Diagnostic value of contrast echocardiography and transcranial Doppler bubble test for patent foramen ovale: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

ZHU Linli , DING Yan ,  ZHANG Chunquan

Department of Ultrasound, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, P. R. China;

Corresponding?author：

ZHANG Chunquan, Email: jxzcq@163.com

Keywords：

Right heart contrast echocardiography; Transcranial Doppler foam test; Patent foramen ovale; Meta-analysis; Diagnostic test

DOI：

10.7507/1672-2531.202508002

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Objective To systematically review the diagnostic value of contrast transthoracic echocardiography (C-TTE) and contrast transcranial Doppler bubble test (C-TCD) for patent foramen ovale (PFO). Methods Computer searches were conducted in PubMed, Embase, Web of Science, CNKI, WanFang Data, and CBM databases to collect studies on the diagnostic value of C-TTE and C-TCD for PFO. The retrieval time limit was from the establishment of the databases to September 30, 2024. Two ultrasound diagnostic physicians independently screened the literature, extracted data, and evaluated the risk of bias in the included studies using the QUADAS-2 and QUADAS-C tools. Then, Meta-analysis was performed using Meta-DiSc version 1.4 software and R 4.4.3. Results A total of 22 studies including 2 487 patients were included. The results of the meta-analysis showed that for C-TCD in diagnosing PFO, the sensitivity (SEN), specificity (SPE), positive likelihood ratio (+LR), negative likelihood ratio (–LR), and diagnostic odds ratio (DOR) were (0.86, 95% CI 0.81 to 0.90), ( 0.85, 95% CI 0.78 to 0.91), (5.80, 95% CI 3.80 to 9.50), (0.17, 95% CI 0.12 to 0.23), and (34, 95% CI 18.00 to 68.00) respectively; for C - TTE in diagnosing PFO, the SEN, SPE, +LR, –LR, and DOR were (0.81, 95% CI 0.74 to 0.86), (0.92, 95% CI 0.87 to 0.96), (10.2, 95% CI 6.10 to 19.20), (0.21, 95% CI 0.15 to 0.28), and (50, 95% CI 26.00 to 101.00) respectively. The areas under the summary receiver - operating characteristic (SROC) curves (AUC) of C-TCD and C-TTE for diagnosing PFO were 0.90 and 0.85 respectively. Conclusion Both C-TCD and C-TTE have good sensitivity and specificity in the diagnosis of PFO and can be used as powerful tools for the examination of right-to-left shunt in PFO. However, C-TCD has slightly higher sensitivity and slightly lower specificity than C-TTE. Limited by the number and quality of the included studies, the above conclusions need to be verified by more studies.

