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


SCD is a complex condition, the disease severity and end organ damage widely vary from one patient to another and clinical management must be adjusted on a case-by-case basis. The therapeutic strategies have a low evidence level and are mostly based on expert consensus. Thus, the management of SCD require a collaborative approach involving haematologists, cardiologists, nephrologists, and other specialists with high expertise of SCD-related complications (Figure 5).

Figure 5.

Principles of managing high-output heart failure in homozygous S patients. HSC, haematopoietic stem cell transplantation.

Cardiovascular Medications

Loop diuretics constitute the most used symptomatic treatment of congestion.[39] As clinical presentation is often right-sided HF, the association with mineralocorticoid antagonists can be useful to improve decongestion when renal function allows it.[39] In our experience, these medications are generally effective and well tolerated. However, due to the increased risk of dehydration and potentially related vaso-occlusive crises, diuretics should be prescribed at the lowest needed dose.

There is no data suggesting an improved prognosis with any cardiovascular drug in SCD patients with HF. However, in accordance with the current HF guidelines, the inhibition of renin–angiotensin–aldosterone system should be considered in the few SCD patients with LV systolic dysfunction.[39] In a study investigating the impact of angiotensin converting enzyme inhibitors on SCD-related nephropathy, this drug seems in secondary analyses to reduce peak TRV.[37]

Platelet activation has been implicated in the complex pathophysiology of acute vaso-occlusive episodes; however, antiplatelet agents were not proven effective in a randomized study.[63] There is no evidence supporting the use of these drugs in primary prevention of SCD cardiovascular complications.

Two clinical trials of agents targeting pulmonary arterial hypertension have been disappointing in SCD. However, these drugs can be discussed in selected patients with invasively proven pre-capillary PH.[46]

Sickle Cell Disease-targeted Therapy

Hydroxyurea therapy could reduce intracellular haemoglobin S polymerization. Randomized trials have demonstrated a beneficial effect on reducing sickling episodes as well as transfusion requirements in homozygous patients. Hydroxyurea therapy was also associated with better survival in these patients, however, conflicting results were reported in observational studies investigating the impact of this drug on cardiac function.[9,15,64,65] Waiting further prospective controlled data, it is currently recommended to consider hydroxyurea in patients with increased mortality risk as defined by peak TRV >2.5 m/s, NT-proBNP >160 pg/mL, or invasively confirmed PH.[46] Hydroxyurea could also be considered on a case-by-case basis in homozygous patients with congestive HF.

It was reported in small case series that high-output HF related to anaemia could be completely reversed by blood transfusion.[20] In addition, blood exchange transfusion could increase SCD exercise capacity[26] and reduce pulmonary pressure.[66,67] The use of transfusion should take into account related potential risks including the frequent erythrocyte allo-immunization.[2] In the absence of definitive data, chronic transfusion can only be discussed on an individual basis after a careful evaluation of the risk/benefit ratio. It is currently recommended to consider transfusion as an alternative therapy in patients at high mortality risk who are not responding to hydroxyurea.[46]

In haemoglobin SC patients, iron restriction induced by phlebotomy decreases the blood viscosity. This therapy should be considered in symptomatic patients with high haemoglobin level, especially in those with history of venous thromboembolism.[14]

Comorbidities and Risk Management

The identification of comorbidities is important to optimize care for SCD patients. For instance, weight loss should be advised to obese patients as extra weight contributes to exercise intolerance and could lead to LVDD.[39,57] In the same way, systemic arterial hypertension and renal failure should be diagnosed at an early stage and managed adequately.[37]