Clinical Use of High-sensitivity Cardiac Troponin in Patients With Suspected Myocardial Infarction

Raphael Twerenbold, MD; Jasper Boeddinghaus, MD; Thomas Nestelberger, MD; Karin Wildi, MD; Maria Rubini Gimenez, MD; Patrick Badertscher, MD; Christian Mueller, MD


J Am Coll Cardiol. 2017;70(8):996-1012. 

In This Article

hs-cTn in Patients With Renal Dysfunction

Patients with suspected MI and renal dysfunction are at substantial higher risk of MI as compared with patients with normal renal function.[84–86] Accurate rule-out and rule-in of MI is of paramount importance because patients with renal dysfunction are more prone to adverse events related to cardiovascular medication (e.g., anticoagulation), as well as to cardiovascular procedures including coronary angiography and coronary intervention.[27,41] However, rapid and accurate diagnosis of MI is challenging in this vulnerable patient subgroup for several reasons: First, patients with renal dysfunction more frequently present with atypical clinical presentation of MI.[87,88] Second, left ventricular hypertrophy is common in renal dysfunction and often results in ECG changes that may mimic or obscure MI. Third, baseline concentrations of cTn are often chronically elevated in patients with renal dysfunction (10% to 20% using s-cTn, up to 70% using hs-cTn) even in conditions other than acute myocardial ischemia and are associated with poor prognosis.[86,89] The underlying pathophysiological mechanism is poorly understood, yet. Initially, it has been hypothesized that hs-cTn elevations are a direct result of reduced glomerular filtration rate. However, data from several studies suggest that elevated levels of cTn, similar to natriuretic peptides, are only to a lesser extent explained by reduced renal clearance (about 20%), particularly because the molecular size of the intact molecule is too large to be filtrated by glomeruli.[90–93] It could be demonstrated that cTnT molecules may be degraded into smaller fragments that are small enough to be filtered by the kidney and can still be detected by cTn assays.[94] However, the renal elimination and half-life of these cTn fragments do not differ between renal dysfunction and normal renal function.[95] Furthermore, in a study examining patients with end-stage renal disease undergoing renal transplantation, levels of cTn did not decrease in the vast majority (82%) after renal transplantation despite substantially improved renal function, further advocating against the concept of elevated cTn concentrations being primarily explained by reduced renal clearance.[90] Recent studies have hypothesized that the underlying mechanism of chronic cTn release may be caused by some forms of cardiorenal syndrome triggered by unknown inflammatory processes leading to chronic myocardial injury and consecutive chronic cTn release in renal dysfunction.[96,97]

Using the uniform assay-specific 99th percentiles as a binary decision level to rule out or rule in MI on the basis of a single blood sample obtained at presentation to the ED is of limited diagnostic value in patients with renal dysfunction.[86] However, it was demonstrated in a large multicenter study investigating the diagnostic utility of 7 more sensitive cTn assays in patients with renal dysfunction and normal renal function that high diagnostic accuracy of hs-cTn can be maintained if adjusted decision levels higher than the assay-specific 99th percentiles are used in renal dysfunction.[86] Although differences in baseline hs-cTn concentrations exist between patients with renal dysfunction and normal renal function, absolute hs-cTn changes during serial sampling do not differ between MI patients with renal dysfunction and normal renal function.[86] Therefore, the diagnostic information of absolute changes during serial sampling is maintained.

Can the different hs-cTn–based rule-out strategies safely be used also in patients with renal dysfunction? These strategies were derived and validated in mixed, all-comers populations including patients with renal dysfunction. Patients requiring dialysis were mostly excluded from the analyses. Safety of all the 6 mentioned rule-out strategies is high in mixed populations and seems to be maintained also in patients with renal dysfunction, according to subgroup analyses.[55,60] However, the efficacy of rule-out is lower because fewer patients have low hs-cTn blood concentrations. Whether the application of hs-cTn–based strategies using renal function-adjusted cutoff values or uniform cutoff levels is more favorable regarding the balance of safety and efficacy needs to be investigated in future studies.