Description of the condition

Pulmonary arteriovenous malformation (PAVM) is an abnormal direct connection between a pulmonary artery and a pulmonary vein. The malformations can manifest as a single focal lesion, or as multiple lesions. It is estimated that about 90% of individuals with PAVMs have hereditary haemorrhagic telangiectasia (HHT) and only about 50% of individuals with HHT have PAVMs (Cottin 2004; Shovlin 2008). Therefore, individuals with PAVMs who have not been previously diagnosed with HHT should be tested for the genetic disorder (Coley 1998; Sabbà 2005). The incidence of PAVM is 1 per 100 000 population with a male to female ratio ranging from 1:1.5 to 1.8 (Abdalla 2006; Kjeldsen 1999; Khurshid 2002). Between 50 and 70% of cases, PAVMs commonly involve the lower lobes. The distribution of PAVMs is unilateral in 70% of individuals; 36% have multiple lesions, and half of those with multiple lesions have bilateral disease (Gossage 1998; Khurshid 2002). A PAVM is described as being either simple or complex. A simple PAVM is supplied by one artery, whereas the complex variety receives blood supply from two or more arteries (Gossage 1998: Lee 1997). Non HHT‐related PAVMs are most commonly sporadic, or secondary to hepato‐pulmonary syndrome, caval pulmonary shunts, or trauma (Shovlin 2009b).

The recognised features of HHT are all due to abnormalities of vascular structure. Individuals with HHT have a tendency to form blood vessels without intervening capillaries between an artery and a vein. The connection segment between an artery and a vein tends to be fragile and can rupture and bleed. The affected small blood vessel is termed telangiectasia and the affected larger blood vessel is termed arteriovenous malformation (AVM). Such malformations in HHT are only occasionally congenital; most develop during puberty. In 1999, the Scientific Advisory Board of the HHT Foundation International Incorporated established clinical criteria for the diagnosis of HHT known as the Curaςao criteria (Shovlin 2000). The HHT diagnosis is definite if three criteria are present. A diagnosis of HHT cannot be established in people with only two criteria; however, a high index of clinical suspicion should be maintained. A diagnosis of HHT is unlikely if fewer than two criteria are present. The Curaςao criteria are as follows:

1. epistaxis ‐ spontaneous, recurrent nosebleeds

2. telangiectases ‐ at characteristic sites (lips, oral cavity, fingers, nose)

3. visceral lesions ‐ such as gastrointestinal telangiectasia (with or without bleeding), pulmonary AVM, hepatic AVM, cerebral AVM, spinal AVM

4. family history ‐ a first‐degree relative with HHT

Most people with PAVMs turn out to have HHT if it is screened for carefully (Bayrak‐Toydemir 2004). It is an autosomal dominant disorder caused by a mutation in one of at least several genes. Three identified gene mutations have been identified to date: HHT type 1 results from gene mutations encoding endoglin and HHT type 2 from gene mutations encoding ALK‐1 (activin receptor‐like kinase1) (Abdalla 2006). A subset of people with HHT in association with juvenile polyposis harbour mutations in the SMAD4 gene (Abdalla 2006). There are at least two further unidentified genes that can cause classical HHT (Govani 2009). The abnormal vascular structure in HHT is in part due to an initiating event combined with abnormal repair from an imbalance in TGF‐β related functions (Shovlin 1999).

Description of the intervention

Currently, percutaneous embolisation therapy is the most commonly used treatment for people with PAVMs. The advantages of embolisation therapy over surgical intervention of PAVMs are that it is less invasive and easy to repeat. The three major indications for treatment include:

1. Prevention of neurological complications including stroke and brain abscess (Shovlin 2008);

2. Improvement in exercise tolerance;

3. Prevention of lung haemorrhage (Gossage 1998; Khurshid 2002).

The radiological literature currently advocates embolisation therapy to be offered to both symptomatic patients and asymptomatic patients with PAVMs of a size amenable to embolisation. In the past, some institutions had considered PAVM of 3mm as a threshold for embolisation; however, such recommendations were withdrawn in 2006 with suggestions that smaller PAVMs may benefit from embolisation. Treatment of PAVMs less than 3mm in size has the benefit of protection against bacterial embolisation as well as paradoxic bland embolisation (Pollack 2006). Moreover, smaller PAVMs have the potential to enlarge over time (Pollack 2006; Shovlin 2008). However, embolisation of smaller vessels is technically difficult because they are harder to cannulate, and this may result in occlusion of larger proximal vessels.

