Cardiovascular Manifestations of Sickle Cell Disease

Nadjib Hammoudi; François Lionnet; Alban Redheuil; Gilles Montalescot


Eur Heart J. 2020;41(13):1365-1373. 

In This Article

Gap in Knowledge and Perspectives

Screening of Cardiac Manifestations

At present, echocardiography is recommended for routine follow-up of all SCD patients regardless of genotype.[46] Considering the compelling evidence showing only mild cardiac involvement in patients with haemoglobin SC disease, echocardiography examination might be limited in this genotype to high-risk patients including those with symptoms[38] and/or with comorbidities.[13]

Considering the cost and the risks related to invasive procedures, it is recommended to perform right heart catheterization as a second line diagnosis method in patients at higher risk of PH defined by a peak TRV ≥3 m/s, or in patients with a TRV between 2.5 and 2.9 m/s with a clinical scenario suggesting PH especially in those with low exercise capacity and/or high NT-proBNP.[46]

The feasibility of TRV assessment is relatively good, knowing however, that this parameter cannot be recorded in 5–29% of the cases.[22,43,57,68] Undetectable TRV could not safely exclude PH[69] and other non-invasive indices should be considered.[41] Importantly, it is well established that using peak TRV as a single parameter with fixed unique threshold at 2.5 m/s for screening PH in SCD patients is associated with a low positive predictive value.[10,11] For ultrasound estimation of PH probability, the use of the ESC guidelines algorithm based on the combination of peak TRV value with additional echocardiographic variables including the analysis of right ventricular morphology should be encouraged.[41] The use of gender, age, and body mass index normal reference ranges rather than a fixed TRV cut-off to screen PH appears interesting in SCD patients and deserves further studies.[43] Finally, pulmonary vascular resistances, estimated non-invasively from TRV and right ventricular stroke volume ratio is promising in these high-output SCD patients.[21,43]

Early Diagnosis of High-output Heart Failure

The diagnosis of high-output HF is not straightforward especially at an early stage[52,56] and could be missed by resting investigations (i.e. echocardiography and/or right heart catheterization).[70] However, invasive low-level exercise testing have demonstrated relevance for the diagnosis of early stage HF which is characterized by exercise-induced LV filling pressure elevation despite normal resting value.[52,56] In SCD patients with clinical suspicion of HF, low-level invasive exercise testing should be considered when measurements at rest are inconclusive, specifically in those with exercise symptoms without history of congestion or those taking diuretics at the time of the investigation (Supplementary material online, Figure S2).

The combination of stress echocardiography with simultaneous measure of expired gas analysis has also emerged in recent years as a valuable method to diagnose early stage HF.[71] This non-invasive procedure allowing a thorough analysis of all the potential mechanisms involved in exercise intolerance is interesting for the evaluation of SCD patients.

Future Therapies

Mineralocorticoid inhibitors may be useful at an early stage of LVDD due to their anti-fibrotic effects. Training could help enhance exercise tolerance in SCD patients similar to patients with other phenotype of HF.[39,72]

Haematopoietic stem cell transplantation represents a curative therapy for SCD. However, this treatment can be used only in selected patients due to risks linked with the procedure and relatively small donor pool.[3] Gene therapy has emerged as the latest promising therapeutic approach in patients suffering from inherited haemoglobinopathies. The efficiency and safety of gene therapy have been demonstrated in patients with transfusion-dependent β-thalassaemia.[73] After successful pre-clinical studies a good clinical response was reported in a first SCD patient[74] and several clinical trials are currently underway.[75]