An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease

Abstract

Background: In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) diagnosed by right heart catheterization (RHC) are independent risk factors for mortality.

Methods: A multidisciplinary committee was formed by clinician-investigators experienced in the management of patients with PH and/or SCD. Clinically important questions were posed, related evidence was appraised, and questions were answered with evidence-based recommendations. Target audiences include all clinicians who take care of patients with SCD.

Results: Mortality risk stratification guides decision making. An increased risk for mortality is defined as a TRV equal to or greater than 2.5 m/second, an NT-pro-BNP level equal to or greater than 160 pg/ml, or RHC-confirmed PH. For patients identified as having increased mortality risk, we make a strong recommendation for hydroxyurea as first-line therapy and a weak recommendation for chronic transfusions as an alternative therapy. For all patients with SCD with elevated TRV alone or elevated NT-pro-BNP alone, and for patients with SCD with RHC-confirmed PH with elevated pulmonary artery wedge pressure and low pulmonary vascular resistance, we make a strong recommendation against PAH-specific therapy. However, for select patients with SCD with RHC-confirmed PH who have elevated pulmonary vascular resistance and normal pulmonary capillary wedge pressure, we make a weak recommendation for either prostacyclin agonist or endothelin receptor antagonist therapy and a strong recommendation against phosphodiesterase-5 inhibitor therapy.

Conclusions: Evidence-based recommendations for the management of patients with SCD with increased mortality risk are provided, but will require frequent reassessment and updating.

Figure 1.

Echocardiogram of a patient with pulmonary hypertension related to sickle cell disease, and determination of tricuspid regurgitant jet velocity. (A) As demonstrated in this echocardiogram of a patient with an estimated pulmonary artery systolic pressure of 44 mm Hg, in patients with pulmonary hypertension of sickle cell disease there is dilation of the right ventricular (RV) chamber so that it is larger than the left ventricle (LV) with shift of the interventricular septum into the LV. (B) Doppler flow of tricuspid regurgitation (demonstrated in blue) from the right ventricle (RV) into the right atrium (RA). The velocity of this flow is measured and allows for calculation of an estimated pulmonary artery systolic pressure. HR = heart rate; p = pressure; TR maxPG = peak gradient of tricuspid regurgitation; TR Vmax = tricuspid regurgitation peak velocity; v = velocity.

Figure 2.

Proposed algorithm for evaluation of pulmonary hypertension related to sickle cell disease. 6MWD = 6-minute walk distance; ANA = anti-nuclear antibody; CXR = chest X-ray; EKG = electrocardiogram; LFTs = liver function tests; mPAP = mean pulmonary artery pressure; NT-pro-BNP = N-terminal pro–brain natriuretic peptide; PAWP = pulmonary artery wedge pressure; PH = pulmonary hypertension; PVR = pulmonary vascular resistance; SCD = sickle cell disease; TRV = tricuspid regurgitant jet velocity. ¹Note: The use of the term screening refers to mortality risk assessment. Echocardiography should be performed while patients are clinically stable. Patients with an mPAP between 20 and 25 mm Hg need further study as they may be at increased mortality risk. Note: PAH therapy is to be considered on the basis of a weak recommendation and very low-quality evidence.