59-Year-Old Woman With Fatigue, Dyspnea, and Lower Extremity Edema

Abstract

A 59-year-old woman presented to the emergency department with progressive lower extremity edema. She reported persistent swelling in her lower extremities over the preceding month. She described generalized fatigue and new-onset dyspnea occurring 2 to 3 days before presentation. She reported no recent fevers, chills, cough, chest pain, orthopnea, or paroxysmal nocturnal dyspnea. Her medical history was notable only for hereditary hemorrhagic telangiectasia (HHT) manifested by frequent nosebleeds since childhood. She had undergone genetic testing at an outside institution 20 years earlier, which revealed a heterozygous mutation in the ACVRL1 gene. She had no history of hypertension, diabetes, hyperlipidemia, or tobacco use. Her only medication was a daily multivitamin. The patient's oxygen saturation was 88% on room air, and supplemental oxygen was administered via nasal cannula. Her blood pressure was 132/65 mm Hg with a heart rate of 110 beats/min. Her body mass index (reference ranges provided parenthetically) was 38.9 kg/m2 (18.5-24.9 kg/m2). Physical examination was notable for: lower lip telangiectasias; a grade 2/6 holosystolic murmur best heard in the left lower sternal border, which increased in intensity with inspiration; jugular venous pressure of 12 cm (≤8 cm) with the patient semirecumbent (45 degrees); positive hepatojugular reflux; pulsatile liver; and 2+ pitting edema to the level of the knees, bilaterally.1.Which one of the following diagnoses is most consistent with this patient's clinical picture?a.Atypical pneumoniab.Right ventricular (RV) heart failurec.Decompensated cirrhosisd.Acute coronary syndromee.Venous insufficiency An atypical pneumonia can present with hypoxia and dyspnea, but it is usually associated with fevers and cough. The patient's jugular venous distention, liver pulsatility, tricuspid regurgitation murmur, and pitting edema are consistent with RV heart failure. Liver cirrhosis can result in high-output heart failure; however, she does not have other sequelae of decompensated cirrhosis (ascites, hepatic encephalopathy, or jaundice). In addition, liver cirrhosis does not lead to a pulsatile liver. The lack of chest pain and traditional risk factors associated with atherosclerotic cardiovascular disease makes acute coronary syndrome less likely. Although venous insufficiency is a common cause of lower extremity edema, this would not explain the patient's hypoxia or other cardiopulmonary findings noted on physical examination. Laboratory testing demonstrated the following: hemoglobin, 10.4 g/dL (12-15.5 g/dL); mean corpuscular volume, 73.8 fL (81.6-98.3 fL); and B-type natriuretic peptide, 1354 pg/mL (≤91 pg/mL). An electrocardiogram revealed atrial flutter with 2:1 conduction; no relevant ST-segment or T-wave changes were noted. Computed tomography (CT) with contrast media showed the following: bilateral pulmonary arteriovenous malformations (AVM) (largest 4.8 x 3.7 cm); multiple hepatic AVMs (largest 2.8 x 1.7 cm); marked dilatation of the central pulmonary arteries without any arterial filling defects; right-sided cardiac chamber enlargement; and a right pleural effusion. No emphysematous changes, ground-glass opacities, or areas of consolidation were noted. Ventilation-perfusion lung scan revealed bilateral segmental perfusion defects without matched ventilation defects that did not correspond with the pulmonary AVMs noted on CT, considered to be highly probable for pulmonary embolism. Transthoracic echocardiography demonstrated severe RV enlargement, severely decreased RV systolic function, severe tricuspid regurgitation, and an estimated RV systolic pressure of 61 mm Hg (<35 mm Hg). The left ventricle was D-shaped, with an ejection fraction of 56% (50%-70%). Severe biatrial enlargement was noted, with a left atrial volume index of 52 mL/m2 (16-34 mL/m2). Diastolic function grading was indeterminate due to underlying atrial flutter. No intracardiac shunts were identified.2.Given the available information, which one of the following statements regarding the patient's pulmonary hypertension is most accurate?a.The negative chest CT definitively rules out both acute and chronic pulmonary embolism as a potential etiology of this patient's pulmonary hypertensionb.Pulmonary arterial hypertension (PAH) is not associated with HHT and therefore is an unlikely cause of this patient's pulmonary hypertensionc.Underlying chronic obstructive pulmonary disease (COPD) is the primary mechanism of this patient's pulmonary hypertensiond.This patient's hepatic AVMs may create a high-flow state, which in turn results in increased pulmonary pressurese.There is low suspicion for heart failure with preserved ejection fraction as a contributing factor to this patient's pulmonary hypertension The World Health Organization classification of pulmonary hypertension comprises 5 groups: PAH (group 1); pulmonary hypertension due to left-sided heart disease (group 2); pulmonary hypertension due to chronic lung disease and/or hypoxia (group 3); chronic thromboembolic pulmonary hypertension (CTEPH; group 4); and pulmonary hypertension due to unclear multifactorial mechanisms (group 5).1Simonneau G. Gatzoulis M.A. Adatia I. et al.Updated clinical classification of pulmonary hypertension.J Am Coll Cardiol. 