Incidence Of Pulmonary Arteriovenous Malformations Research Articles

Molecular mechanisms and clinical manifestations of hereditary hemorrhagic telangiectasia

IntroductionHereditary Hemorrhagic Telangiectasia (HHT) is charactered by telangiectasia and arteriovenous malformations (AVMs). Recurrent visceral and mucocutaneous bleeding is frequently reported among HHT patients, while data on the prevalence of thrombosis remains limited. This study aims to describe the clinical manifestations and molecular biological characteristics of HHT patients. MethodsWe conducted a retrospective study at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. A total of 24 HHT patients, observed between January 2019 and December 2023, were included. We recorded the biological, clinical, and therapeutic events, with particular attention to bleeding and thrombotic events. Gene mutation analysis and blood constituent measurements were performed. ResultsThe prevalence of bleeding among all HHT patients was 100 %, while thrombotic events were noted in 41.70 % of cases. Hepatic arteriovenous malformations (HAVMs) were identified in six patients, pulmonary arteriovenous malformations (PAVMs) in five patients, and cerebral arteriovenous malformations (CAVMs) in one patient. For patients with thrombosis, the discontinuation rates were 23.08 % for antiplatelet therapy and 33.33 % for anticoagulant therapy due to the increased risk of bleeding. Genetic mutations related to HHT were present in 16 patients, with ACVRL1 (activin A receptor-like type 1) mutations being the most frequent at 41.67 %, followed by ENG (endoglin) mutations at 20.83 %, and GDF2 (growth differentiation factor 2) mutations at 4.17 %. The incidence of PAVMs was 75.00 % in HHT1 patients with ENG mutations and 20 % in HHT2 patients with ACVRL1 mutations, while HAVMs occurred in 0 % and 40.00 % of these groups, respectively. Patients were divided into non-AVMs and AVMs groups. Compared to normal controls, von Willebrand factor (vWF) activity was significantly increased in all HHT patients (149.10 % vs. 90.65 %, P < 0.001). In the non-AVMs group, the median level of stromal cell-derived factor-1 (SDF-1) was significantly elevated (124.31 pg/mL vs. 2413.57 pg/mL, P < 0.05), while vWF antigen levels were markedly higher in the AVMs group (165.30 % vs. 130.60 %, P = 0.021). Further grouping of HHT patients based on bleeding and thrombosis phenotypes revealed that those with thrombosis had significantly higher median percentages of schistocytes (3.50 % vs. 0 %, P = 0.002), ferritin concentrations (318.50 μg/L vs. 115.50 μg/L, P = 0.001), and lactate dehydrogenase (LDH) levels (437 U/L vs. 105 U/L, P < 0.001). There were no significant differences in the activity of vWF, protein C (PC), protein S (PS), and factor VIII (FVIII) between the two groups. ConclusionThis study highlighted the complex relationship between arteriovenous malformations and genetic mutations in HHT patients. A comprehensive assessment of bleeding and thrombosis risks should be conducted for each HHT patient, additionally, further clinical studies are needed to explore the risk factors for thrombosis and anticoagulant-related bleeding in HHT.

Identifying racial disparities in hereditary hemorrhagic telangiectasia

BackgroundHereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis (nose bleeds), mucosal telangiectasias (spider veins), and arteriovenous malformations. Although HHT affects all racial groups, few...

Should we always plan a Fontan completion after a Kawashima procedure?

