Early Detection Of Cardiotoxicity Research Articles

Transforming Cardiotoxicity Detection in Cancer Therapies: The Promise of MicroRNAs as Precision Biomarkers

Cardiotoxicity (CDTX) is a critical side effect of many cancer therapies, leading to increased morbidity and mortality if not addressed. Early detection of CDTX is essential, and while echocardiographic measures like global longitudinal strain offer promise in identifying early myocardial dysfunction, the search for reliable biomarkers continues. MicroRNAs (miRNAs) are emerging as important non-coding RNA molecules that regulate gene expression post-transcriptionally, influencing key biological processes such as the cell cycle, apoptosis, and stress responses. In cardiovascular diseases, miRNAs have demonstrated potential as biomarkers due to their stability in circulation and specific expression patterns that reflect pathological changes. Certain miRNAs have been linked to CDTX and hold promise for early detection, prognosis, and therapeutic targeting. These miRNAs not only assist in identifying early cardiac injury, but also offer opportunities for personalized interventions by modulating their expression to influence disease progression. As research advances, integrating miRNA profiling with traditional diagnostic methods could enhance the management of CDTX in cancer patients, paving the way for improved patient outcomes and more tailored therapeutic strategies. Further clinical studies are essential to validate the clinical utility of miRNAs in managing CDTX.

Early Detection of Cardiotoxicity Using [64Cu]Cu-NODAGA-E[(cRGDyK)]2 PET Imaging in a Rat Model of Doxorubicin-Induced Heart Failure.

Doxorubicin (DOX) is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic effects and the lack of methods to detect these at early time points. In the present study, we evaluated if [64Cu]Cu-NODAGA-E[(cRGDyK)]2 positron emission tomography-computed tomography ([64Cu]Cu-RGD PET/CT) could detect cardiotoxicity in a rat model of DOX-induced heart failure. Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg of DOX or left untreated. Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week 8. [64Cu]Cu-RGD PET/CT scans were performed in week 4. DOX treatment led to a decline in pump function as well as an increase in cardiac and thymic uptake of [64Cu]Cu-RGD. In addition, DOX altered cardiac gene expression, led to infiltration of immune cells, reduced endothelial content, and increased interstitial fibrosis. Furthermore, concentrations of inflammatory plasma proteins were increased in the DOX group. In conclusion, DOX treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using [64Cu]Cu-RGD PET/CT at early time points. [64Cu]Cu-RGD uptake in the myocardial septum and thymus predicted a low left ventricular ejection fraction in week 8.

Cancer as an Individual Risk Factor for Heart Failure: A Review of Literature.

The intricate relationship between cancer and cardiovascular diseases (CVD), notably heart failure (HF), is gaining attention in the medical field. This literature review explores the intricate interplay between cancer and CVD, particularly HF, emphasizing their significant impact on global mortality and comorbidity. While preventive measures have contributed to reducing their incidence, challenges persist in predicting and managing cancer-related complications. This review article delves into various risk factors associated with both cancer and HF, including lifestyle factors, genetic predispositions, and immune system dysregulation. It highlights emerging evidence suggesting a direct interaction between cancer and HF, with studies indicating an elevated risk of mortality from cancer in patients with HF and vice versa. Pathological mechanisms such as inflammation, oxidative stress, and tissue hypoxia are implicated in cancer-induced cardiac dysfunction, underscoring the need for comprehensive clinical investigations and ethical considerations in patient care. The review also discusses the potential role of biomarkers in risk assessment, early detection of cardiotoxicity, and understanding common pathophysiological links between cancer and HF, paving the way for multifaceted preventive and therapeutic approaches.

Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond.

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this affects cardiovascular and tumor biomarkers; exploring the role of cardiovascular biomarkers in the risk stratification and in the identification of chemotherapy-induced cardiotoxicity; and providing a summary of the novel potential biomarkers in this clinical setting.

