Reply: Against Another Nonspecific Marker of Perfusion.

From the Authors:

We appreciate the comments from Sibua and Farkas (1) regarding our recent editorial (2). We agree that the mechanisms contributing to elevations of high-sensitivity cardiac troponin I (hs-cTnI) are likely multiple and, as we highlighted, are unlikely to represent ischemic acute coronary events for the vast majority of patients. As an observational study, the MARS (Molecular Diagnosis and Risk Stratification of Sepsis) cohort is not designed to address the mechanism of troponin release; causal inference methodology could be applied if this were the goal and would offer, at best, indirect evidence to support or refute the mechanism. We likewise agree that hs-cTnI may function as a mortality indicator or risk stratification tool rather than specifically indicating cardiac risk, though we note that cardiac events are common in adults, both during and after a sepsis episode (3, 4). Furthermore, because the gene encoding cardiac troponin I protein is exclusively expressed in cardiac muscle (5), this marker is specific for cardiac injury, though cellular mechanisms beyond myonecrosis may contribute to the protein’s release (6).

Sibua and Farkas disagreed with our characterization of hs-cTnI as a potential indicator of inadequate cardiac perfusion and particularly with our rhetorical question of whether hs-cTnI could be applied to guide patient management in the future. A caution against targeting therapy to hs-cTnI decline is valid, noting that a sepsis resuscitation strategy targeting lactate clearance was not superior to one targeting restoration of capillary refill time (7), and there is no evidence warranting a change in clinical practice. We advised against a misinterpretation of elevated hs-cTnI as a marker of cardiac ischemia and highlighted the potential for overuse of cardiac testing as a result. However, we maintain that hs-cTnI may provide information about cardiac organ injury that is not captured by the Sequential Organ Failure Assessment score (SOFA), on which the Sepsis-3 definition (Third International Consensus Definitions for Sepsis and Septic Shock) is predicated (8). If our goal in treating sepsis is to rapidly identify organ dysfunction and sequentially reassess perfusion adequacy, there may be benefit in adopting a broad array of organ injury markers to alert the clinician to potential sepsis-induced organ failures beyond those already codified in the SOFA score.