Cancer Treatment Related Cardiac Dysfunction Research Articles

Abstract PO1-10-04: Racial and Ethnic Disparities in Anthracycline and HER2-targeted Cardiotoxicity in Patients With Breast Cancer Using Global Longitudinal Strain Imaging Techniques

Abstract Purpose: Studies of global longitudinal strain (GLS) as a predictor of cancer treatment-related cardiac dysfunction (CTRCD) have been limited in racial/ethnic minority populations who are more likely to have risk factors associated with CTRCD. Our aim was to assess the utilization of GLS and development of CTRCD in a racially and ethnically diverse population of patients at an academic center in New York City. Methods: Patients were included if they had a breast cancer diagnosis and began treatment with anthracycline or HER2-directed therapies at Columbia University Irving Medical Center (CUIMC) from February 1, 2020-July 31, 2022. All patients and variables were identified via the electronic health record. Cardiovascular comorbidities including obesity, hypertension, diabetes, hyperlipidemia, coronary artery disease, congestive heart failure, and other cardiac disease, were recorded. Receipt of transthoracic echocardiogram(s) (TTE) with/without GLS were recorded, along with GLS and left ventricular ejection fraction (LVEF) values. CTRCD was defined as LVEF decrease of ≥10% to a LVEF value < 53% or GLS decrease of ≥ 15% from baseline or GLS < -18%. Analyses included descriptive statistics and univariable and multivariable logistic regression models to evaluate predictors of CTRCD by either LVEF or GLS definition. Results: We identified 270 eligible patients. Mean age was 51.8 years (standard deviation 13.0), 85 (31.5%) identified as White, 47 (17.4%) as Black/African, and 16 (5.9%) as Asian; 135 (50.0%) identified as Non-Hispanic/Latino, and 79 (29.2%) as Hispanic/Latino. Approximately half of the patient cohort, n=137 (50.7%) had a TTE with GLS during the study period. Of the TTEs done at CUIMC (n=658), 270 (41%) were ordered with GLS assessment, of which 184 (68%) reported a GLS value and 86 (32%) were not assessable due to image quality. Forty-three (16%) patients developed CTRCD: 20 (7%) by GLS criteria, 13 (5%) by LVEF criteria, and 10 (4%) by both GLS and LVEF criteria. In univariable analyses, race (OR 5.78, 95%CI 1.62-20.4 Asian compared to White), treatment with HER2 therapy without anthracycline versus anthracycline (OR 2.78, 95%CI 1.34-6.23), and prescription for cardiac medication prior to systemic therapy (OR 2.27, 95%CI 1.08-4.63) were predictors of CTRCD by any definition. In multivariable analysis, race (OR 7.86, 95%CI 1.71-38.50 Asian compared to White), and receipt of HER2 therapy without anthracycline compared to anthracycline (OR 5.13, 95%CI 1.42-25.00) were predictors of CTRCD. In multivariable analysis of CTRCD by GLS criteria only, race (OR 78.47, 95%CI 1.47-53.96 Asian compared to White), and treatment (OR 11.23, 95%CI 1.85-219 HER2 therapy compared to anthracycline; OR 58.7, 95%CI 1.05-60.59 HER2 therapy and anthracycline compared to anthracycline). Conclusions: In this retrospective analysis of a racially and ethnically diverse patient population, more than a third of Asian patients developed CTRCD, although the study is limited by small sample sizes. Asian race and receipt of anti-HER2 therapy were independent risk factors for CTRCD. Asian race was especially a predictor of CTRCD by GLS definition. Detection bias may explain the differences in CTRCD by drug class, as patients complete serial TTEs while receiving HER2-directed therapy, while patients who receive an anthracycline without HER2-directed therapy typically only receive a baseline TTE. Future research to better characterize racial differences in CTRCD incidence and develop interventions to reduce this disparity is an area warranting further investigation. Demographic and Tumor Related Factors Associated with CTRCD (n=270) Univariable and multivariable analysis of CTRCD by LVEF or GLS definition. Multivariable analysis was adjusted for all variables listed. Citation Format: Amanda Wang, Jayant Raikhelkar, Rohit Raghunathan, Julia McGuinness, Neil Vasan, Meghna Trivedi, Kevin Kalinsky, Katherine Crew, Melissa Beauchemin, Jason Wright, Dawn Hershman, Melissa Accordino. Racial and Ethnic Disparities in Anthracycline and HER2-targeted Cardiotoxicity in Patients With Breast Cancer Using Global Longitudinal Strain Imaging Techniques [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-04.

