Right to Left Shunt and Cryptogenic Stroke in Patients Over 60 Years Old

Sanja Djambazovska Zikova; Anita Arsovska; Danijela Vojtikiv Samoilovska; Svetlana Jovevska; Fatlume Adili Gongo

doi:10.2478/prilozi-2024-0021

Abstract

Objective

To determine the possible role of patent foramen ovale (PFO) as indicated by a right to left shunt and cryptogenic stroke in patients aged ≥ 60 years and to compare the prevalence of patent foramen ovale with stroke of known cause.

Methods

We prospectively examined the prevalence of PFO using contrast enhanced colour Transcranial Doppler ultrasonography (bubble-cTCD) in 86 consecutive patients aged ≥60 years with transient ischaemic attack (TIA) or stroke and 86 consecutive patients aged <60 years with TIA/stroke as a control group. Patients with cryptogenic stroke were compared to stroke patients with known cause.

Results

A significantly higher prevalence of PFO in patients with cryptogenic compared to patients with stroke of known cause was registered in the patients aged < 60 years (56.6% vs.18.8%) and in patients aged ≥ 60 years (37.14% vs.11.76%), respectively. Multivariate analysis adjusted for age, hypertension and coronary disease showed that the existence of R-to-L shunt (RLS) was independently associated with cryptogenic stroke in both, in the younger group (odds ratio 4.012; 95% CI1.323 to 12.171, p =0.0143.70) and in the older group (odds ratio 3.197; 95% CI 1.140 to 10.877, p=0.037).

Conclusion

Our findings suggest that PFO is strongly associated with cryptogenic stroke in patients aged ≥ 60 years. Bubble – cTCD was feasible and suitable as a first-line method for the detection of PFO in older patients.

