Zero-Contrast Left Atrial Appendage Occlusion Using a Hybrid Echocardiography-Fluoroscopy Technique Without Iodinated Contrast.

Contrast exposure during left atrial appendage occlusion may be harmful in those with chronic kidney disease or allergy. This single-center registry (n = 31) demonstrates the feasibility and safety of zero-contrast percutaneous left atrial appendage occlusion using echocardiography, fluoroscopy, and fusion imaging, with 100% procedural success and no device complications at 45 days.

Incidence and time course of atrial fibrillation following patent foramen ovale closure.

OBJECTIVES: Determine the true incidence and time course of atrial fibrillation (AF) after patent foramen ovale closure (PFOc) using implantable loop recorders (ILR) placed during cryptogenic stroke evaluation. BACKGROUND: Published trials report a 2%-6.6% incidence of postimplant atrial fibrillation (PIAF) after PFOc, which is probably a gross underestimation, as only patients presenting in AF were captured. Episodes of paroxysmal and silent AF would have been missed. METHODS: Of 761 patients who underwent PFOc at a single center between January 2016 and December 2020, 35 patients had an ILR implanted before PFOc, without documentation of AF, and had ≥1 month of monitoring post-PFOc. The incidence, onset, and conclusion of AF episodes were determined from a review of patient records. RESULTS: The mean duration of ILR monitoring was 54.6 ± 39.4 weeks after PFOc. AF occurred in 13/35 (37%) patients. PFOc patients who developed PIAF were older than those who did not (62 ± 11 vs. 52 ± 14 years, p = 0.03). In 12/13, the initial PIAF event occurred within 4 weeks of PFOc, with the greatest frequency around 2 weeks and conclusion by 12 weeks in all. No recurrent strokes occurred during ILR monitoring. CONCLUSION: The actual incidence of PIAF was far greater than previously reported and was significantly associated with older age at PFOc. The timing of PIAF onset and termination were consistent with a postimplant inflammatory mechanism. The higher actual PIAF incidence underscores its low stroke potential in this population. A larger prospective trial is required to validate these preliminary results.

Conformal Left Atrial Appendage Seal Device for Left Atrial Appendage Closure: First Clinical Use.

OBJECTIVES: The authors report the first clinical experience with the Conformal Left Atrial Appendage Seal (CLAAS) device. BACKGROUND: The CLAAS device was designed to address the limitations of first-generation left atrial appendage closure (LAAC) devices by providing an implant that is minimally traumatic, can be deployed in a noncoaxial fashion, and does not require postprocedural oral anticoagulation. METHODS: Patients with atrial fibrillation at high stroke risk (CHA2DS2-VASc score ≥2) were recruited using standard selection criteria. The LAAC procedure was guided by transesophageal echocardiography with patients under general anesthesia. The CLAAS device is composed of a foam cup, with a Nitinol endoskeleton with an expanded polytetrafluoroethylene cover, delivered with a standard delivery system using a tether for full recapture. All patients received dual-antiplatelet therapy for 6 months, followed by aspirin alone. Transesophageal echocardiographic follow-up was scheduled for 45 days and 1 year. RESULTS: Twenty-two patients (63.7% with CHA2DS2-VASc scores ≥3, 76.2% with HAS-BLED scores ≥3) were enrolled. The device was successfully implanted in 18 patients and unsuccessfully in 4 patients. There were no serious procedural complications. On transesophageal echocardiography performed at 45 days, 1 significant leak (≥5 mm) was seen, which was due to a large posterior lobe not appreciated at the time of implantation, and 1 device-related thrombus was noted, which resolved on oral anticoagulation. There were no periprocedural strokes, major pericardial effusions, or systemic or device embolization. CONCLUSIONS: This first-in-human study demonstrates the clinical feasibility of the CLAAS device for LAAC.

Preclinical Assessment of a Novel Conformable Foam-Based Left Atrial Appendage Closure Device.

