Presence Of Pulmonary Arteriovenous Malformations Research Articles

High risk of ischaemic stroke amongst patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a genetic disease with fragile blood vessels and vascular malformations, potentially causing neurological manifestations, including stroke and cerebral abscesses. The study aimed to investigate neurological manifestations in the Danish HHT database, focusing on pulmonary arteriovenous malformations (PAVMs) as a risk factor for cerebral events. Retrospective analysis of the Danish HHT database was conducted, cross-referencing neurological outcomes with the Danish Apoplexy Register for accuracy. Patients were stratified by HHT type. Primary outcomes included ischaemic stroke, transient ischaemic attack and cerebral haemorrhage. Secondary outcomes comprised age, age at HHT diagnosis, age at cerebral ischaemic event, and PAVM and cerebral arteriovenous malformation status. Six hundred and sixty-four HHT patients were included. PAVM was diagnosed in 54% of patients, with higher prevalence in HHT type 1 (70%) compared to HHT type 2 (34%) and juvenile polyposis HHT (66%). Ischaemic stroke or transient ischaemic attack occurred in 12.5%, with a higher risk associated with macroscopic PAVM. Logistic regression showed a nearly 10 times increased risk of ischaemic stroke with macroscopic PAVM. Cerebral abscesses occurred in 3.2% of patients, all with macroscopic PAVM. Incomplete PAVM closure increased cerebral abscess risk. This study provides valuable insights into the prevalence of neurological manifestations and vascular events in HHT patients. The presence of PAVM was associated with an increased risk of ischaemic stroke, highlighting the importance of early screening and intervention. The findings emphasize the need for comprehensive management strategies targeting both vascular and neurological complications in HHT patients, especially regarding secondary stroke prevention.

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia

BackgroundApproximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors. We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up.Methods1637 HHT patients (342 with brain VMs) were recruited from 14 HHT centres of the Brain Vascular Malformation Consortium since 2010 and followed prospectively (mean = 3.4 years). We tested whether the presence of brain VM, other HHT organ involvement, and HHT mutation genotype were associated with worse mRS scores at baseline and during follow-up, using linear mixed models, adjusting for age, sex, and year of visit.ResultsPresence of brain VMs was not associated with worse mRS score at baseline and there was no significant worsening of mRS with prospective follow-up in these patients; 92% had baseline mRS of 0–2. HHT-related gastrointestinal (GI) bleeding was associated with worse mRS scores at baseline (0.37, 95% CI 0.26–0.47, p < 0.001), as were history of anemia (0.35, 95% CI 0.27–0.43, p < 0.001) and liver VMs (0.19, 95% CI 0.09–0.30, p < 0.001). Presence of pulmonary arteriovenous malformations (AVMs) was not associated with worse mRS scores at baseline. mRS score was not associated with either HHT genotype (Endoglin vs ACVRL1). Only GI bleeding was associated with a significantly worsening mRS during prospective follow-up (0.64, 95% CI 0.21–1.08, p = 0.004).ConclusionMost HHT-brain VM patients had good functional capacity (mRS scores 0–2) at baseline that did not change significantly over 3.4 mean years of follow-up, suggesting that mRS may not be useful for predicting or measuring outcomes in these patients. However, HHT patients with GI bleeding, anemia history or liver VMs had worse mRS scores, suggesting significant impact of these manifestations on functional capacity. Our study demonstrates the insensitivity of the mRS as an outcomes measure in HHT brain VM patients and reinforces the continued need to develop outcomes measures, and their predictors, in this group.

Genotype-Phenotype Correlations in Children with HHT.

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype–phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype–phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0–18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presence of a combined phenotype—defined as both pulmonary AVMs and brain VMs—was also associated with ENG mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with SMAD4 genotype (p < 0.001). We conclude that genotype–phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with ENG mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.

Pulmonary Arteriovenous Malformations Are Associated with Silent Brain Infarcts in Hereditary Hemorrhagic Telangiectasia Patients

