5034 Troponin I and C-reactive protein as biomarkers for changes in left ventricular ejection fraction in patients with early stage breast cancer treated with dose-dense doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel with trastuzumab and lapatinib

2009 ◽  
Vol 7 (2) ◽  
pp. 271 ◽  
Author(s):  
P.G. Morris ◽  
C. Chen ◽  
N. Lin ◽  
B. Moy ◽  
S. Come ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Left Ventricular Ejection Fraction ◽  
Troponin I ◽  
Early Stage ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
C Reactive Protein ◽  
Ventricular Ejection Fraction ◽  
Reactive Protein ◽  
Dose Dense

scholarly journals Dose-Dense Adjuvant Doxorubicin and Cyclophosphamide Is Not Associated With Frequent Short-Term Changes in Left Ventricular Ejection Fraction

2009 ◽  
Vol 27 (36) ◽  
pp. 6117-6123 ◽  
Author(s):  
Patrick G. Morris ◽  
Maura Dickler ◽  
Heather L. McArthur ◽  
Tiffany Traina ◽  
Steven Sugarman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Radionuclide Angiography ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Short Term ◽  
Ventricular Ejection Fraction ◽  
Dose Dense

Purpose Doxorubicin and cyclophosphamide (AC) every 3 weeks has been associated with frequent asymptomatic declines in left ventricular ejection fraction (LVEF). Dose-dense (dd) AC followed by paclitaxel (P) is superior to the same regimen given every third week. Herein, we report the early cardiac safety of three sequential studies of ddAC alone or with bevacizumab (B). Patients and Methods Patients with HER2-positive breast cancer were treated on two trials: ddAC followed by P and trastuzumab (T) and ddAC followed by PT and lapatinib. Patients with HER2-normal breast cancer were treated with B and ddAC followed by B and nanoparticle albumin–bound P. Prospective LVEF measurement by multigated radionuclide angiography scan before and after every 2 week AC for 4 cycles and at month 6 from all three trials were aggregated to determine the early risks of cardiac dysfunction. Results From January 2005 to May 2008, 245 patients were enrolled. The median age was 47 years (range, 27 to 75 years). Median LVEF pre-ddAC was 68% (range, 52% to 82%). LVEF post-ddAC was available in 241 patients (98%) and the median was unchanged at 68% (range, 47% to 81%). Per protocol no patients were ineligible for subsequent targeted biologic therapy based on LVEF decline post-ddAC. In addition, LVEF was available in 222 patients (92%) at 6 months, at which time the median LVEF was similar at 65% (range, 24% to 80%). Within 6 months of initiating chemotherapy, three patients (1.2%; 95% CI, 0.25% to 3.54%) developed CHF, all of whom received T. Conclusion Dose-dense AC with or without concurrent bevacizumab is not associated with frequent acute or short-term declines in LVEF.

scholarly journals Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial

2019 ◽  
Vol 11 ◽  
pp. 175883591986423 ◽  
Author(s):  
Giuseppe Gullo ◽  
Alex J. Eustace ◽  
Alexandra Canonici ◽  
Denis M. Collins ◽  
Michael J. Kennedy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pilot Study ◽  
Growth Factor ◽  
Troponin I ◽  
Early Stage ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ventricular Ejection Fraction

Background: Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients. Methods: Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m2). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF). Results: A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1–72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12–54) months in TN patients versus 38 (22–71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity. Conclusions: We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further. Trial Registration ClinicalTrials.gov Identifier: NCT00911716.

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.

Lisinopril or carvedilol in prevention of trastuzumab-induced cardiotoxicity in patients with HER2-positive early stage breast cancer: Longitudinal changes of left ventricular ejection fraction below normal levels (LVEF <50%).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 509-509
Author(s):  
Pamela N. Munster ◽  
Roy Tamura ◽  
Jeffrey Krischer ◽  
Worta J. McCaskill-Stevens ◽  
Maya Guglin
Keyword(s):  
Breast Cancer ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Early Stage ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
The Impact

509 Background: Treatment of HER2-positive breast cancer patients with trastuzumab is highly effective. However, a trastuzumab-associated decline in the left ventricular ejection fraction (LVEF) and clinical heart failure often prompt interruption and discontinuation of treatment. We therefore evaluated the preventive impact of an ACE inhibitor or beta blockers on the left ventricular ejection fraction (LVEF) during treatment of trastuzumab and chemotherapy. Methods: In a prospective randomized study, women with early stage HER2 positive breast cancer undergoing (neo)adjuvant chemotherapy with trastuzumab were randomized to receive either once daily lisinopril (10mg), carvedilol (10mg) or placebo during treatment with trastuzumab and further stratified by anthracycline use (AC+T versus nonAC+T). In a follow up to the initially presented primary endpoint of overall cardiotoxicity, we measured the protective effects of lisinopril or carvedilol to prevent a trastuzumab induced LVEF decrease to less than 50% over the course of therapy as well as the impact on LVEF decrease by >10% within normal LVEF levels. Results: A total of 468 women (mean age was 51±10.7 years) with HER2 overexpressing early-stage breast cancer from 127 community-based oncology practices were enrolled, a prespecified minimum target of 189 (40%) patients were treated with AC+T and 279 (60%) with nonAC+T. Baseline cardiac risk factors of this study population included obesity and an elevated blood pressure. Patients in the anthracycline group were younger and without hypertension. A small, not clinically relevant decrease in LVEF was observed during trastuzumab therapy in all patients which was not significantly altered by any of the cardiac interventions. The rate of LVEF decline to <50% was much more frequent in patients treated with an anthracycline than those with a non-anthracycline containing regimen (21% vs 4.1%). Treatment with lisinopril averted the decline in LVEF in the AC+T group compared to placebo (10.8% vs 30.5%, p=0.045). A smaller but not significant effect was seen by carvedilol. The incidence of cardiotoxicity manifesting as LVEF decrease by ≥10% within the normal range was similar in both AC+T and the nonAC+T arms, and not affected by either lisinopril or carvedilol. Conclusions: In patients treated with trastuzumab without anthracyclines, the impact of trastuzumab on LVEF is small and infrequent. In contrast, patients treated with anthracyclines prior to trastuzumab, demonstrated a decrease in LVEF to below normal levels in a larger than previously reported number of women in this community based setting. The trastuzumab-anthracycline induced decline in LVEF could be prevented with concurrent treatment with lisinopril, which was tolerable even in patients without hypertension. Clinical trial information: NCT01009918.