Comparison of Echocardiography and Multi-Planar Gated Acquisition Scans for Predicting Cancer-Treatment-Related Cardiovascular Dysfunction

Current guidelines recommend using sequential cardiac imaging to monitor for cancer treatment-related cardiac dysfunction (CTRCD) in patients undergoing potentially cardiotoxic chemotherapy. Multiple different imaging cardiac modalities are available and there are few prospective head-to-head comparative studies to help guide treatment. To perform an exploratory prospective cohort study of "real-world" CTRCD comparing multigated acquisition nuclear ventriculography (MUGA) at the referring cancer specialist's discretion with a novel echocardiographic strategy at an Australian tertiary hospital. Patients were recruited from haematology and oncology outpatient clinics if they were scheduled for treatment with anthracyclines and/or trastuzumab. Patients underwent simultaneous MUGA-based cardiac imaging (conventional strategy) at a frequency according to evidenced-based guidelines in addition to researcher-conducted echocardiographic imaging. The echocardiographic imaging was performed in all patients at time points recommended by international society guidelines. Outcomes included adherence to guideline recommendations, concordance between MUGA and echocardiographic left ventricular ejection fraction (LVEF) measurements, and detection of cardiac dysfunction (defined as >5% LVEF decrement from baseline by three-dimensional [3D]-LVEF). A secondary end point was accuracy of global longitudinal strain in predicting cardiac dysfunction. In total, 35 patients were recruited, including 15 with breast cancer, 19 with haematological malignancy, and one with gastric cancer. MUGA and echocardiographic LVEF measurements correlated poorly with limits of agreement of 30% between 3D-LVEF and MUGA-LVEF and 37% for 3D-LVEF and MUGA-LVEF. Only one case (2.9%) of CTRCD was diagnosed by MUGA, compared with 12 (34.2%) cases by echocardiography. Four (4) patients had >10% decrement in 3D-LVEF that was not detected by MUGA. Global longitudinal strain at 2 months displayed significant ability to predict CTRCD (area under the curve, 0.75, 95% confidence interval, 0.55-0.94). The MUGA correlates poorly with echocardiographic assessment with substantial discrepancy between MUGA and echocardiography in CTRCD diagnosis. Echocardiographic and MUGA imaging strategies should not be considered equivalent for imaging cancer patients, and a single imaging modality should ideally be used per patient to prevent misdiagnosis by inter-modality variation These findings should be considered hypothesis-generating and require confirmation with larger studies.

Cardiac dysfunction in solid tumours: a neglected problem. A cardio-oncology scoping review

Cardio-oncology is a dynamic field. Research has suggested that cancer itself can damage the heart, independent of cancer treatment-related cardiac dysfunction (CTRCD). The aim of this study was to establish...

Pharmacotherapy for Cancer Treatment-Related Cardiac Dysfunction and Heart Failure in Childhood Cancer Survivors.

The number of childhood cancer survivors is increasing rapidly. According to American Association for Cancer Research, there aremore than 750,000 childhood cancer survivors in the United States and Europe. As the number of childhood cancer survivors increases, so does cancer treatment-related cardiac dysfunction (CTRCD), leading to heart failure (HF). It has been reported that childhood cancer survivors who received anthracyclines are 15 times more likely to have late cancer treatment-related HF and have a 5-fold higher risk of death from cardiovascular (CV) disease than the general population. CV disease is the leading cause of death in childhood cancer survivors. The increasing need to manage cancer survivor patients has led to the rapid creation and adaptation of cardio-oncology. Cardio-oncology is a multidisciplinary science that monitors, treats, and prevents CTRCD. Many guidelines and position statements have been published to help diagnose and manage CTRCD, including those from the American Society of Clinical Oncology, the European Society of Cardiology, the Canadian Cardiovascular Society, the European Society of Medical Oncology, the International Late Effects of Childhood Cancer Guideline Harmonization Group, and many others. However, there remains a gap in identifying high-risk patients likely to develop cardiomyopathy and HF in later life, thus reducing primary and secondary measures being instituted, and when to start treatment when there is echocardiographic evidence of left ventricular (LV) dysfunctionswithout symptoms of HF. There are no randomized controlled clinical trials for treatment for CTRCD leading to HF in childhood cancer survivors. The treatment of HF due to cancer treatment is similar to the guidelines for general HF. This review describes the latest pharmacologic therapy for preventing and treating LV dysfunction and HF in childhood cancer survivors based on expert consensus guidelines and extrapolating data from adult HF trials.

