A critical evaluation of contemporary literature regarding the role of big data, artificial intelligence, and digital technologies in precision cardio-oncology care and survivorship, emphasizing innovative and groundbreaking endeavors.

Artificial intelligence (AI) algorithm models can automate the risk assessment process and augment current subjective clinical decision tools. AI, particularly machine learning (ML), can identify medically significant patterns in large data sets. Machine learning in cardio-oncology care has great potential in screening, diagnosis, monitoring, and managing cancer therapy-related cardiovascular complications. To this end, large-scale imaging data and clinical information are being leveraged in training efficient AI algorithms that may lead to effective clinical tools for caring for this vulnerable population. Telemedicine may benefit cardio-oncology patients by enhancing healthcare delivery through lowering costs, improving quality, and personalizing care. Similarly, the utilization of wearable biosensors and mobile health technology for remote monitoring holds the potential to improve cardio-oncology outcomes through early intervention and deeper clinical insight. Investigations are ongoing regarding the application of digital health tools such as telemedicine and remote monitoring devices in enhancing the functional status and recovery of cancer patients, particularly those with limited access to centralized services, by increasing physical activity levels and providing access to rehabilitation services.

In recent years, advances in cancer survival have increased the prevalence of patients experiencing cancer therapy-related cardiovascular complications. Traditional cardio-oncology risk categorization largely relies on basic clinical features and physician assessment, necessitating advancements in machine learning to create objective prediction models using diverse data sources. Healthcare disparities may be perpetuated through AI algorithms in digital health technologies. In turn, this may have a detrimental effect on minority populations by limiting resource allocation. Several AI-powered innovative health tools could be leveraged to bridge the digital divide and improve access to equitable care.

Patients with cancer undergoing chemotherapy with an anthracycline-based regimen are at increased risk of cardiotoxicity, predisposing to heart failure, arrhythmias and death. Whether carvedilol may confer benefit to prevent anthracycline-induced cardiotoxicity remains to be determined.

CARDIOTOX is a double-blind, placebo controlled randomized clinical trial that plan to enroll 1,018 patients across 25 study sites in Brazil. Patients with active cancer scheduled to undergo an anthracycline-based chemotherapy regimen are eligible. Patients with prior HF or cardiomyopathy are excluded. Patients are randomized in 1:1 ratio to carvedilol (starting dose 6.25mg BID up titrated to 25mg BID or maximum tolerated dose) or placebo, stratified by site and use of renin-angiotensin blockers at baseline. Study drug is administered through the duration of chemotherapy and up to 30 days after the last dose of anthracycline. Patients are scheduled to undergo echocardiographic evaluations at baseline and at 3, 6, and 12 months. The study primary endpoint is the composite of new left ventricle ejection fraction (LVEF) reduction by at least 10% leading to an LVEF <50%, cardiovascular death, myocardial infarction, urgent care visit or hospitalization for heart failure, or clinically significant arrhythmias at 12 months. Echocardiographic images will be analyzed by a central core lab, clinical outcomes will be adjudicated, and safety endpoints include serious adverse events and adverse events of special interest (symptomatic bradycardia, hypotension, syncope and bronchospasm).

The CARDIOTOX trial is the largest trial to date analyzing the potential role of beta-blockers as prophylactic therapy to prevent cardiotoxicity induced by anthracyclines.

Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox).

gov ID NCT04939883. https://clinicaltrials.gov/study/NCT04939883.

Cancer poses a significant threat to human life and health. Cancers treated with cisplatin invariably develop drug resistance. This challenge can be overcome by identifying and exploiting the vulnerabilities acquired by drug-resistant cancer cells, paving the way for finding effective novel treatment options for cisplatin-resistant cancers. Our previous study revealed that cisplatin resistance in cancer cells comes at the cost of increased intracellular hypoxia. In this study, we used 2-nitroimidazole modified hyaluronic acid (HA-NI) as the carrier. The cisplatin-resistant tumor cell specific intracellular hypoxia programmed activation nanomedicine (T/C@HN NPs) was constructed by the hypoxic toxic drug tirapazamine (TPZ) and encapsulating chlorin e6 (Ce6) into HA-NI using polymer assembly technology. The amphiphilic carrier could release free Ce6 molecules under the stimulation of intracellular hypoxic environment, and exhibit specific "activated state" photodynamic properties in cisplatin-resistant tumor cells. Upon irradiation, Ce6-mediated photodynamic therapy further intensifies hypoxia, amplifying its cytotoxicity. This project systematically evaluated the effects of T/C@HN NPs on the identification and recognition of cisplatin-resistant tumors using drug-resistant patient-derived xenograft (PDX) models. This study provides a promising avenue for the development of novel treatment of cisplatin-resistant tumors.

Anthracycline-based chemotherapy is a cornerstone in breast cancer treatment but is associated with cardiotoxicity, including subclinical cardiac damage. This study evaluates the efficacy of ramipril and bisoprolol in preventing subclinical cardiac impairment in patients with nonmetastatic breast cancer undergoing anthracycline-based chemotherapy.

