Patent foramen ovale and cryptogenic stroke in the elderly: advances in understanding their relevance and treatment

doi:10.3877/cma.j.issn.1674-0785.2026.05.006

Abstract

Abstract:

Patent foramen ovale is defined as the failure of the foramen ovale to achieve complete anatomical closure by three years of age. Numerous studies have demonstrated a close association between PFO and the occurrence and prognosis of cryptogenic stroke (CS) in the elderly. This article reviews the epidemiology, pathogenesis, associations, and treatment strategies for elderly CS patients with PFO, along with the latest updates from relevant guidelines, aiming to provide clinicians with diagnostic insights and early intervention strategies.

Key words: Elderly, Patent foramen ovale, Cryptogenic stroke, Epidemiology, Treatment methods, Guidelines

Xinru Chai, Xiaoshan Zhang, Xiaoxiao Liu, Ying Jiang, Jie Zhao, Yilu Shi, Dan Zhang, Shasha Duan. Patent foramen ovale and cryptogenic stroke in the elderly: advances in understanding their relevance and treatment[J]. Chinese Journal of Clinicians(Electronic Edition), 2026, 20(05): 381-385.

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References 54

1	Mac Grory B, Ohman EM, Feng W, et al. Advances in the management of cardioembolic stroke associated with patent foramen ovale [J]. BMJ, 2022, 376: e063161.
2	Li W, Zhang J, Zhang Y, et al. Clinical research progress on pathogenesis and treatment of Patent Foramen Ovale-associated stroke [J]. Front Neurol, 2025, 16: 1512399.
3	王睿, 周碧怡, 马杰, 等. 与卵圆孔未闭相关的不明原因脑卒中的研究进展 [J]. 中华神经医学杂志, 2021, 20(1): 92-97.
4	Tu WJ, Zhao Z, Yin P, et al. Estimated burden of stroke in China in 2020[J]. JAMA network open, 2023, 6(3): e231455.
5	Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: A report from the American heart association [J]. Circulation, 2018, 137(12): e67-e492.
6	Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies [J]. Neurology, 2000, 55(8): 1172-1179.
7	Wang Y, Li Z, Zhao X, et al. Stroke care quality in China: substantial improvement, and a huge challenge and opportunity [J]. Int J Stroke, 2017, 12(3): 229-235.
8	Tu WJ, Wang LD. Special Writing Group of China Stroke Surveillance Report. China stroke surveillance report 2021 [J]. Mil Med Res, 2023, 10(1): 33.
9	张宝荣. 老年卵圆孔未闭相关隐源性卒中研究进展 [J]. 心电与循环, 2024, 43(5): 415-419, 431.
10	Yaghi S, Johansen MC, Ghannam M, et al. Proposal for the ischemic stroke phenotyping system 2025: ISPS25 [J]. Stroke, 2025, 56(12): 3552-3562.
11	Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts [J]. Mayo Clin Proc, 1984, 59(1): 17-20.
12	Mas JL, Saver JL, Kasner SE, et al. Association of atrial septal aneurysm and shunt size with stroke recurrence and benefit from patent foramen ovale closure [J]. JAMA Neurol, 2022, 79(11): 1175-1179.
13	Wang R, Qiao M, Song G, et al. Predictive value of patent foramen ovale diameter for cryptogenic stroke and age-related differences [J]. Front Cardiovasc Med, 2025, 12: 1647313.
14	Nakashima M, Takaya Y, Nakayama R, et al. Morphological features of patent foramen ovale compared between older and young patients with cryptogenic ischemic stroke [J]. Circ J, 2024, 88(9): 1398-1405.
15	Alperi A, Guedeney P, Horlick E, et al. Transcatheter closure of patent foramen ovale in older patients with cryptogenic thromboembolic events [J]. Circ Cardiovasc Interv, 2022, 15(7): e011652.
16	Ioannidis SG, Mitsias PD. Patent foramen ovale in cryptogenic ischemic stroke: direct cause, risk factor, or incidental finding? [J]. Front Neurol, 2020, 11: 567.
17	Lippmann H, Rafferty T. Patent foramen ovale and paradoxical embolization: a historical perspective [J]. Yale J Biol Med, 1993, 66(1): 11-17.
18	Shah P, Jimenez-Ruiz A, Gibson A, et al. Association between acute myocardial infarction and death in 386 patients with a thrombus straddling a patent foramen ovale [J]. Int J Cardiol, 2021, 342: 1-6.
19	Henein M, Waldenström A, Mörner S, et al. The normal impact of age and gender on right heart structure and function [J]. Echocardiography, 2014, 31(1): 5-11.
20	Stein PD, Hull RD, Kayali F, et al. Venous thromboembolism according to age: the impact of an aging population [J]. Arch Intern Med, 2004, 164(20): 2260-2265.
21	Chino S, Mochizuki Y, Mizuma K, et al. Transcranial doppler for stratification of high-risk morphology of patent foramen ovale in patients with cryptogenic stroke [J]. Heart Vessels, 2022, 37(12): 2119-2127.
22	Liu X, Zhang Y, Xie H, et al. Change in patent foramen ovale height is associated with cryptogenic stroke and the construction of a morphology-based scoring system [J]. Front Cardiovasc Med, 2022, 9: 1010947.
23	Yan C, Li H. Preliminary investigation of in situ thrombus within patent foramen ovale in patients with and without stroke [J]. JAMA, 2021, 325(20): 2116-2118.
24	Kasner SE, Lattanzi S, Fonseca AC, et al. Uncertainties and controversies in the management of ischemic stroke and transient ischemic attack patients with patent foramen ovale[J]. Stroke, 2021, 52(12): e806-e819.
25	Hindricks G, Potpara T, Dagres N, et al. Corrigendum to: 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC [J]. Eur Heart J, 2021, 42(40): 4194.