397 HEART FAILURE WITH REDUCE VENTRICULAR EJECTION FRACTION FOLLOWING THERAPY WITH RITUXIMAB IN A PATIENT AFFECTED BY MPO ANCA RELATED MICROSCOPIC POLYANGITIIS

Abstract Introduction Rituximab is a chemotherapeutic drug widely used for the treatment of oncologic and rheumatologic diseases. Its cardiotoxic profile has not yet been defined in detail; only a few isolated case reports delineate cardiovascular adverse reactions following its use. In the cases described in literature, the drug was used to treat neoplastic diseases, often in combination with other chemotherapeutic drugs. We present a clinical case of heart failure with reduced ventricular ejection fraction (HFrEF), developed following therapy with Rituximab and a single administration of Cyclophosphamide, in a patient affected by MPO-ANCA-related Microscopic Polyangiitis. Case Report 54-year-old man arrived at the emergency department for weight loss, fever, asthenia, and lower limbs oedema; laboratory findings where diagnostic for acute kidney injury (AKI). His past history was unremarkable. He was admitted to the nephrology department where he was diagnosed with MPO-ANCA-related microscopic polyangiitis. Echocardiography on admission showed normal left systolic ventricular function. He underwent diuretic therapy, intermittent hemodialysis, plasmapheresis and immunosuppressive therapy with steroids, Rituximab (two administration of 375 mg/m2 i.v. one week apart) and Cyclophosphamide (one administration of 300 mg i.v.). Following the achievement of good clinical and hemodynamic compensation, the patient was discharged. However, 5 days later, the patient came back to the hospital, prior to the follow-up that was scheduled for the continuation of immunosuppressive therapy, with symptoms of worsening dyspnea related to acute pulmonary edema. A transthoracic echo showed severe left ventricular systolic dysfunction for global hypokinesia. Cardiac MRI showed hypokinetic dilated cardiomyopathy with severely depressed systolic function (EF 30%) in the absence of lesions compatible with edema and myocardial fibrosis/necrosis. No coronary artery disease was detected with CT coronary angiogram. Given the absence of signs of ischemic cardiopathy or inflammatory related cardiomyopathy, we considered this new onset of HFrEF likely due to cardiotoxicity from chemotherapy drugs, which, in agreement with nephrology colleagues, were discontinued. The patient was started on heart failure medication with Bisoprolol 2,5 mg once daily and Ramipril 2,5 b.i.d., mineralocorticoid receptor antagonist and glifozines were not administered due to the renal injury. Given the HFrEF and numerous features of non-sustained ventricular tachycardia found on EKG monitoring during hospitalization, the patient was discharged with a wearable ICD. He was discharged after 3 weeks in stable clinical conditions with a follow-up appointment in a month. Conclusion Our clinical case provides further evidence regarding the cardiotoxic effect of Rituximab. In contrast with the other cases in literature, Rituximab was used for the treatment of rheumatologic and non-neoplastic pathology, without being combined with several other chemotherapeutics but only with a low-dose administration of Cyclophosphamide. In light of the above, it is worth mentioning that when chemotherapeutics are used, not only in oncology but also in rheumatology, even when their cardiotoxicity profile has not been defined in detail, as in the case of Rituximab, it is essential to use the utmost caution in assessing cardiac function before and after drug administration, so that early detection of cardiotoxicity will be possible.

Abstract 13359: Added Benefit of Parametric Mapping in Anthracycline-Induced Cardiomyopathy - Avoiding a Misdiagnosis

Case Presentation A 72 year old man presented with progressive dyspnea on exertion, only able to climb 4 stairs prior to symptom onset. He had a history of diffuse large B-cell lymphoma for which he had completed chemotherapy with cyclophosphamide, doxorubicin, rituximab, vincristine, and prednisone a year prior to presentation with recent PET scan showing complete remission. EKG showed rate-controlled atrial fibrillation. TTE confirmed a severely reduced systolic function with LVEF 25% and global hypokinesis. Coronary angiogram revealed no obstructive disease. Cardiac MRI (CMR) was then performed with no evidence of myocardial infarction, infiltration, or scarring on delayed gadolinium enhancement (DGE). T2 mapping, DIR, and TIR sequencing did not show any myocardial edema. However, baseline pre-contrast T1 relaxation time was increased at 1140-1153ms [Figure 1A] with a calculated ECV [Figure 1B] elevated at 37-40%, concerning for anthracycline-induced cardiomyopathy (AIC). Discussion Anthracyclines, such as doxorubicin, are important chemotherapeutic agents; however, their utility is often limited by development of progressive cardiotoxicity. Cumulative dose-dependent exposure can lead to apoptotic myocyte loss, myocardial fibrosis, and dysmotility. DGE usually identifies focal myocardial fibrosis; however, anthracycline-induced fibrosis is frequently diffuse and can be missed by qualitative analysis and DGE burden assessment. Diffuse fibrosis is better demonstrated with use of hematocrit adjusted ECV and pre-/post-T1 mapping. CMR provides additional information about decrease in the LV mass, aortic stiffness, myocardial strain, early fibrosis detection, and myocardial edema that can aid in early detection of cardiotoxicity during anthracycline therapy. Use of CMR parametric imaging is complementary and essential in accurately diagnosing AIC in patients with prior exposure and merits widespread consideration in cardio-oncology.

