Tricuspid Regurgitation Velocity Linked to Cerebrovascular, Kidney Disease in SCD

Chibuzo Ilonze, MD

Credit: University of Alabama at Birmingham

Approximately 1 in 5 children with sickle cell disease (SCD) in two large clinical cohorts experienced elevated tricuspid regurgitation velocity (TRV), a surrogate marker for pulmonary hypertension, according to new research.¹

Evidence from the cross-sectional, multi-center study revealed pediatric patients with a history of chronic kidney disease (CKD) and cerebrovascular disease demonstrated a higher prevalence of abnormal TRV, suggesting the need for an echocardiogram in clinical assessment.

“Our findings suggest that adolescent patients may benefit from universal echocardiography performed at steady state if they have been identified with either cerebrovascular disease or albuminuria,” wrote the investigative team, led by Chibuzo Ilonze, MD, division of pediatric hematology and oncology, University of Alabama at Birmingham (UAB).

Determining those at risk for multi-organ disease progression can be crucial for initiating appropriate disease-modifying therapies in young patients with SCD.² Clinical guidelines in SCD provide screening suggestions for the development of end-organ disease—however, the American Society of Hematology (ASH) and American Thoracic Society (ATS) have differing recommendations for screening echocardiogram for pulmonary hypertension.^3,4

The evidence-based ASH guideline suggests against screening echocardiograms in the absence of cardiopulmonary symptoms, abnormal cardiac examination, or history of pulmonary embolism.³ However, both guidelines admit elevated TRV is associated with early mortality in adults, suggesting more evidence is required to support or refute the role of echocardiograms as a screening tool for pediatric patients at risk of pulmonary hypertension.^3,4

For this analysis, Ilonze and colleagues sought to measure the associations between multi-organ dysfunction in children with SCD aged 1–21 years across two large sickle cell cohorts from 2012 to 2022.¹ The team hypothesized children with SCD, and abnormal surrogate markers of pulmonary hypertension (≥2.5 m/s) would have increased odds of having either cerebrovascular disease or CKD.

Children were recruited from the UAB sickle cell cohort and the Sickle Cell Clinical Research and Intervention Program (SCCRIP) cohort at St. Jude Children’s Research Hospital. A total of 204 patients with SCD received care at the comprehensive sickle cell center at UAB and 166 participants were included for analysis. A total of 1,300 patients were identified in the SCCRIP cohort at St. Jude’s and 325 children completed ≥1 echocardiogram between 2009 - 2019.

These cohorts were combined for 491 children with an echocardiogram performed at a steady state. Together, the prevalence of elevated TRV was 21% (n = 104) in both the UAB and SCCRIP cohorts. The SCCRIP cohort was comparable to the UAB cohort in age, sex, and the prevalence of elevated TRV and persistent albuminuria, but the UAB cohort exhibited a higher statistical prevalence of cerebrovascular disease (55% vs. 42%; P = .008).

Among 104 participants with elevated TRV and cerebrovascular disease assessments, 61% had a history of cerebrovascular disease, correlating with higher odds of elevated TRV than those without history. After controlling for age, sex, SCD-modifying therapy, and site, elevated TRV was significantly associated with greater odds of cerebrovascular disease (odds ratio [OR], 1.88; 95% CI, 1.12 - 3.15; P = .017).

Among 88 individuals with elevated TRV and multiple albumin–creatinine ratio measurements, 36% demonstrated persistent albuminuria, suggesting higher odds of persistent albuminuria than those without elevated TRV. After controlling for age, sex, SCD-modifying therapy, and site, elevated TRV was associated with higher odds of persistent albuminuria (OR, 1.81; 95% CI, 1.07 - 3.06; p = .028).

Ilonze and colleagues indicated these findings provide evidence that children with a history of CKD and cerebrovascular disease exhibit a higher prevalence of abnormal TRV. They noted pediatric sickle cell providers may consider performing echocardiograms in children with these additional comorbidities.

“These data provide additional evidence needed to support future guideline statements for screening echocardiography,” they wrote.¹ “Furthermore, we identified that elevated TRV is more prevalent in adolescent patients, which may reflect early signs of accumulated cardiovascular complications in older children.”

References

1. _{Ilonze C, Rai P, Galadanci N, et al. Association of elevated tricuspid regurgitation velocity with cerebrovascular and kidney disease in children with sickle cell disease. Pediatr Blood Cancer. Published online April 21, 2024. doi:10.1002/pbc.31002}
2. _{DeBaun MR, Kirkham FJ. Central nervous system complications and management in sickle cell disease. Blood. 2016;127(7):829-838. doi:10.1182/blood-2015-09-618579}
3. _{Liem RI, Lanzkron S, D Coates T, et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease [published correction appears in Blood Adv. 2023 Jul 25;7(14):3530]. Blood Adv. 2019;3(23):3867-3897. doi:10.1182/bloodadvances.2019000916}
4. _{Klings ES, Machado RF, Barst RJ, et al. An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease. Am J Respir Crit Care Med. 2014;189(6):727-740. doi:10.1164/rccm.201401-0065ST}