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Original Research: PULMONARY VASCULAR DISEASE |

Contrast Echocardiography Grading Predicts Pulmonary Arteriovenous Malformations on CT* FREE TO VIEW

Katherine Zukotynski, MD, BASc; Raymond P. Chan, MD, FRCPC; Chi-Ming Chow, MD, FRCPC; Justine H. Cohen, MSc; Marie E. Faughnan, MD, MSc, FRCPC
Author and Funding Information

*From the Departments of Medical Imaging (Drs. Chan and Zukotynski) and Medicine (Drs. Chow, Faughnan, and Ms. Cohen), St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada.

Correspondence to: Marie E. Faughnan, MD, MSc, FRCPC, St. Michael’s Hospital, 30 Bond St, Suite 6–049, Toronto, ON, Canada, M5B-1W8; e-mail: faughnanm@smh.toronto.on.ca



Chest. 2007;132(1):18-23. doi:10.1378/chest.06-2356
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Published online

Background: Untreated pulmonary arteriovenous malformations (PAVMs) can present with life-threatening complications. Agitated saline solution transthoracic contrast echocardiography (TTCE) has been recommended as the screening test of choice for PAVMs in hereditary hemorrhagic telangiectasia (HHT). A TTCE grading system has been proposed but not validated. The aim of this study was to determine the positive predictive value (PPV) of TTCE grades for the presence of PAVMs on CT.

Methods: A blinded retrospective review was conducted. All patients screened at the Toronto HHT Center (June 2002 to September 2004) with positive TTCE results were included. TTCE results were scored for delay (number of cardiac cycles) before appearance of microcavitations in the left atrium and graded for intensity of opacification. Grade 1 indicates minimal left ventricular opacification, grade 2 indicates moderate opacification, grade 3 indicates extensive opacification without outlining the endocardium, and grade 4 indicates extensive opacification with endocardial definition. Thoracic CT was performed in all patients, and results were scored as positive, negative, or indeterminate for PAVMs.

Results: Of 155 patients screened for PAVMs, 104 had positive TTCE results. Complete data were available for 90 patients (87%). Mean age was 45 years; 62% were female. Seventeen percent of patients screened and 27% of patients with positive TTCE results had CT detectable PAVMs. There was a significant association between TTCE grade and presence of PAVMs on CT (p < 0.0001). The PPV of grades 1, 2, 3, and 4 were 0.02 (95% confidence interval, 0.00 to 0.06), 0.25 (95% confidence interval, 0.06 to 0.44), 0.56 (95% confidence interval, 0.23 to 0.88), and 1.0 (95% confidence interval, 1.0 to 1.0), respectively.

Conclusions: Increased shunt grade predicts increased probability of PAVMs and may be used to guide decisions in the screening algorithm for PAVMs.

Figures in this Article

Pulmonary arteriovenous malformations (PAVMs) are abnormal fistulous connections between arteries and veins in the lungs, without intervening capillaries, first described in 1897 by Churton.1Only three cases of PAVMs were detected in 15,000 consecutive autopsies according to an early study from Johns Hopkins Hospital2suggesting a prevalence of 1 in 5,000 in the general population. Hereditary hemorrhagic telangiectasia (HHT) is the underlying cause of approximately 80% of PAVMs,34 although mechanisms of development of PAVMs are not well understood.

HHT or Osler-Weber-Rendu disease is an autosomal dominant condition characterized by vascular dysplasia, with an estimated prevalence of 1 in 5,000. Disease expression is age dependent, and > 90% of individuals are symptomatic by age 40 years.5 Approximately 15 to 46% of patients with HHT have PAVMs.48

PAVMs result in direct right-to-left shunt; and although frequently asymptomatic, patients may present with life-threatening complications.3,9 In a study3 of 76 consecutive patients prior to embolotherapy, the prevalence of previous stroke was reported in 18%, transient ischemic attack in 37%, cerebral abscess in 10%, massive hemoptysis in 13%, and spontaneous hemothorax in 9%. Early diagnosis is essential because these complications can be prevented with PAVM embolotherapy and antibiotic prophylaxis for bacteremic procedures.10 Embolotherapy is the treatment of choice and is indicated for PAVMs with a feeding artery diameter ≥ 3 mm.3

