Trastuzumab-Induced Cardiotoxicity: Clinical and Prognostic Implications of Troponin I Evaluation

2010 ◽  
Vol 28 (25) ◽  
pp. 3910-3916 ◽  
Author(s):  
Daniela Cardinale ◽  
Alessandro Colombo ◽  
Rosalba Torrisi ◽  
Maria T. Sandri ◽  
Maurizio Civelli ◽  
...  
Keyword(s):  
At Risk ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Trastuzumab Therapy ◽  
Before And After ◽  
Patients At Risk ◽  
Prognostic Implications

Purpose Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). Conclusion TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

Abstract 13441: D-dimmer is a Predictor of Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Masayoshi Oikawa ◽  
Daiki Yaegashi ◽  
Tetsuro Yokokawa ◽  
Tomofumi Misaka ◽  
Takamasa Sato ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Troponin I ◽  
Uterine Cancer ◽  
Cancer Therapeutics ◽  
Left Ventricular ◽  
Time Dependent ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
D Dimer

Background: D-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD). Methods and Results: Consequtive 202 patients planned for cardiotoxic chemotherapy (anthracyclines, monoclonal antibodies, tyrosine kinase inhibitors, and proteasome inhibitors) were enrolled and followed up for 12 months. Cancer types were as follows: breast cancer (n=112), lymphoma (n=37), ovarian or uterine cancer (n=18), leukemia (n=13), multiple myeloma (n=6), bone cancer (n=4), and others (n=12). All patients underwent echocardiography and blood test at baseline, 3-month, 6-month, and 12-month. The patients were divided into 2 groups based on the value of D-dimer (>1.5 μg/ml or ≦1.5 μg/ml) at baseline before chemotherapy: High D-dimer group (n=52) and Low D-dimer group (n=150). At baseline, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index, and B-type natriuretic peptide levels were similar between two groups. Time-dependent decrease in LVEF was observed after chemotherapy in high D-dimer group (baseline, 66±5%; 3-month, 63±7%; 6-month, 62±7%; 12-month 62±6%; P=0.005, figure), but not in low D-dimer group. Time-dependent increase in troponin I was similarly observed after chemotherapy in both groups. The occurrence of CTRCD was higher in high D-dimer group than in low D-dimer group (11.5% vs. 4.0%, P=0.048). When we set the cut-off value of baseline D-dimer at 1.65 μg/ml from ROC analysis, sensitivity, specificity, and area under the curve to predict CTRCD were 50%, 77%, and 0.679, respectively. Multivariable logistic analysis revealed that baseline D-dimer was an independent factor to predict the decrease in LVEF more than 10% after cardiotoxic chemotherapy (odds ratio 1.210, 95% confidence interval [1.020-1.440], P=0.025). Conclusion: Baseline D-dimer is a pivotal parameter to predict CTRCD.

scholarly journals A Randomized Trial Comparing 3- versus 4-Monthly Cardiac Monitoring in Patients Receiving Trastuzumab-Based Chemotherapy for Early Breast Cancer

2021 ◽  
Vol 28 (6) ◽  
pp. 5073-5083
Author(s):  
Susan Dent ◽  
Dean Fergusson ◽  
Olexiy Aseyev ◽  
Carol Stober ◽  
Gregory Pond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Cardiac Dysfunction ◽  
Controlled Trial ◽  
Left Ventricular ◽  
Cardiac Monitoring ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Trastuzumab Therapy

