Current State of Bioabsorbable Polymer-Coated Drug-Eluting Stents.

Drug-eluting stents (DES) have been shown to significantly reduce clinical and angiographic restenosis compared to bare metal stents (BMS). The polymer coatings on DES elute antiproliferative drugs to inhibit intimal proliferation and prevent restenosis after stent implantation. Permanent polymers which do not degrade in vivo may increase the likelihood of stent-related delayed arterial healing or polymer hypersensitivity. In turn, these limitations may contribute to an increased risk of late clinical events. Intuitively, a polymer which degrades after completion of drug release, leaving an inert metal scaffold in place, may improve arterial healing by removing a chronic source of inflammation, neoatherosclerosis, and/or late thrombosis. In this way, a biodegradable polymer may reduce late ischemic events. Additionally, improved healing after stent implantation could reduce the requirement for long-term dual antiplatelet therapy and the associated risk of bleeding and cost. This review will focus on bioabsorbable polymer-coated DES currently being evaluated in clinical trials.

Phosphorylated STAT5 regulates p53 expression via BRCA1/BARD1-NPM1 and MDM2.

Signal transducer and activator of transcription 5 (STAT5) and nucleophosmin (NPM1) are critical regulators of multiple biological and pathological processes. Although a reciprocal regulatory relationship was established between STAT5A and a NPM-ALK fusion protein in T-cell lymphoma, no direct connection between STAT5 and wild-type NPM1 has been documented. Here we demonstrate a mutually regulatory relationship between STAT5 and NPM1. Induction of STAT5 phosphorylation at Y694 (P-STAT5) diminished NPM1 expression, whereas inhibition of STAT5 phosphorylation enhanced NPM1 expression. Conversely, NPM1 not only negatively regulated STAT5 phosphorylation but also preserved unphosphorylated STAT5 level. Mechanistically, we show that NPM1 downregulation by P-STAT5 is mediated by impairing the BRCA1-BARD1 ubiquitin ligase, which controls the stability of NPM1. In turn, decreased NPM1 levels led to suppression of p53 expression, resulting in enhanced cell survival. This study reveals a new STAT5 signaling pathway regulating p53 expression via NPM1 and uncovers new therapeutic targets for anticancer treatment in tumors driven by STAT5 signaling.

Left Atrial Appendage Closure -The WATCHMAN Device.

Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical cardiology practice. Patients with non-valvular AF have an approximately 5-fold increase in the risk of stroke, with an exponential increase with advancing age. Cardioembolic strokes carry a high mortality risk. Although the potential of warfarin to reduce systemic embolization in AF patients is well established, its use is difficult due to narrow therapeutic windows and additional complications (e.g. increased risk of bleeding), especially for aging patients. Therefore, alternative means of treatment to reduce stroke risk in these patients are needed. The left atrial appendage is the major source of thrombus formation in patients with non-valvular AF. The WATCHMAN device (Boston Scientific, MA) is a percutaneous left atrial appendage closure device which has been tested prospectively in multiple randomized trials. It offers a new stroke risk reduction option for high-risk patients with non-valvular atrial fibrillation who are seeking an alternative to long-term warfarin therapy. Based on the robust WATCHMAN clinical program which consists of numerous studies, with more than 2,400 patients and nearly 6,000 patient-years of follow-up, the WATCHMAN LAAC Device is approved by FDA. In this article we reviewed the preclinical studies and clinical trials, as well as the next generation of the device.

Usefulness of intracardiac echocardiography with a mechanical probe for catheter-based interventions: a 10-year prospective registry.

BACKGROUND: The clinical outcome benefit of intracardiac echocardiography (ICE) with a mechanical probe during congenital heart disease interventions has not been fully investigated. We reported the long-term results of a prospective registry of interatrial shunt closure guided by mechanical ICE. METHODS: We enrolled 537 patients (mean age 48 ± 19.0 years, 378 females) submitted to ICE-aided procedures in a prospective registry over a 10-year period (September 2003-September 2013). All patients underwent transesophageal echocardiography (TEE) before the planned procedure. We evaluated (1) structure identification capability, (2) fossa ovale and interatrial septum component measurement, (3) procedure monitoring capability, (4) procedural and fluoroscopy times, and radiograph dose, (5) probe-related complications. RESULTS: ICE was successfully performed and was able to correctly identify the structures previously assessed by TEE in all patients. In 24 patients (4.5%), ICE allowed better anatomy definition than TEE. In 35 other patients (6.5%), ICE identified structures not observed by TEE, which led to change indications to interventions or the operative technique to be used. In 131 patients (24.4%), ICE evaluation led to change the planned device to be implanted. There was only one probe-related complication (0.2%). CONCLUSIONS: Mechanical ICE may offer a valid alternative to conventional TEE in guiding congenital heart disease interventional procedures.

