Published online before print April 15, 2004, doi: 10.1161/01.STR.0000127038.10584.27
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(Stroke. 2004;35:e135.)
© 2004 American Heart Association, Inc.
Letters to the Editor |
Patent Foramen Ovale and Stroke
Graz-West Hospital, Austria
To the Editor:
I wish to congratulate the authors of the current "Controversies in Stroke" on their critical discussion of secondary prevention in patients with patent foramen ovale (PFO) and cryptogenic stroke.1–3 In the absence of definitive data in this scenario, they focus a large part of their discussion on the possible treatment options quoting the 2 most cited recently published prospective multicenter studies that evaluated the stroke recurrence risk in patients with PFO.4,5 I fully agree with the authors that the best medical therapy has not yet be determined; furthermore, there is no doubt that another trial randomizing patients <55 years of age either to device closure or medical therapy is necessary. More or less all authors accept that there is an association between the presence of PFO and stroke. Unfortunately, despite the controversy surrounding PFO identification/quantification, I am missing a critical discussion on the limitations and flaws of contrast echo technique which is currently used. In my opinion, there is an urgent need for standardization of PFO identification and quantification, which at present does not exist. In the French PFO-ASA study, a PFO was defined if at least 3 contrast-bubbles appeared in the left atrium. The degree of shunting was defined to be small if 3 to 9 contrast-bubbles appeared, it was moderate if 10 to 30 contrast-bubbles appeared, and large if more than 30 contrast-bubbles appeared in the left atrium.4 The authors of this study did not conceal that sonographers disagreed on the presence of patent foramen ovale in 13.9% of patients and the degree of shunting in 26.6%.6 In the Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS) a PFO was considered to be present if >1 contrast-bubble appeared in the left atrium, and the authors used a cut-off point for a large shunt if more than 10 bubbles could be demonstrated in the left atrium.5 Very recently it was nicely shown that for a given PFO, the amount of right-to-left contrast shunting is a matter of expiratory pressure during the Valsava maneuver.7 Previously, we and others have shown that in any PFO right-to-left shunting varies considerably and that the magnitude of contrast shunting does not necessarily correlate with the true anatomical size of the PFO.8–10 Due to the orientation of the inferior vena cava blood (which potentially contains an embolus arising from pelvic or deep vein thrombi) to the fossa ovalis, even a large PFO may be missed if contrast agent is administered through a cubital vein, as these bubbles may be redirected from the fossa ovalis by this blood flow.8,11 These flow patterns are aggravated by an Eustachian valve (VE) which directs the blood from the inferior vena cava preferentially to the area of the fossa ovalis can be studied by contrast administration in to foot vein.9,11,13 By the way, this valve is frequently seen in patients with patent foramen ovale.12,13 Moreover, there are reports showing that transthoracic contrast echocardiography with harmonic imaging mode may be too sensitive at the expense of a decreased specificity for PFO detection.14 Furthermore, the time appearance of contrast-bubbles in the left atrium which is used as one of the distinguishing features between intracardiac and (physiological) intrapulmonary shunts has shown to be unreliable.15–18
Tong and Backer2 state that the relevance of PFO may be analogous to the presumed association between mitral valve prolaps and stroke reported over the last decade. Contrary to this assumption, I believe that by neglecting the underlying pathophysiology of right atrial flow pattern and the methodological limitation of the commonly used contrast echo technique, there is a higher chance of underestimating the genuine risk of a large PFO. Consensus in the identification/quantification of this valve like structure is needed to avoid confusion and to make future interventional studies easier to interpret. I agree with Tong and Becker that studies for PFO closure may be premature in this patients with cryptogenic stroke, not due to doubts on causality but rather due to the fact that we should first acknowledge and close the "hole" of our ignorance on morphological/functional PFO characteristics. Unless we are not able to optimize and standardize our available methods for PFO identification/quantification, we will not be able to randomize comparable patients and the issue of PFO and stroke will not be conclusively resolved.
References
- Furlan AJ. Patent foramen ovale and recurrent stroke: closure is the best option: yes. Stroke. 2004; 35: 803–804.
[Free Full Text] - Tong DC, Becker KJ. Patent foramen ovale and recurrent stroke: closure is the best option: no. Stroke. 2004; 35: 804–805.
[Free Full Text] - Donnan GA, Davis SM. Patent foramen ovale and stroke: closure by further randomized trial is required! Stroke. 2004; 35: 806.
