Paradoxical Events Research Articles

Circulating inflammatory biomarkers can predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome

To identify inflammatory biomarker profiles during paradoxical and unmasking tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS), and determine whether differences in biomarkers prior to antiretroviral therapy (ART) predict subsequent development of TB-IRIS. Case-control study within a cohort of patients initiating ART in South Africa (n = 498). Participants were followed up for 24 weeks for development of TB-IRIS. Plasma samples were collected at baseline and presentation with symptoms. Groups of cases and controls were as follows: pre-ART TB and developed paradoxical TB-IRIS (n = 9); pre-ART TB but no IRIS (n = 12); no pre-ART TB but developed unmasking TB-IRIS (n = 13); no pre-ART TB and no TB or IRIS during treatment (n = 12). Concentrations of 18 cytokines and chemokines, and C-reactive protein (CRP), were measured and compared. Event samples were drawn a median of 28 days after ART initiation [interquartile range (IQR) 14-56 days]. During paradoxical TB-IRIS events, there were lower median concentrations of interleukin-10 [IL-10; 22.1 (IQR 15.3-34.9) vs. 82.2 (29.4-128.4) pg/ml, P = 0.047] and monocyte chemotactic protein-1 [MCP-1; 27.6 (20.0-29.7) vs. 71.4 (40.6-77.8) pg/ml, P = 0.005], and higher CRP: IL-10 ratio [2.2 × 10³ (1.8-3.4) vs. 0.3 × 10³ (0.2-0.5), P = 0.003] than in controls. Patients who developed unmasking TB-IRIS had higher median pre-ART levels of CRP [25 (8-47) vs. 6 (lower limit of detection, LLD-12) mg/l, P = 0.046] and interferon gamma (IFN-γ) [9.1 (4.4-24.7) vs. 0.9 (LLD-8.7) pg/ml, P = 0.032] than controls. Patients with unmasking TB-IRIS had higher pre-ART levels of plasma IFN-γ and CRP, consistent with preexisting subclinical TB. Paradoxical TB-IRIS was associated with lower levels of biomarkers of monocyte and regulatory T-cell activity, and higher CRP.

PFO and paradoxical embolism producing events other than stroke

A patent foramen ovale (PFO) is a risk factor for cerebral events such as cryptogenic stroke, transient ischemic attacks, and migraine headaches. Far less commonly, PFO is associated with non-cerebral, paradoxical systemic embolic events such as myocardial infarction (MI), renal infarct, and limb ischemia. This report details the incidence of systemic paradoxical emboli at our institution. 416 patients were referred for evaluation of PFO related conditions from 2001 to 2009. Clinical history and medical records of the patients were reviewed for incidence of cryptogenic stroke, transient ischemic attack (TIA), migraine headache, arterial desaturation, and noncerebral systemic embolism. As the primary presenting symptom, 219 patients had a diagnosis of cryptogenic stroke, 38 patients had migraine headaches, and 80 patients had transient neurologic deficits consistent with a TIA or complex headache. Twelve patients (2.9% of the total population) presented with a presumptive diagnosis of systemic embolism. Eight of these patients had acute MI diagnosed by elevated cardiac biomarkers, electrocardiogram changes, and/or imaging evidence of a left ventricular wall motion abnormality, without evidence of obstructive coronary disease on angiography. Four patients had evidence of peripheral embolism to a systemic artery, including the popliteal artery, ophthalmic artery, and brachial artery. PFO closure was performed in 197 patients (47.4% of the total population), including eight patients in the systemic embolism group. All closure procedures were successful. Although most paradoxical emboli travel to the brain, noncerebral paradoxical embolism is also associated with PFO. In addition to embolism of thrombus, there may be paradoxical passage of vasoactive chemicals that induce intense coronary spasm and myocardial infarction. Diagnosis is often challenging, given the lack of definitive criteria and the need to exclude other potential etiologies.

