scholarly journals Early detection of anthracycline cardiotoxicity in a rabbit model: left ventricle filling pattern versus troponin T determination

2007 ◽  
pp. 535-545
Author(s):  
M Štěrba ◽  
T Šimůnek ◽  
O Popelová ◽  
A Potáčová ◽  
M Adamcová ◽  
...  
Keyword(s):  
Early Detection ◽  
Plasma Levels ◽  
Troponin T ◽  
Rabbit Model ◽  
Left Ventricular ◽  
Anthracycline Cardiotoxicity ◽  
Anticancer Chemotherapy ◽  
Filling Pattern ◽  
Significant Impairment ◽  
And Control

Anthracycline cardiotoxicity represents a serious risk of anticancer chemotherapy. The aim of the present pilot study was to compare the potential of both the left ventricular (LV) filling pattern evaluation and cardiac troponin T (cTnT) plasma levels determination for the early detection of daunorubicin-induced cardiotoxicity in rabbits. The echocardiographic measurements of transmitral LV inflow as well as cTnT determinations were performed weekly for 10 weeks in daunorubicin (3 mg/kg weekly) and control groups (n=5, each). Surprisingly, no significant changes in LV-filling pattern were observed through the study, most likely due to the xylazine-containing anesthesia, necessary for appropriate resolving of the E and A waves. In contrast to the echographic measurement, the dP/dt(min) index obtained invasively at the end of the study revealed a significant impairment in LV relaxation, which was further supported by observed disturbances in myocardial collagen content and calcium homeostasis. However, at the same time cTnT plasma levels were progressively rising in the daunorubicin-treated animals from the fifth week (0.024+/-0.008 microg/l) until the end of the experiment (0.186+/-0.055 microg/l). Therefore, in contrast to complicated non-invasive evaluation of diastolic function, cTnT is shown to be an early and sensitive marker of anthracycline-induced cardiotoxicity in the rabbit model.

scholarly journals Primary prevention of chronic anthracycline cardiotoxicity with ACE inhibitor is temporarily effective in rabbits, but benefits wane in post-treatment follow-up

2021 ◽  
Author(s):  
Zuzana Pokorna ◽  
Petra Kollárová-Brázdová ◽  
Olga Lenčová-Popelová ◽  
Eduard Jirkovský ◽  
Jan Kubeš ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Troponin T ◽  
Rabbit Model ◽  
Left Ventricular ◽  
Post Treatment ◽  
Cardiac Damage ◽  
Anthracycline Cardiotoxicity ◽  
Related Mortality

Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent anthracycline-induced cardiac damage and provide long-lasting cardioprotection. This study aimed to examine the cardioprotective effects of perindopril on chronic anthracycline cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic daunorubicin treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of daunorubicin-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented heart failure-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for dexrazoxane in the same model. Hence, in this study, perindopril provided only temporary control of anthracycline cardiotoxicity development, which may be associated with the lack of effects on anthracycline-induced and topoisomerase II beta-dependent DNA damage responses in the heart.

Effectiveness of using cardiac biomarkers to detect late anthracycline cardiotoxicity in childhood leukemia survivors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9592-9592
Author(s):  
Beata Mladosievicova ◽  
Dagmar Urbanova ◽  
Eva Radvanska ◽  
Eva Mikuskova ◽  
Iveta Simkova
Keyword(s):  
Childhood Leukemia ◽  
Troponin T ◽  
Combined Therapy ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Anthracycline Cardiotoxicity ◽  
Ventricular Ejection Fraction ◽  
Group I

9592 Background: Cardiotoxicity is usually detected only when clinical symptoms or progressive cardiac dysfunction has already occurred. Cardiac biomarkers (troponin T and N-terminal fragment brain natriuretic peptide precursor) have been hypothesized to reflect subclinical anthracycline cardiotoxicity earlier than echocardiography. This study aims to assess the effectiveness of using cTNT and NTproBNP in asymptomatic long-term survivors of childhood leukemia treated with and without antracyclines (ANT). Methods: Sixty-nine childhood leukemia survivors 5 - 25 years after completion of therapy were evaluated with immunochemical analysis of cTnT and NT-proBNP and echocardiography. Patients from group I (n = 36) received combined therapy with anthracyclines (ANT) with total cumulative dose 95-600 (median 221) mg/m2, patients from group II (n = 33) received therapy without anthracyclines (nonANT). Control group consisted from 44 age- and gender-matched apparently healthy subjects. Results: Levels of NTproBNP were significantly higher in ANT group than in controls (median 51,52 vs 17,37 pg/ml; p=0.0026). Patients treated with ANT had significantly increased median values of NTproBNP compared with patients in non ANT group (51,52 vs 12,24 pg/ml; p=0.0002). CTnT levels remained below the diagnostic cut-off levels in all groups. No patient had echocardiographic abnormalities, but significant differences were found in mean values of left ventricular ejection fraction and deceleration time between patients treated with and without ANT. Conclusions: Assessment of plasma NTproBNP concentrations may be an effective tool for detection of late subclinical cardiac damage in survivors of childhood leukemia previously treated with low ANT doses. Higher NTproBNP levels in patients after ANT therapy might reflect an initial stage of cardiotoxicity before the development of echocardiographic abnormalities. This study was supported by a grant from Ministry of Health 2007/42-UK-18, Slovakia.

