Chemotherapy-related Cardiotoxicity Research Articles

Chemotherapy-related cardiotoxicity and its symptoms in patients with breast cancer: a scoping review

BackgroundChemotherapy-related cardiotoxicity is a significant concern because it is a major cause of morbidity. This study aimed to provide in-depth information on the symptoms of chemotherapy-related cardiotoxicity (CRCT) by exploring literature that concurrently reports the types and symptoms of CRCT in patients with breast cancer.MethodsA scoping review was performed according to an a priori protocol using the Joanna Briggs Institute’s guidelines. The participants were patients with breast cancer. The concept was the literature of specifically reported symptoms directly matched with CRCT and the literature, in English, from 2010, and the context was open. The search strategy included four keywords: “breast cancer,” “chemotherapy,” “cardiotoxicity,” and “symptoms.” All types of research designs were included; however, studies involving patients with other cancer types, animal subjects, and symptoms not directly related to CRCT were excluded. Data were extracted and presented including tables and figures.ResultsA total of 29 articles were included in the study, consisting of 23 case reports, 4 retrospective studies, and 2 prospective studies. There were no restrictions on the participants’ sex; however, all of them were women, except for one case report. The most used chemotherapy regimens were trastuzumab, capecitabine, and doxorubicin or epirubicin. The primary CRCT identified were myocardial dysfunction and heart failure, followed by coronary artery disease, pulmonary hypertension, and other conditions. Major tests used to diagnose CRCT include echocardiography, electrocardiography, serum cardiac enzymes, coronary angiography, computed tomography, and magnetic resonance imaging. In all case reports, CRCT was diagnosed through an incidental checkup according to the patient’s symptom presentation; however, only 10 of these studies showed a baseline checkup before chemotherapy. The five most common CRCT symptoms were dyspnea, chest pain, peripheral edema, fatigue, and palpitations, which were assessed by patient-reported symptom presentation rather than using a symptom assessment tool. Dyspnea with trastuzumab treatment and chest pain with capecitabine treatment were particularly characteristic. The time for first symptom onset after chemotherapy ranged from 1 hour to 300 days, with anthracycline-based regimens requiring 3–55 days, trastuzumab requiring 60–300 days, and capecitabine requiring 1–7 days.ConclusionsThis scoping review allowed data mapping according to the study design and chemotherapy regimens. Cardiac assessments for CRCT diagnosis were performed according to the patient’s symptoms. There were approximately five types of typical CRCT symptoms, and the timing of symptom occurrence varied. Therefore, developing and applying a CRCT-specific and user-friendly symptom assessment tool are expected to help healthcare providers and patients manage CRCT symptoms effectively.

Anthracycline-Induced Cardiomyopathy in Cancer Survivors: Management and Long-Term Implications.

Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.

Cardiotoxicity in Cancer Patients: The Prevalence, Risk Factors, and Cardioprotective Measures in a Cancer Centre in Saudi Arabia.

Chemotherapy-related cardiotoxicity can exhibit several patterns of functional, structural, and vascular complications. This study aims to identify the patterns and the factors associated with cardiotoxicity in cancer patients. A retrospective cross-sectional analysis of 96 adult cancer patients undergoing anticancer therapy was investigated at King Khalid Hospital in Najran, Saudi Arabia, from May 2022 to April 2023. The data on patient and cancer characteristics, treatment, and outcomes were collected and analyzed. Factors associated with cardiotoxicity were investigated through univariate analyses using odds ratio (OR) and 95% confidence interval (CI). Among the 96 cancer patients in the study, cardiotoxicity occurred in 12 individuals (12.5%). The mean age was 57.0 ± 13.3 years (range: 32-81 years), with 32 (33.3%) being above 65 years. The most common comorbidities were diabetes (n=48; 50%), followed by hypertension (n=32; 33.3%), and dyslipidemia (n=20; 20.8%). The most common cancers were gastrointestinal cancer (n=32; 33.3%), followed by breast cancer (n=22; 22.9%) and lymphoma (n=14; 14.6%). Females were disproportionately affected (64.6%), with 57.3% of them in the metastatic stage. The majority of patients (90.6%) had normal ejection fraction before chemotherapy initiation. In univariate analysis, current smoking (OR: 7.00; 95%CI: 1.94-25.25, p= 0.003), history of percutaneous cardiac intervention (OR: 40.24; 95%CI: 1.80-896.26, p= 0.019), diabetes (OR: 6.05; 95%CI: 1.24-29.32, p= 0.025), renal failure (OR: 8.20; 95%CI: 0.91-74.88, p= 0.046), dyslipidemia (OR: 5.00; 95 CI: 1.38-18.32, p=0.012), anthracycline use (OR: 18.33; 95%CI: 4.36-126.55, p <0.001), trastuzumab use (OR: 25.00; 95%CI: 6.25-129.86, p < 0.001), and increased chemotherapy cycles number (> 10 cycles) (OR: 73.00; 95%CI: 8.56- 622.36, p < 0.001) were associated with cardiotoxicity. Additionally, beta-blocker use was associated with lower rates of cardiotoxicity (OR: 0.17; 95%CI: 0.036-0.84, p= 0.029). The incidence of cardiotoxicity among cancer patients treated with chemotherapy is modest, difficult to predict, and independent of baseline cardiac systolic functions. Factors associated with cardiotoxicity include smoking, history of percutaneous cardiac intervention, diabetes, renal failure, dyslipidemia, anthracycline or trastuzumab use, and increased chemotherapy cycle numbers. A combination of various anticancer drugs and chemotherapy may dramatically raise the risk of cardiotoxicity in cancer patients. As a result, patients receiving high-risk cardiotoxic drugs should be monitored with caution to avoid drug-related cardiotoxicity. Furthermore, proactive treatment techniques aiming at reducing the possible cardiotoxic effects of anticancer therapy are critical.

