Could advanced drug delivery systems be the future in cardiovascular revascularization medicine?

Acute myocardial infarction, stroke and pulmonary embolism required a prompt revascularization to restore the normal blood flow as soon as possible. Fibrinolytic treatment has gradually become both dated and underused in the treatment of acute myocardial infarction, after the wide diffusion of cathlab and percutaneous transluminal coronary angioplasty. Conversely, the use of systemic thrombolysis remained a benchmark in the treatment of both ischemic stroke and massive pulmonary embolism. In daily clinical practice, the use of thrombolytic agents is often limited by absolute and/or relative contraindications and possible adverse events after the drug administration, as intracranial and/or extracranial bleeding events. To minimize these problems, during the last years, the introduction of nanotechnology in the field of cardiovascular revascularization medicine has created several fascinating results. In the present article, we describe these recent findings and their possible implications in future clinical practice.

Connective tissue anomalies in patients with spontaneous cervical artery dissection.

OBJECTIVE: To investigate the prevalence of connective tissue abnormalities in patients with spontaneous cervical artery dissections (sCeAD). METHODS: We systematically assessed clinically detectable signs of connective tissue aberration in a series of consecutive patients with sCeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) by a standard examination protocol including 68 items, and performed extensive molecular investigation for hereditary connective tissue disorders in all patients with sCeAD. RESULTS: The study group included 84 patients with sCeAD (mean age, 44.5 ± 7.8 years; 66.7% men) and 84 patients with non-CeAD IS. None of the patients with sCeAD met clinical or molecular diagnostic criteria for established hereditary connective tissue disorder. Connective tissue abnormalities were detected more frequently in the group of patients with sCeAD than in the group of those with non-CeAD IS (mean number of pathologic findings, 4.5 ± 3.5 vs 1.9 ± 2.3; p < 0.001). Eighty-one patients (96.4%) in the sCeAD group had at least one detectable sign compared with 55 patients (66.7%) in the group with non-CeAD IS (p < 0.001). Skeletal, ocular, and skin abnormalities, as well as craniofacial dysmorphisms, were the clinical signs more strongly associated with sCeAD. Signs suggesting connective tissue abnormality were also more frequently represented in patients with sCeAD than in patients with traumatic CeAD (28.6%, p < 0.001; mean number of pathologic findings, 1.7 ± 3.7, p = 0.045). CONCLUSIONS: Connective tissue abnormalities are frequent in patients with sCeAD. This reinforces the hypothesis that systemic aberrations of the connective tissue might be implicated in the pathogenesis of the disease.

Review of West Nile virus epidemiology in Italy and report of a case of West Nile virus encephalitis.

West Nile virus (WNV) is a flavivirus that causes neurological disorders in less than 1 % of infected subjects. Human cases of WNV-associated fever and/or neurological disorders have been reported in Italy since 2008. The first outbreak occurred in the northeastern region of Italy surrounding the Po River and was caused by the Po River lineage 1 strain, and since then, WNV infections have been reported in several regions of central Italy. Although the virus is highly genetically conserved, stochastic mutations in its genome may lead to the emergence of new strains, as was observed in Italy in 2011 with the identification of two new lineage 1 strains, the WNV Piave and WNV Livenza strains. To help further define WNV epidemiology in Italy, we describe a case of an Italian man living in the Po River area who developed fatal encephalitis in 2009 due to infection with the WNV Piave strain. This finding supports the notion that the Piave strain has been circulating in this area of Italy for 2 years longer than was previously believed.

Improving migraine by means of primary transcatheter patent foramen ovale closure: long-term follow-up.

OBJECTIVE: We sought to assess the long-term faith of migraine in patients with high risk anatomic and functional characteristics predisposing to paradoxical embolism submitted to patent foramen ovale (PFO) transcatheter closure. METHODS: In a prospective single-center non randomized registry from January 2004 to January 2010 we enrolled 80 patients (58 female, mean age 42±2.7 years, 63 patients with aura) submitted to transcatheter PFO closure in our center. All patients fulfilled the following criteria: basal shunt and shower/curtain shunt pattern on transcranial Doppler and echocardiography, presence of interatrial septal aneurysm (ISA) and Eustachian valve, 3-4 class MIDAS score, coagulation abnormalities, medication-refractory migraine with or without aura. Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine before and after mechanical closure. High risk features for paradoxical embolism included all of the following. RESULTS: Percutaneous closure was successful in all cases (occlusion rate 91.2%), using a specifically anatomically-driven tailored strategy, with no peri-procedural or in-hospital complications; 70/80 of patients (87.5%) reported improved migraine symptomatology (mean MIDAS score decreased 33.4±6.7 to 10.6±9.8, p<0.03) whereas 12.5% reported no amelioration: none of the patients reported worsening of the previous migraine symptoms. Auras were definitively cured in 61/63 patients with migraine with aura (96.8%). CONCLUSIONS: Transcatheter PFO closure in a selected population of patients with severe migraine at high risk of paradoxical embolism resulted in a significant reduction in migraine over a long-term follow-up.

