Diagnosis and Treatment of Pulmonary Arteriovenous Malformations In

Home , Embolism, Paradoxical embolism

Diagnostic and Interventional Imaging (2013) 94, 835—848

REVIEW / Thoracic imaging

Diagnosis and treatment of pulmonary arteriovenous

malformations in hereditary hemorrhagic telangiectasia: An overview

∗

P. Lacombe, A. Lacout , P.-Y. Marcy, S. Binsse,

J. Sellier, M. Bensalah, T. Chinet,

I. Bourgault-Villada, S. Blivet, J. Roume, G. Lesur,

J.-H. Blondel, C. Fagnou, A. Ozanne, S. Chagnon,

M. El Hajjam

Radiology department, Pluridisciplinary HHT team, Ambroise-Paré Hospital, Groupement des

Hôpitaux Île-de-France Ouest, Assistance Publique—Hôpitaux de Paris, Université de

Versailles-Saint-Quentin-en-Yvelines, 9, avenue Charles-de-Gaulle, 92100

Boulogne-Billancourt, France

KEYWORDS Abstract Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an

Hereditary autosomic dominant disorder, which is characterized by the development of multiple arteriove-

hemorrhagic nous malformations in either the skin, mucous membranes, and/or visceral organs. Pulmonary

telangiectasia; arteriovenous malformations (PAVMs) may either rupture, and lead to life-threatening hemopt-

Rendu-Osler disease; ysis/hemothorax or be responsible for a right-to-left shunting leading to paradoxical embolism,

Pulmonary causing stroke or cerebral abscess. PAVMs patients should systematically be screened as the

arteriovenous spontaneous complication rate is high, by reaching almost 50%. Neurological complications rate

malformations; is considerably higher in patients presenting with diffuse pulmonary involvement. PAVM diagno-

Percutaneous sis is mainly based upon transthoracic contrast echocardiography and CT scanner examination.

embolization; The latter also allows the planiﬁcation of treatments to adopt, which consists of percutaneous

Right-to-left shunt embolization, having replaced surgery in most of the cases. The anchor technique consists of

percutaneous coil embolization of the afferent pulmonary arteries of the PAVM, by ﬁrstly pla-

cing a coil into a small afferent arterial branch closely upstream the PAVM. Enhanced contrast

CT scanner is the key follow-up examination that depicts the PAVM enlargement, indicating

the various mechanisms of PAVM reperfusion. When performed by experienced operators as

the prime treatment, percutaneous embolization of PAVMs, is a safe, efﬁcient and sustained

therapy in the great majority of HHT patients.

Abbreviations: ACVRL1, Activin type-II-like receptor kinase 1; ALK1, Activin receptor like kinase; CT, Computed tomography; HHT,

Hereditary hemorrhagic telangiectasia; MIP, Maximum intensity projection; MRA, Magnetic resonnance angiography; PAH, Pulmonary arterial

hypertension; PAVM, Pulmonary arteriovenous malformations; TTCE, Transthoracic contrast echocardiography. ∗

Corresponding author.

E-mail address: [email protected] (A. Lacout).

836 P. Lacombe et al.

Introduction Pulmonary arteriovenous malformations

Hereditary hemorrhagic telangiectasia (HHT) or Rendu- Pulmonary arteriovenous malformation

Osler-Weber disease is an autosomic dominant disorder,

anatomy and classiﬁcation

which occurs in approximately 10 to 20 individuals per

100,000, characterized by the development of multiple arte- Pulmonary arteriovenous malformations are abnormal direct

riovenous malformations of the skin, mucous membranes, communications between pulmonary arteries and pulmonary

and visceral organs including cerebral, spinal, hepatic, pan- veins without interposition of a capillary bed. Approximately

creatic and pulmonary arteriovenous malformations (PAVMs) 80 to 90% of patients presenting with PAVMs eventually

[1—6]. present HHT, whereas the remaining are sporadic cases

Tw o main types of HHT disease represent 80% of the cases [16,14]. Conversely, 15 to 35% of HHT patients will present

and are due to the mutations in the ENG gene (encoding for PAVMs [16,14]. The PAVMs have a natural tendency to

endoglin) and activin type-II-like receptor kinase 1 (ACVRL1) increase in size over time. Various factors including puberty,

gene (encoding for the activin receptor like kinase (ALK1)), pregnancy and also pulmonary arterial hypertension (PAH)

causing respectively HHT type 1 and HHT type 2 diseases. may explain this phenomenon. Contrary to sporadic forms,