References

Sacco, RL, Ellenberg, JH, Mohr, JP, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 1989; 25: 382–390.
Search in Google Scholar Back to article
Adams, HP Jr, Bendixen, BH, Kappelle, LJ, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial — TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24: 35–41.
Search in Google Scholar Back to article
Hart, RG, Diener, HC, Coutts, SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol2014; 13: 429–438.
Search in Google Scholar Back to article
MeierB.LockJ.E.Contemporary management of patent foramen ovale.Circulation. 2003; 107: 5–91,
Search in Google Scholar Back to article
Hara H.Virmani, R.Ladich E. et al.Patent foramen ovale: current pathology, pathophysiology, and clinical status.J Am CollCardiol. 2005; 46: 1768–1776.
Search in Google Scholar Back to article
Overell JR, Bone I, Lees KR. Interatrialseptal abnormalities and stroke: a metaanalysis of case-control studies. Neurology 2000; 55: 1172–9.
Search in Google Scholar Back to article
Di Tullio M, Sacco RL, Gopal A, Mohr JP, Homma S. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992; 117: 461–5.
Search in Google Scholar Back to article
Jones EF, Calafiore P, Donnan GA, Tonkin AM. Evidence that patent foramen ovale is not a risk factor for cerebral ischemia in the elderly. Am J Cardiol 1994; 74: 596–9.
Search in Google Scholar Back to article
Yeung M, Khan KA, Shuaib A. Transcranial Doppler ultrasonography in the detection of venous to arterial shunting in acute stroke and transient ischaemic attacks. J NeurolNeurosurg Psychiatry 1996; 61:4 45–9.
Search in Google Scholar Back to article
Serena J, Segura T, Perez-Ayuso J, Bassaganys J, Molins A, Dávalos A. The need to quantify right-to-left shunt in acute ischaemic stroke: a case-control study. Stroke 1998; 29: 1322–28.
Search in Google Scholar Back to article
Hausmann D, Mügge A, Becht I, Daniel WG. Diagnosis of patent foramen ovalebytransoesophageal echocardiography and association with cerebral and peripheral embolic events. Am J Cardiol 1992; 70: 668–72.
Search in Google Scholar Back to article
Handke M, Harloff A, Olschewski M, Hetzel A, Geibel A. Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 2007; 357: 2262–68.
Search in Google Scholar Back to article
Force M, Massabuau P, Larrue V. Prevalence of atrial septal abnormalities in older patients with cryptogenic ischemic stroke or transient ischemic attack. ClinNeurolNeurosurg 2008; 110: 779–83.
Search in Google Scholar Back to article
Mesa D, Ruiz M, Delgado M, Suárez de Lezo J, Pan M, TejeroI,et al. Prevalence of patent foramen ovale determined by transesophageal echocardiography in patients with cryptogenic stroke aged 55 years or older. Same as younger patients? Rev EspCardiol. (2010) 63: 315–22. doi: 10.1016/S1885-5857(10)70064-5.
Search in Google Scholar Back to article
Mazzucco S, Li L, Binney L, Rothwell PM, Oxford Vascular Study Phenotyped Cohort. Prevalence of patent foramen ovale in cryptogenic transient ischaemic attack and non-disabling stroke at older ages: a population-based study, systematic review, and meta-analysis. Lancet Neurol. (2018) 17:609–17.doi: 10.1016/S1474-4422(18)30167-4.
Search in Google Scholar Back to article
De Castro S, Papetti F, Di Angelantonio E, et al. Feasibility andclinical utility of transoesophageal echocardiography in the acute phase of cerebral ischaemia. Am J Cardiol 2010; 106: 1339–44.
Search in Google Scholar Back to article
Homma S, DiTullio MR, Sacco RL, Sciacca RR, Mohr JP. Age as a determinant of adverse events in medically treated cryptogenic stroke patients with patent foramen ovale. Stroke 2004; 35: 2145–49.
Search in Google Scholar Back to article
Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an au topsy study of 965 normal hearts. Mayo ClinProc 1984; 59: 17–20.
Search in Google Scholar Back to article
Lee PH, Song JK, Kim JS, Heo R, Lee S, Kim DH, et al.Crypto genic stroke and high-risk patent foramen ovale: the DE FENSE-PFO trial. J Am CollCardiol2018; 71: 2335–2342.
Search in Google Scholar Back to article
Katsanos AH, Giannopoulos S, Frogoudaki A, et al. The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta-analysis. Eur J Neurol2016; 23: 569–79.
Search in Google Scholar Back to article
Mojadidi MK, Roberts SC, Winoker JS, et al. Accuracy of transcranial Doppler for the diagnosis of intracardiac right-to-left shunt: a bivariate meta-analysis of prospective studies. JACC Cardiovasc Imaging 2014; 7: 236–50.
Search in Google Scholar Back to article
Jauss M, Zanette E. Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography. Cerebrovasc Dis 2000; 10: 490–96.
Search in Google Scholar Back to article
Mojadidi MK, Zhang L, Chugh Y, et al. Transcranial Doppler: does addition of blood to agitated saline affect sensitivity for detecting cardiac right-to-left shunt? Echocardiography 2016; 33: 1219–2
Search in Google Scholar Back to article
Del Sette M, Dinia L, Rizzi D, Sugo A, Albano B, Gandolfo C. Diagnosis of right-to-left shunt with transcranial Doppler and vertebrobasilar recording. Stroke 2007; 38: 2254–56.
Search in Google Scholar Back to article
Spencer M.P., Moehring M.A., Jesurum J., Gray W.A., Olsen J.V., Reisman M. Power m-mode transcranial Doppler for diagnosis of patent foramen ovale and assessing transcatheter closure. J. Neuroimaging. 2004;14:342–349. doi: 10.1111/j.1552-6569.2004.tb00261.x.
Search in Google Scholar Back to article
Chatuverdi S. Coagulation abnormalities in adults with cryptogenic stroke and patent foramen ovale. J Neurol Sci. 1998; 160: 158–160.
Search in Google Scholar Back to article
Stöllberger C, Slany J, Schuster I, Leitner H, Winkler WB, Karnik R. The prevalence of deep venous thrombosis in patients with suspected paradoxical embolism. Ann Intern Med. 1993; 119: 461–465.
Search in Google Scholar Back to article