scholarly journals Prodrug of ICRF-193 provides promising protective effects against chronic anthracycline cardiotoxicity on a rabbit model in vivo

2021 ◽  
Author(s):  
Petra Kollárová-Brázdová ◽  
Olga Lencova-Popelova ◽  
Galina Karabanovich ◽  
Júlia Kocúrová-Lengvarská ◽  
Jan Kubes ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Left Ventricular ◽  
Water Soluble ◽  
Drug Candidate ◽  
Protective Effects ◽  
Cardiac Damage ◽  
Anthracycline Cardiotoxicity ◽  
Lv Dysfunction ◽  
Full Protection

The anthracycline (ANT) anticancer drugs such as doxorubicin or daunorubicin (DAU) can cause serious myocardial injury and chronic cardiac dysfunction in cancer survivors. A bisdioxopiperazine agent dexrazoxane has been developed as a cardioprotective drug to prevent these adverse events, but it is uncertain whether it is the best representative of the class. This study used a rabbit model of chronic ANT cardiotoxicity to examine another bisdioxopiperazine compound called GK-667, a water-soluble prodrug of ICRF-193, as a potential cardioprotectant. The cardiotoxicity was induced by DAU (3 mg/kg, i.v. weekly, 10 weeks), and GK-667 (1 or 5 mg/kg, i.v.) was administered before each DAU dose. The treatment with GK-667 was well tolerated and provided full protection against DAU-induced mortality and left ventricular (LV) dysfunction (determined by echocardiography and LV catheterization). Markers of cardiac damage/dysfunction revealed minor cardiac damage in the group co-treated with GK-667 in the lower dose, whereas almost full protection was achieved with the higher dose. This was associated with similar prevention of DAU-induced dysregulation of redox and calcium homeostasis proteins. GK-667 dose-dependently prevented p53-mediated DNA damage response in the LV myocardium not only in the chronic experiment but also after single DAU administration. These effects appear essential for cardioprotection, presumably because of the topoisomerase IIβ inhibition provided by its active metabolite ICRF-193. In addition, GK-667 administration did not alter the plasma pharmacokinetics of DAU and its main metabolite daunorubicinol in rabbits in vivo. Hence, GK-667 merits further investigation as a promising drug candidate for cardioprotection against chronic ANT cardiotoxicity.

Tissue characterization and myocardium strain by cardiac magnetic resonance imaging in the early detection of anthracycline cardiotoxicity

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.B.S.S Costa ◽  
B.M Leal ◽  
C.B.B.V Cruz ◽  
A.V.B Pavani ◽  
J Pereira ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Early Detection ◽  
Ejection Fraction ◽  
Cycle Time ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Public Institution ◽  
Funding Source ◽  
Anthracycline Cardiotoxicity

