Application and Efficacy Evaluation of Optimized cTCD and cTTE Synchronous Detection in the Diagnosis of Right-to-Left Shunt

doi:10.3969/j.issn.1673-5765.2025.09.007

Abstract

Abstract: Objective To evaluate the diagnostic value of optimized contrast transcranial Doppler (cTCD) combined with contrast transthoracic echocardiography (cTTE) in synchronous detection of right-to-left shunt (RLS), optimize the procedural timing, and quantify the timing control between the Valsalva maneuver (VM) and intravenous injection of agitated saline.
Methods A retrospective analysis was conducted on patients who underwent RLS screening at the Second Xiangya Hospital of Central South University from September 2023 to September 2024 due to dizziness, headache, syncope, or cryptogenic stroke. Patients were divided into three groups according to the examination strategy: the optimized synchronous group (underwent optimized cTCD combined with cTTE synchronous detection), the optimized cTCD group (underwent optimized cTCD alone), and the non-optimized cTCD group (underwent conventional cTCD alone). The positive rate and grading distribution of RLS were compared among the groups. In the optimized synchronous group, patients underwent contrast transesophageal echocardiography (cTEE), which was used as the gold standard for diagnosing patent foramen ovale (PFO). The consistency of optimized cTCD combined with cTTE synchronous detection in the diagnosis and grading of PFO was evaluated. The time intervals between the VM and injection of agitated saline, as well as the cardiac cycle, were recorded in the optimized protocol. The correlation between these procedural time intervals and cardiac cycles was analyzed.
Results A total of 342 patients who underwent RLS screening due to dizziness, headache, syncope, or cryptogenic stroke were included in the study. Among them, 99 were male and 243 were female, with a mean age of (38.3±14.8) years. The positive rates of RLS in the optimized synchronous group (192 patients) and the optimized cTCD group (112 patients) were higher than that in the non-optimized cTCD group (38 patients) (78.13% vs. 47.37%, P<0.001; 58.93% vs. 47.37%, P<0.001). Among the 121 patients in the optimized synchronous group who completed cTEE examination, 111 had RLS caused by PFO (58 with RLS solely from PFO and 53 with combined pulmonary-level RLS), and 10 had isolated pulmonary-level RLS. The optimized synchronous cTCD combined with cTTE synchronous detection showed moderate consistency with cTEE in PFO grading (κ=0.44). The optimized synchronous group demonstrated good consistency and procedural efficiency in timing control, with median time intervals of 5.0 seconds (7.0 median cardiac cycles) from the start of agitated saline injection to VM release (injection→VM release), and 2.0 seconds (2.0 median cardiac cycles) from VM release to the first microbubble detection by cTCD (VM release→bubble). The time intervals between procedural points and cardiac cycles showed positive correlations (injection→VM release: r=0.645, P<0.001; VM release→bubble: r=0.827, P<0.001).
Conclusions The optimized cTCD combined with cTTE synchronous detection showed a higher positive rate of RLS compared to optimized cTCD alone or conventional cTCD alone, demonstrating superior procedural guidance.

Key words: Contrast transcranial Doppler; Contrast transthoracic echocardiography; Contrast transesophageal echocardiography; Right-to-left shunt