The SAFE trial is a multicenter, 2 × 2 factorial, randomized, placebo-controlled, double-blind study involving 262 patients. Participants were allocated to one of four groups: placebo-placebo, ramipril-placebo, bisoprolol-placebo, or ramipril-bisoprolol, administered concurrently with chemotherapy. Subclinical cardiac damage was assessed at 24 months using echocardiographic measures, specifically a ≥10% reduction in three-dimensional left ventricular ejection fraction (3D-LVEF) or global longitudinal strain (GLS).

At 24 months, patients receiving ramipril, bisoprolol, or their combination experienced significantly smaller declines in 3D-LVEF compared with placebo (-2.1%, -2.2%, and -3.4%, respectively; all P < 0.001). GLS results were consistent with these findings (P < 0.001). Subclinical cardiac damage occurred in 11.4% of patients receiving ramipril versus 39.3% without ramipril (P < 0.001), and in 9.6% of patients receiving bisoprolol versus 43.5% without bisoprolol (P < 0.001).

Ramipril and bisoprolol significantly reduce the incidence of subclinical cardiac damage in patients with breast cancer undergoing anthracycline-based chemotherapy, thus supporting their use as early prevention cardioprotective strategies.

Cancer therapy-related cardiac dysfunction frequently occurs in patients receiving anthracycline. Ivabradine reduces heart rate without affecting contractility and showed anti-inflammatory, antioxidant, and antiapoptotic effects in experimental cardiotoxicity models. This study aims to evaluate the effect of ivabradine on cancer therapy-related cardiac dysfunction in patients with lymphoma or sarcoma treated with anthracycline.

In a randomized, triple-blind trial, patients starting anthracycline therapy received either ivabradine 5 mg twice daily or placebo until 30 days after completing treatment. The primary outcome was the incidence of cardiotoxicity measured as a ≥10% relative reduction in global longitudinal strain at 12 months from baseline. Secondary outcomes included 12-month clinical outcomes, a ≥10% decrease in the left ventricular ejection fraction to <55%, diastolic dysfunction, and troponin T and N-terminal pro-B-type natriuretic peptide levels.

This study enrolled 107 patients (51 in the ivabradine group and 56 in the placebo group). The median dose of anthracycline was 300 mg/m2 (250-300 mg/m2) in both groups. Cardiotoxicity measured as a ≥10% relative reduction in global longitudinal strain at 12 months was reached in 57% versus 50% in the ivabradine and placebo groups (odds ratio, 1.32 [95% CI, 0.61-2.83]; P=0.477). Fewer patients in the ivabradine group than in the placebo group had troponin T levels ≥14 ng/L (16 [39.0%] versus 23 [62.2%]; P=0.041) at 6 months, with this difference not maintained at the 12-month follow-up. In addition, there were no differences in the other secondary outcomes.

A fixed 10 mg/day dose of ivabradine does not protect patients with cancer against anthracycline cardiotoxicity.

URL: https://clinicaltrials.gov/; Unique Identifier: NCT03650205.

Assessing cardiac risk prior to initiating breast cancer treatment, monitoring cardiac function during treatment, and implementing appropriate follow-up strategies are essential components of managing cardiotoxicity in breast cancer patients. A comprehensive cardiovascular evaluation should be conducted before treatment, including a detailed medical history, physical examination, and baseline cardiac imaging. Risk stratification tools can aid in determining the individual patient's risk profile. Close monitoring of cardiac function, including regular assessment of left ventricular ejection fraction (LVEF) and monitoring for signs and symptoms of cardiac dysfunction, is crucial during treatment. Prompt action should be taken if an adverse cardiovascular event is detected, including considering discontinuing or modifying the treatment regimen. Appropriate follow-up care is essential to monitor for long-term cardiac effects and optimize cardiovascular health in breast cancer survivors. Regular cardiovascular assessments, lifestyle modifications, and collaboration between healthcare professionals are important in managing cardiotoxicity effectively.

Chemotherapy-related cardiotoxicity (CTRTOX) is a profound and common side effect of cancer-based therapy in a subset of patients. The underlying factors and the associated mechanisms contributing to severe toxicity of the heart among these patients remain unknown. While challenges remain in accessing human subjects and their ventricular cardiomyocytes (CMs), advancements in human induced pluripotent stem cell (hiPSC)-technology-based CM differentiation protocols over the past few decades have paved the path for iPSC-based models of human cardiac diseases. Here, we offer a detailed analysis of the underlying mechanisms of CTRTOX. We also discuss the recent advances in therapeutic strategies in different animal models and clinical trials. Furthermore, we explore the prospects of iPSC-based models for identifying novel functional targets and developing safer chemotherapy regimens for cancer patients that may be beneficial for developing personalized cardioprotectants and their application in clinical practice.

