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Introduction Patent foramen ovale is a fairly common defect found in a quarter of the population. PFO has always been associated with an increased risk of stroke, the mechanism of which has been attributed to the paradoxical embolism of venous thrombi passing through the PFO directly into the left atrium, however this mechanism remains debated to date. For the detection of PFO, several modalities exist including transcranial doppler (TCD), transthoracic echocardiography (TTE) and transoesophageal echocardiography. This raises the question of the examination with the best diagnostic performance for its detection. Purpose The majority of studies comparing the different modalities of patient PFO diagnosis have been conducted in the context of stroke assessment. Very few studies have focused on the acute PE patient population. The interest of our study is therefore to evaluate the diagnostic performance of two modalities (TTE versus TCD) for the detection of shunts, especially since this population is at risk of stroke by paradoxical embolism due to the phenomenon of hyperpressure in the right heart chambers increasing the chances of having a paradoxical embolism. Methods We performed a post HOC analysis of the EPIC-FOP study which is a multicenter, prospective, French cohort study. Patients were recruited within 3 days of diagnosis of PE. Patients included were given a transthoracic echocardiography (TTE) with PFO screening by injection of saline contrast and magnetic resonance imaging (MRI) within 7 days of inclusion to look for signs of recent stroke. A proportion of the patients included in this study also received a transcranial doppler in search of PFO, the results of which were used in our study. Results The mean age of the patients was 62±14.66 years with a slight male predominance (55.6%). TCD was able to detect 97 right-left shunts while the TTE detected only 25 shunts. Concordance analysis by Cohen's Kappa Coefficient: 0.1767 [0.0427; 0.3107–p Using TTE as the reference examination, transcranial Doppler has a very good sensitivity 96.00% (79.65% to 99.90%) and a poor specificity 42.06% (33.33% to 51.18%). A good negative likelihood ratio 0.10 (0.01 to 0.66). Using TCD, incidence of stroke in the acute phase of PE was significantly higher in the PFO population. In the ten strokes detected 9 had occurred in patients with PFO, RR=1.43 IC95% (1.1169 to 1.8228) p=0. 0044. The difference in proportion is calculated to be 26.92%. Conclusion It is the first study that compared TCD vs TEE in the setting of acute phase of PE for detection of PFO. TCD showed a good sensitivity and negative likelihood ratio that can be used as a first means to rule out PFO or associated with TTE. Also, our analysis confirms the increased risk of stroke following a PE episode when a PFO is present. Funding Acknowledgement Type of funding source: None

BACKGROUND Up to 40% of ischaemic strokes are cryptogenic. A strong association between cryptogenic stroke and the prevalence of patent foramen ovale (PFO) suggests paradoxical embolism via PFO as a potential cause. Randomized trials failed to demonstrate superiority of PFO closure over medical therapy. METHODS AND RESULTS Randomized trials comparing percutaneous PFO closure against medical therapy or devices head-to-head published or presented by March 2013 were identified through a systematic search. We performed a network meta-analysis to determine the effectiveness and safety of PFO closure with different devices when compared with medical therapy. We included four randomized trials (2963 patients with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex (STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less likely to experience a stroke than patients allocated to medical therapy [rate ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when compared with medical therapy. The probability to be best in preventing strokes was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No significant differences were found for transient ischaemic attack and death. The risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95% CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI 0.33-4.50), when compared with medical therapy. CONCLUSIONS The effectiveness of PFO closure depends on the device used. PFO closure with AMP appears superior to medical therapy in preventing strokes in patients with cryptogenic embolism.

Aims We report our experience with three generations of the Cardia patent foramen ovale (PFO) occluder in patients with cryptogenic thrombo-embolic events (TE). Methods and results Between 1998 and 2004, interventional PFO closure was attempted in 403 patients. Prior to PFO closure, 605 TE occurred, translating into an annual incidence of 3.1%. PFO closure was successful in all patients. Peri-procedural complications occurred in eight patients (2.0%). At 6 months follow-up, residual shunt was present in 10.8% of patients. Transient thrombi developed on 10 devices (predominantly generation II) and asymptomatic wire fractures were detected in 14 cases (generation I and II). The annual incidence of recurrent TE was 2.0% ( n =13). Atrial septal aneurysm and prior device-related thrombus formation were identified as predictors of recurrent TE. Conclusion Owing to technical improvements and modified adjunctive pharmacotherapy, the rate of thrombus formation has declined and wire fractures are virtually absent in generation III devices. The overall rate of recurrent TE is reduced by transcatheter PFO closure with the Cardia PFO occluder, and seems comparable to recurrence rates reported for other devices used for this purpose.

