Elevations in High-Sensitive Cardiac Troponin T and N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Serum Can Predict the Development of Anthracycline-Induced Cardiomyopathy

Abstract

Background: Anthracyclines remain the cornerstone of the treatment in many cancers including lymphomas, leukemia and sarcomas, and breast cancer. The cardiomyopathy that develops from anthracyclines can lead to heart failure and decreased survival. Multiple mechanisms are involved the pathophysiology of anthracycline-induced heart failure. Study Question:We hypothesise that anthracycline induced-cardiac (AIC) pathology can be monitored using a panel of blood biomarkers including High-Sensitive Cardiac Troponin T (hs-cTnT) for myocytes necrosis, and N-Terminal Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) for parietal stress.Study Design: A prospective, institutionally-approved study recruited all cancer patients scheduled to start anthracycline chemotherapy in the Transilvania University cancer clinics.Measures and Outcomes: Transthoracic 2D echocardiography (2D-ETT) and the measurements of NT-proBNP and hs-cTnT plasma levels were performedat the beginning of the study, and 3 months and 6 months after anthracycline treatment initiation. Results:The plasma levels of hs-cTnT at 3 months (rho = 0.439, p = 0.0001) and 6 months (rho = 0.490, p = 0.0001) are correlated with AIC occurrence. For a cut-off value of hs-cTnT at 3 months> 0.008 ng/ml we obtained 66.7% sensitivity, 67.9% specificity for developing AIC at 6 months, with a 54.5% positive predictive value and a 87.8% negative predictive value. The NT-proBNP serum levels at 3 months (rho = 0.495, p = 0.0001) and 6 months (rho = 0.638, p = 0.0001) are correlated with an AIC diagnosis at 6 months. For a cut-off value of NT-proBNP at 3 months > 118.5 pg/ml we obtained 80% sensitivity and 79.2% specificity for evolution to AIC at 6 months, with 52.2% positive predictive value and 93.3% negative predictive value. 4Conclusions: In anthracycline-treated cancer patients, the increase in plasma levels of NT-proBNP and of hs-cTnT can predict the development of anthracycline-induced cardiomyopathy. Early identification of at-risk patients will potentially allow for targeted dose-reductions and will diminish the number of patients developing cardiac pathology.

Delta NT-proBNP predicts cardiotoxicity in HER2-positive breast cancer patients treated with trastuzumab

“…While NT- proBNP increased in TIC patients, NT-proBNP decreased during the 12-month trastuzumab therapy in patients not developing TIC in accordance with previous studies [19]. The majority of patients in our study were exposed to anthracyclines prior to analysing NT-proBNP at baseline, which could have increased baseline NT-proBNP values [21].…”

“…In the adjuvant setting, patients experiencing TIC developed a non-significant increase in NT-proBNP [19]. To note, NT-proBNP may increase in patients exposed to radiotherapy for left-sided breast cancer and NT-proBNP may increase in patients exposed to other cardiotoxic drugs than trastuzumab such as anthracyclines [20,21].…”

Doxorubicin-Induced Cardiotoxicity in Collaborative Cross (CC) Mice Recapitulates Individual Cardiotoxicity in Humans

“…cTNI is utilized in clinical practice (Horacek et al 2008; Jones et al 2017; Simões et al 2018; Ma et al 2019). Cardiac troponin T has been used to monitor anthracycline induced injury in clinical patients (Blaes et al 2015; Bisoc et al 2019), although its elevation following anthracycline treatment is not invariable (Horacek et al 2008; Lipshultz et al 2004). Both cTNI and cTNT are more reliable indicators of injury immediately following anthracycline exposure (Simões R et al , 2018).…”

The Influence of Diabetes Mellitus on Sodium Homeostasis in Patients with Preserved Ejection Fraction Heart Failure

“…The exclusion criteria were: -Acute coronar y syndrome, moderate/Severe valvulopathies, pericarditis, primitive or secondary, primary/secondary lesions of cardiac muscle, primary/ secondar y moderate or severe arterial pulmonar y hypertension; rhythm and conduction disorders -Pulmonary thromboembolism -Oncological [12][13][14][15], hematological or endocrinological disorder -Infection with Clostridium Difficile or other pathogens, diabetic foot [16][17][18] -Acute kidney failure/chronic kidney disease, respiratory failure [19] -Glycosylated hemoglobin value >6.5 % or fasting plasma glucose>110 mg/dL Clinically, it has been noticed the presence of symptoms( breathlessness, ankle swelling and fatigue), that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) [3].…”