[Free Full Text] - Mas JL, Arquizan C, Lamy C, Zuber C, Cabanas L, Derumeaux G, Coste J. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med. 2001; 345: 1740–1746.
[Abstract/Free Full Text] - Cabanes L, Coste J, Derumeaux G, Jeanrenaud, Lamy C, Zuber M, Mas JL. Interobserver and intraobserver variability in detection of patent foramen ovale and atrial septal aneurysm with transesophageal echocardiography. J Am Soc Echocardiogr. 2002; 15: 441–446.[CrossRef][Medline] [Order article via Infotrieve]
- Homma S, Sacco RL, Di Tullio M, Sciacca, Mohr JP. Effect of medical treatment in stroke patients with patent foramen ovale. Circulation. 2002; 105: 2625–2631.
[Abstract/Free Full Text] - Devuyst G, Piechowski-Jozwiak B, Karapanayiotides T, Fitting JW, Kemeny V, Hirt L, Urbano LA, Arnold P, van Melle G, Despland PA, Bogousslavsky J. Controlled contrast transcranial Doppler and arterial blood gas analysis to quantify shunt through patent foramen ovale. Stroke. 2004; 35: 859–863.
[Abstract/Free Full Text] - Schuchlenz HW, Weihs W, Horner S, Quehenberger F. The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events. Am J Med. 2000; 109: 456–462.[CrossRef][Medline] [Order article via Infotrieve]
- Schuchlenz HW, Weihs W, Beitzke A, Stein JI, Gamillscheg A, Rehak P. Transesophageal echocardiography for quantifying size of patent foramen ovale in patients with cryptogenic cerebrovascular events. Stroke. 2002; 33: 293–296.
[Abstract/Free Full Text] - Agmon Y, Khandheria BK, Meissner I, Gentile F, Sicks JD, O’Fallon WM, Whisnant JP, Wiebers DO, Seward JB. Comparison of frequency of patent foramen ovale by transesophageal echocardiography in patients with cerebral ischemic events versus in subjects in the general population. Am J Cardiol. 2001; 88: 330–332.[CrossRef][Medline] [Order article via Infotrieve]
- Gin KG, Huckell VF, Pollick C. Femoral vein delivery of contrast medium enhances transthoracic echocardiographic detection of patent foramen ovale. J Am Coll Cardiol. 1993; 22: 1994–2000.[Abstract]
- Homma S, Sacco RL, Di Tullio M, Sciacca RR, Mohr JP. Atrial anatomy in non-cardioembolic stroke patients. J Am Coll Cardiol. 2003; 42: 1066–1072.
[Abstract/Free Full Text] - Schuchlenz HW, Saurer G, Weihs W, Rehak P. Persisting eustachian valve in adults: relation to patent foramen ovale and cerebrovascular events. J Am Soc Echocardiogr. 2004; 17: 231–233.[CrossRef][Medline] [Order article via Infotrieve]
- Madala D, Zaroff JG, Hourigan L, Foster E. Harmonic imaging improves sensitivity at the expense of specificity in the detection of patent foramen ovale. Echocardiography. 2004; 21: 33–36.[CrossRef][Medline] [Order article via Infotrieve]
- Naqvi TZ, Nagai T, Atar S, Siegel RJ. Early appearance of echo-contrast simulating an intracardiac shunt in a patient with liver cirrhosis and intrapulmonary shunting. J Am Soc Echocardiogr. 2002; 15: 379–381.[CrossRef][Medline] [Order article via Infotrieve]
- Jauss M, Zanette E, for the consensus conference. Detection of right–to-left shunts with ultrasound contrast agent and transcranial doppler sonography. Cerebrovasc Dis. 2000; 10: 490–496.[CrossRef][Medline] [Order article via Infotrieve]
- Nanthakumar K, Graham AT, Robinson TI, Grande P, Pugash RA, Clarke JA, Hutchinson SJ, Mandzia JL, Hyland RH, Faughnan ME. Contrast echocardiography for detection of pulmonary arteriovenous malformations. Am Heart J. 2001; 141: 243–246.[CrossRef][Medline] [Order article via Infotrieve]
- Ahmed S, Nanda NC, Nekkanti R, Yousif AM. Contrast Transesophageal Echocardiographic detection of a pulmonary arteriovenous malformation draining into left lower pulmonary vein. Echocardiography. 2003; 20: 391–394.[CrossRef][Medline] [Order article via Infotrieve]
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