The ENG and ACVRL1 genes code for proteins of the TGF HHT-PAVMs are often multiple, bilateral and preferentially

beta receptor, which is involved in the proper blood vessel located at the pulmonary bases [14,17].

development [7]. The mutation of the SMAD4 gene, which The PAVM consists of three different anatomical com-

is involved in TGF beta signal transduction, may also cause ponents: one or more than one feeding artery(ies), an

HHT disease, in association with juvenile polyposis [8]. aneurismal sac and one or more draining vein (Fig. 1). The

HHT should be precisely clinically diagnosed on the basis feeding artery may be long, (Fig. 1) or very short, thus mak-

of the Curac¸ao criteria. Three criteria are thus needed ing percutaneous embolization more challenging (Fig. 2).

among the following: The aneurismal part of the PAVM may be either a sac or a ser-

•

multiple mucocutaneous telangiectases; piginous network (Figs. 1, 3, 4). Distinction between these

•

spontaneous and recurrent epistaxis; two different patterns is crucial to plan the appropriate per-

•

visceral involvement; cutaneous treatment as the risk of accidental embolization

•

a family ﬁrst degree history of HHT [9]. device migration to the left heart is higher when considering

a single aneurismal sac directly communicating with the left

circulation. Finally, the third portion of the PAVM consists of

Penetrance is age-related and is almost complete by the

one or more draining veins whose diameters are larger than

age of 40-years-old [1]. Mild to moderate epistaxis is the

most common symptom of HHT. Cerebral vascular malfor-

mations have been reported in 3.7% out of 321 HHT patients,

and included ten cases of AVM, one dural arteriovenous

ﬁstula and one cavernomatous malformation [10]. A sub-

stantial proportion of patients presenting with HHT disease

may be affected by liver involvement, which can cause

abdominal pain, abnormal serum liver function tests results,

pseudocirrhosis, biliary necrosis and even high cardiac out-

put failure [11]. Pancreatic involvement has been reported

in 31% of the cases, mainly in association with ALK1 mutation

patients [12].

Pulmonary arteriovenous malformations represent the

most common pattern of the pulmonary involvement to be

encountered in HHT patients. ALK1-type related pulmonary

arterial hypertension may also be observed [13]. Paradoxical

embolism due to de novo in situ cruoric thrombus originating

from the PAVM (tight stenosis related venous stasis, turbu-

lent ﬂow within a large sac) or septic, cruoric thrombus

or air embole originating upstream the PAVMs is one of the

main causes of morbidity, responsible for stroke and cere-

bral abscess events [14]. PAVMs may also rupture, causing

life threatening hemoptysis or hemothorax [15].

This overview article aims:

• Figure 1. Simple pulmonary arteriovenous malformation (PAVM)

ﬁrstly, to describe the progressive development and radio-

located at the lower left posterior basal segment. Positive transtho-

anatomical characteristics of PAVMs, and their potential

racic echocardiography (grade 3) in a hereditary hemorrhagic

complications;

• telangiectasia (HHT) family 35-years-old patient. Thirty degrees

secondly, to report the technical aspects and outcomes

left anterior oblique volume rendering CT scanner shows a simple

of percutaneous embolization to prevent and treat PAVMs

PAVM. A single postero basal afferent feeding artery (arrow) and

related complications;

an aneurismal sac (arrowhead) are shown. The aneurismal sac is

•

thirdly, to show CT scanner/angiographic — pathological located in the subpleural space. Note the draining vein diameter

correlations. that is larger than that of the artery (large arrow).

Diagnosis and treatment of pulmonary arteriovenous malformations 837

Figure 2. Short solitary afferent artery feeding a simple large pulmonary arteriovenous malformation (PAVM) in the left lung in a 79-

years-old woman presenting with multiple discrete PAVMs. Selective angiogram of the left latero basal artery in a 45 degrees right anterior

oblique view before (a) and during embolization (b) discloses a very short subsegmental anterior artery (arrow) feeding the large aneurismal

sac (arrowhead). The anchor technique permitted the coil blockage inside the subsegmental branch (large arrow). Coils are shown into the

aneurismal sac (curved arrow).