BACKGROUND: Left atrial appendage (LAA) occlusion has been established as an alternative to systemic anticoagulation for stroke prevention in patients with atrial fibrillation; however, limitations of current devices have slowed adoption. We present preclinical evaluations of a novel device, the Conformal Left Atrial Appendage Seal (CLAAS). METHODS: An in vitro assessment of conformability was conducted to evaluate the two CLAAS devices (regular 27 mm and large 35 mm) and a Watchman 2.5 (27 mm). Devices were placed within silicone tubes and compressed in a vise submerged in a water bath at 37°C. Changes in device diameter and visual seal were noted. Acute (n = 1) and chronic 60-day (n = 6) canine studies with gross and histologic assessment were performed. RESULTS: Conformability bench tests demonstrated that the regular CLAAS implant was able to seal oval orifices from 20 × 30 mm to 15 × 33 mm and the large from 30 × 35 mm to 20 × 40 mm. As the CLAAS implant was compressed in the minor diameter, it increased in the major diameter, thereby filling the oval space, whereas the Watchman 2.5 showed gaps and maintained its round configuration when compressed in one direction. Seven devices were successfully implanted in the canine model with complete seal without thrombus. Histologic examination showed complete neointima covering with minimal inflammation at 60 days. CONCLUSIONS: Preclinical testing demonstrated the conformability of the CLAAS implant and its ability to seal the LAA. Clinical studies are ongoing to characterize the utility of the CLAAS implant in the treatment of patients with atrial fibrillation.

Proposal for Updated Nomenclature and Classification of Potential Causative Mechanism in Patent Foramen Ovale-Associated Stroke.

Importance: Recent epidemiologic and therapeutic advances have transformed understanding of the role of and therapeutic approach to patent foramen ovale (PFO) in ischemic stroke. Patent foramen ovale is likely responsible for approximately 5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults. Observations: Randomized clinical trials have demonstrated that, to prevent recurrent ischemic stroke in patients with PFO and an otherwise-cryptogenic index ischemic stroke, PFO closure is superior to antiplatelet medical therapy alone; these trials have provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents. Conclusions and Relevance: These new data indicate a need to update classification schemes of causative mechanisms in stroke, developed in an era in which an association between PFO and stroke was viewed as uncertain. We propose a revised general nomenclature and classification framework for PFO-associated stroke and detailed revisions for the 3 major stroke subtyping algorithms in wide use.

ASSURED clinical study: New GORE® CARDIOFORM ASD occluder for transcatheter closure of atrial septal defect.

OBJECTIVE: Assess clinical performance of a new device for transcatheter closure of atrial septal defect (ASD). BACKGROUND: Previously-approved ASD Closure devices have known limitations. Device erosion has been associated with the AMPLATZER® septal occluder in patients with retro-aortic rim deficiency (<5 mm), while defects ≥18 mm are too large for the GORE® CARDIOFORM septal occluder. The GORE® CARDIOFORM ASD occluder (GCA), a hybrid of the approved devices, was designed to expand the eligible ASD population. METHODS: One-hundred and twenty-five ASD patients were enrolled in a prospective, multicenter registry. Descriptive clinical endpoints included: technical implant success, closure success, serious adverse events (SAE), clinically significant new arrhythmia, and wire frame fracture. Procedural outcomes and adverse events were adjudicated by an Echocardiography Core Lab and Independent Data Review Board, respectively. RESULTS: Median subject age was 12.3 years (range 2.9-84.7), with 72% of patients ≤18 years old. Median ASD stop-flow diameter was 17.0 mm (8.0-30.0), with 43% ≥18 mm. Deficient retro-aortic rim occurred in 57% of subjects, and 30% had both diameter ≥ 18 mm and deficient rim. Technical Implant Success was achieved in 120/125 (96%), though three devices were removed within 24 hr. At the scheduled 6-month evaluation, 112/117 returned for evaluation. All 112 had closure success. SAE occurred in 6/125 (4.8%) and 6/125 (4.8%) had clinically significant new arrhythmia. Wire frame fractures occurred in 37/104 (36%), without any associated clinical sequelae, residual shunt, or device instability. CONCLUSION: The GCA performed effectively and safely in this initial cohort, and led to FDA approval based on this data.

Tricuspid Valve Imaging and Intervention in Pediatric and Adult Patients With Congenital Heart Disease.

