Grade of Pulmonary Right-to-Left Shunt on Contrast Echocardiography and Cerebral Complications: A Striking Association

doi:10.1378/chest.12-1599

Chest

Volume 144, Issue 2, August 2013, Pages 542-548

https://doi.org/10.1378/chest.12-1599 Get rights and content

Background

A pulmonary right-to-left shunt (RLS) carries the risk of cerebral paradoxical embolization and severe neurologic complications. Recognizing patients at risk is important to facilitate appropriate management strategies, but a direct relation between pulmonary shunt size and risk of complications remains controversial. This study evaluated the potential relation between pulmonary shunt grade on transthoracic contrast echocardiography (TTCE) and prevalence of cerebral manifestations in patients screened for hereditary hemorrhagic telangiectasia (HHT).

Methods

We conducted a two-center, cross-sectional study of all consecutive patients screened for HHT between 2004 and 2011. Pulmonary shunt grading on TTCE (grade 0, no microbubbles; grade 1, < 30 microbubbles; grade 2, 30-100 microbubbles; grade 3, > 100 microbubbles) was performed according to contrast opacification of the left ventricle. Cerebral complications were defined as ischemic stroke, transient ischemic attack, or brain abscess diagnosed by a neurologist and confirmed by appropriate imaging techniques.

Results

A pulmonary RLS was present in 530 out of 1,038 patients (51.1%; mean age, 44.3 ± 15.6 years; 58.6% women). The presence of a cerebral manifestation (n = 51) differed significantly among pulmonary shunt grades on TTCE: 1.4%, 0.4%, 6.5%, and 20.9% for grades 0, 1, 2 and 3, respectively. A pulmonary shunt grade 1 was not associated with an increased prevalence of cerebral manifestations (OR, 0.44; 95% CI, 0.05-4.13; P = .47), whereas pulmonary shunt grade 2 (OR, 4.78; 95% CI, 1.14-20.0; P = .03) and grade 3 (OR, 10.4; 95% CI, 2.4-45.3; P = .002) were both independent predictors for the prevalence of a cerebral ischemic event or brain abscess.

Conclusions

The pulmonary RLS grade on TTCE is strongly associated with the prevalence of cerebral complications in patients screened for HHT.

Section snippets

Study Population

From May 2004 to March 2011, 1,129 people were screened for HHT at two specialized clinics: the St. Antonius Hospital in Nieuwegein, The Netherlands, and the Maggiore Hospital in Crema, Italy. People > 15 years of age were screened as family members of index patients with HHT or with clinical symptoms suggesting HHT. All patients underwent a complete history and physical examination by a physician with dedicated expertise in HHT. The clinical diagnosis of HHT was established according to the

Study Population

A diagnostic TTCE was available in 1,088 of 1,129 screened patients (96.4%). An indeterminate RLS was found in 50 of 1,088 patients (4.6%), who were excluded to ensure that only purely pulmonary shunts were included in our analysis. In these 50 patients, only one TIA was documented (2%), and their exclusion probably did not influence our results. The remaining 1,038 patients were included for further analysis. Genetic testing was performed in 853 of the 1,038 screened patients (82.2%). HHT was

Discussion

To our knowledge, this is the first large cross-sectional study to evaluate the potential relation between pulmonary shunt size on TTCE and prevalence of cerebral complications. Our study demonstrates that the occurrence of a cerebral ischemic event or brain abscess is strongly associated with the pulmonary shunt grade on TTCE, which has not been established before.

A pulmonary RLS carries the risk of cerebral paradoxical embolization by bypassing the pulmonary capillary filtering system,

Conclusions

The pulmonary RLS grade on TTCE is strongly associated with the prevalence of a cerebral ischemic event or brain abscess in patients screened for HHT. Patients with a pulmonary shunt grade 1 on TTCE do not appear to have an increased risk of cerebral complications.

Acknowledgments

Author contributions: Drs Velthuis and Post are guarantors of the manuscript.

Dr Velthuis: contributed to the concept and design of the study, data acquisition, analysis and interpretation of data, and drafting of the manuscript.

Dr Buscarini: contributed to the concept and design of the study, data acquisition, analysis and interpretation of data, and revision of the manuscript for important intellectual content.

Dr van Gent: contributed to the concept and design of the study, data acquisition,

