the IAS to the left was not possible during TOE, this finding was not mandatory for planning of an FS-procedure.
PFO closure procedure. One of 2 self-expanding double-disc occluders, the Amplatzer PFO occluder (Abbott) or the Figulla Flex II PFO occluder (Occlutech), was used for PFO closure. Implantation procedures for both occluders have been described previously.2,11,12 Briefly, PFO closure was performed under local anesthesia using FS-only or TOE/FS-guiding depending on the chosen strategy. After puncture of a femoral vein, a 5-French (Fr) multipurpose catheter (Cordis) was used to cross the PFO. Then, the multipurpose catheter was exchanged with an 8- or 9-Fr transseptal sheath, which was parked in the left atrium. The size of the occluder was chosen according to the TOE (the pre-procedural TOE or the procedural TOE depending on the chosen strategy). The device was then advanced into the left atrium and the left atrial disc was developed. The occluder was then pulled back to the interatrial septum, and further pulling of the transseptal sheath developed the right atrial disc. The position is then assessed fluoroscopically in a left anterior oblique view. In this view, the occluder is usually in perfect alignment without any overlap of the 2 discs. To document the correct position of the occluder, the “Pacman sign” is of importance; the thick septum secundum is located between the upper left halves of the occluder, which resembles the video game figure Pacman eating a dot.13
Before release, the stability was tested with a strong push and pull. If a satisfying device position was documented, the delivery system was disconnected from the occluder. Following the implantation, the correct position was documented by either FS or FS and TOE. After removal of the delivery sheath, manual compression was applied to the access side until hemostasis was achieved, followed by compression bandage for 6 hours. On the same day, a TTE focusing on device position and mechanical complications (especially pericardial effusion) was performed. Procedural success was defined as the correct position of the PFO occluder as documented by the procedural FS and the post-procedural TTE.
Medical treatment. During the implantation procedure, patients received 80 units of heparin per kilogram of body weight intravenously to achieve an activated clotting time (ACT) of greater than 250 seconds. Periprocedural antibiotic prophylaxis used amoxicillin, or vancomycin in cases of known allergy. Antibiotic prophylaxis was recommended for 6 months after the procedure to prevent endocarditis. During the first 3 months after the procedure, daily antiplatelet therapy with 100 mg aspirin and 75 mg clopidogrel was recommended for all patients, followed by 3 months of aspirin monotherapy.
Statistics. Continuous variables are presented as mean ± standard deviation (SD) and were compared using unpaired and paired Student’s t-tests or the Wilcoxon rank sum test as appropriate. Categorical variables are presented as numbers and frequencies and compared using chi-square or Fisher’s exact tests. STATA´s statistical software package (Version 16.1, StataCorp) was used for statistical analyses. Differences were considered statistically significant at P < .05.
Results
A total of 203 consecutive patients planned for PFO closure were enrolled and assessed regarding the requirements for an FS-only strategy (Figures 1 and 2). Eighty-eight patients (43.3%) qualified for a FS-guidance strategy, whereas 115 (56.7%) were selected for a TOE/FS procedure (Table 1). The mean age was 51.8 ± 12.5 years and 39.4% of the patients were women.
The most common indication for PFO closure was prior paradoxical embolism (192 patients, 94.6%). The Median Risk of Paradoxical Embolism (RoPE) score was 7 (6-7), and in 199 patients (98.0%), a grade 2 or 3 RLS was documented.
Conscious sedation was used in all patients, and in most patients, a 25-mm PFO occluder was implanted (Table 2). Procedure time in the FS group was significantly shorter than in the TOE/FS group (13 [7.0-21.0] minutes vs 16.5 [12-22] minutes, P = .002, Table 2). Fluoroscopic time showed no statistical difference between the 2 strategies (FS group: 3.2 [2.0-5.3] minutes; TOE/FS group: 3.3 [2.2-5.2] minutes, P = .84). Acute procedural success was confirmed in 99.5% of patients. In 1 patient in the TOE/FS group, the right atrial disc was partially entrapped on the left atrial side, and a snare maneuver was used to properly position the device. Transient chest pain occurred in another patient in the TOE/FS group, accompanied by ST-elevation in the inferior leads. Coronary angiography showed air embolism in the distal right coronary artery, which resolved spontaneously without further sequelae.
