Chest
Volume 138, Issue 4, October 2010, Pages 833-839
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Original Research
Pulmonary Circulation
Real Prevalence of Pulmonary Right-to-Left Shunt According to Genotype in Patients With Hereditary Hemorrhagic Telangiectasia: A Transthoracic Contrast Echocardiography Study

https://doi.org/10.1378/chest.09-1849Get rights and content

Background

Transthoracic contrast echocardiography (TTCE) can detect pulmonary right-to-left shunting (RLS) and is used to screen for pulmonary arteriovenous malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia (HHT). We studied the prevalence and size of pulmonary RLS in HHT type 1, HHT type 2, and HHT-negative controls, and its positive predictive value (PPV) and negative predictive value (NPV) for PAVMs that can be treated by embolotherapy.

Methods

In 343 consecutive persons referred for possible HHT as first-degree family members of index patients a TTCE and chest CT scan were performed. All persons were offered genetic analysis.

Results

An HHT-causing mutation was confirmed in 92 (mean age 41 ± 15 y; 59% female) HHT1 relatives and in 97 (mean age 47 ± 14 y; 52% female) HHT2 relatives. TTCE showed a pulmonary RLS in 78 (85%) HHT1- and 34 (35%) HHT2-related mutation carriers, respectively (P < .0001). In HHT1 relatives, 29 of 53 (55%) PAVMs and in HHT2 relatives three of 17 (18%) PAVMS were treated, resulting in a PPV of TTCE for treatable PAVMs of 36.3% and 8.3%, respectively. The accompanying NPV was 100%. A minimal, moderate, or large shunt was present in 12 (13%), 24 (26%), and 42 (46%) HHT1-related, and in 20 (21%), 6 (6%), and 8 (8%) HHT2-related mutation carriers, respectively (P for trend < .0001). A large shunt predicted treatable PAVMs in 55.8% of HHT1 relatives and 37.5% of HHT2 relatives. TTCE was positive in four (6%) of 63 persons without HHT.

Conclusions

A pulmonary shunt on TTCE is more prevalent and larger in HHT1- compared with HHT2-related mutation carriers. Shunt grading is helpful to predict treatable PAVMs, particularly in the HHT2 group. TTCE is also positive in a small fraction of persons without HHT.

Section snippets

Study Population

In the period from May 2004 through December 2008, 466 consecutive persons were screened for possible HHT in the St. Antonius Hospital. In order to guarantee a uniform group of screened persons we only included first-degree relatives of patients with proven HHT (index cases). We excluded 20 persons because they were referred for suggestive findings for HHT and not as family members of known patients with HHT, and 78 persons who were family members but not in the first degree. In 20 persons no

Results

Three hundred forty-three persons (mean age 42 ± 15 y; 58% women) were screened for possible HHT as first-degree family members of index cases (clinically or genetically confirmed HHT) and had an appropriate TTCE. All persons underwent TTCE studies, including shunt grade measurement. In 335 of 343 (98%) persons a chest HRCT scan was performed. In 307 (90%) persons the HHT subtype of the index patient was known. One hundred forty-two screened persons were first-degree family members of index

Discussion

We report for the first time the prevalence of pulmonary shunting on contrast echocardiography in a large homogeneous group of first-degree HHT relatives with an identified HHT-causing mutation. We found a pulmonary RLS in 85% of HHT1- and 35% of HHT2-related mutation carriers, respectively. Furthermore, pulmonary shunts are larger in HHT1 compared with HHT2 relatives. TTCE appears to be also positive in 6% of persons without an HHT-causing mutation. Only a small fraction of PAVMs in the HHT2

Acknowledgments

Author contributions: Dr van Gent: contributed as the primary author of the manuscript and performed contrast echocardiograms.

Dr Post: contributed to revising the manuscript and performing contrast echocardiograms.

Dr Snijder: contributed to the clinical care of patients with HHT and revising the manuscript.

Dr Westermann: contributed to providing clinical and genetic data on all patients with HHT and revising the manuscript.

Dr Plokker: contributed to revising the manuscript.

Dr Mager: contributed

References (33)

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