Variability in Repeat Tricuspid Regurgitation Velocity Among Children with Sickle Cell Disease

Background:

Patients with sickle cell disease (SCD) can suffer early mortality from end-organ diseases including pulmonary hypertension. Elevated tricuspid regurgitation velocity (TRV) ≥ 2.5 m/s, measured by echocardiography, is a surrogate marker of pulmonary hypertension. Elevated TRV is associated with increased risk of mortality in adults and should be confirmed by performing a right heart catheterization. However, performing a right heart catheterization in pediatrics is invasive, costly, and not widely accepted. In contrast, echocardiography is safe, endorsed by sickle cell guidelines in patients with cardiopulmonary symptoms, and readily available for pediatric patients. Prior studies of pulmonary hypertension have used a single TRV measurement; however, it is unclear if patients with a single TRV ≥ 2.5 m/s or repeated elevated TRV measurements define the highest risk population. In this study, we assessed the reliability of TRV measurements in multiple echocardiograms. Second, we examined the associations between persistently elevated TRV (two TRV measurements ≥ 2.5 m/s) with history of cerebrovascular disease (CVD).

Methods:

We performed an IRB-approved retrospective study to evaluate the reliability of TRV measurements among pediatric patients (1-21 years of age) with sickle cell disease (HbSS or HbSbeta0 thalassemia) and 2 echocardiograms that were performed at steady state. We defined elevated TRV as ≥ 2.5 m/s. We categorized participants with persistently elevated TRV if ≥ 2.5 m/s on two measurements. Next, we compared differences in outcomes for CVD by whether participants had persistently elevated TRV as compared to two normal TRV, or one of two abnormal TRV measurements. Cerebrovascular disease was defined as either 1) an overt stroke, 2) silent cerebral stroke defined by MRI, 3) vasculopathy by abnormal magnetic resonance angiography (MRA), 4) transient ischemic event defined by stroke symptoms that resolved within 24 hours, or 5) abnormal TCD (>200 cm/second). We performed Chi-square test between TRV and CVD. All reported P values were 2-sided. Statistical significance was defined as p < 0.05. All analyses were performed using JMP Pro 16.

Results:

We identified 166 pediatric patients with SCD with at least one transthoracic echocardiogram. 61 participants had only one echocardiogram and 71 participants had completed two echocardiograms. Among 166 participants, 35 (21%) had an elevated TRV on their first echocardiogram, and 131 (79%) participants had normal TRV <2.5 m/s. Among 21 participants with a first elevated TRV who had a second echocardiogram, TRV remained elevated in 9 (43%) participants and normalized in 12 57%) participants. Among 50 participants with a first normal echocardiogram, only 3 (6%) out of 50 participants had elevated TRV on their second echocardiogram. We also identified four participants with two initial TRV <2.5m/s who were abnormal on a third echocardiogram.

Forty-three (61%) of 71 participants with two echocardiograms had a history of CVD. Among 47 participants with two normal echocardiograms, 25 (53%) participants had a history of CVD. 10 (66%) out of 15 participants with one abnormal echocardiogram had a history of CVD. Finally, 8 (89%) out of 9 participants with two abnormal echocardiograms had a history of CVD (p=0.09).

Conclusion:

Measurement of TRV by echocardiogram can vary due to operator skill and competence, intra-patient variability, and interpretation by the physician. Our data suggests that performing a second echocardiogram may enhance risk stratification for morbidity among patients with an elevated TRV on echocardiogram.

Lebensburger:Pfizer: Consultancy; Novartis: Consultancy; Agios: Consultancy.