Several screening tests are available for PAVMs. Pulmonary angiography has historically been accepted as the reference standard. With recent technological advances, CT approaches the sensitivity and specificity of angiography.11 Unfortunately, CT results in radiation exposure to the patient and pulmonary angiography is invasive; therefore, these are not ideal screening tests but best used as confirmatory imaging. Alternative methods of screening include chest radiography, arterial oxygen measurements, radionuclide lung scanning, and agitated saline solution transthoracic contrast echocardiography (TTCE).10

TTCE has been recommended as the initial screening test of choice for patients with HHT or suspected PAVMs.67 It is accessible, minimally invasive, and has a sensitivity of 92 to 93%.7 During TTCE, agitated saline solution is injected IV and then resulting microbubbles opacify the right side of the heart. Since the diameter of the pulmonary capillaries is smaller than that of the microbubbles, appearance of bubbles in the left atrium implies a right-to-left shunt. Patients with intracardiac shunt show rapid opacification of the left heart, within one to three cardiac cycles after opacification of the right heart. Patients with PAVMs, and other causes of intrapulmonary shunt, are generally reported to present more delayed opacification of the left heart, at least four cardiac cycles after opacification of the right heart,12 although there are no studies in the literature specifically analyzing bubble appearance timing in relation to location of shunt.

In 1991, Barzilai et al13 proposed a grading system to further characterize intrapulmonary shunt on TTCE. The degree of left ventricular opacification on contrast echocardiography was graded on a four-point scale of 1+ through 4+, with 1+ indicating minimal opacification and 4+ indicating intense opacification with left ventricular endocardial outline. Patients with higher-grade left ventricular opacification were reported to have large feeding vessels or multiple malformations, while those with lower grades were more likely to have small or isolated malformations. Currently, this grading system is not widely used because it has not been further validated. The aims of this study were to determine the positive predictive values (PPV) of the proposed TTCE grades for the presence of PAVMs at CT, and to illustrate the usefulness of TTCE grading in initial screening assessments of patients with HHT.

A retrospective review of charts, TTCE, and imaging was conducted. One hundred fifty-five consecutive newly referred patients to the Toronto HHT Center (adult clinic) were screened with TTCE between June 2002 and September 2004. All patients with positive TTCE results were included in this study and underwent thoracic CT scanning. This was the routine screening protocol followed for all patients referred to the HHT Center from 2002 to 2004. For each patient, the TTCE was reviewed for the presence of a patent foramen ovale (PFO). The Toronto HHT Center at St. Michael’s Hospital and University of Toronto is a specialized clinic at a tertiary care, university-affiliated, teaching hospital that encompasses a national referral base from within Canada. The study protocol was approved by the hospital research ethics board.

TTCE

Standard TTCE was performed on all patients as previously described.6 This procedure was implemented as our laboratory procedure several years prior, and all laboratory technicians and attending echocardiographers have been trained to follow this standard procedure. In each case, an IV line with saline solution lock was placed in the patient’s forearm (typically 19 gauge, 2.5 cm). A three-way stopcock was attached, and two 10-mL syringes were attached to the other two ports. One 10-mL syringe was empty, with air excluded, and the other was filled with saline solution. The agitated saline solution contrast was obtained by flushing the saline solution from one syringe to the other. The patient was positioned in the left lateral decubitus position, and 10 mL of agitated saline solution (bubbles) were injected by hand while echocardiographic images were obtained simultaneously in the apical four-chamber view. If the decubitus TTCE result was negative, the study was repeated in the sitting position in an attempt to increase the sensitivity for detection of shunting due to lower lobe PAVMs.

TTCE results were defined as positive if saline solution contrast was observed in the left atrium after injection. All TTCEs were scored by an experienced echocardiographer (C.M.C.), who was blinded to the CT results, for delay (number of cardiac cycles before appearance of bubbles in the left atrium, after their first appearance in the right atrium) and graded for intensity of opacification. Relative opacification was graded as either 1 (minimal left ventricular opacification), 2 (moderate), 3 (extensive without outlining the endocardium), or 4 (extensive with endocardial definition), according the proposed grading system described by Barzilai et al.13 TTCE grade was also reported at the time of TTCE by an attending echocardiographer (one of five echocardiographers), and these results were for compared with the study TTCE grade by C.M.C., for calculation of interobserver agreement. Examples of the appearance of left ventricular opacification for each TTCE grade are illustrated in Figure 1 .

