Effect of Patent Foramen Ovale Closure After Stroke on Circulatory Biomarkers.

OBJECTIVE: To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers. METHODS: Consecutive patients with PFO-related stroke were prospectively enrolled and followed with serial sampling of cardiac atrial and venous blood pre- and post-PFO closure over time. Candidate biomarkers were identified by mass spectrometry in a discovery cohort first, and lead candidates were validated in an independent cohort. RESULTS: Patients with PFO-related stroke (n = 254) were recruited and followed up to 4 years (median 2.01; interquartile range 0.77-2.54). Metabolite profiling in the discovery cohort (n = 12) identified homocysteine as the most significantly decreased factor in intracardiac plasma after PFO closure (false discovery rate 0.001). This was confirmed in a validation cohort (n = 181), where intracardiac total homocysteine (tHcy) was immediately reduced in patients with complete closure, but not in those with residual shunting, suggesting association of PFO shunting with tHcy elevation (ß 0.115; 95% confidence interval [CI] 0.047-0.183; p = 0.001). tHcy reduction was more dramatic in left atrium than right (p < 0.001), suggesting clearance through pulmonary circulation. Long-term effect of PFO closure was also monitored and compared to medical treatment alone (n = 61). Complete PFO closure resulted in long-term tHcy reduction in peripheral blood, whereas medical therapy alone showed no effect (ß -0.208; 95% CI -0.375∼-0.058; p = 0.007). Residual shunting was again independently associated with persistently elevated tHcy (ß 0.184; 95% CI 0.051-0.316; p = 0.007). CONCLUSIONS: PFO shunting may contribute to circulatory tHcy elevation, which is renormalized by PFO closure. PFO is not just a door for clots, but may itself enhance clot formation and injure neurovasculature by clot-independent mechanisms. Biomarkers such as tHcy can potentially serve as cost-effective measures of residual shunting and neurovascular risk for PFO stroke.

Hypoxemia in COVID-19 patients: An hypothesis.

The current SARS-Cov-2 virus pandemic challenges critical care physicians and other caregivers to find effective treatment for desperately ill patients - especially those with sudden and extreme hypoxemia. Unlike patients with other forms of Acute Respiratory Distress Syndrome, these patients do not exhibit increased lung stiffness or dramatic dyspnea., even in the presence of arterial blood oxygen levels lower than that seen normally in mixed venous blood. Urgent intubation and mechanical ventilation with high inflation pressures and raised inhaled oxygen concentration have proved unhelpful or worse, but why? Our Hypothesis is that sudden opening of a previously undetected probe-patent foramen ovale (PPFO) may explain this mystery. As hypoxemia without acidosis is a rather weak stimulus of dyspnea or increased ventilation, and opening of such an intracardiac shunt would not worsen lung mechanical properties, the absence of dramatic symptom changes would not be surprising. We point out the high frequency of PFO both in life and at autopsy, and the physiological evidence of large shunt fractions found in Covid-19 patients. Published evidence of hypercoagulability and abundant evidence of pulmonary emboli found at autopsy are in accord with our hypothesis, as they would contribute to raised pressure in the pulmonary arteries and right heart chambers, potentially causing a shunt to open. We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein. Search for an open PFO after a large drop in arterial oxygen saturation can be performed at the bedside with a variety of well-established techniques including bedside echocardiography, nitrogen washout test, and imaging studies. Potential treatments might include balloon or patch closure of the shunt, and various drug treatments to lower pulmonary vascular resistance.

Correlations between serum homocysteine levels and RoPE score in patients with patent foramen ovale.

