Aktuelle Neurologie 2011; 38(2): 81-87
DOI: 10.1055/s-0030-1266089
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Persistierendes Foramen ovale, Reinfarktrisiko und Sekundärprophylaxe

Übersicht über die aktuelle EvidenzlagePatent Foramen Ovale, Risk of Stroke Recurrence and Secondary PreventionOutline of Current EvidenceR.  Feurer1 , H.  Poppert1
  • 1Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
Further Information

Publication History

Publication Date:
16 March 2011 (online)

Zusammenfassung

In der aktuellen Schlaganfallbehandlung bestehen nach wie vor erhebliche Unsicherheiten bezüglich der adäquaten sekundärprophylaktischen Behandlung bei Patienten mit einem PFO nach ischämischem Hirninfarkt. Die kontrovers geführte Diskussion gewinnt durch die Möglichkeit des perkutanen PFO-Verschlusses mit stark wachsenden Interventionsraten in den letzten Jahren weiter an Bedeutung. Als diagnostisches Verfahren geringer Invasivität und zufrieden stellender Sensitivität und Spezifität wurde 1991 erstmals die indirekte Darstellung eines RLS über eine transkranielle dopplersonografische Embolidetektion nach periphervenöser Kontrastmittelgabe beschrieben. Aktuelle bevölkerungsbezoge Studien mittels transkranieller Dopplersonografie und multivariater Analyse konnten den in kleinen Fallkontrollstudien vielfach beschriebenen Zusammenhang zwischen PFO und Hirninfarkt nicht bestätigen, sodass sich die Frage stellt, ob sich diese Assoziation durch „Confounding” erklären lässt, da Alter und Geschlecht in vorherigen Studien mit einer positiven Assoziation zwischen PFO und Hirninfarkt nicht berücksichtigt worden sind. Unabhängig von der weiterhin kontroversen Diskussion bezüglich der Kausalität des Zusammenhangs zwischen PFO und Hirninfarkt existieren mittlerweile Ergebnisse großer multizentrischer Studien, welche belegen, dass das PFO keinen unabhängiger Risikofaktor für das erneute Auftreten eines Hirninfarkts darstellt. Es zeigte sich zudem kein Einfluss von Shuntgröße oder begleitendem Vorhofseptumaneurysma auf das erneute Auftreten zerebrovaskulärer Ereignisse. Damit gibt es nach aktueller Studienlage keine Evidenzgrundlage für eine generelle Antikoagulation bei Patienten mit PFO nach (kryptogenem) Schlaganfall. Spätestens nach den Ergebnissen der Closure-1-Studie ist ein interventioneller Verschluss zur generellen Rezidivprophylaxe bei Patienten mit einem PFO von neurologischer Seite aus als nicht indiziert abzulehnen.

Abstract

In current treatment of stroke there are still substantial uncertainties about the appropriate secondary prevention for patients with patent foramen ovale (PFO) after first-ever ischaemic stroke. The contentious issue takes on greater significance by the possibility of interventional PFO closure with sharply growing numbers of interventions in the last few years. In the year 1991 the first implicit evidence of a right-to-left shunt via transcranial detection of emboli after i.v. contrast agent administration (c-TCD) was described and can be considered as a slightly invasive diagnostic tool with sufficient sensitivity and specificity. Currently conducted studies by means of c-TCD and multivariate analysis were not able to verify a causal relationship between PFO and stroke, which was often described in some small, mainly case-control, studies, and brought up the question if this statistical relationship has mainly been brought about by confounding, as age and gender of PFO patients have been disregarded in early studies. Notwithstanding the above, results of multicentric studies show that PFO is not associated with recurrent stroke. Furthermore, neither shunt volume nor concomitant atrial septal aneurysm have a significant impact on the recurrence of stroke. Therefore, there is no sustainable evidence for oral anticoagulation in patients with PFO. Furthermore, an interventional PFO closure should be rejected since the results of the closure I study.