26	Dusonchet A, Varenne O, Puscas T, et al. Does atrial septal anatomy still matter in the etiological evaluation of ischemic stroke beyond the age of 60? [J]. J Am Heart Assoc, 2024, 13(4): e031684.
27	Mazzucco S, Li L, Binney L, et al. 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 [J]. Lancet Neurol, 2018, 17(7): 609-617.
28	Kent DM, Ruthazer R, Weimar C, et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke [J]. Neurology, 2013, 81(7): 619-625.
29	Vidal-Calés P, Llull L, Lanthier S, et al. Patent foramen ovale closure in older patients with cryptogenic stroke: current evidence and next steps [J]. Struct Heart, 2025, 9(8): 100699.
30	Kent DM, Saver JL, Ruthazer R, et al. Risk of paradoxical embolism (RoPE)-estimated attributable fraction correlates with the benefit of patent foramen ovale closure: an analysis of 3 trials [J]. Stroke, 2020, 51(10): 3119-3123.
31	Elgendy AY, Saver JL, Amin Z, et al. Proposal for updated nomenclature and classification of potential causative mechanism in patent foramen ovale-associated stroke [J]. JAMA Neurol, 2020, 77(7): 878-886.
32	Kent DM, Saver JL, Kasner SE, et al. Heterogeneity of treatment effects in an analysis of pooled individual patient data from randomized trials of device closure of patent foramen ovale after stroke [J]. JAMA, 2021, 326(22): 2277-2286.
33	Alperi A, Guedeney P, Horlick E, et al. Transcatheter closure of patent foramen ovale in older patients with cryptogenic thromboembolic events [J]. Circ Cardiovasc Interv, 2022, 15(7): e011652.
34	Nachoski D, Schroeder J, Almalla M, et al. Dual-center experiences with interventional closure of patent foramen ovale: a medium-term follow-up study comparing two patient groups aged under and over 60 years [J]. Clin Cardiol, 2021, 44(3): 386-391.
35	Ng FC, Yassi N, Sharma G, et al. Cerebral edema in patients with large hemispheric infarct undergoing reperfusion treatment: a Hermes meta-analysis [J]. Stroke, 2021, 52(11): 3450-3458.
36	Kim JS, Diener HC, Low TT, et al. Asian-pacific expert opinion on patent foramen ovale closure: review of new evidence and focused update [J]. J Stroke, 2025, 27(3): 329-337.
37	Mazzucco S, Li L, Rothwell PM. Prognosis of cryptogenic stroke with patent foramen ovale at older ages and implications for trials: a population-based study and systematic review [J]. JAMA Neurol, 2020, 77(10): 1279-1287.
38	Pristipino C, Sievert H, D'Ascenzo F, et al. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism [J]. EuroIntervention, 2019, 14(13): 1389-1402.
39	Kniffin WD Jr, Baron JA, Barrett J, et al. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly [J]. Arch Intern Med, 1994, 154(8): 861-866.
40	Farjat-Pasos JI, Chamorro A, Lanthier S, et al. Cerebrovascular events in older patients with patent foramen ovale: current status and future perspectives [J]. J Stroke, 2023, 25(3): 338-349.
41	Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial [J]. JAMA, 2014, 312(23): 2510-2520.
42	Apostolos A, Alexiou P, Papanikolaou A, et al. Patent foramen ovale closure in special clinical situations: more questions than answers? [J]. Life (Basel), 2024, 14(6): 706.
43	Kwon H, Lee PH, Song JK, et al. Patent foramen ovale closure in old stroke patients: a subgroup analysis of the defense-PFO trial [J]. J Stroke, 2021, 23(2): 289-292.
44	Poli S, Siebert E, Mbroh J, et al. Closure or medical therapy of patent foramen ovale in cryptogenic stroke: prospective case series [J]. Neurol Res Pract, 2021, 3(1): 16.
45	Lee PH, Kim JS, Song JK, et al. Device closure or antithrombotic therapy after cryptogenic stroke in elderly patients with a high-risk patent foramen ovale [J]. J Stroke, 2024, 26(2): 242-251.
46	Satpathy R, Rodés-Cabau J, Thaler DE, et al. PFO device closure in patients ＞60 years of a ge with ischemic stroke: results from U.S. medicare beneficiaries [J]. JACC Cardiovasc Interv, 2025, 18(10): 1303-1314.
47	Farjat-Pasos JI, Guedeney P, Horlick E, et al. Determinants of adverse outcomes following patent foramen ovale closure in elderly patients [J]. EuroIntervention, 2024, 20(16): 1029-1038.
48	Alsheikh-Ali AA, Thaler DE, Kent DM. Patent foramen ovale in cryptogenic stroke: incidental or pathogenic? [J]. Stroke, 2009, 40(7): 2349-2355.
49	柴鑫茹, 王雅皙, 张敏洁, 等. 房颤在不明原因栓塞性卒中的研究进展 [J/OL]. 中华临床医师杂志(电子版), 2025, 19(01): 68-74.
50	Gladstone DJ, Lindsay MP, Douketis J, et al. Canadian stroke best practice recommendations: secondary prevention of stroke update 2020 [J]. Can J Neurol Sci, 2022, 49(3): 315-337.
51	Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association [J]. Stroke, 2021, 52(7): e364-e467.
52	Kavinsky CJ, Szerlip M, Goldsweig AM, et al. SCAI guidelines for the management of patent foramen ovale [J]. J Soc Cardiovasc Angiogr Interv, 2022, 1(4): 100039.
53	Messé SR, Gronseth GS, Kent DM, et al. Practice advisory update summary: patent foramen ovale and secondary stroke prevention: report of the guideline subcommittee of the American Academy of Neurology [J]. Neurology, 2020, 94(20): 876-885.
54	Caso V, Turc G, Abdul-Rahim AH, et al. European Stroke Organisation (ESO) guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke [J]. Eur Stroke J, 2024, 9(4): 800-834.