Rescue of cardiac dysfunction during chemotherapy in acute myeloid leukaemia by blocking IL-1α.

Patients with acute myeloid leukaemia (AML) suffer from severe myocardial injury during daunorubicin (DNR)-based chemotherapy and are at high risk of cardiac mortality. The crosstalk between tumour cells and cardiomyocytes might play an important role in chemotherapy-related cardiotoxicity, but this has yet to be demonstrated. This study aimed to identify its underlying mechanism and explore potential therapeutic targets. Cardiac tissues were harvested from an AML patient after DNR-based chemotherapy and were subjected to single-nucleus RNA sequencing. Cardiac metabolism and function were evaluated in AML mice after DNR treatment by using positron emission tomography, magnetic resonance imaging, and stable-isotope tracing metabolomics. Plasma cytokines were screened in AML mice after DNR treatment. Genetically modified mice and cell lines were used to validate the central role of the identified cytokine and explore its downstream effectors. In the AML patient, disruption of cardiac metabolic homeostasis was associated with heart dysfunction after DNR-based chemotherapy. In AML mice, cardiac fatty acid utilization was attenuated, resulting in cardiac dysfunction after DNR treatment, but these phenotypes were not observed in similarly treated tumour-free mice. Furthermore, tumour cell-derived interleukin (IL)-1α was identified as a primary factor leading to DNR-induced cardiac dysfunction and administration of an anti-IL-1α neutralizing antibody could improve cardiac functions in AML mice after DNR treatment. This study revealed that crosstalk between tumour cells and cardiomyocytes during chemotherapy could disturb cardiac energy metabolism and impair heart function. IL-1α neutralizing antibody treatment is a promising strategy for alleviating chemotherapy-induced cardiotoxicity in AML patients.

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

Bioinformatics and experimental studies jointly reveal that Sacubitril Valsartan improves myocardial oxidative stress and inflammation by regulating the MAPK signaling pathway to treat chemotherapy related cardiotoxicity

BackgroundCRC is a common but serious complication or sequela of tumor treatment, and new coping strategies are urgently needed. SV is a classic clinical cardiovascular protective drug, which has been widely used in the treatment of heart failure, hypertension and other diseases. It has good therapeutic effect in other cardiovascular diseases such as diabetes cardiomyopathy, ischemic cardiomyopathy and vascular disease, but it has not been proved by research that SV can prevent and treat CRC. MethodIn this study, DOX was used to induce a rat CRC model and evaluate the therapeutic effect of SV on it. Subsequently, R software was applied to analyze the control group, SV group, and DOX group in databases GSE207283 and GSE22369, and to screen for common differentially expressed genes. Use the DAVID website for enrichment analysis and visualization. Use STRING website to analyze and visualize protein interaction networks of key genes. Finally, experimental verification was conducted on key genes. ResultOur research results show that SV has a protective effect on DOX induced myocardial injury by alleviating Weight loss, increasing Ejection fraction, and reducing the level of biomarkers of myocardial injury. Meanwhile, SV can effectively alleviate the above abnormalities. Bioinformatics and KEGG pathway analysis showed significant enrichment of metabolic and MAPK signaling pathways, suggesting that they may be the main regulatory pathway for SV treatment of CRC. Subsequent studies have also confirmed that SV can inhibit DOX induced myocardial injury through the MAPK signaling pathway, and alleviate DOX induced oxidative stress and inflammatory states. ConclusionOur research indicates that SV is a potential drug for treating CRC and preliminarily elucidates its molecular mechanism of regulating the MAPK pathway to improve oxidative stress and inflammation.

