REVIEWS

Pulmonary arteriovenous malformations: a clinicalreview

Mobeen Iqbal, Leonard J RossoV, Harry N Steinberg, Kamel A Marzouk, David N Siegel

AbstractPulmonary arteriovenous malformations(PAVMs) are a rare clinical entity. Most ofthem are associated with hereditaryhaemorrhagic telangiectasia. The usualclinical presentation is exertional dys-pnoea and hypoxaemia. The initial test ofchoice for screening is the 100% oxygenmethod. A pulmonary angiogram isneeded to define the anatomy and guidetranscatheter embolisation (TCE). TCEhas been shown to be eVective and safewith a very low recanalisation rate and haslargely replaced surgery for PAVMs. Com-puted tomography of the chest can be usedfor the follow up of asymptomatic PAVMsand TCE.(Postgrad Med J 2000;76:390–394)

Keywords: arteriovenous malformation; hypoxaemia;shunt study; embolisation

Pulmonary arteriovenous malformations(PAVMs) are abnormal direct communicationsbetween the pulmonary artery and vein. MostPAVMs are congenital but acquired causes ofPAVMs include post-thoracic surgery, trauma,tuberculosis, actinomycosis, and schisto-somiasis.1 PAVMs results in a right to leftshunt, which if significant can cause symptoms.PAVMs can impair the normal filtering func-tion of lungs and be a source of paradoxicalembolism and systemic infections.2 Surgerywas the only curative treatment available beforethe introduction of transcatheter embolisation(TCE), which is now generally accepted as theprocedure of choice.

Association with hereditaryhaemorrhagic telangiectasiaMost of congenital PAVMs (60% to 90%)2 areassociated with hereditary haemorrhagic tel-angiectasia an autosomal dominant disorderwith mutations localised to chromosome locus9q3.3 This gene encodes endoglin, which isthe transforming growth factor-â bindingprotein.4 Other mutations have been identifiedfor activin receptor-like kinase 1 gene onchromosome locus 12q, which controls bloodvessel development and repair. Geneticheterogeneity in hereditary haemorrhagic tel-angiectasia has been shown in families thatshow linkage to other regions on the long armof chromosome 12.5

Clinical featuresSymptoms related to PAVMs often developbetween the fourth and sixth decades. Theclassical triad of hereditary haemorrhagictelangiectasia consists of epistaxis, telangiecta-sias, and a family history of the disorder. Com-mon clinical features are epistaxis, dyspnoeahaemoptysis, telangiectasias, cyanosis, club-bing (in the presence of right to left shunt), andgastrointestinal bleeding.6 7 Sometimes a bruitis audible on chest auscultation. As most ofPAVMs are located at the bases of the lung,orthostatic hypoxaemia (orthodeoxia) can alsooccur. Platypnoea (improvement in dyspnoeaon reclining) is associated with decreasedblood flow through PAVMs in the supineposition.8

ComplicationsPAVMs may result in serious complications,which can frequently be prevented with appro-priate treatment. Neurological complicationsare the most commonly seen. These includestrokes (18%), transient ischaemic attacks(37%), cerebral abscess (9%), migraine (43%),and seizures (8%).9 Paradoxical embolism isthe most common cause of non-infectious cere-brovascular accidents. Polycythaemia and co-existent cerebral arteriovenous malformationsare rare causes of cerebrovascular accidents.9

Less common, but potentially life threateningcomplications, include haemothorax andhaemoptysis.10

Box 1 lists the complications.

Box 1: Complications of PAVMsNeurologicalx Cerebral abscess

x Cerebrovascular accidents

x Migraine

x Seizures

Cardiovascularx Pulmonary hypertension

x High output cardiac failure

x Paradoxical embolism

Pulmonaryx Haemoptysis

x Haemothorax

Haematologicalx Polycythaemia

Postgrad Med J 2000;76:390–394390

Division of Pulmonaryand Critical CareMedicine, Long IslandJewish Medical Centre,Long Island Campus ofthe Albert EinsteinCollege of Medicine,Room C-20, 270-0576th Avenue, NewHyde Park, NY 11042,USAM IqbalL J RossoVH N SteinbergK A Marzouk

Division of Vascularand InterventionalRadiology, Long IslandJewish Medical CentreD N Siegel

Correspondence and reprintrequests to: Dr RossoV

Submitted 23 July 1999Accepted 27 October 1999

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DiagnosisDepending on the clinical presentation thediagnosis of PAVMs is established by evidenceof right to left shunt and imaging studies.

