Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients

As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal pro–B-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal pro–B-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardiotoxicity and its associated morbidity and mortality

Socio-Economic Variations Determine the Clinical Presentation, Aetiology and Outcome of Infective Endocarditis: a Prospective Cohort Study from the ESC-EORP EURO-ENDO (European Infective Endocarditis) Registry.

peer reviewedBACKGROUND: Infective endocarditis (IE) is a life-threatening disease associated with high mortality and morbidity worldwide. We sought to determine how socio-economic factors might influence its epidemiology, clinical presentation, investigation and management, and outcome, in a large international multi-centre registry. METHODS: The EurObservationalProgramme (EORP) of the European Society of Cardiology (ESC) EURO-ENDO registry comprises a prospective cohort of 3113 adult patients admitted for IE in 156 hospitals in 40 countries between January 2016 and March 2018. Patients were separated in 3 groups, according to World Bank economic stratification (Group 1 - high income [75.6%]; Group 2 - upper-middle income [15.4%]; Group 3 - lower-middle income [9.1%]). RESULTS: Group 3 patients were younger (median age [IQR]: Group 1 - 66 [53-75] years; Group 2 - 57 [41-68] years; Group 3 - 33 [26-43] years; p<0.001) with a higher frequency of smokers, intravenous drug use and human immunodeficiency virus (HIV) infection (all p<0.001) and presented later (median [IQR) days since symptom onset: Group 1 - 12 [3-35]; Group 2 - 19 [6-54]; Group 3 - 31 [12-62]; p<0.001) with a higher likelihood of developing congestive heart failure (13.6%; 11.1%; and 22.6%, respectively; p<0.001) and persistent fever (9.8%; 14.2%; 27.9%; p<0.001). Among 2157 (69.3%) patients with theoretical indication for cardiac surgery, surgery was performed less frequently in Group 3 patients (75.5%, 76.8% and 51.3%, respectively p<0.001) who also demonstrated the highest mortality (15.0%, 23.0% and 23.7%, respectively; p<0.001). CONCLUSIONS: Socio-economic factors influence the clinical profile of patients presenting with IE across the world. Despite younger age, patients from the poorest countries presented with more frequent complications and higher mortality associated with delayed diagnosis and lower use of surgery

Cardiotoxicity of cancer therapeutics: current issues in screening, prevention and therapy

In the context of modern cancer chemotherapeutics, cancer survivors are living longer and being exposed to potential comorbidities related to non-cancer side effects of such treatments. With close monitoring of cancer patients receiving potentially cardiotoxic medical therapies, oncologists and cardiologists alike are identifying patients in both clinical and subclinical phases of cardiovascular disease related to such chemotherapies. Specifically, cardiotoxicity at the level of the myocardium and potential for the development of heart failure are becoming a growing concern with increasing survival of cancer patients.Traditional chemotherapeutic agents used commonly in the treatment of breast cancer and hematologic malignancies, such as anthracyclines and HER-2 antagonists, are well known to be associated with cardiovascular sequelae. Patients often present without symptoms and an abnormal cardiac imaging study performed as part of routine evaluation of patients receiving cardiotoxic therapies. Additionally, patients can present with signs and symptoms of cardiovascular disease months to years after receiving the chemotherapies. As the understanding of the physiology underlying the various cancers has grown, therapies have been developed that target specific molecules that represent key aspects of physiologic pathways responsible for cancer growth. Inhibition of these pathways, such as those involving tyrosine kinases, has lead to the potential for cardiotoxicity as well. In view of the potential cardiotoxicity of specific chemotherapies, there is a growing interest in identifying patients who are at risk of cardiotoxicity prior to becoming symptomatic or developing cardiotoxicity that may limit the use of potentially life-saving chemotherapy agents. Serological markers and novel cardiac imaging techniques have become the source of many investigations with the goal of screening patients for pre-clinical cardiotoxicity. Additionally, studies have been perform

Sex-specific cardiovascular responses to control or high fat diet feeding in C57bl/6 mice chronically exposed to bisphenol A.

The increased pericardial fat which often accompanies overall obesity is thought to alter cardiac structure/function and increase the risk for atrial fibrillation. We hypothesized that chronic exposure to bisphenol A (BPA) would induce pericardial fat, cardiac hypertrophy or arrhythmia. C57bl/6n dams were exposed to BPA (25 ng/ml drinking water) beginning on gestation day 11 and progeny continued on 2.5 ng BPA/ml drinking water. The progeny of control dams (VEH) and dams treated with diethylstilbestrol (DES, 1 μg/kg/day, gestation days 11–14) had tap water. After weaning progeny were fed either a control (CD) or high fat diet (HFD) for 3 months. Pericardial fat was present in CD-BPA and CD-DES and not CD-VEH mice, and was increased in all HFD mice. Catecholamine challenge revealed no differences in males, but BPA-exposed females had longer P-wave and QRS complex duration. Only CD-BPA and CD-DES females developed cardiac hypertrophy which was independent of increased blood pressure. Calcium homeostasis protein expression changes in HFD-BPA and HFD-DES mice predict reduced SERCA2 activity in males and increased SERCA2 activity in females. Thus, chronic BPA exposure induced pericardial fat in the absence of HFD, and female-specific changes in cardiac hypertrophy development and cardiac electrical conduction after a catecholamine challenge

Time trends of left ventricular ejection fraction and myocardial deformation indices in a cohort of women with breast cancer treated with anthracyclines, taxanes, and trastuzumab

Background: Trastuzumab, a HER2 monoclonal antibody, has transformed the prognosis of patients with the aggressive HER2-positive breast cancer type. Trastuzumab augments the cardiotoxic effects of anthracyclines, but its effect is thought to be at least partially reversible. The objective of this study was to examine the time trends of left ventricular (LV) size and function in a cohort of women treated with anthracyclines and trastuzumab. Methods: Twenty-nine patients >18 years of age with first-time breast cancer treated with anthracyclines and trastuzumab were monitored using echocardiography before, at the completion of, and at a median follow-up of 24.7 months (interquartile range, 15.9-34 months) after the end of their cancer treatment. LV volume, LV ejection fraction, and global peak systolic longitudinal strain and strain rate were measured in the apical four- and two-chamber views. Left ventricular ejection fraction was measured using a modified Simpson's biplane method. Results: LV end-diastolic and end-systolic volumes increased at the end of treatment compared with baseline and did not recover during follow-up. Left ventricular ejection fraction, strain, and strain rate decreased at the end of treatment compared with baseline (from 64 +/- 6% to 59 +/- 8%, from -20.0 +/-2.5% to -17.6 +/- 2.6%, and from -1.26 +/- 0.23 to -1.13 +/- 0.16 sec2 years after the end of anthracycline and trastuzumab treatment, without significant recovery after trastuzumab cessation, suggestive of long-term underlying cardiac damage and remodeling