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

Pulmonary Hypertension

Initial studies using echocardiography to measure peak tricuspid regurgitation velocity (TRV) as an index of systolic pulmonary artery pressure demonstrated a high prevalence (≈30%) of PH in SCD patients.[9,38] On the contrary, recent reports using right heart catheterization have found a lower PH prevalence ranging from 6% to 10% in adult patients.[10,11,40]

Due to the complex pathophysiology involving multiple mechanisms and haemodynamic singularities, the PH related to SCD has been moved from Group 1 (i.e. pulmonary arterial hypertension) to Group 5 (i.e. unclear and/or multifactorial mechanisms) in the recent ESC guidelines.[41] In fact, SCD patients with PH demonstrate features of post-capillary PH due to left HF in half of the cases and pre-capillary PH phenotype in the other half (Table 2, Figure 4, and Supplementary material online, Video S5).[10,11,40] Furthermore, compared to the classic Type 1 PH patients, SCD subjects with pre-capillary PH exhibit a different haemodynamic profile including a remarkably lower level of pulmonary vascular resistances and pulmonary pressure as well as higher cardiac output.[10,11,41] The further subclassification of post-capillary PH in isolated post-capillary and combined post-capillary and pre-capillary PH was rarely described in clinical studies. Although combined post-capillary and pre-capillary PH could be observed in SCD patients,[42] data are lacking regarding the prevalence of this haemodynamic profile.

Figure 4.

Representative clinical scenarios in patients with homozygous S sickle cell disease. Case 1, adaptive cardiac remodelling; Case 2, pre-capillary pulmonary hypertension; Case 3, post-capillary pulmonary hypertension; and Case 4, cardiac magnetic resonance diagnosis of transmural myocardial infarction in the absence of coronary artery disease. Supplementary material online, Videos S5–S9. CMR, cardiac magnetic resonance; IVS, interventricular septum; LV, left ventricle; mPAP, mean pulmonary artery pressure; MVO, microvascular obstruction; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistances; TRV, tricuspid regurgitation velocity.

SCD-related PH involves several mechanisms. First, as pulmonary pressure is the product of flow and pulmonary vascular resistances, high cardiac output in SCD induces elevated pulmonary pressure whether pulmonary vascular resistances are altered or not.[21,43] Second, chronic volume overload might lead to LV failure and subsequent pulmonary venous hypertension.[10,11] Third, intravascular haemolysis could induce pulmonary arterial vasculopathy mainly driven by nitric oxide scavenging due to free plasma haemoglobin.[44] Finally, several other mechanisms may participate including, chronic hypoxaemia, post-embolic PH, SCD-related lung injury, chronic liver disease, and asplenia (Supplementary material online, Table S1).[9,44,45] Importantly, several of these factors are often present simultaneously in a same SCD patient who suffers from PH. This represents a major challenge for clinical care management of the disease.

PH is associated with altered exercise tolerance and higher mortality in adult SCD patients.[9,10,38,40] However, the causality between PH, even if invasively proven, and worse prognosis is still debated as the link between PH and premature death could also reflect the severity of the underlying SCD.[10,11] Accordingly, PH is considered as a marker of risk rather than an aetiology of poor outcomes in SCD patients.[46] The relative high prevalence of pulmonary venous hypertension among SCD patients with PH underscores the need for a better understanding and an early diagnosis of LV dysfunction.