•

the afferent feeding artery (Figs. 1 and 5). A simple PAVM small vessels that are visible within the ground glass nod-

(approximately 80% of the cases) is characterized by one or ule represent vascular branching and connection between

more afferent feeding arteries originating from a single seg- the precapillary pulmonary artery and the postcapillary

mental pulmonary artery (Fig. 1), while a complex PAVM has venules, throughout the capillary bed;

•

multiple afferent feeding arteries originating from several enlargement of the draining vein;

•

segmental arteries (Fig. 4) [14,18]. the deﬁnitive PAVM corresponds to a feeding pulmonary

PAVMs development comprises three main steps as fol- artery, an aneurysmal sac and an enlarged draining vein

lows: with concomitant disappearance of the ground glass pat-

•

a ground glass nodule corresponds to the initial enlarge- tern (Fig. 6) [19]. At this stage, the PAVM will evolve for

ment of the postcapillary venules associated with an its own account. Rarely, PAVMs will evolve to a giant form

inﬂammatory cell inﬁltrate; (Fig. 7).

Figure 3. Various patterns of aneurismal arterio venous connections. Thirty degrees left anterior angiogram of a subsegmental branch of

the posterior segment of the left upper lobe (a) shows a serpiginous network channel (arrow) drained by two efferent veins. Thirty degrees

right anterior oblique angiogram of a latero basal segmental artery (b) shows stenosis of the arteriovenous connection (large arrow). The

risk of accidental distal device migration to the left circulation is higher in case of a large straight channel aneurismal sac. The presence of

a stenosis of a pulmonary arteriovenous malformation (PAVM) may represent a local factor for spontaneous PAVM thrombosis.

838 P. Lacombe et al.

Figure 6. Spectrum of pulmonary arteriovenous malformation

(PAVM) disease development on CT scanner. CT scanner ﬁrst step

shows isolated nodular or ill deﬁned ground-glass attenuation. It

corresponds to the initial venous telangiectasic stage. This initial

telangiectasic stage is followed by the pulmonary venous enlarge-

Figure 4. Complex pulmonary arteriovenous malformation

ment, which correspond to microscopic arteriovenous connections.

(PAVM) with afferent feeding arteries originating from different seg-

In next stages, vascular branching is depicted on CT: the feeding

mental pulmonary arteries. 82-years-old hypoxemic female with a

artery lies within the ground-glass nodule, while draining veins are

persistent positive transthoracic echocardiography (grade 3) after

visible in the periphery of the nodule. Finally the development of

percutaneous closure of a patent foramen ovale. Thirty degrees left

a true PAVM occurs with an aneurismal sac and concomitant disap-

anterior oblique volume rendering CT scanner shows a complex PAVM

pearance of the nodule or ground glass densities.

fed by two afferent arteries: a small lingular artery (arrow) and a

large antero basal artery (curved arrow). The CT scanner also shows

a serpiginous aneurismal sac (arrowhead) and an enlarged draining

Pulmonary arteriovenous malformation vein (large arrow).

repartition

The repartition type of the PAVM in HHT patient lungs may be

either discrete or diffuse (5—7%). Diffuse pattern of PAVMs

is variably deﬁned as PAVMs involving every segmental or

every subsegmental artery of at least one lobe [20]. Dif-

fuse involvement has also minimally been deﬁned as one

segment diffusely involved [21]. A more clinically relevant

classiﬁcation has been proposed, as follows: patients pre-

senting with involvement of every subsegmental artery of at

least one lobe (diffuse subsegmental form) (Fig. 8), patients

presenting with involvement of every segmental artery of

at least one lobe (diffuse segmental form) (Fig. 9), and

patients presenting with a combination of subsegmental

and segmental involvement of at least one lobe (diffuse

mixed segmental/subsegmental form) [22]. Symptoms that

include hypoxemia, hemoptysis, and neurological symptoms

are more frequently correlated to diffuse patterns [20].

Paradoxical embolism is more frequently encountered in the

diffuse subsegmental form [22].

Figure 5. Simple pulmonary arteriovenous malformation (PAVM)

presenting with an enlarged draining vein. Twenty degrees right

anterior oblique angiogram of a left anterior basal artery shows Spontaneous pulmonary arteriovenous

a simple PAVM presenting a fusiform aneurism of the draining vein

malformations complications

(arrow). The pattern of draining veins is presumably related to the

high ﬂow output within the PAVM and/or to the pulmonary hyperten-

PAVMs may be responsible for a paradoxical clot embolism

sion. Moreover, angiogram displays dynamic variations of the ﬁlling

due to the absence of the capillary ﬁlter bed interpo-

of draining veins according to the cardiac cycle. In case of a high

sition between the arterial and venous circulation. As a

output cardiac failure with pulmonary venous hypertension, a ret-

matter of fact, stroke and cerebral abscess events are

rograde ﬁlling of a successfully embolized PAVM can be observed

uncontrolled right-to-left shunt related complications due

(Fig. 21).