The pathophysiological relationship between elevated serum homocysteine (Hcy) levels and patent foramen ovale (PFO) has not yet been completely clarified. In the present study, we assess the correlation between serum homocysteine levels and the RoPE score in PFO patients. We retrospectively reviewed clinical and instrumental data of 244 subjects referred to a single tertiary center for PFO evaluation and/or treatment between January 2010 and January 2018,stratified as closure and control group, respectively. Patients in the closure group had an higher serum Hcy levels compared to the control group (28.5 ± 8.5 vs 10.2 ± 6.6 µg/dL, p < 0.0001). A significant direct correlation was observed between serum Hcy levels and the RoPE Score in the entire population. A positive significant correlation continued to exist also in the closure and control groups (r = 0.472, p < 0.0001 and r = 0.378, p < 0.0001, respectively). A receiver operating characteristics curve identified the optimal cutoff value of homocysteinemia as a predictor of RoPE score > 7 in the closure group (AUC 0.90, 95% CI 0.81-0.94, p < 0.0001) when 19.5 µg/dL. Multivariate logistic regression analysis demonstrated that an Hcy serum level ≥ 19.5 µg/dL predict an RoPE score > 7 (OR 3.21, 95% CI 2.82-3.26, p < 0.0001) in closed patients independently from the presence of permanent right-to-left (RLS) (OR 2.28, 95% CI 2.01-2.43, p = 0.001) and atrial septal aneurysm (ASA) (OR 3.04, 95% CI 2.64-3.51, p < 0.0001). Serum homocysteine levels in PFO patients are positively correlated with the RoPE score. Moreover, a homocysteinemia ≥ 19.5 µg/dL predicts an RoPE score > 7 independently from the presence of a permanent RLS and a concomitant ASA.

Pityriasis Rosea during Pregnancy: Major and Minor Alarming Signs.

BACKGROUND: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with human herpesvirus (HHV)-6 and/or HHV-7 reactivation. In pregnant women, PR may be associated with pregnancy complications. OBJECTIVE: To determine relevant risk factors in the development of negative pregnancy outcome in PR. METHODS: Between 2005 and 2017 at the Department of Dermatology, University of Genoa, we recruited 76 women who developed PR during pregnancy. In 60 patients without known risk factors for intrauterine fetal death (30 with pregnancy complications and 30 without) we analyzed the pregnancy week of PR onset, presence of enanthem and of constitutional symptoms, PR body surface area involvement, age, and in 50 patients (20 with pregnancy complications and 30 without), the viral load of HHV-6 and HHV-7 (copies/mL). RESULTS: In logistic regression analysis, early onset of PR (p = 0.0017) and enanthem (p = 0.0392) proved to be significantly associated with pregnancy complications. HHV-6 viral load (copies/mL) (p < 0.0001), constitutional symptoms (p < 0.001), and PR body surface area involvement (p < 0.004) were also significantly associated with pregnancy complications. CONCLUSION: The onset of PR before week 15 and enanthem may be considered major risk factors that should alarm the dermatologist. Constitutional symptoms and involvement of > 50% of the body area may be considered minor risk factors.

Multiple Cerebral Infarctions Due to Patent Foramen Ovale in a Patient with Eosinophilic Granulomatosis with Polyangiitis.

A 51-year-old man was diagnosed with eosinophilic granulomatosis with polyangiitis 6 years ago due to asthma, sinusitis, hypereosinophilia, and peripheral neuropathy based on the diagnostic criteria of American College of Rheumatology, and corticosteroid therapy achieved a remission. One year ago, he was hospitalized due to deep venous thrombosis (DVT) and pulmonary embolism, and rivaroxaban was administrated. He was admitted to our hospital for acute onset of diplopia and right hemiparesis. Peripheral blood examinations disclosed leukocytosis with hypereosinophilia. Perinuclear anti-neutrophil cytoplasmic antibodies were positive. Diffusion-weighted imaging showed multiple fresh ischemic lesions. Chronic ischemic lesions were seen in subcortical cerebral region. No stenosis or occlusion was shown in extracranial and intracranial arteries on magnetic resonance angiography. Ultrasonography of leg vein showed DVT. Right-to-left shunt through patent foramen ovale after Valsalva maneuver was seen on transesophageal echocardiography. Treatment with corticosteroid and cyclophosphamide alleviated clinical deterioration. Rivaroxaban was changed to warfarin. Diplopia and muscle strength of right limbs were improved. This is a first case of multiple cerebral infarction caused by paradoxical embolism due to patent foramen ovale with DVT based on hypercoagulable state of hypereosinophilia. Overall this case illustrates that eosinophilic granulomatosis with polyangiitis can be a risk factor for multiple cerebral infarction in the systemic phase and that transesophageal echocardiography and ultrasonography of leg vein should be conducted in stroke patient with eosinophilic granulomatosis with polyangiitis.