CT of Thorax

All patients with positive TTCE results underwent thoracic CT. Twelve patients had previously undergone scanning at their referring institutions. The remaining 92 patients underwent imaging with a helical scanner (LightSpeed QXi; General Electric; Milwaukee, WI) at our center using the following protocol: noncontrast-enhanced helical acquisitions during a single breath-hold in the supine position, with a collimation of 7.5 mm, table speed of 11.25 cm/s with no overlap, 120 kilovolt peak, current of 200 mA, and exposure time of 0.8 s per rotation. Images were reconstructed at a slice thickness of 3.75 mm with 1.8 mm of overlap in both standard soft-tissue and lung algorithms. All CTs were reviewed by an experienced radiologist, blinded to the TTCE results, and scored as positive, negative, or indeterminate for PAVMs.

Statistical Analysis

A Pearson χ2 test for association was performed (SAS v8.2; SAS Institute; Cary, NC) in order to determine if there was a significant association between TTCE grade and presence of PAVMs on CT scan with a significance level of α = 0.05. The PPV of TTCE was calculated using CT as the reference standard. The PPV represents the percentage of the sample with a given TTCE grade that was determined to have PAVMs on CT. A multivariate logistic regression analysis with was also performed in SAS v8.2 to determine if there was a significant association between presence of PAVM and TTCE grade and/or number of cardiac cycles before bubble appearance (the level of significance utilized for this analysis was α = 0.05).

Of 155 patients screened with TTCE, 104 patients (67%) had positive TTCE results. Mean patient age was 45 years (range, 16 to 75 years). The majority of patients screened were female (62%).

Of 104 patients with positive TTCE results, we had complete data for 90 patients (87%). In 14 patients, data were incomplete because the echocardiography tapes were lost and the studies could not be reviewed. Twenty-four of the 90 patients (27%) for whom we had both TTCE and CT data had CT detectable PAVMs. Two CTs were scored as indeterminate and were considered positive for the purpose of the analysis. One of these patients was later shown not to have a PAVM on pulmonary angiography, while the second patient had not undergone angiography at the time of our analysis. Six of 104 patients had a PFO, and 5 of the 6 patients did not have a CT detectable PAVM. Table 1 shows the PPVs for the 90 patients for whom complete data were available. TTCE grade was significantly associated with the probability of detecting PAVMs on CT (p < 0.0001). PAVMs were detected in only 1 of 51 patients with grade 1 TTCE, who had four PAVMs, each with feeding artery diameter < 1 mm. Of 12 patients with grade 4 TTCE, all had CT detectable PAVM with at least one feeding vessel ≥ 3 mm. More than half of the patients (8 of 12 patients, 67%) with grade 4 TTCE had multiple PAVMs.

The number of cardiac cycles before the appearance of bubbles in the left ventricle was not statistically significantly associated with the presence of PAVMs on CT (p > 0.05). Table 2 lists the mean number of cardiac cycles before the appearance of bubbles in the left ventricle for each TTCE grade (this includes all patients, those with and those without PAVMs). In patients with CT detectable PAVMs, bubbles were seen in the left ventricle after 3 to 10 cardiac cycles (mean, 6 cardiac cycles). In patients without CT detectable PAVMs, bubbles were seen in the left ventricle after 1 to 17 cardiac cycles (mean, 6 cardiac cycles). There was overlap in bubble appearance timing among patients with PAVMs, with PFO, and “false-positives” (without PAVMs or PFO). Patients with early appearance of bubbles (less than or equal to three cardiac cycles) and PAVM on CT were TTCE grade 3 or 4. Most patients with very late appearance of bubbles were TTCE grade 1 and had no PAVMs on CT.

In 87 of 90 patients, attending echocardiographer TTCE grade was available and was compared to TTCE grade (by C.M.C.), with an interobserver agreement of 87%. Of the 11 cases for which there was disagreement, the disagreement was within 1 grade in 10 cases (91%).

