Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension

Abstract

Rationale: Although pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) associated with high mortality, there exist few data characterizing hemodynamics and cardiopulmonary function in this population.

Objectives: To characterize hemodynamics and cardiopulmonary function in patients with SCD with and without PH.

Methods: Patients with SCD with PH (n = 26) were compared with control subjects with SCD but without PH (n = 17), matched for age, hemoglobin levels, and fetal hemoglobin levels.

Measurements and main results: Upon catheterization, 54% of the patients with PH had pulmonary arterial hypertension, and 46% had pulmonary venous hypertension. When compared with control subjects, patients with PH exhibited lower six-minute-walk distance (435 +/- 31 vs. 320 +/- 20 m, p = 0.002) and oxygen consumption (50 +/- 3% vs. 41 +/- 2% of predicted, p = 0.02), and also had mild restrictive lung disease and more perfusion abnormalities on radionuclide lung scans. The six-minute-walk distance in this population inversely correlated with tricuspid regurgitant jet velocity (r = -0.55, p < 0.001), and mean pulmonary artery pressure (r = -0.57, p < 0.001), and directly correlated with maximal oxygen consumption (r = 0.49, p = 0.004), even after adjustment for hemoglobin, supporting an independent contribution of increasing pulmonary artery pressures to loss of exercise capacity.

Conclusions: Patients with SCD-associated PH have both pulmonary arterial and venous PH associated with severe limitations in exercise capacity, likely compounded by interstitial lung fibrosis and severe anemia. These data support the use of the six-minute-walk distance as an index of PH and cardiopulmonary function in patients with SCD.

Figure 1.

Pulmonary arterial hypertension (PAH) is the most common cause of high pulmonary artery pressures in patients with sickle cell disease. Mean values ± SEM of hemodynamic variables for patient subgroups with PAH and pulmonary venous hypertension (PVH) are shown. CO = cardiac output; mPAP = mean pulmonary artery pressure; PAD = pulmonary artery diastolic pressure; PAS = pulmonary artery systolic pressure; PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance; RAP = right atrial pressure; TPR = total pulmonary resistance.

Figure 2.

Six-minute-walk distance (A) is significantly lower in patients with sickle cell disease and pulmonary hypertension (PHT) compared with those without PHT, (B) is inversely correlated with tricuspid regurgitant jet velocity (n = 40), and (C) is inversely correlated with mean pulmonary artery pressure (mPAP) (n = 35). Six-minute-walk distance is directly correlated with (D) maximal oxygen consumption (V̇o₂max) (n = 34).

Figure 3.

Mild interstitial lung disease and lung perfusion defects in patients with sickle cell disease and pulmonary hypertension (PHT). (A and B) Patients with PHT have more abnormalities on high-resolution computed tomography (CT) scans graded as mild to moderate interstitial lung disease, compared with patients without PHT. (C and D) Patients with PHT have more lung perfusion scans graded as low, intermediate, and high probability compared with patients without PHT whose scans are largely normal. *p < 0.05 when compared with patients with normal perfusion scans.