Skeletal and myocardial microvascular blood flow in hydroxycarbamide‐treated patients with sickle cell disease

Abstract

In sickle cell disease (SCD), abnormal microvascular function combined with chronic anaemia predisposes patients to perfusion-demand mismatch. We hypothesized that skeletal muscle and myocardial perfusion, normalized to the degree of anaemia, is reduced at basal-state compared to controls, and that this defect is ameliorated by hydroxycarbamide (HC; also termed hydroxyurea) therapy. Twenty-one SCD patients, of whom 15 were treated with HC, and 27 controls underwent contrast-enhanced ultrasound (CEU) perfusion imaging of the forearm as well as the myocardium. HC treatment was associated with lower white cell and reticulocyte counts, and higher fetal haemoglobin and total haemoglobin levels. When corrected for the degree of anaemia in SCD patients, skeletal flow in HC-treated patients was significantly higher than in untreated SCD patients (217.7±125.4 vs 85.9±40.2, p=0.018). Similarly, when normalized for both anaemia and increased myocardial work, resting myocardial perfusion was also significantly higher in HC-treated patients compared with untreated SCD patients (0.53±0.47 vs 0.13±0.07, p=0.028). Haemoglobin F (HbF) levels correlated with skeletal muscle microvascular flow (r=0.55, p=0.01). In conclusion, patients with SCD not on HC therapy have resting flow deficits in both skeletal muscle and myocardial flow. HC therapy normalizes flow and there is a direct correlation with HbF levels.

Contrast-enhanced ultrasound detects changes in microvascular blood flow in adults with sickle cell disease

“…After a destructive pulse is delivered, the intravascular replenishment of the microbubbles provides data about MBF and its components, microvascular blood volume and flux velocity [14,15]. In this study, we extend findings by members of our research team that previously demonstrated the ability of CEUS to detect an increase in MBF between SCD patients treated with hydroxyurea compared to those without hydroxyurea [16]. We evaluated the ability of CEUS to detect changes in MBF in forearm skeletal muscle: 1) in SCD patients during vaso-occlusive crisis and after recovery, as a proof-of-concept to demonstrate the ability to detect dynamic perfusion abnormalities; and 2) sequentially in subjects undergoing an infusion of regadenoson, an adenosine A 2A agonist that has been investigated as a therapy for SCD.…”

“…An imbalance between vasoconstrictor and vasodilator compounds, impaired rheology, microvascular thrombosis, and even anemia itself could all affect perfusion. To this last point, a recent study performed in patients with SCD under steady state conditions found that the true extent of their perfusion abnormality was only apparent after correcting for hemoglobin [16], which was why we corrected for anemia in this study as well.…”

Contrast Enhanced Ultrasound Perfusion Imaging in Skeletal Muscle

“…CEU perfusion imaging studies have investigated whether these mechanisms lead to overt hypoperfusion of key tissues, such as the myocardium or skeletal muscle. In one study, forearm muscle and myocardial perfusion in SCD patients, some of whom were treated with hydroxycarbamide (HC), was compared with that of control subjects 37). When corrected for the degree of anemia in SCD patients, skeletal muscle blood flow in HC-treated SCD patients was similar to that of control subjects and significantly higher than that of untreated SCD patients.…”

Myocardial injury and coronary microvascular disease in sickle cell disease

“… 14 In a recent study evaluating the effect of hydroxyurea on skeletal and cardiac muscles, SCD patients treated with hydroxyurea had higher resting myocardial perfusion as compared to those without hydroxyurea. 15 Newer therapies that target Hb modification could also have a role in the management, but prospective trials are needed to assess the effectiveness of various treatment strategies. We suggest that cardiac MRI with stress testing can be considered as a screening tool for patients with evidence of myocardial damage and recurrent chest pain.…”