Myocardial work analysis for early detection of type 1 CTRCD and patient risk stratification

Abstract Aim This prospective longitudinal study analyses the potential role of Myocardial Work in early detection of cardiotoxicity during chemotherapy and its added value for prognosis and patients' risk stratification. Methods We enrolled 47 consecutive female patients with HER2-positive breast cancer referred for anti-cancer therapy based on anthracycline and taxane. Patients with depressed LV function at baseline were excluded. Medical therapy, clinical parameters and echocardiographic data were recorded at baseline and at 3, 6, 12 months follow-up. Additionally, cuff blood pressure was measured at the time of 2D-TTE examination and adequate echocardiographic images were stored for off-line analysis. Results CTRCD was detected in 17 patients (36%) while 30 patients remained free of CTRCD (64%). There were no intergroup differences for age, body mass index, resting heart rate and brachial arterial pressure. Both groups presented unaltered LV systolic function after 3 months follow-up yet overt cardiac dysfunction showed up in the CTRCD group at 6 months with significant decline in LVEF, GLS, MWI, MWE and CW from baseline values (LVEF, %: 56.0±4.1 vs 52.2±6.5; GLS, %: −20.9±1.9 vs −17.6±3.2; MWI, mmHg%: 2125±348 vs 1704±620; MWE, %: 95±2.6 vs 93±3.9 and CW, mmHg%: 2562±3567 vs 2212±455, p<0.05). Additionally, GLS, MWI and MWE at 6 months were significantly worse in the CTRCD group vs non-CTRCD group (GLS, %: −17.6±3.2 vs −20.6±1.8; MWI, mmHg%: 1704±620 vs 2087±347; MWE, %: 93±3.9 vs 96±1.5, p<0.05). Depressed LV systolic function persisted after 1 year follow-up (Figure 1). After 3 months, only de relative change in GLS and WW from baseline were significantly worse in CTRCD vs non-CTRCD (ΔGLS: +3.7±11 vs −3.9±10, ΔWW: +46.1±83 vs +2.2±45). Whereas no correlation was found, the combination of both ΔGLS and ΔWW at 3 months showed stronger prognostic value for CTRCD than each parameter alone, AUC of 0.72 (Figure 2). Conclusion These findings point the superiority of Myocardial Work for early type 1 CTRCD detection in comparison to the current diagnostic tools. Additionally, we suggest the add-on value of ΔWW on top of ΔGLS quantification for better patient risk stratification. These are promising results for better clinical surveillance of cardiac function during cancer treatment. Funding Acknowledgement Type of funding sources: None.

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...

Bidirectional Relationship Between Cancer and Heart Failure: Insights on Circulating Biomarkers.

Cancer and heart failure are the two leading causes of death in developed countries. These two apparently distinct clinical entities share similar risk factors, symptoms, and pathophysiological mechanisms (inflammation, metabolic disturbances, neuro-hormonal and immune system activation, and endothelial dysfunction). Beyond the well-known cardiotoxic effects of oncological therapies, cancer and heart failure are thought to be tied by a bidirectional relationship, where one disease favors the other and vice versa. In this context, biomarkers represent a simple, reproducible, sensitive and cost-effective method to explore such relationship. In this review, we recapitulate the evidence on cardiovascular and oncological biomarkers in the field of cardioncology, focusing on their role in treatment-naïve cancer patients. Cardioncological biomarkers are useful tools in risk stratification, early detection of cardiotoxicity, follow-up, and prognostic assessment. Intriguingly, these biomarkers might contribute to better understand the common pathophysiology of cancer and heart failure, thus allowing the implementation of preventive and treatment strategies in cardioncological patients

Myocardial FDG uptake variation and its relationship with survival during immunotherapy.