To determine the late incidence of pulmonary arteriovenous malformations after bidirectional Glenn in patients with azygos continuation of the inferior vena cava (Kawashima operation). From 1990 to 2006, 21 patients underwent a Kawashima procedure at a median age of 2.3 years (0.5-8 years). Underlying anatomy included atrioventricular septal defect [14], double-outlet right ventricle [13], pulmonary atresia [3], pulmonary stenosis [11], total anomalous pulmonary venous drainage [4] and bilateral superior vena cavae [14]. There was one hospital death after Kawashima due to low output syndrome. Follow-up was complete in all but one patient. Two patients died 23 days and 4 years after Kawashima following cardiac reinterventions (one atrioventricular valve replacement and one Fontan completion). Thirteen patients developed pulmonary arteriovenous malformations after a median of 4 years (2-9 years) after Kawashima. Freedom from development of arteriovenous malformations was 47% at 5 years (95% CI: 23-69%). A total of 16 patients underwent Fontan completion, 12 for cyanosis related to pulmonary arteriovenous malformations and four for decreased exercise capacity. Only three patients were left without Fontan completion at 4, 9 and 13 years after Kawashima. The two patients who had more than 9 years of follow-up after Kawashima had antegrade flow preserved between the ventricle and the pulmonary arteries. Unless some hepatic blood flow is directed to both lungs, most, if not all patients with a Kawashima procedure will ultimately develop pulmonary arteriovenous malformations. Elective non-fenestrated Fontan completion in the years following Kawashima procedure should be recommended.

Can the Kawashima Procedure Be Performed in Younger Patients?

The prudence of performing early palliative cavopulmonary connection that includes superior vena cava in association with azygous-hemiazygous continuation of the inferior vena cava, Kawashima procedure (KP), has been questioned. We document our experience with KP performed at a relatively younger age than usually reported. A retrospective review of patients undergoing KP (October 2000 to April 2008) was done. Initial palliation was carried out in 13 of 15 patients. Age and weight at KP was 8.4 months (5.1 to 15.1) and 6.8 kg (4.6 to 11.0). The pre-KP catheterization showed the following: pulmonary artery pressure = 14.5 mm Hg (9 to 17); end-diastolic pressure of systemic ventricle = 8 (2 to 14); oxygenation saturation = 76% (63 to 82); and atrioventricular (AV) valve insufficiency moderate or greater in 5 patients. The post-KP characteristics included the following intubation = 1 day (0 to 19); nitric oxide = 4 patients; superior caval pressure = 14 mm Hg (6 to 18); inotrope score = 7.5 (2.5 to 14.3); intensive care unit stay = 3 days (1 to 9); hospital stay = 7 days (3 to 77); and oxygen saturation at discharge = 84% (76 to 90%). There was one hospital death that required takedown of KP. Fontan completion was performed in 8 patients at an interval of 2.7 years (1.8 to 5.8) after KP. There was one post-Fontan mortality from severe ventricular and AV valve dysfunction. Pulmonary arteriovenous malformations (PAVMs) were diagnosed in 4 patients with 3 resolving post-Fontan. With a median follow-up of 4.2 years (0.1 to 7.9), 13 of 15 remain alive yielding a series survival of 87%. The Kawashima procedure can be safely performed at an earlier age than previously reported. The incidence of PAVMs after the KP appears to be similar to other reports where KP was performed at a later age.

Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia type 1 (HHT1) is a vascular dysplasia caused by mutations in the endoglin (ENG) gene and associated with epistaxis, telangiectases, and a high incidence of pulmonary arteriovenous malformations. To efficiently detect deletions and insertions, we optimized a quantitative multiplex polymerase chain reaction (QMPCR) analysis. We report 17 novel mutations, of which six were detected by QMPCR. Three deletions occurring in intronic sequences were associated with a single copy of exons 9a-14, exon 5, and exons 7-8, respectively. A transient 70kDa monomeric mutant protein resulted from the in-frame deletion of exons 7 and 8 but no mutant protein was present in the other cases. Deletion (in exon 10) or insertion (in exon 7) of two nucleotides, as well as a 1-bp deletion in the small exon 9a were found by QMPCR. Sequencing was required to detect single nucleotide deletions/insertions in exons 2, 5, 6, and 8. No mutant proteins were associated with these frame shift mutations. Two novel splice site mutations resulted in skipping of exons 2 and 4, respectively, while a previously reported intron 3 splice mutant was observed as a de novo mutation. We also report five novel nonsense and missense mutations, including one de novo. Review of the 80 HHT1 families reported to date indicates that 10% would not be resolved by sequencing and that an additional 25% could be revealed by QMPCR performed prior to sequencing. Thus the use of QMPCR accelerates genetic screening for HHT1 and resolves mutations affecting whole exons.