Skin Manifestations Induced by TNF-Alpha Inhibitors in Juvenile Idiopathic Arthritis

The tumor necrosis factor alpha (TNFα) inhibitors have been used with good clinical results in the treatment of juvenile idiopathic arthritis (JIA). Anti TNFα therapy is generally well tolerated. Besides the site injection reactions, other various cutaneous manifestations have been encountered as adverse events. Here, we report four young patients receiving treatment with anti-TNFα (infliximab, adalimumab, and etanercept) for JIA developing different skin manifestations more than 1year after the initiation of therapy. They underwent a dermatological exam. All four patients were ACR-Ped 30 responders to anti-TNF drugs. The first patient developed cutaneous vasculitis, the second one had lichen planus manifestations, while the third and the fourth developed psoriatic palmoplantar pustulosis accompanied by plaque-type psoriasis localized to the scalp. None of the patients had a personal or family history of dermatological diseases. In the first two patients, skin lesions healed with topical treatment after the discontinuation of anti-TNF agent, while psoriatic lesions did not resolve despite discontinuation of the drug and dermatological treatment. TNF inhibition can be both anti-inflammatory and pro-inflammatory. Cutaneous manifestations could be considered as a paradoxical adverse event of the anti-TNF-alpha treatment not only in rheumatoid arthritis but also in juvenile idiopathic arthritis.

Multiple paradoxical adverse events in a patient affected with ankylosing spondylitis treated with TNF blockers

ejd.2010.1235 Auteur(s) : Alessandro LO NIGRO1 alessandro.lonigro@sanita.padova.it, Roberta RAMONDA1, Mauro ALAIBAC2, Valentina MODESTI1, Leonardo PUNZI1 1 Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy 2 Dermatology Unit, Department of Medical and Surgical Sciences, University of Padova, Italy TNF blockers represent a milestone in the treatment of inflammatory joint diseases, including ankylosing spondylitis (AS). Some [...]

The clinical pattern, prevalence, and factors associated with immune reconstitution inflammatory syndrome in Ugandan children

To determine clinical pattern, prevalence, and factors associated with pediatric immune reconstitution inflammatory syndrome (IRIS) in Uganda. A prospective, multicenter cross-sectional study. We enrolled HIV-infected children receiving antiretroviral therapy (ART) between 0.5 and 6 months duration from December 2006 to October 2007 at three pediatric clinics in Uganda. Children were evaluated for IRIS at a one-time study visit by a standardized pediatric case definition. The IRIS prevalence was 38% [95% confidence interval (CI) 31-46] among 162 children (57% female) with a median age of 6 years (interquartile range 2.5-11 years). Of the IRIS events, 77% were unmasking of a new opportunistic infection and 23% were probable paradoxical IRIS events toward prior opportunistic infections. The majority of IRIS events (55%) occurred in the first month of ART. The clinical events were diverse, with tuberculosis-IRIS (29%) being the most frequent presentation. Independent risk factors for IRIS were pre-ART CD4(+) cell percentage below 15% (odds ratio = 3.1, 95% CI 1.2-8.4, P = 0.027), current CD8(+) cell absolute count below 1000 cells/microl (odds ratio = 4.3, 95% CI 1.8-10.4, P = 0.001), male sex (odds ratio = 2.6, 95% CI 1.06-8.4, P = 0.01), and a cough of more than 1 week duration at the current clinic visit (odds ratio = 4.3, 95% CI 1.7-10.7, P = 0.002). A more than 25 CD4(+) T-cells increase at current study visit from the pre-ART baseline was associated with IRIS by univariate (P = 0.005) but not multivariate analysis. IRIS events commonly occur early after ART initiation in children with advanced immunosuppression, as commonly seen in resource-limited areas. Both healthcare providers and caregivers of the children need awareness of IRIS to minimize ART nonadherence.

