Robert

I. White,

Jr. MD

Pulmonary Arteriovenous How Do We Diagnose Important to Do So?’ RE pulmonary

arteriovenous malfor(PAVMs) simply a “medical” curiosity considered by putmonologists and radiologists in the differential diagnosis of coin lesions of the lung, or do they have real meaning for patients who have them? The answer to this rhetorical question is surely the latter. Recent data suggest that PAVMs are more commonly associated with hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, than previously recognized (i). HHT is an uncommon, autosomal dominant disorder that affects arteries of the brain, lung, nose, and gastrointestinal system, causing serious morbidity and a iO% mortality in affected patients. PAVMs are a significant cause of morbidity in HHT and are possibly the leading cause of death in this disorder. These low-resistance, extracardiac rightto-left shunts cause cyanosis, dyspnea, and fatigue and are a major cause of stroke and brain abscess because the lung no longer serves as a filter for small clots or bacteria (1,2; Charnas LR et al [unpublished data, i99i]). The radiologist is in a unique position to detect PAVMs, understand their pathophysiologic characteristics, and treat them by means of interventional techniques. The article by Remy et al in this issue of Radiology and a previous article by Remy-Jardin et a! in the September i99i mations

issue

provide

knowledge changes

us with

important

new

about the diagnosis and that occur after embolotherapy

Index terms: Arteries, therapeutic blockade, 944.1299 #{149}Arteriovenous malformations, pulmonary, 60.1494 #{149} Computed tomography (CT), comparative studies #{149}Editorials #{149}Pulmonary arteries, abnormalities, 564.1559, 60.1494 Pulmonary veins, abnormalities, 565.1559, 60.1494 #{149}Thorax, CT, 564.1211, 565.1211

Radiology

1992; 182:633-635

Them

of PAVMs

with

colleagues tients with angiography.

minor

From Yale Cedar St. Received ber

25. ,

the Department of Diagnostic Radio!University School of Medicine, 333 P0 Box 3333, New Haven, CT 06510. November 22, 1991; accepted Novern-

Address

RSNA,

See also in this

issue.

reprint

requests

to the

author.

1992

the

article

by Remy

et al (pp

809-816)

tomography

Remy

and

jection. Diagnostic pulmonary angiography also failed in 40% of patients to ac-

his

for the diagnosis

PAVMs were developed: eurysm, angioarchitecture (including determination single [simple] or multiple

arteries

and

studied 109 PAVMs in 40 paCT and selective pulmonary The following major and

CT criteria

veins

of

size of the anof the PAVM of whether [complex]

entered

and

exited

the aneurysm), location of the PAVM by lobe and segmental anatomy, and timing of the enhancement of the PAVM in relation to adjacent, normal pulmonary arteries and the aorta. Remy et al also reported immediate and intermediate

(4-year) gression

follow-up results, including (or lack of regression) of on CT scans obtained after

re-

PAVMs coil embolotherapy or surgical ligation. Finally, the authors presented an algorithm for clinical and radiologic evaluation of patients suspected of having PAVMs on the basis of CT and pulmonary angiographic findings. All patients were divided into three

curately This

reflect

the angioarchitecture.

is illustrated

Figure

well

3, in which

apparent primary

only branch.

the secondary

in the

authors’

multiple

feeders

after embolization As the authors

feeders,

which

are

of the suggest,

occur

in

20% of patients with multiple PA VMs, may enlarge with time and reduce arterial oxygen content. Finally, with both modalities, values for the diameter of

the vascular pedicles leading to and from the aneurysm were within acceptable

error

in two-thirds

of PAVMs

and

were dissimilar in one-third. In group 2, the size of the aneurysm decreased in 47% of patients within 30 days of the occlusion and did not change significantly in 43% of patients.

Remy

et al attributed

in aneurysm ber of coils or thrombosis

CT examinations, riod

the lack of change

size to an insufficient numplaced (continued patency) of the aneurysm. Delayed

performed

of 4 years,

over

demonstrated

of the aneurysms

that

could

no longer

a pe68%

be

groups: Group 1 consisted of 20 patients who underwent CT of the chest and pulmonary angiography, both of which

detected, while 28% had diminished in size but were still detectable. Pulmonary parenchymal and pleural changes oc-

were Group

curred in 43% of patients after embolotherapy, whereas no changes were de-

evaluated in detection of PAVMs. 2 consisted of 27 patients who

underwent

follow-up

CT after

embolo-

therapy or surgery. Group 3 consisted of 11 patients screened by means of CT

of the chest CT findings

alone. In group and angiographic

1 patients, findings

tween

both

modalities

for measuring

the diameter of the aneurysmal portion of the PAVM and determining the segmental location of the malformation within the lung.