Vasomotor function and re-endothelialisation after implantation of biodegradable abluminal polymer coated paclitaxel-eluting stents in rabbit iliac arteries: a time-course study.

AIMS: To evaluate the time-course of vasomotor function and re-endothelialisation after implantation of a novel platinum-chromium (PtCr) abluminal biodegradable polymer-coated paclitaxel-eluting stent (PES, Labcoat Element) in rabbit iliac arteries. METHODS AND RESULTS: Either PES (n=18) or an identical platform of bare metal stents (BMS, Element, n=18) were implanted in rabbit iliac arteries (six animals per time-point). At 14, 30, and 90 days, acetylcholine- and nitroglycerine-induced vasomotor reactivity at 5-10 mm distal to the stent was measured. Subsequently, the animals were terminated. The stented artery was bisected longitudinally for either SEM or en face CD31 immunochemistry examination. All arteries were patent with normal angiographic flow. Decreased endothelial-dependent vasomotion was found at both 14 and 30 days for PES compared to BMS (p<0.01, respectively); however, these differences resolved by 90 days. Endothelial-independent vasorelaxation was similar at all three time-points. Both SEM and en face staining demonstrated equivalent endothelial coverage on the surface of the stented segments above and between struts at all time-points. CONCLUSIONS: This novel bioabsorbable polymer abluminal-coated PES demonstrated vasomotor function comparable to BMS within three months post-deployment in the rabbit iliac model. Despite indistinguishable endothelial cell coverage on the stent surface between groups, earlier differences in vasomotion were detected: this finding suggests that the timing of restoration vasomotor function lags morphologic endothelial recovery.

Transradial Szabo technique for intervention of ostial lesions.

OBJECTIVES: The aim of our study is to assess the feasibility and safety of transradial intervention (TRI) of coronary ostial lesions using the Szabo technique. BACKGROUND: When performing TRI of coronary ostial lesions, precise stent positioning is of paramount importance. TRI has experienced increasing popularity in the U.S.; however, utilization of the Szabo technique has not been systematically evaluated in this setting. We report the results of ostial stent deployment using the Szabo technique for 2 experienced TRI operators and centers. METHODS: This was a retrospective analysis of 40 consecutive patients who underwent PCI from April 2009 to September 2011. All patients who underwent PCI via the transradial route with the Szabo technique for ostial lesions performed by experienced transradial operators (>200 cases/yr) were included. RESULTS: In our study of 40 patients with 41 coronary ostial lesions, overall procedural success rate was 100%. Stent dislodgement was seen in 1 patient. Clinical follow up was 100%, with a mean duration of 292.7±200 days. Target lesion revascularization (TLR) was seen in 2 patients (5%). One patient had an episode of transient ischemic attack (TIA) at 33 days after PCI; another experienced subacute stent thrombosis at 81 days while on dual antiplatelet therapy. MACE was 7.5% overall. CONCLUSION: In our study, treatment of coronary ostial lesions with the Szabo technique via TRI is associated with a high procedural success rate and a low MACE of 7.5%.

Nobori stent shows less vascular inflammation and early recovery of endothelial function compared with Cypher stent.

OBJECTIVES: The current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model. BACKGROUND: Nobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available. METHODS: A total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured. RESULTS: Histological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents. CONCLUSIONS: Our data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model.

Long-term results of the amplatzer cribriform occluder for patent foramen ovale with associated atrial septal aneurysm: impact on occlusion rate and left atrial functional remodelling.

BACKGROUND: Treatment of patients with concomitant patent foramen ovale (PFO) and atrial septal aneurysm (ASA) poses a number of challenges; while some authors have suggested the off-label use of the Amplatzer Cribriform Occluder in such anatomy, the long-term outcomes of this strategy is unknown. Our study aimed to assess the long-term impact on closure rate, left atrial functional remodelling, and clinical outcomes of off-label implantation of Amplatzer ASD Cribriform Occluder in patients with PFO and ASA. METHODS: We prospectively enrolled 160 consecutive patients with previous stroke (mean age 36 ± 9.5 years, 109 females), significant PFO and ASA. All patients were treated with Amplatzer Cribriform Occluder to ensure the most complete possible coverage of the ASA. Residual shunt and LA passive and active emptying, LA conduit function, and LA ejection fraction were computed before and after 6 months from the procedure and then yearly. All patients underwent successful transcatheter closure (mean ratio device/diameter of interatrial septum = 0.74). RESULTS: Incomplete ASA coverage during intraprocedural intracardiac echocardiography was observed in 71 patients. During mean follow-up of 3.6 ± 1.8 years, when compared to patients with complete coverage, there were no differences in LA functional parameters and complete occlusion achieved in 150/160 patients (93.7%). No new cerebral ischemic events, aortic erosions or device thrombosis were recorded during the follow-up. CONCLUSIONS: THE USE OF THE AMPLATZER ASD CRIBRIFORM TO TREAT PFO AND ASSOCIATED ASA SEEMS SAFE AND EFFECTIVE: relatively small Occluder devices are probably effective enough to promote left atrial functional remodelling.