Cardiotoxic, anthracycline-based therapies have high value in selected patients with breast cancer. We aimed to describe the effect of anthracycline plus taxane and single taxane chemotherapies on echocardiographic parameters in women with breast cancer.

We retrospectively analysed data of 68 women (> 18 years old) treated for breast cancer in 2018-2021 in the Cardiology Outpatient Clinic of Semmelweis University, Department of Internal Medicine and Oncology. Cardiovascular medical history was collected at baseline and transthoracic echocardiography was completed at each visit. Also, we reviewed electronic medical records for other relevant medical information. Measured echocardiography parameters were assigned to five periods (0-14 days, then every half year and beyond day 545) based on the time since the first treatment. Trajectories of ejection fraction and diastolic function associated markers over the follow-up periods were analysed by linear mixed models.

Mean age of the anthracycline plus taxane group was 52.7 ± 14.1 years, of the single taxane group 55.2 ± 13.1 years. The mean anthracycline dose was equivalent to 240 mg/m2 of doxorubicin. Overall pre-existing cardiovascular burden was low. Statistically significant changes were found only in the anthracycline plus taxane group: ejection fraction decreased mildly from 65.5 ± 3.1% at baseline to 62.1 ± 3.2% at 181-365 days (p = 0.007) while deceleration time decreased mildly from 227.9 ± 33.9 msec to 197.4 ± 29.4 msec at 15-180 days (p = 0.028). Both drops were only temporary and values neared baseline values over follow-up (p = NS vs. baseline). Other important determinants of ejection fraction were age and hypertension among the investigated risk factors.

Our study confirms the overall safety on cardiac function of both single taxane and anthracycline plus taxane chemotherapy, as we found no changes in echocardiographic parameters associated with single taxane therapy, while anthracycline plus taxane chemotherapy was associated with a temporary and clinically insignificant reduction of ejection fraction and deceleration time over 1.5 years of follow-up. Our study is limited by its retrospective nature and the low number of participants.

The increasing efficacy of cancer therapies has significantly improved survival rates, but it has also highlighted the prevalence of cancer-therapy-related cardiac dysfunction (CTRCD). This review provides a comprehensive overview of the identification, monitoring, and management of CTRCD, a condition resulting from several treatments, such as anthracyclines, HER2-targeted therapies, target therapies, and radiotherapy. The paper includes a discussion of the mechanisms of CTRCD associated with various cancer treatments. Early detection through serum biomarkers and advanced imaging techniques is crucial for effective monitoring and risk stratification. Preventive strategies include pharmacological interventions such as ACE inhibitors/angiotensin receptor blockers, beta-blockers, and statins. Additionally, novel agents like sacubitril/valsartan, sodium-glucose co-transporter type 2 inhibitors, and vericiguat show promise in managing left ventricular dysfunction. Lifestyle modifications, including structured exercise programs and optimized nutritional strategies, further contribute to cardioprotection. The latest treatments for both asymptomatic and symptomatic CTRCD across its various stages are also discussed. Emerging technologies, including genomics, artificial intelligence, novel biomarkers, and gene therapy, are paving the way for personalized approaches to CTRCD prevention and treatment. These advancements hold great promise for improving long-term outcomes in cancer patients by minimizing cardiovascular complications.

Anthracycline chemotherapy leads to cardiotoxicity in patients with breast cancer. We performed a double-blind randomized controlled trial to assess the efficacy of crocin (crocin tablets) in reducing anthracycline-induced cardiotoxicity in breast cancer patients. Eligible patients were randomly assigned to receive either treatment with crocin tablets or placebo for 6 months. Primary efficacy outcome was the proportion of patients with a drop in left ventricular ejection fraction (LVEF) of at least 10 % from baseline until 6 months. We randomized 200 patients; 7 of them had no valid randomization as the change in chemotherapy scheme. A total of 193 eligible participants (mean [SD] age, 50.9 [9.6] years; all women) were randomly assigned to receive crocin tablets or placebo. The incidence of the primary efficacy outcome was 7.2 % (7/97) in the crocin group and 17.7 % (17/96) in the placebo group (P = 0.027). At 6 months, there were significant differences in the mean change of N-terminal pro-brain natriuretic peptide (NT-pro BNP) between the groups (3.06 [-25.18-6.95] vs. 3.06 [-4.85-24.98] pg/ml; P = 0.017). The changes in heart rate from baseline to 6 months showed a significant difference as the mean difference of -4.00 (95 %CI, -6.95 to -1.05) bpm (P = 0.008). Conclusively, among patients with breast cancer treated with anthracycline-based chemotherapy, crocin tablets reduced the incidence of LVEF reduction. This finding indicated that crocin tablets might be a safe and effective therapy to prevent the cardiotoxicity in this population. (Chictr.org.cn, ID Number: ChiCTR2000041134).