Defining Immune Reconstitution Inflammatory Syndrome: Evaluation of Expert Opinion versus 2 Case Definitions in a South African Cohort

There is no validated case definition for human immunodeficiency virus-associated immune reconstitution inflammatory syndrome (IRIS). We measured the level of agreement of 2 published case definitions (hereafter referred to as CD1 and CD2) with expert opinion in a prospective cohort of patients who were starting antiretroviral therapy in South Africa. A total of 498 adult patients were monitored for the first 6 months of antiretroviral therapy. All new or worsening clinical events were reviewed by 2 investigators and classified on the basis of expert opinion, CD1, and CD2. Events were categorized according to whether they were paradoxical or unmasking in presentation. We measured positive, negative, and chance-corrected agreement (kappa) with expert opinion for CD1 and CD2, and reviewed areas of disagreement. A total of 620 clinical events were recorded, of which, on the basis of expert opinion, 144 (23.2%) were defined as probable IRIS and 112 (18.1%) were defined as possible IRIS. Of the 144 probable IRIS events, 93 (64.6%) were unmasking in presentation, 99 (68.8%) were associated with dermatological or orogenital disease, and 45 (31.3%) were associated with tuberculosis or major opportunistic infections. Of the 620 clinical events recorded, 41 (6.6%) were classified as IRIS on the basis of CD1, and 156 (25.2%) were classified as IRIS on the basis of CD2. Positive agreement between CD1 and expert opinion was low for both unmasking (17.2%; kappa = 0.24) and paradoxical events (37.3%; kappa = 0.43), mainly because 1 major criterion requires IRIS to be atypical and either an opportunistic infection or a tumor, although negative agreement was >98%. In contrast, CD2 had good positive agreement (>75% for most event types), with a kappa value of 0.75 for paradoxical and 0.62 for unmasking. CD2 agreed well with expert opinion, with additional clinical events, such as arthropathy and inflammatory dermatoses, being classified as IRIS and added to CD2. We propose revised case definitions for both paradoxical and unmasking IRIS.

Illusory shadow person causing paradoxical gaze deviations during temporal lobe seizures

Generally, activation of the frontal eye field during seizures can cause versive (forced) gaze deviation, while non-versive head deviation is hypothesised to result from ictal neglect after inactivation of the...

W1181 Long-Term Efficacy and Safety of Maintenance Infliximab for the Treatment of Moderate-to-Severe Pediatric Crohn's Disease: Results from the Reach Study

Background: Infliximab, a chimeric anti-tumour necrosis factor alpha antibody, is now an established therapy for both Crohn disease (CD) and psoriasis. Among patients treated for CD, however, the paradoxical development of new-onset psoriasis has been reported in up to 15% of adult patients. We reviewed the prevalence of psoriasis developing in pediatric CD patients during infliximabmaintenance therapy, and examined the role of polymorphisms in the interleukin 23-receptor (IL-23R) gene, known to contribute to CD and psoriasis susceptibility. Methods: The medical records of all CD patients with documented skin abnormalities following the instigation of infliximab, at our center, were reviewed. DNA from patients developing psoriasis following infliximab was compared with that of diseasematched controls to examine the association of Il-23R polymorphisms with this paradoxical event. Results: 118 children received infliximab from January 2000 to August 2008. Thirteen children (11%), (9 males), developed new onset psoriasis following infliximab therapy. Persistent luminal disease despite conventional therapy (n=10) and perianal disease (n=3) were the indications for initiation of infliximab. The median duration of infliximab exposure at the time of psoriasis onset was 1.0 year (IQR 0.6 2.1). The median age at diagnosis of psoriasis or psoriasiform lesions was 14.7 years (IQR 14.2 15.2). 11 of 13 responded well to topical steroid therapy. 2 patients discontinued infliximab, both with resolution of their psoriasis. DNA was available on 8 of the 13 patients who developed psoriasis, 137 diseasematched controls and 86 ulcerative colitis (UC) patients. 75% of cases were homozygous for the Il-23R rs10489629 single nucleotide polymorphism (SNP) compared with 42% of CD controls and 28% of UC controls, with an allele frequency of 88%, 65% and 53% for cases, CD controls and UC controls respectively. The odds ratio for an infliximab-exposed patient developing psoriasis was 3.8 for heterozygotes and 14 for homozygotes (p=0.07). Conclusion: The frequency of new-onset psoriasis in this pediatric cohort of CD patients treated with infliximab mirrors that reported in adult series. Most patients respond well to topical therapy and in the majority of cases, anti-TNF therapy can be continued. We found a trend towards association of this adverse event with a variation in the Il-23R gene. However, the true significance of this variation warrants further investigation in large, adequately powered, studies.