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178. This study is listed on cinicaltrials.gov with identifier NCT05118178.

Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial.

The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity. Using the Agena Bioscience MassARRAY system, we genotyped TRPC6 rs77679196, BRINP1 rs62568637, LDB2 rs55756123, RAB22A rs707557, intergenic rs4305714, LINC01060 rs7698718, and CBR3 rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure (N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates. Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6 rs77679196 and CBR3 rs1056892 were significantly associated with congestive heart failure, p < 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab. TRPC6 rs77679196 and CBR3 rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.

P382 TEAMWORK IS SUCCESSFUL (2): PATIENT WITH DIFFUSE LARGE B–CELL LYMPHOMA (DLBCL) AND MULTIPLE HEART MASSES

Abstract Introduction Patients (Pts) with lymphoma are at high risk of cardiovascular events for the cardiotoxic effects of therapies and direct involvement of the heart. Autopsy series, indeed, indicate that cardiac localization may be observed in 10 – 25% of DLBCL Pts. The presence of cardiac mass, in DLBCL poses further complexity to the management beyond myocardial chemotherapy–related cardiotoxicity for the possible unfavorable/unpredictable evolution of the lymphoma mass (arrhythmias, AV block, myocardial ischemia, pericardial effusion and cardiac tamponade). We report the case of pt. with diffuse DLBCL, and multiple cardiac locations discovered, incidentally, on total body PET performed for disease stratification. Clinical case A 72–year–old woman with worsening asthenia and advanced stage non–GCB DLBCL presented multiple cardiac radiotracer uptake at 18FDG PET. The basal echocardiogram evidenced a roundish pedunculated mass at the level of the outflow tract of the right ventricle (24 x 22 mm) with significant obstruction of the RVOT, an oval formation at right ventricular apex with possible myocardial infiltration and a further mass in the right atrial site. Mild (&amp;lt; 1 mm) circumferential pericardial effusion, finally, was appreciated. No other notable alterations . After multi–disciplinary discussion, the patient underwent R–COMP based induction regimen, thus substituting conventional doxorubicin (R–CHOP) with non–pegylated liposomal doxorubicin in order to reduce the risk of acute cardiotoxicity. The first cycle was administered as inpatient under close cardiac monitoring, that was subsequently carried on before each cycle. No embolic and/or mechanical complications occurred. The response to chemotherapy was excellent: after the first cycle a substantial reduction in size of the cardiac masses was observed and after 3 cycles a complete resolution of the same was observed. Interim response evaluation by 18FDG PET after cycle 3 upheld early ultrasound observations by displaying a complete disappearance of pathological uptake. Conclusions In the case of patients with advanced DLBCL, multi–imaging evaluation enable appropriate assessment of cardiac conditions, including possible cardiac location and nature of masses. The personalized multidisciplinary management allows a tailored management of complex cases that enables both the achievement of treatment goals and the avoidance of acute complications.

RING Finger Protein 10 Regulates AP-1/Meox2 to Mediate Pirarubicin-Induced Cardiomyocyte Apoptosis.

Pirarubicin (THP) is one of the classic chemotherapy drugs for cancer treatment. It is often clinically limited because of its cardiotoxicity. The occurrence and development of THP-mediated chemotherapy-related cardiotoxicity (CRC) may be reversed by RING finger protein 10 (RNF10). This study was performed with the aim of evaluating the inhibitory effect of RNF10 on THP-mediated CRC and its molecular mechanism. In vivo, we found that the expression of RNF10 decreased in THP-induced CRC rats, accompanied by Meox2 inhibition and AP-1 activation, resulting in increased cardiomyocyte apoptosis. After small interfering RNA (siRNA) and lentivirus transfection (Lv) of RNF10 in vitro, the expression of RNF10, Meox2, and AP-1 proteins and the degree of cardiomyocyte apoptosis were detected. We found that overexpression of RNF10 in H9C2 cardiomyocytes significantly promoted Meox2 and inhibited AP-1, alleviated apoptosis, and showed further inhibitory activity on THP-induced cardiomyocyte toxicity. Silencing RNF10 showed the opposite result. Our study showed that RNF10 inhibited THP-induced CRC through the activity of Meox2 and AP-1 proteins. RNF10 may be the next drug target for the treatment of CRC and other related cardiovascular diseases.

