Cardiovascular Manifestations of Sickle Cell Disease

Nadjib Hammoudi; François Lionnet; Alban Redheuil; Gilles Montalescot

Disclosures

Eur Heart J. 2020;41(13):1365-1373. 

In This Article

Abstract and Introduction

Abstract

Sickle cell disease (SCD) is the most frequent genetic haemoglobinopathy worldwide. Early childhood mortality has dramatically decreased in high-income countries, and most patients now survive beyond the 5th decade. However, in the aging SCD population, the morbidity related to chronic organ damage, especially kidney and heart, has become a major concern. While pulmonary hypertension has attracted most attention, it appears that this condition is frequently linked to left heart failure (HF). Accordingly, SCD-associated cardiomyopathy is emerging as a major cause of reduced quality of life and early mortality in these patients. The diagnosis of this particular phenotype of high-output HF is challenging. Exercise intolerance and dyspnoea in SCD patients are linked to multiple causes including chronic anaemia. Moreover, echocardiographic features are unusual and can be misinterpreted. The classical diagnosis algorithm for HF is generally not suitable in SCD patients, and HF is poorly recognized and mostly diagnosed at a late congestive stage in routine practice. Such patients need to be identified at an earlier stage of myocardial dysfunction via improved phenotyping. This constitutes the first step towards further investigations in SCD needed to improve the prognosis and the quality of life. This article provides an updated review of the recent advances in the pathophysiology and diagnosis, and in addition, perspectives of new therapeutic approaches in SCD-related cardiac manifestations.

Introduction

Sickle cell disease (SCD) is one of the most common genetic disorders worldwide with over 300 000 children born with it every year.[1] Despite the fact that the disease is prevalent in sub-Saharan Africa, the Middle East, and India, SCD progressively spread to other regions of Europe and Americas[1] accelerated by higher global mobility.

The disease is caused by a mutation of the beta-globin gene inherited in an autosomal recessive way.[2] The diagnosis and genotype of SCD are based on haemoglobin electrophoresis from blood sampling. In western countries, newborns from parents at risk of the disease mostly benefit from early screening. Otherwise, the diagnosis should be highly suspected in patients coming from affected geographic areas in case of clinical symptoms or unexplained anaemia.

The pathophysiology of SCD includes a chronic haemolytic anaemia and red blood cells sickling because of acute haemoglobin polymerization with deoxygenation leading to repeated painful vaso-occlusive crises, endothelial cell dysfunction, inflammation, and tissue ischaemia–reperfusion injuries.[2]

Continued progress in medical care led to a dramatic reduction of the mortality rate in high-income countries during the last decades. At present, most SCD patients (>98%) live to adulthood.[3] Recent data showed that an estimated median survival rate was 67 years in homozygous patients.[4] However, this survival rate remains 15 years inferior to the life expectancy of the general population. The disease profile has changed over time, mostly due to vaccine therapy and antibiotics prophylaxis; therefore, acute severe infections are no longer the main cause of death.[5,6] According to contemporary studies, chronic progressive end organ damage with cardiac involvement has become the main cause of death affecting 20–32% of the patients.[5,7,8]

The heart involvement in SCD has multiple causes. Haemolytic anaemia induces a high-output state associated with cardiac morphological remodelling. While pulmonary hypertension (PH) has attracted most attention and was suspected to be caused mainly by pulmonary vasculopathy,[9] it appears that this condition is more complex and frequently secondary to left heart failure (HF).[10,11] Thus, functional alteration of the left ventricle (LV) is emerging as a major complication caused by the disease.[12] The diagnosis of SCD-associated cardiomyopathy representing a particular phenotype of HF with hyperdynamic state is challenging. Identifying myocardial alteration at an early stage and improving management of this complication is an important step to improve quality of life and survival rate of the patients.

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