Patients with PAVMs are at significantly increased risk of complications including stroke, cerebral abscess, and massive pulmonary hemorrhage.34,10 Early diagnosis of PAVMs is important so that preventative treatment with embolotherapy may be performed.34,10 TTCE has been recommended as the screening test of choice for PAVMs, although the intensity of shunting on TTCE remains of uncertain clinical significance. We demonstrate here that TTCE shunt grading predicts the probability of PAVMs on CT.

Prior studies67 have found that TTCE is a sensitive screening tool for PAVMs in HHT patients. Our results demonstrate a statistically significant association between proposed TTCE grade and the probability of detecting a PAVM on thoracic CT (p < 0.0001). Our results indicate that patients with grade 1 TTCE are unlikely to have a CT detectable PAVM, although we have previously reported one patient with a grade 1 TTCE who presented with stroke secondary to PAVM.14 Patients with grade 4 TTCE will almost certainly require antibiotic prophylaxis as well as transcatheter embolotherapy for PAVMs.

TTCE is accessible, minimally invasive, and has a high sensitivity, making it a desirable initial screening method.67 The advantage of a screening algorithm using TTCE first with CT for confirmation is demonstrated in our series, in which one third of patients screened for PAVM were spared the radiation dose of CT. In addition, the TTCE grade, and therefore the probability of detecting PAVMs on CT, can be used to make decisions about the timing or urgency of confirmatory CT. One of the challenges of TTCE is the high number of false-positive results.7 Only 5 of the 66 patients with false-positive TTCE results were found to have PFO as a possible explanation. The high false-positive rate may reflect interobserver variability in TTCE interpretation, although our group has previously demonstrated an excellent κ (0.926) for identifying microcavitations in the left atrium,6 and here we report very good interobserver agreement (87%) for TTCE grading. More likely the false-positive results represent the presence of microscopic PAVMs, detected with TTCE but too small to visualize on CT or angiography. Our group15 has previously demonstrated that 90% of patients with PAVMs retain a positive TTCE result after successful embolotherapy, which we have interpreted as evidence that patients with CT detectable PAVMs also have other smaller PAVMs, not visualized at CT or angiography. In other words, we hypothesize that many of the false-positive results reported here may in fact be cases of microscopic PAVMs. We have therefore elected to follow these patients prospectively for growth of PAVMs and also have recommended antibiotic prophylaxis.

At this point, we do not have sufficient long-term follow-up data to report on outcomes in the group of patients with false-positive results. With long-term follow-up, likely in the order of 10 years, we should be able to better conclude about whether PAVMs do become detectable on CT or whether complications from PAVMs develop in these patients. Until we have these data, it is unclear how these patients should be followed up and even, in fact, whether CT is necessary in the patient with a grade 1 TTCE. With our previous reported experience of one patient with a grade 1 TTCE who presented with stroke secondary to PAVM,14 and the fact that our patients are very motivated to avoid preventable stroke and other complications of PAVMs, our approach continues to include CT assessment of patients with grade 1 TTCE and follow-up CT within 1 to 3 years afterwards.

The timing of appearance of opacification during TTCE by convention has been used to discern intracardiac from intrapulmonary shunt, although there is little literature validating this approach. We observed that in fact patients with intrapulmonary shunt could have appearance of bubbles as early as three cardiac cycles, often in patients with high grades of shunt (grade 3 or 4). In addition, we observed considerable overlap in bubble appearance timing among patients with PAVMs, patients with PFO, and false-positive results. In other words, the timing of appearance of bubbles is often not a reliable indicator of location of shunt and may be influenced by intensity of shunt.

There are some limitations to this study. The TTCE grading system is subjective because the quantity of bubbles in the left ventricle used to define a specific TTCE grade is approximate. Also, variability secondary to the intensity of hand agitation, rapidity of injection, and cardiac output may result in small differences in timing and grade. We believe that these limitations should not significantly influence the interpretation of our results because they would have been expected to have weakened the significance of the observed association, and yet in this study the grading was highly statistically significantly associated with the probability of detecting PAVMs on CT. In order to clarify our interpretation of the grading system and provide a standard for other studies, a reference set of images illustrating the appearance of each TTCE grade has been presented in Figure 1. We report very good interobserver variability for TTCE grading, but this may not be generalizable to centers with less experience.