Echocardiographic outcomes. Effective PFO closure, defined as an RLS of grade 0 or 1 at the 6-month follow up, was observed in 195 patients (96.1%), specifically in 86 patients (97.7%) in the FS group and 109 patients (94.8%) in the TOE/FS group. This difference did not reach statistical significance (P = .29) (Table 3, Figure 3). No pericardial effusion, endocarditis, or thrombus on the PFO device were observed during follow-up.
Clinical outcomes. No death was observed during the 6-month follow-up. One patient in the FS group (1.1%) suffered a stroke. Subsequent echocardiography showed only mild RLS without evidence of a thrombus. No atrial fibrillation was documented. The patient recovered and lifelong aspirin monotherapy was recommended.
Atrial fibrillation was documented in 8 patients (3.9%) during follow-up, 2 in the FS group (2.3%) and 6 in the TOE/FS group (5.2%). However, this difference was not statistically significant (P = .47). One patient was urgently readmitted within the first month after the procedure due to new onset of atrial fibrillation.
Seven of 8 patients with new onset atrial fibrillation were subsequently treated with oral anticoagulation, and antiplatelet therapy was stopped. In 5 of these patients, the atrial fibrillation resolved within 6 months.
Discussion
This report compares the 6-month outcomes of patients undergoing PFO closure either with FS-only or TOE/FS guidance. Patients were selected for 1 of these 2 strategies depending on pre-procedural echocardiography completeness, quality, and findings. This study confirms high procedural success and low periprocedural complication rates for both strategies when the optimal strategy is chosen based on specific pre-procedural echocardiographic criteria. Compared to TOE/FS-guided PFO closure, procedure time with FS-only guidance is significantly shorter with no difference in radiation exposure. Effective PFO closure with no or only mild RLS was found in 96% of patients at the 6-month follow-up, with no difference between the procedural strategies.
Periprocedural outcome. PFO occluders were implanted with high procedural success rates, regardless of the guiding strategy (100% for the FS group vs 99.1% for the TOE/FS group). This is in line with previous studies reporting high procedural success rates with both strategies, ranging from 97% to 100%.5-7,13 In 1 patient in the TOE/FS group, air embolized during development of the left atrial disc, causing transient chest pain and ST-elevation without further sequelae. There were no other major periprocedural complications, confirming excellent safety of both procedural strategies.5-7,11,13-17
PFO closure with FS-only guidance was suggested to potentially reduce procedure time5,6 and radiation exposure.6 In our study, the procedure time with FS-only guidance was significantly shorter. We did not find differences in radiation exposure. However, this is in contrast with another study that reported higher radiation exposure for FS only compared with TOE/FS-guided PFO closure.7
Independent of the procedural strategy, all our patients were treated in an outpatient setting. In other studies, most patients were treated during a short hospital stay.2,5,11,15-18 One study reported that an FS-only strategy may have the potential to shorten the hospital stay in comparison with a TOE/FS strategy.5 Our findings suggest that outpatient treatment (which has a large potential to reduce constraints on our health system) is safe for both guiding strategies. Further data on the safety of outpatient strategies is warranted.
Six-month follow-up. Similar effective closure rates were reported in recent literature for both procedural strategies.5,6 However, both cited studies have relevant limitations. Achim et al used a swift TOE prior to device release within their “FS-only” group.5 Mangieri et al selected less complex patients for the FS-only group.6 Notably, some studies report higher rates of severe RLS (17% vs 8%) when PFO closure is performed with an FS-only strategy.7
In our study, we used an FS-only strategy after definite exclusion of other IAS pathologies but independent of PFO anatomy. At 6-month follow-up, the rate of effective closure was 96.1%. Specifically, effective closure rates were 97.7% in the FS group and 94.8% in the TOE/FS group.