Aims Interventional PFO closure has previously been reported to reduce the risk for recurrent thromboembolic events. The aim of the present study was to evaluate three different occluder systems in respect to (a) the safety and practicability and (b) the mid-term risk of recurrent thromboembolic events. Methods and results Since 08/98 until 12/02, 307 consecutive patients (138 women, 169 men, mean age 43 years) with a symptomatic PFO underwent PFO closure using the PFO-Star (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=177\) \end{document}), AmplatzerTM PFO occluder (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=69\) \end{document}) and CardioSeal/Starflex (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=61\) \end{document}). Implantation was successful in all patients. Periinterventional complications occurred in 9 patients (5× ST-segment elevations, 1× arteriovenous fistula, 2× TIA, 1× device dislodgement). All of them were reversible and not associated with a specific type of device. During the median follow-up of 24 months (25/75th percentiles: 14/37 months), the annual risk of recurrence was 0.6% for TIA, 0% for stroke and 0.2% for peripheral embolism (PFO-Star: 0.8%, AmplatzerTM PFO occluder: 0.7% and CardioSeal/Starflex: 1.0%). Conclusion Interventional PFO closure appears to be safe and a promising technique in symptomatic PFO patients with a low incidence of periinterventional complications and recurrent thromboembolic events using three different devices (PFO-Star, AmplatzerTM PFO occluder or the CardioSeal/Starflex).

A 30-year-old woman presented with sudden onset left flank pain 10 days following an uncomplicated delivery. She was normotensive with an electrocardiogram showing sinus-rhythm and pre-excitation ( Panel A ). Abdominal-computed tomography revealed a large wedge-shaped infarct in the left kidney ( Panel B , arrows). Lower-extremity doppler-imaging showed small bilateral deep-vein thromboses and anti-coagulation was initiated. Echocardiography suggested apical displacement of the …

Aims Percutaneous patent foramen ovale (PFO) closure for secondary stroke prevention is discussed controversially. Long-term data comparing different closure devices are limited. The objective is the prospective comparison of procedural complications and long-term results after PFO closure in patients with cryptogenic stroke randomized to three different closure devices. Methods and results Between January 2001 and December 2004, 660 patients with cryptogenic stroke were randomized to three different closure devices (Amplatzer, CardioSEAL-STARflex, and Helex occluder, 220 patients per group). The primary endpoint was defined as recurrent cerebral ischaemia [stroke, transient ischaemic attacks (TIA), or Amaurosis fugax], death from neurological cause, or any other paradoxical embolism within 5 years after the index procedure. Device implantation was technically successful in all interventions ( n = 660; 100%). The procedure was complicated by pericardial tamponade requiring surgery in one patient (Amplatzer group) and device embolization in three patients (all Helex group). Thrombus formation on the device was detected in 12 cases (11 CardioSEALSTARflex, 1 Helex, 0 Amplatzer; P < 0.0001), of which 2 required surgery. Complete closure after single device implantation was more common with the Amplatzer and with the CardioSEAL-STARflex than with the Helex occluder: Amplatzer vs. Helex vs. CardioSEAL-STARflex: n = 217 (98.6%) vs. n = 202 (91.8%) vs. n = 213 (96.8%; P = 0.0012). Within 5 years of follow-up, the primary endpoint occurred in 25 patients (3.8%; 10 TIAs, 12 strokes and 3 cases of cerebral death). Compared with the CardioSEAL-STARflex (6%; 6 TIAs, 6 strokes, 1 cerebral death) and Helex groups (4%; 4 TIAs, 4 stroke, 1 cerebral death), significantly fewer events ( P = 0.04) occurred in the Amplatzer group (1.4%; 2 strokes, 1 cerebral death). Conclusion Although procedural complications and long-term neurological event rates are low regardless of the device used, the recurrent neurological event rate was significantly lower after Amplatzer than after CardioSEAL-STARflex or Helex implantation. This has important implications regarding the interpretation of trials comparing PFO closure with medical management.