We used CT of the thorax as the “gold standard” for the diagnosis of PAVMs in this study. CT was shown in 1992 to be approximately 97% sensitive for the detection of PAVMs, compared to the conventional “gold standard,” pulmonary angiography.16 With the dramatic advances in CT technology over the last 10 to 15 years, and the ability to detect smaller and smaller PAVMs (feeding artery as small as 1 mm in diameter), although there are no recent studies of the sensitivity of CT for PAVM detection, the sensitivity of CT now likely exceeds that of conventional pulmonary angiography. CT has therefore become the accepted “gold standard” for the detection of PAVMs in recent clinical studies. We therefore did not feel that the use of CT as the “gold standard” was a limitation to this study.

We have demonstrated that TTCE shunt grading, on a four-point scale, is significantly associated with the probability of detecting PAVMs on CT. This provides additional information that is clinically relevant in guiding decision making about further diagnostic testing.

Abbreviations: HHT = hereditary hemorrhagic telangiectasia; PAVM = pulmonary arteriovenous malformation; PFO = patent foramen ovale; PPV = positive predictive value; TTCE = transthoracic contrast echocardiography

Financial support (M.E.F) was provided by the Nelson Arthur Hyland Foundation, St. Michael’s Hospital Research Institute.

This study was conducted at St. Michael’s Hospital.

The authors have no conflicts of interest to disclose.

Figure Jump LinkFigure 1. Appearance of left ventricular opacification following injection of agitated saline solution for each TTCE grade. Top left, A: grade 1, minimal left ventricular opacification; top right, B: grade 2, moderate left ventricular opacification; bottom left, C: grade 3, extensive left ventricular opacification without outlining the endocardium; and bottom right, D: grade 4, extensive left ventricular opacification with endocardial definition. RV = right ventricle; RA = right atrium; LV = left ventricle; LA = left atrium.Grahic Jump Location
Table Graphic Jump Location
Table 1. Number of Patients and PPV for Each TTCE Grade (n = 90)
Table Graphic Jump Location
Table 2. Timing of Appearance of Bubbles in the Left Ventricle for Each TTCE Grade
* 

NIL = no PAVM and no PFO.

 

One patient had PFO in addition to PAVM.

Churton, T (1897) Multiple aneurysms of the pulmonary artery.BMJ1,1223-1225
 
Sloane, RD, Cooley, RN Congenital pulmonary arteriovenous aneurysm.AJR Am J Roentgenol1953;70,183-210
 
White, RI, Jr, Lunch-Nyhan, P, Terry, P, et al Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy.Radiology1988;169,663-669. [PubMed]
 
Gossage, J, Kanj, G Pulmonary arteriovenous malformations: a state of the art review.Am J Respir Crit Care Med1998;158,643-661. [PubMed]
 
Plauchu, H, de Chadarevian, JP, Bideau, A, et al Age related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population.Am J Med Gen1989;32,291-297. [CrossRef]
 
Nanthakumar, K, Graham, AT, Robinson, TI, et al contrast echocardiography for detection of pulmonary arteriovenous malformations.Am Heart J2001;141,243-246. [PubMed]
 
Cottin, V, Plauchu, H, Bayle, JY, et al Pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.Am J Respir Crit Care Med2004;169,994-1000. [PubMed]
 
Guttmacher, AE, Marchuk, DA, White, RI, Jr Current concepts: hereditary hemorrhagic telangiectasia.N Engl J Med1995;333,919-924
 
Shovlin, CL, Letarte, M Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms.Thorax1999;54,714-729. [PubMed]
 
Wirth, JA, Pollak, J, White, R Pulmonary arteriovenous malformations. George, RB eds.Current pulmonology and critical care medicine1996;vol 17,261-298 Mosby Year Book. St. Louis, MO:
 
Remy, J, Remy-Jardin, M, Giraud, F, et al Angioarchitecture of pulmonary arteriovenous malformations: clinical utility of three-dimensional helical CT.Radiology1994;191,657-664. [PubMed]
 
Weyman, AE Analysis of contrast echograms. Weyman, AE eds.Principles and practice of echocardiography 2nd ed.1994,310-311 Lea & Febiger. Philadelphia, PA:
 
Barzilai, B, Waggoner, AD, Spessert, C, et al Two-dimensional contrast echocardiography in the detection and follow-up of congenital pulmonary arteriovenous malformations.Am J Cardiol1991;68,1507-1510. [PubMed]
 
