Transcranial Doppler quantification of residual shunt after percutaneous patent foramen ovale closure: correlation of device efficacy with intracardiac anatomic measures.

BACKGROUND: Percutaneous, mechanical closure of defects of the atrial septum fails to completely resolve shunting in up to 20% of cases. Little is known about the factors associated with device failure. METHODS: We measured the left atrial opening (X), right atrial opening (Z), tunnel length (Y), septum secundum, device-septum primum separation, and tunnel compressibility of the patent foramen ovale (PFO) in 301 patients with cryptogenic neurological events, PFO anatomy, and severe Valsalva shunting (Spencer Grade 5-5+). All patients then underwent percutaneous closure with the GORE®HELEX Septal Occluder device and were evaluated at 3 months for residual shunt by transcranial Doppler (TCD). RESULTS: Severe residual Valsalva shunt (TCD Grade 5-5+) was found at 3 months in 21 of 301 (7%) patients. X, Y, and Z were associated with failure with a high degree of statistical significance, whereas the width of the septum secundum, device-septum primum separation, and tunnel compressibility were not. An unanticipated finding was that 14 of 35 (40%) patients sized with a large balloon failed compared with 9 of 280 (3%) sized with a small balloon (P < 0.0001). In the multivariate logistic regression model, X (P = < 0.0001) and balloon size (P < 0.0001) were both strong predictors of failure. CONCLUSIONS: In an intracardiac echocardiography-defined PFO population, characterized by severe baseline Valsalva shunt and a high incidence of persistent (rest) shunting, association of six intracardiac measurements to closure device failure by multivariate logistic regression showed that the width of the left atrial opening was a strong predictor of residual shunting. An unanticipated finding was that use of a large sizing balloon was also strongly associated with failure.

Transcranial doppler quantification of residual shunt after percutaneous patent foramen ovale closure: efficacy of the GORE(®) HELEX septal occluder.

BACKGROUND: Ideally, percutaneous, mechanical closure of defects of the atrial septum should completely resolve shunt. To achieve this goal, more information is needed about the factors associated with device failure. METHODS: Consecutive patients with cryptogenic neurological events who had severe baseline Valsalva shunt (Spencer Grade 5-5+) and intracardiac echocardiography (ICE) defined patent foramen ovale (PFO) who underwent percutaneous PFO closure with the GORE(®) HELEX Septal Occluder device were evaluated for residual 3-month shunt by transcranial Doppler (TCD). RESULTS: We closed 315 PFO patients with the HELEX devices: 15, 20, 25, 30 mm devices in 19, 138, 150, and 8 patients, respectively. Severe residual Valsalva shunt (TCD Grade 5-5+) at 3 months occurred in 23 of 315 (7%) of all patients and in 2 of 108 (2%), 5 of 86(6%), and 16 of 121 (13%) patients with none, Grade 4, and Grade 5-5+ baseline rest shunt, respectively (P = 0.002). At 3 months, rest shunting was essentially abolished by closure. The percent of patients with severe residual Valsalva shunt was also related to device size: 15 mm (0%), 20 mm (4%), 25 mm (10%), and 30 mm (25%) (P = 0.008) and to atrial septal aneurysm. All of these variables were independent predictors of failure by multivariate logistic regression. CONCLUSIONS: In an ICE-defined PFO population characterized by severe baseline Valsalva shunt and a high incidence of persistent (rest) shunting, the GORE(®) HELEX Septal Occluder device effectively reduces both provoked and persistent shunt. The causes of device failure are multifactorial. Larger devices perform less reliably suggesting the need for size-specific modifications to improve closure of more severe defects. (J Interven Cardiol 2011;24:366-372).

Pooled Analysis of PFO Occluder Device Trials in Patients With PFO and Migraine.