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.

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.

May migraine post-patent foramen ovale closure sustain the microembolic genesis of cortical spread depression?

BACKGROUND: Cortical spreading depression has been suggested to be the main substrate for migraine, but its pathobiology is not completely understood. Recently, the microembolic hypothesis as a promoting factor of cortical spreading depression has been demonstrated in an animal model. Our study is aimed to present a series of patients in whom early migraine attacks immediately after closure procedure predicted migraine with aura resolution on the long term, suggesting a role for microembolization in migraine genesis. METHODS: Our study consisted of 42 patients with migraine (36 female, mean age 35±6.7 years, mean Migraine Disability Assessment Score 29.9±9) and previous stroke who underwent transcatheter PFO closure during the last 2 years at the Rovigo General Hospital using different devices selected on the basis of specific anatomies. Procedural, technical, and clinical variables have been recorded and analyzed searching for potential relationships among postprocedural migraine, migraine improvement, and microembolization. RESULTS: Sixteen patients (38%) experienced a migraine attack of mean duration 3.5±2.4 h immediately (<60 min) after closure procedure. These patients more frequently had a severe migraine with aura and a permanent shunt on transcranial Doppler. There were no differences in terms of procedure time, occlusion time, and type of device used. After a mean follow-up of 32.2±10.6 months, only patients with postprocedural migraine attacks reported resolution of aura and a significant improvement in migraine symptoms. CONCLUSIONS: Our series seem to indirectly confirm in vivo the experimental animal data of microembolization-driven cortical spreading depression. It also confers the recent hypothesis about air microbubble-induced cerebral deoxygenation linking the micromebolic hypothesis with cortical spreading depression.

Premere occlusion system for transcatheter patent foramen ovale closure: mid-term results of a single-center registry.

BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) with rigid devices may be problematic in patients with long channel PFO: alternative devices with asymmetrical opening and more physiological positioning may be preferable in such cases. We present the mid-term results of transcatheter closure of PFO with Premere Occlusion System, a device studied for this specific anatomy, in a single-center registry of adults with previous cerebral ischemia. METHODS: During a 53-months period (July 1, 2005 to December 1, 2009) 70 patients (48 females and 22 males, mean age 38 ± 6.7 years) with previous stroke were admitted in our center for transcatheter closure of PFO with Premere Occlusion System on the basis of absence of moderate or severe atrial septal aneurysm (ASA) on Transesophageal echocardiography and intracardiac echocardiography (< 3RL or 3LR ASA and length of PFO channel >10 mm). RESULTS: The procedure was successful in all of the patients with no peri-operative and in-hospital complications. Forty-six 20 mm and twenty-four 25 mm Premere devices were implanted. Rates of procedural success, predischarge occlusion, and complication were: 100%, 95.7% and 0%, respectively. On mean follow-up of 40 ± 10.9 months (range 6-54), the follow-up occlusion rate was 98.5%. During follow-up, no cases of permanent atrial fibrillation, aortic/atrial erosion, device thrombosis, or atrioventricular valve inferences were noted. CONCLUSION: The mid-term outcomes of our registry suggests that the Premere Occlusion System may be an excellent device for patients with long-channel PFO and absence of moderate/severe ASA, offering a physiological and anatomically respective closure of PFO also in patients with hypertrophic rims.

Could genetic analysis be useful in reducing cerebrovascular risk in hypertensive subjects with hyperhomocysteinemia and patent foramen ovale? A 2-year follow-up study.

