Pulmonary Haemodynamics in Sickle Cell Disease Are Driven Predominantly by a High-Output State Rather Than Elevated Pulmonary Vascular Resistance: A Prospective 3-Dimensional Echocardiography/Doppler Study

Abstract

Aims: Patients with sickle cell disease have significant morbidity and mortality. Pulmonary hypertension is suggested to be an important contributor but its nature and severity in these patients and how best to non-invasively assess it are controversial. We hypothesised that a high-output state rather than primary pulmonary vascular pathology may be the major abnormality in sickle cell disease. This study aimed to evaluate the characteristics and severity of pulmonary hypertension in patients with sickle cell disease using detailed echocardiography.

Methods and results: We undertook a prospective study in 122 consecutive stable outpatients with sickle cell disease and 30 age, gender and ethnicity-matched healthy controls. Echocardiographic evaluation included 3D ventricular volumes, sphericity, tissue Doppler, and non-invasive estimation of pulmonary vascular resistance. 36% of patients had a tricuspid regurgitant velocity ≥2.5 m.s(-1) but only 2% had elevated pulmonary vascular resistance and the prevalence of right ventricular dysfunction was very low. Patients with raised tricuspid regurgitant velocity had significantly elevated biventricular volumes and globular left ventricular remodelling, related primarily to anaemia. In a subgroup of patients who underwent cardiac catheterization, invasive pulmonary haemodynamics confirmed the echocardiographic findings.

Conclusions: Elevated cardiac output and left ventricular volume overload secondary to chronic anaemia may be the dominant factor responsible for abnormal cardiopulmonary haemodynamics in patients with sickle cell disease. 3D echocardiography with non-invasive estimation of pulmonary vascular resistance represents a valuable approach for initial evaluation of cardiopulmonary haemodynamics in sickle cell disease.

Fig 1. Scatter plots showing the distribution of values for echocardiographic parameters in SCD and control subjects.

LVEDVI, LV end-diastolic volume index; RVEDVI, RV end-diastolic volume index.

Fig 2. Correlation between echocardiographic estimates and invasive values of pulmonary haemodynamic parameters.

A) TRV versus mean PAP; B) PVR_echo versus PVR_RHC. In A, solid symbols denote patients with PVR_echo ≥ 2 Wood units. In B, solid symbols denote patients with TRV ≥ 3 m/s.