摘要： 目的评估优化的对比增强经颅多普勒超声（contrast transcranial Doppler，cTCD）联合对比增强经胸超声心动图（contrast transthoracic echocardiography，cTTE）同步检测对右向左分流（right-to-left shunt，RLS）的诊断价值，并优化流程操作时机，量化瓦氏动作（Valsalva maneuver，VM）与静脉推注激活生理盐水的时间控制。
方法回顾性分析2023年9月—2024年9月在中南大学湘雅二医院因头晕、头痛、晕厥和不明原因型卒中接受RLS筛查的患者，根据检查策略将患者分为3组：优化同步组（进行优化的cTCD联合cTTE同步检测），优化单项组（进行优化cTCD检测），以及非优化单项组（进行传统cTCD检测）。比较各组RLS阳性检出率及分级分布情况。优化同步组中患者完善对比增强经食管超声心动图（contrast transesophageal echocardiography，cTEE）检查，以cTEE诊断卵圆孔未闭（patent foramen ovale，PFO）为金标准，比较优化的cTCD联合cTTE同步检测对PFO诊断及分级的一致性。统计优化后流程中VM与激活生理盐水注射的时间间隔及心动周期，分析各操作节点时间间隔与心动周期之间的相关性。
结果共纳入342例因头晕、头痛、晕厥、不明原因型卒中进行RLS筛查的患者，其中男性99例，女性243例，平均年龄为（38.3±14.8）岁。优化同步组（192例）及优化单项组（112例）RLS阳性率高于非优化单项组（38例）（78.12% vs. 47.37%，P＜0.001；58.93% vs. 47.37%，P＜0.001）。在完善cTEE检查的优化同步组121例患者中，111例存在由PFO引起的RLS（58例单纯由PFO引起的RLS，53例合并肺水平RLS），10例为单纯肺水平RLS，优化的cTCD联合cTTE同步检测与cTEE在PFO分级诊断中具有中等一致性（κ=0.44）。优化同步组在激活生理盐水开始推注到VM释放（简称推→V松）、VM释放后cTCD检测到第一个微气泡信号（简称V松→泡）的时间点控制上，展现出了良好的一致性与操作效率，推→V松和V松→泡的中位时间间隔分别为5.0 s和2.0 s，中位心动周期分别为7.0个和2.0个心动周期，各动作节点的时间间隔和心动周期呈正相关（推→V松：r=0.645，P＜0.001；V松→泡：r=0.827，P＜0.001）。
结论优化的cTCD联合cTTE同步检测RLS的阳性检出率高于优化cTCD单项检测与传统cTCD单项检测，具有较高的操作指导价值。

关键词: 对比增强经颅多普勒超声; 对比增强经胸超声心动图; 对比增强经食管超声心动图; 右向左分流

CLC Number:

R74
R445

WANG Changlun, LIU Yanjun, AI Qi, WU Qin, ZHAN Yajing. Application and Efficacy Evaluation of Optimized cTCD and cTTE Synchronous Detection in the Diagnosis of Right-to-Left Shunt[J]. Chinese Journal of Stroke, 2025, 20(9): 1121-1130.

王昶仑, 刘艳君, 艾祁, 吴勤, 占雅静. 优化的cTCD联合cTTE同步检测在右向左分流诊断中的应用与效能评估[J]. 中国卒中杂志, 2025, 20(9): 1121-1130.