Literatur

  • 1 Holmes Jr D R, Cabalka A. Was your mother right – do we always need to close the door?.  Circulation. 2002;  106 1034-1036
  • 2 Halperin J L, Fuster V. Patent foramen ovale and recurrent stroke: another paradoxical twist.  Circulation. 2002;  105 2580-2582
  • 3 Adams Jr H P. Patent foramen ovale: paradoxical embolism and paradoxical data.  Mayo Clin Proc. 2004;  79 15-20
  • 4 Mas J L. Specifics of patent foramen ovale.  Adv Neurol. 2003;  92 197-202
  • 5 Rodriguez C J, Homma S. Patent Foramen Ovale and Stroke.  Curr Treat Options Cardiovasc Med. 2003;  5 233-240
  • 6 Rosin L. Neurological aspects of patent foramen ovale: in search of the optimal treatment.  J Interv Cardiol. 2001;  14 197-201
  • 7 Meier B, Lock J E. Contemporary management of patent foramen ovale.  Circulation. 2003;  107 5-9
  • 8 Sacco R L, Adams R, Albers G et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association / American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.  Circulation. 2006;  113 e409-449
  • 9 Khositseth A, Cabalka A K, Sweeney J P et al. Transcatheter Amplatzer device closure of atrial septal defect and patent foramen ovale in patients with presumed paradoxical embolism.  Mayo Clin Proc. 2004;  79 35-41
  • 10 Tobis J. The case for closing PFOs.  Catheter Cardiovasc Interv. 2002;  55 195-196
  • 11 Onorato E, Melzi G, Casilli F et al. Patent foramen ovale with paradoxical embolism: mid-term results of transcatheter closure in 256 patients.  J Interv Cardiol. 2003;  16 43-50
  • 12 Krumsdorf U, Ostermayer S, Billinger K et al. Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1,000 consecutive patients.  J Am Coll Cardiol. 2004;  43 302-309
  • 13 Trepels T, Zeplin H, Sievert H et al. Cardiac perforation following transcatheter PFO closure.  Catheter Cardiovasc Interv. 2003;  58 111-113
  • 14 Krumsdorf U, Keppeler P, Horvath K et al. Catheter closure of atrial septal defects and patent foramen ovale in patients with an atrial septal aneurysm using different devices.  J Interv Cardiol. 2001;  14 49-55
  • 15 Sievert H, Horvath K, Zadan E et al. Patent foramen ovale closure in patients with transient ischemia attack / stroke.  J Interv Cardiol. 2001;  14 261-266
  • 16 Berdat P A, Chatterjee T, Pfammatter J P et al. Surgical management of complications after transcatheter closure of an atrial septal defect or patent foramen ovale.  J Thorac Cardiovasc Surg. 2000;  120 1034-1039
  • 17 Martin F, Sanchez P L, Doherty E et al. Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism.  Circulation. 2002;  106 1121-1126
  • 18 Cetta F, Arruda M J, Graham L C. Large left atrial thrombus formation despite warfarin therapy after device closure of a patent foramen ovale.  Catheter Cardiovasc Interv. 2003;  59 396-398
  • 19 Nkomo V T, Theuma P, Maniu C V et al. Patent foramen ovale transcatheter closure device thrombosis.  Mayo Clin Proc. 2001;  76 1057-1061
  • 20 Vanderheyden M, Willaert W, Claessens P et al. Thrombosis of a patent foramen ovale closure device: thrombolytic management.  Catheter Cardiovasc Interv. 2002;  56 522-526
  • 21 van Buuren F, Horstkotte D. 22. Bericht über die Leistungszahlen der Herzkatheterlabore in der Bundesrepublik Deutschland.  Der Kardiologe. 2008;  2 320-324
  • 22 Van Buuren F, Horstkotte D. 21st report about the statistis of the heart catheterization laboratory in the german federal republic. Results of the joint inquiry of the commission for clinical cardiology and of the working groups for interventional cardiology and angiology of the german society for cardiology and circulatory research in the year 2004.  Clin Res Cardiol. 2006;  95 383-387
  • 23 Van Buuren F, Horstkotte D. 24. Bericht über die Leistungszahlen der Herzkatheterlabore in der Bundesrepublik Deutschland.  Der Kardiologe. 2009;  3 512-518
  • 24 Kuehn C. De usu partium libri xvii.. 1907. 1 1907, 1902: 1909, Repr. 1968
  • 25 Hanley P C, Tajik A J, Hynes J K et al. Diagnosis and classification of atrial septal aneurysm by two-dimensional echocardiography: report of 80 consecutive cases.  J Am Coll Cardiol. 1985;  6 1370-1382
  • 26 Hagen P T, Scholz D G, Edwards W D. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts.  Mayo Clin Proc. 1984;  59 17-20