Retnakaran, R, Faughnan, ME, Chan, RP, et al Pulmonary arteriovenous malformation: a rare, treatable cause of stroke in the young adult.Int J Clin Pract2003;57,731-733. [PubMed]
 
Lee, WL, Graham, AF, Pugash, RA, et al Contrast echocardiography remains positive after treatment of pulmonary arteriovenous malformations.Chest2003;123,351-358. [PubMed]
 
Remy, J, Remy-Jardin, M, Wattinne, L, et al Pulmonary arteriovenous malformations: evaluation with CT of the chest before and after treatment.Radiology1992;182,809-816. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Appearance of left ventricular opacification following injection of agitated saline solution for each TTCE grade. Top left, A: grade 1, minimal left ventricular opacification; top right, B: grade 2, moderate left ventricular opacification; bottom left, C: grade 3, extensive left ventricular opacification without outlining the endocardium; and bottom right, D: grade 4, extensive left ventricular opacification with endocardial definition. RV = right ventricle; RA = right atrium; LV = left ventricle; LA = left atrium.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Number of Patients and PPV for Each TTCE Grade (n = 90)
Table Graphic Jump Location
Table 2. Timing of Appearance of Bubbles in the Left Ventricle for Each TTCE Grade
* 

NIL = no PAVM and no PFO.

 

One patient had PFO in addition to PAVM.

References

Churton, T (1897) Multiple aneurysms of the pulmonary artery.BMJ1,1223-1225
 
Sloane, RD, Cooley, RN Congenital pulmonary arteriovenous aneurysm.AJR Am J Roentgenol1953;70,183-210
 
White, RI, Jr, Lunch-Nyhan, P, Terry, P, et al Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy.Radiology1988;169,663-669. [PubMed]
 
Gossage, J, Kanj, G Pulmonary arteriovenous malformations: a state of the art review.Am J Respir Crit Care Med1998;158,643-661. [PubMed]
 
Plauchu, H, de Chadarevian, JP, Bideau, A, et al Age related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population.Am J Med Gen1989;32,291-297. [CrossRef]
 
Nanthakumar, K, Graham, AT, Robinson, TI, et al contrast echocardiography for detection of pulmonary arteriovenous malformations.Am Heart J2001;141,243-246. [PubMed]
 
Cottin, V, Plauchu, H, Bayle, JY, et al Pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.Am J Respir Crit Care Med2004;169,994-1000. [PubMed]
 
Guttmacher, AE, Marchuk, DA, White, RI, Jr Current concepts: hereditary hemorrhagic telangiectasia.N Engl J Med1995;333,919-924
 
Shovlin, CL, Letarte, M Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms.Thorax1999;54,714-729. [PubMed]
 
Wirth, JA, Pollak, J, White, R Pulmonary arteriovenous malformations. George, RB eds.Current pulmonology and critical care medicine1996;vol 17,261-298 Mosby Year Book. St. Louis, MO:
 
Remy, J, Remy-Jardin, M, Giraud, F, et al Angioarchitecture of pulmonary arteriovenous malformations: clinical utility of three-dimensional helical CT.Radiology1994;191,657-664. [PubMed]
 
Weyman, AE Analysis of contrast echograms. Weyman, AE eds.Principles and practice of echocardiography 2nd ed.1994,310-311 Lea & Febiger. Philadelphia, PA:
 
Barzilai, B, Waggoner, AD, Spessert, C, et al Two-dimensional contrast echocardiography in the detection and follow-up of congenital pulmonary arteriovenous malformations.Am J Cardiol1991;68,1507-1510. [PubMed]
 
Retnakaran, R, Faughnan, ME, Chan, RP, et al Pulmonary arteriovenous malformation: a rare, treatable cause of stroke in the young adult.Int J Clin Pract2003;57,731-733. [PubMed]
 
Lee, WL, Graham, AF, Pugash, RA, et al Contrast echocardiography remains positive after treatment of pulmonary arteriovenous malformations.Chest2003;123,351-358. [PubMed]
 
Remy, J, Remy-Jardin, M, Wattinne, L, et al Pulmonary arteriovenous malformations: evaluation with CT of the chest before and after treatment.Radiology1992;182,809-816. [PubMed]
 
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