References

[1] AGNOLETTI G，BOUDJEMLINE Y，OU P，et al. Right to left shunt through interatrial septal defects in patients with congenital heart disease：results of interventional closure[J]. Heart，2006，92（6）：827-831.
[2] SOMMER R J，HIJAZI Z M，RHODES J F，Jr. Pathophysiology of congenital heart disease in the adult. Part Ⅰ：shunt lesions[J]. Circulation，2008，117（8）：1090-1099.
[3] PUSHPARAJAH K. Non-invasive imaging in the evaluation of cardiac shunts for interventional closure[J/OL]. Front Cardiovasc Med，2021，8：651726[2025-06-01]. https://doi.org/10.3389/fcvm.2021.651726.
[4] ZHAO Q X，LIU R，ZHOU J，et al. Prevalence and grade of RLS in migraine：a prospective study of 251 migraineurs by synchronous test of c-TTE and c-TCD[J/OL]. Medicine（Baltimore），2021，100（4）：e24175[2025-06-01]. https://doi.org/10.1097/MD.0000000000024175.
[5] MOJADIDI M K，ZAMAN M O，ELGENDY I Y，et al. Cryptogenic stroke and patent foramen ovale[J]. J Am Coll Cardiol，2018，71（9）：1035-1043.
[6] LIU D，CHEN K Y，GONG J，et al. Right-to-left shunts in unexplained syncope：an age- and sex-matched case-control study[J]. Quant Imaging Med Surg，2022，12（7）：3592-3602.
[7] PICK A，DESCHAMPS C，STANSON A W. Pulmonary arteriovenous fistula：presentation，diagnosis，and treatment[J]. World J Surg，1999，23（11）：1118-1122.
[8] RAPTIS D A，SHORT R，ROBB C，et al. CT appearance of pulmonary arteriovenous malformations and mimics[J]. Radiographics，2022，42（1）：56-68.
[9] SARIC M，ARMOUR A C，ARNAOUT M S，et al. Guidelines for the use of echocardiography in the evaluation of a cardiac source of embolism[J]. J Am Soc Echocardiogr，2016，29（1）：1-42.
[10] RODRIGUES A C，PICARD M H，CARBONE A，et al. Importance of adequately performed Valsalva maneuver to detect patent foramen ovale during transesophageal echocardiography[J]. J Am Soc Echocardiogr，2013，26（11）：1337-1343.
[11] 中国医师协会神经内科医师分会神经超声专业委员会，中华医学会神经病学分会神经影像协作组. 中国神经超声的操作规范（二）[J]. 中华医学杂志，2017，97（41）：3208-3212.
Neurosonology Committee，Neurology Branch，Chinese Medical Doctor Association； Neuroimaging Group of Chinese Society of Neurology. Chinese consensus guidelines for neurosonography practice（part Ⅱ）[J]. Natl Med J China，2017，97（41）：3208-3212.
[12] 中国医师协会心血管内科医师分会结构性心脏病学组，心源性脑卒中人群的高危预测模型及治疗策略的临床研究课题组. 卵圆孔未闭超声诊断中国专家共识[J]. 中国介入心脏病学杂志，2023，31（1）：4-11.
Chinese College of Cardiovascular Physicians Structural Cardiology Group，Clinical Study Group on High-risk Prediction Model and Treatment Strategy of Cardiogenic Stroke Population. Chinese expert consensus on ultrasound diagnosis of patent foramen ovale[J]. Chin J Intervent Cardiol，2023，31（1）：4-11.
[13] 李贺智，何亚峰，王琦光，等. 卵圆孔未闭超声心动图及右心声学造影临床操作规范[J]. 中国实用内科杂志，2022，42（5）：376-380.
LI H Z，HE Y F，WANG Q G，et al. Standard operating specifications for echocardiography and contrast[J]. Chinese Journal of Practical Internal Medicine，2022，42（5）：376-380.
[14] VELTHUIS S，BUSCARINI E，VAN GENT M W F，et al. Grade of pulmonary right-to-left shunt on contrast echocardiography and cerebral complications：a striking association[J]. Chest，2013，144（2）：542-548.
[15] SONG L，SHI P X，ZHENG X Z，et al. Echocardiographic characteristics of transcatheter closure of patent foramen ovale with mallow biodegradable occluder：a single-center，phase Ⅲ clinical study[J/OL]. Front Cardiovasc Med，2022，9：945275[2025-06-01]. https://doi.org/10.3389/fcvm.2022.945275.
[16] WAMMES-VAN DER HEIJDEN E A，TIJSSEN C C，EGBERTS A C G. Right-to-left shunt and migraine：the strength of the relationship[J]. Cephalalgia，2006，26（2）：208-213.
[17] KANEMARU K，UENO Y，KIKUNO M，et al. High-risk patent foramen ovale and elderly in cryptogenic stroke[J/OL]. J Stroke Cerebrovasc Dis，2023，32（11）：107344[2025-06-01]. https://doi.org/10.1016/j.jstrokecerebrovasdis.2023.107344.
[18] PÖYHÖNEN P，KUUSISTO J，PIRINEN J，et al. Right atrium and cryptogenic ischaemic stroke in the young：a case-control study[J/OL]. Open Heart，2021，8（1）：e001596[2025-06-01]. https://doi.org/10.1136/openhrt-2021-001596.