e14604 Background: The rise of Immune Checkpoint Inhibitors (ICI) as a cancer treatment has been followed by the increase of cardiotoxicity events reports. Retrospective studies with anthracycline revealed a relationship between increased myocardial 18F-FDG uptake (MGU) and a slight drop in Left Ventricular Ejection Fraction (LVEF) values, suggesting that this may be a useful tool for early detection of cardiotoxicity. Our study is intended to evaluate the prognostic impact of the variation in MGU in advanced lung cancer undergoing treatment with ICI. Methods: This is a unicentric, retrospective study, that evaluated lung cancer patients treated with ICI from 2016 to 2020 and submitted to at least two positron emission tomography (PET-CT). The primary objective was to evaluate the MGU variation during ICI treatment (ΔSUV) and its impact on survival outcomes. Numerical variables are described using a median and interquartile range. Categorical variables are described using absolute and relative frequencies. Mann-Whitney test was applied to compare the median between groups. progression-free survival and overall survival were calculated using the Kaplan-Meier method and the Log Rank test was used to compare survival curves. Alpha level = 0.05. Results: 43 patients fulfilled all inclusion criteria. 51% received Immunotherapy plus chemotherapy and 49% received only immunotherapy. Global median ΔSUV was +0.14; among patients in the disease control group, the median ΔSUV was +0.3, while the median ΔSUV of the disease progression group was -0.47. Considering patients with positive myocardial ΔSUV versus negative ΔSUV, there was a median increase of progression-free survival (PFS) of 112 days in favour of the positive myocardial ΔSUV group (p = 0.087). The overall survival (OS) of patients that used beta-blockers(BB) was higher than those who did not, with an increase of 575 days on median OS (p = 0.159). The increase in the PFS median by 112 days on those patients who presented a positive ΔSUV may suggest that better treatment outcomes are related to the rise of myocardial SUV, although the sample size was not sufficient to reach statistical significance. Another important association, albeit not statistically significant, was the growth of PFS mean by 575 days with the usage of BB, such growth was not evidenced on the patients which used ACE inhibitors or ARBs; indicating that BB could have a supporting role on ICI treatment. Those findings correlate to recent evidence that shows an increase in MGU after BB usage and that BB may work as immune-modulating agents improving ICI therapies. Conclusions: The increase in MGU was associated with better outcomes, suggesting that it could be studied as a predictor of treatment response, in addition to the benefit also shown with the use of BB, which strengthens their possible synergistic effect in treatment. However, more robust studies are needed to better understand the MGU role on ICI treatment.

Abstract 9828: Active Surveillance of Cardiotoxicity with Cardiac Biomarkers During Chimeric Antigen Receptor T-Cell Therapy

Introduction: Chimeric Antigen receptor T- Cell (CAR-T) immunotherapy has been a breakthrough for various hematological malignancies. Cardiotoxicites such as heart failure, arrhythmia and acute coronary syndrome occur in approximately 1/3 of patients who develop cytokine release syndrome (CRS) following CAR-T. High grade CRS (Grade ≥ 2) and elevated troponin level are associated with increased risk of cardiotoxicity. It is unclear whether active cardiotoxicity surveillance with serial cardiac biomarker measurements during CAR-T would allow early detection of cardiotoxicity. Methods: This was retrospective cohort study involving patients diagnosed with non-Hodgkin lymphoma treated with CAR-T therapy (Axicabtagene ciloleucel- Yescarta, tisagenlecleucel- Kymriah, Brexucabtagene autoleucel- Tecartus). Baseline cardiac workup with electrocardiogram (ECG), transthoracic echocardiogram (TTE), troponin (Reference <0.03ng/mL), B-natriuretic peptide (BNP, <100pg/mL) were uniformly performed in all participants. Follow up ECG, Troponin and BNP were obtained at day 5 after CAR-T and at development of CRS Grade ≥2. When clinically indicated, cardiac MRI with gadolinium contrast was performed. Cardiac MRI diagnosis of myocarditis was based on Lake Louise Criteria. Results: A total of 47patients undergoing CAR-T therapy were studied. Baseline comorbidities were not predictive of CRS or cardiac events. There were 39 patients with low grade CRS (82.9%) and 8 patients (17.0%) with grade 2 CRS. Five patients had elevated troponin I levels (Grade 1 CRS - 3; Grade 2 CRS - 2). Cardiac MRIs were performed in three patients (two normal studies, one with mild myocarditis). Five patients (10.6%) had an adverse cardiac event (Myocarditis with heart failure - 1; new-onset atrial fibrillation - 3; Type 2 myocardial infarction -1). Conclusion: Adverse cardiac events are a relatively common occurrence in patients receiving CART therapy. Active surveillance for cardiotoxicity using cardiac biomarkers in CAR-T patients may play an adjunctive role in the early identification of adverse cardiac events. Larger studies are needed to adjudicate the use of such screening measures in these high-risk patients.