  • 27 Wright R R, Anson B J, Cleveland H C. The vestigial valves and the interatrial foramen of the adult human heart.  Anat Rec. 1948;  100 331-355
  • 28 Sweeney L J, Rosenquist G C. The normal anatomy of the atrial septum in the human heart.  Am Heart J. 1979;  98 194-199
  • 29 Parsons F G, Keith A. Seventh Report of the Committee of Collective Investigation of the Anatomical Society of Great Britain and Ireland, 1896–97.  J Anat Physiol. 1897;  32 164-186
  • 30 Fawcett E, Blachford J V. The Frequency of an Opening between the Right and Left Auricles at the Seat of the Foetal Foramen Ovale.  J Anal Physiol. 1900;  35 67-70
  • 31 Patten B. The closure of the foramen ovale.  Am J Anat. 1931;  48 19-44
  • 32 Fisher D C, Fisher E A, Budd J H et al. The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study.  Chest. 1995;  107 1504-1509
  • 33 Schroeckenstein R F, Wasenda G J, Edwards J E. Valvular competent patent foramen ovale in adults.  Minn Med. 1972;  55 11-13
  • 34 Meissner I, Whisnant J P, Khandheria B K et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study. Stroke Prevention: Assessment of Risk in a Community.  Mayo Clin Proc. 1999;  74 862-869
  • 35 Schneider B, Hanrath P, Vogel P et al. Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events.  J Am Coll Cardiol. 1990;  16 1000-1009
  • 36 Mugge A, Daniel W G, Angermann C et al. Atrial septal aneurysm in adult patients. A multicenter study using transthoracic and transesophageal echocardiography.  Circulation. 1995;  91 2785-2792
  • 37 Mas J L, Arquizan C, Lamy C et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both.  N Engl J Med. 2001;  345 1740-1746
  • 38 Marber M S, de Belder M A, Pumphrey C W et al. Transoesophageal echocardiography in the diagnosis of paradoxical embolism.  Int J Cardiol. 1992;  34 283-288
  • 39 Belkin R N, Pollack B D, Ruggiero M L et al. Comparison of transesophageal and transthoracic echocardiography with contrast and color flow Doppler in the detection of patent foramen ovale.  Am Heart J. 1994;  128 520-525
  • 40 Chen W J, Kuan P, Lien W P et al. Detection of patent foramen ovale by contrast transesophageal echocardiography.  Chest. 1992;  101 1515-1520
  • 41 Langholz D, Louie E K, Konstadt S N et al. Transesophageal echocardiographic demonstration of distinct mechanisms for right to left shunting across a patent foramen ovale in the absence of pulmonary hypertension.  J Am Coll Cardiol. 1991;  18 1112-1117
  • 42 Langenfeld M R, Forst T, Hohberg C et al. Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study.  Circulation. 2005;  111 2525-2531
  • 43 Ofili E O, Rich M W. Safety and usefulness of transesophageal echocardiography in persons aged greater than or equal to 70 years.  Am J Cardiol. 1990;  66 1279-1280
  • 44 Stoddard M F, Longaker R A. The safety of transesophageal echocardiography in the elderly.  American heart journal. 1993;  125 1358-1362
  • 45 Geibel A, Kasper W, Behroz A et al. Risk of transesophageal echocardiography in awake patients with cardiac diseases.  Am Heart J. 1988;  62 337-339
  • 46 Schuchlenz H W, Weihs W, Beitzke A et al. Transesophageal echocardiography for quantifying size of patent foramen ovale in patients with cryptogenic cerebrovascular events.  Stroke. 2002;  33 293-296
  • 47 Lamy C, Giannesini C, Zuber M et al. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: the PFO-ASA Study. Atrial Septal Aneurysm.  Stroke. 2002;  33 706-711
  • 48 Chimowitz M I, Nemec J J, Marwick T H et al. Transcranial Doppler ultrasound identifies patients with right-to-left cardiac or pulmonary shunts.  Neurology. 1991;  41 1902-1904
  • 49 Teague S M, Sharma M K. Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound.  Stroke. 1991;  22 740-745
  • 50 Karnik R, Stollberger C, Valentin A et al. Detection of patent foramen ovale by transcranial contrast Doppler ultrasound.  Am J Cardiol. 1992;  69 560-562
  • 51 Horner S, Ni X S, Weihs W et al. Simultaneous bilateral contrast transcranial doppler monitoring in patients with intracardiac and intrapulmonary shunts.  J Neurol Sci. 1997;  150 49-57
  • 52 Hamann G F, Schatzer-Klotz D, Frohlig G et al. Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale.  Neurology. 1998;  50 1423-1428
  • 53 Jauss M, Zanette E. Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography.  Cerebrovasc Dis. 2000;  10 490-496