[Postural effect in patients with patent foramen ovale: evaluation of right-to-left shunt with transcranial Doppler and transthoracic echocardiography and correlation with arterial oxygen saturation]. / L'effetto della postura nei pazienti con forame ovale pervio: valutazione dello shunt destro-sinistro con Doppler transcranico ed ecocardiografia transtoracica e correlazione con la saturazione arteriosa di ossigeno.

BACKGROUND: Transcranial Doppler echocardiography and transthoracic echocardiography may detect with high accuracy right-to-left shunt (RLS) due to patent foramen ovale (PFO). However, a standardized diagnostic protocol has never been established. It has been suggested that standing or sitting positions may improve sensitivity of transcranial Doppler due to increased LRS in such positions. We aimed to test efficacy of the sitting position in addition to the supine position in the grading of RLS in patients with PFO. We have also evaluated whether an increase in RLS is associated with a fall in oxygen saturation (SaO2). METHODS: From September 2015 to February 2016, 70 consecutive patients with suspected PFO underwent transcranial Doppler echocardiography and transthoracic echocardiography with microbubble count and evaluation of SaO2. RESULTS: RLS due to PFO was diagnosed in 58 patients (82.9%). An increase in RLS grade in the sitting position was observed in 28 out of 58 patients (48.3%) (group 1), whereas no increase was detected in 30 patients (51.7%) (group 2). Among the clinical and echocardiographic variables considered, group 1 and group 2 differed only in the prevalence of atrial septal aneurysm (35.7 vs 3.3%, p=0.002). Postural changes were not associated with a fall in SaO2. CONCLUSIONS: RLS increases in about half of patients with PFO in the sitting position compared with the supine position, whereas no changes occur in SaO2.

Decompression illness with hypovolemic shock and neurological failure symptoms after two risky dives: a case report.

Hypovolemia is known to be a predisposing factor of decompression illness (DCI) while diving. The typical clinically impressive neurological symptoms of DCI may distract from other symptoms such as an incipient hypovolemic shock. We report the case of a 61-year-old male Caucasian, who presented with an increasing central and peripheral neural failure syndrome and massive hypovolemia after two risky dives. Computed tomography (CT) scans of the chest and Magnetic resonance imaging scans of the head revealed multiple cerebral and pulmonary thromboembolisms. Transesophageal echocardiography showed a patent foramen ovale (PFO). Furthermore, the patient displayed hypotension as well as prerenal acute kidney injury with elevated levels of creatinine and reduced renal clearance, indicating a hypovolemic shock. Early hyperbaric oxygen (HBO) therapy reduced the neurological deficits. After volume expansion of 11 liters of electrolyte solution (1000 mL/h) the cardiopulmonary and renal function normalized. Hypovolemia increases the risk of DCI during diving and that of hypovolemic shock. Early HBO therapy and fluid replacement is crucial for a favorable outcome.

Relationship between mean platelet volume and ischemic stroke in patients with patent foramen ovale.

OBJECTIVE: Patent foramen ovale (PFO) is commonly encountered in patients with cryptogenic stroke. Mean platelet volume (MPV), an indicator of platelet reactivity, has been reported in recent trials to be higher in patients with PFO than in normal population. The aim of this study was to investigate whether there is a difference in MPV between patients with PFO and stroke or transient ischemic attack (TIA) and that of patients with asymptomatic PFO. METHODS: Patients with PFO who were younger than 55 years of age were enrolled in this retrospective study. Hemogram parameters of patients with ischemic stroke or TIA (symptomatic group) were obtained during hospitalization once they had stable clinical status. RESULTS: Total of 108 patients, 51 of whom were symptomatic, were included in the study. MPV was determined to be higher in symptomatic group compared with asymptomatic group (median 10.0 fl [25th-75th percentile: 9.0-11.0] vs median 8.56 fl [25th-75th percentile: 8.0-9.0], respectively; p<0.001,. Cut-off point of 9.0 fl for MPV had 70% sensitivity and 86% specificity in predicting symptomatic PFO patients. CONCLUSION: MPV is higher in symptomatic than in asymptomatic PFO patients. This finding may be a subsidiary risk factor to identify patients with PFO and high risk of cardioembolic stroke.

Antiplatelet effects of clopidogrel and aspirin after interventional patent foramen ovale/ atrium septum defect closure.