A comparative study on efficacy of global longitudinal strain versus left ventricular ejection fraction in detection of anthracycline chemotherapy related cardiotoxicity

A comparative study on efficacy of global longitudinal strain versus left ventricular ejection fraction in detection of anthracycline chemotherapy related cardiotoxicity

Strain Longitudinal Global como Preditor de Cardiotoxicidade Induzida por Quimioterapia

Background: Chemotherapy-induced cardiotoxicity (ChC) is an important complication among patients receiving anthracyclines. Biomarkers and imaging parameters have been studied for their ability to identify patients at risk of developing ChC. Left ventricular global longitudinal strain (LV-GLS) is a sensitive parameter for detecting systolic dysfunction despite the presence of preserved left ventricular ejection fraction (LVEF). Objective: To evaluate the role of the LV-GLS as a predictor of ChC. Methods: This was a post-hoc analysis of the Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity trial, which evaluated the primary prevention of cardiotoxicity with carvedilol during doxorubicin chemotherapy in a population of patients with breast cancer. Cardiotoxicity was defined as a reduction ≥10% in LVEF. LV-GLS was determined before chemotherapy in patients with no prior cardiovascular disease or echocardiogram abnormalities. Results: Thirty-one patients for whom a complete echocardiography study including measurement of LV-GLS was performed before chemotherapy were included in this analysis. An absolute LV-GLS&lt;16.9% before chemotherapy showed 100% sensitivity and 73% specificity for predicting cardiotoxicity (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.680–0.959; p&lt;0.001). In this population, LVEF values before chemotherapy did not predict ChC (95% CI, 0.478 to -0.842; p=0.17). The association of low LV-GLS (&lt;17%) and brain-type natriuretic peptide serum levels (&gt;17 pg/mL) at 2 months after chemotherapy increased the accuracy for detecting early-onset ChC (100% sensitivity, 88% specificity; AUC, 0.94; 95% CI, 0.781–0.995; p&lt;0.0001). Conclusions: Our data suggest that LV-GLS is a potential predictor of ChC. Larger studies are needed to confirm its clinical relevance in this clinical setting.

The pediatric oncology exercise field speeds up to address important issues regarding chemotherapy-related cardiotoxicity.

The pediatric oncology exercise field speeds up to address important issues regarding chemotherapy-related cardiotoxicity.

Baseline left atrial reservoir strain provides independent and incremental prognostic value in predicting chemotherapy related cardiotoxicity

Abstract Background Currently, few baseline imaging biomarkers can predict chemotherapy induced cardiotoxicity (CTx). The early identification of CTx is critically important as it determines the prospect of LV function recovery (1). Purpose We aimed to determine if baseline left atrial (LA) reservoir strain (LAS) is predictive of CTx. Methods We performed retrospective analysis of the SUCCOUR study, an international multicentre randomized controlled trial. CTx was defined as an asymptomatic drop of &amp;gt;10% in left ventricular ejection fraction (LVEF) compared to baseline to &amp;lt;55%. LAS analysis was performed using semi-automated speckling tracking of the LA in the four and two chamber views using EchoPAC. Analysis was performed at one year follow up. Cox proportional hazard analysis, c-statistics and Akaike information criterion (AIC) statistical analysis was performed. Results After excluding 78 with inadequate images, 229 were included in the analysis. Most participants were female (n=215, 94%), with a mean age of 54±12 years. Median follow up was 1.02 years (IQR 0.98–1.07). A smoking history was the commonest cardiac risk factor (n=68, 30%). Breast cancer was the main cancer type (n=205, 90%). The mean baseline 3D LVEF, LV global longitudinal strain (GLS), LAS, and LA volume index (LAVI) were 61±4%, 20.6±2.5%, 28.6±7.9%, and 28±9ml/m2, respectively. Participants that developed CTx had a lower LAS at baseline compared to those that did not (25.5±7.4% vs 29.0±7.9% respectively; p=0.027). At 1-year follow-up, 29 patients (13%) developed CTx. On univariable Cox proportional hazard analysis, higher baseline LAS was associated with a lower risk of CTx (HR 0.95, 95% CI 0.90–0.99; p=0.026) but other parameters including baseline GLS was not (p=0.17). In nested Cox models (Figure 1), adding LAS significantly improved the model's predictive accuracy for CTx compared to other clinical and imaging parameters. When LAS was added to the same models it showed improvements in the c-statistics and AIC score (Figure 1). Conclusion Baseline LAS is an independent and incremental predictor of CTx. LAS could be used for baseline risk stratification in oncology patients who receive potentially cardiotoxic chemotherapy. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): GE Healthcare