  • 54 Belvis R, Leta R G, Marti-Fabregas J et al. Almost perfect concordance between simultaneous transcranial Doppler and transesophageal echocardiography in the quantification of right-to-left shunts.  J Neuroimaging. 2006;  16 133-138
  • 55 Klotzsch C, Janssen G, Berlit P. Transesophageal echocardiography and contrast-TCD in the detection of a patent foramen ovale: experiences with 111 patients.  Neurology. 1994;  44 1603-1606
  • 56 Zanette E M, Mancini G, De Castro S et al. Patent foramen ovale and transcranial Doppler. Comparison of different procedures.  Stroke. 1996;  27 2251-2255
  • 57 Di Tullio M, Sacco R L, Venketasubramanian N et al. Comparison of diagnostic techniques for the detection of a patent foramen ovale in stroke patients.  Stroke. 1993;  24 1020-1024
  • 58 Di Tullio M, Sacco R L, Massaro A et al. Transcranial Doppler with contrast injection for the detection of patent foramen ovale in stroke patients.  Int I Card Imaging. 1993;  9 1-5
  • 59 Jauss M, Kaps M, Keberle M et al. A comparison of transesophageal echocardiography and transcranial Doppler sonography with contrast medium for detection of patent foramen ovale.  Stroke. 1994;  25 1265-1267
  • 60 Job F P, Ringelstein E B, Grafen Y et al. Comparison of transcranial contrast Doppler sonography and transesophageal contrast echocardiography for the detection of patent foramen ovale in young stroke patients.  Am J Cardiol. 1994;  74 381-384
  • 61 Nemec J J, Marwick T H, Lorig R J et al. Comparison of transcranial Doppler ultrasound and transesophageal contrast echocardiography in the detection of interatrial right-to-left shunts.  Am J Cardiol. 1991;  68 1498-1502
  • 62 Homma S, Di Tullio M R, Sacco R L et al. Characteristics of patent foramen ovale associated with cryptogenic stroke. A biplane transesophageal echocardiographic study.  Stroke. 1994;  25 582-586
  • 63 Schuchlenz H W, Weihs W, Horner S et al. The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events.  Am J Med. 2000;  109 456-462
  • 64 Serena J, Segura T, Perez-Ayuso M J et al. The need to quantify right-to-left shunt in acute ischemic stroke: a case-control study.  Stroke. 1998;  29 1322-1328
  • 65 Gross P. The patency of the so-called „Anatomically open but functionally closed” Foramen ovale.  Am Heart J. 1934;  49 11-13
  • 66 Prec K J, Cassels D E. Oximeter studies in newborn infants during crying.  Pediatrics. 1952;  9 756-763
  • 67 Moorthy S S, Losasso A M. Patency of the foramen ovale in the critically ill patient.  Anesthesiology. 1974;  41 405-407
  • 68 Kronik G, Mosslacher H. Positive contrast echocardiography in patients with patent foramen ovale and normal right heart hemodynamics.  Am J Cardiol. 1982;  49 1806-1809
  • 69 Kovacs G S, Hill J D, Aberg T et al. Pathogenesis of arterial hypoxemia in pulmonary embolism.  Arch Surg. 1966;  93 813-823
  • 70 Daly J J. Venoarterial shunting in obstructive pulmonary disease.  N Engl J Med. 1968;  278 952-953
  • 71 Selzer A, Carnes W H. The role of pulmonary stenosis in the production of chronic cyanosis.  Am Heart J. 1953;  45 382-395
  • 72 Pieroni D R, Valdes-Cruz L M. Atrial right-to-left shunt in infants with respiratory and cardiac distress but without congenital heart disease. Demonstration by contrast echocardiography.  Pediatr Cardiol. 1982;  2 1-5
  • 73 Morris A L, Donen N. Hypoxia and intracardiac right-to-left shunt. Complicating inferior myocardial infarction with right ventricular extension.  Arch Intern Med. 1978;  138 1405-1406
  • 74 Manno B V, Bemis C E, Carver J et al. Right ventricular infarction complicated by right to left shunt.  J Am Coll Cardiol. 1983;  1 554-557
  • 75 Horton S C, Bunch T J. Patent foramen ovale and stroke.  Mayo Clin Proc. 2004;  79 79-88
  • 76 Cohnheim J. Thrombose und embolie in den Vorlesungen über allgemeine pathologie: Ein handbuch für ärzte und studierende.. Berlin: Verlag von August Hirschwald; 1877
  • 77 Cohnheim J. Thrombose und embolie in den vorlesungen über allgemeine pathologie: Ein handbuch für ärzte und studierende.. Berlin: Verlag von August Hirschwald; 1888
  • 78 Valdes-Cruz L M, Pieroni D R, Roland J M et al. Echocardiographic detection of intracardiac right-to-left shunts following peripheral vein injections.  Circulation. 1976;  54 558-562
