Left atrial reservoir strain as a novel echocardiographic marker of diastolic dysfunction and mortality risk in sickle cell cardiomyopathy

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Abstract Background: Cardiac involvement is a leading contributor to premature mortality in sickle cell disease (SCD), yet the diagnosis of diastolic dysfunction (DD) remains challenging in this population. Conventional echocardiographic markers—such as tricuspid regurgitation velocity (TRV) or left atrial volume (LAV) often lack sensitivity or are confounded by anemia-driven hemodynamic adaptations. Left atrial reservoir strain (LA-SR), a preload-sensitive marker of left ventricular filling pressure, has emerged as a reliable surrogate of DD in heart failure, but has never been evaluated in SCD. Methods: We prospectively studied 150 adults with SS or Sβ⁰-thalassemia enrolled in the DREPACOEUR cohort, a multicenter initiative aimed at phenotyping sickle cell cardiomyopathy. All patients were in steady state and underwent comprehensive transthoracic echocardiography, including speckle-tracking imaging to quantify LA-SR (Figure). LA-SR was compared with LAV and correlated with conventional DD markers (lateral E’<11 cm/s, NT-proBNP>160 ng/L and TRV), renal function, hemolysis parameters, and hemoglobin concentration [Hb]. Prognostic performance was evaluated using ROC analysis and Cox regression. Results: Mean age was 44 ± 12 years; 51% were female and 82% received hydroxyurea. LA-SR correlated more strongly with diastolic function than LAV, including NT-proBNP (r = –0.51, p<0.001), E’ lat (r = –0.48, p<0.001), and eGFR (r = 0.44, p<0.001). Unlike LAV (r = –0.34, p<0.001), LA-SR was independent of hemoglobin levels, suggesting greater specificity for true diastolic impairment. An LA-SR threshold <26% identified patients with elevated NT-proBNP (AUC = 0.77) and impaired relaxation (E’<11 cm/s, AUC = 0.73), with sensitivity/specificity between 65–80%. Patients with LA-SR <26% were older (50 ± 10 vs. 39 ± 12 years, p<0.001), with more advanced DD (E/E’ = 8.7 ± 3.2 vs. 6.6 ± 2.2, p<0.001), higher TRV and LAV, and worse renal function. They also displayed more frequent atrial and ventricular ectopy. During a median 3.3 ± 1.2 years of follow-up, a LA-SR<26% was independently associated with all-cause mortality (OR=7, p=0.006), unlike TRV or LAV in this population. Conclusions: Left atrial reservoir strain offers incremental diagnostic and prognostic value over conventional echocardiographic parameters in sickle cell cardiomyopathy. Unlike LAV, which reflects both anemia and diastolic burden, LA-SR is not influenced by hemoglobin concentration, making it a specific and robust marker of DD. An LA-SR <26% identifies patients with early ventricular dysfunction and higher mortality risk, supporting its integration into routine SCD echocardiographic evaluation.

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