Schina MJ, Meumyer MM, Healy DA, Atnip RG, Thiele BL. Influence of age on venous physiologic parameters. J Vasc Surg. 1993; 18: 749–752.
Search in Google Scholar Back to article
Vilén L, Jacobsson S, Wadenvik H, Kutti J. ADP-induced platelet aggregation as a function of age in healthy humans. ThrombHaemost. 1989; 61: 490–492.
Search in Google Scholar Back to article
Dib JC, Abergel E, Rovani C, Raffoul H, Diebold B. The age of the patient should be taken into account when interpreting Doppler assessed pulmonary artery pressures. J Am SocEchocardiog. 1997; 10: 72–7.
Search in Google Scholar Back to article
Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001;345:1740-613.
Search in Google Scholar Back to article
Stafford MB, Bagley JE, DiGiacinto D. Comparison of Transthoracic Echocardiography, Transesophageal Echocardiography, and Transcranial Doppler in the Detection of Patent Foramen Ovale as the Etiology for Cryptogenic Stroke. Journal of Diagnostic Medical Sonography. 2019; 35(2): 127–133. doi:10.1177/8756479318816983
Search in Google Scholar Back to article
Souteyrand G, Motreff P, Cassagnes J, et al: Comparison of transthoracic echocardiography using second harmonic imaging, transcranial Doppler and transesophageal echo cardiography for the detection of patent foramen ovale in stroke patients. Eur J Echocardiogr 2006; 7(2): 147–154
Search in Google Scholar Back to article
Nemec JJ, Marwick TH, Lorig RJ, et al: Comparison of transcranial Doppler ultrasound and transesophageal con trast echocardiography in the detection of interatrial right to-left shunts. Am J Cardiol 1991; 68(15): 1498–15.
Search in Google Scholar Back to article
Zito C, Dattilo G, Oreto G, et al: Patent foramen ovale: comparison among diagnostic strategies in cryptogenic stroke and migraine. Echocardiography 2009; 26(5): 495–503.
Search in Google Scholar Back to article
Caputi L, Carriero MR, Falcone C, et al: Transcranial Doppler and transesophageal echocardiography: comparison of both techniques and prospective clinical relevance of transcranial Doppler in patent foramen ovale detection. J Stroke Cerebrovasc Dis 2009; 18(5): 343–34.8
Search in Google Scholar Back to article
Mangiafico S, Scandura S, Ussia GP, et al: Transesophageal echocardiography and transcranial-color Doppler: independent or complementary diagnostic tests for cardiologists in the detection of patent foramen ovale? J Cardiovasc Med2009; 10: 143–148.
Search in Google Scholar Back to article
Devuyst G, Despland PA, Bogousslavsky J, et al: Complementarity of contrast transcranial Doppler and contrast transesophageal echocardiography for the detection of patent foramen ovale in stroke patients. EurNeurol1997; 38: 21–25.
Search in Google Scholar Back to article
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(6): 1265–1267.
Search in Google Scholar Back to article
Jacobs BS, Boden-Albala B, Lin IF, Sacco RL: Stroke in the young in the northern Manhattan stroke study. Stroke2002; 33: 2789–2793.
Search in Google Scholar Back to article
Belkin R, Pollack B, Ruggiero M, et al: Comparison of transesophageal and transthoracic echo-cardiography with contrast and color flow Doppler in the detection of patent foramen ovale. Am Heart J 1994; 128(3): 520–525.
Search in Google Scholar Back to article
Belvis R, Leta RG, Matri-Fabregas J, et al: Almost perfect concordance between simultaneous transcranial Doppler and transesophageal echo-cardiography in the quantification of right-to-left shunts. J Neuroimaging 2006; 16(2): 133–138
Search in Google Scholar Back to article
Klötzsch C, Janben G, Berlit P, et al: Transesophageal echocardiography and contrast-TCD in the detection of a patent foramen ovale. Neurology 1994;44:1603–160.
Search in Google Scholar Back to article
Komar M, Olszowska M, Podolec P, et al: Transcranial Doppler ultrasonography: should it be the first choice for persistent foramen ovale screening? Cardiovasc Ultrasound. 2014; 12: 16.
Search in Google Scholar Back to article
Mojadidi MK, Roberts SC, Winoker JS, et al. Accuracy of transcranial Doppler for the diagnosis of intracardiac right-to-left shunt: a bivariate meta-analysis of prospective studies. JACC Cardiovasc Imaging 2014; 7: 236–50.
Search in Google Scholar Back to article
Droste DW, Reisener M, Kemény V, et al. Contrast transcranial Doppler ultrasound in the detection of right-to-left shunts. Reproducibility, comparison of 2 agents, and distribution of microemboli.Stroke 1999; 30: 1014–18.
Search in Google Scholar Back to article
Madison B. Stafford, Jennifer E. Bagley, and Dora DiGiacinto.Comparison of Transthoracic Echocardiography, Transesophageal Echocardiography, and Transcranial Doppler in the Detection of Patent Foramen Ovale as the Etiology for Cryptogenic Stroke. Journal of Diagnostic Medical Sonography 2018 35: 2, 127–133.
Search in Google Scholar Back to article
Daniel WG, Erbel R, Kasper W, et al. Safety of transesophageal echocardiography. A multicenter survey of 10 419 examinations.Circulation 1991; 83: 817–21.
Search in Google Scholar Back to article
Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med 2017; 377: 1022–32.
Search in Google Scholar Back to article
Søndegaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke.NEngl J Med 2017; 377: 1033–42.
Search in Google Scholar Back to article
Mas J-L, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vsanti-platelets after stroke. N Engl J Med 2017; 377: 1011–21.
Search in Google Scholar Back to article
Huber C, Wachter R, Pelz J, Michalski D. Current challenges and future directions in handling stroke patients with patent foramen ovale-a brief review. Front Neurol.2022; 13: 855656.
Search in Google Scholar Back to article
Kwon H, Lee PH, Song JK, Kwon SU, Kang DW, Kim JS. Patent foramen ovale closure in old stroke patients: A subgroup analysis of the DEFENSE-PFO trial. J Stroke.2021; 23: 289–292.
Search in Google Scholar Back to article