scholarly journals A case series about the favorable effects of sacubitril/valsartan on anthracycline cardiomyopathy

2020 ◽  
Vol 8 ◽  
pp. 2050313X2095218
Author(s):  
Renato De Vecchis ◽  
Andrea Paccone

Anthracyclines are the cornerstone of treatment for many solid and hematological cancers such as breast cancer or lymphoma for the past 50 years. Nevertheless, in a non-negligible proportion of patients, they elicit dilated cardiomyopathy as a side effect, which causes in turn cardiac decompensation. Conversely, for some years, sacubitril/valsartan has been proposed as a new therapeutic paradigm for all varieties of heart failure with reduced left ventricular ejection fraction, due to its balanced enhancement of natriuretic peptides’ properties coupled with a blocking effect on the AT1 angiotensin receptors. In this article, two clinical cases are illustrated in which the therapeutic action of sacubitril/valsartan against anthracycline cardiomyopathy would seem to be demonstrated by the improvement of symptoms and echocardiographic parameters. Thus, further studies would be warranted for better evaluating the potential role of sacubitril/valsartan as a novel therapeutic tool against anthracycline cardiotoxicity.

Kardiologiia ◽  
2019 ◽  
Vol 59 (7S) ◽  
pp. 15-22
Author(s):  
S. N. Shilov ◽  
A. T. Teplyakov ◽  
A. A. Popova ◽  
E. N. Berezikova ◽  
M. N. Neupokoeva ◽  
...  

Aims. To study the prognostic significance of polymorphism of the p53 gene (polymorphism Arg72Pro exon 4, rs1042522) on the development of cardiotoxic remodeling of the left ventricle and heart failure. Material and methods. A total of 176 women with breast cancer who received anthracycline antibiotics as part of polychemotherapeutic treatment regimens were examined. Based on the results of the survey, 12 months after the end of polychemotherapy, patients in the remission of the underlying disease were divided into 2 groups: patients with cardiotoxic remodeling (52 patients) and women with preserved heart function (124 patients). All patients before the start of the course of chemotherapy, in the dynamics of treatment with anthracyclines and after therapy with such were carried out the study of echocardiographic parameters. All the patients were taken genetic material, followed by typing alleles of the gene for the protein p53 (rs1042522). Results. Analysis of echocardiographic parameters in patients 12 months after the completion of polychemotherapy in comparison with those before treatment showed a significant difference in the final systolic (33 mm [31; 35] and 28 mm [26; 31], p<0.00001) and terminal diastolic dimensions (51 mm [49; 54.5] and 44 mm [42; 48.5], p=0.0003), as well as a significant decrease in the left ventricular ejection fraction (54.5% [51.5; 58] and 65.5% [62; 70], p<0.00001) in the group of women with developed anthracycline cardiotoxicity. The presence of the Arg/Arg genotype was associated with the development of cardiotoxic myocardial damage during polychemotherapy (OR=3.86, 95% C.I.=1.45-10.26, p=0.005). The Pro/Pro genotype has proved to be a protective factor (OR=0.26, 95% C.I.=0.09-0.69, p=0.015). The conclusion. Predicting the cardiotoxicity of chemotherapy using the polymorphism of the p53 gene is an effective measure of early pre-symptom diagnosis of an increased risk of anthracyclineinduced cardiotoxicity.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.


Open Heart ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. e001346
Author(s):  
Aénora Roger-Rollé ◽  
Eve Cariou ◽  
Khailène Rguez ◽  
Pauline Fournier ◽  
Yoan Lavie-Badie ◽  
...  

BackgroundCardiac amyloidosis (CA) is a life-threatening restrictive cardiomyopathy. Identifying patients with a poor prognosis is essential to ensure appropriate care. The aim of this study was to compare myocardial work (MW) indices with standard echocardiographic parameters in predicting mortality among patients with CA.MethodsClinical, biological and transthoracic echocardiographic parameters were retrospectively compared among 118 patients with CA. Global work index (GWI) was calculated as the area of left ventricular pressure–strain loop. Global work efficiency (GWE) was defined as percentage ratio of constructive work to sum of constructive and wasted works. Sixty-one (52%) patients performed a cardiopulmonary exercise.ResultsGWI, GWE, global longitudinal strain (GLS), left ventricular ejection fraction (LVEF) and myocardial contraction fraction (MCF) were correlated with N-terminal prohormone brain natriuretic peptide (R=−0.518, R=−0.383, R=−0.553, R=−0.382 and R=−0.336, respectively; p<0.001). GWI and GLS were correlated with peak oxygen consumption (R=0.359 and R=0.313, respectively; p<0.05). Twenty-eight (24%) patients died during a median follow-up of 11 (4–19) months. The best cut-off values to predict all-cause mortality for GWI, GWE, GLS, LVEF and MCF were 937 mm Hg/%, 89%, 10%, 52% and 15%, respectively. The area under the receiver operator characteristic curve of GWE, GLS, GWI, LVEF and MCF were 0.689, 0.631, 0.626, 0.511 and 0.504, respectively.ConclusionIn CA population, MW indices are well correlated with known prognosis markers and are better than LVEF and MCF in predicting mortality. However, MW does not perform better than GLS.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Kim ◽  
H L Kim ◽  
K T Park ◽  
W H Lim ◽  
J B Seo ◽  
...  