Study of usefulness of speckle-tracking echocardiography in detecting left ventricular dysfunction among adult cancer patients undergoing chemotherapy

Objective: Cancer treatment-related cardiac dysfunction (CTRCD) is a significant concern for patients undergoing chemotherapy. The aim of the present study was to study the accuracy and value of longitudinal strain in prediction of left ventricular dysfunction (LVD) in cancer patients undergoing cancer therapy. Methods: This was a prospective observational study conducted among 183 adult patients undergoing chemotherapy between 2018 and 2020. Patients with congenital or acquired valvular disease, prior myocardial infarction, coronary revascularization, or cardiac surgery were excluded. The patients were evaluated using a detailed history, clinical examination and echocardiography at baseline, 1 month, 3 months, and 6 months after chemotherapy. Speckle-tracking strain analysis was used to evaluate left ventricular (LV) global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS). LVD was defined as &qt;15% decrease in GLS, GCS, or GRS from baseline to 6 months. Accuracy of longitudinal strain in prediction of LVD was studied using ROC analysis. Results: Of the 183 patients, 59% were male, and 54.1% were between 46-60 years of age. Breast cancer was the most common malignancy (10.9%). The most common chemotherapy regimen was doxorubicin + paclitaxel (9.9%). At baseline, the mean GLS, GCS, and GRS were -18.6 (1.03)%, -20.4 (1.11)%, and 39.9 (6.09)%, respectively. At the 6-month follow-up, 27 (14.8%) patients had LVD. The incidence of LVD was higher (51.48%) in patients who received doxorubicin-containing regimens compared to non-doxorubicin-containing regimens (P <0.0001). GLS has good accuracy in prediction of LVD at 6 months of follow-up (88.37%). Conclusions: The incidence of LV dysfunction was higher (51.48%) in patients who received doxorubicin-containing regimens. GLS is different in LVD vs non LVD and the accuracy of GLS is more in prediction of LVD development during 6-month follow-up (88.37%).

Early diagnostic value of high-sensitivity cardiac troponin T for cancer treatment-related cardiac dysfunction: a meta-analysis.

Early diagnosis of cancer treatment-related cardiac dysfunction (CTRCD) is important as cancer therapy increases the risk of cardiac dysfunction. High-sensitivity cardiac troponin T (hs-cTnT) is a highly specific marker of myocardial injury. However, its diagnostic value for CTRCD has not been systematically evaluated. This meta-analysis aimed to evaluate whether hs-cTnT could be used as an early diagnostic biomarker for CTRCD. We systematically surveyed PubMed, Embase, Cochrane Library, and Web of Science databases for studies of hs-cTnT for the diagnosis of CTRCD before 1 April 2022. Patients of all ages and all cancer types who underwent echocardiographic left ventricular ejection fraction assessment and blood hs-cTnT and received anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, immune checkpoint inhibitors, and other treatments) were included in this study, resulting in a total of eight studies with 1294 patients. The occurrence of CTRCD was associated with elevated hs-cTnT [sensitivity: 0.78, 95% confidence interval (CI): 0.64-0.88; specificity: 0.75, 95% CI: 0.59-0.86; area under the curve (AUC): 0.83, 95% CI: 0.80-0.86]. We further performed subgroup analysis and found that the AUC of hs-cTnT elevation for the diagnosis of CTRCD increased from 0.83 to 0.90 (95% CI: 0.87-0.92) at 3-6months, suggesting a higher early diagnostic value of hs-cTnT compared with echocardiography for CTRCD. In terms of clinical applicability, the Fagan plot showed pre-test and post-test probabilities of 51% and 9%, respectively, indicating that hs-cTnT testing can improve the accuracy of clinical diagnosis of CTRCD. However, it was not possible to determine the optimal cut-off value for early diagnosis of CTRCD with hs-cTnT. The Deeks funnel plot was largely symmetrical (P=0.74); hence, publication bias was not observed. Hs-cTnT allowed early CTRCD diagnosis at 3-6months. However, further high-quality research is needed to determine the optimal cut-off value for early CTRCD diagnosis with this biomarker.