Dilated cardiomyopathy (DCM) is a complex disease with multiple causes and various pathogenic mechanisms. Despite improvements in the prognosis of patients with DCM in the past decade, this condition remains a leading cause of heart failure and premature death. Conventional treatment for DCM is based on the foundational therapies for heart failure with reduced ejection fraction. However, increasingly, attention is being directed towards individualized treatments and precision medicine. The ability to confirm genetic causality is gradually being complemented by an increased understanding of genotype-phenotype correlations. Non-genetic factors also influence the onset of DCM, and growing evidence links genetic background with concomitant non-genetic triggers or precipitating factors, increasing the extreme complexity of the pathophysiology of DCM. This Review covers the spectrum of pathophysiological mechanisms in DCM, from monogenic causes to the coexistence of genetic abnormalities and triggering environmental factors (the 'two-hit' hypothesis). The roles of common genetic variants in the general population and of gene modifiers in disease onset and progression are also discussed. Finally, areas for future research are highlighted, particularly novel therapies, such as small molecules, RNA and gene therapy, and measures for the prevention of arrhythmic death.

Introduction of modern cancer therapies has led to increased survival of affected patients. With this advantage, the incidence of cancer therapy-related cardiac dysfunction (CTRCD) has increased and reasonable prevention strategies become necessary. This review outlines the major approaches to limit development and progression of CTRCD.

A broad range of cancer therapies can provoke CTRCD ranging from mild asymptomatic forms to severe heart failure. Profound cardiological assessment of cardiovascular comorbidities before initiation of cancer therapy allows identification of cancer patients at higher risk developing CTRCD which may also require closer surveillance. Cardioprotective adjustment of cancer therapy and initiation of cardioprotective medication and lifestyle optimization prior to anti-cancer treatment additionally limit the risk of CTRCD. During therapy, regular examination of cancer patients using high-sensitive cardiological diagnostic tools as three-dimensional (3D) echocardiography and global longitudinal strain (GLS) enables early detection of mild forms of CTRCD. This allows appropriate adjustment of cancer therapy and initiation of CTRCD treatment to prevent further progression to severe forms. Cardiological risk stratification before treatment initiation, cardioprotective interventions before and during cancer therapy, along with regular monitoring of treated cancer patients, can help prevent the development of CTRCD. This maintains the antitumor effects of cancer therapy while limiting cardiotoxic side effects resulting in improved quality of life and mortality of affected cancer patients.

Anthracycline chemotherapy is associated with cardiotoxicity, predominantly manifesting as left ventricular systolic dysfunction within the first year of treatment. Early detection is possible through biomarkers and cardiovascular imaging before clinical symptoms develop. Comprehensive cardiovascular risk assessment is essential for all patients prior to anthracycline therapy to stratify their risk of cardiotoxicity. Preventive measures, including cardiovascular risk optimization, as well as anthracycline dose adjustments, the use of liposomal anthracyclines, and dexrazoxane in high-risk patients, are crucial to mitigate the risk of cardiotoxicity. Long-term follow-up and cardiovascular risk optimization are critical for cancer survivors to optimize cardiovascular outcomes.

Thanks to the fantastic progress in cancer therapy options, there is a growing population of cancer survivors. This success has resulted in a need to focus much effort into improving the quality of life of this population. Cancer and cardiovascular disease share many common risk factors and have an interplay between them, with one condition mechanistically affecting the other and vice versa. Furthermore, widely prescribed cancer therapies have known toxic effects in the cardiovascular system. Anthracyclines are the paradigm of efficacious cancer therapy widely prescribed with a strong cardiotoxic potential. While some cancer therapies cardiovascular toxicities are transient, others are irreversible. There is a growing need to develop cardioprotective therapies that, when used in conjunction with cancer therapies, can prevent cardiovascular toxicity and thus improve long-term quality of life in survivors. The field has three main challenges: (i) identification of the ultimate mechanisms leading to cardiotoxicity to (ii) identify specific therapeutic targets, and (iii) more sensible diagnostic tools to early identify these conditions. In this review we will focus on the cardioprotective strategies tested and under investigation. We will focus this article into anthracycline cardiotoxicity since it is still the agent most widely prescribed, the one with higher toxic effects on the heart, and the most widely studied.

Anthracyclines are the cornerstone of treatment for many malignancies. However, anthracycline cardiotoxicity is a considerable concern given that it can compromise the clinical effectiveness of the treatment and patient survival despite early discontinuation of therapy or dose reduction. Patients with cancer receiving anthracycline treatment can have a reduction in their quality of life and likelihood of survival due to cardiotoxicity, irrespective of their oncological prognosis. Increasing knowledge about anthracycline cardiotoxicity has enabled the identification of patients who are candidates for anthracycline regimens and those who might develop anthracycline-induced cardiomyopathy. Anthracycline cardiotoxicity is a unique and evolving phenomenon that begins with myocardial cell damage, progresses to reduced left ventricular ejection fraction, and culminates in symptomatic heart failure if it is not promptly detected and treated. Early risk stratification can be guided by imaging or biomarkers. In this Review, we present a comprehensive and clinically useful approach to cardiomyopathy related to anthracycline therapy, encompassing its epidemiology, definition, mechanisms, novel classifications, risk factors and patient risk stratification, diagnostic approaches (including imaging and biomarkers), treatment guidelines algorithms, and the role of new cardioprotective drugs that are used for the treatment of heart failure.