1, the anatomic

structure

of

identified with CT in 26% of patients and with pulmonary angiography in 60% of patients. Analysis of the anatomic structure of PAVMs was considered complicated because the arteries

that

was

supply

PAVMs is often

and

the veins

have an undulating outside the plane

that

drain

tected in 57% point out that parenchymal minimal or no

without

were the same in 60% of cases and differed in the other 40% . Forty-two PAVMs (38%) were identified with CT only, a result that indicates the superiority of CT compared with angiography in diagnosis of smaller vascular malformations. Good agreement existed be-

In group I

computed

(CT) (3,4). For 12 years,

PAVMs

01W,

Malformations: and Why Is It

the

course that of the CT pro-

of patients. The authors most patients who had or pleural changes had symptoms and recovered

specific

cluded

PAVMs

a 4-year consistent surements,

treatment.

Nonoc-

changed

follow-up

very

period,

with arterial which have

little

over

a finding

blood been

remain fairly constant over riod of follow-up (i,5).

gas meanoted to

a 3-year

pe-

In group 3, PAVMs requiring angiography and embolotherapy were identifled in three of eight patients without symptoms. In three elderly patients

with

contraindications

to angiography,

PAVMs were identified with CT. Finally, Remy et at conclude that CT is the best noninvasive modality for evalua-

tion of PAVMs

and

giography

was

essential

that

therapy

or surgical

pulmonary before

treatment

anembolo-

was

considered.

The authors

did not discuss

late their CT and angiographic with chest radiographs, nor

or corredid

findings they 633

attempt

correlation

gas measurements

with

arterial

blood

in room

air

and with the patient receiving iOO% oxygen, which provides quantification of the percentage right-to-left shunt.

It

is necessary

obtained

to consider

physiologic

tests, since they provide a useful nonimaging approach for screening patients with HHT who may or may not have PAVMs. It is also useful to consider the results of Remy et al in the context of other imaging studies, including evaluation of PAVMs with radionucide imaging, ultrasound (US), and magnetic resonance (MR) imaging. Patients with PAVMs have interesting physiology because of the basal location of most of the PAVMs and the degree of hypoxemia, which may be severe when multiple PAVMs are present (i,5). Orthodeoxia is the term used whenever the arterial oxygen content is significantly reduced on assumption of the sitting or standing position (6). This change in arterial oxygen content, which occurs whenever patients assume the upright position, is most likely associated with gravitational shifts of putmonary blood flow to the base of the lung. Orthodeoxia occurs in a high percentage of patients with PAVMs and is the basis for measurement of arterial blood gases with the patient in the supine and sitting or standing position as a screening method (5). Another useful and simple approach to diagnosis of PAVMs is measurement of the percentage of blood shunted right to left across the PAVM. Measurement of the percentage shunt is easily and routinely performed with administration of 100% oxygen to the patient and measurement of arterial oxygen content after 20 mmutes (7). Thus, measurement of arterial oxygen content with the patient in the sitting and supine positions and after the administration of 100% oxygen with the patient in the sitting position is a valuable, low-cost screening method for detection and quantification of PAVMs (7). These techniques are also very useful in the intermediate evaluation and long-term follow-up of these patients after embolotherapy (1,5,7). Long-term follow-up and actual measurement of the growth of unocciuded PAVMs is generally lacking. The results of studies with CT by Remy et al and our own resuits with arterial blood gas measurements are in agreement in showing that little change occurs in the degree of right-to-left shunting or the size of unoccluded PAVMs over follow-up of 3-4 years

(1,4,5).