This 57-year-old male presented to the emergency department with presyncope and a right hemianopia 1 month after knee surgery. A computerized tomographic pulmonary angiogram confirmed extensive bilateral pulmonary emboli with a suspicion of a paradoxical embolus ( Panel A ). Transthoracic echocardiography revealed a moderately dilated right ventricle with mild systolic dysfunction, pulmonary …

Mortelmans et al. 1 report new onset of migraine with aura (MA+) and migraine without aura (MA−) following percutaneous closure of atrial septal defect (ASD). Sudden or immediate worsening of MA+ attacks following closure of ASD has also been noted.2,3 Because closure of ASD cannot possibly have any influence on brain neuronal function or cortical spreading depression, the widely favoured pathogenetic paradigm, or paradoxical embolism or paradoxical transfer of putative headache-provoking neurotransmitters, such aggravation of the tendency to develop migraine has important pathophysiological implications. De novo development of migraine or dramatic aggravation of migraine following atrial shunt closures indicates a substantial or definitive alteration of some physiological variable with a critical influence on the primary pathophysiological process in migraine. …

Purpose: Patent foramen ovale (PFO) is associated with paradoxical embolism and mortality in pulmonary embolism (PE). The aim of this study was to assess the prevalence of PFO comparing trans-thoracic echocardiography (TTE) and trans-oesophageal echocardiography (TOE) and its association with ischaemic stroke (as assessed by magnetic resonance imaging (MRI)) in patients hospitalized for PE. Methods and results: We prospectively enrolled 40 consecutive patients hospitalized in the cardiology department for intermediate early-mortality risk PE. Patients with recent history of stroke or contra-indication to TOE were excluded from this study. Local ethics approval was obtained for the study. Contrast TTE and TOE were performed within 5 days after admission. Mean time from admission to TOE was 3.4±1.2 days, whereas mean time to MRI was 14±5.8 days. On admission, mean systolic arterial pressure was 132±40 mmHg, mean troponine Ic was 0.4±1.7 ng/ml (normal reference value < 0.06 ng/ml) and mean BNP was 585±2200 pg/ml. PFO was found in 22.5% (n=9) and 52.5% (n=21) of our patients, respectively with TTE and TOE. Compared with TTE, TOE significantly improved the sensitivity of echocardiography in detecting PFO (p = 0.002). No significant difference on admission's characteristics was found between patients without PFO (PFO-; n=19) and patients with PFO (PFO+; n=21). On MRI evidence of recent ischaemic stroke was found in 7 PFO+ patients (33.3%), versus none in PFO- patients (p=0.004). In the sub-group of stroke patients (n=7), TOE was positive for PFO in all, whereas TTE failed to identify PFO in 3 of them (recognition of PFO, TOE vs TTE: 100 vs 57%, p=0.02). No complication of TOE occurred in our cohort (including GI-bleeding). Conclusion: PFO is frequent in patients hospitalized for intermediate risk-PE, and occurred in 52.5% of our patients. In our study, PFO is strongly associated with ischaemic stroke on MRI and recognition of PFO in patients with PE could help identifying patients with high-risk of stroke and potential bleeding complications.

Introduction: Acute Myocardial Infarction in young people can be challenging to manage, as the underlying pathology can be different to the conventional atherosclerosis with plaque rupture. Case Description: A 36-year old man presented with sudden onset central chest pain and diaphoresis. Apart from smoking he did not have other risk factors for coronary disease. One week prior he underwent elective hip replacement and had been treated with prophylactic clexane to prevent venous thromboembolism. He was on no other regular prescribed or recreational medication. The EKG showed changes consistent with an inferoposterior STEMI. Emergency angiography revealed an occluded left circumflex with heavy thrombus burden. Following prolific thrombus aspiration TIMI 3 flow was restored, the patient became pain-free and the EKG started to normalize. The circumflex artery appeared smooth with no evidence of plaque rupture. An embolic cause was suspected and given that the patient was pain-free he was managed medically with aspirin, clopidogrel, beta-blockers and ace inhibitors and planned to re-study him in 48 hours. Bilateral lower limb ultrasound and CT pulmonary angiography did not reveal deep vein thrombosis or pulmonary embolus. Transthoracic bubble echocardiography revealed right to left shunting on valsava manoevre consistent with a PFO, also visualized on 3D transesophageal echocardiography. At coronary angiography 48 hours later, the circumflex coronary remained smooth with no evidence of further obstruction thus no stent insertion was needed. Histology of the thrombus confirmed a platelet thrombus forming on a foreign plastic material that was likely part of an intravenous cannula. It is likely that the plastic entered the circumflex at the time of orthopedic surgery and acted as nidus for thrombus formation. He has since underwent successful percutaneous closure of his PFO. Discussion: Paradoxical coronary embolism is a rare but recognized clinical entity. It requires a high index of suspicion for diagnosis and should always be considered in young patients presenting with acute myocardial infarction and no obvious coronary lesion as its correct identification can guide appropriate management and preclude inappropriate stent implantation. Implications to clinical practice: 1. Always beware of paradoxical embolism in young patients presenting with a STEMI, particularly if coronary arteries appear smooth. 2. Always be meticulous when inserting intravenous cannulae. Avoid needle re-insertion as this increases the risk of the cannula breaking off and embolizing with adverse outcomes as exemplified in our case.