Multimodal assessment of acute cardiac toxicity induced by thoracic radiotherapy in cancer patients. Study protocol

BackgroundToday, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart’s volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage.MethodologyThis protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage.DiscussionThe presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy.With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

Role of myocardial work index in early detection of cardiotoxicity in breast cancer patient

Abstract Introduction Breast cancer patients receiving anthracyclines are particularly prone to develop cancer therapeutics-related cardiac dysfunction. Early detection of cardiotoxicity onset is required for optimal timing of cardio protection treatment. The latest guidelines consider a relative reduction of 15% in global longitudinal strain (GLS) from baseline as risk for cardiotoxicity. Nevertheless, the more recent Myocardial Work Index (MWI) offers a load-independent tool for detection of subclinical heart failure (HF). However, data in cancer patients are still scarce. Purpose This study analyses the predictive value of MWI for cardiotoxicity diagnosis after 6 months chemotherapy. Methods The study population consists of breast cancer patients referred for chemotherapy with anthracyclines and taxanes. Patients with a history of HF previous to chemotherapy or depressed LV function at baseline were excluded. Echocardiography was performed before onset of the chemotherapy (baseline) and after 6 months follow-up. LVEF, GLS and MWI were assessed offline using EchoPAC software. The values at baseline and 6 months follow-up were pairwise compared to detect subclinical cardiac dysfunction. LVEF, GLS and MWI means at baseline were taken as cut-off to compare the predictive value of each parameter. Moreover, patients were categorized in one group with GLS reduction >15% (Group 1) and one group with GLS reduction <15% (Group 2). Results From April 2016 to July 2020, 28 women with breast cancer were included (age 54±11 years, LVEF 58±4%, GLS −21±2%, MWI 2160±308 mmHg). All patients underwent the same standard chemotherapy protocol (4xEC, 12xTaxol). No difference in baseline characteristics between group 1 (n=13) and group 2 (n=15) was observed. At 6 months follow up a significant decrease in LVEF (53±8%, p=0.003), GLS (−19±3%, p=0.002) and MWI (1920±391 mmHg, p=0.005) was shown without any change in blood pressure. However, while mean LVEF and GLS at baseline did not predict any significant change, patients with MWI under the mean value at baseline (n=15) presented significant lower LVEF (50±8 vs 57±6% p=0.006), GLS (−17±3 vs −20±2%, p=0.01), MWI (1733±320 vs 2136±362 mmHg, p=0.005) after 6 months. Additionally, both groups had similar MWI at baseline (2148±335 mmHg vs 2170±294 mmHg, p=0.85), whereas those patients with GLS reduction >15% showed significant lower MWI after 6 months (1694±332 mmHg vs 2116±334 mmHg, p=0.003, Figure 1). Conclusions At 6 months follow up, a decline of the LV systolic function as side effect of chemotherapy can be seen. MWI at baseline shows the best predictive value for development of cardiotoxicity, in comparison to LVEF and GLS. Further studies are warranted to better understand the role of MWI for early detection of cardiotoxicity and its clinical relevance. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Onze-Lieve-Vrouw hospital in Aalst (Belgium)

Right ventricle strain changes in patients with breast cancer during anthracycline therapy