2013; 62 ([published correction appears in J Am Coll Cardiol. 2014;63(7):746]): D34-D41Crossref PubMed Scopus (2042) Google Scholar Although the sensitivity of CT angiography in detecting acute pulmonary embolism is somewhat variable (in part due to pretest probability), it is generally accepted to be greater than 90%. However, chronic thromboembolic disease, which can increase pulmonary pressures and cause RV dysfunction, may be missed by a CT scan.2Mos I.C. Klok F.A. Kroft L.J. de Roos A. Huisman M.V. Imaging tests in the diagnosis of pulmonary embolism.Semin Respir Crit Care Med. 2012; 33: 138-143Crossref PubMed Scopus (16) Google Scholar The ventilation-perfusion mismatch identified on ventilation-perfusion scan also raises concern for pulmonary embolism. Pulmonary arterial hypertension is a proliferative vasculopathy characterized by restricted flow through the pulmonary arterial vasculature, which in turn causes elevated RV pressures and eventual right-sided heart failure. Pulmonary arterial hypertension can be seen in familial disorders such as HHT and therefore is a plausible explanation for this patient's pulmonary hypertension and RV dysfunction. Although COPD may be associated with mild pulmonary hypertension, it is very rarely the only etiology of right-sided heart failure.3McLaughlin V.V. Archer S.L. Badesch D.B. et al.ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association.Circulation. 2009; 119 ([published correction appears in Circulation. 2009;120(2):e13]): 2250-2294Crossref PubMed Scopus (888) Google Scholar In addition, the patient had no history of tobacco use or evidence of emphysematous disease to suggest that she had underlying COPD. The large hepatic AVMs seen on CT can create a high-flow state from left-to-right shunting and trigger high-output heart failure with subsequent RV dysfunction. The patient had risk factors associated with heart failure with preserved ejection fraction (atrial arrhythmias and obesity), which can lead to elevated pulmonary capillary wedge pressures (PCWPs) and group 2 pulmonary hypertension. Despite attempts at diuresis, the patient remained substantially dyspneic with minimal activity. To determine next steps in management, additional testing to elucidate the underlying etiology of her cor pulmonale was pursued.3.Which one of the following is the most appropriate next step in evaluating this patient's condition?a.Right-sided heart catheterization (RHC)b.Dobutamine stress echocardiographyc.Regadenoson radionuclide myocardial perfusion imagingd.Transesophageal echocardiographye.Cardiac magnetic resonance imaging Right-sided heart catheterization is the criterion standard for the evaluation and diagnosis of pulmonary hypertension and is therefore the most appropriate test in this scenario. Pharmacological stress testing modalities, such as dobutamine stress echocardiography and regadenoson radionuclide myocardial perfusion imaging, are helpful in the identification of underlying coronary artery disease but do not contribute additional information regarding the cause of the patient's pulmonary hypertension. Transesophageal echocardiography provides complementary views of cardiac structures and may identify intracardiac shunts not visualized on transthoracic echocardiography; however, it does not provide the hemodynamic data required in the work-up of pulmonary hypertension. Cardiac magnetic resonance imaging allows for detailed visualization of cardiovascular anatomy and function, and it can be clinically useful in the assessment of multiple disorders, including cardiomyopathy and pericarditis.4Grunig E. Peacock A.J. Imaging the heart in pulmonary hypertension: an update.Eur Respir Rev. 2015; 24: 653-664Crossref PubMed Scopus (31) Google Scholar However, it is not the first-line test for identifying the etiology of pulmonary hypertension. The patient underwent RHC the following day. At rest, right atrial pressure (30 mm Hg [<6 mm Hg]), mean pulmonary arterial pressure (49 mm