The Impact of Polymorphisms in ATP-Binding Cassette Transporter Genes on Anthracycline-Induced Early Cardiotoxicity in Patients with Breast Cancer.

BACKGROUND: Cardiac side effects associated with anthracycline-based treatment may seriously compromise the prognosis of patients with breast cancer (BC). Evidence shows that genes that operate in drug metabolism can influence the risk of anthracycline-induced cardiotoxicity (AIC). ATP-binding cassette (ABC) transporters could serve as one of the potential biomarkers for AIC risk stratification. We aimed to determine the link between single-nucleotide polymorphisms (SNPs) in several ABC genes (ABCB1 rs1045642, ABCC1 rs4148350, ABCC1 rs3743527) and cardiotoxicity. METHODS: The study included 71 patients with BC, who were treated with doxorubicin-based chemotherapy. Two-dimensional echocardiography and speckle-tracking echocardiography were performed. AIC was defined as a new decrease of 10 percentage points in the left ventricular ejection fraction (LVEF). SNPs in ABCB1 and ABCC1 genes were evaluated using real-time PCR. RESULTS: After a cumulative dose of 236.70 mg/m2 of doxorubicin, 28.2% patients met the criteria of AIC. Patients who developed AIC had a larger impairment in left ventricular systolic function compared to those who did not develop AIC (LVEF: 50.20 ± 2.38% vs. 55.41 ± 1.13%, p < 0.001; global longitudinal strain: -17.03 ± 0.52% vs. -18.40 ± 0.88%, p < 0.001). The ABCC1 rs4148350 TG genotype was associated with higher rates of cardiotoxicity (TG vs. GG OR = 8.000, 95% CI = 1.405-45.547, p = 0.019). CONCLUSIONS: The study showed that ABCC1 rs4148350 is associated with AIC and could be a potential biomarker to assess the risk of treatment side effects in patients with BC.

Prognostic Impact of Global Longitudinal Strain and NT-proBNP on Early Development of Cardiotoxicity in Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy.

Background. The most important anthracycline side effect is cardiotoxicity, resulting in congestive heart failure (HF). Early detection of cardiac dysfunction and appropriate treatment can improve outcomes and reduce the progression of HF. The aim of our study was to evaluate changes in clinical data, echocardiographic parameters, and NT-proBNP, as well as their associations with early anthracycline-induced cardiotoxicity (AIC) in patients treated with anthracycline-based chemotherapy. Methods and Materials. Patients with breast cancer were prospectively assessed with echocardiography, as well as NT-proBNP testing at baseline, (T0), after two cycles (T1) and four cycles (T2) of chemotherapy. AIC was defined as a new decrease in the LVEF of 10 percentage points, to a value below the lower limit of normal. Results. We evaluated 85 patients aged 54.5 ± 9.3 years. After a cumulative dose of 237.9 mg/m2 of doxorubicin, 22 patients (25.9%) met the criteria of AIC after chemotherapy. Patients who subsequently progressed to cardiotoxicity had demonstrated a significantly larger impairment in LV systolic function compared to those who did not develop cardiotoxicity (LVEF: 54.0 ± 1.6% vs. 57.1 ± 1.4% at T1, p < 0.001, and 49.9 ± 2.1% vs. 55.8 ± 1.6% at T2, p < 0.001; GLS: -17.8 ± 0.4% vs. -19.3 ± 0.9% at T1, p < 0.001, and -16.5 ± 11.1% vs. -18.5 ± 0.9% at T2, p < 0.001, respectively). The levels of NT-proBNP increased significantly from 94.8 ± 43.8 ng/L to 154.1 ± 75.6 ng/L, p < 0.001. A relative decrease in GLS ≤ -18.0% (sensitivity: 72.73%; specificity: 92.06%; AUC, 0.94; p < 0.001) and a relative increase in NT-proBNP > 125 ng/L (sensitivity: 90.0%; specificity: 56.9%; AUC, 0.78; p < 0.001) from baseline to T1 predicted subsequent LV cardiotoxicity at T2. Conclusions. Decrease in GLS and elevation in NT-proBNP were significantly associated with AIC, and these could potentially be used to predict subsequent declines in LVEF with anthracycline-based chemotherapy.

Cardiovascular Disorder after Cardiotoxic Non-Hodking's Lymphoma Treatment: A Case Report.

The non-Hodgkin's lymphomas are a diverse group of lymphoid neoplasms that collectively rank fifth in cancer incidence and mortality. Patients treated with mediastinal radiotherapy and/or anthracycline-containing chemotherapy are known to have increased risks of coronary heart disease, valvular heart disease, and heart failure. This may be the result of cancer treatment cardiotoxicity or may be due to accelerated development of cardiovascular disease. We presented 41-year-old male who was admitted to the hospital because of congestive heart failure. He has a medical history of non-Hodgkin's lymphoma treated with anthracycline-based chemotherapy and mediastinal radiotherapy almost 20 years ago. Echocardiography showed significant aortic valve stenosis, thickened and fibrotic pericardium. Coronary angiography showed diffuse three-vessel coronary artery disease. The patient was referred for surgical treatment. Aortic valve replacement, coronary artery bypass grafting and pericardiectomy were successfully performed, symptoms of heart failure reduced.