Neurohormonal blocking drugs, like beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), are recommended for treating anthracycline-induced left ventricular dysfunction (AILVD). However, there is limited evidence supporting their benefit. Therefore, this study evaluated associations of neurohormonal blockers and other clinical factors with recovery of left ventricular ejection fraction (LVEF) in patients with AILVD.

This retrospective chart review assessed patients treated with at least one dose of anthracycline, then had ≥10% LVEF reduction or post-anthracycline LVEF value <50%, and then had a follow-up LVEF measurement ≥90 days later. The primary endpoint was LVEF recovery (highest follow-up LVEF-lowest LVEF post-anthracycline). Variables from univariable tests with P < .1 were incorporated in a multiple linear regression model for independent factors significantly associated with LVEF recovery (P < .05).

Out of 104 patients, 83% were female, 86% self-reported white race, 53% had breast cancer, median (IQR) age was 52 (22) years, and LVEF recovery was 14% (16%). The final multivariable model included 2 significant variables: beta-blocker dose after anthracycline exposure (every 25 mg increase in beta-blocker dose was associated with 5.0% increase in LVEF recovery; P = .0005) and the time between the start of the anthracycline and the lowest LVEF post-anthracycline (every 5-year increase in time was associated with 1.8% decrease in LVEF recovery; P = .0379).

In patients with AILVD, a higher beta-blocker dose and earlier detection of LVEF reduction post-anthracycline were significantly and independently associated with improved LVEF recovery. These findings need to be validated in a larger, independent cohort.

During the last decades, progress in the treatment of oncological diseases has led to an increase in the survival of cancer patients: cancer survivors (CS). Thus, the incidence of CS has increased enormously, in both adult CS and childhood and adolescent CS. Unfortunately, CS treated with anthracyclines, chest radiotherapy (RT) and other potentially cardiotoxic drugs have a higher risk of cardiovascular (CV) toxicity: heart failure with reduced ejection fraction (HFrEF), valve diseases, coronary artery diseases, vascular diseases and pericardial diseases. In fact, chest irradiation can cause coronary artery diseases that can be latent until at least 10 years after exposure; also, valvular heart diseases can appear after >20 years following irradiation; heart failure may appear later, several years after anticancer drugs or RT. Therefore, it is very important to stratify the CV risk of cancer patients at the end of cardiotoxic drugs, to plan the most appropriate long-term surveillance program, in accordance with 2022 ESC Guidelines on Cardio-Oncology, to prevent late cardiovascular complications. Monitoring of cancer patients must not stop during anticancer treatment but it must continue afterwards, depending on the patient's CV risk. CV toxicity risk should be reassessed 5 years after therapy to organize long-term follow-up. Considering late cardiotoxicity in CS, our review aims to evaluate the incidence of cardiovascular diseases in CS, their mechanisms, surveillance protocols, preventive strategies, diagnosis and treatment.

Cancer therapy-related cardiac dysfunction (CTRCD) has emerged as a significant concern with the rise of effective cancer treatments like anthracyclines and targeted therapies such as trastuzumab. While these therapies have improved cancer survival rates, their unintended cardiovascular side effects can lead to heart failure, cardiomyopathy, and arrhythmias. The pathophysiology of CTRCD involves oxidative stress, mitochondrial dysfunction, and calcium dysregulation, resulting in irreversible damage to cardiomyocytes. Inflammatory cytokines, disrupted growth factor signaling, and coronary atherosclerosis further contribute to this dysfunction. Advances in cardio-oncology have led to the early detection of CTRCD using cardiac biomarkers like troponins and imaging techniques such as echocardiography and cardiac magnetic resonance (CMR). These tools help identify asymptomatic patients at risk of cardiac events before the onset of clinical symptoms. Preventive strategies, including the use of cardioprotective agents like beta-blockers, angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors have shown promise in reducing the incidence of CTRCD. This review summarizes the mechanisms, detection methods, and emerging treatments for CTRCD, emphasizing the importance of interdisciplinary collaboration between oncologists and cardiologists to optimize care and improve both cancer and cardiovascular outcomes.

Trastuzumab therapy for HER2-positive cancers is associated with cardiotoxicity. This umbrella review synthesizes evidence from systematic reviews and meta-analyses on cardioprotective interventions during trastuzumab treatment.

A comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Systematic reviews and meta-analyses examining cardioprotective interventions in patients receiving trastuzumab were included. The methodological quality was assessed using the AMSTAR-2 tool. Data on cardiac events, treatment interruptions, left ventricular ejection fraction (LVEF) changes, and exercise interventions were synthesized.

Ten systematic reviews met the inclusion criteria. Statins demonstrated the strongest cardioprotective effect (RR = 0.47, 95% CI: 0.26-0.84), potentially preventing more than half of cardiac events during trastuzumab therapy, followed by beta-blockers (RR = 0.61, 95% CI: 0.39-0.93). Beta-blockers and ACEIs effectively reduced treatment interruptions, enabling approximately 40% more patients to maintain treatment continuity (RR = 0.63, 95% CI: 0.47-0.86). Among non-pharmacological interventions, structured exercise programs showed significant benefits in preserving cardiac function, demonstrating meaningful improvements in resting LVEF (WMD = -3.27%, 95% CI: -5.86 to -0.68).

This review demonstrates that cardioprotective interventions, particularly statins and beta-blockers, significantly reduce the risk of cardiac complications during trastuzumab therapy. The positive impact on cardiac events and treatment interruptions suggests these interventions may enhance overall treatment efficacy by allowing more patients to complete their prescribed course.

Evidence strongly supports the systematic implementation of cardioprotective strategies in clinical practice, particularly statins and beta-blockers, as part of routine care protocols for patients receiving trastuzumab therapy. These interventions demonstrate significant potential in preventing cardiac complications and maintaining treatment continuity. Further research should focus on optimizing personalized approaches and evaluating long-term outcomes.

Chemotherapy-induced cardiotoxicity (CIC) is a significant challenge in cancer treatment, leading to heart failure and myocardial infarction. With rising cancer survival rates, the long-term cardiovascular health of survivors has gained importance. While several cardioprotective medications have been studied to mitigate chemotherapy's harmful effects on the heart, more research is needed to confirm their effectiveness and optimal use.

This review synthesizes evidence on cardioprotective drugs in managing CIC. The authors conducted a comprehensive literature search of peer-reviewed articles, clinical trials, and meta-analyses published between January 2000 and May 2024. Studies were selected based on relevance, quality, and focus on mechanisms, efficacy, and clinical outcomes of cardioprotective agents such as beta-blockers, ACE inhibitors, ARBs, statins, and dexrazoxane.

Cardioprotective medications show potential in alleviating the impact of chemotherapy on heart function. Beta-blockers and ACE inhibitors effectively reduce heart failure incidence and improve cardiac outcomes. Statins, with their anti-inflammatory and antioxidative properties, and dexrazoxane, which reduces anthracycline-induced cardiotoxicity, also show promise. However, variability in study designs, patient groups, and chemotherapy treatments complicates the establishment of standardized treatment protocols.

Cardioprotective drugs hold significant promise in managing CIC and improving cardiac outcomes for cancer patients. Current evidence supports the efficacy of beta-blockers, ACE inhibitors, statins, and dexrazoxane. Further research is needed to establish standardized protocols, evaluate long-term safety, and optimize treatment timing. Integrating cardioprotective strategies into oncological care can enhance the quality of life and prognosis for cancer survivors.

This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT).

Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software.

In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5 Gy; for patients with subclinical heart damage, the mean MHD was 1.6 Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage.

Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events.

Specific cancer treatments can lead to cancer therapy-related cardiac dysfunction (CTRCD). Sodium glucose cotransporter-2 inhibitors (SGLT2is) can potentially prevent these cardiotoxic effects.

This study sought to determine whether SGLT2i use is associated with a lower incidence of CTRCD in patients with type 2 diabetes mellitus (T2DM) and cancer, exposed to potentially cardiotoxic antineoplastic agents, and without a prior documented history of cardiomyopathy or heart failure.

We conducted a retrospective analysis of patients aged ≥18 years within the TriNetX database with T2DM, cancer, exposure to cardiotoxic therapies, and no prior documented history of cardiomyopathy or heart failure. Patients were categorized by SGLT2i use. After propensity score matching, outcomes were compared over 12 months using Cox proportional HRs. Subgroup analyses focusing on different cancer therapy classes were performed.

The study included 8,675 propensity-matched patients in each cohort (mean age = ∼65 years, 42% females, 71% White, ∼19% gastrointestinal malignancy, and ∼25% anthracyclines). Patients prescribed SGLT2is had a lower risk of developing CTRCD (HR: 0.76: 95% CI: 0.69-0.84). SGLT2is also reduced heart failure exacerbations (HR: 0.81; 95% CI: 0.72-0.90), all-cause mortality (HR: 0.67; 95% CI: 0.61-0.74), and all-cause hospitalizations/emergency department visits (HR: 0.93; 95% CI: 0.89-0.97). Subgroup analyses also demonstrated reduced CTRCD risk across various classes of cancer therapies in patients prescribed SGLT2is.

SGLT2i administration was associated with a significantly decreased risk of developing CTRCD in patients with T2DM and cancer.