Rapid onset of pulmonary arteriovenous malformations after cavopulmonary anastomosis

The reported incidence of pulmonary arteriovenous malformations after superior cavopulmonary anastamosis in patients with heterotaxia syndrome is 18%–21%. The manifestation is usually in young children and the onset is gradual. We report an unusual case of pulmonary arteriovenous malformations developing within 72 hours of bilateral superior cavopulmonary anastamosis (Kawashima procedure) in an adolescent with heterotaxia syndrome.

Computational fluid dynamic simulations of cavopulmonary connections with an extracardiac lateral conduit

Complex congenital heart defects due to the absence of a ventricular chamber can often be treated by the Fontan surgical procedure. The objective of this work was to quantify the haemodynamics in the Fontan operation (cavopulmonary connection) with extracardiac lateral conduit. Four different models based on the finite element method were constructed with different lengths of inferior anastomosis (range 18–25 mm) and inclinations of the conduit (33 and 47.5°). Mass conservation and Navier–Stokes equations were solved by means of the FIDAP code, based on the finite element method. The left-to-right pulmonary flow ratio and percentage inferior caval blood to the left lung were the highest with the smallest anastomosis and highest inclination: 1.35 and 83.26%, respectively. Dissipated power percentage was higher with the largest anastomosis than with the smallest (19.4 vs 15.8%). It was concluded that, when performing a total cavopulmonary connection, an extracardiac lateral conduit: (i) diverts more flow to the left lung, and (ii) shows higher energy losses when compared with a connection with intra-atrial tunnel. This study could be useful to evaluate the incidence of pulmonary arteriovenous malformations.

Pulmonary AV Malformations After Superior Cavopulmonary Connection: Resolution After Inclusion of Hepatic Veins in the Pulmonary Circulation

Background. A high incidence of pulmonary arteriovenous malformations (PAVMs) has been reported in patients who have polysplenia and congenital heart disease after superior cavopulmonary anastomosis. Interruption of hepatic venous return to the pulmonary circulation is believed to potentiate the development of PAVMs. Surgical inclusion of hepatic flow in the pulmonary circulation may result in their resolution.Methods. We reviewed 3 patients with congenital heart disease and polysplenia in whom PAVMs developed and who had subsequent hepatic vein inclusion in the pulmonary circulation.Results. Patients underwent superior cavopulmonary connection at a median age of 8 months. The PAVMs were diagnosed at a median duration of 8 months after operation (arterial saturation <75% in room air). Hepatic venous flow was included in the pulmonary circulation at operation. Resolution of PAVMs occurred at a median duration of 7 months after operation (arterial saturation >90% in room air).Conclusions. Surgical inclusion of hepatic venous blood in the pulmonary circulation results in the resolution of PAVMs. Electively associating the hepatic veins with the pulmonary vasculature may prevent the development of PAVMs in patients who are at risk.(Ann Thorac Surg 1997;63:960–3)

Advances in surgical care of infants and children with congenital heart disease

Recent important technical developments in the field of surgery for congenital heart disease have included the Ross pulmonary autograft replacement of the aortic valve, video-assisted thoracoscopic surgery, and the double-switch and switch-Rastelli procedure for congenitally corrected transposition. Although the growth potential of the pulmonary autograft has been confirmed, an important incidence of late aortic regurgitation has been noted. Expanding indications for video-assisted thoracoscopic surgery have been described, including division of the vascular ring. Late hemodynamic assessment after the double-switch or switch-Rastelli procedure will encourage increased application of this repair. Both clinical and laboratory studies have focused on neurologic and developmental outcome after cardiac surgery. Perioperative seizures in young infants have been found to be associated with impaired psychomotor development at 1 year of age. In the area of perioperative management, the antifibrinolytic agents tranexamic acid, epsilon-aminocaproic acid, and aprotinin have been found to be useful in reducing postoperative hemorrhage. Nitric oxide is useful in reducing postoperative pulmonary hypertension. Late clinical follow-up studies of patients with single ventricle have revealed an important incidence of pulmonary arteriovenous malformations after a bidirectional Glenn shunt and atrial flutter after a Fontan procedure. Late assessment of patients after the arterial switch procedure for transposition has revealed preservation of ventricular function and an extremely low incidence of late arrhythmias.