Critically Appraised Topic: How can high sensitivity troponin testing be used in the setting of chronic renal disease to diagnose ACS?
Study #1: This was a retrospective cohort study that utilized two cohorts from different studies, one that included 1494 patients from a multicenter cohort study with high-sensitivity troponin I measurements, and one clinical data set from a retrospective cohort study that included 7059 patients with high-sensitivity troponin T measurements. The objective of this study was to determine an optimized algorithm of high-sensitivity troponin testing for suspected NSTEMI in CKD patients. The first study set enrolled adults who presented with acute chest pain to 1 of 3 German study centers, exclusion criteria included major surgery or trauma in the previous 4 weeks, pregnancy, IV drug abuse, anemia (hemoglobin <10), and dialysis patients, and for this particular study, those with ST-segment elevation were excluded because researchers were interested in cases with suspected NSTEMI. The second study set included cases from a Cardiology Department that had at least 2 measurements of and clinically suspected AMI, and for this particular study, those with ST-segment elevation were excluded. Creatinine for both cohorts was measured enzymatically, and eGFR determined CKD stage. In the study data set, 19% of patients had impaired renal function (eGFR <60), and AMI was diagnosed in 15% of non-CKD patients, and 26% of CKD patients (P<0.001). In the clinical data set, 22% of patients had impaired renal function. Initial levels were higher in CKD patients than in non-CKD patients, and they correlated inversely with eGFR. The 99th percentile cutoffs that served to rule in/out NSTEMI were less specific in CKD patients with both assays, especially with the assay. When comparing conventional cutoffs in CKD patients, in the assay the sensitivity was 92% and specificity was 82%, while for the assay the sensitivity was 94% and specificity was 26%. The proposed algorithm outperforms the conventional 99th percentile cutoffs for high sensitivity troponin testing in CKD patients with suspected acute MI.
Study #2: This was a multi-center, prospective cohort study of 4739 patients with suspected ACS to the emergency departments of 2 secondary care hospitals and a tertiary care hospital. All patients in whom the attending clinician requested cardiac troponin for suspected ACS were enrolled and had at least 1 measurement of serum creatinine during the index presentation for eGFR estimation and CKD classification. Exclusion criteria included previous diagnosis of STEMI, had been admitted previously during the study period, and patients did not live in Scotland. 19% of patients had renal impairment with eGFR <60. Troponin concentrations were >99th percentile at presentation in 40% of patients with and 15% of patients without CKD. During index presentation, adjudicated diagnosis was type 1 MI in 23% with renal impairment and 12% without renal impairment; type 2MI was more frequent in patients with renal impairment with 7%, compared to 3% without impairment. The PPV and specificity were similar in patients with renal impairment stratified by age or sex, but were lower in those >65 years old and in women without renal impairment. Sensitivity was similar in patients with and without renal impairment, both at presentation and on repeat sampling.
Conclusions: While these studies differ in their conclusions and their findings, I think it is important to recognize that high sensitivity troponin testing needs to be more specialized and optimized with a specified algorithm for differing stages of CKD patients. Study 1 creates an algorithm with higher sensitivities/specificities/NPV/PPV compared with traditional cutoff levels for diagnosing and ruling out acute MI, however given its narrow focus on solely NSTEMI as an outcome and exclusion of dialysis patients, I think further research needs to be performed on how to optimize such an algorithm. On the other hand, study 2 centers on the fact that generally troponin levels are elevated in those with CKD, however there needs to be a further element of risk stratification because these patients often suffer more frequently from cardiac complications. Based on my review of the literature, I think more research needs to be done to further optimize an algorithm for varying CKD stages to better risk stratify and diagnose those with ACS.
1. Kraus D, von B, Tzikas S, et al. Cardiac Troponins for the Diagnosis of Acute Myocardial Infarction in Chronic Kidney Disease. J Am Heart Assoc. 2018;7(19008032. doi:10.1161/JAHA.117.008032
2. Miller-Hodges E, Anand A, Shah ASV, et al. High-Sensitivity Cardiac Troponin and the Risk Stratification of Patients Renal Impairment Presenting Suspected Acute Coronary Syndrome. Circulation. 2018;137(5):425-435. doi:10.1161/CIRCULATIONAHA.117.030320