Recurrent Stroke after Transcatheter PFO Closure in Cryptogenic Stroke or Tia: Long-Term Follow-Up.

BACKGROUND: There are few data on the mechanism of recurrent neurological events after transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA. METHODS: We retrospectively reviewed PFO closure procedures for the secondary prevention of cryptogenic stroke/TIA performed between 1999 and 2014 in Bologna, Italy. RESULTS: Written questionnaires were completed by 402 patients. Mean follow-up was 7 ± 3 years. Stroke recurred in 3.2% (0.5/100 patients-year) and TIA in 2.7% (0.4/100 patients-year). Ninety-two percent of recurrent strokes were not cryptogenic. Recurrent stroke was noncardioembolic in 69% of patients, AF related in 15% of patients, device related in 1 patient, and cryptogenic in 1 patient. AF was diagnosed after the procedure in 21 patients (5.2%). Multivariate Cox's proportion hazard model identified age ≥ 55 years at the time of closure (OR 3.16, p=0.007) and RoPE score < 7 (OR 3.21, p=0.03) as predictors of recurrent neurological events. CONCLUSION: Recurrent neurological events after PFO closure are rare, usually noncryptogenic and associated with conventional vascular risk factors or AF related. Patients older than 55 years of age and those with a RoPE score < 7 are likely to get less benefit from PFO closure. After transcatheter PFO closure, lifelong strict vascular risk factor control is warranted.

Transcatheter patent foramen ovale closure mitigates aura migraine headaches abolishing spontaneous right-to-left shunting.

BACKGROUND: Patent foramen ovale (PFO) has been implicated in the etiology of migraine headache with aura (MHA), but the mechanisms that link right-to-left (R-to-L) shunt to MHA are unclear, and the reports on the efficacy of transcatheter PFO closure on MHA prevention are scarce. METHODS: We reviewed the clinical records of 131 consecutive patients who underwent successful transcatheter PFO closure at our institution at a mean age of 45 +/- 13 years because of cryptogenic stroke. Of the 131 patients, 35 (27%) had a diagnosis of MHA made by the primary care physician or the referring neurologist. Migraine headache with aura incidence and severity were assessed by using Migraine Disability Assessment (MIDAS) questionnaire. Presence and magnitude of R-to-L shunt were assessed in all patients by means of transesophageal echocardiography and also by means of transcranial Doppler (TCD) in the last 50 patients (38%). RESULTS: Patients with MHA had a higher prevalence of thrombophilia (P = .007), a more complex atrial septal anatomy (P = .001), and they also had higher prevalence of spontaneous R-to-L shunt and of spontaneous large shunt, both at transesophageal echocardiography (P = .015, and .028, respectively) and at TCD (P = .036, and .038, respectively). After the procedure, 32 (91%) of 35 patients had either complete resolution or significant improvement in their MHA. At a mean follow-up of 1.7 +/- 1.3 years, MHA disappeared completely in 29 (83%) of 35 patients. Of the remaining 6 patients, 3 patients (8%) had an improvement of > or = 2 grades in the incidence and severity of MHA, 2 patients did not show any improvement of their MHA, whereas 1 patient reported a severe relapse of MHA about 1 year after the procedure. CONCLUSIONS: In patients with PFO, MHA is associated with spontaneous large R-to-L shunt and thrombophilic conditions. Transcatheter defect closure seems to be an effective and safe means to treat MHA in patients with PFO.

Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics.

INTRODUCTION: Direct oral anticoagulant (DOAC) intra- and inter-individual variability was previously reported, but its magnitude is still considered negligible for patient management. OBJECTIVE: To evaluate inter- and intra-individual variability in real-world atrial fibrillation patients on dabigatran, rivaroxaban or apixaban in four Italian anticoagulation clinics and to assess the correlation between DOAC plasma concentration and creatinine-clearance (CrCl). MATERIALS AND METHODS: A total of 330 consecutive patients were enrolled, of which 160 were on dabigatran (70 and 90 taking 150 mg or 110 mg twice-daily, respectively), 71 on rivaroxaban (37 and 34 taking 20mg or 15 mg once-daily) and 99 on apixaban (73 and 26 taking 5mg or 2.5mg twice-daily). Blood was taken at trough and peak within the first month (15-25 days) of treatment. Diluted-thrombin-time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban was performed. RESULTS: Mean inter-individual variability expressed as overall CV values for all drugs was lower at peak (CV=46%) than at trough (CV=63%). Mean CV% intra-individual variability was 36.6% at trough and 34.0% at peak. Correlation with CrCl was poor for all drugs and only dabigatran at trough showed a significant correlation. CONCLUSION: This multicenter study confirms high DOAC inter-individual variability that cannot be explained by the rate of renal clearance to which the three DOAC were subjected since the correlation with CrCl was relatively poor. This poor correlation suggests caution in using CrCl as the sole laboratory parameter to indirectly evaluate residual circulating DOAC.