Abstract Background Cardiotoxicity has become a significant adverse effect of cancer therapy, with Anthracyclines (ANT) in particular. There is a crucial need for the early subclinical detection of cardiotoxic effect. We aimed to evaluate Right ventricle (RV) two-dimensional speckle tracking echocardiography (2D-STE) changes during ANT therapy and to assess the correlation between RV 2D-STE and the routine echocardiographic RV parameters. Methods Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). All female patients with breast cancer, planned for ANT therapy were included. All patients underwent serial echocardiography exams including baseline RV 2D-STE (before chemotherapy, T1) and shortly after the completion of ANT therapy (T3). RV 2D-STE was evaluated using the apical 4 chamber (4C) RV-focused view, assessing both the combined RV free wall and inter-ventricular septum (RV GLS) and solely the RV free wall strain (RV FWLS). Significant reduction in both RV GLS and RV FWLS was determined by either a relative reduction of >10% or an absolute value of >−25% for RV GLS and >−29% for RV FWLS. Results From September 2016 to June 2019, 40 patients were evaluated with a mean Doxorubicin (type of ANT) dose of 238.5±9.4 mg/m2. RV FWLS showed significant correlation to Tricuspid annular plane systolic excursion. At T3, significant reduction in both RV GLS and RV FWLS was observed among 77% and 62% of the patients with a mean RV GLS and RV FWLS reduction from −26.8 (±4.7) % to −21.5 (±4.4) % and −28.9 (±5.1) % to −25.6 (±5.9) % (p<0.001, p=0.002), respectively. Left ventricle (LV) ejection fraction and LV GLS were within the normal range. Conclusions RV GLS and RV FWLS reduction are frequent and occur early in the course of ANT therapy, preceding LV dysfunction, which may imply for the role of RV 2D-STE in the detection of early cardiotoxicity. Funding Acknowledgement Type of funding sources: None.

The role of cardiac biomarkers in early detection of cardiotoxicity in breast cancer treated with trastuzumab in the adjuvant setting: a systematic review

Trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER-2) prolongs disease-free survival (DFS) and overall survival (OS) in patients with early-stage breast cancer. Although it is generally well tolerated, it has been associated with cardiotoxicity, mainly a reduction of left-ventricular ejection fraction (LVEF), especially if the patient has received anthracyclines.It is generally known that a drop in LVEF has limited diagnostic ability. Therefore, the identification of serum biomarkers of cardiotoxicity, able to detect damage at an earlier phase, has become ideal. Troponins (conventional and high sensitive), natriuretic peptides, reactive C protein (CRP), myeloperoxidase (MPO), etc are different molecular markers which have been assessed to check their role in the detection of treatment induced cardiotoxicity (CTIC) with controversial results.OBJECTIVEThis systematic review will synthesize available evidence assessing the role of different serum biomarkers in early prediction of cardiotoxicity in breast cancer patients treated with adjuvant trastuzumab.METHODS/DESIGNSystematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Distinct scientific databases such as Google Scholar, Pubmed, EBSCOhost, and PsycINFO were searched to aid in the investigation of the research problem.Randomized clinical trials (RCT) and observational studies of patients with early breast cancer receiving adjuvant trastuzumab were eligible for inclusion. Two investigators have independently evaluated those studies and used standardized data extraction templates to collect data on the study and patients’ characteristics.RESULTS 11 articles were selected, one RCT and ten observational studies. The most studied biomarker was N-terminal-pro-brain natriuretic peptide (NT-proBNP) followed by troponins. Findings showed that NT-proBNP was not predictive of CTIC while conflictive results were seen with troponins.One study showed a predictive role of high sensitive (hs) CRP and another found a relationship with the levels of MPO.CONCLUSIONBiomarkers offer a unique potential to improve the effectiveness and safety of trastuzumab through timely detection of CTIC and prompt initiation of appropriate treatment. Troponins I and T have shown a predictive role in early detection of CTIC but further research would be needed to enable more insight and improve the overall patient outcome.

Left Atrial Strain changes in patients with breast cancer during anthracycline therapy

BackgroundCardiotoxicity has become a significant adverse effect of cancer therapy, with Anthracyclines (ANT) in particular. There is a crucial need for new imaging techniques for the early subclinical detection of cardiotoxic effect. We aimed to evaluate left atrial strain (LAS) changes during ANT therapy and to assess the correlation between LAS and the routine echocardiographic diastolic parameters. Methods and resultsData were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). All female patients with breast cancer, planned for ANT therapy were included. All patients underwent serial echocardiography exams including baseline LAS (before chemotherapy, T1) and shortly after the completion of ANT therapy (T3). LAS was assessed in 3 phases: Reservoir (LASr), Conduit (LASc) and Pump (LASp). Significant reduction in LASr was determined by either a relative reduction of >10% or an absolute value of <35%. From September 2016 to June 2019, 40 patients were evaluated with a mean Doxorubicin (type of ANT) dose of 237±13.24mg/m2. At T3, significant reduction in LASr was observed among 50% of the patients with a mean LASr reduction from 40.15 ± 6.83% to 36.04 ± 7.73% (p < 0.001). LASc showed significant reduction as well (p < 0.004) as opposed to LASp (p=0.076). Both LASr and LASc showed significant correlation to the routine diastolic parameters. ConclusionsLASr and LASc reduction are frequent and occur early in the course of ANT therapy, showing significant correlation to the routine echocardiographic diastolic parameters, which may imply a role in the detection of early cardiotoxicity.