Hg [<25 mm Hg]), and pulmonary vascular resistance (12.8 Wood units [<2 Wood units]) were severely elevated. Mean PCWP was normal at 8 mm Hg (<15 mm Hg). Arterial saturation was 86%; which corrected to 96% with supplemental oxygen. Systemic and pulmonary flow, calculated using the Fick equation, were 2.5 L/min and 3.2 L/min, respectively. The cardiac index based on systemic flow was 1.2 L/min per m2 (2.5-4.0 L/min per m2). With administration of nitric oxide, mean pulmonary artery (PA) pressure was unchanged at 49 mm Hg. Invasive pulmonary angiography, performed given discordant CT angiographic and ventilation-perfusion scan findings, revealed no pulmonary embolism.4.On the basis of the test results for this patient, which one of the following statements is the most appropriate interpretation?a.There is no evidence of a left-to-right shuntb.A substantial intrapulmonary shunt is presentc.The patient's pulmonary hypertension is not due to left-sided heart failured.RHC does not indicate PAHe.Pulmonary hemodynamics are likely to improve with use of calcium channel blockers In a normal individual, systemic flow should be equivalent to pulmonary flow. In this patient, the two differ (Qs/Qp, 1.3), consistent with a small, extracardiac, left-to-right shunt due to the presence of hepatic AVMs. The known pulmonary AVMs point toward the possibility of intrapulmonary shunting. However, the fact that her arterial oxygen saturation normalized with oxygen supplementation makes this less likely. Measuring PCWP provides an estimate of left atrial pressure through “wedging” of a balloon-tipped, end-hole catheter in the distal pulmonary vasculature. In this patient, a high PA pressure in the presence of normal PCWP indicates that her pulmonary hypertension is not due to left-sided heart failure. In the absence of left-sided heart disease, chronic lung disease, and CTEPH, the elevated pulmonary vascular resistance is consistent with intrinsic pulmonary vascular disease due to group 1 PAH associated with HHT. Vasodilator administration during RHC is used to identify patients who may respond to high-dose calcium channel blocker therapy.5Galie N. Humbert M. Vachiery J.L. et al.2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS); endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46 ([published correction appears in Eur Respir J. 2015;46(6):1855-1856]): 903-975Crossref PubMed Scopus (2057) Google Scholar A positive response is defined as a decrease in mean PA pressure of 10 mm Hg or more to an absolute value of 40 mm Hg or less without a decrease in cardiac output. The patient did not meet criteria for a positive response during vasodilatory testing, and therefore calcium channel blockers are unlikely to be effective. Hereditary hemorrhagic telangiectasia–associated PAH was diagnosed on the basis of the hemodynamic data, and the decision to initiate PAH-specific vasodilator therapy was made. Embolization of the hepatic AVMs was considered but not pursued given the lack of efficacy in improving hemodynamics and the high risk of complications (ischemic hepatitis, hepatic encephalopathy, and pain) associated with the procedure.6Garcia-Tsao G. Liver involvement in hereditary hemorrhagic telangiectasia (HHT).J Hepatol. 2007; 46: 499-507Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar5.Which one of the following medications is most likely to decrease long-term morbidity and mortality in this patient?a.Treprostinilb.Sildenafilc.Iloprostd.Macitentane.Riociguat Several targeted therapies have been developed to decrease resistance through the pulmonary circuit and thereby improve overall blood flow.3McLaughlin V.V. Archer S.L. Badesch D.B. et al.ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association.Circulation. 2009; 119 ([published correction appears in Circulation. 2009;120(2):e13]): 2250-2294Crossref PubMed Scopus (888) Google Scholar, 5Galie N. Humbert M. Vachiery J.L. et al.2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS); endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46 ([published correction appears in Eur Respir J. 2015;46(6):1855-1856]): 903-975Crossref PubMed Scopus (2057) Google Scholar, 7McLaughlin V.V. Shah S.J. Souza R. Humbert M. Management of pulmonary arterial hypertension.J Am Coll Cardiol. 2015; 65: 1976-1997Crossref PubMed Scopus (253) Google Scholar Treprostinil is a prostanoid analogue that has vasodilatory and antiproliferative effects on the pulmonary arteries. Administered via inhalation or through subcutaneous/intravenous infusions, it is associated with an improvement in exercise capacity but not mortality.7McLaughlin V.V. Shah S.J. Souza R. Humbert M. Management of pulmonary arterial hypertension.J Am Coll Cardiol. 