Assessment of left heart dysfunction to predict doxorubicin cardiotoxicity in children with lymphoma.

The objectives of this study were to assess the changes in the left myocardial function after chemotherapy for childhood lymphoma and observe the predictive or monitor value for cancer treatment-related cardiac dysfunction (CTRCD) by speckle-tracking echocardiography. A total of 23 children with histopathological diagnoses of lymphoma were included, with age-matched normal controls. Comparative analysis of clinical serological tests and left heart strain parameters in children with lymphoma, including left ventricular global longitudinal strain (LVGLS); global myocardial work (GMW) indices, which include global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency; and the LS of subendocardial, middle, and subepicardial layer myocardium during left ventricular systole were measured: left atrial strain of reservoir phase (LASr), left atrial strain of conduit phase (LAScd), and left atrial strain of contraction phase (LASct). One-way ANOVA showed that GLS, GWI, GCW, LASr, and LAScd were closely associated with CTRCD and multivariate logistic regression analysis showed that GLS was the most sensitive predictor for detecting patients at lofty risk of anthracycline-related cardiotoxicity. Both before and after chemotherapy, GLS in the left ventricle showed a pattern of basal segment < middle segment < apical segment and subepicardial < middle < subendocardial layer (p < 0.05), and the degree of decrease also showed a regular pattern of epicardial layer < middle layer < subendocardial layer while the difference was not significant (p > 0.05). After chemotherapy, maximum flow rate in early mitral relaxation/left atrial systolic maximum flow rate (E/A) and left atrial volume index of each group were in the normal range, and the values of LASr, LAScd, and LASct slightly increased in the second cycle and decreased significantly in the fourth cycle after chemotherapy, reaching the lowest level; LASr and LAScd were positively correlated with GLS. LVGLS is a more sensitive and earlier indicator to predict CTRCD compared with conventional echocardiography-related parameters and serological markers, and GLS of each myocardial layer showed a certain regularity. Left atrial strain can be used for early monitoring of cardiotoxicity in children with lymphoma after chemotherapy.

Diagnosis and Management of Cancer Treatment-Related Cardiac Dysfunction and Heart Failure in Children.

It is disheartening for parents to discover that their children have long-term cardiac dysfunction after being cured of life-threatening childhood cancers. As the number of childhood cancer survivors increases, early and late oncology-therapy-related cardiovascular complications continues to rise. It is essential to understand that cardiotoxicity in childhood cancer survivors is persistent and progressive. A child's cancer experience extends throughout his lifetime, and ongoing care for long-term survivors is recognized as an essential part of the cancer care continuum. Initially, there was a lack of recognition of late cardiotoxicities related to cancer therapy. About 38 years ago, in 1984, pioneers like Dr. Lipshultz and others published anecdotal case reports of late cardiotoxicities in children and adolescents exposed to chemotherapy, including some who ended up with heart transplantation. At that time, cardiac tests for cancer survivors were denied by insurance companies because they did not meet appropriate use criteria. Since then, cardio-oncology has been an emerging field of cardiology that focuses on the early detection of cancer therapy-related cardiac dysfunction occurring during and after oncological treatment. The passionate pursuit of many healthcare professionals to make life better for childhood cancer survivors led to more than 10,000 peer-reviewed publications in the last 40 years. We synthesized the existing evidence-based practice and described our experiences in this review to share our current method of surveillance and management of cardiac dysfunction related to cancer therapy. This review aims to discuss the pathological basis of cancer therapy-related cardiac dysfunction and heart failure, how to stratify patients prone to cardiotoxicity by identifying modifiable risk factors, early detection of cardiac dysfunction, and prevention and management of heart failure during and after cancer therapy in children. We emphasize serial longitudinal follow-ups of childhood cancer survivors and targeted intervention for high-risk patients. We describe our experience with the new paradigm of cardio-oncology care, and collaboration between cardiologist and oncologist is needed to maximize cancer survival while minimizing late cardiotoxicity.