Role of myocardial deformation analysis in the early detection of subclinical Left Ventricular dysfunction in breast cancer under anthracyclines and trastuzumab

Abstract Funding Acknowledgements Type of funding sources: None. Introduction : Cardio-oncology field has notably raised interest this past decade, it considerably improved cancer patients’ quality of care by monitoring and preventing complications of cardiotoxic treatment like anthracyclines and trastuzumab. Transthoracic echocardiography (TEE) plays a major role in the baseline assessment and follow-up of cardio-oncology patients. While left ventricular ejection fraction (LVEF) still has its place in cardiac monitoring, new modalities like myocardial deformation imaging with speckle tracking strain analysis, show great potential for early detection of subclinical LV dysfunction. Purpose : The aim of this study was to evaluate the role of Global Longitudinal Strain (GLS) in the early detection of cardiotoxicity and its correlation to LVEF. Methods : We conducted a longitudinal prospective study including all the breast cancer patients treated with anthracyclines and/or trastuzumab followed in the Casablanca cardio-oncology unit from January 2017 to December 2019. All patients underwent baseline TEE, and were followed-up every 3 months after that, with GLS assessment whenever it was possible. We evaluated the frequency of GLS drop and its correlation to LVEF reduction. Results : Out of a total of 793 patients, 677 had available LV GLS assessment. Among them, 83 (12,3%) decreased their GLS during follow-up, 67% of which had no concomitant drop in LVEF. In these patients, impaired LV GLS values were noted at 1 month after chemotherapy and at 3, 6, and 12 months compared with baseline (-22,3 ± 1.8% at baseline, -18.1 ± 2.3% at 1 month, -17.7 ± 2.1% at 3 months, -17.1 ± 2.2% at 6 months, and -16.9 ± 2.1% at 12 months (p &amp;lt; 0,0001). LV GLS at 3 months was strongly correlated to cardiotoxicity (LVEF &amp;lt; 50%) at 12 months (p &amp;lt; 0,0001). A cut-off LV GLS value of -17,7% was then retained to identify LVEF alteration at the end of follow-up. Moreover, lower GLS values were observed in patients under Doxorubicin with a mean cumulative dose &amp;gt;180 mg/m2 (p = 0,0019), while LVEF remained normal. Finally, our study found that GLS at 1 month and 3 months had a prognostic value, since the lower GLS was, the poorest the patient’s clinical outcome was, with further development of symptomatic heart failure (p = 0,0038). Conclusion : Our study demonstrates that myocardial deformation analysis enables detection of early and progressive subclinical cardiac dysfunction, and GLS at 3 month was positively correlated to LVEF drop at 12 months. Thus, routine GLS should be used in patients undergoing cardiotoxic chemotherapy in order to early detect cardiotoxicity and prevent irreversible cardiac dysfunction by early initiating cardio-protective treatment.

Myocardial work index: a novel tool for detection of early cardiotoxicity in breast cancer patient