The 100% oxygen method, contrast echo-cardiography, and radionuclide imaging arenearly 100% sensitive for the detection of clini-cally significant PAVMs. The specificity ofcontrast echocardiography and radionuclideimaging is higher than the 100% oxygenmethod.9

100% OXYGEN METHOD

The ease of performance and low cost makethe 100% oxygen method a preferred initialstudy. The patient breathes 100% oxygen for20 minutes. In normal persons partial pressureof oxygen (pO2) rises to 80 kPa. Shunt fractioncan be calculated by measuring pO2 and thenusing a shunt equation. If the shunt fraction ismore than 5% further studies are indicated. Aformula for shunt fraction is shown below:

Shunt fraction = (CcO2−CaO2)/(CcO2−CvO2)11

CcO2 is end capillary oxygen content ofblood, CaO2 is arterial oxygen content, andCvO2 is venous oxygen content. The aboveequation is the most accurate method of calcu-lating shunt fraction but it requires measure-ment of the mixed venous saturation and thusright heart catheterisation. There are simplifiedversions of above equation including:

Shunt fraction =(PAO2−PaO2)/(PAO2−PaO2+1670)11

PAO2 is alveolar oxygen tension and PaO2 isarterial oxygen tension.

The 100% oxygen method is not an errorfree method. The technique (air leaks) andduration of oxygen breathing (nitrogen washout) can aVect the results; 100% oxygen itselfcan cause atelectasis and small shunt fraction(up to 11%).12

CONTRAST ECHOCARDIOGRAPHY

Contrast echocardiography is perhaps the mostsensitive method for detection of PAVMs. It isnon-invasive and widely available. Agitatedsaline is injected (to create bubbles) in aperipheral vein and echocardiography is per-formed. In normal conditions bubbles will betrapped in the lungs but in the presence ofPAVMs they will quickly appear in the leftatrium after three to five cardiac cycles in theabsence of intracardiac shunt (where bubblesappear in less than three cardiac cycles).13

Contrast echocardiography does not quantifyshunt fraction. It may be too sensitive for clini-cally insignificant PAVMs and for follow up ofTCEs.

RADIONUCLIDE IMAGING

Radionuclide imaging is also a sensitivemethod and can quantify the shunt fraction butit cannot diVerentiate between a cardiac orpulmonary source of shunt.14

ULTRAFAST CONTRAST ENHANCED COMPUTED

TOMOGRAPHY

Ultrafast contrast enhanced computed tomo-graphy has been shown to be more sensitive

than conventional pulmonary angiograms forPAVMs and better in defining their architec-ture. Three dimensional helical computedtomography has also shown to be very accuratein analysing the PAVMs especially if combinedwith concomitant cross sectional images.15 Themain advantage of helical computed tomogra-phy is non-invasiveness and avoidance ofcontrast injection. The disadvantage is falsepositive results with vascular tumours.

MAGNETIC RESONANCE IMAGING

The data on magnetic resonance imaging ofPAVMs is not extensive. Recently, phase con-trast cine sequences have been shown to be themost accurate of magnetic resonance imagingtechniques (conventional spin magnetic reso-nance and rotation gated magnetic resonance).16

The main limitation to magnetic resonancetechniques is expense and availability.

PULMONARY ANGIOGRAPHY

Pulmonary angiography remains the goldstandard especially when a therapeutic inter-vention is planned.15 Subtraction angiographyhas largely replaced the conventional angio-gram for PAVMs. Angiography supplies de-tailed information on morphology, complexity,and size of PAVMs.

ScreeningAll patients with hereditary haemorrhagic tel-angiectasia should undergo routine screeningwith the non-invasive techniques preferably withthe 100% oxygen method. Family members ofpatients with hereditary haemorrhagic tel-angiectasia should also be screened forPAVMs.17 Though radionuclide imaging andcontrast echocardiography are very sensitive andmore specific than the 100% oxygen method,the cost and availability are the main limitingfactors. Moreover contrast echocardiographycan be too sensitive by detecting clinicallyinsignificant microvascular shunts and radio-nuclide imaging does not diVerentiate betweena cardiac or pulmonary source of AVMs.