Cardio-Protection Against Cancer Treatment-Related Cardiac Dysfunction: Who is at Risk?

Long-term survival of cancer patients has improved, and the sequelae of treatment have become more evident. Mortality rates of cancer patients, adjusted for age, have decreased globally, with a reduction by 17% from 1990 to 2019. The prevention of left ventricular dysfunction secondary to cancer treatment is still a medical challenge. Drug-induced cardiotoxicity is the main limiting factor for the administration of higher doses of anthracyclines. Addressing the anthracycline-induced cardiotoxicity is particularly important for pediatric cancer survivors, as it remains [...]

Use of emgliflozine in cardiotoxicity treatment. EMPACARD-treatment registry. Six-months follow-up

Abstract Background Despite improvements in cancer management, cancer treatment related cardiac dysfunction (CTRCD) is a growing medical problem that impact cancer patients' prognosis, especially when it leads to early interruptions of effective anticancer therapies. Heart failure (HF) therapies are recommended in patients who develop symptomatic CTRCD or asymptomatic decrease in left ventricular ejection fraction (LVEF). However, the beneficial effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors was not prospectively tested in patients with cancer and CTRCD Purpose EMPACARD-treatment is a prospective registry aiming at evaluating the usefulness of empagliflozin on left ventricular remodelling in patients with metastatic breast cancer and refractory CTRCD. Methods Metastatic breast cancer patients, who develop refractory CTRCD during or after anthracycline chemotherapy and/or HER2 targeted therapies were prospectively included in our study and treated with empagliflozin 10mg/day on top of their current HF therapies. Refractory CTRCD was defined as symptomatic HF in patients treated with optimal doses of neurohormonal HF therapies, including sacubitril/valsartan. Clinical and echocardiographic variables were analysed to determine the potential benefits of empagliflozin on left ventricular remodelling (LVEF and left ventricular diastolic diameter (LVDD)), NT-proBNP levels, NHYA class and 6 minutes walking test (6MWT). The median follow-up was 6 months. Continuous variables were summarized as medians with interquartile ranges (IQR) and compared with Wilcoxon's test for paired samples. Categorical values were expressed as percentages and compared with the chi-squared test. Statistical significance was considered with a p-value of less than 0.05. All analyses were performed with R version 4.1.1. Results 19 metastatic breast cancer patients were included. Baseline characteristics and HF treatments are described in table 1. One patient received a heart transplant, and there were no deaths. At 6 months follow up LVEF significantly improved from 30% (IQR 27.5–32) to 38% (IQR (33.5–39), (p&amp;lt;0.001), NT-proBNP decreased from 1342 pg/ml (IQR (977–1756) to 784 pg/ml (IQR 641–1099.5) (p&amp;lt;0.0001), and similar improvements were observed in LVDD and 6MWT (Table 2). NYHA functional class improved in 95% of patients from class III to I or II at 6 months follow-up (p&amp;lt;0.003). Conclusions Guideline-based HF therapy, including empagliflozin improves LV remodelling in patients with cancer and refractory CTRCD. Empagliflozin might be a promising treatment option in patients with refractory CTRCD Funding Acknowledgement Type of funding sources: None.

The Impact of Exercise on Cardiotoxicity in Pediatric and Adolescent Cancer Survivors: A Scoping Review.

Childhood and adolescent cancer survivors are disproportionately more likely to develop cardiovascular diseases from the late effects of cardiotoxic therapies (e.g., anthracycline-based chemotherapy and chest-directed radiotherapy). Currently, dexrazoxane is the only approved drug for preventing cancer treatment-related cardiac damage. While animal models highlight the beneficial effects of exercise cancer treatment-related cardiac dysfunction, few clinical studies have been conducted. Thus, the objective of this scoping review was to explore the designs and impact of exercise-based interventions for managing cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors. Reviewers used Joanna Briggs Institute’s methodology to identify relevant literature. Then, 4616 studies were screened, and three reviewers extracted relevant data from six reports. Reviewers found that exercise interventions to prevent cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors vary regarding frequency, intensity, time, and type of exercise intervention. Further, the review suggests that exercise promotes positive effects on managing cancer treatment-related cardiac dysfunction across numerous indices of heart health. However, the few clinical studies employing exercise interventions for childhood and adolescent cancer survivors highlight the necessity for more research in this area.