Stroke/thromboembolism and intracranial hemorrhage in a real-world atrial fibrillation population: the Complications of Atrial Fibrillation in the Bologna Area (CAFBO) study.

BACKGROUND: Ischemic events (IEs) and intracranial hemorrhages (ICHs) are feared complications of atrial fibrillation (AF) and of antithrombotic treatment in patients with these conditions. METHODS: Patients with AF admitted to the EDs of the Bologna, Italy, area with acute IE or ICH were prospectively recorded over 6 months. RESULTS: A total of 178 patients (60 male patients; median age: 85 years) presented with acute IE. Antithrombotic therapy was as follows: (1) vitamin K antagonists (VKAs) in 31 patients (17.4%), with international normalized ratio (INR) at admission of < 2.0 in 16 patients, 2.0 to 3.0 in 13 patients, and > 3.0 in two patients; (2) aspirin (acetylsalicylic acid) (ASA) in 107 patients (60.1%); and (3) no treatment in 40 patients (22.5%), mainly because AF was not diagnosed. Twenty patients (eight male patients; median age: 82 years) presented with acute ICH: 13 (65%) received VKAs (INR, 2.0-3.0 in 11 patients and > 3.0 in two patients), while six (30%) received ASA. Most IEs (88%) and ICHs (95%) occurred in patients aged > 70 years. A modeling analysis of patients aged > 70 years was used to estimate annual incidence in subjects anticoagulated with VKAs in our Network of Anticoagulation Centers (NACs), or those expected to have AF but not included in NACs. The expected incidence of IE was 12.0%/y (95% CI, 10.7-13.3) in non-NACs and 0.57%/y (95% CI, 0.42-0.76) in NACs (absolute risk reduction [ARR], 11.4%/y; relative risk reduction [RRR], 95%; P < .0001). The incidence of ICH was 0.63%/y (95% CI, 0.34-1.04) and 0.30%/y (95% CI, 0.19-0.44), respectively (ARR, 0.33%/y; RRR, 52.4%/y; P = .04). CONCLUSIONS: IEs occurred mainly in elderly patients who received ASA or no treatment. One-half of patients with IEs receiving anticoagulant treatment had subtherapeutic INRs. Therapeutic approaches to elderly subjects with AF require an effective anticoagulant treatment strategy.

Role of atrial fibrillation after transcatheter closure of patent foramen ovale in patients with or without cryptogenic stroke.

BACKGROUND: Atrial fibrillation (AF) after transcatheter closure of patent foramen ovale (PFO) is not a rare complication. However little is known about the effect of atrial septal device implantation on the occurrence of this arrhythmia. OBJECTIVE: The aim of this study was to evaluate the occurrence of AF in two groups of patients who underwent transcatheter PFO closure: those with a previous cryptogenic stroke and those with other index events respectively. MATERIALS AND METHODS: Patient population included 276 patients with documented PFO who underwent percutaneous closure at our institution. Patients were grouped on the basis of two distinct clinical presentations: a) 246 patients with history of previous cryptogenic cerebrovascular ischemic event (CIE) or b) 30 patients with other different index events. AF after PFO closure was detected by 12-lead electrocardiography or by 24-h-Holter monitoring. RESULTS: During a mean follow-up of 17 months, new-onset AF was documented in 10 patients (4%), all included in the group with a previous cryptogenic CIE, at a mean of 1.6 months post-procedure. Comparing patients with and without AF, age (mean 56 years vs 46 years, p = 0.012) and left atrial size (4.4 cm vs 3.7 cm, p = 0.001) resulted to differ significantly. The type and size of occluder devices do not seem to impact the occurrence of AF after PFO closure. CONCLUSION: In patients presenting with cryptogenic stroke, especially in those with slightly enlarged left atria and age above 50­55 years, detection of a PFO should prompt an extended monitoring for excluding AF.

Spontaneous large right-to-left shunt and migraine headache with aura are risk factors for recurrent stroke in patients with a patent foramen ovale.

