Patent Foramen Ovale as a Risk Factor for Cryptogenic Stroke

Tullio, Marco Di; Sacco, Ralph L.; Gopal, Aasha S.; Mohr, J. P.; Homma, Shunichi

doi:10.7326/0003-4819-117-6-461

Cited by 553 publications

(298 citation statements)

References 23 publications

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“…[1][2][3][4] The number of patients in each report, however, was small. In this study, with a significantly larger number of patients, we confirm that PFO is associated with cryptogenic stroke.…”

Section: Discussionmentioning

confidence: 99%

Effect of Medical Treatment in Stroke Patients With Patent Foramen Ovale

et al. 2002

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for the PFO in Cryptogenic Stroke Study (PICSS) Investigators* Background-Patent foramen ovale (PFO) is associated with stroke, but there are no randomized studies to evaluate the efficacy of antithrombotic therapies. Methods and Results-The PFO in Cryptogenic Stroke Study was a 42-center study that evaluated transesophageal echocardiographic findings in patients randomly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study. In this study, 630 stroke patients were enrolled, of whom 312 (49.5%) were randomized to warfarin and 318 (50.5%) to aspirin. Of these, 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes. End points were recurrent ischemic stroke or death. PFO was present in 203 patients (33.8%). There was no significant difference in the time to primary end points between those with and those without PFO in the overall population (Pϭ0.84; hazard ratio 0.96; 95% CI 0.62 to 1.48; 2-year event rates 14.8% versus 15.4%) or in the cryptogenic subset (Pϭ0.65; hazard ratio 1.17; 95% CI 0.60 to 2.37; 2-year event rates 14.3% versus 12.7%). There was no significant difference among those with no, small, or large PFO (Pϭ0.41 for small PFO and Pϭ0.16 for large PFO; 2-year event rates for no, small, and large PFO, 15.4%, 18.5%, and 9.5%, respectively). There was no significant difference between patients with isolated PFO and those with PFO in association with atrial septal aneurysm (Pϭ0.84; 2-year event rates 14.5% versus 15.9%). In patients with PFO, there was no significant difference in the time to primary end points between those treated with warfarin and those treated with aspirin (Pϭ0.49; hazard ratio 1.29; 95% CI 0.63 to 2.64; 2-year event rates 16.5% versus 13.2%). Conclusions-On

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Section: Discussionmentioning

confidence: 99%

Effect of Medical Treatment in Stroke Patients With Patent Foramen Ovale

et al. 2002

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“…The association between PFO and cryptogenic stroke has been described from observational clinical trials. 16,17 However, appropriate therapy for these patients is still undetermined. The rate of recurrent TIA and stroke in patients with cryptogenic stroke is estimated at 3.8% to 5.5% per year despite adequate anticoagulation or antiplatelet therapy.…”

Section: Discussionmentioning

confidence: 99%

Five-Year Experience With Percutaneous Closure of Patent Foramen Ovale

Slavin

Tobis

Rangarajan

et al. 2007

The American Journal of Cardiology

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Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke, arterial desaturation, decompression illness, and migraine headache (MH). This study evaluated the safety of percutaneous transcatheter PFO closure in patients with cryptogenic stroke, transient ischemic attack, or arterial desaturation. Additionally, symptomatic reduction in MH was determined after interatrial shunt closure. Of the 252 patients referred to the University of California, Los Angeles, with PFO, 131 underwent closure of the interatrial communication with a CardioSEAL (n ‫؍‬ 30) or Amplatzer (n ‫؍‬ 101) device. PFO morphology was evaluated with transesophageal echocardiography. Follow-up was conducted at 1 to 2 months with echocardiography, with clinical assessment annually thereafter. At an average follow-up of 30 months, there was no recurrence of any thromboembolic event (transient ischemic attack, stroke, or peripheral). There was a reduction in MH, defined as the complete resolution of headache or a >50% reduction in the number of headache days, in 85% of patients after PFO closure. Temporary problems after device implantation, including chest discomfort and palpitations, were reported in 23% of patients and occurred more frequently in patients with nickel hypersensitivity (p <0.05). In conclusion, transcatheter PFO closure is an effective and safe therapeutic modality in the prevention of thromboembolic events and MH associated with interatrial shunting in patients who present with cryptogenic stroke. Pending randomized, controlled trials are necessary to determine if this invasive approach is preferable to medical therapy for the prevention of recurrent stroke or as primary treatment for patients with MH.