Abstract Background Cardiotoxicity (CT) remains an important cause of morbidity and mortality in patients with lymphomas treated with anthracyclines. Current strategies for early detection of CT during chemotherapy are not yet fully established. Purpose To evaluate the performance of cardiac magnetic resonance with T1 mapping and myocardium strain by feature tracking during chemotherapy in detecting anthracycline CT in patients with lymphoma. Methods From June 2017 to March 2019, patients with lymphoma planned to start chemotherapy with anthracyclines were evaluated by a cardiologist to check the eligibility criteria. At baseline (Time 1), at the end of 3° cycle (Time 2) and 30 days after the final cycle (Time 3), patients were evaluated through cardiac biomarkers, electrocardiogram and cardiac magnetic resonance (CMR). Strain, MapT1 and extracellular volume (ECV) were evaluated in all patients. CT was defined as drop of the left ventricular fraction (LVEF) >10% or LVEF decrease below 50%. A p value <0.05 was considered statistically significant. Result We included 48 patients, mean age was 45.32 (± 17.84) years-old and 25 (52.1%) were female. The prevalence of hypertension, diabetes and dyslipidemia was 18.8%, 10.4% and 10.4%, respectively. CT was diagnosed in 13 patients (27%). At baseline, there was no difference between cardiotoxicity group (CTG) and no cardiotoxicity group (nCTG) in CMR diastolic volume, systolic volume, nativeT1 map and global longitudinal strain (GLS), respectively (116 [103.6–138.1]ml vs 136.3 [115.7–173.8], p=0.069), (46 [38.0–58.5] ml vs 63.0 [44.5–74.2, p=0.069), (1540.6 [1478.3–1591.1]ms vs 1514.8 [1487.5–1786.3]ms, p=0.568) and (−15.94±2.91% vs −14.84±2.65%, p=0.243). Regarding the others CMR parameters, we showed that comparing CTG patients with nCTG patients at Time 3, systolic volumes were higher (54.8 [45.0–67.0] ml vs 78.51 [53.9–96.3] ml, p=0.007), right ejection fraction was lower (53.41±9.73% vs 46.29±3.93%, p=0.002), LVEF was lower (58.7±5.69% vs 46.67±8.12%, p<0.001) and GLS and radial strain were also reduced (−13.92±1.76% vs −12.44±2.7%, p=0.043) and (22.9 [21.18–27.43]% vs 19.84 [17.12–21.73], p=0.017), respectively. We did not observe any difference between groups in the native T1 map between groups at Time 2 and 3 1537.75 (1493.76–1589.72)ms vs 1601.99 (1501.12–1673.44)ms (p 0.383) and 1538.43 (1479.03–1633.6)ms and 1612.85 (1522.74–1638.34) ms (p=0.289). Similarly, the ECV value was no difference between groups at Time 2 and 3 (25.17 [23.62–32.83]% vs 24.42 [22.75–27.47], p=0.281 and 27.5 [23.59 - 31,9]% vs 27.2 [23.84–28.47]%, p=0.529, respectively). Conclusions Cardiotoxicity is a frequent complication in anthracycline treated patients. CMR evaluation, through analysis of volumes, ejection fraction and strain might early identify these patients, allowing prevention strategies to be initiated to improve cardiovascular outcomes. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Fundação de Apoio a pesquisa do estado de São Paulo - FAPESP

scholarly journals Prognostic Value of MicroRNAs in Patients after Myocardial Infarction: A Substudy of PRAGUE-18

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
M. Hromádka ◽  
V. Černá ◽  
M. Pešta ◽  
A. Kučerová ◽  
J. Jarkovský ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Plasma Levels ◽  
Troponin T ◽  
Statistical Significance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Major Adverse Cardiovascular Events ◽  
Ventricular Ejection Fraction ◽  
Risk Of Death ◽  
Increased Risk

Background. The evaluation of the long-term risk of major adverse cardiovascular events and cardiac death in patients after acute myocardial infarction (AMI) is an established clinical process. Laboratory markers may significantly help with the risk stratification of these patients. Our objective was to find the relation of selected microRNAs to the standard markers of AMI and determine if these microRNAs can be used to identify patients at increased risk. Methods. Selected microRNAs (miR-1, miR-133a, and miR-499) were measured in a cohort of 122 patients from the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI treated with primary percutaneous coronary intervention (pPCI)). The cohort was split into two subgroups: 116 patients who did not die (survivors) and 6 patients who died (nonsurvivors) during the 365-day period after AMI. Plasma levels of selected circulating miRNAs were then assessed in combination with high-sensitivity cardiac troponin T (hsTnT) and N-terminal probrain natriuretic peptide (NT-proBNP). Results. miR-1, miR-133a, and miR-499 correlated positively with NT-proBNP and hsTnT 24 hours after admission and negatively with left ventricular ejection fraction (LVEF). Both miR-1 and miR-133a positively correlated with hsTnT at admission. Median relative levels of all selected miRNAs were higher in the subgroup of nonsurvivors (N=6) in comparison with survivors (N=116), but the difference did not reach statistical significance. All patients in the nonsurvivor subgroup had miR-499 and NT-proBNP levels above the cut-off values (891.5 ng/L for NT-proBNP and 0.088 for miR-499), whereas in the survivor subgroup, only 28.4% of patients were above the cut-off values (p=0.001). Conclusions. Statistically significant correlation was found between miR-1, miR-133a, and miR-499 and hsTnT, NT-proBNP, and LVEF. In addition, this analysis suggests that plasma levels of circulating miR-499 could contribute to the identification of patients at increased risk of death during the first year after AMI, especially when combined with NT-proBNP levels.