Cancer treatment-related cardiac dysfunction in breast cancer survivors: A retrospective descriptive study using electronic health records from a Korean tertiary hospital.

The population overlap of breast cancer and cardiovascular diseases (CVDs) has increased due to early breast cancer detection and treatment and aging population trends. Moreover, breast cancer patients are at an increased risk for CVDs consequent to cancer treatments. We aimed to understand the characteristics of breast cancer patients with pre-existing CVDs and of those diagnosed with CVDs after receiving chemotherapy, and cancer treatment-related cardiac dysfunction's occurrence among Korean breast cancer patients with CVDs. This retrospective descriptive study, which collected clinical data from electronic health records from a Korean tertiary hospital, included 1200 female breast cancer patients with CVDs, aged 15-75 years. A total of 45.7% had pre-existing CVDs, and 91.6% were classified as very high-risk for cardiotoxicity in the pre-existing CVDs group. Among the 1200 breast cancer patients with CVDs, only 439 patients had left ventricular ejection fraction (LVEF) data during their cancer treatment, and 121 received baseline assessment for LVEF. Of the 439 patients with LVEF data, 134 patients have been classified into cancer treatment-related cardiac dysfunction (CTRCD), and the median period from cancer diagnosis to CTRCD occurrence was 26.5 months. Despite the high cardiotoxicity risk of breast cancer patients with pre-existing CVDs, baseline studies of the risk assessment before chemotherapy were insufficient to support the prevention and early detection of cardiotoxicity. Therefore, it is paramount to consider how nurses focus on risk stratification before chemotherapy and support the regular monitoring of breast cancer survivors' cardiac functioning, to maintain optimal health status.

Cancer treatment-related cardiac dysfunction

ObjectivesThis paper describes cardiotoxicity and cancer treatment-related cardiac dysfunction (CTRCD). Long-term sequelae of treatment are important, and changing, and may manifest when a patient is under the care of a...

Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy–Related Cardiotoxicity

BackgroundEchocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment–related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation. ObjectivesThis work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD. MethodsIn this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD. ResultsBaseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change. ConclusionsGLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538)

Incremental Value of Myocardial Work over Global Longitudinal Strain in the Surveillance for Cancer-Treatment-Related Cardiac Dysfunction: A Case-Control Study.

The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case–control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP−), and matched with patients without CTRCD (CTRCD−BP+ and CTRCD−BP−). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD−BP+ patients. The CTRCD+BP− patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD−BP− peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001–1.042; p < 0.04) was the only feature independently associated with CTRCD−BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment.

Advances in Biomarkers for Detecting Early Cancer Treatment-Related Cardiac Dysfunction.

With the gradual prolongation of the overall survival of cancer patients, the cardiovascular toxicity associated with oncology drug therapy and radiotherapy has attracted increasing attention. At present, the main methods to identify early cancer treatment-related cardiac dysfunction (CTRCD) include imaging examination and blood biomarkers. In this review, we will summarize the research progress of subclinical CTRCD-related blood biomarkers in detail. At present, common tumor therapies that cause CTRCD include: (1) Chemotherapy—The CTRCD induced by chemotherapy drugs represented by anthracycline showed a dose-dependent characteristic and most of the myocardial damage is irreversible. (2) Targeted therapy—Cardiovascular injury caused by molecular-targeted therapy drugs such as trastuzumab can be partially or completely alleviated via timely intervention. (3) Immunotherapy—Patients developed severe left ventricular dysfunction who received immune checkpoint inhibitors have been reported. (4) Radiotherapy—CTRCD induced by radiotherapy has been shown to be significantly associated with cardiac radiation dose and radiation volume. Numerous reports have shown that elevated troponin and B-type natriuretic peptide after cancer treatment are significantly associated with heart failure and asymptomatic left ventricular dysfunction. In recent years, a few emerging subclinical CTRCD potential biomarkers have attracted attention. C-reactive protein and ST2 have been shown to be associated with CTRCD after chemotherapy and radiation. Galectin-3, myeloperoxidas, placental growth factor, growth differentiation factor 15 and microRNAs have potential value in predicting CTRCD. In this review, we will summarize CTRCD caused by various tumor therapies from the perspective of cardio-oncology, and focus on the latest research progress of subclinical CTRCD biomarkers.