2015; 65: 1976-1997Crossref PubMed Scopus (253) Google Scholar Sildenafil causes vasodilation through the nitric oxide/cyclic guanosine 3′,5′-monophosphate pathway via the inhibition of phosphodiesterase type 5. On the basis of data from 4 randomized controlled trials, it is associated with improvements in exercise capacity, symptoms, and hemodynamics; however, no trial data have confirmed a mortality benefit.5Galie N. Humbert M. Vachiery J.L. et al.2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS); endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46 ([published correction appears in Eur Respir J. 2015;46(6):1855-1856]): 903-975Crossref PubMed Scopus (2057) Google Scholar Iloprost is an inhaled prostanoid analogue that has been found to improve exercise capacity and symptoms but not mortality.5Galie N. Humbert M. Vachiery J.L. et al.2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS); endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46 ([published correction appears in Eur Respir J. 2015;46(6):1855-1856]): 903-975Crossref PubMed Scopus (2057) Google Scholar Macitentan acts as an antagonist of the endothelin 1 pathway, which promotes vasoconstriction and mitogenesis in the pulmonary arterial vasculature. In the SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) trial, macitentan was associated with lower rates of morbidity and mortality than placebo.8Pulido T. Adzerikho I. Channick R.N. et al.Macitentan and morbidity and mortality in pulmonary arterial hypertension.N Engl J Med. 2013; 369: 809-818Crossref PubMed Scopus (959) Google Scholar Riociguat is a soluble guanylate cyclase stimulator that improves exercise capacity and symptoms in patients who have PAH and CTEPH; however, no survival benefit has been found.5Galie N. Humbert M. Vachiery J.L. et al.2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS); endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46 ([published correction appears in Eur Respir J. 2015;46(6):1855-1856]): 903-975Crossref PubMed Scopus (2057) Google Scholar No randomized controlled trials have been conducted to evaluate outcomes of pharmacological therapy in HHT-associated PAH, owing to its relative rarity.9Parambil J.G. Hereditary hemorrhagic telangiectasia.Clin Chest Med. 2016; 37: 513-521Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Given the patient's clinical symptoms, severely elevated PA pressure, and RV dysfunction, a combination therapy of intravenous treprostinil with oral sildenafil and macitentan was initiated under the guidance of the Pulmonary Hypertension consultative service. Despite administration of these medications, oliguric acute kidney injury secondary to cardiorenal syndrome developed, requiring renal replacement therapy. Her hospital course was additionally complicated by bilateral soleal vein thromboses and an RV thrombus; therapeutic anticoagulation with warfarin was therefore initiated. She improved clinically after a month of inpatient medical treatment and was subsequently discharged home with outpatient dialysis. Hereditary hemorrhagic telangiectasia, or Osler-Weber-Rendu syndrome, is a familial vascular disorder that is associated with the formation of abnormal blood vessels within mucocutaneous tissues.10Shovlin C.L. Guttmacher A.E. Buscarini E. et al.Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).Am J Med Genet. 2000; 91: 66-67Crossref PubMed Scopus (1306) Google Scholar It exhibits an autosomal dominant pattern with variable penetrance. Three putative disease-causing genes are available for laboratory testing: ENG (HHT type 1); ACVRL1 (HHT type 2); and MADH4 (combined syndrome of HHT and juvenile polyposis syndrome).9Parambil J.G. Hereditary hemorrhagic telangiectasia.Clin Chest Med. 2016; 37: 513-521Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar The Curaçao criteria for diagnosing HHT include (1) spontaneous, recurrent nosebleeds, (2) mucocutaneous telangiectasias at characteristic sites, including fingertips, lips, and oral mucosa, (3) visceral involvement, including gastrointestinal telangiectasias and cerebral, pulmonary, and/or hepatic AVMs, and (4) family history of an affected first-degree relative.10Shovlin C.L. Guttmacher A.E. Buscarini E. et al.Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).Am J Med Genet. 