Success Does Not Always Leave A ‘Footprint’
Stroke is one of the leading causes of mortality and morbidity in the United States (US). Approximately one‐third of all ischemic strokes are considered cryptogenic, i.e not attributed to large‐vessel atherosclerosis, small‐artery disease, or embolism despite extensive vascular, serological, and cardiac evaluation. Until recently, the relationship between patent foramen ovale (PFO) and cryptogenic stroke was highly debated. Prior to 2006, use of transcatheter based PFO closure procedures were only permitted under Food and Drug Administration (FDA) Humanitarian Device Exemption for recurrent cryptogenic stroke from a PFO after failed conventional medical therapy1. However, the number of eligible patients exceeded the regulatory mandated annual limit of 4,000 patients in 2006. Thus, the Humanitarian Device Exemption process was voluntarily withdrawn1.
In the past two decades, several randomized clinical trials using the Amplatzer PFO Occluder, the Starflex Septal Occluder (NMT Medical Inc, Boston, MA), and the Gore Cardioform Septal Occluder were conducted. Based on long term follow up results of the RESPECT [Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment] and REDUCE [GORE® Septal Occluder Device for PFO Closure in Stroke Patients] trials, US FDA approved the Amplatzer PFO Occluder in 2016 and the Gore Cardioform Septal Occluder in 20181,2. FDA approval for these devices for PFO closure in the United States is “to reduce the risk of recurrent ischemic stroke in patients, predominantly between the ages of 18 and 60 years, who have had a cryptogenic stroke due to a presumed paradoxical embolism, as determined by a neurologist and cardiologist following an evaluation to exclude known causes of ischemic stroke2.”
Despite proven efficacy, the use of device based PFO closure techniques have potential risks of several early and late complications, including infection, thrombosis, device dislodgement, atrial wall erosion, perforation, fracture, migration-embolization, allergic reaction to nickel used in PFO occluder device, and induction of arrhythmias3,4. Further, there is need of post procedure antiplatelet therapy after implantation of these devices. These concerns lead to need for a ‘deviceless’ transcatheter system to close PFO. Ruiz et al have performed first-in-man transcatheter suture closure of a PFO in an 18-year-old female with chronic migraine with aura in 2008 without leaving ‘footprint’5. Results of this novel approach were exciting; however, safety and efficacy of ‘deviceless’ transcatheter techniques on large scale was not established until early results of the NobleStitch EL Italian Registry were reported few months ago6. In this prospective registry, investigators successfully used suture based PFO closure system in 186 (out of 192) patients across 12 sites in Italy with no device related complication on 206±130 days follow-up6. FDA approves the NobleStitch™ EL for Vascular and Cardiovascular suturing in the US (interestingly the technique is not specifically labeled for treating PFOs).
Due to projected increase in numbers of left sided transcatheter interventions (e.g. left atrial appendage closure, arrhythmia ablation and mitral valve interventions), the deviceless technique could be a very attractive option in selected patient population as presence of interatrial septal prosthesis make trans-septal puncture more challenging. Though this technology has huge potential, we should still wait for long term data on safety and efficacy of this no foot print PFO closure system before advocating and supporting its widespread use.
- Writing Group Members , American Heart Association Statistics Committee; Stroke Statistics Subcommittee . Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016; 133:e38–e360
- Luermans JG, Post MC, Yilmaz A. Late device thrombosis after atrial septal defect closure. Eur Heart J. 2010;31:142
- Merkler AE, Gialdini G, Yaghi S, Okin PM, Iadecola C, Navi BB, Kamel H. Safety Outcomes After Percutaneous Transcatheter Closure of Patent Foramen Ovale. Stroke. 2017;48:3073-7
- Ruiz CE, Kipshidze N, Chiam PT, et al. Feasibility of patent foramen ovale closure with no-device left behind: first-in-man percutaneous suture closure. Catheter Cardiovasc Interv. 2008 Jun 1;71(7):921-6.
- Gaspardone A, De Marco F, Sgueglia GA, et al. Novel percutaneous suture-mediated patent foramen ovale closure technique: early results of the NobleStitch EL Italian Registry. EuroIntervention. 2018 Jun 8;14(3):e272-e279.