for prevention of paradoxical embolism is not only far from being the gold standar but also far from being evidence based medicine. Catheter closure of PFO is by definition effective in reducing the risk of paradoxical embolism where complete closure can be achieved, at least in the majority of the patients. Nonetheless, the risk of complications arising either through the procedure or from complications related to the device itself during follow-up may be higher than the spontaneous risk without any preventive treatment. If PFO closure could be achieved without risks, we would not have to discuss the clinical value of the procedure. As with medical treatment, we remain far from evidence based medicine. Currently, there are several trials planned or already in progress, comparing medical treatment and catheter closure. Because there is a general agreement that medical treatment is probably better than nothing, none of these trials are placebo controlled. Surgical closure has probably the same risk as surgical ASD closure (which means 0.5% mortality, 1‐2% stroke) and so is also not investigated. As enrolment in these trials is slower than expected, results will not be available within the next 5 years.

A 71-year-old woman with a recent onset of recurrent transient ischaemic attacks was referred for further diagnostic assessment. Stroke occurred each time shortly after performing a Valsalva manoeuvre. The patient mentioned a stable dyspnoea NYHA II, a mildly reduced exercise capacity, and no …

A 52-year-old woman presented at the emergency department with deep vein thrombosis and pulmonary embolism (PE). Transthoracic echocardiography revealed right ventricular dysfunction and disclosed an echogenic serpentine mass in all four heart …

A 45-year-old woman with previous apoplexia due to paradoxical embolism via atrial septal defect (ASD) received a 28 mm Amplatzer ASD occluder (AGA Medical Corp., USA). The device was explanted by surgery 15 months later when transoesophageal echocardiography documented that a small residual interatrial shunt post-intervention increased continuously. Macroscopic inspection of …

A 46-year-old adipose woman was admitted to hospital with tachycardia and progressive dyspnoea. The week before hospitalization she collapsed several times and two days before admission she experienced an intermittent motorical weakness of her right hand. Transthoracal echocardiography revealed decreased right ventricular (RV) function, RV dilatation, and signs of pulmonary hypertension with a pressure gradient of 43 mmHg across the tricuspid valve. A patent foramen ovale was found with a mobile continuous structure in both atria spanning through the foramen and prolapsing over both tricuspid and mitral valve in diastole (Movie …

Paradoxical embolism occurs following the passage of embolic material from the venous to the arterial circulation through a right to left shunt--frequently a patent foramen ovale. The diagnosis is usually presumptive when arterial emboli occur in the appropriate clinical setting. We describe a case of impending paradoxical embolism in a patient with massive pulmonary embolism. Transoesophageal echocardiography revealed a thromboembolus straddling a patent foramen ovale. The patient underwent emergency removal of the intracardiac clot with closure of the patent foramen ovale.

A patient with a three-year history of recurrent pulmonary embolism is presented. Thromboembolic pulmonary hypertension was proven in the final stage of disease in the presence of repeated episodes of systemic embolic events. Paradoxical embolism was assumed to be present on the basis of blood-gas analysis and contrast echocardiography that demonstrated a right-to-left shunt at atrial level. Autopsy revealed a patent foramen ovale and provided strong evidence for the accuracy of the clinical diagnosis.