Background and Purpose: There is a high prevalence of right-to-left shunting pulmonary arteriovenous malformations (PAVMs), which are stroke risk factors, in hereditary hemorrhagic telangiectasia (HHT) patients. While the prevalence of ischemic complications in HHT patients is known, the prevalence of silent brain infarcts (SBI) remains unknown. The purpose of this study was to determine the prevalence and risk factors for SBI in HHT patients. Materials and Methods: Our institutional HHT database was queried to identify HHT patients who received a baseline screening brain MRI from January 2000 to February 2017. This study group was further refined by excluding patients who had a history of clinical ischemic disease as defined by having a stroke or transient ischemic attack (TIA). Brain MRIs were reviewed for SBI. Baseline data on demographics, Curacao criteria, presence of PAVMs, and cardiovascular risk factors were collected. The primary outcome was SBI prevalence. We also examined which baseline patient characteristics were associated with SBI through univariate chi-square and Student t tests and multivariate logistic regression analyses. Results: Three hundred fifty three consecutive HHT patients from January 2000 to February 2017 with a screening brain MRI and no prior history of stroke/TIA were included. SBI prevalence was 9.9% (35/353). SBI patients were more likely to have PAVMs than non-SBI patients (80.6 vs. 53.1%, p = 0.005). The median age was 66 in the SBI group and 52 in the non-SBI group (p = 0.006). SBI patients had higher prevalence of hyperlipidemia (34.3 vs. 9.8%, p < 0.0001), hypertension (48.6 vs. 22.0%, p = 0.005), and tobacco use (25.7 vs. 9.8%, p = 0.005). No patients under 30 had SBI. In the 60-69 age group, the prevalence of SBI was 18.8% with rates of 28.6% in the PAVM group and 10.5% in the non-PAVM group. For patients ≥70 years old, the prevalence of SBI was 21.4% overall and 27.6% in the PAVM group and 10.5% in the non-PAVM group. On multivariate analysis, PAVMs (OR 3.62, 95% CI 1.46-10.40) and increasing age (OR 1.04, 95% CI 1.01-1.07) were independently associated with SBI. Conclusions: Overall, a similar 10% SBI prevalence in the HHT cohort was noted as compared to the general population. However, the prevalence of SBI was higher in HHT patients with PAVMs when compared to that of the general population, particularly among patients than 60 years old. These findings highlight the need to accurately identify, and when appropriate, treat PAVMs in the HHT population especially given the multiple significant, clinical consequences of SBI.

Is the Hepatic Factor a miRNA that Maintains the Integrity of Pulmonary Microvasculature by Inhibiting the Vascular Endothelial Growth Factor?

Background:The “hepatic factor,” a molecule or group of molecules present in the hepatic venous blood, essential for the prevention of the development of pulmonary arteriovenous malfor-mations (PAVMs) and right-to-left shunting has been a conceptual enigma in the understanding of many related conditions.Methods:Patients with various forms of liver diseases including acute hepatic failure, and others with normal hepatic function like hereditary hemorrhagic telangiectasia (HHT), inflammatory and parasitic disorders, cardiogenic hepatopulmonary syndrome (cHPS) and skin disorders like Dyskeratosis con-genita are all known to cause PAVMs. Over a period of the last two decades our understanding of the pathogenesis of PAVMs has changed, but the mechanisms are still not clearly understood. The pres-ence of PAVMs once considered a contraindication for liver transplantation is now a cure for PAVMs in patients with HPS.Results:In this article the molecular mechanisms and the underlying pathogenesis of PAVMs are dis-cussed and the role of microRNA (miRNA) in its pathogenesis is favorably argued. Identifying and preventing or treating the underlying mechanisms will significantly influence the management of a large group of patients who at present cannot be effectively treated with a very poor prognosis. Progressive polycythemia, desaturation, stroke, and infection are serious complications of PAVMs.Conclusion:The clinical data and current understanding leads to the possible role of miRNA, which inhibits Vascular Endothelial Growth Factor (VEGF) synthesis as a pathogenic mechanism for the development of PAVMs.

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14.

HHT shows clinical variability within and between families. Organ site and prevalence of arteriovenous malformations (AVMs) depend on the HHT causative gene and on environmental and genetic modifiers. We tested whether variation in the functional ENG allele, inherited from the unaffected parent, alters risk for pulmonary AVM in HHT1 mutation carriers who are ENG haploinsufficient. Genetic association was found between rs10987746 of the wild type ENG allele and presence of pulmonary AVM [relative risk = 1.3 (1.0018–1.7424)]. The rs10987746-C at-risk allele associated with lower expression of ENG RNA in a panel of human lymphoblastoid cell lines (P = 0.004). Moreover, in angiogenically active human lung adenocarcinoma tissue, but not in uninvolved quiescent lung, rs10987746-C was correlated with expression of PTPN14 (P = 0.004), another modifier of HHT. Quantitative TAQMAN expression analysis in a panel of normal lung tissues from 69 genetically heterogeneous inter-specific backcross mice, demonstrated strong correlation between expression levels of Eng, Acvrl1, and Ptpn14 (r2 = 0.75–0.9, P < 1 × 10−12), further suggesting a direct or indirect interaction between these three genes in lung in vivo. Our data indicate that genetic variation within the single functional ENG gene influences quantitative and/or qualitative differences in ENG expression that contribute to risk of pulmonary AVM in HHT1, and provide correlative support for PTPN14 involvement in endoglin/ALK1 lung biology in vivo. PTPN14 has been shown to be a negative regulator of Yap/Taz signaling, which is implicated in mechanotransduction, providing a possible molecular link between endoglin/ALK1 signaling and mechanical stress. EMILIN2, which showed suggestive genetic association with pulmonary AVM, is also reported to interact with Taz in angiogenesis. Elucidation of the molecular mechanisms regulating these interactions in endothelial cells may ultimately provide more rational choices for HHT therapy.