2000; 91: 66-67Crossref PubMed Scopus (1306) Google Scholar Definite and suspected HHT are defined as having fulfilled 3 or more and 2 of the 4 criteria, respectively, whereas the presence of 0 to 1 criterion makes the diagnosis unlikely. Pulmonary vascular disease is common in patients who have HHT. Pulmonary AVMs are found in approximately 50% of patients who have HHT and may result in hypoxia from right-to-left shunting and increase the risk of paradoxical embolism.9Parambil J.G. Hereditary hemorrhagic telangiectasia.Clin Chest Med. 2016; 37: 513-521Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Pulmonary hypertension is another manifestation of HHT that occurs via 2 main mechanisms: (1) increased flow from left-to-right shunting (usually from hepatic AVMs) leading to high-output heart failure and (2) PAH due to true fibroproliferative arteriopathy.9Parambil J.G. Hereditary hemorrhagic telangiectasia.Clin Chest Med. 2016; 37: 513-521Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Various mutations in HHT have been associated with a higher risk of PAH; specifically, ACVRL1 mutations have been implicated in patients with HHT who have concomitant PAH.9Parambil J.G. Hereditary hemorrhagic telangiectasia.Clin Chest Med. 2016; 37: 513-521Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Pulmonary hypertension due to high-output heart failure may be managed by salt restriction and diuretics.11Lyle M.A. Fenstad E.R. McGoon M.D. et al.Pulmonary hypertension in hereditary hemorrhagic telangiectasia.Chest. 2016; 149: 362-371Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Antiangiogenic agents such as bevacizumab may also be useful in reducing high cardiac output among patients who have hepatic AVMs.12Dupuis-Girod S. Ginon I. Saurin J.C. et al.Bevacizumab in patients with hereditary hemorrhagic telangiectasia and severe hepatic vascular malformations and high cardiac output.JAMA. 2012; 307: 948-955Crossref PubMed Scopus (254) Google Scholar Transarterial embolization or surgical ligation of hepatic AVMs can be considered as well, although these procedures are associated with substantial morbidity and mortality risk.6Garcia-Tsao G. Liver involvement in hereditary hemorrhagic telangiectasia (HHT).J Hepatol. 2007; 46: 499-507Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar Finally, liver transplant is a potentially curative option for patients who have refractory high-output heart failure from hepatic AVMs.6Garcia-Tsao G. Liver involvement in hereditary hemorrhagic telangiectasia (HHT).J Hepatol. 2007; 46: 499-507Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar, 11Lyle M.A. Fenstad E.R. McGoon M.D. et al.Pulmonary hypertension in hereditary hemorrhagic telangiectasia.Chest. 2016; 149: 362-371Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Pulmonary arterial hypertension is rare among patients who have HHT (estimated prevalence of <1%),11Lyle M.A. Fenstad E.R. McGoon M.D. et al.Pulmonary hypertension in hereditary hemorrhagic telangiectasia.Chest. 2016; 149: 362-371Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar so treatment options are extrapolated from standard guidelines used in PAH.9Parambil J.G. Hereditary hemorrhagic telangiectasia.Clin Chest Med. 2016; 37: 513-521Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar In addition to the vasodilator therapies described earlier, other aspects of treating HHT-associated PAH include supervised exercise rehabilitation, infection prevention, diuretics, and iron supplementation.3McLaughlin V.V. Archer S.L. Badesch D.B. et al.ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association.Circulation. 2009; 119 ([published correction appears in Circulation. 2009;120(2):e13]): 2250-2294Crossref PubMed Scopus (888) Google Scholar, 5Galie N. Humbert M. Vachiery J.L. et al.2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS); endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46 ([published correction appears in Eur Respir J. 2015;46(6):1855-1856]): 903-975Crossref PubMed Scopus (2057) Google Scholar Screening for concomitant pulmonary hypertension may be appropriate in patients with HHT, as recent data suggest a trend toward decreased survival rates among these individuals.11Lyle M.A. Fenstad E.R. McGoon M.D. et al.Pulmonary hypertension in hereditary hemorrhagic telangiectasia.Chest. 2016; 149: 362-371Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Hereditary hemorrhagic telangiectasia is a rare genetic disorder that frequently involves multiple organs, including the liver, lungs, and heart. Pulmonary hypertension is an uncommon but palpable complication of HHT, with several potential causative mechanisms. The present case outlines the key steps in the work-up and treatment of newly diagnosed pulmonary hypertension in a patient known to have HHT. Systematically determining the underlying etiology of concomitant pulmonary hypertension is crucial because it has important therapeutic and prognostic implications in this patient population.