BACKGROUND: We sought to determine whether migraine headache with aura (MHA) and spontaneous large right-to-left (R-L) shunt are risk factors for recurrent cerebral ischemic events in cryptogenic stroke patients with a patent foramen ovale (PFO). METHODS: 140 patients with a PFO and cryptogenic stroke underwent transcatheter defect closure at our institution at a mean age of 45+/-13 years. We retrospectively analyzed follow-up data from the first cerebral ischemic event to the time of PFO closure. Before the procedure, all patients underwent transesophageal echocardiography (TEE); Transcranial Doppler scanning (TCD) was additionally performed on the last 59 patients. We analyzed the impact of MHA, thrombophilia, spontaneous large R-L shunt, and atrial septal aneurysm (ASA) on the risk of recurrent cerebral ischemic events. RESULTS: 44 patients (31%) had had at least 1 recurrent event during a follow-up of 2.2+/-2.6 years. Patients with recurrent events were more commonly females (p=0.0001), had more often an associated thrombophilia (p=0.0077), and had a higher prevalence of spontaneously large R-L shunt both at TEE and at TCD (p<0.05). They also had more commonly a history of MHA (p=0.0009) and more frequent episodes of MHA (p=0.0048). Patients with MHA had a higher risk of recurrent events when compared to patients without (odds ratio 3.87, 95% CI 1.75 to 8.50). Thrombophilia (p=0.001) and spontaneous large R-L shunt (p=0.02) were independent predictors of recurrent stroke. CONCLUSIONS: In cryptogenic stroke patients with a PFO, a history of MHA, large spontaneous large R-L shunt, and thrombophilia are all associated with a higher risk of recurrent events.

Transcatheter patent foramen ovale closure using the Premere PFO occlusion system.

OBJECTIVES: To evaluate the safety and efficacy profile of the new Premere patent foramen ovale (PFO) occlusion system. BACKGROUND: Several different devices have been used so far for transcatheter PFO closure but no data has been published so far on the efficacy and safety of the Premere PFO occlusion system. METHODS: Since September 2005, 15 patients (seven males, eight females; mean age 51.2 +/- 10.8 years) at our institution underwent transcatheter PFO closure because of cryptogenic stroke, using the Premere PFO occlusion system. The procedure was performed under fluoroscopic and transesophageal echocardiographic (TEE) guidance in all patients. Seven patients (47%) had an associated atrial septal aneurysm and two patients had had >1 stroke. Five patients (33%) had an associated thrombophilia, whereas three patients (20%) had a diagnosis of migraine headache with aura, by the referring neurologist. Residual shunt was assessed immediately after and 1 month (only in 11 patients) after the procedure by both transcranial Doppler and TEE. RESULTS: Premere PFO devices could be implanted in all patients (20 mm size in seven patients, 25 mm size in eight). Fluoroscopy time was 7.3 +/- 1.9 and procedural time was 11 +/- 3 min (range 7-17 min), reflecting our initial learning curve with this device. No complication occurred during the procedure or at follow-up. A residual shunt was noted immediately after the procedure in eight patients (53%) and at 1 month in 4/11 patients (36%). Residual shunt was mild in all patients. After a median follow-up of 4.2 months (0.2-5.8 months), no patient had a recurrent stroke. All patients with migraine headache with aura had resolution of symptoms. CONCLUSIONS: Our preliminary experience with the Premere PFO occlusion system shows that this device is safe and effective.

Long-term efficacy of transcatheter patent foramen ovale closure on migraine headache with aura and recurrent stroke.

OBJECTIVES: To assess the long-term results of transcatheter patent foramen ovale (PFO) closure on migraine headache with aura (MHA) and on the risk of recurrent stroke. BACKGROUND: Transcatheter PFO closure is associated with an early improvement of MHA, and a reduction or the risk of recurrent cerebral ischemia, but the long-term outcome after the procedure is unknown. METHODS: We analyzed follow-up data of 38 consecutive patients who had undergone transcatheter PFO closure at our institution because of cryptogenic stroke and had been followed-up for at least 3 years after the procedure. Mean age at closure was 43 +/- 13 years. Thirteen patients (34%) had a diagnosis of MHA made by the primary care physician or the referring neurologist. Migraine disability assessment questionnaire (MIDAS) was used to assess MHA incidence and severity. RESULTS: After a mean follow-up of 4.8 +/- 1.4 years, two patients had a recurrent stroke (13 and 15 months after the procedure, respectively). Recurrence rate 5 years after the procedure was 5.3%. After 4.9 +/- 1.4 years from the intervention, 12/13 patients (92%, 95% CI 65-99%) had complete resolution in their MHA. Overall, MIDAS score decreased significantly (38.6 +/- 26.3 vs. 4.4 +/- 5.1, P < 0.0001) after the procedure. One patient did not report any improvement of MHA after transcatheter PFO closure, whereas one patient reported a severe relapse of MHA about 1 year after PFO closure. Freedom from recurrent MHA 5 years after the procedure was 85% (95% CI 57-97%). CONCLUSIONS: The rate of recurrent cerebral ischemia and recurrent MHA seems to be low at long-term follow-up after transcatheter PFO closure. Recurrent cerebral ischemia and relapse of MHA seem to be confined to the first 15 months after the procedure.