Abstract Background/Introduction Previous studies have focused on only 1 or 2 echocardiographic parameters as prognostic marker in patients with acute ischemic stroke (AIS). Purpose Various echocardiographic parameters in the same patient were systemically evaluated for their prognostic significance in AIS. Methods A total of 900 patients with AIS who underwent transthoracic echocardiography (TTE) (72.6 ± 12.0 years and 60% male) were retrospectively reviewed. Composite events including all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and coronary revascularization were assessed during clinical follow-up. Results During a median follow-up of 3.3 years (interquartile range, 0.6-5.1 years), there were 151 (16.8%) composite events. Univariable analyses showed that low left ventricular ejection fraction (LVEF) (&lt; 60%), increased peak tricuspid regurgitation (TR) velocity (&gt; 2.8 m/s) and aortic valve (AV) sclerosis were associated with composite events (P &lt; 0.05 for each). In the multivariable analyses after controlling for potential confounders, LVEF &lt; 60% (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.30-2.77; P = 0.001) and AV sclerosis (HR, 1.56; 95% CI, 1.10-2.21; P = 0.013) were independent prognostic factors associated with composite events. Multivariable analysis showed that HR for composite events gradually increased according to LVEF and AV sclerosis: HR was 2.8-fold higher in the highest-risk group than in the lowest group (P = 0.001). Conclusions In patients with AIS, LVEF &lt; 60% and the presence of AV sclerosis predicts the future vascular events. Patients with AIS exhibiting reduced LVEF and AV sclerosis may benefit from aggressive secondary prevention Abstract P1348 Figure. COX plot for composite event


2005 ◽  
Vol 23 (31) ◽  
pp. 7820-7826 ◽  
Author(s):  
Michael S. Ewer ◽  
Mary T. Vooletich ◽  
Jean-Bernard Durand ◽  
Myrshia L. Woods ◽  
Joseph R. Davis ◽  
...  

PurposeTrastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity.Patients and MethodsOver a 4-year period, 38 patients with HER2/neu–positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy.ResultsAfter doxorubicin but before trastuzumab, the mean (± standard deviation) left ventricular ejection fraction (LVEF) was 0.61 ± 0.13, and the LVEF decreased to 0.43 ± 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 ± 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen.ConclusionPatients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction.


2020 ◽  
Author(s):  
Kartik Pandurang Jadhav ◽  
Pankaj Jariwala

ABSTRACT Various publications have increasingly reported the development of the prothrombotic state and its consequences associated with coronavirus disease 2019 (COVID-19). Although the exact etiology is uncertain, various factors collectively increase the risk of thrombus formation in COVID-19 patients. We present a case series of four patients with left ventricular (LV) thrombus formation along with simultaneous COVID-19 infection. All these patients had acute myocardial infarction with left ventricular ejection fraction (LVEF) between 35-45%. Among the series, two patients had favourable outcomes with complete resolution of LV thrombus, whereas the other two suffered cerebral embolization followed by mortality. This study looks in depth at all cases of intracardiac thrombi formation in patients with COVID-19 published worldwide. n addition to the increased predisposition for venous/ arterial thrombosis, even a few cases of intra- cardiac thrombus have been reported. Systemic thrombolysis is an initial treatment of choice for the management of right cardiac thrombi with pulmonary thromboembolism (PTE) and ST-elevation myocardial infarction (STEMI) in COVID-19. Right cardiac thrombi have better outcomes when compared to left cardiac thrombi.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9592-9592
Author(s):  
Beata Mladosievicova ◽  
Dagmar Urbanova ◽  
Eva Radvanska ◽  
Eva Mikuskova ◽  
Iveta Simkova

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.


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