Evaluation of the efficacy of global longitudinal strain in detection of anthracycline chemotherapy related cardiotoxicity

Evaluation of the efficacy of global longitudinal strain in detection of anthracycline chemotherapy related cardiotoxicity

The role of cellular senescence in cardiac disease: basic biology and clinical relevance.

Cellular senescence, classically defined as stable cell cycle arrest, is implicated in biological processes such as embryogenesis, wound healing and ageing. Senescent cells have a complex senescence-associated secretory phenotype (SASP), involving a range of pro-inflammatory factors with important paracrine and autocrine effects on cell and tissue biology. Clinical evidence and experimental studies link cellular senescence, senescent cell accumulation, and the production and release of SASP components with age-related cardiac pathologies such as heart failure, myocardial ischaemia and infarction, and cancer chemotherapy-related cardiotoxicity. However, the precise role of senescent cells in these conditions is unclear and, in some instances, both detrimental and beneficial effects have been reported. The involvement of cellular senescencein other important entities, such as cardiac arrhythmias and remodelling, is poorly understood. In this Review, we summarize the basic biology of cellular senescence and discuss what is known about the role of cellular senescence and the SASP in heart disease. We then consider the various approaches that are being developed to prevent the accumulation of senescent cells and their consequences. Many of these strategies are applicable in vivo and some are being investigated for non-cardiac indications in clinical trials. We end by considering important knowledge gaps, directions for future research and the potential implications for improving the management of patients with heart disease.

The Predictive role of speckle-tracking and left ventricular ejection fraction estimation using 2D and 3D echocardiography in the detection of chemotherapy related cardiotoxicity

Abstract Background 2D left ventricular ejection fraction (LVEF) estimation through echocardiography has been the classic parameter for cancer therapy–related cardiac dysfunction (CTrCD) detection. However, it is hypothesized that other parameters can be used in order to detect early stages of subclinical cardiotoxicity when LVEF is still preserved. Therefore, 3D LVEF and 2D and 3D strain parameters assessments have been evaluated in patients submitted to anthracyclines treatment. Objectives To compare 2D and 3D LVEF and strain parameters estimation using echocardiography regarding its ability to predict and detect subclinical and clinical cardiotoxicity during and after anthracyclines treatment. Search methods and criteria A systematic review was done and search was performed on PubMed and EMBASE from January 1st of 2000 to October 31th of 2020. Observational studies comparing 2D and 3D echocardiographic exams performed in adult patients submitted to anthracyclines were analyzed. Studies that evaluated survivors of pediatric cancer were excluded. 11 studies were included (n=844 patients). Main results 2D and 3D LVEF decreased throughout the echocardiographic assessments of 7 studies, but 2D LVEF drops were not statistically significant in 4 studies and 3 studies showed that 3D LVEF detected a superior number of patients with abnormal LVEF. Compared to 3D LVEF, 2D GLS decreased at an earlier point of treatment and detected a superior number of patients with subclinical LV dysfunction. Despite 2D and 3D GLS decreased throughout treatment, 3D GLS measurements were consistently lower and had higher relative variation. All 3D strain parameters decreased during and after the treatment and have higher relative variations than 2D GLS, with the exception of 1 study. 3D GLS reference values are not yet recognized by guidelines, so subclinical LV dysfunction was not evaluated. Conclusions LVEF estimation through 3D proved to be a better parameter for CTrCD detection vs 2D imaging. GLS is superior to 3D LVEF in detecting earlier LV changes, even if calculated using 2D echocardiography. Moreover, GLS reduction can be a predictor of subsequent LVEF decrease. 3DE is a growing potential technique and may be superior to 2DE in detecting and predicting subclinical LVEF dysfunction and CTrCD, respectively. Though 3D strain parameters presented promising results, more studies are needed to prove its incremental value over 2D strain echocardiography Funding Acknowledgement Type of funding sources: None.