Few comparative imaging studies have been published in which the sensitivity, specificity, and accuracy of imaging PAVMs have been assessed. In the study reported by Remy et al in this issue of Radiology, correlation was not performed with the chest radiographic 634

#{149} Radiology

findings in their 40 patients. If our own experience is any indication, it is likely that chest radiographs in 80% or more of the patients examined by Remy et a! were abnormal at the time of clinical evaluation. Assessment of PAVMs with technetium-labeled albumin microspheres has been reported by Chilvers and associates as an extremely useful method for detection and quantification of shunting before and after embolotherapy (8). Chilvers et at measured the right-to-left shunt through the lungs by quantifying the fraction of the injected dose of microspheres that reached the kidneys. With this technique, they also evaluated the results of embolotherapy (8). Detection of right-to-left shunting with cardiac US has also been reported (9-il). This examination depends on the early appearance of microcavitations in the left atrium, assessed with M-mode or two-dimensional fourchamber echocardiography after intravenous injection of agitated saline. This technique is very useful for detection of small amounts of right-to-left shunting, but findings obtained with it cannot be quantified currently. To my knowledge, no one has published a study on (a) the sensitivity, specificity, or accuracy of chest radiographs compared with quantitative arterial blood gas measurements, (b) radionuclide shunt studies, or (c) qualitative echocardiographic studies for screening large numbers of patients with HHT. Until comparative studies are done with these modalities and with CT or angiography, the suggestion by Remy et a! that CT of the thorax should be performed as part of the routine imaging assessment of PAVMs is premature. If quantitative measurement of arterial blood gas, along with detection of left atrial microcavitations by means of echocardiography, does prove to be

as valuable

as suggested,

the algorithm

for screening patients may start with chest radiography and these procedures rather than with CT. If the results of

future

prospective

with these confirmed

studies

screening as sensitive

pulmonary angiography, CT of the thorax, may cal procedure

performed

procedures are and specific, then

rather than be the next logi-

in evaluation

of these

pa-

tients.

One cannot leave a discussion of imaging techniques for detection of PAVMs without consideration of MR imaging. Diagnosis of PAVMs with MR imaging has been reported, but assessment of the usefulness of MR imaging for diagnosis of this condition is still in

its infancy

(i2,l3).

As is true

for so many

other techniques that are still developing and are expensive, the previously described imaging and physiologic tests, rather than MR imaging, likely will be the mainstay of diagnosis and follow-up in these patients.

Before one considers further the algorithm proposed by Remy et al for radiologic evaluation of PAVMs, it is necessary to consider the natural history of the PAVM and the clinical implication in patients with this abnormality. The recent cardiopulmonary literature suggests that 40%-50% of patients with PAVMs are at risk for paradoxical embolization leading to transient ischemic attacks and stroke (i,i4,15; Charnas LR et al [unpublished data, 1991]). An additional 5%-9% of patients are at risk for cerebral abscess that has been correlated to follow dental cleaning or dental procedures in patients with PA VMs (1,15,16). On the basis of our own experience with this disorder, we estimate that the annual risk of stroke is approximately i.5% per year among patients with PAVMs (Charnas LR et at [unpublished data, 1991]). There is also evidence that detection of PAVMs and their obliteration by means of embolotherapy is an effective means of preventing stroke and transient ischemic attacks but does not reduce the risk for brain abscess (1,15; Charnas LR et at [unpublished data, 199i]). Because of the complications associated with untreated PAVM, it is important to urge physicians to perform screening in all patients at risk for PAVM. It is proper to query, Who should be screened? Previous work has suggested that 5%-l5% of patients with HHT have PAVMs (17,18). Unfortunately, modern imaging techniques were either not available or not applied when the number of patients with HHT who also have PAVMs was estimated. Previous studies have also suggested that whenever one patient in a large family with HHT has PAVMs, it is likely that other family members (who have no symptoms) have PAVMs (1). These observations have led us to conclude that all patients with HHT and their families should undergo screening for PAVM as simply and cost-effectively as possible, because those with PAVM are at risk of serious morbidity and death (1,13; Charnas LR et at [unpublished data, i991]). Although it is presumptuous, without prospective data, to present an alternative algorithm to the one proposed by Remy et at for the workup of families with HHT and suspected PAVMs, I wilt take editorial license and do so anyway. The Figure is a proposal for an imaging and “physiologic” algorithm for the screening, evaluation, and therapeutic management of families with HHT or patients with sporadic PAVM without HHT. Were it possible to arrange for a consensus conference, most physicians would likely agree that a family member or patient with significant epistaxis should undergo chest radiography and perhaps measurement of arterial blood March

1992

MACINC OF PA11ENT

AND FHYSIOLOGIC STUDY WITh HHV AND/OR PAVM

ography, measurement gases, and echocardiography

performed and compared with pulmonary angiography before one can condude that additional, more sophisticated imaging, such as CT or MR

CHEST RADIOGRAPH ABG/EGHO BUBBLE’

imaging, is required these patients.