  • 79 Fraker Jr T D, Harris P J, Behar V S et al. Detection and exclusion of interatrial shunts by two-dimensional echocardiography and peripheral venous injection.  Circulation. 1979;  59 379-384
  • 80 Lechat P, Mas J L, Lascault G et al. Prevalence of patent foramen ovale in patients with stroke.  N Engl J Med. 1988;  318 1148-1152
  • 81 Overell J R, Bone I, Lees K R. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies.  Neurology. 2000;  55 1172-1179
  • 82 Cabanes L, Mas J L, Cohen A et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography.  Stroke. 1993;  24 1865-1873
  • 83 Webster M W, Chancellor A M, Smith H J et al. Patent foramen ovale in young stroke patients.  Lancet. 1988;  2 11-12
  • 84 Bogousslavsky J, Garazi S, Jeanrenaud X et al. Stroke recurrence in patients with patent foramen ovale: the Lausanne Study. Lausanne Stroke with Paradoxal Embolism Study Group.  Neurology. 1996;  46 1301-1305
  • 85 Giardini A, Donti A, Formigari R et al. Spontaneous large right-to-left shunt and migraine headache with aura are risk factors for recurrent stroke in patients with a patent foramen ovale.  Int J Cardiol. 2007;  120 357-362
  • 86 Hausmann D, Mugge A, Becht I et al. Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events.  Am J Cardiol. 1992;  70 668-672
  • 87 Aggarwal K, Jayam V K, Meyer M A et al. Thrombus-in-transit and paradoxical embolism.  J Am Soc Echocardiogr. 2002;  15 1021-1022
  • 88 Fabricius A M, Kruger M, Hanke M et al. Caught in the act: impending paradoxical embolism.  Asian Cardiovasc Thorac Ann. 2002;  10 342-343
  • 89 Rachko M, Safi A M, Yeshou D et al. Cryptogenic ischemic stroke and paradoxical embolism: should a patent foramen ovale be closed? Case report and literature review.  Angiology. 2001;  52 793-799
  • 90 Poppert H MM, Bockelbrink A, Schwarze J et al. Lack of association between right-to-left shunt and cerebral ischemia after adjustment for gender and age.  J Negat Results Biomed. 2008;  7 7
  • 91 Feurer R, Sadikovic S, Esposito L et al. Lesion patterns in patients with cryptogenic stroke with and without right-to-left-shunt.  Eur J Neurol. 2009;  16 1077-1082
  • 92 De Castro S, Cartoni D, Fiorelli M et al. Morphological and functional characteristics of patent foramen ovale and their embolic implications.  Stroke. 2000;  31 2407-2413
  • 93 Zabalgoitia M, Norris L P, Garcia M. Atrial septal aneurysm as a potential source of neurological ischemic events.  Am J Card Imaging. 1994;  8 39-44
  • 94 Schuchlenz H W, Saurer G, Weihs W. Patent foramen ovale, atrial septal aneurysm, and recurrent stroke.  N Engl J Med. 2002;  346 1331-1332; author reply 1331–1332
  • 95 Fox E R, Picard M H, Chow C M et al. Interatrial septal mobility predicts larger shunts across patent foramen ovales: an analysis with transmitral Doppler scanning.  Am Heart J. 2003;  145 730-736
  • 96 Mattioli A V, Bonetti L, Aquilina M et al. Association between atrial septal aneurysm and patent foramen ovale in young patients with recent stroke and normal carotid arteries.  Cerebrovasc Dis. 2003;  15 4-10
  • 97 Meissner I, Khandheria B K, Heit J A et al. Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study.  JJ Am Coll Cardiol. 2006;  47 440-445
  • 98 Homma S, Sacco R L, Di Tullio M R et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study.  Circulation. 2002;  105 2625-2631
  • 99 Serena J, Marti-Fabregas J, Santamarina E et al. Recurrent stroke and massive right-to-left shunt: results from the prospective Spanish multicenter (CODICIA) study.  Stroke. 2008;  39 3131-3136
  • 100 Feurer R, Sadikovic S, Sepp D et al. Patent foramen ovale is not associated with an increased risk of stroke recurrence.  Eur J Neurol. 2010;  17 1339-1345
  • 101 Goldstein J A, Beardslee M A, Xu H et al. Infective endocarditis resulting from CardioSEAL closure of a patent foramen ovale.  Catheter Cardiovasc Interv. 2002;  55 217-220; discussion 221
  • 102 Furlan A J. A prospective multicenter, randomized controlled trial to evaluate the safety and efficacy of the STARflex septal closure system versus best medical therapy in patients with a stroke or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale. [online]. Available

Dr. Regina Feurer

Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München

Ismaningerstr. 22

81675 München

Email: regina.feurer@gmx.de

    >