Role of Cardiac Biomarkers in Cancer Patients

Abstract

In patients with cancer-and especially some specific subtypes-the heart can be pathologically affected due to the direct action of the tumor or its secretion products or due to the toxicity of some oncological treatments. Cardiac biomarkers have been investigated as inexpensive and easily accessible tools for prediction, early diagnosis, monitoring, or prognosis of various forms of cancer-related cardiac diseases. However, their clinical usefulness was not always clearly demonstrated in every area of cardioncology. For the identification of anthracycline related cardiotoxicity in the very early stages troponins proved to be more efficient detectors than imaging methods. Nevertheless, the lack of a standardized dosage methodology and of cardiotoxicity specific thresholds, do not yet allow to outline the precise way to employ them in clinical routine and to incorporate them into appropriate diagnostic or managing algorithms. Cardiac biomarkers proved also effective in patients with primary cardiac amyloidosis, in which both troponins and natriuretic peptides were able to predict adverse outcome, and carcinoid heart disease, where a precise diagnostic cut-off for N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was identified to screen patients with valvular involvement. Likewise, NT-proBNP proved to be an excellent predictor of postoperative atrial fibrillation (POAF). On the contrary, evidence is still not sufficient to promote the routine use of cardiac biomarkers to early diagnose myocarditis due to immune check points inhibitors (ICIs), radiotherapy induced cardiotoxicity and cardiac complications related to androgenetic deprivation. In this review we present all the evidence gathered so far regarding the usefulness and limitations of these relatively inexpensive diagnostic tools in the field of cardio-oncology.

Keywords: NT-proBNP; androgen deprivation; carcinoid; cardiac amyloidosis; cardiac biomarkers; cardio-oncology; cardiotoxicity; immune check-point inhibitors; predictive; troponin.

Figure 1

Main cardiac biomarkers and pathophysiological mechanisms involved in their plasma increase. Modified from McLean et al. [8].

Figure 2

Mechanisms of Troponin release. From Taggart et al. [14].

Figure 3

Mechanism of troponin release caused by anthracyclines [27].

Figure 4

Linear correlation between TnI peak detected during chemotherapy and subsequent % EF drop [33].

Figure 5

Troponin progressive increase as cumulative anthracycline doses increases with chemotherapy advancement. From Tzolos et al. [42].

Figure 6

Troponin behavior during trastuzumab therapy following previous chemotherapy with other drugs including anthracyclines [45].

Figure 7

Algorithm for early detection of ICIs related myocarditis proposed by Spallarossa et al. The timing of troponin assays repetition differs due to the presence/absence of symptoms. * Result of integration and interpretation of clinical, anamnestic, laboratory, ECG and echocardiographic data [53].

Figure 8

Troponin level variation before, during and after RT in patients treated with higher radiation doses and who had a hscTnT increase > 30% from baseline (Group a) versus patients treated with lower radiation doses and who did not experience a significant increase in hscTnT (Group b) [61].

Figure 9

Prognostic value (Kaplan–Meier estimates) for all-cause mortality of (A) N-terminal pro B-type natriuretic peptide (NT-proBNP) with a threshold of 125 pg/mL and (B) hsTnT with a threshold of 0.005 ng/mL for patients with newly diagnosed tumour disease (p < 0.001 between two groups for NT-proBNP and hsTnT, log-rank test). Modified from Pavo et al. [82].

Figure 10

Difference in mean NT-proBNP (top box) and ANP (bottom box) levels between patients with carcinoid heart disease (CHD) and without (No CHD). Values beyond the lines are considered outliers (+) [86].

Figure 11

Correlation between severity of right ventricular dilatation and NT-proBNP values. Values beyond the lines are considered outliers (+) [86].

Figure 12

Receiver operator curve of NT–proBNP for diagnosis of carcinoid heart disease [6].

Figure 13

Screening algorithm for carcinoid heart disease (CHD) based on NT-proBNP values [89].