After embolisation of PAVMs follow upscreening may be indicated at one month andagain at one year. Generally treated PAVMsdisappear or are reduced to a fibrous strand bythe end of one year. Any evidence of persist-ence suggests recanalisation and is an indica-tion for re-embolisation. Thereafter spiralcomputed tomography scan should be doneafter every three to five years for developmentof new or growth of small PAVMs.2 19 Anti-biotic prophylaxis is recommended for anyprocedure that may induce bacteraemia. Preg-nant females with PAVMs are at high risk forcomplications such as increase in size, right toleft shunt, pulmonary haemorrhage, andstrokes. This suggests a hormonal influence onPAVMs and is an indication for screening.18

TreatmentTCE has revolutionised the treatment ofPAVMs by virtually eliminating the need forsurgery. Stainless steel coils and detachableballoons are the commonly used devices forTCE. The size of coil is critical, as larger coils

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may be diYcult to form a tight nest and if toosmall can result in paradoxical coil embolism.The introduction of new detachable steel coilshas eased the problem of selecting the rightsize. Detachable coils can be withdrawn if theyare not of right size or can be reinserted if notproperly placed. Detachable balloons are pre-ferred by some workers due to their ability tobe retrieved if of the incorrect size but with theavailability of detachable coils this is no longeran issue.1 2

The femoral vein is the preferred site forcatheterisation. Both right and left sidedpulmonary angiograms are performed usingdigital subtraction technique. The feedingartery of a PAVM is selectively catheterised andthe steel coil is advanced through the catheterin the feeding artery close to the PAVM sac.The pulmonary angiogram is repeated to seethe blood flow to the PAVM. Multiple coilsmay be required until the blood flow to thePAVM has stopped. If the balloon technique isemployed, after selective catheterisation of thefeeding artery a silicon or gold valve balloon isadvanced over the catheter and inflated withcontrast material. A pulmonary angiogram isperformed to ensure PAVM occlusion and theballoon is detached.1 2 9

EYcacy and safety of TCE has been demon-strated in many studies. In a long term study,45 patients with PAVMs more than 8 mm weretreated successfully with embolotherapy andonly 16% required repeated TCE for persistentPAVMs or recanalisation.19 Current indicationsfor TCE include the prevention of complica-tions in larger (feeding artery diameter >3 mm)and symptomatic PAVMs. Persistence ofPAVMs at one year after TCE on computedtomography is evidence of recanalisation orinadequate embolisation and represents anindication for pulmonary angiography withrepeat TCE.2

The most common complications of TCEare procedure related (contrast allergy, localhaematoma at puncture site, etc) and pleurisy.Delayed pleurisy (four to six weeks after theprocedure) with fever and infiltrates has beenreported mainly with larger PAVMs.2 19 Rarely,angina and migration of coils from PAVM sacto pulmonary vein can result in a paradoxicalcoil embolism. Recanalisation after embolisa-tion is not common and has been attributed toelongation of or an insuYcient number of coils.This can be avoided by placing coils or detach-able balloons within or as near to a PAVM aspossible. This prevents bronchial arterial com-munication with the pulmonary artery.20

MEDICAL THERAPY

Medical therapy in the form of hormones,danazol, octreotide, desmopressin, and amino-caproic acid have been tried with variable suc-cess only in epistaxis and gastrointestinalbleeding. There are no data of their use inPAVMs.21

LUNG TRANSPLANTATION

Lung transplantation can be considered forpatients with diVuse multiple PAVMs unrespon-sive to TCE, however, relative survival data are

sparse. The timing of transplantation remainsdiYcult. Our third patient with diVuse diseasedid not respond to multiple embolisations anddemonstrated pulmonary hypertension withborderline oxygen saturation on room air. Sucha patient likely represents a good candidate forearly referral for lung transplantation.

In conclusion, PAVMs are most commonlyassociated with hereditary haemorrhagic tel-angiectasia. Family members of the indexpatient with hereditary haemorrhagic tel-angiectasia should be screened for the disease.The 100% oxygen method for shunt calcula-tion remains the preferred initial screeningmethod. TCE is the treatment of choice andcan be repeated as needed. Ultrafast computedtomography is the imaging modality of choicefor follow up after TCE and also for asympto-matic PAVMs <3 mm.

Case reportsCASE 1

A 66 year old white women was referred to ourclinic for non-resolving pneumonia. She wastreated with antibiotics for mild haemoptysiswith mucopurulent sputum. Follow up chestradiography showed no improvement. Herexertional dyspnoea worsened and she devel-oped new cognitive deficits. She had a transientischaemic attack four years before. Her familyhistory was unremarkable.

Figure 1 High resolution computed tomography showinga PAVM with a feeding artery and draining veins in theright lower lobe.

Figure 2 Pulmonary angiogram showing the anatomyand size of a PAVM.