OBJECTIVES: Potential causes of cryptogenic cerebrovascular (CV) events are patent foramen ovale (PFO) and hyper homocysteinemia (H-Hcys), this latter a well-established risk factor for thrombosis particularly in the presence of mutation for the methylenetetrahydrofolate reductase (MTHFR) gene. This study investigated if in uncomplicated hypertensive subjects (HTs) with isolated PFO and H-Hcys, a different MTHFR polymorphism pattern for C667→T gene mutation could influence PFO management and to reduce the CV risk. METHODS: In thirty-two HTs aged 55.6±14.4years, PFO was diagnosed by echocardiography. MTHFR genotype was evaluated by a multiplex polymerase chain reaction with reverse line blot hybridization assay. In relation to the T allele distribution, HTs were divided in normal (CC), heterozygote (CT) and homozygote (TT) for the MTHFR genotype. All subjects received a supplementation of oral folate (5mg daily) and were evaluated yearly for 2years. Analysis of variance for repeated measures (ANOVA) was used to compare changes of Hcys at baseline and at the end of follow-up and differences between continuous variables were evaluated in the three MTHFR groups with the Tukey's post hoc test after adjustment for confounders. RESULTS: At the follow-up, Hcys levels significantly normalized from baseline both in TT (38.1±6.7 vs. 15±3.6, p<0.01) and CT (26.6±2.3 vs. 9.2±1.6, p<0.01) but not in CC subjects (18.2±1.8 vs. 16.0±1.6, NS). Independently of age, BMI, vitamin treatment both systolic and diastolic blood pressure (BP) significantly decrease at the follow-up in all the MTHFR genotypes. No CV events were observed during the follow-up. CONCLUSIONS: In HTs with isolated PFO and H-Hcys, oral folate supplementation reduces Hcys levels both in TT and CT subjects with C667→T mutation of MTHFR. In addition the BP normalization probably contributed to reduce CV risk in these genotypes.

Left atrial dysfunction in patients with patent foramen ovale and atrial septal aneurysm scheduled for transcatheter closure may play a role in aura genesis.

BACKGROUND: It has been suggested that a left atrial (LA) dysfunction induced by large shunt and large atrial septal aneurysm (ASA) may act as a concurrent mechanism of arterial embolism in patients with patent foramen ovale (PFO) and prior stroke. We aimed to evaluate the potential contribution of this mechanism as trigger of migraine in patients with PFO. METHODS: From January 2007 to September 2009, we prospectively enrolled subjects with migraine who underwent percutaneous PFO closure. Echocardiographic parameter of LA dysfunction was evaluated: pre- and postoperative values were compared to values of different sex and heart rate matched populations: 30 healthy patients, 21 migraine patients without PFO (MwoPFO), and a group of 25 PFO patients without migraine (PFOwoM). The Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine. RESULTS: Forty-five patients (38 females, mean age 38 +/- 6.7 years, mean MIDAS 35.8 +/- 4.7, and 28 patients with migraine with aura) fulfilled the inclusion criteria. After successful percutaneous closure (mean follow-up of 18.2 +/- 4.8 months), PFO closure remained complete in 95%; 35 of 45 patients reported resolution or amelioration of migraine (mean MIDAS score 12.3 +/- 8.8, P < 0.03). All patients with aura reported aura resolution. Preclosure values demonstrated significantly greater LA dysfunction, when compared with healthy and MwoPFO groups. Among patients in the study group, only patients with migraine with aura showed LA dysfunction comparable to PFOwoM patients. CONCLUSION: This study suggests that LA dysfunction probably does not contribute to migraine itself but may play a role in the genesis of aura symptoms.

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.

Transcatheter patent foramen ovale closure is effective in reducing migraine independently from specific interatrial septum anatomy and closure devices design.