Quality of life in breast cancer patients with cancer treatment-related cardiac dysfunction: a qualitative study.

Although improved breast cancer (BC) treatment has decreased mortality, these anti-cancer regimens may have serious cardiovascular side effects that affect patients' long-term prognosis and quality of life (QoL). BC patients with cancer treatment-related cardiac dysfunction (CTRCD) can suffer from a variety of symptoms, such as dyspnoea and fatigue. The impact of CTRCD after BC treatment on patients' daily life has not been qualitatively explored yet. This study aims to explore the influence of CTRCD on QoL of women with BC, as defined by the concept of positive health. Second, we aim to evaluate the personal experience with cardiac surveillance during the BC trajectory. A qualitative study with semi-structured interviews was conducted and thematically analysed to explore the QoL and healthcare experiences of BC patients with CTRCD. Twelve patients participated in this study. Five themes are selected in response to the study objective: (i) patients: overwhelming fatigue, (ii) patients: mental burden of anxiety, (iii) social setting: lack of understanding and acceptance, (iv) medical specialists: lack of knowledge and acknowledgement, and (v) patients: need for personalized care. This study identified core components of the impact CTRCD has on the QoL of BC patients. Patients experienced an increased health-related burden due to CTRCD, affecting their physical, social, and psychosocial well-being. Healthcare experiences were largely affected by a lack of acknowledgement and professional communication. Patients underlined the need for personalized care during follow-up.

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Extended Follow-Up of a 2×2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol.

Adjuvant breast cancer therapy containing anthracyclines with or without anti-human epidermal growth factor receptor-2 antibodies and radiotherapy is associated with cancer treatment-related cardiac dysfunction. In the PRADA trial (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy), concomitant treatment with the angiotensin receptor blocker candesartan attenuated the reduction in left ventricular ejection fraction (LVEF) in women receiving treatment for breast cancer, whereas the β-blocker metoprolol attenuated the increase in cardiac troponins. This study aimed to assess the long-term effects of candesartan and metoprolol or their combination to prevent a reduction in cardiac function and myocardial injury. In this 2×2 factorial, randomized, placebo-controlled, double-blind, single-center trial, patients with early breast cancer were assigned to concomitant treatment with candesartan cilexetil, metoprolol succinate, or matching placebos. Target doses were 32 and 100 mg, respectively. Study drugs were discontinued after adjuvant therapy. All 120 validly randomized patients were included in the intention-to-treat analysis. The primary outcome measure was change in LVEF assessed by cardiovascular magnetic resonance imaging from baseline to extended follow-up. Secondary outcome measures included changes in left ventricular volumes, echocardiographic peak global longitudinal strain, and circulating cardiac troponin concentrations. A small decline in LVEF but no significant between-group differences were observed from baseline to extended follow-up, at a median of 23 months (interquartile range, 21 to 28 months) after randomization (candesartan, 1.7% [95% CI, 0.5 to 2.8]; no candesartan, 1.8% [95% CI, 0.6 to 3.0]; metoprolol, 1.6% [95% CI, 0.4 to 2.7]; no metoprolol, 1.9% [95% CI, 0.7 to 3.0]). Candesartan treatment during adjuvant therapy was associated with a significant reduction in left ventricular end-diastolic volume compared with the noncandesartan group (P=0.021) and attenuated decline in global longitudinal strain (P=0.046) at 2 years. No between-group differences in change in cardiac troponin I and T concentrations were observed. Anthracycline-containing adjuvant therapy for early breast cancer was associated with a decline in LVEF during extended follow-up. Candesartan during adjuvant therapy did not prevent reduction in LVEF at 2 years, but was associated with modest reduction in left ventricular end-diastolic volume and preserved global longitudinal strain. These results suggest that a broadly administered cardioprotective approach may not be required in most patients with early breast cancer without preexisting cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01434134.

