Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease

Abstract

Objectives: The goal of this study was to characterize left ventricular diastolic function in the sickle cell disease (SCD) population and to relate echocardiographic measures of dysfunction with pulmonary hypertension and mortality.

Background: Pulmonary hypertension has been identified as a predictor of death in the adult SCD population. Although diastolic dysfunction is also observed in this population, its prevalence, association with high pulmonary artery systolic pressure, and attributable mortality remain unknown.

Methods: Diastolic function assessment using tissue Doppler imaging was performed in a group of 141 SCD patients. Conventional echocardiographic parameters of diastolic function were performed in a total of 235 SCD patients.

Results: Diastolic dysfunction was present in 18% of patients. A combination of diastolic dysfunction and pulmonary hypertension was present in 11% of patients, and diastolic dysfunction accounted for only 10% to 20% of the variability in tricuspid regurgitation (TR) jet velocity. Diastolic dysfunction, as reflected by a low E/A ratio, was associated with mortality with a risk ratio of 3.5 (95% confidence interval 1.5 to 8.4, p < 0.001), even after adjustment for tricuspid regurgitation (TR) jet velocity. The presence of both diastolic dysfunction and pulmonary hypertension conferred a risk ratio for death of 12.0 (95% confidence interval 3.8 to 38.1, p < 0.001).

Conclusions: Diastolic dysfunction and pulmonary hypertension each contribute independently to prospective mortality in patients with SCD. Patients with both risk factors have an extremely poor prognosis. These data support the implementation of echocardiographic screening of adult patients with SCD to identify high-risk individuals for further evaluation.

Figure 1. Prevalence of Diastolic Dysfunction in Sickle Cell Disease

(A) Distribution of patients with pulmonary arterial hypertension (PH) and diastolic dysfunction (DD). Venn diagram indicating the number of patients without PH (tricuspid regurgitation [TR] <2.5 m/s), with PH (TR ≥2.5) and tissue Doppler results indicating DD. (B) Detailed distribution by degree of PH and DD. The number of patients without or with mild, moderate, or severe DD are shown in groups based on their TR jet velocity (TR <2.5 m/s, TR 2.5 to 2.9 m/s, and TR ≥3 m/s). In the 2 high TR velocity groups, there were no patients with severe DD.

Figure 2. Kaplan-Meier Survival Curve According to Both TR Jet Velocity and E/A Ratio

Patients were classified as low risk if they had a tricuspid regurgitation (TR) jet velocity of <2.5 m/s and an E/A ratio of ≥1.0. The high-risk group of patients had either a TR velocity of ≥2.5 m/s or an E/A ratio of <1.0 or both. Mortality was significantly increased in the group having one or both risk factors (p < 0.0001).