BACKGROUND: Relationships between migraine improvement after transcatheter patent foramen ovale (PFO) closure and both specific interatrial septum anatomy and different devices design have not been investigated yet. We sought to assess effectiveness of transcatheter PFO closure in reducing or curing migraine with aura in patients with previous paradoxical embolism in relation with specific interatrial septum anatomy and different closure devices. METHODS AND RESULTS: We prospectively enrolled 34 patients (22 female and 12 male, mean age 40 + or - 3.7 years) who were referred to our centre over a 12-month period for PFO transcatheter closure and migraine with aura and previous paradoxical embolism. All procedures were performed using mechanical intracardiac echocardiographic guidance. Patients were assigned to Amplatzer PFO or ASD Multifenestrated Occluder and Premere Occlusion System implantation dependently from intracardiac echocardiography anatomical findings, which included short-channel with moderate atrial septal aneurysm (ASA) in 6 patients (17.6 %), long-channel with moderate ASA in 3 patients (8.8%), short-channel with huge ASA in 5 patients (14.7%), multifenestrated ASA in 4 patients (11.7%), long-channel PFO without ASA in 10 patients (29.4%), and long-channel PFO with mild ASA in 6 patients (17.6%). Accordingly, 18 patients received an Amplatzer Occluder (9 PFO Occluder and 7 ASD Multifenestrated Occluder), and 16 received a Premere Occlusion System. After a mean follow-up of 9.0 + or - 2.8 months, all patients improved their migraine symptoms (mean Migraine Disability Assessment Score 30 + or - 1.5 at baseline versus 6.0 + or - 2.9 in the follow up, P<.03) independently from specific interatrial septum anatomy and different closure devices. CONCLUSION: Although our study had several limitations, it suggests that independently from interatrial septum anatomy and device type, PFO closure in patients with migraine with aura resulted in a high rate of migraine improvement.

Left atrial dysfunction in patients with patent foramen ovale and atrial septal aneurysm: an alternative concurrent mechanism for arterial embolism?

OBJECTIVES: We postulate that, in patients with large patent foramen ovales (PFO) and atrial septal aneurysms (ASA), left atrial (LA) dysfunction simulating "atrial fibrillation (AF)-like" pathophysiology might represent an alternate mechanism in the promotion of arterial embolism. BACKGROUND: Despite prior reports concerning paradoxical embolism through a PFO, the magnitude of this phenomenon as a risk factor for stroke remains undefined, because deep venous thrombosis is infrequently detected in such patients. METHODS: To test our hypothesis, we prospectively enrolled 98 consecutive patients with previous stroke (mean age 37 +/- 12.5 years, 58 women) referred to our center for catheter-based PFO closure. Baseline values of LA passive and active emptying, LA conduit function, LA ejection fraction, and spontaneous echocontrast (SEC) in the LA and LA appendage were compared with those of 50 AF patients as well as a sex/age/cardiac risk-matched population of 70 healthy control subjects. RESULTS: Pre-closure PFO subjects demonstrated significantly greater reservoir function as well as passive and active emptying, with significantly reduced conduit function and LA ejection fraction, when compared with AF and control patients. Furthermore, in PFO patients, 66.3% (65 of 98) had moderate-to-severe ASA and basal shunt; SEC was observed in 52% of PFO plus ASA patients before closure. Multivariate stepwise logistic regression revealed moderate-to-severe ASA (odds ratio: 9.4, 95% confidence interval: 7.0 to 23.2, p < 0.001) as the most powerful predictor of LA dysfunction. After closure, all LA parameters normalized to the levels of control subjects: no SEC, device-related thrombosis, or aortic erosion were observed on follow-up echocardiography. CONCLUSIONS: This study suggests that moderate-to-severe ASA might be associated with LA dysfunction in patients with PFO. The resultant similarities to the pathophysiology of AF might represent an additional contributing mechanism for arterial embolism in such patients.

Embolic implications of combined risk factors in patients with patent foramen ovale (the CARPE criteria): consideration for primary prevention closure?

BACKGROUND: Large patent foramen ovale (PFO), spontaneous right-to-left shunt, large atrial septal aneurysm (ASA), coagulation abnormalities, and prominent eustachian valve (EV) have all been independently suggested as risk factors for recurrent stroke. We sought to retrospectively evaluate risk of stroke and impact of transcatheter PFO closure in patients with concurrent large PFO, spontaneous right-to-left shunt, large ASA, coagulation abnormalities, and prominent EV. METHODS: Between March 2006 and October 2008, 36 (mean age 44 +/- 10.9 years, 28 females) out of 120 consecutive patients referred to our center for transcatheter PFO closure had concomitant diagnosis of (a) large PFO on transcranial Doppler (TCD) and transesophageal echocardiography (TEE), (b) spontaneous right-to-left shunt on TCD, (c) large ASA, (d) prominent EV, and (e) coagulation abnormalities. All patients fulfilled the standard current indications for transcatheter closure and underwent preoperative TEE and brain magnetic resonance imaging (MRI), with subsequent intracardiac echocardiographic-guided transcatheter PFO closure. RESULTS: Compared to the remaining PFO population in the same period, patients with all five concomitant features had more ischemic brain lesions on MRI, previous history of recurrent stroke, more frequently a history of venous thromboembolism, and more severe migraine with aura. The concomitance of all the features confers the highest risk of recurrent stroke (OR 9.9, 3.0-18 [95% CI], P < 0.001). CONCLUSIONS: Despite its small sample size and nonrandomized retrospective nature, this is the first study to suggest that patients with concurrence of all the investigated characteristics have potentially a higher risk of stroke compared to controls. We thus propose the CARP criteria as a basis for further larger, longitudinal studies to assess the potential benefits of transcatheter closure in this patient subset in the absence of clinical recurrent stroke.