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“…Microspheres were detected in the epicardium of the left ventricle in two of our exercising dogs, suggesting that recruitment of I-P shunts could play a role in embolic heart disease. In addition, previous work has shown that stroke patients have a higher prevalence of patent foramen ovale (38)(39)(40), and hereditary hemorrhagic telangiectasia patients are more susceptible to embolic stroke and neurologic symptoms (41), indicating that blood flow bypassing the pulmonary microcirculation may have important physiological relevance. Isolated lung work has shown that I-P arteriovenous shunts are up to 420 m in diameter in the dog (11), 390 m in the cat (9), and 200 m in the adult human (13).…”

Section: Shunt Consequencementioning

confidence: 99%

Exercise-induced Arteriovenous Intrapulmonary Shunting in Dogs

Stickland

Lovering²,

Eldridge³

2007

Am J Respir Crit Care Med

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Rationale:We have previously shown, using contrast echocardiography, that intrapulmonary arteriovenous pathways are inducible in healthy humans during exercise; however, this technique does not allow for determination of arteriovenous vessel size or shunt magnitude. Objectives: The purpose of this study was to determine whether large-diameter (more than 25 m) intrapulmonary arteriovenous pathways are present in the dog, and whether exercise recruits these conduits. Methods: Through the right forelimb, 10.8 million 25-m stable isotope-labeled microspheres (BioPAL, Inc., Worcester, MA) were injected either at rest (n ϭ 8) or during high-intensity exercise (6-8 mph, 10-15% grade, n ϭ 6). Systemic arterial blood was continuously sampled during and for 3 minutes after injection. After euthanasia, tissue samples were obtained from the heart, liver, kidney, and skeletal muscle. In addition, 25-and 50-m microspheres were infused into four isolated dog lungs that were ventilated and perfused at constant pressures similar to exercise. Measurements and Main Results: Blood and tissue samples were commercially analyzed for the presence of microspheres. No microspheres were detected in the arterial blood or tissue samples from resting dogs. In contrast, five of six exercising dogs showed evidence of exercise-induced intrapulmonary arteriovenous shunting, as microspheres were detected in arterial blood and/or tissue. Furthermore, shunt magnitude was calculated to be 1.4 ؎ 0.8% of cardiac output (n ϭ 3). Evidence of intrapulmonary arteriovenous anastomoses was also found in three of four isolated lungs. Conclusions: Consistent with previous human findings, these data demonstrate that intrapulmonary arteriovenous pathways are functional in the dog and are recruited with exercise.Keywords: intrapulmonary arteriovenous anastomoses; shunt; pulmonary gas exchange; pulmonary circulationThe classic understanding of the normal pulmonary circulation is that all the blood leaving the right ventricle passes through the pulmonary microcirculation via capillaries before returning to the left side of the heart through the pulmonary venous circulation. Studies using saline contrast echocardiography in humans have demonstrated that exercise results in the transpulmonary passage of contrast bubbles, suggesting that large-diameter intrapulmonary (I-P) arteriovenous pathways are recruited with exercise (1-3). These findings are controversial in that they are in contrast with prior research, using inert gas and/or inspired 100% Previous studies, using contrast echocardiography, suggest that intrapulmonary shunts are recruited during exercise in health. However, the size of the contrast is unknown, and thus arteriovenous diameter is undefined. What This Study Adds to the FieldLarge-diameter intrapulmonary arteriovenous shunts are functional in healthy animals, and exercise recruits these vessels.oxygen (4)(5)(6)(7)(8), that has failed to detect substantial right-to-left physiological I-P shunt during exercise.Despite an absence of right-to-left I-P...

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Patent Foramen Ovale as a Risk Factor for Cryptogenic Stroke

Cited by 553 publications

References 23 publications

Effect of Medical Treatment in Stroke Patients With Patent Foramen Ovale

Effect of Medical Treatment in Stroke Patients With Patent Foramen Ovale

Five-Year Experience With Percutaneous Closure of Patent Foramen Ovale

Exercise-induced Arteriovenous Intrapulmonary Shunting in Dogs

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