Echocardiography workup before PFO closure. A thorough echocardiographic workup, including TOE, before PFO closure is mandatory.19 If the indication is systemic embolism, it is crucial to rule out other causes such as left-sided intracardiac thrombi, vegetations, tumors, or thrombi on aortic plaques. After this, the interatrial septum should be assessed thoroughly. We suggest doing this in a standardized manner, ensuring exclusion of an ASD, as depicted in Figure 1.
This study suggests that, by following this pre-procedural echocardiography protocol, an FS-only guided strategy can be pursued with safety and success comparable to a TOE/FS strategy. Furthermore, a high-quality pre-procedural TOE allows selection of an adequate device type and size.19
Limitations. The current study has limitations. It is an observational study. Echocardiography and other assessments were carried out according to standards of our center. Our center does not use intracardiac echocardiography (ICE). Therefore, the role of ICE vs TOE for PFO closure guidance cannot be judged from our study. We only used the Amplatzer and Figulla Flex II PFO occluders; thus, it should be noted that our results might not be valid for other umbrella devices. For instance, the Gore Cardioform occluder tends to be more difficult to position and might benefit more from echocardiographic guidance. Echocardiographic outcomes and adverse events were based on site-reported data. The described echocardiography protocol enabled a well-grounded choice of strategy, according to our own standards. However, the operator’s decision was not bound to it.
Conclusions
After thorough pre-procedural echocardiography workup, PFO closure with FS-only guidance seems as safe and effective as TOE/FS guidance when evaluated at short- and mid-term follow-up. Additionally, FS-only guided PFO closure has the potential to reduce procedure time with similar radiation exposure. We suspect that a standardized pre-procedural echocardiography protocol facilitates procedural planning with excellent outcome. Still, randomized controlled trials are warranted to support this hypothesis.
Affiliations and Disclosures
Mathias Wolfrum, MD1; Federico Moccetti,MD1; Nina Conrad1; Lucca Loretz, MD1; Mehdi Madanchi, MD1; Matthias Bossard, MD1; Adrian Attiger-Toller, MD1; Florim Cuculi, MD1; Simon F. Stämpfli, MD, MSc1,2; Stefan Toggweiler, MD1
From the 1Heart Center Lucerne, Luzerner Kantonsspital, Lucerne, Switzerland; 2Center for Molecular Cardiology, University of Zurich, Switzerland.
Drs Stämpfli and Toggweiler contributed equally to this article and are joint last authors.
Disclosures: Dr Wolfrum serves as a proctor for Biosensors. Dr Stämpfli has received travel grants, speaker fees, consulting fees, and/or proctoring fees from Abbott Structural Heart, Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Polares Medical, Pfizer, and Takeda. Dr Toggweiler serves as a consultant and proctor for Medtronic, Boston Scientific, and Biosensors; as a proctor for Edwards Lifesciences and Abbott Vascular; as a consultant for Medira, Shockwave, Teleflex, atHeart Medical, Cardiac Dimensions, Polares Medical, and Amarin; has received speaker honoraria from Sanofi, AstraZeneca, ReCor Medical, and Daiichi Sankyo; has received institutional research grants from Edwards Lifesciences, Boston Scientific, Fumedica, Novartis, Boehringer Ingelheim, and Polares Medical; and holds equity in Hi-D Imaging. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.
Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Address for correspondence: Mathias Wolfrum, MD, Cardiology Division, Heart Center Lucerne, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Luzern, Switzerland. Email: mathias.wolfrum@luks.ch
References
1. Mas JL, Derumeaux G, Guillon B, et al; CLOSE Investigators. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-1021. doi:10.1056/NEJMoa1705915
2. Saver JL, Carroll JD, Thaler DE,et al; RESPECT Investigators. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N. Engl. J. Med. 2017;377(11):1022-1032. doi:10.1056/NEJMoa1610057
3. Søndergaard L, Kasner SE, Rhodes JF, et al; Gore REDUCE clinical study investigators. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033-1042. doi:10.1056/NEJMoa1707404
4. Ahmad Y, Howard JP, Arnold A, et al. Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta-analysis of randomized controlled trials. Eur Heart J. 2018;39(18):1638-1649. doi:10.1093/eurheartj/ehy121
5. Achim A, Hochegger P, Kanoun Schnur SS, et al. Transesophageal echocardiography-guided versus fluoroscopy-guided patent foramen ovale closure: a single center registry. Echocardiography. 2023;40(7):657-663. doi:10.1111/echo.15630
6. Mangieri A, Godino C, Montorfano M, et al. PFO closure with only fluoroscopic guidance: 7 years real-world single centre experience. Catheter Cardiovasc Interv. 2015;86(1):105-112. doi:10.1002/ccd.25735
7. Scacciatella P, Meynet I, Giorgi M, et al. Angiography vs transesophageal echocardiography-guided patent foramen ovale closure: a propensity score matched analysis of a two-center registry. Echocardiography. 2018;35(6):834-840. doi:10.1111/echo.13842
8. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053
9. The Swiss Federal Council. Ordinance on Human Research with the Exception of Clinical Trials (Human Research Ordinance, HRO). September 30, 2011. Accessed March 1, 2023. http://www.admin.ch/opc/en/classified-compilation/20121177/201401010000/810.301.pdf
10. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16(3):233-270. doi:10.1093/ehjci/jev014
11. Neuser J, Akin M, Bavendiek U, Kempf T, Bauersachs J, Widder JD. Mid-term results of interventional closure of patent foramen ovale with the Occlutech Figulla® Flex II Occluder. BMC Cardiovasc Disord. 2016;16(1):217. doi:10.1186/s12872-016-0391-3
12. Pedra C, Pedra S, Costa R, Ribeiro M. The Figulla-Occlutech device. In: Sievert H, Qureshi SA, Wilson N, Hijazi ZM, eds. Interventions in Structural, Valvular and Congenital Heart Disease. 2nd ed. CRC Press; 2014:449.
13. Wahl A, Praz F, Stinimann J, et al. Safety and feasibility of percutaneous closure of patent foramen ovale without intra-procedural echocardiography in 825 patients. Swiss Med Wkly. 2008;138(39-40):567-572. doi:10.4414/smw.2008.12255
14. Higgins JP, Thompson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J R Stat Soc Ser A Stat Soc. 2009;172(1):137-159. doi:10.1111/j.1467-985X.2008.00552.x
15. Krizanic F, Sievert H, Pfeiffer D, Konorza T, Ferrari M, Figulla HR. Clinical evaluation of a novel occluder device (Occlutech) for percutaneous transcatheter closure of patent foramen ovale (PFO). Clin Res Cardiol. 2008;97(12):872-877. doi:10.1007/s00392-008-0699-9
16. Thanopoulos BV, Dardas PD, Karanasios E, Mezilis N. Transcatheter closure versus medical therapy of patent foramen ovale and cryptogenic stroke. Catheter Cardiovasc Interv. 2006;68(5):741-746. doi:10.1002/ccd.20868
17. Trabattoni D, Gaspardone A, Sgueglia GA, et al. AMPLATZER versus Figulla occluder for transcatheter patent foramen ovale closure. EuroIntervention. 2017;12(17):2092-2099. doi:10.4244/EIJ-D-15-00499.
18. Hildick-Smith D, Williams T, MacCarthy P, et al. Occlutech percutaneous patent foramen ovale closure: safety and efficacy registry (OPPOSE). Int J Cardiol. 2017;245:99-104. doi:10.1016/j.ijcard.2017.07.058
19. Silvestry FE, Cohen MS, Armsby LB,et al; American Society of Echocardiography; Society for Cardiac Angiography and Interventions. Guidelines for the echocardiographic assessment of atrial septal defect and patent foramen ovale: From the American Society of Echocardiography and Society for Cardiac Angiography and Interventions. J Am Soc Echocardiogr. 2015;28(8):910-958. doi:10.1016/j.echo.2015.05.015