Purpose: The optimal frequency for cardiac monitoring of left ventricular ejection fraction (LVEF) in patients receiving trastuzumab-based therapy for early breast cancer (EBC) is unknown. We conducted a randomized controlled trial comparing 3- versus 4-monthly cardiac monitoring. Patients and Method: Patients scheduled to receive trastuzumab-containing cancer therapy for EBC with normal (>53%) baseline LVEF were randomized to undergo LVEF assessments every 3 or 4 months. The primary outcome was the change in LVEF from baseline. Secondary outcomes included the rate of cardiac dysfunction (defined as a decrease in the LVEF of ≥10 percentage points, to a value <53%), delays in or discontinuation of trastuzumab therapy, and cardiology referral. Results: Of the 200 eligible and enrolled patients, 100 (50%) were randomized to 3-monthly and 100 (50%) to 4-monthly cardiac monitoring. Of these patients, 98 and 97 respectively underwent at least one cardiac scan. The estimated mean difference in LVEF from baseline was −0.94% (one-sided 95% lower bound: −2.14), which exceeded the pre-defined non-inferiority margin of −4%. There were also no significant differences between the two study arms for any of the secondary endpoints. The rate of detection of cardiac dysfunction was 16.3% (16/98) and 12.4% (12/97) in the 3- and 4-monthly arms, respectively (95% CI: 4.0 [−5.9, 13.8]). Conclusions: Cardiac monitoring every 4 months was deemed non-inferior to that every 3 months in patients with HER2-positive EBC being treated with trastuzumab-based therapy. Given its costs and inconvenience, cardiac monitoring every 4 months should be considered standard practice. Registration: NCT02696707, 18 February 2016.

scholarly journals CORRELATION BETWEEN CHANGES OF NT-PRO BNP AND HS-TROPONIN I LEVEL WITH CARDIOTOXICITY IN LOCALLY ADVANCED BREAST CANCER AFTER THREE CYCLES OF NEOADJUVANT CAF CHEMOTHERAPY

2019 ◽  
Vol 26 (1) ◽  
pp. 71
Author(s):  
Cicilia Indriaty ◽  
Leonita Anniwati ◽  
J.Nugroho Eko Putranto ◽  
Desak Gede Agung Suprabawati
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Troponin I ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Before And After

Chemotherapy with cyclophosphamide, adriamycin, and fluorouracil (CAF) regiment in patients with locally advanced breast cancer have a risk of cardiotoxicity. Cardiotoxicity examination standards using left ventricular ejection fraction (LVEF) by echocardiography are considered insensitive for detection of subclinical ventricular dysfunction. NT-pro BNP and Hs-Troponin I (hs-TnI) as cardiac biomarkers are expected to help detect early cardiotoxicity. This study intended to analyze the correlation between changes of NT-pro BNP and hs-TnI levels with cardiotoxicity in breast cancer after three cycles of chemotherapy.This was a cross-sectional observational study, conducted at the Dr. Soetomo General Hospital Surabaya. The subjects consisted of 23 breast cancer patients who underwent chemotherapy with CAF regiment. NT-proBNP and hs-TnI examination used CLIA methods (Immulite 1000, ADVIA Centaur TnI-Ultra). Cardiotoxicity based on decreased  LVEF to more than 10% of the initial LVEF value using echocardiography. Significant increases in NT pro BNP and hs-TnI levels were obtained before and after treatment (p=0.000, p=0.002). A significant decrease in LVEF was obtained before and after treatment (p=0.000), but only 2 patients (8.7%) showed cardiotoxicity. There was no correlation between changes in NT-pro BNP and hs-TnI levels with changes in LVEF before and after chemotherapy (p=0.666 and r=0.095; p=0.254 and r=-0.28). There was no correlation between changes in NT-pro BNP and hs-TnI levels with cardiotoxicity, which was assessed based on LVEF reduction, in locally advanced breast cancer after three-cycles of chemotherapy with CAF regiment.

scholarly journals Detecting early onset of anthracyclines-induced cardiotoxicity using a novel panel of biomarkers in West-Virginian population with breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hari Vishal Lakhani ◽  
Sneha S. Pillai ◽  
Mishghan Zehra ◽  
Benjamin Dao ◽  
Maria Tria Tirona ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Cardiac Dysfunction ◽  
Early Onset ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Circulating Mirnas ◽  
Ventricular Ejection Fraction