Tricuspid valve abnormalities in congenital heart disease comprise a wide spectrum, with the most common being Ebstein anomaly and tricuspid valve dysplasia. Tricuspid valve dysfunction may also be secondary to other types of congenital heart disease, including functional tricuspid regurgitation seen in right heart volume overload conditions, such as atrial septal defect and repaired tetralogy of Fallot with severe pulmonary valve regurgitation. Congenitally corrected transposition and Mustard and Senning procedures maintain the right ventricle as the systemic ventricle, and the tricuspid valve is subject to unique hemodynamic stress not typically seen in normal circulation. Surgical treatment of tricuspid valve disease remains the mainstay of therapy; primary catheter-based interventions are uncommon. However, once a tricuspid valve has been replaced with a bioprosthesis, the patient may be a candidate for tricuspid valve-in-valve catheter-based replacement.

Retrospective review of thienopyridine therapy in migraineurs with patent foramen ovale.

OBJECTIVE: We retrospectively reviewed our clinical experience using off-label thienopyridine agents in patients with migraine headache (MHA) and patent foramen ovale (PFO). METHODS: Between 2011 and 2017, MHA/PFO patients referred to our practice were clinically treated with clopidogrel specifically for MHA. Those with ≥50% reduction in monthly MHA days compared with baseline were deemed MHA responders. MHA nonresponders with inadequate platelet inhibition by PRU testing were offered prasugrel. Thienopyridine-responsive patients were then offered PFO closure. RESULTS: Of 136 patients (86% female, mean age 37.9 years, mean MHA burden 14.7 days/month), 80 (59%) were MHA responders to clopidogrel. The clopidogrel responder rate was equivalent in episodic, chronic, aura, and nonaura subgroups. A total of 19/45 (40%) MHA nonresponders had inadequate platelet inhibition by PRU testing on clopidogrel. Sixteen of those patients received prasugrel, were adequately platelet inhibited by PRU, and 10/16 (62%) converted to MHA responders. A total of 56/90 thienopyridine-responsive patients underwent subsequent PFO closure with thienopyridine discontinuation after 3 months. Ninety-four percent had ongoing MHA relief. A total of 8/8 responders who stopped thienopyridine without PFO closure had resumption of MHA symptoms. CONCLUSION: Successful P2Y12 platelet inhibition seemed to reduce MHA symptoms in some patients with PFO, suggesting a platelet-based mechanism/trigger. The nearly parallel response to PFO closure may mechanistically link venous platelet activation with the right-to-left shunt of PFO. Thienopyridine responsiveness could be used to enrich the study population for a new MHA/PFO trial. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with PFO, P2Y12 inhibition improved MHA symptoms.

Ticagrelor for Refractory Migraine/Patent Foramen Ovale (TRACTOR): An open-label pilot study.

OBJECTIVE: After finding that the thienopyridines clopidogrel and prasugrel reduced migraine headache (MHA) symptoms in some patients with patent foramen ovale (PFO), this small pilot study was undertaken to determine whether ticagrelor, a nonthienopyridine P2Y12 inhibitor, would have similar MHA effects and might be better suited for a future randomized trial. METHODS: MHA patients were screened for PFO. Participants with documented right to left shunt (RLS) and ≥6 monthly MHA days received ticagrelor therapy for 28 days. Those with ≥50% reduction in monthly MHA days were deemed responders and completed 2 additional treatment months. RESULTS: The 40 participants had a mean age of 36.2 years and mean MHA frequency of 17.4 d/mo. A total of 39/40 were female. A total of 14/40 met criteria for episodic MHA, 26/40 for chronic MHA, 14/40 had migraine with aura, and 22/40 had a moderate-large RLS (Spencer grade ≥4). Seventeen of 40 participants (43%) were responders. MHA reduction continued through 3 treatment months in all responders. MHA responder rates were not statistically different in participants with episodic or chronic MHA, with or without aura, or with small/larger RLS shunt magnitude. Thirteen (32%) patients had medication side effects, without serious adverse events. CONCLUSION: P2Y12 inhibition with ticagrelor reduced MHA symptoms similarly to our previous thienopyridine experience, but participants seemed to have a less robust MHA benefit and more frequent side effects than with the thienopyridines, making it an inferior choice for a randomized trial. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ticagrelor reduced MHA symptoms in patients with PFO.

Percutaneous Closure of Intracardiac Defects in Adults: State of the Art.