W1178 Clinical Efficacy and Safety of Mesalamine Suppositories in the Treatment of Pediatric Patients with Ulcerative Proctitis: A Multicenter, Open-Label Study

Background: Infliximab, a chimeric anti-tumour necrosis factor alpha antibody, is now an established therapy for both Crohn disease (CD) and psoriasis. Among patients treated for CD, however, the paradoxical development of new-onset psoriasis has been reported in up to 15% of adult patients. We reviewed the prevalence of psoriasis developing in pediatric CD patients during infliximabmaintenance therapy, and examined the role of polymorphisms in the interleukin 23-receptor (IL-23R) gene, known to contribute to CD and psoriasis susceptibility. Methods: The medical records of all CD patients with documented skin abnormalities following the instigation of infliximab, at our center, were reviewed. DNA from patients developing psoriasis following infliximab was compared with that of diseasematched controls to examine the association of Il-23R polymorphisms with this paradoxical event. Results: 118 children received infliximab from January 2000 to August 2008. Thirteen children (11%), (9 males), developed new onset psoriasis following infliximab therapy. Persistent luminal disease despite conventional therapy (n=10) and perianal disease (n=3) were the indications for initiation of infliximab. The median duration of infliximab exposure at the time of psoriasis onset was 1.0 year (IQR 0.6 2.1). The median age at diagnosis of psoriasis or psoriasiform lesions was 14.7 years (IQR 14.2 15.2). 11 of 13 responded well to topical steroid therapy. 2 patients discontinued infliximab, both with resolution of their psoriasis. DNA was available on 8 of the 13 patients who developed psoriasis, 137 diseasematched controls and 86 ulcerative colitis (UC) patients. 75% of cases were homozygous for the Il-23R rs10489629 single nucleotide polymorphism (SNP) compared with 42% of CD controls and 28% of UC controls, with an allele frequency of 88%, 65% and 53% for cases, CD controls and UC controls respectively. The odds ratio for an infliximab-exposed patient developing psoriasis was 3.8 for heterozygotes and 14 for homozygotes (p=0.07). Conclusion: The frequency of new-onset psoriasis in this pediatric cohort of CD patients treated with infliximab mirrors that reported in adult series. Most patients respond well to topical therapy and in the majority of cases, anti-TNF therapy can be continued. We found a trend towards association of this adverse event with a variation in the Il-23R gene. However, the true significance of this variation warrants further investigation in large, adequately powered, studies.

W1177 Infliximab-Induced Psoriasis in Pediatric Crohn Disease; Experience of This Paradoxical Skin Manifestation At a Tertiary Centre and a Potential Association with a Variation in the IL-23r Gene