The embolisation procedure is performed by an interventional radiologist. There are variations in practice regarding the use of antibiotic prophylaxis before catheter‐directed embolisation which has the potential to produce bacteraemia (Borrero 2006; Coley 1998; Shovlin 2008). A right femoral venous puncture is used and a catheter is directed into the right and then left pulmonary arteries. The initial angiograms of each side provide a general overview of the number and distribution of PAVMs. During embolisation of PAVM, the target is the supplying artery immediately preceding the aneurysmal sac. The use of coaxial catheters allows precise placement of the embolisation device and is critical to the outcome of the procedure (White 2007). In the co‐axial catheter, the outer or guide catheter is essential for stable placement while the inner catheter is used for deployment of embolisation device. Once the embolisation device is securely in place, angiography is repeated to determine whether all possible conduits to the aneurysmal sac have been occluded.

How the intervention might work

The choice of embolisation device depends on the vascular anatomy of the individual. In general, PAVMs with feeding artery diameters of 3 to 9mm are treated with either balloons or coils and those with feeding artery diameters greater than 8mm are treated with coils alone or with an over‐inflated balloon impacted within a nest of coils (Lee 1997; Saluja 1999).

Types of embolisation device:

1. Coil (various types of fibered and unfibered, detachable, and pushable coils)

2. Detachable balloon

3. Amplatzer Vascular Plugs, most recent device (Ferro 2007)

The deployed coils are designed to coil within the vessel lumen and carry microfibres which activate platelets to generate an occluding platelet plug, while Amplatzer and balloon devices provide direct obstruction to vascular flow. Balloon embolisation offers additional advantage in that balloon inflation, placement, and location may be adjusted before detachment of the device (Borrero 2006).The most recent embolisation device on the market is the Amplatzer Vascular Plug. This self‐expanding cylindrical mesh cage allows a chance of recapture and redeploy until proper positioning is achieved (Ferro 2007). The choice of embolisation device is operator‐dependent and correct angiographic assessment of vessel size can prevent device‐associated complications such as down‐stream migration of the devices.

Since embolisation became standard practice in the 1980s, surgical resection of PAVMs have largely been reserved for PAVMs not amenable to embolisation. Surgery is also used as an emergency procedure to control haemorrhage, when loss of lung tissue is justified. Available surgical techniques include different extent of surgical excision of PAVMs: local excision, segmental resection, lobectomy, ligation, and even pneumonectomy, but whenever possible lung conservation resection is the preferred choice of treatment (Khurshid 2002).

Neither embolisation therapy nor surgery will completely eradicate PAVMs in people with HHT as small PAVMs may persist and new PAVMs may be formed. On the other hand, shunting can be abolished even in people with HHT if large PAVMs are treated. The majority of patients have small shunts. Hence, the use of antibiotic prophylaxis in interventional procedures, such as embolisation therapy, and dental procedures is still recommended (Coley 1998; Borrero 2006; Sabbà 2005; Shovlin 2008). Embolisation therapy and surgery for PAVMs both require specialised techniques and experience. Procedure complications are operator‐dependent and are related to the number of procedures performed annually (Hannan 1989). Since HHT is a multi‐organ disease, it is best managed in specialised HHT centres with high‐volume experience as well as access to multidisciplinary experts.

Why it is important to do this review

Although the natural history of untreated PAVMs has not been optimally defined, data from observational studies of untreated PAVM cases show considerable morbidity including stroke, brain abscess, hypoxaemia (exercise tolerance is usually preserved) and haemorrhage (Shovlin 2009; Whyte 1993). Mortality is considered to be caused by PAVM if death is due to brain abscess, stroke, haemoptysis or haemothorax. From the HHT life‐expectancy series, it can be extrapolated that life expectancy must be near normal in people with PAVM and deaths are only rarely a direct consequence of PAVMs (Sabbà 2006). Additional evidence suggests that PAVMs progressively enlarge over time and incidence of progression is higher in individuals with HHT versus those without HHT (Khurshid 2002; Gossage 1998). Individual with multiple PAVM The current practice recommends embolisation of all PAVMs in the absence of contraindications such as severe pulmonary hypertension, renal failure, and early pregnancy.

In 2008, a cohort study by Shovlin et al concluded that it is difficult to predict which HHT patients are at risk of PAVM complications with reference to PAVM size, severity and symptoms (Shovlin 2008). The study suggests greater emphasis on HHT diagnosis, PAVM screening and the necessity of implementing PAVM treatment programmes (Shovlin 2008). Embolisation therapy is currently rendered first line treatment for PAVM; we wish to perform a systemic review to determine the efficacy and safety of the embolisation procedure. We believe that a systemic review will provide an overview of the available evidence from the literature and will show the strength of evidence available in order to make recommendations for current practice and future research.