Migraine-patent foramen ovale connection: role of prominent eustachian valve and large Chiari network in migrainous patients.

BACKGROUND: We postulated that eustachian valve (EV) and Chiari network (CN) play a role in the pathophysiology of both migraine and paradoxical embolism. We sought to prospectively investigate the potential role of EV/CN in migraine-patent foramen ovale (PFO) connection assessing their prevalence by intracardiac echocardiography (ICE) in patients with migraine submitted to PFO transcatheter closure. METHODS: Over a 24-month period, we prospectively enrolled 50 consecutive patients (mean age 37+/-12.5 years, 38 females) with previous stroke and migraine referred to our centre for PFO catheter-based closure. Migraine with aura (MwA) and migraine without aura (MwoA) were diagnosed according to the International Headache Society criteria and Migraine Disability Assessment Score (MIDAS). Patients who met the inclusion criteria for closure underwent ICE study and closure attempt. RESULTS: After ICE study, a prominent EV or CN were diagnosed on ICE in 41 patients (82%): 100% in MwA patients, 60% in MwoA patients (p<0.001) and in 55.5% of patients with no migraine. Patients with EV and CN had more frequently a curtain pattern on TC Doppler, a larger right-to-left shunt, more recurrent cerebral paradoxical embolism before closure, and a higher preoperative MIDAS score. Patients with EV/CN had a larger decrease in MIDAS score after closure. CONCLUSIONS: This study suggests that EV and CN have a deep impact on MwA and paradoxical embolism pathophysiology: EV, CN, and MwA should be considered as adjunctive risk factors for paradoxical embolism in the work-up of both symptomatic and asymptomatic PFO patients.

Persistent venous valves correlate with increased shunt and multiple preceding cryptogenic embolic events in patients with patent foramen ovale: an intracardiac echocardiographic study.

BACKGROUND: It has been suggested that prominent Eustachian valve (EV) and Chiari's network (CN) predispose to paradoxical embolism but their presence in patients with presumed paradoxical stroke is not always easily detectable by transesophageal echocardiography (TEE). We sought to prospectively assess the frequency of EV/CN as assessed by intracardiac echocardiography (ICE) in patients submitted to patent foramen ovale (PFO) transcatheter closure in order to investigate their role in determining shunt severity and risk of multiple paradoxical embolisms. METHODS: Over a 36-month period, we prospectively enrolled 98 consecutive patients (mean age 37 +/- 12.5 years, 68 females) with previous stroke referred to our center for PFO catheter-based closure. All patients underwent transcranial Doppler ultrasound (TC-D), TEE and ICE-guided transcatheter closure. RESULTS: After ICE study and measurements, a prominent EV or CN were diagnosed on ICE in 72 patients (73.4%), whereas in 45 (45.9%, P < 0.01) on TEE. Patients with EV/CN had more frequently a curtain pattern on TC-D, a larger right-to-left shunt, and recurrent cerebral paradoxical embolisms before closure. EV/CN and medium-large shunt on TEE were the strongest predictors of recurrent paradoxical embolisms. CONCLUSIONS: This study suggests that EV and CN have a deep impact on the pathophysiology of paradoxical embolism: EV and CN should be considered as adjunctive risk factors for paradoxical embolism in the decision-making process involving PFO patients.

The association of different right atrium anatomical-functional characteristics correlates with the risk of paradoxical stroke: an intracardiac echocardiographic study.