Five-year follow-up of intracardiac echocardiography-assisted transcatheter closure of complex ostium secundum atrial septal defect.

OBJECTIVE: We sought to prospectively evaluate long-term follow-up results of intracardiac echocardiography-aided transcatheter closure of complex atrial septal defects (ASD) in the adults. DESIGN AND SETTINGS: Prospective multicenter registry in tertiary care hospitals. PATIENTS AND INTERVENTIONS: Over a 5-year period, we prospectively enrolled 56 patients (mean age 49 ± 16.7 years, 24 females) who have been referred to our center for catheter-based closure of complex secundum ASD (> 25 mm diameter, deficiency of ≥ 1 rim, multiple secundum ASD, multiperforated ASD, associated incomplete floor of the fossa ovalis with or without aneurysm, embryonic remnants of incomplete atrial septation). All patients were screened by means of transesophageal echocardiography before the operation. Eligible patients underwent intracardiac echocardiography study and closure attempt. RESULTS: Forty patients underwent a transcatheter closure attempt: transesophageal echocardiography-planned device type and size were modified in 32 patients (64%). Rates of procedural success, predischarge occlusion, and major complications rate were 100%, 90%, and 2%, respectively. On mean follow-up of 5.4 ± 1.8 years, the follow-up occlusion rate was 98%. During follow-up, only one case of permanent atrial fibrillation was observed. There were no cases of aortic/atrial erosion, device thrombosis, or new atrioventricular valve dysfunction. CONCLUSIONS: Intracardiac echocardiography-guided complex secundum ASD transcatheter closure is safe and effective and appears to have excellent long-term results, thus minimizing potential complications resulting from the complex anatomy.

Permanent right-to-left shunt is the key factor in managing patent foramen ovale.

OBJECTIVES: We sought to prospectively evaluate risk of stroke and impact of transcatheter patent foramen ovale (PFO) closure in patients with permanent right-to left shunt compared with those with Valsalva maneuver-induced right-to-left shunt. BACKGROUND: Pathophysiology and properly management of PFO still remain far from being fully clarified: in particular, the contribution of permanent right-to-left shunt remains unknown. METHODS: Between March 2006 and October 2010, we enrolled 180 (mean age 44 ± 10.9 years, 98 women) of 320 consecutive patients referred to our center for transcatheter PFO closure, who had spontaneous permanent right-to-left shunt on transcranial Doppler and transthoracic/transesophageal echocardiography. All patients fulfilled the standard current indications for transcatheter closure and underwent preoperative transesophageal echocardiography and brain magnetic resonance imaging, with subsequent intracardiac echocardiographic-guided transcatheter PFO closure. We compared the clinical echocardiographic characteristics of these patients (Permanent Group) with the rest of 140 patients with right-to-left shunt only during Valsalva maneuver (Valsalva Group). RESULTS: Compared with the Valsalva Group patients, patients of the Permanent Group had increased frequency of multiple ischemic brain lesions on magnetic resonance imaging, previous recurrent stroke, previous peripheral arteries embolism, migraine with aura, and-more frequently-atrial septal aneurysm and prominent Eustachian valve. The presence of permanent shunt confers the highest risk of recurrent stroke (odds ratio: 5.9, 95% confidence interval: 2.0 to 12, p < 0.001). No differences were recorded between the 2 groups with regard to recurrence of ischemic events after the closure procedure. CONCLUSIONS: Despite its small-sample nature, our study suggests that patients with permanent right-to-left shunt have potentially a higher risk of paradoxical embolism compared with those without.

Transradial cardiac catheterization: a review of access site complications.

