Accuracy of Transcranial Doppler Bubble Study as a Screening Method for Pulmonary Arteriovenous Malformation in Patients with Hereditary Hemorrhagic Telangiectasia and Utility of the Valsalva Maneuver Y. Raphael, P. Mulligan, J. Tobis, R. Gevorgyan, J. Giannini, J. McWilliams Departments of Radiology and Cardiology; University of California, Los Angeles INTRODUCTION MATERIALS & METHODS Results RESULTS DISCUSSION • 47 consecutive patients with clinically or genetically confirmed • TCD bubble study was positive in 28 patients:• Affecting approximately 1 in 5-8000 people, Hereditary • The study is limited by a small sample size, owing to the rarity of HHT. • 13 of these demonstrated pAVMs on chest CT. Hemorrhagic Telangiectasia (HHT) is an autosomal dominant HHT received TCD bubble study to screen for pAVM: • 5 with clinically insignificant pAVMs (< 2 mm artery). vascular disorder with a variety of clinical manifestations. • A positive TCD result (grade > 2 on either pre- or post-Valsalva) • 8 with clinically significant pAVMs (> 2 mm artery). • TCD has high sensitivity, both at rest and with Valsalva, for the detection prompted acquisition of a chest CT (28 patients). • 11 of these demonstrated no pAVMs on chest CT. of pAVM. The specificity of TCD is relatively low, and thus other imaging• Arteriovenous malformations (AVMs) typically occur in the • 3 patients with positive TCD results had pending chest CT at • 4 of these had pending chest CT at time of study. modalities are readily employed to definitively confirm the diagnosis (i.e. pulmonary, hepatic, and cerebral circulations, necessitating time of study. chest CT, pulmonary angiography). • A negative TCD result (grades 0-2) warranted no further study (19 • TCD bubble study was negative in 19 patients: early screening and intervention. At least 30-40% of patients patients). * • 15 were not further evaluated with chest CT.4 • Valsalva maneuver is useful in detecting PFO, but does not appear useful demonstrate pulmonary involvement. • 4 were evaluated with chest CT, despite negative TCD and showed no • 4 patients proceeded to evaluation with chest CT despite a in detection of pulmonary AVM. In our study, Valsalva maneuver decreased negative TCD result. radiographic evidence for pAVM. specificity without increasing sensitivity. This may be explained by the fact• The majority of pulmonary AVMs (pAVMs) cause no • Effect of Valsalva maneuver on TCD grade: out of 19 patients with that pAVMs exhibit continuous shunting, making Valsalva unnecessary to respiratory symptoms; fewer than one-third of patients exhibit negative TCD at rest, 6/19 became positive with Valsalva maneuver. All 6 augment the RLS as with PFO. • TCD bubble study was performed with Power M-mode TCD. stigmata of right-to-left shunting (e.g. cyanosis, clubbing, and had no evidence for pAVM on chest CT. polycythemia). • A head frame with mounted sonars over the temporal acoustic • TCD has several benefits, including: windows to was placed to monitor the flow in the bilateral middle TCD at rest TCD with Valsalva • Less technical expertise is required.• However, patients with pAVMs are at increased risk of cerebral arteries (MCAs). Sensitivity 12/12 (100%) 13/13 (100%) • Sedation is not needed, and procedure is well tolerated. • An agitated mixture of 8 cc saline, 0.5 cc air, and 1 cc blood was paradoxical embolism, evading the filtering capacity of Specificity 10/15 (67%) 5/15 (33%) • Performed at bedside or in the office setting. injected through the antecubital vein. • Preferred during pregnancy, when pAVMs are at higher risk for pulmonary capillary beds. • Injection was repeated during calibrated Valsalva strain (40 mmHg) Table 1: Sensitivity and specificity of TCD, both at rest and with Valsalva, with chest CT used as the gold standard. enlargement and rupture, due to ease of posture and access. with manometer for visual feedback.