to clot/septic thrombus embolization through out the PAVM

[14]. The right-to-left blood shunting may cause hypoxia

Diagnosis and treatment of pulmonary arteriovenous malformations 839

Figure 7. Incidental diagnosis of a giant sporadic pulmonary arteriovenous malformation (PAVM) on a chest X-ray in a 16-years-old male

patient presenting a right chest pain. Frontal chest x-ray (a) and coronal contrast-enhanced MIP CT scanner reformation (b) show a giant

simple PAVM in the middle lobe, a single afferent artery (arrow), feeding a giant aneurismal sac larger than left ventricle (arrowhead), and

a large single efferent draining vein (large arrow). Axial contrast-enhanced CT scanner (c) shows peripheral clots (arrows) and a parietal

calciﬁcation (arrowhead). PAVM transparietal ultrasonography (d) conﬁrms the presence of parietal thrombus, possible source of paradoxical

embolism (arrow). Factors that contribute to plan surgery rather than embolization were the age of the patient with a single PAVM, the

presence of pain suggesting a complication, the large volume and clot ﬁlled aneurismal sac. Before surgery, hemoglobin level was 22 g/dL.

Pulmonary artery pressures were 24 (systolic), 11 (diastolic) and 16 mmHg (mean). The pulmonary capillary wedge pressure was 12 mmHg.

The cardiac output and cardiac index were 5.4L/min, and 2.8L/min/m , respectively. The patient underwent middle lobectomy, and post

operative full recovery. Photograph (e) of the resected middle lobe showing the giant PAVM at gross examination, with fresh (dark) and

organized (white) thrombi within the aneurismal sac.

and subsequent polycythemia (Fig. 7) [23]. Spontaneous PAH may occur and be favoured by both pulmonary arte-

thrombosis of a PAVM is rare and may be symptomatic and rial vasconstriction secondary to PAVMs induced chronic

responsible for embolism to the left circulation (Fig. 10). hypoxemia and high blood ﬂow output due to intrahepatic

The thin-walled PAVM aneurismal sac may also rupture. shunts (arterioportal, portohepatic and/or arteriohepatic

Most of the PAVMs have a subpleural localisation and may shunts) [25]. ALK1 and more rarely endoglin mutations

be revealed by a combination of potential life threat- may also be a proper cause of heritable PAH [13,14,26].

ening hemoptysis/hemothorax and neurological signs due Also, PAH may contribute to the PAVM enlargement

to cough favoured systemic air embolism (when rupture [3].

occurs into lung parenchyma, alveolar haemorrhage triggers

patient’s cough, increased intrathoracic pressure and sub-

sequent paradoxical air embolism through the parietal PAVM Diagnosis of pulmonary arteriovenous

tear) (Figs. 11 and 12). Ruptures may be favoured by preg- malformation

nancy probably due to the increased blood volume as well as

alterations in the vascular tone related to changing serum Transthoracic Contrast Echocardiography (TTCE) and Chest

estrogen and progesterone concentrations [15,24]. CT scanner examination are the two main tools permitting

840 P. Lacombe et al.

Figure 8. Subsegmental diffuse pulmonary arteriovenous malformation of the middle lobe in a 31-years-old female patient presenting with

a low PaO2 level (34 mm Hg). CT scanner (a) showing all peripheral subpleural subsegmental arterial branches dysplaying tiny arteriovenous

connections (arrows). Selective angiogram of the left latero basal segment (b), in a right anterior projection showing diffuse subsegmental

arterio venous connections (arrows).

PAVMs screening and evaluation in patients presenting with

HHT [26]. Both TTCE and CT scanner examinations should

be performed carefully to prevent intravenous gazeous or

septic injection that may lead to iatrogenic paradoxical

embolism. Isotopic and blood oxygen levels right-to-left

shunt measurements are insufﬁciently sensitive to exclude

PAVMs diagnosis [26,27]. Chest radiograph is an easy, fast,

low radiation exposure examination used as a ﬁrst line PAVM

screening test although its sensitivity is low, particularly

for the detection of small diameter PAVM. PAVMs appear as

rounded well circumscribed lesions with branching afferent

feeding and dilated efferent draining vessels (Fig. 13) [27].