The Utility of Cardiac Reserve for the Early Detection of Cancer Treatment-Related Cardiac Dysfunction: A Comprehensive Overview.

With progressive advancements in cancer detection and treatment, cancer-specific survival has improved dramatically over the past decades. Consequently, long-term health outcomes are increasingly defined by comorbidities such as cardiovascular disease. Importantly, a number of well-established and emerging cancer treatments have been associated with varying degrees of cardiovascular injury that may not emerge until years following the completion of cancer treatment. Of particular concern is the development of cancer treatment related cardiac dysfunction (CTRCD) which is associated with an increased risk of heart failure and high risk of morbidity and mortality. Early detection of CTRCD appears critical for preventing long-term cardiovascular morbidity in cancer survivors. However, current clinical standards for the identification of CTRCD rely on assessments of cardiac function in the resting state. This provides incomplete information about the heart's reserve capacity and may reduce the sensitivity for detecting sub-clinical myocardial injury. Advances in non-invasive imaging techniques have enabled cardiac function to be quantified during exercise thereby providing a novel means of identifying early cardiac dysfunction that has proved useful in several cardiovascular pathologies. The purpose of this narrative review is (1) to discuss the different non-invasive imaging techniques that can be used for quantifying different aspects of cardiac reserve; (2) discuss the findings from studies of cancer patients that have measured cardiac reserve as a marker of CTRCD; and (3) highlight the future directions important knowledge gaps that need to be addressed for cardiac reserve to be effectively integrated into routine monitoring for cancer patients exposed to cardiotoxic therapies.

P1750 Association of high-sensitivity troponin elevation and LVEF decline in anthracycline-treated breast cancer patients

Abstract Introduction Cancer therapies have been linked to a wide variety of side effects, with cardiotoxicity being the most significant one. Early detection of subclinical cardiac dysfunction in cancer patients (pts) is necessary in order to prevent unfavorable outcomes. High-sensitivity troponin I (hsTI) levels have been proposed as predictors of cancer therapy related cardiotoxicity and may guide cardioprotective therapy initiation. Purpose To describe the incidence of cancer treatment related cardiac dysfunction (CTRCD) in a population of breast cancer pts under chemotherapy in a single center cardio-oncology unit and to assess its relationship with hsTI levels. Methods We retrospectively evaluated 83 women on anthracycline therapy for breast cancer, with or without anti-HER2 therapy, followed-up between January 2017 and July 2018. CTRCD was defined as more than 10% absolute reduction of LV ejection function (LVEF) to a value below 50%. Elevation of hsTI was defined as at least one measurement above the 99th percentile upper reference limit during follow-up (&amp;gt;34 ng/L). Pts had an organized follow-up in our cardio-oncology unit, consisting of a clinical, laboratorial (with dosing of cardiac biomarkers) and echocardiographic assessment at 0, 3, 6 and 12 months (or more frequently in selected high-risk cases). Results A total of 83 women with a mean age of 49 years (26-76) were included. 4 pts (4.8%) developed CTRCD. 17 pts (20.5%) were considered at high risk of cardiac dysfunction due to hsTI elevation. During follow-up, the percent increase in the hsTI level (from basal level) correlated with CTRCD (p = 0.02). On the other hand, the absolute maximum value of hsTI did not (p = 0.159). In fact, pts who developed CTRCD had a significantly higher percent increase in the hsTI levels (142.9% +- 57.5%) vs those without CTRCD (14.29% +- 4.6%), p &amp;lt; 0.001. On ROC curve analysis, percent increase in troponin was a good identifier of CTRCD (AUC of 0.986; 95% CI 0.95-1.00; p = 0.022) and the best cut-off value was a 79.8% increase in hsTI (sensitivity: 100%; specificity: 97.2%). Conclusion In our population, the percent increase in the hsTI levels correlated with CTRCD. Larger studies are needed to prove this parameter as a predictor of CTRCD. Abstract P1750 Figure.