• Catastrophic embolic cerebral events (i.e. abscesses and • The appearance of the bubbles in cerebral circulation, signified by TCD results performed at rest • Disadvantages of TCD include: stroke) as well as transient ischemic attacks (TIAs) impose sharp wave deflections, confirmed the presence of RLS. Negative CT Insignificant AVM Significant AVM 10/10 (100%) 0 0 • A positive TCD does not confer information about the anatomic origin of significant morbidity and mortality in this population. Grades 0-2 RLS and is unable to distinguish between intra- and extracardiac shunts. Grade 3 2/4 (50%) 1/4 (25%) 1/4 (25%) • In contrast, TTE or TEE can often differentiate between PFO and pAVM• Since neither AVM size nor patient symptom severity can Grade 4 4/6 (67%) 2/6 (33%) 0 by noting the number of cardiac cycles between bubble injection and adequately assess the risk of paradoxical emboli, all pAVMs Grade 5 0 1/7 (14%) 6/7 (86%) appearance of bubbles in the left ventricle. with feeding arteries > 2-3 mm are treated with embolization. TCD results performed during Valsalva maneuver • TTE and TEE provide additional information about heart function and Negative CT Insignificant AVM Significant AVM pulmonary arterial pressure.• Due to high risk, HHT patients should be screened for Grades 0-2 5/5 (100%) 0 0 asymptomatic pAVM. A variety of diagnostic modalities are Grade 3 7/8 (88%) 0 1/8 (12%) • Causes of false negative TCD include: Grade 4 3/7 (43%) 4/7 (57%) 0 • Operator inexperience. available, but the optimal study has yet to be determined. Grade 5 0 1/8 (12%) 7/8 (88%) • Faulty agitated saline injection technique. Table 2. CT results stratified by TCD grade. CT result was classified as • Supine positioning (decreases sensitivity compared with upright position).• Transcranial doppler (TCD) bubble study is a non-invasive negative (no AVM), insignificant (AVM up to 2 mm) or significant (AVM ultrasound procedure that uses high frequency sound waves to >2 mm). monitor blood flow through cerebral blood vessels. If bubbles • Using the Spencer logarithmic scale, a grade of 0-5 is designated, CONCLUSION are seen following infusion of agitated saline bubbles into a according to the number of microbubbles visualized in both MCAs •TCD bubble study offers an equally sensitive and simple office-based peripheral IV, pAVM is suggested. within one minute of injection. alternative to TTE for the detection of pAVM in patients with known or Grade # of Microbubbles suspected HHT. 5• During TCD, a Valsalva maneuver is commonly performed to 0 0 reverse the interatrial pressure gradient (normally left-to- Negative TCD 1 1-10 • TCD grades 0-2 confer negative CT for pAVMs. With increasing right ) and theoretically augment a potential right-to-left shunt 2 11-30 grade >2, there is increasing likelihood of significant pAVM on chest (RLS). This is particularly relevant in detecting patent 3 31-100 CT. Most significant pAVMs on CT demonstrate grade 5 results on foramen ovale, but its value in detecting pAVM is uncertain. Positive TCD 4 101-300 TCD. 5 > 300• A recent study showed that TCD had the same sensitivity but • No increased sensitivity is bestowed with performance of the Valsalva improved specificity compared to transthoracic maneuver during TCD, and specificity for pAVM actually decreases. Figure 1. Sample TCD report. During normal respiration, the result is echocardiography (TTE) in detecting pAVM in HHT patients.5 grade 2 (negative). With Valsalva maneuver, the result is grade 3 (positive). Chest CT was negative. • Use of Valsalva maneuver is unnecessary and leads to extraneous CT scans in the HHT population. PURPOSE Grade 0 Grade 1 Grade 2 LITERATURE CITED 1. Govani, F and Shovlin, C. Hereditary Haemorrhagic Telangiectasia: a Clinical and Scientific Review. European Journal of Human Genetics 2009; 17: 860-871.• Hypothesis 1: The Valsalva maneuver, routinely performed 2. 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