Background: Infliximab, a chimeric anti-tumour necrosis factor alpha antibody, is now an established therapy for both Crohn disease (CD) and psoriasis. Among patients treated for CD, however, the paradoxical development of new-onset psoriasis has been reported in up to 15% of adult patients. We reviewed the prevalence of psoriasis developing in pediatric CD patients during infliximabmaintenance therapy, and examined the role of polymorphisms in the interleukin 23-receptor (IL-23R) gene, known to contribute to CD and psoriasis susceptibility. Methods: The medical records of all CD patients with documented skin abnormalities following the instigation of infliximab, at our center, were reviewed. DNA from patients developing psoriasis following infliximab was compared with that of diseasematched controls to examine the association of Il-23R polymorphisms with this paradoxical event. Results: 118 children received infliximab from January 2000 to August 2008. Thirteen children (11%), (9 males), developed new onset psoriasis following infliximab therapy. Persistent luminal disease despite conventional therapy (n=10) and perianal disease (n=3) were the indications for initiation of infliximab. The median duration of infliximab exposure at the time of psoriasis onset was 1.0 year (IQR 0.6 2.1). The median age at diagnosis of psoriasis or psoriasiform lesions was 14.7 years (IQR 14.2 15.2). 11 of 13 responded well to topical steroid therapy. 2 patients discontinued infliximab, both with resolution of their psoriasis. DNA was available on 8 of the 13 patients who developed psoriasis, 137 diseasematched controls and 86 ulcerative colitis (UC) patients. 75% of cases were homozygous for the Il-23R rs10489629 single nucleotide polymorphism (SNP) compared with 42% of CD controls and 28% of UC controls, with an allele frequency of 88%, 65% and 53% for cases, CD controls and UC controls respectively. The odds ratio for an infliximab-exposed patient developing psoriasis was 3.8 for heterozygotes and 14 for homozygotes (p=0.07). Conclusion: The frequency of new-onset psoriasis in this pediatric cohort of CD patients treated with infliximab mirrors that reported in adult series. Most patients respond well to topical therapy and in the majority of cases, anti-TNF therapy can be continued. We found a trend towards association of this adverse event with a variation in the Il-23R gene. However, the true significance of this variation warrants further investigation in large, adequately powered, studies.

Paradoxical adverse events of anti-tumour necrosis factor therapy for spondyloarthropathies: a retrospective study

Several paradoxical adverse events (PAEs), e.g. IBDs, acute anterior uveitis (AAU) and psoriasis, have been described in patients taking anti-TNF drugs. This retrospective study aimed to describe the different PAEs that have occurred in a population of SpA patients treated with anti-TNF drugs, and to determine whether they are drug specific. Since 2000, we have followed 296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis, 12 Crohn's disease) and 77 psoriatic arthritis] treated with at least one anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated only with conventional DMARDs who served as controls. Considering the cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in exposed patients were calculated. Respective cumulative exposure times were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We observed the following PAEs: five psoriasis (three under infliximab and one with etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept) and four IBD (three under etanercept and one under infliximab). There was no significant association among any of these PAEs and a specific anti-TNF agent; nor significant difference in the overall PAEs among patients receiving anti-TNF drugs or controls (P = 0.303), the latter experiencing two psoriasis and three AAU. Undesirable side effects--IBD, AAU and psoriasis--may appear with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence supports any PAEs to be anti-TNF agent-specific in SpA.

Transesophageal echocardiography and transcranial color Doppler: independent or complementary diagnostic tests for cardiologists in the detection of patent foramen ovale?

Contrast-enhanced transesophageal echocardiography (c-TEE) is considered the gold standard for the diagnosis of patent foramen ovale. The purpose of this study was to compare the practical use of contrast-enhanced transcranial color Doppler (c-TCD) to define its role in the diagnostic pathway of patent foramen ovale. Two hundred and eighty-six consecutive patients with a presumed paradoxical cerebrovascular event were investigated by both c-TEE and c-TCD for the detection of patent foramen ovale. Considering c-TEE as the gold standard for statistical comparison, the sensitivity, specificity, positive predictive value, negative predictive value and global diagnostic accuracy of c-TCD were assessed. Among the entire cohort of patients (286), 156 (54%) showed positive and 116 (41%) negative findings with both the examinations; 10 patients (3%) had a negative result with c-TCD and a positive one with c-TEE; four (1%) had a positive result with c-TCD and a negative one with c-TEE. Thus, for c-TCD, we defined a sensitivity of 94% (95% confidence limits 90-98) and a specificity of 97% (94-100). The positive predictive value for the detection of the shunt was 98% (95% confidence limit 96-100) and the negative predictive value was 92% (95% confidence limit 87-97). Global diagnostic accuracy was 95% (95% confidence limit 92-98). The two examinations showed a strong statistical correlation (r = 0.90; R = 0.81; P < 0.001). c-TDC results in an effective, safe and low cost examination, with excellent sensitivity and specificity as compared with c-TEE.