Although contrast-enhanced magnetic resonance angiogra-

phy (MRA) is not currently performed for PAVMs screening,

recent studies have concluded that MRA was a contributive

adjunct to pre-embolization planning [28—30]. The main

Figure 9. Axial MIP CT scanner shows diffuse segmental pul-

advantage of MRA over the other techniques is to avoiding

monary arteriovenous malformation (PAVM) of the middle lobe. All

ionizing radiation exposure.

the segmentar arteries of the middle lobe display arteriovenous

malformations (arrows). Multiple discrete PAVMs are shown within TTCE is a rapid simple and minimally invasive exam-

the right lower lobe (arrowheads). ination used as an initial PAVMs screening examination

Figure 10. Asymptomatic partial thrombosis of the pulmonary arteriovenous malformation (PAVM) aneurismal sac. Contrast-enhanced CT

scanner in a 34-years-old female paient without any clinical signs of systemic paradoxical cruoric or septic embolism. Axial reformation (a)

shows a thrombus within the aneurismal sac of a PAVM in the anterior segment of the right upper lobe (arrow). Anticoagulant therapy was

planned for one month. Pre-embolization angiogram disclosed a tiny residual clot abutting the feeding artery (not shown). Embolization was

successfully performed. Angiogram (b) showing an incidental clot within the aneurismal sac of a simple PAVM of the laterobasal segment of

the left inferior lobe (arrow). Immediate embolization was performed without any immediate or delayed complication.

Diagnosis and treatment of pulmonary arteriovenous malformations 841

Figure 11. Acute hemothorax revealing a ruptured subpleural pulmonary arteriovenous malformation (PAVM). A 56-years-old female

patient presenting with acute hemothorax and systemic hypotension due to intra pleural rupture of a peripheral PAVM during transatlantic

air ﬂight travel. The diagnosis of hereditary hemorrhagic telangiectasia (HHT) was suspected on recurrent spontaneous epistaxis and multiple

cutaneous telangiectases. Sagittal (a) contrast-enhanced CT scanner reformation shows the PAVM herniation into the pleural space (arrow),

hematic pleural effusion (large arrow) and a large fresh clot adjacent to the PAVM (arrowhead). The diagnosis of HHT was conﬁrmed by

the presence of the pulmonary and hepatic involvement. Prior to embolization, pulmonary artery pressure level assessment indicated

severe pulmonary hypertension (systolic 92, diastolic 35, mean, 56 mmHg), secondary to a severe HHT hepatic involvement. Percutaneous

emergency embolization was successfully performed. Angiograms (b and c) show a tortuous afferent feeding artery and a tiny PAVM wall

rupture (arrow). Coils were successfully anchored into the artery and the aneurismal sac (arrowhead). Pulmonary artery pressures remained

unchanged after embolization. Indication for anti-angiogenic (Bevacizumab) treatment of the hepatic involvement of HHT was discussed.

[31]. After intravenous injection of agitated saline solution, Indeed, CT scanner is considered as the gold standard

echoic microbubbles can be easily depicted in the left car- diagnosis tool as it provides an easy patient screening, a

diac cavities after two to ﬁve cardiac beats, thus suggesting high anatomical resolution, a precise location (multiple dis-

the presence of a right-to-left pulmonary shunt (whereas crete or diffuse form) and type deﬁnition (e.g. simple versus

microbubbles that are immediately visible after injection complex) of the PAVM. Furthermore, this tool is useful for

may suggest the presence of an intra cardiac shunt) (Fig. 13). percutaneous embolization planiﬁcation and follow-up [34].

Interestingly, a grading of positive TTCE results has been As a matter of fact, we usually perform a contrast-

established according to the number of microbubbles that enhanced thoraco abdominal CT examination at our

could be detected (Fig. 14) [31,32]. The reported diagnos- institution. This allows us to depict the PAVM feeding ves-

tic sensitivity of TTCE is high (up to 97%) and the negative sels and the aneurismal sac lumen that can be spontaneously

predictive value is 99% in published series where chest CT thrombosed before treatment (Fig. 10), to detect the PAVMs

scanner was used as the gold standard for PAVMs diagnosis systemic supply (Fig. 15), and the subphrenic speciﬁc vis-

[33]. ceral involvement (liver and/or pancreatic involvement)

842 P. Lacombe et al.

Figure 12. Spontaneous pulmonary rupture of a pulmonary arte-

riovenous malformation (PAVM). This 35-years-old man presented a

sudden cough immediately followed by hemoptysis and concomitant

transient right hemiparesis. PAVM parenchymal rupture (hemopty-

Figure 14. Transthoracic contrast echocardiography shows Grade

sis) of a PAVM and a systemic cerebral gas embolism (that may be

3 right-to-left shunt. Microbubbles ﬁll in the left atrium and

facilitated by cough) were suspected. Contrast-enhanced CT scan-

ventricle after three cardiac beats (arrow). A large pulmonary

ner examination revealed alveolar hemorrhage related ground glass

arteriovenous malformation was suspected and conﬁrmed on CT

attenuation (arrow) circumscribing the ﬁssured PAVM aneurismal

scanner.

sac. Emergency embolization of the culprit PAVM was successfully

performed, as well as embolization of three other non complicated

PAVMs. The patient remains asymptomatic ten years after the initial

onset of symptoms.