BACKGROUND: Although observational studies have shown percutaneous patent foramen ovale (PFO) closure to be a safe means of reducing the frequency and duration of migraine, randomized clinical trials have not met their primary efficacy endpoints. OBJECTIVES: The authors report the results of a pooled analysis of individual participant data from the 2 randomized trials using the Amplatzer PFO Occluder to assess the efficacy and safety of percutaneous device closure as a therapy for episodic migraine with or without aura. METHODS: The authors analyzed individual patient-level data from 2 randomized migraine trials (the PRIMA [Percutaneous Closure of Patent Foramen Ovale in Migraine With Aura] and PREMIUM [Prospective Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects with Migraine and PFO Using the Amplatzer PFO Occluder Compared to Medical Management] studies). Efficacy endpoints were mean reduction in monthly migraine days, responder rate (defined as ≥50% reduction in monthly migraine attacks), mean reduction in monthly migraine attacks, and percentage of patients who experienced complete cessation of migraine. The safety endpoint was major procedure- and device-related adverse events. RESULTS: Among 337 subjects, 176 were randomized by blocks to device closure and 161 to medical treatment only. At 12-month follow-up, the analysis met 3 of the 4 efficacy endpoints: mean reduction of monthly migraine days (-3.1 days vs. -1.9 days; p = 0.02), mean reduction of monthly migraine attacks (-2.0 vs. -1.4; p = 0.01), and number of subjects who experienced complete cessation of migraine (14 [9%] vs. 1 [0.7%]; p < 0.001). For the safety analysis, 9 procedure-related and 4 device-related adverse events occurred in 245 subjects who eventually received devices. All events were transient and resolved. CONCLUSIONS: This pooled analysis of patient-level data demonstrates that PFO closure was safe and significantly reduced the mean number of monthly migraine days and monthly migraine attacks, and resulted in a greater number of subjects who experienced complete migraine cessation.

Transcranial Doppler quantification of residual shunt after percutaneous patent foramen ovale closure. Comparison of two devices.

BACKGROUND: Recurrent paradoxical embolism after catheter-based closure of right-to-left shunt (RLS) can be related to residual RLS. To improve closure success, we need a better understanding of the anatomic and device-related factors associated with closure efficacy. METHODS: Patients with cryptogenic neurologic events and severe RLS (Valsalva Spencer transcranial Doppler [TCD] grade 5/5+) who underwent patent foramen ovale (PFO) closure by either central pin (Amplatzer(®) PFO [A-PFO]) or central occluding (Amplatzer(®) SO [A-SO]) devices were evaluated for residual shunt by quantitative TCD evaluation at 3 months. The findings were correlated with atrial septal aneurysm (ASA), device type, and device size. RESULTS: We closed 628 consecutive patients with either the A-PFO (n = 327) or A-SO (n = 301) device. The frequency of large defects, small defects, and ASA was 12%, 88%, and 44% of cases, respectively. Severe residual shunt was detected in 13% of A-PFO and 7% of A-SO recipients (P = 0.005). This difference was attributable to a much higher frequency of severe residual shunt among patients with large defects closed with the A-PFO compared to the A-SO device (12 out of 29 [41%] vs. 3 out of 42 [7%], respectively; P < 0.001). There was no significant difference in device failure frequency for small defects. The presence of ASA increased the frequency of severe residual shunt compared to those without this feature (36 out of 275 [13%] vs. 28 out of 353 [8%], respectively; P = 0.046) but did not influence device-related differences. CONCLUSIONS: (1) Both noncentering and central occluding closure devices effectively reduce RLS after PFO closure. (2) Large PFO defects with or without ASA have lower residual shunt grades at 3 months when closed by central occluding devices.

Transient neurological symptoms during contrast transcranial Doppler right-to-left shunt testing in patients with cryptogenic neurological disease.

BACKGROUND: Paradoxical embolization from right-to-left shunt (RLS) resulting in neurological events is well described and patients with cryptogenic neurological disease are commonly evaluated for this condition. In the course of testing for RLS by bubble contrast transcranial Doppler (TCD), we observed that some patients developed transient neurological symptoms. This report describes our findings. METHODS: We performed diagnostic TCD on 445 consecutive patients with cryptogenic neurological disease (cerebral vascular accident, 21%; transient ischemic attack, 30%; migraine, 48%; and abnormal magnetic resonance brain imaging, 68%). Immediately following the procedure, patients were questioned about neurological symptoms. RESULTS: One hundred and sixty-three (37%) of the 445 patients had absent or minimal shunting (Spencer grades 0-1) and 233 of 445 (52%) had severe RLS (Spencer grades 4-5+). One or more TCD-associated neurological symptoms (TCD-SX) developed in 95 of 445 (21%) of the patients. Compared to patients with absent or minimal shunting, patients with shunt grades 2-5+ were two and one half times more likely to develop TCD-SX (18/164 [11%] vs. 77/283 [27%], P < 0.001). TCD-SX were fourfold more common among patients with a history of migraine compared to history-negative subjects (35 vs. 8.7%, P < 0.0001). CONCLUSIONS: Diagnostic bubble-contrast TCD provoked transient neurological symptoms. The symptoms correlated with the severity of RLS and were more common in migraine patients, suggesting that migraine patients are sensitized to chemical and/or microembolic shunt factors. There was no significant residual morbidity, and bubble-contrast echocardiograph continues to be a safe and valuable diagnostic procedure.