Long-term outcome of transcatheter patent foramen ovale closure in patients with paradoxical embolism

Background Optimal management of patients with PFO and paradoxical embolic events is still debated. Moreover, data from long-term studies on large patient populations are lacking. Aim of the study is to assess immediate and long-term clinical outcome of patients with PFO and paradoxical thrombo-embolic events submitted to transcatheter PFO closure. Methods Only patients with PFO-related transient ischemic attack or stroke underwent PFO closure. Patients were evaluated clinically and echocardiographically at 1, 6 and 12 months after the procedure and yearly thereafter. Primary endpoints were death, recurrent stroke or TIA. Residual right-to left shunt (RLS) was monitored by transthoracic echocardiography (TTE) or transcranial Doppler (TCD) at 6 months'follow-up. Results 202 consecutive patients underwent percutaneous PFO closure for secondary prevention of TE. Device migration was observed in one patient 24 h after the procedure. No cases of procedure-related death or stroke occurred during a median follow-up of 3 ± 1.3 years. Three recurrent TIAs were observed within the first 6 months of follow-up. The cumulative estimated probability of recurrent TE-free survival rate after PFO closure was 99% in patients ≤ 55 years, 84% in patients > 55 years ( p < 0.05) and 94% and 100% in patients with PFO, with or without atrial septal aneurysm (ASA), respectively ( p < 0.05). Of the 188 (93%) patients submitted to TTE or TCD at 6 months' follow-up, 8 (4%) presented a small RLS. Conclusion Transcatheter PFO closure is associated with low incidence of in-hospital complications and low frequency of recurrent TE at long-term follow-up.

Efficacy of Cyclosporine in the Treatment of a Case of Infliximab-Induced Erythrodermic Psoriasis

A clinical case is described of infliximab-induced erythrodermic psoriasis resistant to conventional topical therapy and high-dose corticosteroids. Cyclosporine therapy for some months resolved the severe psoriasis picture. Pathogenetic mechanisms are considered through which anti-TNF agents could induce psoriasis. An activation of T lymphocytes with cutaneous overexpression of a CXCR3 subset and, mainly, an increase in IFN-alpha due to the blockage of TNF-alpha could be the causes for this paradoxical adverse event of biological agents. Cyclosporine can work in psoriasis induced by biological agents thanks to its peculiar suppressive activity on T lymphocytes and the concomitant specific action on keratocytes and angiogenesis.

Infliximab-induced psoriasis in pediatric Crohn Disease; Experience of this paradoxical event at a tertiary centre

Infliximab-induced psoriasis in pediatric Crohn Disease; Experience of this paradoxical event at a tertiary centre

Infliximab-induced psoriasis in pediatric Crohn Disease; Experience of this paradoxical event at a tertiary centre

Infliximab-induced psoriasis in pediatric Crohn Disease; Experience of this paradoxical event at a tertiary centre

Complications and mid-term outcome after percutaneous patent foramen ovale closure in patients with cryptogenic stroke.

Percutaneous patent foramen ovale (PFO) closure seems to reduce the risk of recurrent thromboembolism. We report the safety and efficacy of percutaneous PFO closure in our centre. All patients, >16 years of age, who underwent a percutaneous PFO closure in our centre were included. Reoccurrence of stroke, transient ischaemic attack (TIA) and peripheral thromboembolism were assessed. Periprocedural and midterm complications are reported. Eighty-three consecutive patients (mean age 49+/-13 years) were included. Indications for PFO closure were cryptogenic stroke (59.0%), TIA (33.7%), peripheral embolism (2.4%) and other (4.8%). For PFO closure, a Cardioseal/Starflex device was used in 63 patients and an Amplatzer PFO occluder device in 20 patients. Stroke recurred in 1.2%, TIA in 3.6%, peripheral embolism in 0% during a mean follow-up of 1.9+/-1.2 years. Major periprocedural complications occurred in 1.2%. The mid-term complication rate was 2.4% and only consisted of minor complications. During follow-up, a residual right-to-left shunt was present in 5.7% of the patients. No significant difference in outcome, complications or residual shunting could be documented between the two device types. In our centre, the percutaneous closure of a PFO seems to be a safe and effective procedure to prevent recurrence of paradoxical thrombo-embolic events. (Neth Heart J 2008;16:332-6.).