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Cardiovascular Research Center Aalst, (Aalst, Belgium) Introduction Breast cancer patients receiving anthracyclines are particularly prone to develop cancer therapeutics-related cardiac dysfunction (CTRCD). Early detection of cardiotoxicity onset is required for optimal timing of cardio protection treatment. The latest guidelines consider a relative reduction of 15% in global longitudinal strain (GLS) from baseline as risk for cardiotoxicity. Nevertheless, the more recent Myocardial Work Index (MWI) offers a load-independent tool for detection of subclinical heart failure (HF). Data in cancer patients are still scarce. Purpose This study analyses the predictive value of MWI for cardiotoxicity diagnosis after 6 months chemotherapy. Methods The study population consists of breast cancer patients referred for chemotherapy with anthracyclines and taxanes. Patients with a history of HF previous to chemotherapy or depressed LV function at baseline were excluded. Echocardiography was performed before onset of the chemotherapy (baseline) and after 6 months follow-up. LVEF, GLS and MWI were assessed offline using EchoPAC software. The values at baseline and 6 months follow-up were pairwise compared to detect subclinical cardiac dysfunction. Mean LVEF, GLS and MWI at baseline were taken as cut-off value to compare the predictive value of each parameter. Moreover, patients were categorized in one group with GLS reduction &amp;gt;15% (Group 1) and one group with GLS reduction &amp;lt;15% (Group 2). Results From April 2016 to January 2020, 24 women with breast cancer were included (age 54 ± 11 years, LVEF 58 ± 4%, GLS -21 ± 2%, MWI 2181 ± 325 mmHg). All patients underwent the same standard chemotherapy protocol (4xEC, 12xTaxol). No difference in baseline characteristics between group 1 (n = 9) and group 2 (n = 15) was observed. At 6 months follow up a significant decrease in LVEF (53 ± 8%, p = 0.003), GLS (-19 ± 3%, p = 0.002) and MWI (1933 ± 410 mmHg, p = 0.005) was shown without any change in blood systolic pressure. However, while mean LVEF and GLS at baseline did not predict any significant change, patients with MWI under the mean value at baseline (n = 13) presented significant lower LVEF (49 ± 8%, p = 0.006), GLS (-18 ± 4%, p = 0.045), MWI (1753 ± 341 mmHg, p = 0.018) after 6 months. Additionally, both groups had similar MWI at baseline (2199 ± 390 mmHg vs 2170 ± 294 mmHg, p = 0.85), whereas those patients with GLS reduction &amp;gt;15% showed significant lower MWI after 6 months (1626 ± 344 mmHg vs 2116 ± 334 mmHg, p = 0.003, Figure 1). Conclusions At 6 months follow up, a decline of the LV systolic function as side effect of chemotherapy can be seen. In comparison to LVEF and GLS, MWI shows the best predictive value for development of early cardiotoxicity. Further studies are warranted to better understand the role of MWI in predicting CTRCD and its clinical relevance. Abstract Figure. Change in MWI

Healthcare utilization and hospital variation in cardiac surveillance during breast cancer treatment: a nationwide prospective study in 5000 Dutch breast cancer patients

BackgroundVarious breast cancer (BC) treatments, such as chemotherapy and targeted therapies, increase cardiotoxicity-risk and lead to premature ischemic heart disease and heart failure among survivors. Reducing this adverse risk through early recognition and (preventive) treatment is therefore important. Conversely, we feel that screening for cardiotoxicity is currently insufficiently standardized in daily practice. A fundamental first step in identifying areas of improvement is providing an overview of current practice.ObjectiveThis study aims to describe current cardiac surveillance for women with BC during and after cardiotoxic cancer treatment, using routinely collected hospital data in the Netherlands. The study also describes hospital variation in cardiac surveillance.MethodsThis observational study was performed on claims data provided by Statistics Netherlands. From the data, newly diagnosed BC patients in 2013 (N = 16,040) were selected and followed up until 2015. Healthcare utilization analyses were performed for all cardiac and oncologic healthcare activities but with a specific focus on cardiac surveillance healthcare activities. In addition, differences between types and individual hospitals were evaluated.ResultsAlmost one third of all BC patients received high risk cardiotoxic treatments (N = 5157), but cardiac surveillance was rarely performed. Cardiac care provided to patients mainly consisted of ECGs (52.0%) and MUGA scans (26.5%). Cardiac MRI was performed in 0.7% of the patients, echocardiography in 17.7%, and measurement of Troponin and NT-proBNP in 5.1 and 5.8%, respectively. Moreover, we observed a substantial variation in cardiac surveillance between different hospital types and between individual hospitals.ConclusionThis study shows that women treated for BC with cardiotoxic treatments do not receive recommended cardiac surveillance. Standardized approaches in clinical care are lacking, resulting in low rates of diagnostic testing and a substantial variation in surveillance between hospitals. A structured approach and increased interprofessional collaboration could lead to tailored cardiac surveillance for early detection of cardiotoxicity and therefore start of treatment.