Percutaneous Closure of Patent Foramen Ovale in Patients With Migraine: The PREMIUM Trial.

BACKGROUND: Migraine is a prevalent and disabling disorder. Patent foramen ovale (PFO) has been associated with migraine, but its role in the disorder remains poorly understood. OBJECTIVES: This study examined the efficacy of percutaneous PFO closure as a therapy for migraine with or without aura. METHODS: The PREMIUM (Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management) was a double-blind study investigating migraine characteristics over 1 year in subjects randomized to medical therapy with a sham procedure (right heart catheterization) versus medical therapy and PFO closure with the Amplatzer PFO Occluder device (St. Jude Medical, St. Paul, Minnesota). Subjects had 6 to 14 days of migraine per month, had failed at least 3 migraine preventive medications, and had significant right-to-left shunt defined by transcranial Doppler. Primary endpoints were responder rate defined as 50% reduction in migraine attacks and adverse events. Secondary endpoints included reduction in migraine days and efficacy in patients with versus without aura. RESULTS: Of 1,653 subjects consented, 230 were enrolled. There was no difference in responder rate in the PFO closure (45 of 117) versus control (33 of 103) groups. One serious adverse event (transient atrial fibrillation) occurred in 205 subjects who underwent PFO closure. Subjects in the PFO closure group had a significantly greater reduction in headache days (-3.4 vs. -2.0 days/month, p = 0.025). Complete migraine remission for 1 year occurred in 10 patients (8.5%) in the treatment group versus 1 (1%) in the control group (p = 0.01). CONCLUSIONS: PFO closure did not meet the primary endpoint of reduction in responder rate in patients with frequent migraine. (Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management [PREMIUM]; NCT00355056).

Improved long-term survival associated with stent deployment during percutaneous coronary interventions: results from a registry of 3399 patients.

INTRODUCTION: The use of stents in percutaneous coronary intervention (PCI) improves procedural success and reduces restenosis. However, few studies have had a sufficient sample size or adequate follow-up to determine whether this advantage results in a positive effect on mortality. METHODS: A total of 3399 patients undergoing PCI (stented [with dual antiplatelet therapy]: n = 2456, nonstented [balloon PCI or rotational atherectomy]: n = 942) at a single institution from 1994 to 2001 were followed up prospectively (43 +/- 22 and 54 +/- 25 months, respectively) for acute and long-term clinical outcomes. RESULTS: Angiographic success (< 50% residual stenosis) (99.7% vs 97.7%, P < .001) and acute gain (3.02 +/- 0.55 vs 2.08 +/- 0.62 mm, P < .001) were both greater for stented lesions. Likewise, procedural complications of death (0.04% vs 0.4%, P = .02) and dissection (4.9% vs 8.0%, P = .001) were lower in the stent group, as were rates of 6-month clinical restenosis (10.3% vs 16.3%, P < .001). Eight-year mortality (12.0% vs 18.2%, hazard ratio = 0.78, P = .009) was lower among the stent group, as was long-term major adverse cardiac events (36.2% vs 50.6%, P < .001), but no difference in long-term myocardial infarction was found (6.5% vs 7.6%, P = .28). In multivariable Cox regression, stent use (hazard ratio = 0.76, 95% CI [0.58-0.99], P = .04) remained associated with significantly reduced mortality. CONCLUSION: This large prospective study demonstrates that, in addition to a general improvement in procedural success and a reduced need for repeat revascularization, the use of stents with dual antiplatelet therapy was associated with a significant reduction in long-term mortality. Consideration should be given for the use of stents whenever feasible during PCI.