Sickle Cell Diastolic Cardiomyopathy and Mortality Risk: A Novel Echocardiographic Framework for Prognostic Stratification

Abstract

Cardiovascular complications are the leading cause of mortality in sickle cell anemia (SCA) patients. While extensive data have identified diastolic dysfunction (DD) to increase morbidity and mortality, the unique hemodynamic conditions inherent to SCA challenge the current recommendations to assess diastolic function. Thus, there is an urgent need to refine the echocardiographic definition of DD to improve risk stratification and therapeutic strategies in SCA patients. We analyzed data from the French multicentric Etendard cohort and compared them with an age- and sex-matched control group from the Copenhagen City Heart Study (CCHS). We focused on left ventricular diastolic parameters, specifically lateral e' velocity (e' lat), E/e' ratio, and indexed left atrial volume (LAVi), assessing their association with clinical outcomes over a 12-year follow-up. Etendard SCA patients (n = 379) had an early impaired diastolic function compared to the CCHS controls (n = 672). This was particularly obvious in young SCA patients (n = 252, age ≤ 38 years) in whom e' lat was associated with prognosis (p = 0.01), with an optimal cut-off value below 11 cm/s. Indeed, young SCA patients with DD had a fourfold increased 12-year mortality rate as compared with SCA patients without DD (16 vs. 4%, p < 0.001). Additionally, e' lat correlated with 6-min walk test, NT pro-BNP levels, diastolic blood pressure, and lactate dehydrogenase levels. In young SCA patients, our data contribute to refine the diagnosis of diastolic dysfunction evaluation. We highlight the prognostic value below 11 cm/s of lateral e' velocity and its association with key contributors of cardiac impairment such as hemolysis and systemic vasculopathy. Trial Registration: ClinicalTrials.gov identifier: NCT00434902.

Keywords: diastolic dysfunction; echocardiography; pulmonary hypertension; sickle cell disease.

FIGURE 1

Comparison of left ventricular diastolic function parameters between Etendard cohort and a matched subgroup of the Copenhagen City Heart Study. Panels A and B show e′ lat and LAVi evolution through age in both cohorts—Blue line refer as the limit of normal value in non‐SCA populations. Panels C–F compare value or distribution of diastolic function parameters across both cohors. *** stands for p < 0.001. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

(A) Kaplan–Meier curves with log rank analysis evaluating e′ lat ≤ 11 cm/s impact on 12‐year mortality. (B) 12‐year survival function plots with e′ lateral wave and 95% individual confidence interval. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Kaplan–Meier curves with log rank analysis evaluating e′ lat ≤ 11 cm/s impact on short term mortality in Drepacoeur cohort. [Color figure can be viewed at wileyonlinelibrary.com]