IS_.__#

I

F

#{149}L

In their

IN;wE CT SCAN

OFNORAX

/

I’ GIOGRAPHY

INTERVAL

F

PAVM

An algorithm for workup HHT and PAVMs. ABC

arterial

blood

FOLLOW UP SCAN

YEARS) MG

GROWTh

UNOCCLUDED

=

in families with measurement of

gases in patients

breathing

room air and after 20 minutes of their breathing 100% oxygen; ECHO BUBBLE** appearance of right atrial and, soon thereafter, left atnal microcavitations on apical fourchamber

view

of the

injection

of agitated

epistaxis, telangiectasia, tive with HHT (18). present, the patient growth of unoccluded

pulmonary

heart

after intravenous saline (10,11); HHT* and first-degree

If two of these has

HHT.

PAVM

angiography

three

After

rela-

are

interval

be added

examina-

to this

In patients

with

screening

normal

find-

ings at screening procedures, no additional imaging would likely be required. In patients with abnormal findings at screening procedures, pulmonary angiography would probably be the next logical step, because angiography is

necessary

to help

the thorax

plan

the approach

for

would

be helpful.

In the vast

majority of patients with HHT and their affected family members, these screening procedures would be expected to

PAVM,

and

CT or MR imaging

of the thorax would not be required. Clearly, a study that establishes the sensitivity, specificity, and accuracy of screening large numbers of patients at risk for PAVM by means of medical history, physical examination, chest radi-

Volume

after

tion is that,

should mainder

182

#{149} Number

3

brain

should

abscess

initial

therapy.

The

once

PAVM

has been

these

follow-up

and

patients

after

should

7.

8.

there

right-to-left

9.

11.

patients

first

it is clear that small, grow slowly with data, 1992) and repeat study and years after their procedure. a

Med 1983; 308:1197-1210. Robin ED, Laman D, Horn related

results

of N EnglJ

J.

DR, Theodore

to orthodeoxia

caused

by

true vascular lung shunts. N EngI J Med 1976; 294:941-943. Chilvers ER, Mona KB, Whyte JE, et al. Effect of percutaneous transcatheter embolization on pulmonary function, right-toleft shunt, and arterial oxygenation in patients with pulmonary arteriovenous malformations. Am Rev Respir Dis 1990; 142:420-425. Chilvers ER, Peters AM, George P, et al.

Chub C, Tajik AJ, Seward JB, Dines DE. Detecting intrapulmonary right-to-left shunt with contrast echocardiography.

Clin Proc 1976; 51:81-84.

Ozkutlu contrast

S, Sara#{231}larM. echocardiography

425-430. Barzilai

fisttila.

12.

AD,

D.

Spessert

in the

Pulmonary

J 1989; 30: C, Picus

Two-dimensional

of congenital

detection

and

fol-

pulmonary arterioAm J Cardiol 1991;

venous malformations. 68:1507-1510. Dinsmore BJ, Gefter HY.

Two-dimensional in pulmonary

Jpn Heart

B, Waggoner

low-up

WB,

Hatabu

arteriovenous

H, Kressel malforma-

tions: diagnosis by gradient refocused MR imaging. J Comput Assist Tomogr 1990; 14:918-923.

13.

Bergin CJ, Pauly JM, Macovski A. parenchyma: projection reconstruction imaging.

14.

Hewes monary

tients

RC, Auster first

M, White RIJr. manifestation

arteriovenous

with

MR Cereof pul-

malformation

hereditary

telangiectasia.

Lung

1991; 179:777-781.

Radiology

bral embolism:

in pa-

hemorrhagic

Cardiovasc

Intervent

Radiol

1985; 8:151-155. 15.

White

RI Jr.

Case

and pulmonary 16.