1.	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. Mayo Clin Proc, 1984, 59(1): 17-20.
2.	Voudris KV, Poulin MF, Kavinsky CJ. Updates on patent foramen ovale (PFO) closure. Curr Cardiol Rep, 2024, 26(7): 735-746.
3.	Honasoge AP, Suradi HS, Tobis JM, et al. patent foramen ovale closure for nonstroke indications. J Soc Cardiovasc Angiogr Interv, 2023, 2(6Part A): 101135.
4.	Diener HC, Gerloff C, Thaler DE, et al. Closure of patent foramen ovale and cryptogenic stroke: unresolved issues. Curr Neurol Neurosci Rep, 2018, 18(12): 92.
5.	Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol, 2014, 13(4): 429-438.
6.	Kent DM, Wang AY. Patent foramen ovale and stroke: a review. JAMA, 2025, 334(16): 1463-1473.
7.	馬為, 楊穎, 吳永健, 等. 卵圓孔未閉超聲診斷中國專家共識. 中國介入心臟病學雜志, 2023, 31(01): 4-11.
8.	Hu X, Jiang W, Wang X, et al. Intracardiac vs transesophageal echocardiography in atrial fibrillation ablation: a randomized clinical trial. JAMA Cardiol, 2025, 10: e253687.
9.	Zhang D, Jiang L, Chen YN, et al. The diagnostic value of contrast-enhanced transcranial Doppler and contrast-enhanced transthoracic echocardiography for right to left shunt in patent foramen ovale: a systematic review and meta-analysis. Front Neurol, 2024, 15: 1447964.
10.	Tian L, Zhang M, Nie H, et al. Contrast-enhanced transcranial doppler versus contrast transthoracic echocardiography for right-to-left shunt diagnosis. J Clin Monit Comput, 2023, 37(5): 1145-1151.
11.	Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med, 2011, 155(8): 529-536.
12.	Yang B, Mallett S, Takwoingi Y, et al. QUADAS-C: a tool for assessing risk of bias in comparative diagnostic accuracy studies. Ann Intern Med, 2021, 174(11): 1592-1599.
13.	杭丹萍, 梁棟, 馬雪亮, 等. 基于貝葉斯雙變量模型和Contourlet變換相結合的紅外圖像去噪. 紅外技術, 2010, 32(10): 591-594,600.
14.	Schwab TC, Perrig L, G?ller PC, et al. Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis, 2024, 24(10): 1162-1176.
15.	Egger M, Davey SG, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
16.	Duval S. The trim and fill method//Rothstein HR, Sutton AJ, Borenstein M. Publication bias in meta-analysis-prevention, assessment and adjustments. Chichester: John Wiley&Sons Ltd, 2005: p127-144.
17.	Kent DM, Wang AY. Patent foramen ovale and stroke: a review. JAMA, 2025, 334(16): 1463-1473.
18.	Teshome MK, Najib K, Nwagbara CC, et al. Patent foramen ovale: a comprehensive review. Curr Probl Cardiol, 2020, 45(2): 100392.
19.	Krishnamurthi RV, Feigin VL, Forouzanfar MH, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the global burden of disease study 2010. Lancet, 2013, 1: e259-e281.
20.	He D, Shi Q, Xu G, et al. Clinical and infarction patterns of PFO-related cryptogenic strokes and a prediction model. Ann Clin Transl Neurol, 2018, 5(11): 1323-1337.
21.	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. Eur Heart J, 2019, 40(38): 3182-3195.
22.	Song JK. Pearls and pitfalls in the transesophageal echocardiographic diagnosis of patent foramen ovale. J Am Soc Echocardiogr, 2023, 36(9): 895-905.
23.	Palazzo P, Heldner MR, Nasr N, et al. Transcranial doppler with microbubbles: screening test to detect and grade right-to-left shunt after an ischemic stroke: a literature review. Stroke. 2024, 55(12): 2932-2941.
24.	Souteyrand G, Motreff P, Lusson JR, et al. Comparison of transthoracic echocardiography using second harmonic imaging, transcranial Doppler and transesophageal echocardiography for the detection of patent foramen ovale in stroke patients. Eur J Echocardiogr, 2006, 7(2): 147-154.
25.	Zhang D, Jiang L, Chen YN, et al. The diagnostic value of contrast-enhanced transcranial Doppler and contrast-enhanced transthoracic echocardiography for right to left shunt in patent foramen ovale: a systematic review and meta-analysis. Front Neurol, 2024, 15: 1447964.
26.	Zhao H, Yue Q, Wang T, et al. Sensitivity of contrast-enhanced transthoracic echocardiography for the detection of residual shunts after percutaneous patent foramen ovale closure. Medicine (Baltimore), 2019, 98(4): e14276.