[19] FILOMENA D，CIMINO S，MAESTRINI V，et al. The evolving role of echocardiography in the assessment of patent foramen ovale in patients with left-side thromboembolism[J]. Echocardiography，2021，38（4）：657-675.
[20] 翟亚楠，李爱莉，谢万木，等. 右心声学造影检测肺血管病心内及肺循环右向左分流的临床价值[J]. 中国超声医学杂志，2021，37（9）：1002-1005.
ZHAI Y N，LI A L，XIE W M，et al. The value of saline contrast echocardiography in clinical evaluation of right to left shunt in pulmonary vascular disease[J]. Chinese J Ultrasound Med，2021，37（9）：1002-1005.
[21] OMURO A，WADA Y，YOSHIGA Y，et al. Prevalence and characteristics of transesophageal echocardiography-related esophageal mucosal injury in patients with atrial fibrillation who underwent pulmonary vein isolation[J/OL]. Int J Cardiol，2022，350：118-124[2025-06-01]. https://doi.org/10.1016/j.ijcard.2021.12.057.
[22] CHEN L Z，YANG Y J，TANG L，et al. Embolic stroke associated with a pulmonary arteriovenous fistula：an unignorable rare causes of stroke[J]. Neurologist，2023，28（3）：180-183.
[23] XU S P，HONG M F，ZHOU Z H. Images of the month 1：ischaemic stroke due to pulmonary arteriovenous fistula[J]. Clin Med（Lond），2022，22（3）：278-279.
[24] GAZZANIGA P，BUSCARINI E，LEANDRO G，et al. Contrast echocardiography for pulmonary arteriovenous malformations screening：does any bubble matter？[J]. Eur J Echocardiogr，2009，10（4）：513-518.
[25] LEE M，OH J H. Echocardiographic diagnosis of right-to-left shunt using transoesophageal and transthoracic echocardiography[J/OL]. Open Heart，2020，7（2）：e001150[2025-06-01]. https://doi.org/10.1136/openhrt-2019-001150.
[26] GOLDBERG H，ELISBERG E I，KATZ L N. The effects of the Valsalva-like maneuver upon the circulation in normal individuals and patients with mitral stenosis[J]. Circulation，1952，5（1）：38-47.
[27] KORNER P I，TONKIN A M，UTHER J B. Reflex and mechanical circulatory effects of graded Valsalva maneuvers in normal man[J]. J Appl Physiol，1976，40（3）：434-440.
[28] 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]. J Am Coll Cardiol，1991，18（4）：1112-1117.
[29] WANG S B，WANG X C，MA Y，et al. Right-to-left shunt detection using contrast-enhanced transcranial Doppler：a comparison of provocation maneuvers between coughing and a modified Valsalva maneuver[J/OL]. PLoS One，2017，12（4）：e0175049[2025-06-01]. https://doi.org/10.1371/journal.pone.0175049.
[30] DROSTE D W，SILLING K，STYPMANN J，et al. Contrast transcranial Doppler ultrasound in the detection of right-to-left shunts：time window and threshold in microbubble numbers[J]. Stroke，2000，31（7）：1640-1645.
[31] DROSTE D W，LAKEMEIER S，WICHTER T，et al. Optimizing the technique of contrast transcranial Doppler ultrasound in the detection of right-to-left shunts[J]. Stroke，2002，33（9）：2211-2216.
[32] DROSTE D W，JEKENTAITE R，STYPMANN J，et al. Contrast transcranial Doppler ultrasound in the detection of right-to-left shunts：comparison of Echovist-200 and Echovist-300，timing of the Valsalva maneuver，and general recommendations for the performance of the test[J]. Cerebrovasc Dis，2002，13（4）：235-241.
[33] LANGE M C，ZÉTOLA V F，PIOVESAN E J，et al. Valsalva maneuver procedures in the diagnosis of right-to-left shunt by contrast-enhanced transcranial Doppler using agitated saline solution with blood as a contrast agent[J]. Arq Neuropsiquiatr，2010，68（3）：410-413.
[34] XU K，TIAN X G，HAO M F，et al. Diagnostic value of contrast-enhanced ultrasonography for patent foramen ovale detection[J]. J Thorac Dis，2024，16（5）：3282-3290.
[35] YANG X X，WANG H，WEI Y J，et al. Diagnosis of patent foramen ovale：the combination of contrast transcranial Doppler，contrast transthoracic echocardiography，and contrast transesophageal echocardiography[J/OL]. Biomed Res Int，2020：8701759[2025-06-01]. https://doi.org/10.1155/2020/8701759.