Impact of Pulmonary Arteriovenous Malformations on Respiratory–Related Quality of Life in Patients with Hereditary Haemorrhagic Telangiectasia

Fifteen to fifty percent of patients with hereditary haemorrhagic telangiectasia have pulmonary arteriovenous malformations. The objective of this study was to measure the effect of the presence of pulmonary arteriovenous malformations and of their embolisation on respiratory-related quality of life (QoL). We prospectively recruited patients with a diagnosis of hereditary haemorrhagic telangiectasia based on the Curaçao criteria and/or the identification of a pathogenic mutation. Respiratory-related quality of life was measured using the Saint George’s Respiratory Questionnaire (SGRQ). Patients who underwent embolisation of pulmonary arteriovenous malformations completed the questionnaire before and 6–12 mo after the procedure. The 56 participants were divided into three groups: no pulmonary arteriovenous malformation (group A, n = 10), small pulmonary arteriovenous malformations not accessible to embolotherapy (group B, n = 19), and large pulmonary arteriovenous malformations accessible to embolotherapy (group C, n = 27). The SGRQ score was significantly higher in group C compared to the other groups, indicating a worse respiratory-specific QoL. There was no significant difference between groups A and B. Among the 17 patients who underwent an embolisation, the SGRQ score decreased significantly after the procedure, to a value similar to that in patients without pulmonary arteriovenous malformation. Our results indicate that the presence of large but not small pulmonary arteriovenous malformations negatively affects the respiratory-related quality of life and that embolisation of pulmonary arteriovenous malformations normalizes the respiratory-related quality of life.

Role of Transthoracic Contrast Echocardiography in the Clinical Diagnosis of Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) can be diagnosed according to the four clinical Curaçao criteria, including the presence of pulmonary arteriovenous malformations (PAVMs). In the past few years, transthoracic contrast echocardiography (TTCE) replaced chest high-resolution CT (HRCT) imaging for the screening of PAVMs. The objective of this study was to determine whether the presence of any pulmonary shunt on TTCE can be accepted as a new clinical Curaçao criterion in diagnosing HHT. Between 2004 and 2012, we included 487 first-degree relatives of known HHT-causing mutation carriers who underwent both TTCE and chest HRCT imaging to screen for PAVMs. A quantitative three-point grading scale was used to differentiate among minimal, moderate, or extensive pulmonary shunt on TTCE (grade 1-3). Genetic testing was performed in all people and considered the gold standard for the diagnosis of HHT. Chest HRCT imaging demonstrated PAVMs in 114 of 218 patients (52.3%) with a pulmonary shunt on TTCE. The addition of any pulmonary shunt on TTCE to the current clinical Curaçao criteria increased the number of positive criteria in 92 of 487 individuals (18.9%), which increased the sensitivity in diagnosing HHT from 88% to 94% at the expense of a decreased specificity from 74% to 70%. Accepting only pulmonary shunt grades ≥ 2 on TTCE as a diagnostic criterion for HHT enhanced the number of positive criteria in 30 (6.2%) individuals, which led to an increased sensitivity of 90% with no decrease in specificity (74%). The addition of only pulmonary shunt grades ≥ 2 on TTCE to the current clinical Curaçao criteria increases its sensitivity without affecting specificity in the diagnosis of HHT.

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

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.