机构	建议
美国神经病学学会（AAN）^[53]	其他年龄段人群也可考虑实施PFO封堵术，例如60~65岁患者，若其传统血管风险因素（如高血压、糖尿病、高脂血症或吸烟）较低，且经全面评估（包括长期监测心房颤动）后未发现其他的卒中风险因素，则可考虑实施PFO封堵术。
美国心脏协会/美国卒中协会（AHA/ASA）^[51]	老年患者应极少实施PFO封堵术，仅在特殊的临床情况下可采用。
加拿大卒中最佳实践指南^[50]	建议仅限18至60岁人群。
欧洲卒中组织（ESO）^[54]	专家组建议，若条件允许，应尽可能在随机对照试验中纳入60岁以上卒中及PFO 患者，或至少将其纳入注册研究。若无法实现，则多数专家建议采用PASCAL分类系统，并结合临床判断选择治疗方案。
美国心血管血管造影与介入学会（SCAI）^[52]	对于曾发生过PFO相关卒中的60岁及以上患者，建议采用PFO封堵术。对于60岁及以上既往有PFO相关卒中病史且无其他抗凝治疗指征的患者，建议采用PFO封堵术联合抗血小板治疗，而非长期单独使用抗凝治疗。

机构	建议
美国神经病学学会（AAN）^[53]	其他年龄段人群也可考虑实施PFO封堵术，例如60~65岁患者，若其传统血管风险因素（如高血压、糖尿病、高脂血症或吸烟）较低，且经全面评估（包括长期监测心房颤动）后未发现其他的卒中风险因素，则可考虑实施PFO封堵术。
美国心脏协会/美国卒中协会（AHA/ASA）^[51]	老年患者应极少实施PFO封堵术，仅在特殊的临床情况下可采用。
加拿大卒中最佳实践指南^[50]	建议仅限18至60岁人群。
欧洲卒中组织（ESO）^[54]	专家组建议，若条件允许，应尽可能在随机对照试验中纳入60岁以上卒中及PFO 患者，或至少将其纳入注册研究。若无法实现，则多数专家建议采用PASCAL分类系统，并结合临床判断选择治疗方案。
美国心血管血管造影与介入学会（SCAI）^[52]	对于曾发生过PFO相关卒中的60岁及以上患者，建议采用PFO封堵术。对于60岁及以上既往有PFO相关卒中病史且无其他抗凝治疗指征的患者，建议采用PFO封堵术联合抗血小板治疗，而非长期单独使用抗凝治疗。

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