Prognostic Value of Troponin I in Cardiac Risk Stratification of Cancer Patients Undergoing High-Dose Chemotherapy

Abstract

Background— In patients with aggressive malignancies who are undergoing high-dose chemotherapy, even minimal elevation of troponin I (TnI) is associated with late left ventricular dysfunction. The time course of the subclinical myocardial damage and its impact on the clinical outcome have never been investigated previously. Methods and Results— In 703 cancer patients, we measured TnI soon after chemotherapy (early TnI) and 1 month later (late TnI). Troponin was considered positive for values ≥0.08 ng/mL. Clinical and left ventricular ejection fraction evaluation (echocardiography) were performed before chemotherapy, 1, 3, 6, and 12 months after the end of the treatment, and again every 6 months afterward. Three different TnI patterns were identified, and patients were grouped accordingly. In 495 patients, both early and late TnI values were <0.08 ng/mL (TnI −/− group); in 145, there was only an early increase (TnI +/− group); and in 63 patients, both values increased (TnI +/+ group). In the TnI −/− group, no significant reduction in ejection fraction was observed during the follow-up, and there was a very low incidence of cardiac events (1%). In contrast, a greater incidence of cardiac events occurred in TnI-positive patients, particularly in the TnI +/+ group (84% versus 37% in the TnI +/− group; P <0.001). Conclusions— TnI release pattern after high-dose chemotherapy identifies patients at different risks of cardiac events in the 3 years thereafter. This stratification allows us to differentiate the monitoring program and to plan, in selected patients, preventive strategies aimed at improving clinical outcome.

Cardiac toxicity of high-dose chemotherapy

“…In a recent update of their series, the same authors could stratify patients at different risk of cardiac events following HD chemotherapy based on even minimal elevations of cTnI levels recorded soon after chemotherapy and 1 month later. 119 However, the vast majority of patients showing a rise in cTnI received high-dose epirubicin, while cTnI measurements after single-agent HD cyclophosphamide (7 g/m 2 ) in 49 patients of these series were not reported. 97 In our experience and that of other groups, serial plasma measurements of cTnI or cTnT after single-agent HD cyclophosphamide were uniformly negative.…”

“…The technically simpler dosage of circulating markers is partly countered by the lack of knowledge about optimal timing of measurement, and its potential use as a diagnostic and predictive tool also remains investigational. However, the reported potential for cTnI to stratify patients at risk for cardiac complications following anthracyclinecontaining HD chemotherapy 119 warrants further investigation. Finally, dosage of cardiac markers in patients undergoing conditioning regimens associated with unexpected and completely unexplained cardiac toxicity 59,69-71 may provide insights into the underlying pathophysiology.…”

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Cardiac troponins are well‐established markers of myocardial injury and appear to correlate best with incident cardiac dysfunction following chemotherapy. Three studies have reported that elevated and increasing troponin I following chemotherapy, particularly if such increase persists at 1 month after treatment,84 is associated with subsequent cardiac dysfunction as well as with lower likelihood of cardiac recovery in patients receiving trastuzumab 85, 86, 87. During treatment, negative cardiac troponin has a high negative predictive value; however, minute elevations can be commonly detected in patients following chemotherapy and have low positive predictive value 88.…”

Cardiac Imaging: Multimodality Advances and Surveillance Strategies in Detection of Cardiotoxicity

“…Cardiac troponins are sensitive markers of myocardial injury with both troponin I (Tn-I) and T (Tn-T) assays. Cardinale et al demonstrated that the timing and degree of Tn-I rise was predictive of developing LV dysfunction, and also correlated with anthracycline cumulative dosing [43][44][45][46]. Tn-I monitoring also served effectively as risk stratification in their studied population; patients treated with high-dose chemotherapy who developed an increased in Tn-I were the ones who benefited more from the initiation of an angiotensin-converting enzyme inhibitor treatment (enalapril), preventing LVEF decrease [47].…”

“…In regards to biomarkers, troponin levels appear to have the best predictive value in detecting cardiotoxicity monitoring, with the timing and the degree of the rise correlated with risk of CTRCD [43][44][45][46]. Troponin elevations during treatment also identify a high risk cohort of cancer patients who may benefit from early cardioprotective medication [47].…”