The role of transthoracic contrast echocardiography in the clinical diagnosis of hereditary haemorrhagic telangiectasia

Abstract

Background: Hereditary haemorrhagic telangiectasia (HHT) can be diagnosed according to the four clinical Curacao criteria, including presence of pulmonary arteriovenous malformations (PAVMs). In the last few years, transthoracic contrast echocardiography (TTCE) replaced chest high-resolution tomography (HRCT) for the screening of PAVMs. Purpose: We evaluated the added value of TTCE to the current clinical Curacao criteria in diagnosing HHT. Methods: Between 2004 and 2012, a total of 487 first-degree relatives of HHT-causing mutation carriers were included, who underwent both TTCE and chest HRCT. Genetic testing was performed in all persons and considered as gold standard for the presence or absence of HHT. A quantitative three-point grading scale was used to classify the pulmonary shunt on TTCE (grade 0, no microbubbles; 1, 100 microbubbles). Results: Genetic testing demonstrated the presence of HHT in 334 patients (68.6%, mean age 43.9±14.8, 57.2% female). Chest HRCT confirmed PAVMs in 114 out of 218 patients with a pulmonary shunt on TTCE (52.3%). Addition of any pulmonary shunt grade on TTCE to the current criteria changed the number of positive criteria in 92 persons (18.9%), which increased the sensitivity from 88% (95% CI 0.84-0.91) to 94% (95% CI 0.91-0.96), but decreased the specificity from 74% (95% CI 0.66-0.80) to 70% (95% CI 0.62-0.77). The contribution of only pulmonary shunt grades ≥ 2 on TTCE to the current criteria altered the number of positive criteria in 30 persons (6.2%) and resulted in a sensitivity of 90% (95% CI 0.86-0.93), with a specificity of 74% (95% CI 0.66-0.80). Conclusion: The addition of only pulmonary shunt grades ≥2 on TTCE increases the sensitivity without affecting specificity of the current clinical Curacao criteria in diagnosing HHT.