Elevated tricuspid regurgitation velocity in congenital hemolytic anemias: Prevalence and laboratory correlates

Abstract

Elevated tricuspid valve regurgitation jet velocity (TRV ≥ 2.5 m/s) is associated with mortality among adults with sickle cell disease (SCD), but correlative biomarkers are not studied according to treatment exposure or genotypes. To investigate the associations between biomarkers and TRV elevation, we examined the relationship between TRV and hemolytic, inflammatory, and cardiac biomarkers, stratified by disease‐modifying treatments and SCD genotype. In total, 294 participants with SCD (mean age, 11.0 ± 3.7 years) and 49 hereditary spherocytosis (HS; mean age, 22.9 ± 19.75 years) were included for comparison and enrolled. TRV was elevated in 30.7% of children with SCD overall: 18.8% in HbSC/HbSβ+‐thalassemia, 28.9% in untreated HbSS/HbSβ0‐thalassemia, 34.2% in HbSS/HbSβ0‐thalassemia hydroxyurea‐treated, and 57% in HbSS/HbSβ0‐thalassemia chronic transfusion treated. TRV was elevated in 10.7% and 27.8% in HS children and adults, respectively. In children with SCD, elevated TRV was correlated with hemoglobin (odds ratio [OR] = 0.78, P = 0.004), lactate dehydrogenase (LDH; OR = 2.52, P = 0.005), and N‐terminal pro‐brain natriuretic peptide (NT‐pro BNP; OR = 1.003, P = 0.004). In multivariable logistic regression, adjusting for genotype, sex, hemolytic index, and treatment, hemoglobin concentration remained the only significant variable associated with elevated TRV in untreated HbSS/HbSβ0‐thalassemia participants. TRV was not associated with inflammatory markers, other markers of hemolysis, or NT‐pro BNP in untreated HbSS/HbSβ0‐thalassemia. Neither hemoglobin nor LDH was associated with TRV in HbSC/HbSβ+‐thalassemia. These results suggest that elevated TRV is influenced by the degree of anemia, possibly reflecting sickling as part of the disease pathophysiology. Prospective studies should monitor hemoglobin concentration as children with SCD age into adulthood, prompting initiation of TRV screening and monitoring.

Longitudinal analysis of cardiac abnormalities in pediatric patients with sickle cell anemia and effect of hydroxyurea therapy

“…The prevalence in our cohort is somewhere in-between these 2 reported values, given that the mean age of our study population was 12.0 ± 4.9 years. A recent study by Yates et al 25 reported a similar prevalence of elevated TR in their study group with a mean age of 11.0 ± 3.7 years. In our HU treatment group, there was a significant improvement in the number of patients with elevated TR from baseline to last visit (37% of patients with elevated TR at baseline, 11% of patients with elevated TR at last visit).…”

Tricuspid regurgitation velocity and other biomarkers of mortality in children, adolescents and young adults with sickle cell disease in the United States: The PUSH study

“…Some studies have found that a higher TRV cut‐off of 3.0 m/second is more strongly associated with mortality than the 2.5 m/second cut‐off 38,39 . The definition of elevated TRV of ≥2.5 m/second has been adopted for studying children with SCD, 25‐29 although it is not clear that the same definition of elevated TRV would apply to both adults and children. The PUSH study enrolled a non‐SCD control group contemporaneous with the SCD patients, and we utilized this control group to define an elevated TRV to be ≥2.7 m/second, or more than 2 SD above the mean in non‐SCD controls.…”

“…30,[35][36][37] Some studies have found that a higher TRV cut-off of 3.0 m/second is more strongly associated with mortality than the 2.5 m/second cut-off. 38,39 The definition of elevated TRV of ≥2.5 m/second has been adopted for studying children with SCD, [25][26][27][28][29] although it is not clear that the same definition of elevated TRV would apply to both adults and children. [41][42][43] Serum ferritin also increases with inflammation or with hepatocellular damage in the absence of increased iron stores.…”

“…Most studies of children and adolescents with SCD have defined an elevated TRV to be ≥2.5 m/second, [25][26][27][28][29] but this cut-off represents 2 SD above the mean value in adult rather than pediatric non-SCD controls. 30 For the present study, we performed echocardiograpy in 75 control children without SCD, 67 of whom had a measurable TRV.…”

Longitudinal effect of disease-modifying therapy on tricuspid regurgitant velocity in children with sickle cell anemia

“…Our group recently showed that, in individuals with HbSS or HbSb 0 thalassemia not on disease-modifying therapies (DMTs), TRV elevation was strongly influenced by the degree of anemia. 22 Use of DMTs, such as hydroxyurea and chronic erythrocyte transfusions, have impacted the natural history of SCA by improving laboratory parameters of anemia and hemolysis, preventing acute complications, and preserving organ function. [23][24][25][26][27][28][29][30] However, data regarding their effect on TRV are conflicting.…”