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Pulmonary arteriovenous malformations (PAVMs) are direct connections between the pulmonary artery and the pulmonary vein, mostly associated with hereditary hemorrhagic telangiectasia (HHT). PAVMs can lead to severe neurologic complications such as stroke and brain abscess. The risk of complications decreases after embolization. Therefore, screening for PAVMs using transthoracic contrast echocardiography (TTCE) is recommended, including a rescreening interval of 5 years.
Is extension of the interval for rescreening patients without a pulmonary right-to-left shunt (RLS) of up to 10 years appropriate?
Adult patients with HHT with 5- or 10-year follow-up TTCE, or both, were included. Patients who underwent PAVM embolization in the past or at baseline were excluded. The RLS grades and presence of a treatable PAVM were compared with baseline.
In total, 387 patients (median age, 45 years [interquartile range, 33-54 years]; 56% women) involving 5- and 10-year follow-up data in 363 and 166 patients, respectively, were included. None of the patients (n = 148) without a pulmonary RLS at baseline demonstrated a treatable PAVM after 5 and 10 years. Of the patients with a pulmonary RLS at baseline, 20 patients (9%) and three patients (3%) demonstrated a treatable PAVM at the 5- and 10-year follow-up, respectively. In most patients, the RLS grade remained stable over time.
On the basis of the results of this retrospective study, we believe that the rescreening interval for patients with HHT without a pulmonary RLS at initial screening may be extended to 10 years. Those with a pulmonary RLS should be rescreened every 5 years because treatable PAVMs can evolve.
Pulmonary Arteriovenous Malformations
2021, Encyclopedia of Respiratory Medicine, Second Edition
Pulmonary arteriovenous malformations (PAVMs) are abnormal vascular structures that result in a right-to-left shunt. While usually silent, patients are at risk of ischemic stroke, brain abscess and other complications due to paradoxical emboli; hypoxemia; and rarely, bleeding from PAVMs, particularly if the individual is pregnant. PAVMs are treated by embolization, and occasionally surgery. All patients require prophylactic antibiotics for dental and surgical procedures, written advice on pregnancy management, and evaluation to determine if there is an underlying cause (usually, hereditary hemorrhagic telangiectasia, HHT). A 2017 Clinical Statement on pulmonary arteriovenous malformations is available from the British Thoracic Society.
Heritable pulmonary arterial hypertension complicated by multiple pulmonary arteriovenous malformations
2021, Respiratory Medicine Case Reports
Citation Excerpt :
Patients with concomitant PAH and PAVM have complicated hemodynamics, and treatment needs to be planned accordingly. PAVMs exhibit low vascular resistance and high cardiac output [20,21]. High cardiac output and shunt-related hypoxemia can increase pulmonary artery pressure.
Heritable pulmonary arterial hypertension (HPAH) is a type of familial pulmonary arterial hypertension, while pulmonary arteriovenous malformations (PAVMs) are abnormal communications between pulmonary arteries and veins that occur frequently in patients with hereditary hemorrhagic telangiectasia (HHT). A 21-year-old woman on continuing medication for HPAH was hospitalized. She had been diagnosed with HPAH at age 4 years and had been receiving epoprostenol infusion from age of 9 years. Although lung perfusion scintigraphy showed a shunt fraction of 18.9% at age of 19 years, the cause of the shunt was unclear. At the time of the present hospitalization, enhanced computed tomography (CT) of the chest and four-dimensional reconstructed images revealed multiple abnormal communications between the peripheral pulmonary arteries and veins. Furthermore, right heart catheterization revealed an elevated mean pulmonary arterial pressure. Wedged angiography of the pulmonary artery of the right lower lobe revealed several PAVMs. Multiple PAVMs and suspected HHT with HPAH was diagnosed. The possibility of PAVMs should be considered even in patients with HPAH. Moreover, evaluation of the shunt fraction by lung perfusion scintigraphy and morphological examination of PAVM by contrast-enhanced CT may facilitate PAVM detection in patients with HPAH
Postembolotherapy Pulmonary Arteriovenous Malformation Follow-Up: A Role for Graded Transthoracic Contrast Echocardiography Prior to High-Resolution Chest CT Scan
2020, Chest
High-resolution chest CT (HRCT) scan is recommended after pulmonary arteriovenous malformation (PAVM) embolotherapy to assess for PAVM persistence and untreated PAVM growth. Graded transthoracic contrast echocardiography (TTCE) predicts the need for embolotherapy in PAVM screening. This study sought to determine whether postembolotherapy graded TTCE can similarly predict the need for repeat embolotherapy.
Thirty-two patients (8 men and 24 women; mean age, 51.1 ± 12.6 years) with prior PAVM embolotherapy and follow-up HRCT scan were prospectively enrolled. Patients underwent graded TTCE using a validated three-point quantitative grading scale. TTCE grade and HRCT findings were compared.
Median time between most recent HRCT scan and TTCE was 7 days (interquartile range, 0-272 days). Thirty patients (94%) had no PAVMs requiring repeat embolotherapy on HRCT scan. Two patients (6%) had PAVMs requiring repeat embolotherapy (feeding artery [FA] ≥ 3 mm), one with untreated PAVM growth and one with treated PAVM persistence. TTCE was positive in 88% of patients (n = 28). All patients (n = 4, 12%) with negative TTCE had no visible PAVMs on HRCT scan. Nine patients (32%) had grade 1 shunt, 10 (35%) had grade 2 shunt, and nine (32%) had grade 3 shunt. No patients with grade 1 shunt had PAVMs amenable to repeat embolotherapy on HRCT scan. All patients (n = 2) with PAVMs requiring repeat embolotherapy (FA ≥ 3 mm) had grade 3 shunt. TTCE grade was significantly associated with PAVM FA diameter (P < .001).