The optimal antiplatelet therapy after patent foramen ovale (PFO)/ atrium septum defect (ASD) closure is a matter of discussion. It is challenging as inter-individual responses to antiplatelet medication vary significantly and common complications are bleeding and ischemic events. In this study, we aimed to analyze the incidence of high on-treatment platelet reactivity (HTPR) to antiplatelet medication in patients undergoing PFO/ASD closure as well as clinical complications and thrombus formation on the occluder during six-month follow-up. This hypothesis generating pilot study was observed, which included 140 patients undergoing PFO/ASD closure. The primary endpoint was pharmacodynamic response to antiplatelet medication. A composite of death, myocardial infarction, bleeding, stroke and thrombus formation on the occluder during six-month follow-up was the secondary endpoint. HTPR to clopidogrel was analyzed using the vasodilator-stimulated protein phosphorylation (VASP), HTPR to aspirin by light-transmission aggregometry (LTA). In 71% of patients HTPR to clopidogrel was detected, HTPR to aspirin in only 4%. We observed 12 complications, 9 bleeding events (including 3 major bleeding events) and 3 transient ischemic attacks. No stroke and no thrombus formation on the occluder occurred. The primary endpoint was not associated with the secondary endpoint. The incidence of HTPR to clopidogrel in PFO/ASD closure patients is very high. Despite this high incidence, no stroke or thrombus formation on the occluder occurred at all. This leads to the hypothesis, that the benefit of additional clopidogrel medication is questionable and has to be investigated in large-scale clinical trials.

D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale.

Patent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648-17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

Effect of body position and oxygen tension on foramen ovale recruitment.

While there is an increased prevalence of stroke at altitude in individuals who are considered to be low risk for thrombotic events, it is uncertain how venous thrombi reach the brain. The patent foramen ovale (PFO) is a recruitable intracardiac shunt between the right and left atrium. We aimed to determine whether body position and oxygen tension affect blood flow through the PFO in healthy adults. We hypothesized that hypoxia and body positions that promote right atrial filling would independently recruit the PFO. Subjects with a PFO (n = 11) performed 11 trials, combining four different fractions of inhaled oxygen (FiO2) (1.0, 0.21, 0.15, and 0.10) and three positions (upright, supine, and 45° head down), with the exception of FiO2 = 0.10, while 45° head down. After 5 min in each position, breathing the prescribed oxygen tension, saline bubbles were injected into an antecubital vein and a four-chamber echocardiogram was obtained to evaluate PFO recruitment. We observed a high incidence of PFO recruitment in all conditions, with increased recruitment in response to severe hypoxia and some contribution of body position at moderate levels of hypoxia. We suspect that increased pulmonary vascular pressure, secondary to hypoxia-induced pulmonary vasoconstriction, increased right atrial pressure enough to recruit the PFO. Additionally, we hypothesize that the minor increase in breathing resistance that was added by the mouthpiece, used during experimental trials, affected intrathoracic pressure and venous return sufficiently to recruit the PFO.

Decline in mean platelet volume in patients with patent foramen ovale undergoing percutaneous closure.

INTRODUCTION: The presence of patent foramen ovale (PFO) is considered a possible cause for cryptogenic stroke. The mechanism underlying the ischaemic neurological events in the presence of PFO has not been firmly established. The purpose of this study was to compare: (1) the mean platelet volume levels in PFO patients with and without a cryptogenic stroke, and (2) pre- and post-procedural mean platelet volumes (MPV) in patients undergoing percutaneous PFO closure. METHODS: Sixteen PFO patients undergoing percutaneous closure to prevent recurrent ischaemic events and 15 asymptomatic patients with PFO were enrolled in the study. Mean platelet volume was compared between patients with and without a history of stroke. We also compared pre- and post-procedural MPV levels in patients undergoing percutaneous PFO closure. RESULTS: Mean platelet volume, which is a marker for platelet activity, was similar in PFO patients with and without stroke (9.34 ± 1.64 vs 9.1 ± 1.34 fl; p = 0.526). Interestingly, MPV decreased significantly after percutaneous closure compared to pre-procedural levels (9.34 ± 1.64 vs 8.3 ± 1.12 fl; p = 0.001). CONCLUSION: Our findings suggest interatrial communication through a PFO may be related to increased MPV and increased platelet activity.

Mean platelet volume, an indicator of platelet reactivity, is increased in patients with patent foramen ovale.

