Evaluating High-Sensitivity Troponin Levels in Patients with Sickle Cell Disease Presenting to the Emergency Department

Background: Sickle cell disease (SCD) is the most common, inherited blood disease in the US. Pain due to vaso-occlusive crisis is the most common reason for emergency department (ED) visits however, SCD also causes multiple organ complications and increases the risk for early mortality. Recent data published from the Sickle Cell Disease Implementation Centers¹ revealed an increase in cardiac death in adults with SCD (18%) compared to earlier data. As individuals with SCD are now routinely surviving into adulthood, it is necessary to better understand their cardiac risk. Cardiac troponin I (cTnI) and troponin T (cTnT) are specific myocardial injury markers used for acute coronary syndromes. However, their utility in SCD is uncertain due to possible elevation without acute coronary events.

The Universal Definition of Myocardial Infarction requires evidence of an elevated troponin (at least one value> 99^th %tile) and 1 sign of myocardial injury². The 99^th %tile is sex-specific (males>females). In the ED, initial troponin levels are drawn to rule out cardiac injury followed by serial assessments if elevated and additional work-up as warranted. However, some people can have elevated troponin levels below the 99^th%tile in absence of identifiable cardiac injury for unclear reasons. To understand the association of elevated high sensitivity cardiac troponin I (hs-cTnl) with clinical outcomes in SCD, we evaluated a large cohort of adult patients with SCD seen in the ED.

Methods: This was an IRB-approved retrospective study of adults with SCD presenting to the ED at an academic center over a 24 month period (6/2021-5/2023). All patients included had confirmed SCD. Patients were identified using SCD surveillance data and included those with an ED visit at the center in this time-period who had a least one hs-cTnI level.

Results:

There were 1,229 patients with SCD seen in the ED over 24 months and 524 (42.6%) had hs-cTnI measured. At the initial blood draw 373 (71.18%) had elevated hs-cTnl levels (3-848 ng/L). Patients were divided into 3 groups based on hs-cTnl results: Not detected (Group 1), >1ng/L but below the 99^th %tile (Group 2), and hs-cTnl >99^th percentile for sex (males>20 ng/L, females>15 ng/L) (Group 3). In this cohort, 151 people (29%) were in group 1, 334 people (63.7%) were in group 2 and 39 people (7.4%) were in group 3 with concerning levels. Only 1 person (3%) in group 3 was diagnosed with myocardial infarction (MI).

Heart failure was most seen in patients in group 3 (14 (36%). There were no differences in the number of patients with a diagnosis of heart failure between groups 1 and 2. Increased age was associated with higher levels of hs-cTnl (p<0.01) consistent with findings in adults without SCD. There were no differences between groups 1 and 2 in hydroxyurea use (85% in group 1 and 83% in group 2), crizanlizumab (30% and 28%), or voxelotor (3% and 4%) use. There was a significant difference in mean hemoglobin between group 1 and groups 2 and 3 [10.1g/dl (1.9) in group 1, 9.2g/dl (1.8) in group 2 and 9.2g/dl (2.6) in group 3, P<.01]. People in group 2 with elevated troponin levels<99^th %tile were not diagnosed with MI or NSTEMI but more frequently required admission for uncontrolled pain compared to those in group 1 (42% vs 27%). People in group 3 were most frequently admitted (85%) but this was due to several reasons including persistent and/or for cardiac observation in others.

Conclusions:
There are several learning points from these data. First, even in the group 3 patients with high initial hs-cTnl, there was a low incidence of MI or NSTEMI. However, individuals in this group were more likely to have a history of heart failure suggesting that higher troponin levels may indicate subclinical myocardial injury in people with SCD rather than acute coronary syndrome. More people with SCD had elevated hs-cTnl levels (group 2) that were <99^th %tile but were above normal compared to a non-SCD population. The cause of these elevations is not known but could be due to hypoxia or vaso-occlusion that did not result in measurable cardiac injury or evidence of early (not yet diagnosed heart failure).

A longitudinal prospective study is needed to assess whether high sensitivity troponin may indicate vaso-occlusion in SCD or predict subclinical cardiac findings. Research should explore integrating troponin measurement with other biomarkers and imaging for comprehensive cardiac health assessment in SCD.