The number of adults with congenital heart disease is expected to increase over the next decade. Although acquired defects are being increasingly recognized in adults, congenital heart disease remains the most common etiology. With advances in cardiac imaging, device technology, and transcatheter techniques, percutaneous closure is now feasible and safe for most intracardiac defects. Device closure is considered the first-line therapy for a variety of congenital intracardiac defects, including ostium secundum atrial septal defects and muscular ventricular septal defects. Percutaneous closure may prevent recurrent cerebrovascular events after a cryptogenic stroke in high-risk patients with patent foramen ovale. It is also an alternative therapeutic option for patients with acquired defects such as posttraumatic or postinfarction ventricular septal defects and paravalvular regurgitation associated with prosthetic valves. Complications after device closure are uncommon, and may be avoided with appropriate patient and device selection. This is a comprehensive review of the current transcatheter management of the most common intracardiac defects encountered in the adult population.

A retrospective review of clopidogrel as primary therapy for migraineurs with right to left shunt lesions.

BACKGROUND: The association of patient foramen ovale (PFO) and migraine headache (migraine) with aura (MA) is well established. Current research suggests a mechanistic link between platelet activation, paradoxical embolization and migraine in some patients. METHODS: Clopidogrel, a platelet inhibitor, was added to existing migraine therapy, as a 4-week open-label trial in 15 women, aged 16-56 years, with severe migraine and documented right to left shunt (RLS). RESULTS: 13/15 had > 50% reduction or complete elimination of migraine symptoms. After completing the trial period, five responders remain on clopidogrel with ongoing benefit at 11.9 ± 4.5 months (6.5-20), one stopped clopidogrel because of side effects. Nine other responders underwent PFO closure and clopidogrel discontinuation. Eight of nine have had ongoing benefit. CONCLUSIONS: Clopidogrel may have a primary prophylactic role in migraine/RLS patients, but may also help select candidates who would benefit from PFO closure. A randomized clinical trial is being established.

A meta-analysis of transcatheter closure of patent foramen ovale versus medical therapy for prevention of recurrent thromboembolic events in patients with cryptogenic cerebrovascular events.

OBJECTIVES: We sought to perform a meta-analysis of randomized controlled trials (RCTs) comparing percutaneous patent-foramen-ovale (PFO) closure with medical therapy for preventing recurrent thromboembolic events after cryptogenic stroke. BACKGROUND: Observational studies suggested that transcatheter PFO closure decreases recurrent events after cryptogenic stroke; however, three recent RCTs failed to demonstrate such benefit. METHODS: Trials were identified from the PubMed and Cochrane databases. Primary endpoint was the composite of transient ischemic attack (TIA) and ischemic cerebrovascular events (CVA). Both intention-to-treat (ITT) and as-treated analyses (AT) were performed. RESULTS: Three RCTs met inclusion criteria. The pooled data provided 2,303 patients, of which 1,150 were in the PFO closure group and 1,153 in the medical therapy group. In the ITT analysis, there were 43 events (3.7%) of the composite end point in the closure group compared with 61 events (5.3%) in the medical therapy group, with a trend in favor of the PFO closure (OR = 0.70; 95% CI, 0.47-1.05, P = 0.08). The incidences of TIA, ischemic CVA, and bleeding were not statistically different between the groups. There was a trend for the more frequent occurrence of atrial fibrillation in the PFO closure group (OR = 3.29; 95% CI, 0.86-12.60, P = 0.08). In the AT analysis, the composite end point was significantly less frequent in the PFO closure group (OR = 0.62; 95% CI, 0.41-0.94, P = 0.02). CONCLUSIONS: In this meta-analysis of contemporary RCTs, successful transcatheter closure of PFO might be more effective than medical therapy alone for the prevention of recurrent thromboembolic events.

Patent foramen ovale: where are we in 2009?

Patent Foramen Ovale (PFO) is present in 20 - 25% of the population, and is known to be associated with a number of clinical syndromes. However, it is less clear that there is a causal (or contributory) role for the PFO in the development of thromboembolic stroke, systemic thromboembolization, decompression illness in divers, hypoxemia with obstructive sleep apnea, or migraine headaches. On-going and new randomized prospective trials are testing these relationships and are attempting to prove therapeutic benefit to closing the defects. This paper will review the existing literature on PFO, and will attempt to clarify some of the outstanding clinical management issues.