AbstractCardiotoxic manifestation associated with breast cancer treatment by anthracycline regimen increases patients’ susceptibility to myocardial injury, reduction in left ventricular ejection fraction and complications associated with heart failure. There is currently no standardized, minimally invasive, cost effective and clinically verified procedure to monitor cardiotoxicity post-anthracycline therapy initiation, and to detect early onset of irreversible cardiovascular complications. This study aims to create a panel of novel biomarkers and circulating miRNAs associated with cardiotoxicity, further assessing their correlation with cardiac injury specific markers, troponin I and T, and demonstrate the development of cardiac dysfunction in breast cancer patients. Blood obtained from West Virginian females clinically diagnosed with breast cancer and receiving anthracyclines showed upregulated level of biomarkers and circulating miRNAs after 3 and 6 months of chemotherapy initiation with increased levels of cardiac troponin I and T. These biomarkers and miRNAs significantly correlated with elevated troponins. Following 6 months of anthracycline-regimens, 23% of the patient population showed cardiotoxicity with reduced left ventricular ejection fraction. Our results support the clinical application of plasma biomarkers and circulating miRNAs to develop a panel for early diagnosis of chemotherapy related cardiac dysfunction which will enable early detection of disease progression and management of irreversible cardiac damage.

scholarly journals Incidence and outcomes of chronic total occlusion percutaneous coronary intervention in the Netherlands: data from a nationwide registry

2020 ◽  
Vol 29 (1) ◽  
pp. 4-13 ◽  
Author(s):  
A. van Veelen ◽  
◽  
B. E. P. M. Claessen ◽  
S. Houterman ◽  
L. P. C. Hoebers ◽  
...  
Keyword(s):  
At Risk ◽  
Percutaneous Coronary Intervention ◽  
The Netherlands ◽  
Renal Insufficiency ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Percutaneous Coronary ◽  
Patients At Risk

Abstract Background Patients with chronic total coronary occlusions (CTO) are at increased risk for poor clinical outcomes. We aimed to determine the incidence of CTO percutaneous coronary intervention (PCI) and to identify CTO patients at risk for cardiac events in the nationwide Netherlands Heart Registration (NHR). Methods We included all PCI procedures with ≥1 CTO registered in the NHR from January 2015 to December 2018, excluding acute interventions. We used multivariable logistic regression of baseline characteristics to calculate the risk for events as odds ratios (OR) with 95% confidence intervals (CI). Results Of the PCIs performed during the study period, 6.3% (8,343/133,042) were for CTOs, with the percentage increasing significantly over time from 5.9% in 2015 to 6.6% in 2018 (p < 0.001). Coronary artery bypass grafting <24 h was carried out in 0.3%, and the only significant predictor was diabetes mellitus (OR 2.97, 95% CI 1.04–8.49, p = 0.042). Myocardial infarction (MI) <30 days occurred in 0.5%, and renal insufficiency (i.e. estimated glomerular filtration rate <30 ml/min per 1.73 m2) was identified as an independent predictor (OR 4.70, 95% CI 1.07–20.61, p = 0.040). Among patients undergoing CTO-PCI, 1‑year mortality was 3.7%, and independent predictors included renal insufficiency (OR 5.59, 95% CI 3.25–9.59, p < 0.001), left ventricular ejection fraction <30% (OR 3.43, 95% CI 2.00–5.90, p < 0.001), previous MI (OR 1.62, 95% CI 1.14–2.31, p = 0.007) and age (OR 1.06 per year increment, 95% CI 1.04–1.07, p < 0.001). Target-vessel revascularisation <1 year occurred in 11.3%. Conclusion CTO-PCI is still infrequently performed in the Netherlands. The most important predictor of mortality after CTO-PCI was renal insufficiency. Identification of patients at risk may help improve the prognosis of CTO patients in the future.

scholarly journals Comparison of the Levels of Cardiac Troponin I in Patients with Duchenne and Becker Muscular Dystrophies to Assess Cardiac Dysfunction