Transradial catheterization (TRC) has been associated with a lower incidence of major access site related complications as compared to the transfemoral approach. With the increased adoption of transradial access, it is essential to understand the potential major and minor complications of TRC. The most common complication is asymptomatic radial artery occlusion, which rarely leads to clinical events, owing to the dual collateral perfusion of the hand. Adequate anticoagulation, appropriate compression techniques, and smaller sheath size can minimize the risk of radial artery occlusion. Hand ischemia with necrosis has never been reported during TRC with thorough pre-examination of intact collateral circulation. Radial artery spasm is relatively common, and can result in access and procedural failure. It can be prevented by the use of vasodilator cocktails and hydrophilic sheaths. Radial artery perforation can lead to severe forearm hematoma and compartment syndrome if not managed promptly. Careful observation, prompt detection of the hematoma, and management with a pressure bandage dressing are critical to avoid serious complications. Pseudoaneurym and arteriovenous fistula are rare complications, which can likely be managed conservatively without surgical intervention. Nerve injury occurring during access has been reported. Close observation for improvement is necessary, although symptoms usually improve over time. In summary, to prevent access site complications, avoidance of multiple punctures, gentle catheter manipulation, use of guided compression, coupled with careful observation for adverse warning signs such as hematoma, loss of pulse, pain, are critical for safe and effective TRC.

Efficacy and safety of Firebird sirolimus-eluting stent in treatment of complex coronary lesions in Chinese patients: one-year clinical and eight-month angiographic outcomes from the FIREMAN registry.

BACKGROUND: Off-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry. METHODS: The FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted. RESULTS: Long lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST. CONCLUSIONS: The results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)

Vasomotor function after paclitaxel-coated balloon post-dilation in porcine coronary stent model.

OBJECTIVES: The purpose of this study was to evaluate endothelial function after post-dilation of bare-metal stents with paclitaxel-coated balloons (PCB) or non-drug-coated balloons (non-DCB) in a porcine model. BACKGROUND: DCB are an attractive alternative to drug-eluting stents because they provide short duration of drug exposure, while potentially inhibiting in-stent restenosis. Drug-eluting stents are associated with impaired endothelial function. It is unknown whether this abnormal vasomotor function is mitigated by reduced duration of drug exposure. METHODS: Thirteen pigs underwent bare-metal stent implantation (arteries, n = 30), followed by post-dilation with either PCB (SeQuent Please, B. Braun Melsungen AG, Berlin, Germany) (n = 17) or non-DCB (n = 13). Five pigs with unstented arteries (n = 14) were controls. Coronary vasomotion was assessed 1 month after stent implantation, using acetylcholine (Ach) and nitroglycerin. Measurements were obtained for distal segments. RESULTS: Angiographic late loss and histological area stenosis were similar between PCB and non-DCB. However, the percentage of diameter change in response to Ach was diminished with PCB (p < 0.05), when compared with either non-DCB or naive arteries. There was no difference between non-DCB and naive arteries. Inflammatory score and intramural fibrin grading were significantly greater in PCB than non-DCB (p < 0.05). Additionally, inflammatory cell infiltration in the stented segments correlated with the degree of percentage of diameter change in response to Ach, at distal regions. CONCLUSIONS: Post-dilation of bare-metal stents with PCB was associated with impaired vasodilatory response to Ach distal to the treated segments. Vasodilatory response after post-dilation with non-DCB was similar to control arteries.

Comparison between the NERS (New Risk Stratification) score and the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score in outcome prediction for unprotected left main stenting.

OBJECTIVES: This study aimed to compare the NERS (New Risk Stratification) and SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) scores for prognostication after stenting of unprotected left main stenosis in a "real-world" setting. BACKGROUND: In contrast to existing systems, the NERS score encompasses clinical, procedural, and angiographic characteristics. METHODS: The NERS score was derived from 260 patients with unprotected left main stenosis who underwent percutaneous coronary intervention and tested in 337 patients in a consecutive left main registry (66.55 +/- 10.49 years, 78.9% men) undergoing percutaneous coronary intervention in a prospective, multicenter trial. Six-month clinical and angiographic follow-up was obtained in 100% and 88.9% of patients, respectively. The primary end point was major adverse cardiac events (MACE), encompassing myocardial infarction, all-cause death, and target vessel revascularization. Receiver-operator characteristic (ROC) curve was generated for the comparison of NERS versus SYNTAX scores. RESULTS: The NERS score consisted of 54 variables (17 clinical, 4 procedural, and 33 angiographic). A NERS score > or =25 demonstrated a sensitivity and specificity of 92.0% and 74.1% (MACE as state variable), respectively, significantly higher than SYNTAX intermediate risk (20.5% and 25.4%) or SYNTAX higher risk (70.5% and 35.2%, p for all <0.001). At follow-up, myocardial infarction, cardiac death, and target vessel revascularization occurred in 3.0%, 5.6%, and 13.1% of patients, respectively, for a composite MACE of 26.0%. A NERS score > or =25 (hazard ratio: 1.13; 95% confidence interval [CI]: 1.11 to 1.16; p < 0.001) was the only independent predictor of cumulative MACE and stent thrombosis at follow-up (odds ratio: 31.04; 95% CI: 19.36 to 67.07; p < 0.001). CONCLUSIONS: The NERS score was more predictive of MACE than the SYNTAX score was. Further study is needed to address their relative roles in assessment for appropriateness of coronary artery bypass graft versus percutaneous coronary intervention for unprotected left main coronary artery stenosis.

