Unexplained Hypoxia and Shunting on Echocardiography in Patients with Sickle Cell Disease: A Retrospective Review

Introduction: During an episode of vaso-occlusive crisis, some patients with sickle cell disease may develop a transient hypoxemia. While frequently attributed to acute chest syndrome or pulmonary embolism, clinically a portion of patients develop hypoxemia without a clear etiology. On echocardiography, some patients were noted to have Patent Foramen Ovale (PFO) and others were noted to have intrapulmonary shunting. We sought to further characterize this clinical finding in sickle cell patients.

Methods: We conducted a single institution retrospective chart review from 2008 through 2015 to evaluate the incidence of pulmonary shunting and PFOs in patients with SCD, as demonstrated on an echocardiography. We further characterize each of these episodes with clinical and laboratory findings at the time of the event. The presence of absence of shunting and type of shunting was further verified by a single cardiologist reviewing all episodes. Kruskal-Wallis test or Fisher's exact test was used to compare characteristics between patients with intracardiac or intrapulmonary shunting.

Results: A total of 36 (18 female (F), 18 male (M)) of the 352 (10%) patients seen at the Ohio State Comprehensive Sickle Cell Center were noted to have shunting on their echocardiogram reported over the 7 year time period. Independent review by cardiology confirmed the presence of a shunt in 32 patients (9%, 95% CI: 6-13%) (15F, 17M). The median age at the time of reporting was 29 (range: 18-51 yrs). Shunting was observed in patients of all genotypes (94% SS/SB0; 6% SC/SBeta+). Fourteen (6 F, 8 M) of the thirty-two (44%, 95% CI: 26-62%) patients under study were noted to have cardiac shunting and eighteen (9 F, 9 M) (56%, 95% CI: 38-74%) were noted to have pulmonary shunting. In the patients with cardiac shunting, all 14/14 were confirmed to have a PFO by independent cardiac review. At the time of echo, 27/32 (87%) were hospitalized and 19/32 (59%) had clinical hypoxia on the day of the echocardiography. Patients with cardiac shunting tended to have higher proportion of hypoxia compared with patients with pulmonary shunting (71% vs. 50%). 19/32 (59%) had concurrent CT angiography and 1/32 (5%) patients was confirmed to have a pulmonary embolism. This patient demonstrated a concurrent PFO. 9 (28%) had a concurrent diagnosis of acute chest syndrome (4 with cardiac shunting and 5 with pulmonary shunting). The median value of TR jet velocity at baseline was 2.64 (range: 2.0-4.0) (n=18) and the median TR jet velocity at the time of event was 2.67 m/s (range: 2.0-3.8 m/s) (n=27). In the cardiac shunting group, the TR jet velocity was 2.85 m/s (range: 2.0 -3.27m/s) and in the pulmonary shunting group, the TR jet velocity was 2.6 m/s (range: 2.2-3.8 m/s).

Conclusion: Patients with SCD presenting with increasing hypoxia may have intracardiac or intrapulmonary shunting. A patent foramen ovale that opens during vaso-ossclusive crisis may cause transient hypoxemia. This opening is thought to be due to increasing pulmonary pressures. While the long term implications of this finding are currently being studied, intracardiac shunting should be considered in the differential of patients with SCD presenting with increasing hypoxia of unclear etiology.