Pulmonary hypertension in hereditary hemorrhagic telangiectasia: A clinical review

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectasias, and solid organ arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is an increasingly recognized complication in patients with HHT, most often precipitated by high-output heart failure in the presence of hepatic AVMs as well as pulmonary arterial hypertension in the form of a proliferative vasculopathy. The presence of PH in patients with HHT is associated with significant elevations in rates of morbidity and mortality. Additionally, there is growing recognition of a thromboembolic propensity in this population that increases the risk of chronic thromboembolic PH, posing unique clinical considerations regarding the use of anticoagulation. Patients with HHT are also at risk of PH due to disorders commonly seen in the general population, including left-sided heart and lung disease. The etiology of PH in HHT is multifaceted and complex; the diagnostic approach and treatment strategies must consider the underlying pathophysiology of HHT. This comprehensive review summarizes current knowledge of PH in HHT, detailing the pathogenesis of known etiologies, diagnostic evaluation, and suggested treatment modalities as well as emerging therapies that may be of future interest.

Keywords: chronic thromboembolic pulmonary hypertension; hereditary hemorrhagic telangiectasia; high‐output heart failure; pulmonary arterial hypertension; pulmonary hypertension.

Figure 1

A practical algorithm to assist in the detection of and treatment for pulmonary hypertension (PH) in patients with hereditary hemorrhagic telangiectasia (HHT). Etiologies of precapillary PH in patients with HHT are in blue text and/or on the left‐hand flowchart line, while etiologies of postcapillary PH are in red text and/or on the right‐hand flowchart line. The latter is divided by cardiac index, in which a value greater than 4 L/min/m² indicates a high output state., Recommendations are on the basis of the most recently established guidelines for the treatment of PH in the general population as well as for the management of complications of HHT., In PH due to hypoxic lung disease, inhaled treprostinil may be indicated in cases of pathologic interstitial subtypes. AVM, arteriovenous malformation; BPA, balloon pulmonary angioplasty; CTEPH, chronic thromboembolic pulmonary hypertension; HOHF, high‐output heart failure; mPAP, mean pulmonary artery pressure; PAH, pulmonary arterial hypertension; PAWP, pulmonary arterial wedge pressure; PTEA, pulmonary thromboendarterectomy; PVR, pulmonary vascular resistance; RHC, right heart catheterization; V/Q, ventilation/perfusion lung scan; WU, Wood unit.