HFE Gene Variants' Impact on Anthracycline-Based Chemotherapy-Induced Subclinical Cardiotoxicity.

Progress in oncology has allowed to improve outcomes in many breast cancer patients. The core stone of breast cancer chemotherapy is anthracycline-based chemotherapy. Unfortunately, anthracyclines cause cardiotoxicity which is a limiting factor of its use and lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. With evolution of echocardiography subclinical damage is identified, and more sensitive evaluation can be performed. This leads to understanding the heart damage beyond cumulative dose in early phase and importance of other risk factors. There are many risk factors for anthracycline-based chemotherapy cardiotoxicity (ABCC) like arterial hypertension, obesity, diabetes, genetic predisposition, etc. One of possible pathophysiological pathways is iron metabolism, especially HFE gene-regulated iron metabolism pathway. Pre-existing genetic iron metabolism dysregulation increases risk for ABCC. Clinical studies and experimental models in mice have shown potential impact of HFE gene SNP on ABCC. The main objective of our study was to identify the impact of HFE C282Y and H63D SNP on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. Data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in the outpatient clinic were analyzed and SNP RT-PCR tests were performed. Statistically significant association between H63D and ABCC after completion of chemotherapy was observed (p < 0.005). Consequently, our study demonstrated that H63D SNP has an important role in the development of ABCC. HFE SNP mutation status could be used as one of important tools to identify high-risk patients for ABCC.

Impact of Arterial Hypertension on Doxorubicin-Based Chemotherapy-Induced Subclinical Cardiac Damage in Breast Cancer Patients.

Advances in oncologic therapies have allowed to achieve better outcomes and longer survival in many patients with breast cancer. Anthracyclines are cytotoxic antibiotics widely used in daily oncology practice. However, anthracyclines cause cardiotoxicity which is a limiting factor of its use. Cumulative dose of anthracyclines is the major cause of induced cardiotoxicity. According to previous clinical trials, the major predisposing high-risk factors for anthracycline-based chemotherapy-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as diabetes and hypertension. Experimental studies in animals confirm that hypertension may be a significant factor predisposing anthracycline-based chemotherapy cardiotoxicity. The main objective of our study was to identify the effect of pre-existing arterial hypertension on the development of subclinical cardiac damage during or after doxorubicin-based chemotherapy in breast cancer patients. The study was performed prospectively between March 2016 and January 2017 in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics Department of Oncology and Department of Cardiology. Data of 73 women with breast cancer treated with doxorubicin-based chemotherapy in outpatient clinic were analyzed. Statistically significant association between pre-existing arterial hypertension and left ventricular systolic dysfunction after completion of chemotherapy was observed (P < 0.004). Our study demonstrated that pre-existing arterial hypertension has a very important role in the development of anthracycline-based chemotherapy-induced cardiotoxicity, despite arterial hypertension control quality. Consequently, further studies evaluating impact of other risk factors and how early and sufficient management of arterial hypertension could influence the development of cardiotoxicity are needed to avoid permanent cardiac damage.

Accuracy of three-dimensional systolic dyssynchrony and sphericity indexes for identifying early left ventricular remodeling after acute myocardial infarction.

OBJECTIVE: Left ventricle (LV) geometry and dyssynchrony are associated with LV remodeling after acute myocardial infarction (AMI). The aim of this prospective study was to assess the diagnostic value of new three-dimensional echocardiography (3DE) parameters [sphericity (SI) and systolic dyssynchrony indexes (SDI)] for the prediction of LV remodeling after AMI and to compare them with two-dimensional echocardiography (2DE) parameters. METHODS: 2DE and 3DE were performed in 75 patients with AMI within 3 days from the onset of MI and 6 months later. LV remodeling was defined as a ≥15% increase in the LV end-diastolic volume (EDV) at follow-up. 3D SI was calculated by dividing EDV by the volume of a sphere whose diameter was derived from the major end-diastolic LV long axis. SDI was considered as a standard deviation of the time from cardiac cycle onset to minimum systolic volume in 16 LV segments. RESULTS: LV remodeling was identified in 34 (45%) patients using the 2DE method and in 22 (29%) patients using the 3DE method. Evaluated 3DE parameters, such as EDV [area under the receiver operating characteristic (ROC) curve (AUC) 0.742, sensitivity 71%, specificity 79%], end-systolic volume (AUC 0.729, sensitivity 69%, specificity 78%), SDI (AUC 0.777, sensitivity 73%, specificity 77%), and SI, had significant prognostic value for LV remodeling. According to the AUC, the highest predictive value had 3D SI (AUC 0.957, sensitivity 90%, specificity 91%). CONCLUSION: 3DE parameters, especially 3D SI and SDI, play important roles in the prediction of LV remodeling after AMI and can be used in clinical practice.

Severe vancomycin-induced anaphylactic reaction.

Vancomycin is widely used against methicillin-resistant Staphylococcus aureus infections, but it is associated with many adverse effects such as nephrotoxicity, ototoxicity, gastrointestinal disturbances, blood disorders, and two types of hypersensitivity reactions - an anaphylactoid reaction known as "red man syndrome" and anaphylaxis. We report a case of a 23-year-old man who developed a vancomycin-induced anaphylactic reaction in the treatment of methicillin-resistant Staphylococcus aureus infection.