Polymer-free cerivastatin-eluting stent shows superior neointimal inhibition with preserved vasomotor function compared to polymer-based paclitaxel-eluting stent in rabbit iliac arteries.

AIMS: The present study was designed to evaluate vasomotor function and vascular biological responses following a novel non-polymeric cerivastatin-eluting stent (CES) versus polymer-based paclitaxel-eluting stent (PES) in a rabbit iliac artery model. Optimisation of DES components and non-polymeric stents may contribute to vascular healing and beneficial to vasomotor function. METHODS AND RESULTS: In vitro human aortic and coronary smooth muscle cells (hASMC & hCSMC), as well as endothelial cells (hAEC & hCEC) were cultured. IC50 curves were determined for cerivastatin (CER). In vivo PES (n=6) and CES (n=12) stents were implanted in nine rabbits. Vasomotor function was investigated at 28 days by acetylcholine (ACh) followed by histopathological and histomorphometric analyses. CER was cytotoxic to hASMC and hCSMC (IC50s of 10-6 M and 10-5 M, respectively), although such cytotoxic effects were not observed for hAEC and hCEC at maximal study dose. PES-associated vasodilation response to endothelial-dependent ACh was significantly suppressed at both proximal and distal adjacent arterial segments, as compared to CES. Furthermore, microscopically, neointimal inhibition quantified by the neointimal cross-sectional area (IA) was superior with CES (0.60 + or - 0.27 mm(2)) compared to PES (1.35 + or - 0.16 mm(2); P <0.05). Medial area was smaller for PES (0.3 + or - 0.04 mm(2)) than CES (0.5 + or - 0.03 mm(2), p <0.001). Additionally, significant inflammation and fibrin deposition was clearly evidenced in PES compared to CES (p <0.05). CONCLUSIONS: CER elicits a differential effect on hSMC compared to hEC in vitro. In contrast to PES, a novel bioabsorbable sol-gel coated CES demonstrated effective neointimal inhibition with less vessel wall toxicity accompanied by preservation of vasomotor function in the rabbit iliac model.

Primary transcatheter patent foramen ovale closure is effective in improving migraine in patients with high-risk anatomic and functional characteristics for paradoxical embolism.

OBJECTIVES: In the present study, we sought to assess the effectiveness of migraine treatment by means of primary patent foramen ovale (PFO) transcatheter closure in patients with anatomical and functional characteristics predisposing to paradoxical embolism without previous cerebral ischemia. BACKGROUND: The exact role for transcatheter closure of PFO in migraine therapy has yet to be elucidated. METHODS: We enrolled 86 patients (68 female, mean age 40.0 +/- 3.7 years) referred to our center over a 48-month period for a prospective study to evaluate severe, disabling, medication-refractory migraine and documented PFO. The Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine. Criteria for intervention included all of the following: basal shunt and shower/curtain shunt pattern on transcranial Doppler and echocardiography, presence of interatrial septal aneurysm and Eustachian valve, 3 to 4 class MIDAS score, coagulation abnormalities, and medication-refractory migraine with or without aura. RESULTS: On the basis of our inclusion criteria, we enrolled 40 patients (34 females, mean age 35.0 +/- 6.7 years, mean MIDAS 35.8 +/- 4.7) for transcatheter PFO closure; the remainder continued on previous medical therapy. Percutaneous closure was successful in all cases, with no peri-procedural or in-hospital complications. After a mean follow-up of 29.2 +/- 14.8 months (range 6 to 48 months), PFO closure was complete in 95%; all patients (100%) reported improved migraine symptomatology (mean MIDAS score 8.3 +/- 7.8, p < 0.03). Specifically, auras were eliminated in 100% of patients after closure. CONCLUSIONS: Primary transcatheter PFO closure resulted in a very significant reduction in migraine in patients satisfying our criteria.