Abnormal Ventilation–Perfusion Scan Is Associated with Pulmonary Hypertension in Sickle Cell Adults

Abstract

Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality. Chronic thromboembolic pulmonary hypertension (CTEPH) is an important complication and contributor to PH in SCD, but likely underappreciated. Guidelines recommend ventilation-perfusion scintigraphy (V/Q) as imaging modality of choice to exclude CTEPH. Data on V/Q are limited in SCD. To compare the performance of V/Q with computed tomography pulmonary angiography (CTPA) and to report clinical outcomes associated with abnormal V/Q. Laboratory data, echocardiography, six-minute walk test, V/Q, CTPA, and right heart catheterization (RHC) were prospectively obtained. High-probability and intermediate-probability V/Q scan findings were considered to be abnormal. 142 SCD adults (aged 40.1±13.7 years, 83 women, 87% HbSS) in stable state enrolled consecutively between March 13, 2002 and June 8, 2017 were included for analysis. V/Q scan was abnormal in 65/142 (45.8%). CTPA was positive for pulmonary embolism in 16/60 (26.7%). RHC confirmed PH (mean pulmonary artery pressure (mPAP) ≥25mmHg) in 46/64 (71.9%), of which 34 (73.9%) had abnormal V/Q. Among those without PH by RHC ( = 18), 2/18 patients showed abnormal V/Q. Thirty-three patients had a complete dataset of V/Q, CTPA and RHC; 29/33 had abnormal RHC, of which 26/29 had abnormal V/Q compared to 11/29 with abnormal CTPA. There was a greater concordance of V/Q with RHC (kappa value =0.53; p<0.001) compared to CTPA with RHC (kappa value =0.13; = 0.065). The sensitivity and specificity for V/Q was 89.7% and 75.0% respectively, whereas CTPA had sensitivity 37.3% and specificity 100%. Abnormal V/Q was associated with hemodynamic severity (mPA = 35.2±9.6 vs. 26.9±10.5 mmHg, = 0.002; transpulmonary gradient 21.5±9.7 vs. 12.16±11mmHg, = 0.005, and pulmonary vascular resistance=226.5±135 vs.140.7±123.7 dynes.s.cm-5, = 0.013), and lower exercise capacity (6MWD 382.8±122.3 vs. 442.3±110.6m, p<0.010). Thirty-four deaths were observed over 15 years. All-cause mortality was higher in the abnormal V/Q (21(61.8%)) compared to normal V/Q (13(38.2%)) group (log-rank test, = 0.006, Hazard Ratio=2.54). V/Q scan is superior to CTPA in detecting thrombotic events in SCD. Abnormal V/Q is associated with PH, worse hemodynamics, lower functional capacity and increased mortality. Despite the high sensitivity of the V/Q scan in detecting CTEPH it is underutilized. We recommend the use of V/Q in the evaluation of dyspnea in SCD adults given the important implications in management.

Clinical phenotypes and outcomes of precapillary pulmonary hypertension of sickle cell disease

“…In our cohort, V/Q lung scintigraphy was frequently abnormal in this population as previously described [17], with a high frequency of mismatched segmental perfusion defects in SC patients. Similarly, a recent study observed that perfusion abnormalities on V/Q scintigraphy were associated with a higher proportion of PH [24]. In our present report, we have performed DSA in 18 patients, making it possible to identify two main patterns: patients with isolated poor subpleural perfusion and patients with lobar, segmental or subsegmental CTEPH lesions, as illustrated in figure 2.…”

Predicting risk factors for thromboembolic complications in patients with sickle cell anaemia – lessons learned for prophylaxis

“…However, it is difficult to conclude (from the current data), whether PE is a cause or a consequence of ACS. 28 It is believed that patients with SCA are more prone to infection as a result of immune impairment because of asplenia. 29 Infection, by promoting an increase in inflammatory cytokines, can provoke thrombosis, especially in asplenic patients.…”

Chronic blood exchange transfusions in the management of pre-capillary pulmonary hypertension complicating sickle cell disease

“…Chronic haemolysis may lead to depletion of nitric oxide (NO) and its precursors, thereby impairing vascular endothelial function [4][5][6]. A hypercoagulable state in SCD is promoted by several pathways, including NO depletion, platelet activation and functional asplenia, which could lead to in situ thrombosis [7][8][9]. A high cardiac output due to chronic anaemia may also induce endothelial dysfunction from flow-induced shear stress.…”