Venovenous malformation: a common finding after Kawashima operation

It has been reported that systemic venovenous malformation (VVM) can develop in patients with interrupted inferior vena cava (IVC) and univentricular type of congenital heart disease who undergo superior vena cava to pulmonary artery connection (Kawashima operation). These malformations can lead to profound systemic desaturation postoperatively. However, there have been few reports that characterise the prevalence, anatomic details and clinical correlations of these systemic VVM arising after Kawashima operation. In this study, we describe our experience with VVM after Kawashima operation, and discuss issues regarding their evaluation and postoperative management. Eight patients with median age 19 months (range: 5-238) who underwent Kawashima operation were subjected to postoperative angiography, prospectively. Sites of VVM origin and entry, as well as their course, were documented. The presence of pulmonary arteriovenous malformations (AVMs) was also documented. At median follow-up of 31 months (range: 16-72 months), a total of 14 VVM were found in different supra- and infra-diaphragmatic sites in six patients (75%); four of them had concomitant pulmonary AVM while the remaining two patients had only pulmonary AVM. Our findings suggest that systemic VVM can occur frequently after Kawashima operation and can produce significant desaturation postoperatively, and hence we support hepatic incorporation. Performing detailed angiographic studies of the supra- and infra-diaphragmatic systemic veins in routine assessment of patients before Kawashima operation is, probably, warranted.

Systemic arteriovenous fistulae for end-stage cyanosis after cavopulmonary connection: A useful bridge to transplantation

Intractable cyanosis after partial or complete cavopulmonary connection may rarely be managed by creating a systemic arteriovenous fistula. We investigated the long-term performance of arteriovenous fistulae. All 21 patients who received an arteriovenous fistula at The Hospital for Sick Children since the 1950s were investigated using parametric competing risk techniques. Primary arteriovenous fistula indication was (1) suboptimal pulmonary blood flow (N = 15) or (2) pulmonary shunting via pulmonary arteriovenous malformations (N = 6). Arteriovenous fistula longevity was determined by time to "occlusion" (absence of arteriovenous fistula flow via surgical ligation or spontaneous occlusion). All 21 patients had previously undergone second-stage palliation (Glenn shunt = 13; bidirectional shunt = 9). Five patients had undergone Fontan completion. Death in the presence of a functioning arteriovenous fistula occurred in 5 patients. Patients with bidirectional shunts had a significantly higher risk of death with a functioning arteriovenous fistula in situ (P = .04). High hemoglobin concentrations were associated with best outcome, and levels less than 170 g/L were associated with a high risk of death despite a functioning arteriovenous fistula (P < .01). Arteriovenous fistula occlusion occurred in 10 patients. Earlier occlusion was associated with previous Fontan completion (P = .02) and pulmonary arteriovenous malformations (P = .03). Surgical ligation during cardiac transplantation was the cause of occlusion in 7 patients. In these 7 patients, the arteriovenous fistula functioned for a median of 4.8 years. After transplantation, survival was 67% + or - 19% at 5 years. Overall survival was 73% + or - 10% 15 years after receiving an arteriovenous fistula (longest survival, 27.3 years). In patients with adequate hematocrit, arteriovenous fistula offers an effective bridge to transplantation when a high-risk Fontan procedure is deferred. Performance is best after unidirectional cavopulmonary connection and worse in the presence of pulmonary arteriovenous malformations. Survival is 75% at 15 years, despite being considered end stage.

Mutation study of Spanish patients with Hereditary Hemorrhagic Telangiectasia

BackgroundHereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes.MethodsHere, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT.ResultsWe identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM) in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model.ConclusionOverall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1) in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy), but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.

MR Angiography for Detection of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia

The purpose of our study was to evaluate contrast-enhanced MR angiography (CE-MRA) as a screening procedure for the detection of pulmonary arteriovenous malformations (AVMs) in patients with hereditary hemorrhagic telangiectasia (HTT). Two hundred three consecutive subjects (patients with diagnosed HHT or first-degree relatives; 87 males, 116 females; 6-83 years old) underwent pulmonary CE-MRA with 0.1 mmol/kg of gadobenate dimeglumine. The presence of pulmonary AVM was scored as 0 (none present), 1 (definitely present), or 2 (uncertain) and was evaluated by patient sex and pulmonary AVM size (< 5, 5-10, 11-15, 16-20, > 20 mm). Patients scored as 1 or 2 with at least one pulmonary AVM of > or = 5 mm underwent conventional pulmonary angiography for possible embolization. Pulmonary AVM detection on CE-MRA and pulmonary angiography was compared using paired Student's t tests. The presence of pulmonary AVM was considered definite in 56 of 203 (27.6%) patients and uncertain in one of 203 patients on CE-MRA. Of 156 pulmonary AVMs detected on CE-MRA, 124 (49 in 27 males, 75 in 30 females) were detected on first screening CE-MRA and 32 on follow-up CE-MRA. Pulmonary AVMs on CE-MRA were solitary in 25 patients, multiple in 31 patients, and predominantly small (< 5 mm, n = 32; 5-10 mm, n = 45). Significantly (p < 0.0001) fewer pulmonary AVMs were detected on pulmonary angiography (76/96 [79.2%] evaluable pulmonary AVMs in 40 patients before first pulmonary angiography; 92/119 [77.3%] pulmonary AVMs overall). Three-dimensional maximum-intensity-projection reconstructions permitted improved pulmonary AVM visualization and embolization planning of complex pulmonary AVMs. CE-MRA is suitable for screening patients with HHT. It permits accurate detection and staging of pulmonary AVMs, appropriate differentiation of lesions requiring embolization and accurate orientation, and visualization and planning of embolization therapy.