[11,12]. In patients presenting without PAVM, identiﬁcation

of liver/pancreatic involvement provides the third visceral

diagnostic item and subsequently helps to early clinical diag-

nosis and improved management of HHT disease. A steal

phenomenon might be encountered on both angiographic

and CT scanner examination due to the PAVMs high blood

ﬂow output (Fig. 16) in a low-resistance vascular system, and

Figure 15. Initial systemic supply to a large pulmonary arteri-

ovenous malformation (PAVM) of the middle lobe. Frontal MIP CT

scanner MIP shows off a huge PAVM in the middle lobe (arrowhead).

Right multiple enlarged bronchial and intercostobronchial arterial

pedicles are disclosed (arrows).

to the positive pressure gradient directed from the feeding

arteries to the lesion center. As such, the afferent feeding

arteries, particularly the PAVM accessory feeders, may thus

be overlooked on imaging studies (Fig. 16).

A systemic supply has been reported in 29% of 70

Figure 13. Pulmonary arteriovenous malformation (PAVM) depic- pre-embolization work-up PAVMs patients (Fig. 15). A rela-

tion by using MRA. Frontal SSFP (Fiesta) MRA in a 23-years-old tionship between the steal phenomenon (which decreases

pregnant woman presenting with dysraphism related hydronephro- the local pulmonary arterial vascularization) and the devel-

sis and orthodeoxia syndrome. A single PAVM was fortuitously

opment of a systemic supply to PAVMs has not been

detected within the lateral-basal segment (arrow) of the right lung.

established to date.

Transthoracic echocardiography was positive. Low radiation dose CT

scanner examination conﬁrmed the presence of a lateral-basal seg-

ment PAVM and other multiple discrete PAVMs. Embolization of two

PAVMs in the right lower lobe was successfully performed without Lacombe P et al., oral communication, 8th International Hered-

immediate complication. The child was born by caesarean section itary Hemorrhagic Telangiectasia Scientiﬁc Conference. Santander

2 days later. Spain 2009.

Diagnosis and treatment of pulmonary arteriovenous malformations 843

Figure 16. Pulmonary arteriovenous malformation (PAVM) related steal phenomenon. Frontal Mini MIP CT scanner (a) shows a subpleural

peripheral low density area distal to a simple PAVM thought to correspond to the vascular steal phenomenon (arrow). Right common A7-A8

arterial trunk selective angiogram (b) shows the main feeding arteries of the simple PAVMs of A7 (arrowhead) and A8. The A8 feeding artery

looks very long owing to the reverse flow related absence of collateral opacification (arrow). The collateral reverse flow upstream the

PAVM is favoured by the low-resistance high ﬂow. After successful A7-A8 PAVMs embolization occlusion (c), A8 collateral ﬂow (arrows) is

reopaciﬁed, due to the steal phenomenon disappearance.

However, Antibiotic prophylaxis remains recommended if

Treatment of pulmonary arteriovenous

malformation TTCE has positive ﬁndings, even if CT scanner does not show

any image suggestive for PAVM [6].

PAVMs should be treated before the complication may Surgery has long been the treatment of reference until

appear, owing to the high complication rate reaching almost the seventies, including pneumonectomy, lobectomy, seg-

50%, and even more during pregnancy [21]. In diffuse clinical mentectomy, wedge resection or vascular ligation (Fig. 7)

forms, the neurological morbidity (stroke and brain abscess) [14]. Pulmonary transplantation has been performed in dif-

of untreated PAVMs is higher and reaches 70% [20]. This fuse forms associated with respiratory insufﬁciency [37].

underlines the necessity of screening PAVMs by using non- Percutaneous image-guided embolotherapy is nowadays

invasive tests in HHT families, in both children and adults preferable in most disease cases as this avoids major surgery,

[15]. general anesthesia, and loss of pulmonary parenchyma func-

It is recommended that patients presenting with PAVMs tion. The aim of transcatheter embolization is to occlude all

should undergo antibiotic prophylaxis prior to dental and the PAVM feeding arteries by a selective catheterization of

surgical interventions to reduce paradoxical embolic abscess pulmonary arteries by using a coaxial system, via a percuta-

risks [6]. neous femoral approach. CT scanner is the key examination

The risk of cerebral complications is usually considered tool for the planiﬁcation of percutaneous embolization.