392 Iqbal, RossoV, Steinberg, et al

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On physical examination all vital signs werenormal. The significant findings were centralcyanosis and a systolic murmur best heard atthe apex and radiating to the axilla. Chest

radiography revealed a right lower lobe lobu-lated mass. Computed tomography revealed alobulated opacity with a feeding artery and twodraining veins (fig 1). A diagnosis of PAVM wasmade on the clinical information. The calcu-lated shunt fraction was 14%. Pulmonaryangiography was performed with successfulTCE by metalic coils (figs 2 and 3). The shuntfraction immediately decreased to 6% after theprocedure and the patient was dischargedwithin 24 hours. Her clinical improvementpersisted in subsequent follow up.

CASE 2

A 34 year old white man and lifelong non-smoker with hereditary haemorrhagic tel-angiectasia was admitted for fever and head-ache. There was no history of cough,haemoptysis, or chest pain. He noted graduallyworsening exertional dyspnoea for eight to ninemonths and complained of an episode odepistaxis a few months before. He had a historyof right middle lobectomy 20 years before forsymptomatic PAVM. The family history wasunremarkable. Physical examination revealedscattered telangiectasias on the oral mucosa andscalp. Examination of the lungs was normal andno neurological deficits were detected. Magneticresonance imaging of the brain revealed a rightparietal lesion consistent with cerebral abscess.The abscess was aspirated stereotactically andtreated with broad spectrum antibiotics. Heimproved clinically but was persistently hypox-aemic on room air. The calculated shuntfraction was 18%. Computed tomography with-out contrast showed a 2.0 × 2.5 cm PAVM in theright upper lobe (fig 4) and a 1 cm PAVM in theright lower lobe (not shown). Pulmonary angio-graphy was performed with TCE using titaniumcoils with successful occlusion of both PAVMs.The subsequent shunt calculation was normal(less than 5%).

Figure 3 Pulmonary angiogram after embolisation andcomplete obliteration of a PAVM.

Figure 4 Computed tomography demonstrating a PAVMin the right upper lobe.

Figure 5 Pulmonary angiogram showing multiple bilateral PAVMs and evidence of previous embolisations.

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CASE 3

A 31 year old white women with a known diag-nosis of Osler-Wber-Rendu disease ( heredi-tary haemorrhagic telangiectasia) presentedwith increasing dyspnoea on exertion. Hersymptoms started at age 13 when she noted aninability to keep up with her peers in normalactivities. In her late 20s she had two transientischaemic attacks with no residual deficit.Three previous pulmonary angiograms wereperformed with multiple TCEs with the lastdone six years before (fig 5, left and right). Heronly current medication was an oral contracep-tive for hereditary haemorrhagic telangiectasia.Her family history was significant for PAVMsin her father and grandmother. Physical exam-ination revealed telangiectasias on her foreheadand buccal surface of the oral mucosa. A bruitwas heard in the distribution of the right lowerlobe posteriorly. The calculated shunt fractionwas 24%. Echocardiography showed an en-larged hyperdynamic left ventricle with evi-

dence of mild pulmonary hypertension. TCEwas not attempted for fear of worsening thepulmonary hypertension.

1 Coley SC, Jackson JE. Pulmonary arteriovenous malforma-tions. Clin Radiol 1998;53:396–404.

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3 Shovlin CL, Hughes JM, Tuddenham EG, et al. A gene forhereditary hemorrhagic telangiectasia maps to chromosome9q3. Nat Genet 1994;6:205–9.

4 McAllister KA, Grogg KM, Johnson DW, et al. Endoglin, aTGF-beta binding protein of endothelial cells, is the genefor hereditary haemorrhagic telangiectasia type 1. Nat Genet1994;8:345–51.

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Learning pointsx PAVMs are usually present with

dyspnoea and unexplained hypoxaemia.

x PAVMs can cause neurologicalcomplications like cerebral abscess andcerebrovascular accidents.

x The 100% oxygen method to calculateshunt fraction is the initial screeningmethod of choice.

x Pulmonary angiography is required toevaluate size, anatomy, and guidetreatment for symptomatic PAVMs.

x TCE is the treament of choice and canbe repeated safely.

x High resolution computed tomographycan also screen for PAVMs, followlesions <3 mm in diameter, and monitorfor recurrence after treatment.

x Patients with PAVM should receiveantibiotic prophylaxis for procedureslikely to induce bacteraemia.

x Family members of patients with PAVMsshould be screened.

394 Iqbal, RossoV, Steinberg, et al

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doi: 10.1136/pmj.76.897.390 2000 76: 390-394Postgrad Med J

 Mobeen Iqbal, Leonard J Rossoff, Harry N Steinberg, et al. clinical reviewPulmonary arteriovenous malformations: a

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