Early-life pulmonary arterial hypertension with subsequent development of diffuse pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia type 1

The case history is presented of a male infant who was thought to have idiopathic pulmonary arterial hypertension (PAH) at 3 months of age. Subsequently the PAH decreased unexpectedly and...

Subcutaneous temporal abscess as a clinical manifestation of pulmonary arteriovenous malformations in a patient with hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease)

This is the report of a rare case of a temporal abscess that developed in the presence of pulmonary arteriovenous malformations in a patient with hereditary haemorrhagic telangiectasia (HHT). Little has been described about abscesses occurring in soft tissues in patients with HHT in previous reports. In the case of a subcutaneous abscess of unknown primary in the head and neck region in patients with HHT, the clinician needs to consider septic microemboli due to pulmonary arteriovenous malformations as a possible cause. The classic dermal manifestation of HHT should be enlarged to include subcutaneous abscess secondary to metastatic septic microembolism.

Hemorrhagic Hereditary Telangiectasia (Rendu-Osler Disease) and Infectious Diseases: An Underestimated Association

Among 353 patients with hereditary hemorrhagic telangiectasia retrospectively analyzed during the period 1985-2005, we identified 67 cases of severe infection that affected 48 patients (13.6%). Extracerebral infections accounted for 67% of all infections, and most involved Staphylococcus aureus and were associated with prolonged epistaxis. Cerebral infections accounted for 33% of all infections, were mainly due to multiple and anaerobic bacteria, and were associated with the presence of pulmonary arteriovenous malformations and a short duration of epistaxis.

Pulmonary Arteriovenous Malformations: Screening Procedures and Pulmonary Angiography in Patients With Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited disease with a high prevalence of pulmonary arteriovenous malformations (PAVMs). The first symptom of HHT may be stroke or fatal hemoptysis associated with the presence of PAVM. To evaluate different screening methods applied for the identification of PAVMs. Odense University Hospital. HHT patients with positive findings on contrast echocardiography (CE) who participated in a screening investigation and underwent pulmonary angiography (PA). Different screening methods were evaluated against the results of PA. In a group of patients with positive findings on CE, we compared results of PA with the following: severity of dyspnea; results of pulse oximetry arterial oxygen saturation (SaO2) supine and upright; supine PaO2 in room air and while breathing 100% oxygen; size of arteriovenous shunt in supine position; chest radiograph; and intensity of contrast at CE. PA was performed in 25 HHT patients with positive findings on CE, 15 of whom had PAVM. Embolization therapy was recommended in 12 patients, and 3 patients had small PAVMs not accessible for therapy. In 10 patients, PAVM could not be demonstrated at PA. The sensitivity and specificity calculated for the screening procedures are as follows: 53% and 90%, respectively, for SaO2; 60% and 100%, respectively, for chest radiograph; 73% and 80%, respectively, for PaO2 in room air; 100% and 40%, respectively, for PaO2 breathing 100% oxygen; and 64% and 80%, respectively, for shunt measurement. Initial screening with CE followed by measurement of PaO2 while breathing 100% oxygen seemed to be the best screening procedure for identification of patients with PAVM. Screening with chest radiograph and pulse oximetry was shown to be insufficient.

Linkage of hereditary haemorrhagic telangiectasia to chromosome 9q34 and evidence for locus heterogeneity.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with unknown pathophysiology that is characterised by arteriovenous lesions and recurrent haemorrhage in virtually every organ. Linkage of HHT to markers on chromosome 9q has recently been reported. In this study we report confirmation of this localisation in three unrelated families of Dutch origin. A fourth unrelated HHT family, in which considerably fewer pulmonary arteriovenous malformations (PAVM) were present, yielded evidence for non-linkage to this region. We conclude that HHT is a genetically heterogeneous disorder and our results indicate that the presence of PAVM may be more common in patients with a chromosome 9 linked form of HHT than in patients with the non-linked form.