signiﬁcant when the feeding artery of the PAVM exceeds Firstly, CT scanner determines the number and location of

3 mm in diameter, and may also increase in patients with the PAVMs, secondly their precise angioarchitecture char-

multiple PAVMs [35]. The 3 mm cut-off size is solely based acteristics, thirdly the presence of complications (e.g.

on empirical data regarding patients who never experi- thrombosis) [34]. The device diameter is chosen accord-

enced such cerebral ischemic events below that size [35,36]. ing to the measurement data of the afferent feeding artery

844 P. Lacombe et al.

diameter on both CT scanner and angiography examinations.

Results of pulmonary arteriovenous

We stress upon the necessity to perform an intravenous

malformation transcatheter embolization

contrast medium injection owing to the potential underes-

and follow-up

timation of catheterization difﬁculties on unenhanced CT

scanner examination.

Successful transcatheter embolization is assessed by com-

Many different embolic devices are now available:

plete retraction of the embolized PAVM (afferent artery

fibered steel coils, fibered platinium coils Nester, fibered

located downstream the coils/aneurismal sac) on a follow-

microcoils, hydrophilic coils, self expandable nitinol plug.

up control CT scanner (Figs. 18 and 19). However, TTCE still

Detachable balloons are no longer available [38,39].The

remains positive in 80—90% of successfully treated patients

anchor technique consists of coil blockage within a small

[40]. This may be due to the occult presence of tiny addi-

collateral branch of the main feeding artery immedi-

tional PAVMs that were not detected by both conventional

ately upstream the PAVM, allows cross sectional optimal

angiography and CT scanner examinations or the presence

occlusion and prevents further accidental device mobi-

of a tiny PAVMs feeding artery too small to be catheterized

lization and distal migration to the left circulation

[40]. Transcatheter embolization of PAVMs is eventually efﬁ-

[39] (Figs. 2 and 17). The ﬁrst positioned coil cre-

cient and durable in the majority of patients (83% of patients

ates a scaffold and permits the blockage of other

in Mager’s study) [41—43].

devices. By packing decreasing diameter devices an opti-

Immediate complications are rare in experienced hands

mal transsectional occlusion of the feeding artery can be

achieved. and include device migration, gazeous embolism, stroke,

Figure 17. Therapeutic anchor technique. The therapeutic anchor technique consists of placing the ﬁrst coil into a small normal afferent

branch, closely upstream the pulmonary arteriovenous malformation (PAVM) (arrow). The ﬁrst coil creates a scaffold which facilitates the

placement of other coils, lowering the risk of migration of embolization devices through the PAVM. Progressive occlusion of the feeding artery

is performed by using complementary coils, of decreasing diameters. Coil packing is mandatory to achieve a complete lumen occlusion of

the feeding artery (arrowhead). Success of percutaneous embolization is assessed by the complete retraction of the aneurismal sac over

time.

Figure 18. Successful transcatheter embolization. Axial CT scanner (a) shows a complex racemous sporadic pulmonary arteriovenous mal-

formation (PAVM) of the apical segment of the right inferior lobe (arrow) in a cyanotic 18-years-old female with clubbing. Post-embolization

axial CT scanner (b) shows coil occlusion of the afferent feeding artery and subsequent complete retraction of the PAVM (arrow).

Diagnosis and treatment of pulmonary arteriovenous malformations 845

Figure 19. Pulmonary arteriovenous malformation (PAVM) incomplete retraction at follow-up corresponding to secondary recanalization.

Work-up axial enhanced CT scanner (a) shows a simple peripheral PAVM in the anterior segment of the right lower lobe (arrow). Post-

embolization CT scanner one year after embolization (b) shows persistent or recurrent contrast enhancement of the partially retracted

PAVM (arrow). Central recanalization through the previously deposited coils was disclosed on angiography.

pulmonary infarctions and hemoptysis (Figs. 20 and 21). incomplete PAVM retraction — and directly by using I.V.

Regarding mid- to long-term complications, reperfusion of contrast iodinated medium injection [44,45]. CT scanner

the embolized PAVM may be due to the following mech- imaging follow-up is mandatory every year in subsegmental

anisms, as follows: reperfusion through or around the diffuse PAVMs types, and every ﬁve years in the other cases,

anchored coils (Figs. 22 and 23); development of pul- owing to the risk of late PAVM recanalization and regrowth

monary to PAVM neovasculature anastomoses (Fig. 23), of untreated PAVMs [5,41—43].

reperfusion by systemic bronchial and/or non bronchial

arteries (Fig. 24) [41—43]. In case of systemic bronchial

artery supply, post-embolization systemic supply may be

responsible for delayed hemoptysis.