Numerous studies have shown an association between patent foramen ovale (PFO) and cryptogenic stroke suggesting that paradoxical emboli may be an important cause of stroke. In addition, some authors have proposed that platelet activation is present in PFO patients and this might be the cause of the stroke. The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation and/or reactivity in patients with PFO. The study group consisted of 77 patients with PFO. An age, sex, BMI-matched control group was composed of 43 healthy volunteers. We measured serum MPV values in patients and controls. MPV was significantly higher among PFO patients when compared with control group (9.0±0.8 vs. 8.3±0.9 fl, respectively; P<0.001). We have shown that MPV was significantly elevated in patients with PFO compared with controls.

Heart-brain signaling in patent foramen ovale-related stroke: differential plasma proteomic expression patterns revealed with a 2-pass liquid chromatography-tandem mass spectrometry discovery workflow.

Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the optimal treatment for this multiorgan disease is unclear. Therefore, mapping the changes in systemic circulation of PFO-related stroke is crucial in understanding the pathophysiology to individualize the best clinical treatment for each patient. We initiated a study using a novel quantitative, 2-pass discovery workflow using high-resolution liquid chromatography-mass spectrometry/mass spectrometry coupled with label-free analysis to track protein expression in PFO patients before and after endovascular closure of the PFO. Using this approach, we were able to demonstrate quantitative differences in protein expression between both PFO-related and non-PFO-related ischemic stroke groups as well as before and after PFO closure. As an initial step in understanding the molecular landscape of PFO-related physiology, our methods have yielded biologically relevant information on the synergistic and functional redundancy of various cell-signaling molecules with respect to PFO circulatory physiology. The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute-phase response, LXR/RXR activation, and coagulation system. In particular, after PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke.

G1691A factor V and G20210A FII mutations, acute ischemic stroke of unknown cause, and patent foramen ovale.

BACKGROUND: Genetic polymorphisms of haemostatic factors such as G1691A factor V (FV Leiden) and G20210A prothrombin (FII) may be involved in the onset of patent foramen ovale (PFO)-related cerebral ischaemia. We assessed the possible association between such inherited thrombophilic alterations and right-to-left shunt in patients with stroke. METHODS: We investigated the presence of G20210A FII and FV Leiden mutations in 340 Caucasian patients consecutively evaluated by our Angiology Unit for stroke of unknown cause. PFO was assessed in all patients with Transcranial Doppler with intravenous injection of agitated saline. Stroke patients were divided into two groups: patients with PFO (n=136), and patients without PFO (n=204). As control group, we studied 272 subjects with early venous insufficiency. RESULTS: The prevalence of FII G20210A mutation was significantly higher in patients with PFO vs. controls (OR: 2.90; 95% CI: 1.19-7.07) and in patients without PFO vs. controls (OR: 2.88; 95% CI: 1.25-6.60) but was similar in patients with and without PFO (OR: 1.11; 95% CI: 0.51-2.44). The frequency of FV Leiden mutation was similar in the three groups. Across the population the presence of the FII G20210A mutation (OR: 2.97;95% CI: 1.32-6.69), a history of DVT (OR: 1.04; 95% CI: 1.02-1.06), and oestrogen-containing contraceptive therapy (OR: 1.14; 95% CI: 1.09-1.18) were all associated with stroke of unknown cause after adjustment for other risk factors, This was not the case with PFO. CONCLUSIONS: Our data do not support the assumption that these inherited thrombophilic alterations are associated with PFO in patients with cryptogenic stroke. FII G20210A mutation may be associated with cryptogenic stroke irrespective of the presence of PFO.

Double-edged sword in the heart: trapped deep venous thrombus in a patent foramen ovale.

Trapped thrombus in a patent foramen ovale is a rare condition. Echocardiography is the main tool for diagnosis and for determination of the treatment to choose. There are a number of treatment options for trapped deep venous thrombus in a patent foramen ovale, including surgical thrombectomy, thrombolytics, and anticoagulant therapy. All patients should be evaluated individually, because the systemic and pulmonary thromboembolism risk of all treatment options is like a 'double-edged sword'. Here, we report a case of a patient with trapped thrombus in the patent foramen ovale detected by echocardiography, and successfully treated with surgical thrombectomy under extracorporeal circulation.

Patent foramen ovale-obstructive sleep apnea relationships: pro and cons.