scholarly journals The role of systemic inflammation in heart failure

2021 ◽  
Vol 102 (4) ◽  
pp. 510-517
Author(s):  
E V Khazova ◽  
O V Bulashova
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Systemic Inflammation ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
C Reactive Protein ◽  
Ventricular Ejection Fraction ◽  
Reactive Protein ◽  
Highly Sensitive

The discussion continues about the role of systemic inflammation in the pathogenesis of cardiovascular diseases of ischemic etiology. This article reviews the information on the role of C-reactive protein in patients with atherosclerosis and heart failure in risk stratification for adverse cardiovascular events, including assessment of factors affecting the basal level of highly sensitive C-reactive protein. Research data (MRFIT, MONICA) have demonstrated a relationship between an increased level of C-reactive protein and the development of coronary heart disease. An increase in the serum level of highly sensitive C-reactive protein is observed in arterial hypertension, dyslipidemia, type 2 diabetes mellitus and insulin resistance, which indicates the involvement of systemic inflammation in these disorders. Currently, the assessment of highly sensitive C-reactive protein is used to determine the risk of developing myocardial infarction and stroke. It has been proven that heart failure patients have a high level of highly sensitive C-reactive protein compared with patients without heart failure. The level of C-reactive protein is referred to as modifiable risk factors for cardiovascular diseases of ischemic origin, since lifestyle changes or taking drugs such as statins, non-steroidal anti-inflammatory drugs, glucocorticoids, etc. reduce the level of highly sensitive C-reactive protein. In patients with heart failure with different left ventricular ejection fraction values, it was found that the regression of the inflammatory response is accompanied by an improvement in prognosis, which confirms the hypothesis of inflammation as a response to stress, which has negative consequences for the cardiovascular system.

scholarly journals Long-term clinical prognosis predictors in patients with chronic heart failure and reduced left ventricular ejection fraction

2019 ◽  
Vol 26 (5) ◽  
pp. 33-43 ◽  
Author(s):  
L. G. Voronkov ◽  
К. V. Voitsekhovska ◽  
S. V. Fedkiv ◽  
T. I. Gavrilenko ◽  
V. I. Koval
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Left Atrium ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
C Reactive Protein ◽  
Ventricular Ejection Fraction ◽  
Reactive Protein ◽  
Vasodilator Response

The aim – to identify prognostic factors for the development of adverse cardiovascular events (death and hospitalization) in patients with chronic heart failure (CHF) and left ventricular ejection fraction (LVEF) ≤ 35 % after long-term observation. Materials and methods. 120 stable patients with CHF, aged 18–75, II–IV functional classes according to NYHA, with LVEF ≤ 35 % were examined. Using multiple logistic regression according to the Cox method, we analyzed independent factors that affect the long-term prognosis of patients with heart failure. Results and discussion. During the observation period, out of 120 patients, 61 patients reached combined critical point (CCР). In the univariate regression model, predictors of CCР reaching were NYHA functional class, weigh loss of ≥ 6 % over the past 6 months, systolic and diastolic blood pressure, patient’s history of myocardial infarction, angina pectoris, anemia, number of hospitalizations over the past year and parameters reflecting the functional state of the patient (6-minute walk distance, number of extensions of the lower limb). The risk of CCP developing is significantly higher in patients with lower body mass index, shoulder circumference of a tense and unstressed arm, hip, thickness of the skin-fat fold over biceps and triceps, estimated percentage of body fat. Рredictors CCP reaching are higher levels of uric acid and C-reactive protein. Echocardiographic predictors of CCP onset were LVEF, size of the left atrium, TAPSE score, as well as its ratio to systolic pressure in the pulmonary artery, index of final diastolic pressure in the left ventricle. Also, the risk of CCP reaching is greater at lower values of the flow-dependent vasodilator response. Independent predictors of CCP onset were the circumference of the shoulder of an unstressed arm, the level of C-reactive protein in the blood, and the rate of flow-dependent vasodilator response. When analyzing the indices in 77 patients, who underwent densitometry, it was revealed that the E/E´ index, the index of muscle tissue of the extremities, the index of fat mass, and the ratio of fat mass to growth affect CCP reaching. In a multivariate analysis, taking into account densitometry indices, independent predictors of CCP onset were the size of the left atrium, the index of muscle mass of the extremities, the rate of flow-dependent vasodilator response and the presence of myocardial infarction in anamnesis. Conclusions. Independent predictors of CCP reaching in patients with CHF and LVEF ≤ 35 % are myocardial infarction in anamnesis, lower arm circumference of the arm, limb muscle mass index, flow-dependent vasodilator response, higher levels of C-reactive protein, sizes of the left atrium.

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