BACKGROUND: The contribution of different right atrium anatomical-functional characteristics to the risk of paradoxical stroke has not been extensively investigated, probably in part because of the limits of standard echocardiography. OBJECTIVE: We sought to assess, using intracardiac echocardiography (ICE), the right atrium anatomical-functional characteristics and their role in the pathophysiology of paradoxical embolism in a sample of patent foramen ovale (PFO) patients undergoing transcatheter PFO closure. METHODS: Over a 36-month period, we prospectively enrolled 114 consecutive patients (mean age 38+/- 10.5 years, 67 female) referred to our center for PFO catheter-based closure. On ICE study, all sensible characteristics other than PFO and mild ASA were recorded, including prominent EV or large CN, basal shunt without Valsalva maneuver, moderate to severe ASA, and multiperforated fossa ovalis. RESULTS: After TEE and ICE study and measurements, a prominent EV or CN was diagnosed on ICE in 73%, a basal shunt was present in 48%, a moderate to severe ASA in 47%, and a multiperforated FO in 24% of patients. A tight correlation between number of concurrent factors and proportion of patients with curtain pattern on TC Doppler, larger right-to-left shunt, recurrent cerebral paradoxical embolism before closure, and migraine with aura was clearly evident (r > or = 0.97). Basal shunt and concurrent > or = 3 anatomical functional right atrium characteristics resulted as independent predictors of recurrent paradoxical embolisms. CONCLUSIONS: Our data suggest that right atrium anatomical-functional characteristics other than PFO and mild ASA as assessed by ICE deeply affect the pathophysiology of paradoxical stroke.

Asymptomatic significant patent foramen ovale: giving patent foramen ovale management back to the cardiologist.

Percutaneous closure of patent foramen ovale (PFO) is still a much debated issue. Although many questions remain open, patients are finding out about PFO management and are beginning to ask for the most rapid and complete solution to their potential problems in spite of the warnings from the medical profession about off-label indications for transcatheter closure. As a result, asymptomatic patients with PFO are coming into medical offices to be assured about stroke risk or treated for any degree of migraine. The cardiologist should be the preferred interlocutor in asymptomatic significant PFO: he is competent in assessing the associated anatomical and functional risk factors, and he is the only specialist who can evaluate on the basis of the anatomo-functional picture the potential risk of paradoxical embolism and discuss with patients eventual off-label indications to closure.

Incidence of extracerebral paradoxical embolisms in patients with intracardiac shunts.

BACKGROUND: Although extracerebral embolism accounts for 5-10% of all paradoxical embolisms, it still remains a ghostlike entity in cardiovascular pathophysiology. The aim of this brief report was to analyze the profile of patients with paradoxical extracerebral embolism and intracardiac shunts, and the role of shunt closure on the recurrence of extracerebral paradoxical embolism (EPE) in a population of patients evaluated for patent foramen ovale (PFO)/atrial septal defect (ASD) transcatheter closure. METHODS: From July 2003 to December 2006, 150 patients (mean age 51.4+/-15.1 years, range13-78 years, M/F=49/101) were planned for transcatheter closure of PFO/ASD at our institutional program of Adult Congenital Heart Disease Management. Clinical history and medical records of all patients were reviewed searching for association of PFO/ASD, stroke, and presumptive EPE. RESULTS: Association of PFO with presumptive EPE was found in nine patients (6%, mean age 40.1+/-14 years, M/F=3/6). Five patients had ST-elevation myocardial infarction (mean value of troponin was 15.3+/-2.1 ng/ml), while four patients had inferior limb acute ischemia. In patients with coronary embolism, coronary angiography was performed immediately after chest pain onset revealing normal coronary artery and only a mild hypokinesia. In patients with peripheral acute ischemia, early (>4 h from symptoms onset) angiography demonstrated normal main peripheral vessel and an embolic closure of popliteal artery (one patient), distal tibial artery (two patients), or peroneal artery (one patient) that normalized with heparin therapy in a few hours except in one patient. Migraine with aura was present in seven of nine patients. Cerebral MRI revealed previous ischemic areas in four of nine patients. Coagulation disorders were detected in six of nine patients. Echocardiography demonstrated a large to medium PFO in seven patients and a cribrosus ASD in two patients. CONCLUSION: Although a large study is required to assess optimal diagnosis and clinical implications of EPE, the clinical profile emerging from our study may help to identify some easy criteria of diagnosis in order to improve diagnosis and decrease the recurrence of such probably underestimated manifestations of PFO/ASD.