Statin use can attenuate the decline in left ventricular ejection fraction during the cardiotoxic chemotherapy: a systemic review and meta-analysis

Abstract Background Antineoplastic medications such as anthracyclines and trastuzumab are effective in treating various hematologic and solid organ malignancies, however an increased risk of cardiotoxicity in patients has been reported. A decline in left ventricular ejection fraction (LVEF) is a common finding in chemotherapy-induced cardiomyopathy and is sometimes irreversible and lethal. Several agents such as beta blockers and angiotensin-converting enzyme (ACE) inhibitors have shown to reduce the chemotherapy-induced cardiotoxicity in cancer patients. The use of statins, however, to prevent chemotherapy-related cardiotoxicity is not as well studied as other cardioprotective agents. In this study, we aimed to investigate the difference in the degree of decline in the LVEF in patients who received concurrent statin during the chemotherapy compared to those who received chemotherapy alone. Methods A systematic search of MEDLINE and EMBASE databases was performed from inception to March 2021 for studies that reported the mean LVEF before and after chemotherapy in patients who received concurrent statin therapy and those who did not receive statin along with the chemotherapy. A random effects meta-analysis was performed to obtain the pooled WMD of LVEF between the intervention (statin with chemotherapy) and the control group (chemotherapy alone) before and after chemotherapy treatments using STATA 16. Results Four studies with a total of 297 patients were included in this meta-analysis. Of the 297 patients, 115 patients were in the intervention group and received statin with chemotherapy, while 182 patients were in the control group and received chemotherapy alone. Baseline mean LVEF had no statistically significant difference between the intervention (statin) and the control (no statin) group, and the WMD was −0.38% (95% CI: −1.27 to 0.51, p=0.342). Upon follow-up, the control group patients showed a significantly greater decline in LVEF, with WMD of −6.08% (95% CI: −8.55 to −3.61, p=0.013), compared to the intervention group. Conclusion Patients who did not receive statin during the chemotherapy period had a greater mean decline in LVEF from baseline compared to that of the control group after the chemotherapy treatments. Funding Acknowledgement Type of funding sources: None.

Four-year follow-up of a patient with mixed cardiomyopathy and an implanted cardiac contractility modulation device: a case report

The article presents a case report of a 28-year-old male patient with mixed dilated cardiomyopathy: myocardial noncompaction and chemotherapy-related cardiotoxicity, which led to severe heart failure (HF). With optimal drug therapy, the patient was implanted with a cardiac contractility modulation device in order to improve exercise tolerance, quality of life and relieve HF symptoms. Complex therapy has led to significant clinical and echocardiographic improvement. This case demonstrates a 4-year follow-up of a patient with a reduced left ventricular ejection fraction and an implanted cardiac contractility modulation device, whose condition, after several severe HF decompensations, was stabilized.

Cost-effectiveness of cardio-oncology clinical assessment for prevention of chemotherapy-induced cardiotoxicity

IntroductionCancer chemotherapy increases the risk of heart failure. This cost-effectiveness study analyzes cardio-oncology imaging assessment of left ventricular ejection fraction (LVEF) using a Portuguese healthcare payer perspective and a five-year time horizon. MethodsTwo cardioprotective strategies were assessed: universal cardioprotection (UCP) for all patients and cardioprotection initiated on diagnosis of LVEF-defined cardiotoxicity (EF-CTX). A Markov model, informed by the retrospective clinical course of breast cancer patients followed in a Portuguese public hospital, was developed to assess the cost-effectiveness of LVEF cardio-oncology imaging assessment. Data on transition probabilities, costs and utilities were retrieved from both the retrospective data and published literature to assess the cost-effectiveness of LVEF echocardiographic assessment. Costs and utilities of the cardioprotective strategies were assessed over a five-year range, using probabilistic sensitivity analyses. ResultsIn the reference case of a 63-year-old breast cancer patient treated with cardioprotection initiated on diagnosis of EF-CTX, the five-year time horizon (4.22 QALYs and €2594 cost over five years) dominated UCP (3.42 QALYS and €3758 cost over five years). Under a time horizon of five years at a willingness-to-pay threshold of €22 986, over 65.7% of simulations provided additional QALYs. Monte Carlo simulation of the Markov model had no effect on the model's conclusions. ConclusionIn the Portuguese public healthcare system and under specific hypotheses, from a healthcare payer perspective, EF-CTX-guided cardioprotection for patients at risk of chemotherapy-related cardiotoxicity provides more QALYs at lower cost than UCP.