Cardiac biomarkers are a vital component within the first edition of the European Society of Cardiology guidelines in Cardio-Oncology. Specifically, they are mentioned in the definition of mild asymptomatic cancer therapy-related cardiac dysfunction, where left ventricular systolic function is ≥50 % with two outcomes; either a new decrease in global longitudinal strain >15 % from baseline and/or a new rise in cardiac biomarkers above the defined 99th percentile cut off values. Cardiac troponin is one such biomarker. Many of the treatments for breast cancer have published data on cardiac dysfunction and/or cardiovascular toxicity, and such may lead to an elevation in cardiac troponin. However, there is conflicting and incomplete data regarding how to approach an elevated cardiac troponin during anti-cancer treatment, which has confounded patient care in the clinical trial setting. We propose a novel framework to guide physicians in treatment-related elevation of cardiac troponin in the breast cancer population. Secondly, the additive role which the recommendation that cardiac troponin carries within mild asymptomatic definitions of CTRCD is the subject of great debate. We suggest a reflection on the role of biomarkers, specifically in reference to cardiac troponin.

Global longitudinal strain (GLS) has been used to identify patients at risk for cancer-therapy related cardiac dysfunction (CTRCD). However, there is limited data on the effectiveness of initiating cardioprotective therapy based on a strain-guided strategy in early stage HER2+ breast cancer patients. This randomized clinical trial assessed if treatment with carvedilol based on a strain-guided strategy can prevent development of CTRCD in HER2+ breast cancer patients on non-anthracycline based regimens.

Study participants were prospectively assigned to one of four arms. Patients with normal LVEF and GLS remained in Arm A. Patients whose GLS decreased by > 15% from baseline or to < -15% during follow up were randomized 1:1 to prophylactic carvedilol (Arm B) or no therapy (Arm C). Patients who developed CTRCD were assigned to Arm D. The primary endpoint was GLS stability. The secondary endpoints were development of CTRCD and rate of anti-HER2 treatment interruption.

Among 110 patients who completed follow up, 84 were assigned to Arm A, 10 each were randomized to Arms B or C, and 6 were assigned to Arm D. At the end of the study period, there were no significant differences in GLS stability, development of CTRCD, or number of cancer therapy cycles completed between patients who did and did not receive cardioprotective therapy.

In this prospective randomized GLS-guided study of prophylactic carvedilol in early stage HER2+ breast cancer patients on non-anthracycline regimens, there were no significant difference between groups in GLS stability, CTRCD or trastuzumab cycles held. These findings may identify a low-risk group of patients who may be considered for less intensive cardiac surveillance.

https://clinicaltrials.gov/study/NCT02993198 . Start date: 4/2015. This trial included patients who were retrospectively registered.

Defined as scarce expression of hormone receptors and human epidermal growth factor receptor 2, triple-negative breast cancer (TNBC) is labeled as the most heterogeneous subtype of breast cancer with poorest prognosis. Despite rapid advancements in precise subtyping and tailored therapeutics, the ensuing cancer therapy-related cardiovascular toxicity (CTR-CVT) could exert detrimental impacts to TNBC survivors. Nowadays, this interdisciplinary issue is incrementally concerned by cardiologists, oncologists and other pertinent experts, propelling cardio-oncology as a booming field focusing on the whole-course management of cancer patients with potential cardiovascular threats. Here in this review, we initially profile the evolving molecular subtyping and therapeutic landscape of TNBC. Further, we introduce various monitoring approaches of CTR-CVT. In the main body, we elaborate on typical cardiotoxicities ensuing anti-TNBC treatments in detail, ranging from chemotherapy (especially anthracyclines), surgery, anesthetics, radiotherapy to immunotherapy, with future perspectives on promising directions in the era of artificial intelligence and traditional Chinese medicine.

There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC.

REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population.

The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population.

Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.

The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.

This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.

Myocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.

Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574).

Nanotechnology has emerged as a promising approach for the targeted delivery of therapeutic agents while improving their efficacy and safety. As a result, nanomaterial development for the selective targeting of cancers, with the possibility of treating off-target, detrimental sequelae caused by chemotherapy, is an important area of research. Breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases. However, chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy are common side effects that can affect breast and ovarian cancer survivors quality of life. Therefore, there is an urgent need to develop effective prevention and treatment strategies for these adverse effects. Nanoparticles (NPs) have extreme potential for enhancing therapeutic efficacy but require continued research to elucidate beneficial interventions for women cancer survivors. In short, nanotechnology-based approaches have emerged as promising strategies for preventing and treating chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy. NP-based drug delivery systems and therapeutics have shown potential for reducing the side effects of chemotherapeutics while improving drug efficacy. In this article, the latest nanotechnology approaches and their potential for the prevention and treatment of chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy in breast and ovarian cancer survivors are discussed.

Data on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited.

We evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels.

CTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period.

Approximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required.

Objectives: Several studies have indicated that dietary interventions may offer protection against the development of cardiac damage in the case of anthracycline-induced cardiomyopathy (AIC). The goal of this study was to assess whether an evidence-based cardioprotective diet can be effective in preventing AIC in patients with breast cancer. Design: Randomized, open-label, controlled trial. The study period was set for 18 weeks, and the data were analyzed by generalized estimating equation modeling and one-way repeated measures analysis of variance. Setting/Location: Shahid Rajaie Hospital affiliated (Tehran, Iran). Subjects: Fifty anthracycline-treated patients with breast cancer. Interventions: Patients were randomized to receive either a 2-hour training in evidence-based cardio-protective diet or Carvedilol 6.25 mg bid. Outcome Measures: The primary outcome was the number of patients with abnormal left ventricular ejection fraction (LVEF) after 18 weeks. Results: At week 18, 12 (48%) out of 25 participants in the cardioprotective diet group had abnormal LVEF in comparison with 21 (84%) out of 25 in the carvedilol group (p = 0.007). Also, 2 (8%) out of 25 in the cardioprotective diet group compared with 7 (28%) out of 25 participants in the carvedilol group had abnormal global longitudinal strain (p = 0.066). The diet group showed significant improvements in the quality-of-life dimensions named "health change" and "general health" compared with the carvedilol group using the Short Form-36 Health Survey questionnaire. Conclusions: This study suggests that an evidence-based cardioprotective diet can contribute to the prevention of AIC. Although current treatments for AIC can be effective, further research is mandatory for more options.

Since their introduction in the 1960s, anthracyclines have been a significant breakthrough in oncology, introducing dramatic changes in the treatment of solid and hematologic malignancies. Although new-generation targeted drugs and cellular therapies are revolutionizing contemporary oncology, anthracyclines remain the cornerstone of treatment for lymphomas, acute leukemias, and soft tissue sarcomas. However, their clinical application is limited by a dose-dependent cardiotoxicity that can reduce cardiac performance and eventually lead to overt heart failure. The field of cardio-oncology has emerged to safeguard the cardiovascular health of cancer patients receiving these therapies. It focuses on controlling risk factors, implementing preventive strategies, ensuring appropriate surveillance, and managing complications. This state-of-the-art review summarizes the current indications for anthracyclines in modern oncology, explores recent evidence on pathophysiology and epidemiology, and discusses advances in cardioprotection measures in the anthracycline-treated patient. Additionally, it highlights key clinical challenges and research gaps in this area.

The aim of this review is two-fold: (1) To examine the mechanisms by which statins may protect from anthracycline-induced cardiotoxicity and (2) To provide a comprehensive overview of the existing clinical literature investigating the role of statins for the primary prevention of anthracycline-induced cardiotoxicity.

The underlying cardioprotective mechanisms associated with statins have not been fully elucidated. Key mechanisms related to the inhibition of Ras homologous (Rho) GTPases have been proposed. Data from observational studies has supported the beneficial role of statins for the primary prevention of anthracycline-induced cardiotoxicity. Recently, several randomized controlled trials investigating the role of statins for the primary prevention of anthracycline-induced cardiotoxicity have produced contrasting results. Statins have been associated with a lower risk of cardiac dysfunction in cancer patients receiving anthracyclines. Further investigation with larger randomized control trials and longer follow-up periods are needed to better evaluate the long-term role of statin therapy and identify the subgroups who benefit most from statin therapy.

Doxorubicin (DOX) is an anthracycline chemotherapy drug widely employed in the treatment of various cancers, known for its potent antineoplastic properties but often associated with dose-dependent cardiotoxicity, limiting its clinical use. This review explores the complex molecular details that determine the heart-protective effectiveness of carvedilol in relation to cardiotoxicity caused by DOX. The harmful effects of DOX on heart cells could include oxidative stress, DNA damage, iron imbalance, disruption of autophagy, calcium imbalance, apoptosis, dysregulation of topoisomerase 2-beta, arrhythmogenicity, and inflammatory responses. This review carefully reveals how carvedilol serves as a strong protective mechanism, strategically reducing each aspect of cardiac damage caused by DOX. Carvedilol's antioxidant capabilities involve neutralizing free radicals and adjusting crucial antioxidant enzymes. It skillfully manages iron balance, controls autophagy, and restores the calcium balance essential for cellular stability. Moreover, the anti-apoptotic effects of carvedilol are outlined through the adjustment of Bcl-2 family proteins and activation of the Akt signaling pathway. The medication also controls topoisomerase 2-beta and reduces the renin-angiotensin-aldosterone system, together offering a thorough defense against cardiotoxicity induced by DOX. These findings not only provide detailed understanding into the molecular mechanisms that coordinate heart protection by carvedilol but also offer considerable potential for the creation of targeted treatment strategies intended to relieve cardiotoxicity caused by chemotherapy.