Postembolotherapy graded TTCE can predict the need for repeat embolotherapy on HRCT scan. Patients with negative TTCE and grade 1 shunt may not require HRCT follow-up and can potentially be followed with serial graded TTCE.
ClinicalTrials.gov; No.: NCT02936349; URL: www.clinicaltrials.gov.
Medical management of haemorrhagic hereditary telangiectasia in adult patients
2019, Medicina Clinica
La telangiectasia hemorrágica hereditaria es una enfermedad minoritaria con herencia autosómica dominante que ocasiona un crecimiento vascular anómalo de forma sistémica. El abordaje y seguimiento de estos pacientes debería hacerse desde unidades multidisciplinares. Su diagnóstico es clínico según los criterios de Curaçao. Las telangiectasias en la mucosa nasal ocasionan epistaxis recurrentes, principal síntoma de esta enfermedad y de difícil control. Los 3 patrones de afectación hepática, comunicaciones entre arteria hepática y venas suprahepáticas, entre arteria hepática y vena porta o entre vena porta y venas suprahepáticas pueden causar insuficiencia cardiaca por hiperaflujo, hipertensión portal o encefalopatía hepática, respectivamente. Estos tipos de afectación vascular se pueden establecer mediante tomografía computarizada. Se debe realizar un cribado de fístulas arteriovenosas pulmonares a todos los pacientes mediante una ecocardiografía con contraste. Nuestro principal objetivo es realizar una revisión del manejo de las epistaxis, afectación hepática y pulmonar del paciente adulto con telangiectasia hemorrágica hereditaria.
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant inherited Rare Disease that causes a systemic anomalous vascular overgrowth. The approach and follow-up of these patients should be from multidisciplinary units. Its diagnosis is carried out according to Curaçao clinical Criteria. Telangiectasia in the nasal mucosa cause recurrent epistaxis, the main symptom of HHT and difficult to control. The three types of hepatic shunting, hepatic artery to hepatic vein, hepatic artery to portal vein or to portal vein to hepatic vein, can cause high-output heart failure, portal hypertension or porto-systemic encephalopathy, respectively. These types of vascular involvement can be established using computerised tomography. Pulmonary arteriovenous fistula should be screened for all HHT patients by contrast echocardiography. The main objective is to review the management of epistaxis, liver and lung involvement of the adult patient with HHT.
Ischemic Stroke Secondary to Paradoxical Embolism Through a Pulmonary Arteriovenous Malformation: Case Report and Review of the Literature
2018, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
In patients with treated PAVMs, TTCE can be falsely positive and should no longer be used for follow up screening, and current guidelines recommend repeating pulmonary CT scans 6-12 months after embolization and then every 3 years thereafter.5 For patients with grade 1 or 2 shunts and no treatable PAVM on CT, transthoracic echocardiogram every 5 years may be advised.8 For patients who have already suffered from ischemic stroke due to PAVM and do not undergo embolization, long-term anti-coagulation may be considered for secondary prevention, although supportive evidence is lacking.14
Paradoxical embolism due to isolated pulmonary arteriovenous malformation (AVM) is an uncommon cause of ischemic stroke, with the majority occurring in patients who have not yet been diagnosed with their malformation. We report a 32-year-old man who presented with an abrupt onset of right facial weakness and expressive aphasia. Brain magnetic resonance imaging revealed an acute infarct in the left middle cerebral artery territory and chronic infarcts in the bilateral cerebellar hemispheres. A cardioembolic mechanism was initially considered in the setting of perimyocarditis diagnosed a few months earlier. Transthoracic and transesophageal echocardiograms revealed high volume right to left shunting, but no septal defects. A pulmonary AVM was confirmed with computed tomography angiography and fistualization was successfully treated with embolization. This report highlights a case of undiagnosed pulmonary AVM leading to recurrent paradoxical emboli to the brain. We review the epidemiology, pathophysiology, and management of pulmonary AVMs in relation to stroke risk.

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Funding/Support: The authors have reported to CHEST that no funding was received for this study.

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Chest

Original ResearchPulmonary Vascular DiseaseGrade of Pulmonary Right-to-Left Shunt on Contrast Echocardiography and Cerebral Complications: A Striking Association

Background

Methods

Results

Conclusions

Section snippets

Study Population

Study Population

Discussion

Conclusions

Acknowledgments

J Vasc Interv Radiol

Am J Hum Genet

Lancet

Chest

Chest

Chest

Chest

J Am Coll Cardiol

Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century

Postgrad Med J

Pulmonary arteriovenous malformations. A state of the art review

Am J Respir Crit Care Med

Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms

Thorax

Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)

Am J Med Genet

Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1

Nat Genet

Original Research
Pulmonary Vascular Disease
Grade of Pulmonary Right-to-Left Shunt on Contrast Echocardiography and Cerebral Complications: A Striking Association