Screening for pulmonary arteriovenous malformations using transthoracic contrast echocardiography: a prospective study

Abstract

Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of the present study was to prospectively establish the diagnostic value of transthoracic contrast echocardiography (TTCE) as a screening technique for PAVM using chest highresolution computed tomography (HRCT) as the gold standard for PAVMs.All consecutive adult patients referred for HHT screening underwent a chest HRCT (n5299), TTCE (n5281), arterial blood gas analysis (n5291), shunt fraction measurement (n5111) and chest radiography (n5296).TTCE was positive in 87 (58.8%), 12 (16.7%) and four (6.7%) patients, and chest HRCT was positive in 54 (36.5%), three (4.2%) and zero (0%) patients with a definite, possible and negative clinical diagnosis of HHT, respectively. Two patients with a negative TTCE were diagnosed with PAVMs after computed tomography; in both cases the PAVMs were too small to be treated by embolotherapy. The sensitivity of TTCE was 97% (95% confidence interval (CI) 93.6-98.3) and negative predictive value 99% (95% CI 96.9-99.8). The other diagnostic tests showed a considerable lower diagnostic value.The present prospective study shows that transthoracic contrast echocardiography has an excellent diagnostic value and can be used as an initial screening procedure for pulmonary arteriovenous malformations. The high false-positive rate of transthoracic contrast echocardiography possibly represents microscopic pulmonary arteriovenous malformations.KEYWORDS: Contrast echocardiography, hereditary haemorrhagic telangiectasia, pulmonary arteriovenous malformations A pulmonary arteriovenous malformation (PAVM) is a direct communication between a pulmonary artery and pulmonary vein. A PAVM results in a right-to-left shunt (RLS) causing hypoxaemia and risk of paradoxal embolism through bypassing the filtering capillary network. Complications occurring in patients with PAVM and hereditary haemorrhagic telangiectasia (HHT) are stroke (10-19%), transient ischaemic attacks (6-37%), cerebral abscess (5-9%), migraine headaches, seizures, massive haemoptysis and (spontaneous) haemothorax [1][2][3]. Antibiotic prophylaxis prior to procedures carrying the risk of bacteraemia is recommended [3][4][5]. At least 80% of PAVMs are associated with HHT [3]. HHT is an autosomal dominant disorder characterised by vascular abnormalities varying from small telangiectases to large arteriovenous malformations. The clinical diagnosis is based on the Curaçao criteria [6]. Based on genetic analysis, HHT is divided into types 1 and 2, corresponding with mutations in the genes ENG and ACVRL1, coding for endoglin and activin A receptor type-like kinase 1, respectively [7,8]. The prevalence of PAVM, as documented by chest high-resolution computed tomography (HRCT), in all HHT patients is 20-45% [4,9]. The PAVM prevalence differs between these two subtypes, in HHT type 1 the prevalence is 48%, whereas the prevalence in HHT type 2 is 5% [10]. PAVMs can...

Screening for pulmonary and cerebral arteriovenous malformations in children with hereditary haemorrhagic telangiectasia

“…Pulmonary and cerebral AVMs can cause complications, such as intracranial bleeding, brain abscess, ischaemic stroke and pulmonary haemorrhage, and screening of at-risk populations has been advocated [23][24][25][26][27][28][29][30][31][32]. Studies in adult patients have demonstrated that significant pulmonary and cerebral AVMs can be detected in asymptomatic patients [5,6,22,[31][32][33][34][35][36][37][38][39], and that preventative treatment can reduce the rate of complications [32]. This is less well established in children, and recent studies have suggested that the overall rate of complications is low in this age group [23,32].…”

Transthoracic contrast echocardiography for detection of pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: How can the process be improved for patient safety?

“…Recent literature [9] has highlighted the possibility that TTCE alone may be sufficient for screening purposes, although this remains controversial.…”

“…TTCE alone [8] or in combination with plain chest radiography [5] has been reported to be 100% sensitive for, and able to definitively rule out, PAVMs in patients with shunts. At least some authors have argued, however, that addition of plain chest radiography to TTCE exposes patients to ionizing radiation without demonstrated improvement in detection of PAVMs [9] . Given the need for lifelong screening required in HHT, minimizing use of modalities which utilize ionizing radiation is preferred to reduce the cumulative lifetime radiation exposure [1,5] .…”

Detection of Intracardiac and Intrapulmonary Shunts at Rest and During Exercise Using Saline Contrast Echocardiography

“…With a prevalence of 30 to 40%, it is difficult to argue the existence of a PFO if intravenously injected saline contrast bubbles appear in the left heart. Alternatively, saline contrast echocardiography as a technique for intrapulmonary right-to-left shunts remains less well established, despite the fact that it is more sensitive than pulmonary angiography for detection of even the smallest right-to-left intrapulmonary shunts (Cottin et al, 2004;van Gent et al, 2009).…”

“…The second injection should confirm the presence of an intracardiac shunt if there is increased contrast and/or if the contrast bubbles continue to appear in the left heart in ≤ 3 heartbeats. Alternatively, if saline contrast bubbles appear in the left heart in > 3 heartbeats after their appearance in the right heart, then an intrapulmonary shunt is suspected, e.g., pulmonary arteriovenous malformation, pulmonary arteriovenous anastomoses (Nanthakumar et al, 2001;Lee et al, 2003;van Gent et al, 2009;Elliott et al, 2011a). The different types of intracardiac and intrapulmonary shunts are outlined in detail below.…”