scholarly journals Evaluation of ECG time intervals in a rabbit model of anthracycline-induced cardiomyopathy: a useful tool for assessment of cardioprotective agents

2007 ◽  
pp. 251-254 ◽  
Author(s):  
A Potáčová ◽  
M Adamcová ◽  
H Čajnáková ◽  
L Hrbatová ◽  
M Štěrba ◽  
...  
Keyword(s):  
Troponin T ◽  
Plasma Concentrations ◽  
Rabbit Model ◽  
Time Intervals ◽  
Anthracycline Cardiotoxicity ◽  
Anthracycline Cardiomyopathy ◽  
Non Invasive ◽  
Qrs Duration ◽  
Chelating Compounds ◽  
First Time

The aim of this study was to analyze the ECG time intervals in the course of the development of chronic anthracycline cardiomyopathy in rabbits. Furthermore, this approach was employed to study the effects of a model cardioprotective drug (dexrazoxane) and two novel iron chelating compounds--salicylaldehyde isonicotinoyl hydrazone (SIH) and pyridoxal 2-chlorobenzoyl hydrazone (o-108). Repeated daunorubicin administration induced a significant and progressive prolongation of the QRS complex commencing with the eighth week of administration. At the end of the study, we identified a significant correlation between QRS duration and the contractility index dP/dt(max) (r = -0.81; P<0.001) as well as with the plasma concentrations of cardiac troponin T (r = 0.78; P<0.001). In contrast, no alterations in ECG time intervals were revealed in the groups co-treated with either dexrazoxane or both novel cardioprotective drugs (SIH, o-108). Hence, in this study, the QRS duration is for the first time shown as a parameter suitable for the non-invasive evaluation of the anthracycline cardiotoxicity and cardioprotective effects of both well established and investigated drugs. Moreover, our results strongly suggest that novel iron chelators (SIH and o-108) merit further study as promising cardioprotective drugs against anthracycline cardiotoxicity.

Plasma Brain Natriuretic Peptide, Serum Troponin T and Echocardiographic Evaluation in Children Treated with Doxorubicin*.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4583-4583
Author(s):  
Teresa Jackowska ◽  
Robert Wasilewski ◽  
Maria Wasik ◽  
Malgorzata Golabek ◽  
Michal Matysiak
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Levels ◽  
Troponin T ◽  
Systolic Function ◽  
Clinical Signs ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Healthy Children ◽  
Plasma Brain Natriuretic Peptide

Abstract Background: Doxorubicin (DOX) is one of the most effective agents in treatment of acute lymphoblastic leukaemia (ALL). However, a potential heart damage caused by DOX in patients who have been cured of ALL may lessen the success of their cure. Plasma brain natriuretic peptide levels and cardiac Troponin T are highly sensitive biochemical markers for myocardial damage. Objectives of the study: We aimed to measure N-terminal proBNP (8–29) (Nt-proBNP) and serum Troponin T(cTnT) levels in 125 children (98 with ALL after completion of treatment with DOX and 27 healthy children). Median age at diagnosis was 5.5 years. Methods used: Concentration of plasma N-terminal proBNP was measured in children by enzyme immunoassay (Biomedica). cTnT levels were measured by an electrochemiluminescence immunoassay process (Third generation) on the Elecsys 1010 System (Roche Diagnostic). Echocardiograms were performed by paediatric cardiologists. Using two-dimensional M-mode echocardiography shortening fraction (%SF) and ejection fraction (%EF) were determined as systolic function. Results: The cumulative DOX doses were 240mg/m2. None of the patients had clinical signs or symptoms of cardiotoxicity. All of the patients had normal systolic function parameters. Mean Nt-proBNP plasma levels were normal − 64 fmol/ml (10.3–597.3 fmol/ml) in all examined children. Mean Nt-proBNP both in ALL patients (63.8 fmol/ml) and in healthy (58.4 fmol/ml) were within the normal range. Out of the 98 patients 45 (46%) had slightly elevated Nt-proBNP levels in comparison with healthy subjects. Nt-proBNP plasma levels were not significantly different in boys (55.8 fmol/mL) in comparison with girls (56.3 fmol/mL. In all patients the serum levels of cTnT were below the detection limit (<0.010 ng/ml). Conclusion: Our preliminary results suggest that measurement of Nt-proBNP plasma levels is useful in the detection of subclinical left ventricular dysfunction in children with ALL receiving DOX therapy.

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