Elevated Tricuspid Regurgitation Jet Velocity on Echocardiogram In Patients with Sickle Cell Disease Is Associated with Worse Steady State Functional Class, Poor Lung Function and Low Haemoglobin but Not Other Markers of Haemolysis or Endothelin-1.

Pulmonary hypertension (PH) in Sickle cell disease (SCD) is defined as a tricuspid regurgitation jet velocity ≥2.5 metres/second on trans thoracic echocardiogram. World health organisation functional class (WHO FC), a measure of physical limitation due to symptoms of PH (class 1–4, class 1 describing no symptoms with ordinary activity and class 4 describing symptoms with any physical activity) and diffusion capacity (DLCOc, KCO) are important tools in the management of non SCD patients with PH.

We have examined the association of WHO FC, lung function data, haemolytic and inflammatory markers in haemoglobin SS (HbSS) adults with PH (TRV≥ 2.5 m/s) and without PH (TRV < 2.5 m/s). Cytokines studied included interleukin 8 (IL-8), which may have a role in promoting adhesion of sickle red cells to vascular endothelium, stem cell factor (SCF), which acts on erythroid progenitor cells and endothelin-1, a potent pulmonary vasoconstrictor.

32 adult HbSS patients (median 37 years, range 20–59) were recruited at steady state defined as at least two weeks or more following an acute crisis. Serum levels of haemolytic and inflammatory markers, asymmetric dimethylarginine (ADMA a naturally occurring nitric oxide synthase inhibitor), ferritin, SCF and IL 8 were measured.

Results are given in table and expressed as mean ± standard deviation.

Of patients with PH 36% (5/14) were WHO FC ≥3 compared to 6% (1/18) without PH. There was a significant difference in functional class in patients with and without PH on echocardiogram (p< 0.05). There was a significant correlation between TRV and WHO functional class (p=0.002, r= 0.54). The correlation between TRV and functional class remained significant after correction for Hb.

Neither PH nor WHO FC was associated with parenchymal abnormalities or chronic sickle lung disease visible on CT and/or chest radiograph.

PH was also associated with a lower diffusion capacity (DLCOc mmol/min/kPa: 3.60 ± 0.79 vs. 7.60 ± 2.66, p=0.034) and a lower diffusion capacity corrected for alveolar volume (KCOc mmol/min/kPa/l: 1.04 ± 0.31 vs. 1.96 ± 0.3, p=0.034). TRV was significantly correlated with DLCOc only (p=0.036 r= -0.79).

Conclusion: PH in SCD is associated with lower haemoglobin and elevated ADMA but not other markers of haemolysis. Patients with elevated TRV also had a significantly higher WCC, IL 8 and SCF which would support the possible role of inflammatory mediated endothelial dysfunction in the pathogenesis of PH associated with SCD.

The elevated ferritin associated with patients with TRV ≥ 2.5 m/s may reflect cardiac dysfunction from iron overload as a cause of right heart dysfunction.

Although patients with SCD may have a number of reasons to account for their breathlessness, echo, WHO functional class and measurements of gas transfer may be useful markers in screening patients for pulmonary hypertension regardless of low steady state anaemia. This may allow early detection, treatment and reduction in mortality.

No relevant conflicts of interest to declare.