Swiss Cheese–Like Atrial Septal Defect

Atrial septal defects (ASDs), apart from the bicuspid aortic valve, are the most common congenital heart malformations, and it is not uncommon for them to go undiscovered until a patient reaches adulthood.1 An ostium secundum ASD is the most common septal defect, comprising 75% of all these defects.2 Elective closure should be considered in patients with signs of right heart dilatation and in those who have a presumed paradoxical event.3 In patients with an ostium secundum ASD, percutaneous closure–first reported in 19744—is now well established. Before a percutaneous closure attempt, the suitability of the defect for device implantation should be assessed with transesophageal echocardiography. Associated malformations (eg, partial anomalous pulmonary venous drainage) and the number, location(s), and the dimensions of the defect(s) should be known before the procedure. A defect in the atrial septum can exist when the flap valve derived from the septum primum does not overlap its rim (eg, because of atrial dilation) or because the flap …

Optimization of patent foramen ovale detection by contrast transthoracic echocardiography using second harmonic imaging

Patent foramen ovale is an anomaly responsible for paradoxical embolizations and cerebral ischemic events. Aims. - We want to show second harmonic transthoracic echography sensitized by contrast agent perfusion is as well as transesophageal echography to patent foramen ovale detection. Onene hundred twenty one patients referred for transesophageal echocardiography for patent foramen ovale detection, underwent additive second harmonic transthoracic echocardiography with one of three randomized contrast agents: a mixture A of dextrose and air, mixture B of dextrose and air and blood, or mixture C of hydroxyethylamidon. The severity of atrial shunting was evaluated on recordings by semi-quantitative scoring. Intensity of contrast was also assessed by objective quantitative videodensitometry. No difference was observed between the two techniques, nor between mixture A, B and C in terms of PFO detection during each exam. However, quantitative contrast analysis showed higher intensity with mixtures B and C with mixture A during transthoracic echography. When performed with a contrast agent, second harmonic transthoracic echography and transoesophageal echography are comparable when it comes to patent foramen ovale detection. Although the composition of the contrast agent does not appear to affect the rate of this detection, contrast quality in the right atrium during transthoracic exam is better with mixtures B and C than with mixture A.

Outcome after percutaneous closure of a patent foramen ovale using the Intrasept™ device

This multi-centre study reports safety and efficacy of percutaneous patent foramen ovale (PFO) closure, using the fourth generation Intrasept device. PFO has been associated with paradoxical embolism and cryptogenic stroke. Percutaneous PFO closure seems to reduce the risk for recurrent paradoxical thrombo-embolism. Currently, different devices are used for PFO closure. Patients, who underwent a PFO closure with the Intrasept device (Cardia, Eagan, MN) between July 2002 and September 2006, were included in the study. The primary endpoint was defined as reoccurrence of stroke, transient ischemic attack (TIA), or peripheral thrombo-embolism. Peri-procedural and mid-term complications were reported. Four-hundred thirty patients (mean age 50.7 +/- 13.0 years, 231 men) underwent closure. The indications were cryptogenic stroke (69.8%), TIA (23.5%), peripheral embolism (3.3%), and other (3.5%). The median follow-up time was 0.8 years, range 3.9 years. The primary endpoint occurred in 0.5% for stroke, in 2.5% for TIA, and in none for peripheral embolism. Peri-procedural complications were reported in 11.5% of cases, from which 0.2% was defined as major. No severe complications occurred during mid-term follow-up. A residual shunt was present in 12.5% of patients who did not suffer from a recurrent event, compared to 36.4% of patients who reached the primary endpoint (P = 0.04). This multi-centre study suggests that percutaneous closure of a symptomatic PFO with the fourth generation Intrasept device is safe and might be effective to prevent the recurrence of paradoxical thrombo-embolic events.