Unique Nature of Sickle Cell Diastolic Cardiomyopathy: A Tailored Echocardiographic Definition to Refine Prognostic Stratification in Young Adults

Background: 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. 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.

Methods: To refine the definition of diastolic dysfunction 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, marker or LV compliance), E/e’ ratio (hallmark of LV filling pressure), and indexed left atrial volume (LAVi). Then, a young subgroup within Etendard cohort was defined, among which age exerted no impact on diastolic function parameters, facilitating the formulation of an adapted definition for early DD. The 12-year prognosis was used to further define the optimal diastolic impairment definition.

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, mean age of 28±5 years, 57% females), e’lat emerged as the sole independent diastolic parameter associated with prognosis (p=0.01), with an optimal cut-off value of 11 cm/s selected for prognostic stratification and further defined as DD (Se=89%, Sp=50%, p=0.01). Strikingly, young SCA patients with DD exhibited a fourfold higher 12-year mortality rate (16 vs. 4%, p<0.001), mainly from cardiovascular causes. Consistantly with previous studies, e’lat (i.e diastolic function) correlated with 6-minute walking test (6MWT), NT pro-BNP levels, diastolic blood pressure, and lactate dehydrogenase levels. Three-year follow-up revealed a decline in 6MWT distance among the DD group, a more important GFR drop and a trend toward higher tricuspid regurgitation velocity.

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