Unique nature of sickle sell diastolic cardiomyopathy: A tailored echocardiographic definition to refine prognostic stratification in young adults

Introduction

Cardiovascular complications are the leading cause of mortality in sickle cell anemia (SCA) patients. While cardiac diastolic dysfunction (DD) is a well-documented mechanism contributing to heightened morbidity and mortality, the unique hemodynamic conditions inherent to SCA pose challenges to the application of standard diastolic evaluation methods.

Objective

To date, there remains an absence of a suitable echocardiographic definition for early DD in SCA, which could significantly improve risk stratification and management strategies.

Method

To delineate the uniqueness of diastolic function parameters in SCA and propose an adapted echocardiographic definition of early SCA diastolic cardiomyopathy, we leveraged data from the French multicentric cohort Etendard alongside a matched subgroup from the Copenhagen City Heart Study (CCHS) cohort as control. Our investigation focused on early left ventricular (LV) diastolic impairment parameters, including e’ lateral wave (e’lat), E/e’ ratio, and indexed left atrial volume (LAVi), integrating hemodynamic data and 12-year prognostic outcomes. We then identified a young subgroup within Etendard cohort among which age exerted no impact on diastolic function parameters, facilitating the formulation of an adapted definition for early DD.

Results

SCA patients from the Etendard cohort (n = 379) exhibited significantly and early impaired diastolic function parameters compared to the matched CCHS subgroup (n = 672). Among younger SCA patients (n = 252, age ≤ 38 years), e’lat emerged as the sole independent diastolic parameter associated with prognosis (P = 0.01), with an optimal cutoff of 11 cm/s selected for prognostic stratification and further definition as DD (Se = 89%, Sp = 50%, AUC = 0.66, 95% CI = [0.52; 0.81], P = 0.01). Strikingly, young SCA patients with DD exhibited a fourfold higher 12-year mortality rate (16% vs. 4%, P < 0.001) (Fig. 1). Additionally, e’lat correlated with 6-minute walk test, NT pro-BNP levels, diastolic blood pressure, and lactate dehydrogenase levels. A three-year follow-up revealed a decline in 6MWT distance among the DD group and a trend toward higher tricuspid regurgitation velocity (TRV).

Conclusion

In young SCA patients, diastolic function evaluation requires dedicated definition. Lateral e’ wave demonstrates associations with key indicators of cardiac impairment, hemolysis, and systemic vasculopathy, with a value below 11 cm/s dramatically increasing 12-year mortality.