16-1990:

brain

abscess

arteriovenous

malformation. N EngI J Med 1991; 324:1439-1440. Mohler ER, Monahan B, Canty MD, Flock-

hart DA. Cerebral abscess associated with dental procedure in hereditary haemorrhagic telangiectasia. Lancet 1991; 338:507-

5-10

embolization

and embolization.

echocardiography

require

embototherapy

balloon

D, Goodenberger

(5,7). It is

air arterial oxygen content with the patient in the sitting position and enlargement of unoccluded PAVMs detected on a chest radiograph are indications for further evaluation with angiogra-

most

observations

therapeutic

arteriovenous

is at-

also conjectural to recommend the most accurate physiologic test or imaging examination to use in the follow-up of these patients, but our impression is that a 10% or more decrement in room-

or CT of the thorax, unoccluded PAVMs time (19) (unpublished

physiologic

Mayo 10.

shunting

PAVMs

PB, White RIJr, Barth 1(1-I, et al. Pulmonary arteriovenous malformations:

Terry

Quantification of right-to-left shunt through pulmonary arteriovenous malformations using ‘Tc’ albumin microspheres. Clin Radiol 1988; 39:611-614.

diag-

reclean-

Remy J, Remy-Jardin M, Wattinnes L, Deffontaines C. Pulmonary arteriovenous malformations: evaluation with CT of the chest before and after treatment. Radiology 1992; 182:809-816. Remy-Jardin M, Wattinne L, Remy J. Transcatheter occlusion of pulmonary arterial circulation and collateral supply: failures, incidents, and complications. Radiology 1991; 180:699-705.

Platypnea

They

because

unoccluded

6.

5-15

undergo

receive antibiotics for the of their life before dental residual

5.

implica-

embolotherapy.

work

4.

phy. Whether we follow up patients by means of physiologic detection of increasing shunt and arterial hypoxemia

embolotherapy. Whenever findings on screening chest radiographs, measurements of arterial blood gases, echocardiographic results, or alt of these are inconclusive, then perhaps a CT scan of

exclude

years

through

might

regimen.

the risk of stroke

ways

gases performed white breathing room air and after breathing 100% oxygen in the sitting position. With further experition

et al also

CT scan

ual malformations is extremely stow but does occur, exposing these patients to

ing or dental

is detected,

and embolotherapy

the echocardiographic

Remy

a follow-up

In detection of serial growth of small, unocctuded PAVMs, evidence is accumulating that the growth of these resid-

nosed,

are performed.

ence,

algorithm, that

3.

in

PAVMs. Our experience and theirs suggest that the parenchymal and pleural changes after embolotherapy of pulmonary AVMs are clinically benign and disappear with time, so that CT is likely unnecessary in the diagnostic evaluation of these patients during their immediate follow-up after embolization.

EMBOLOThERAPY

FOLLOW UP (EYERY TWO CHEST RADIOGRAPHY,

suggest

for evaluation

be obtained after embolotherapy or surgery in order to evaluate parenchymat and pleural changes and also for the detection of enlargement of small

I

ABNOLIAL

PULMONARY

of arterial blood must be

509.

Acknowledgments: acknowledges

preparation sha

The the assistance

provided

17.

author gratefully in manuscript

by Carol

Pacelli

and Mar-

Dobson. 18.

References

Robert

1.

White

2.

techniques and long-term outcome of embolotherapy. Radiology 1988; 169:663-669. Hughes JMB, Allison DJ. Pulmonary arteriovenous malformations: the radiologist replaces the surgeon. Clin Radiol 1990; 41:

Pulmonary

Hodgson CH, Burchell HB, Good CA, Clagett OT. Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous fistula: survey of a large family. N EnglJ Med 1959; 261:625-636. Plauchu H, de Chadarevian JP, Bideau A,

RIJr,

Lynch-Nyhan arteriovenous

A, Terry

P, et a!.

hereditary

malformations:

JM.

Age-related hemorrhagic

clinical

profile

telangiectasia

of in

an epidemiologically recruited population. Am J Med Genet 1989; 32:291-297. 19.

Vase P, Holm M, Arendrup nary arteriovenous fistulas hemorrhagic telangiectasia. Scand 1985; 218:105-109.

H. Pulmoin hereditary

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Radiology

635

#{149}