Not Just Another "Bloody" Case of Right Heart Failure.

Question: A 47-year-old woman with right heart failure and hepatomegaly presented with worsening dyspnea, fatigue, and new jaundice. Her medical history included pulmonary hypertension, atrial fibrillation, and recurrent epistaxis. There was a history of epistaxis and heart failure on her father’s side, without any specific known diagnosis. Physical examination demonstrated multiple chest wall telangiectasias and an enlarged pulsatile liver. Liver function tests (LFTs) on presentation revealed a mixed picture, with alanine aminotransferase of 105 U/L, aspartate aminotransferase of 125 U/L, gamma-glutamyl transferase of 635 U/L, alkaline phosphatase of 759 U/L, and total bilirubin of 75 μmol/L. A transthoracic echocardiogram revealed functional tricuspid regurgitation, biatrial dilatation, and a markedly dilated right ventricle with no intracardiac shunt and a depressed ejection fraction of 33%. Left and right heart catheterization showed normal coronary arteries, confirmed pulmonary hypertension, and demonstrated hyperdynamic function on left ventriculogram with no evidence of ventricular septal defect or intracardiac shunt. A nuclear medicine scan demonstrated a left-to-right shunt with increased intake with a high liver uptake of isotope; however, cardiac magnetic resonance imaging suggested no intracardiac shunt. Abdominal doppler ultrasound examination demonstrated an enlarged right and left lobe of the liver, with extensive dilated tortuous intrahepatic portal varicosities with high turbulent flow. The acoustic radiation force index value was 2.83, indicating high intrahepatic pressure and cirrhosis. A computed tomographic liver quadriphasic scan was performed (Figure A). Based on the clinical vignette and the accompanying imaging, what is the likely diagnosis? Look on page 539 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Cross-sectional imaging of the liver (Figure A) demonstrates an enlarged hypervascular liver with multiple arteriovenous malformations (AVM), a dilated right hepatic artery with a diameter of 13 mm (A), with the common hepatic artery (B), and the inferior vena cava (C) also demarcated. A hepatic digital subtraction angiography via the common hepatic artery (Figure B) further illustrates the markedly dilated and tortuous hepatic arterial anatomy. In patients presenting with heart failure and hepatomegaly with deranged LFTs, the foremost differential is cor pulmonale with associated congestive hepatopathy. Primary cardiac causes were ruled out in this case through echocardiogram and cardiac catheterization. Despite the pulmonary blood flow:systemic blood flow ratio (Qp:Qs) of >2.5:1.0, suggesting a large left-to-right shunt, cardiac magnetic resonance imaging demonstrated no intracardiac shunt. In the absence of intracardiac causes of left-to-right circulatory shunts, extrathoracic causes for left-to-right shunt should be considered, including hepatic or cerebral AVM. On review of imaging in a multidisciplinary meeting, the presence of hepatic AVMs and the dilated hepatic arteries, in conjunction with the clinical history, the diagnosis of hepatic hereditary hemorrhagic telangiectasia (HHT), eponymously known as Osler–Rendu–Weber syndrome, was made. The characteristic imaging findings, multiple cutaneous telangiectasias and recurrent epistaxis fulfils the Curaçao criteria1Faughnan M.E. Mager J.J. Hetts S.W. et al.Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia.Ann Intern Med. 2021; 174: 1035-1036Crossref PubMed Scopus (7) Google Scholar for the diagnosis of this condition on clinical grounds. Subsequent genetic testing demonstrated ACVRL1 gene mutation, associated with HHT. The patient had no features of cerebral or pulmonary AVMs on cross-sectional imaging upon establishing the diagnosis. HHT is an autosomal dominant disorder due to abnormalities in multiple genes, the majority affecting transforming growth factor β, with patients typically presenting with recurrent epistaxis, mucocutaneous telangiectasias, and gastrointestinal bleeding.1Faughnan M.E. Mager J.J. Hetts S.W. et al.Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia.Ann Intern Med. 2021; 174: 1035-1036Crossref PubMed Scopus (7) Google Scholar The diagnosis is made clinically through the Curaçao criteria (fulfilling 3 out of 4 of [1] recurrent epistaxis, [2] mucocutaneous telangiectasias, [3] visceral vascular malformations, and [4] a first-degree relative diagnosed with HHT) and/or with corroborative genetic testing.1Faughnan M.E. Mager J.J. Hetts S.W. et al.Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia.Ann Intern Med. 2021; 174: 1035-1036Crossref PubMed Scopus (7) Google Scholar Imaging of the liver can demonstrate hepatic AVMs, markedly dilated hepatic arteries (typically >10 mm) and telangiectasias, with the latter two pathognomonic for hepatic Osler’s syndrome.2Wu J. Saluja S. Garcia-Tsao G. et al.Liver involvement in hereditary hemorrhagic telangiectasia: CT and clinical findings do not correlate in symptomatic patients.Am J Roentgenol. 2006; 187: W399-W405Crossref PubMed Scopus (64) Google Scholar Treatment depends on the organ involved and severity of symptoms, with potential pulmonary, cerebral, gastrointestinal, and hepatic system involvement among those affected. Bevacizumab has been studied for the management of high-output cardiac failure related to hepatic AVMs, and for endoscopic-refractory or transfusion-dependent gastrointestinal bleeding.3Dupuis-Girod S. Intravenous bevacizumab in hereditary hemorrhagic telangiectasia: a role that is still to be defined.Mayo Clin Proc. 2020; 95: 1565-1566Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Liver transplantation is reserved for patients who have high-output cardiac failure and liver-centric disease who do not improve with, or are intolerant to, bevacizumab. The patient was commenced on fortnightly bevacizumab intravenous infusions of 300 mg, a monoclonal antibody neutralizing vascular endothelial growth factor, which acts by inhibiting neovascularization. This led to marked improvement of the patients LFTs after a period of 6 months of therapy, with an alanine aminotransferase of 88 U/L, aspartate aminotransferase of 82 U/L, gamma-glutamyl transferase of 204 U/L, alkaline phosphatase of r380 U/L, and total bilirubin of 29 μmol/L. The patients LFTs both prior to and since commencement of Bevacizumab are illustrated in Figure C. After 12 months of therapy, her Model for End-stage Liver Disease score decreased from 18 before treatment to 8, with continued stabilization of her LFTs. She had no further epistaxis and the symptoms of heart failure had resolved, with a repeat transthoracic echocardiogram demonstrating normalization of the ejection fraction and right ventricular size. As such, the infusions were drawn out to a schedule of every 4 weeks. There was no known family history of HHT, and the patient’s immediate family declined genetic testing when offered. The patient continues to be symptom free with bevacizumab infusions planned to continue indefinitely, and is reviewed every 6 months with serial monitoring of her clinical status, biochemistry, and assessment for complications of bevacizumab infusions.