1. 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. Mayo Clin Proc, 1984, 59(1): 17-20.
2. Voudris KV, Poulin MF, Kavinsky CJ. Updates on patent foramen ovale (PFO) closure. Curr Cardiol Rep, 2024, 26(7): 735-746.
3. Honasoge AP, Suradi HS, Tobis JM, et al. patent foramen ovale closure for nonstroke indications. J Soc Cardiovasc Angiogr Interv, 2023, 2(6Part A): 101135.
4. Diener HC, Gerloff C, Thaler DE, et al. Closure of patent foramen ovale and cryptogenic stroke: unresolved issues. Curr Neurol Neurosci Rep, 2018, 18(12): 92.
5. Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol, 2014, 13(4): 429-438.
6. Kent DM, Wang AY. Patent foramen ovale and stroke: a review. JAMA, 2025, 334(16): 1463-1473.
7. 馬為, 楊穎, 吳永健, 等. 卵圓孔未閉超聲診斷中國專家共識. 中國介入心臟病學雜志, 2023, 31(01): 4-11.
8. Hu X, Jiang W, Wang X, et al. Intracardiac vs transesophageal echocardiography in atrial fibrillation ablation: a randomized clinical trial. JAMA Cardiol, 2025, 10: e253687.
9. Zhang D, Jiang L, Chen YN, et al. The diagnostic value of contrast-enhanced transcranial Doppler and contrast-enhanced transthoracic echocardiography for right to left shunt in patent foramen ovale: a systematic review and meta-analysis. Front Neurol, 2024, 15: 1447964.
10. Tian L, Zhang M, Nie H, et al. Contrast-enhanced transcranial doppler versus contrast transthoracic echocardiography for right-to-left shunt diagnosis. J Clin Monit Comput, 2023, 37(5): 1145-1151.
11. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med, 2011, 155(8): 529-536.
12. Yang B, Mallett S, Takwoingi Y, et al. QUADAS-C: a tool for assessing risk of bias in comparative diagnostic accuracy studies. Ann Intern Med, 2021, 174(11): 1592-1599.
13. 杭丹萍, 梁棟, 馬雪亮, 等. 基于貝葉斯雙變量模型和Contourlet變換相結合的紅外圖像去噪. 紅外技術, 2010, 32(10): 591-594,600.
14. Schwab TC, Perrig L, G?ller PC, et al. Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis, 2024, 24(10): 1162-1176.
15. Egger M, Davey SG, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
16. Duval S. The trim and fill method//Rothstein HR, Sutton AJ, Borenstein M. Publication bias in meta-analysis-prevention, assessment and adjustments. Chichester: John Wiley&Sons Ltd, 2005: p127-144.
17. Kent DM, Wang AY. Patent foramen ovale and stroke: a review. JAMA, 2025, 334(16): 1463-1473.
18. Teshome MK, Najib K, Nwagbara CC, et al. Patent foramen ovale: a comprehensive review. Curr Probl Cardiol, 2020, 45(2): 100392.
19. Krishnamurthi RV, Feigin VL, Forouzanfar MH, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the global burden of disease study 2010. Lancet, 2013, 1: e259-e281.
20. He D, Shi Q, Xu G, et al. Clinical and infarction patterns of PFO-related cryptogenic strokes and a prediction model. Ann Clin Transl Neurol, 2018, 5(11): 1323-1337.
21. 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. Eur Heart J, 2019, 40(38): 3182-3195.
22. Song JK. Pearls and pitfalls in the transesophageal echocardiographic diagnosis of patent foramen ovale. J Am Soc Echocardiogr, 2023, 36(9): 895-905.
23. Palazzo P, Heldner MR, Nasr N, et al. Transcranial doppler with microbubbles: screening test to detect and grade right-to-left shunt after an ischemic stroke: a literature review. Stroke. 2024, 55(12): 2932-2941.
24. Souteyrand G, Motreff P, Lusson JR, et al. Comparison of transthoracic echocardiography using second harmonic imaging, transcranial Doppler and transesophageal echocardiography for the detection of patent foramen ovale in stroke patients. Eur J Echocardiogr, 2006, 7(2): 147-154.
25. Zhang D, Jiang L, Chen YN, et al. The diagnostic value of contrast-enhanced transcranial Doppler and contrast-enhanced transthoracic echocardiography for right to left shunt in patent foramen ovale: a systematic review and meta-analysis. Front Neurol, 2024, 15: 1447964.
26. Zhao H, Yue Q, Wang T, et al. Sensitivity of contrast-enhanced transthoracic echocardiography for the detection of residual shunts after percutaneous patent foramen ovale closure. Medicine (Baltimore), 2019, 98(4): e14276.

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