2021 ◽  
Author(s):  
Hiroshi Yamaguchi ◽  
Hiroyuki Awano ◽  
Tetsushi Yamamoto ◽  
Masafumi Matsuo ◽  
Kazumoto Iijima
Keyword(s):  
Cardiac Dysfunction ◽  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Genetic Modifier ◽  
Becker Muscular Dystrophy ◽  
Left Ventricular ◽  
Cardiac Troponin I ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Background: Cardiac troponin I (cTnI), uniquely expressed in the myocardium, is a marker for acute myocardial injury. Its clinical significance in Duchenne and Becker muscular dystrophy (DMD and BMD) and its relation to alpha-actinin-3 (ACTN3) genotype as a genetic modifier of cardiomyopathy are still unknown.Methods and Results: Overall, 529 and 131 serum cTnI values of 127 DMD and 47 BMD patients, respectively, were reviewed. cTnI elevation was generally observed in the second decade of life. Both cTnI levels and the proportion of abnormal cTnI levels were significantly higher in DMD patients than in BMD patients (age range: 1< years ≤10 and 10< years ≤18 and 10< years ≤18, respectively). Decreased left ventricular ejection fraction was observed after cTnI elevation in both populations. cTnI levels by age in DMD patients with ACTN3 null genotype tended to increase highly and early.Conclusions: Myocardial injury indicated by cTnI was more common and severe in DMD patients than in BMD patients. cTnI elevation preceding cardiac dysfunction may represent an early phase of cardiomyopathy progression and may be a biomarker for early detection of cardiomyopathy in DMD and BMD patients. The ACTN3 null genotype may be a risk factor for early myocardial injury.

scholarly journals N-Terminal Pro-B-Type Natriuretic Peptide after High-Dose Chemotherapy: A Marker Predictive of Cardiac Dysfunction?

2005 ◽  
Vol 51 (8) ◽  
pp. 1405-1410 ◽  
Author(s):  
Maria T Sandri ◽  
Michela Salvatici ◽  
Daniela Cardinale ◽  
Laura Zorzino ◽  
Rita Passerini ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Cardiac Dysfunction ◽  
High Dose Chemotherapy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Ventricular Ejection Fraction ◽  
Patients At Risk ◽  
Predictive Role

Abstract Background: Chronic cardiac dysfunction may develop after administration of aggressive chemotherapy, sometimes leading to development of congestive heart failure (CHF). Recently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was implicated as a marker of CHF. In this study we evaluated the predictive role of NT-proBNP in patients treated with high-dose chemotherapy (HDC). Methods: NT-proBNP was measured after 62 chemotherapy treatments in 52 patients affected by aggressive malignancies. Blood samples were drawn before the start of HDC, at the end of HDC administration, and 12, 24, 36, and 72 h thereafter. In these patients, echocardiograms were performed regularly during a 1-year follow-up. Results: Seventeen patients (33%) had persistently increased NT-proBNP, 19 patients (36%) had only transient increases (concentrations went back to baseline at 72 h), and 16 (31%) had no increases [mean (SD) values at 72 h, 1163 (936) ng/L vs 185 (101) ng/L vs 39 (19) ng/L, respectively; P &lt;0.0001]. Only patients with persistently increased NT-proBNP had a significant worsening of the left ventricular diastolic indexes from baseline to 12 months [ratio of peak early to peak late flow velocities from 1.42 (0.33) to 0.78 (0.11); P &lt;0.0001; isovolumetric relaxation time from 90 (15) to 141 (26) ms; P &lt;0.0001; E-wave deceleration time from 162 (17) to 224 (32) ms; P = 0.0004] and of the left ventricular ejection fraction [from 62.8 (3.4)% to 45.6 (11.5)%; P &lt;0.0001]. Conclusions: Persistently increased NT-proBNP early after administration of HDC is strongly associated with development of cardiac dysfunction. This finding has important implications for identifying patients at risk of developing chemotherapy-induced cardiotoxicity.

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