CT scanner follow-up examination may highlight abnor-

mal secondary PAVM reperfusion — indirectly by showing

Figure 21. Post-embolization pulmonary arteriovenous malfor-

mation (PAVM) thrombosis. This 36-years-old man presenting with

multiple PAVMs and liver involvement with hepatic artery enlarge-

ment (11 mm). Enhanced CT scanner was performed at stroke onset

(hemiplegia) seven hours after PAVMs embolization. The feeding

artery was completely occluded but a clot is shown within the

aneurismal sac extending downstream reaching the draining vein

(arrow). The enhancement of the aneurismal sac comes from a ret-

rograde ﬁlling of the pulmonary vein related to the high cardiac

output secondary to the liver involvement. On cerebral MR imag-

ing, a non obstructive clot was detected within the middle cerebral

artery, without cerebral infarction. Anticoagulant therapy was ini-

Figure 20. Acute pulmonary ischemia after percutaneous pul- tiated and patient had an immediate full clinicaly recovery. In our

monary arteriovenous malformation embolization. Axial CT scanner practice, anticoagulation is initiated after PAVM embolization as

shows multiple areas of pleural base pulmonary infarction and left soon as a retrograde ﬁlling of the embolized PAVM is depicted on

pleural effusion 10 days after bilateral embolization (arrows). control angiography.

846 P. Lacombe et al.

Figure 22. Recanalization around the previously deposited coils two years after pulmonary arteriovenous malformation (PAVM) emboliza-

tion. Imaging work-up before re treatment. Enhanced oblique MIP CT scanner (a) shows recanalization of a previously treated right laterobasal

PAVM. A recurrent ﬂow through previously deposited coils is present. The feeding artery of the PAVM is shown patent immediately beyond

coils. Selective angiography (b) shows reopening channels around the anchored coils (arrow).

Figure 23. Pulmonary arteriovenous malformation (PAVM)

recanalization through the anchored coils and pulmonary-to-PAVM

anastomoses. Angiogram shows the recanalization of the affer-

ent feeding artery (left A10) throughout previously thrombosed

anchored coils (arrow) and the development of pulmonary-to-PAVM

neovasculature anastomoses (large arrow). Both mechanisms

explain the opaciﬁcation of the draining vein (arrowhead).

Diagnosis and treatment of pulmonary arteriovenous malformations 847

Figure 24. Reperfusion of pulmonary arteriovenous malformation (PAVM) due to post-embolization systemic neovasculature development.

High cardiac output failure in a 33-years-old female presenting with diffuse subsegmental form of PAVMs throughout both lungs ﬁve years

after serial peripheral-to-proximal percutaneous embolization. Axial enhanced CT scanner (a) shows huge enlargement of systemic bronchial

(arrow), intercostal and internal thoracic arteries (large arrow), and concomitant reperfusion of a left anterior PAVM (arrowhead). Axial

enhanced CT scanner examination (b) shows huge enlargement of both inferior phrenic arteries (arrows) with retrograde ﬁlling of multiple

peripheral embolized PAVMs (arrowheads). This reperfusion can be overlooked on angiograms because of the retrograde ﬁlling of feeding

arteries via systemic supplies (false negative angiograms).

Conclusion editors. GeneReviews [Internet]. Seattle (WA): University of

Washington, Seattle; 1993—2000.

[7] Bayrak-Toydemir P, Mao R, Lewin S, McDonald J. Heredi-

PAVMs are one of the main causes of morbidity in patients

tary hemorrhagic telangiectasia: an overview of diagnosis and

presenting with HHT disease, owing to the risks of rupture

management in the molecular era for clinicians. Genet Med

as well as paradoxical embolism exposing to stroke and/or

2004;6:175—91.

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[8] Iyer NK, Burke CA, Leach BH, Parambil JG. SMAD4 mutation

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BE. Cerebrovascular manifestations in 321 cases of hereditary

The authors declare that they have no conﬂicts of interest hemorrhagic telangiectasia. Stroke 2001;32:877—82.

[11] Garcia-Tsao G, Korzenik JR, Young L, Henderson KJ, Jain D, Byrd

concerning this article.

B, et al. Liver disease in patients with hereditary hemorrhagic

telangiectasia. N Engl J Med 2000;343:931—6.

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