Patent foramen ovale (PFO) has a prevalence of 25%-27% in the general population [1] and it has been suggested to be the mediator for a wide variety of syndromes based on the paradoxical embolism. The obstructive sleep apnea syndrome (OSAS) is a common disorder in the middle-aged population. An echocardiographically visible PFO was detected in 27%-69% of patients with documented OSAS suggesting a relationship between PFO and OSAS, but the pathophysiology of this potential relationship is still unclear. It has been shown that obstructive apnea can induce right-to-left shunting (RLS) through PFO with two proposed mechanisms including a large swing in pleural pressure and pulmonary hypertension. Pulmonary artery hypertension and oxygen desaturation have been suggested to be caused by the concurrence of OSAS and PFO. Arguments against and in favour of this potential relationship are discussed in this brief review.

Percutaneous closure of atrial right-to-left shunt in patients with Ebstein's anomaly of the tricuspid valve.

AIMS: Patients with Ebstein's anomaly of the tricuspid valve may have right-to-left shunt at atrial level resulting in hypoxaemia, high haematocrit and hyperviscosity syndrome. The purpose of this study was to assess the results of percutaneous closure of atrial right-to-left shunt in patients with Ebstein's anomaly. METHODS AND RESULTS: Records of patients treated between January 2002 and June 2010 were reviewed. Their condition before and after shunt closure (clinical data, oxygen saturation and haematocrit) were studied. During this period nine selected patients with Ebstein's anomaly and right-to-left shunt at atrial level were treated. Ages ranged from six to 67 years; seven were male. Mean pulmonary artery pressures were under 25 mmHg in all. Three patients had previous episodes of stroke and three had very high haematocrit, two of whom required therapeutic phlebotomies. Test occlusion of the shunt was performed in all patients with a balloon catheter, revealing an increase in systemic oxygen saturation, with right atrial pressures remaining <18 mmHg in all. Percutaneous closure of atrial shunt was achieved in all. There were no major complications. Arterial oxygen saturations increased in all patients from 85.0 ± 4.5% to 96.7 ± 1.5% (mean ± standard deviation). Medium follow-up was five years. The three patients with very high haematocrit levels had a decrease in its values from 62.9 ± 2.8% to 45.5 ± 3.9% after device occlusion. Both therapeutic phlebotomy programs were discontinued. All patients reported a marked improvement in effort tolerance. CONCLUSIONS: Percutaneous closure of atrial right-to-left shunt in selected patients with Ebstein's anomaly offers significant improvement, abolishing hypoxaemia and hyperviscosity and preventing paradoxical embolisation.

Provoked exercise desaturation in patent foramen ovale and impact of percutaneous closure.

OBJECTIVES: This study was designed to assess the prevalence of provoked exercise desaturation (PED) in patients with patent foramen ovale (PFO) referred for cardiovascular evaluation and to evaluate the impact of PFO closure. BACKGROUND: Platypnea orthodeoxia syndrome is a rare, mechanistically obscure consequence of PFO that results in oxygen desaturation during postural changes. In our clinical experience, however, it is far less common than desaturation during exercise. METHODS: This was a single-center prospective study of 50 patients with newly diagnosed PFO. Each patient underwent standardized assessment for arterial oxygen saturation with pulse oximetry during postural changes and stair climbing exercise. Provoked exercise desaturation was defined as a desaturation of at least 8% from baseline to <90%. All patients who underwent closure were reevaluated 3 months after the procedure. Those with baseline PED were similarly reassessed for desaturation at follow-up. RESULTS: Mean age of the cohort was 46 ± 17 years, 74% were female, 30% had migraines, and 48% had experienced a cerebrovascular event. Seventeen patients (34%) demonstrated PED. Provoked exercise desaturation patients seemed demographically similar to non-PED patients. Ten PED patients underwent PFO closure (2 surgical, and 8 percutaneous). Drop in oxygen saturation was improved by an average of 10.1 ± 4.2% after closure (p < 0.001), and New York Heart Association functional class improved by a median of 1.5 classes (interquartile range: 0.75 to 2.00, p = 0.008). CONCLUSIONS: One-third of patients referred for assessment of PFO experience oxygen desaturation during stair exercise. Closure of PFO seems to ameliorate this phenomenon and improve functional status.