Metabolomic signatures of carfilzomib-related cardiotoxicity in patients with multiple myeloma.

As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib-CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post-baseline plasma samples of 60 MM patients treated with carfilzomib-based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post-baseline/baseline metabolite ratios that differ between the CVAE and no-CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T-UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21-0.94, p = 0.044) compared with the no-CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver-operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31-0.87, p = 0.023) was significantly lower in post-baseline/baseline ratios of CVAE patients compared with no-CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib-CVAE and potential cardioprotective strategies.

Cardiovascular magnetic resonance parametric techniques to characterize myocardial effects of anthracycline therapy in adults with normal left ventricular ejection fraction: a systematic review and meta-analysis.

BACKGROUND: The cardiotoxic effects of anthracyclines therapy are well recognized, both in the short and long term. Echocardiography allows monitoring of cancer patients treated with this class of drugs by serial assessment of left ventricle ejection fraction (LVEF) as a surrogate of systolic function. However, changes in myocardial function may occur late in the process when cardiac damage is already established. Novel cardiac magnetic resonance (CMR) parametric techniques, like native T1 mapping and extra-cellular volume (ECV), may detect subclinical myocardial damage in these patients, recognizing early signs of cardiotoxicity before development of overt cancer therapy-related cardiac dysfunction (CTRCD) and prompting tailored therapeutic and follow-up strategies to improve outcome. METHODS AND RESULTS: We conducted a systematic review and a meta-analysis to investigate the difference in CMR derived native T1 relaxation time and ECV values, respectively, in anthracyclines-treated cancer patients with preserved EF versus healthy controls. PubMed, Embase, Web of Science and Cochrane Central were searched for relevant studies. A total of 6 studies were retrieved from 1057 publications, of which, four studies with 547 patients were included in the systematic review on T1 mapping and five studies with 481 patients were included in the meta-analysis on ECV. Three out of the four included studies in the systematic review showed higher T1 mapping values in anthracyclines treated patients compared to healthy controls. The meta-analysis demonstrated no statistically significant difference in ECV values between the two groups in the main analysis (Hedges´s g =3.20, 95% CI -0.72-7.12, p =0.11, I2 =99%), while ECV was significantly higher in the anthracyclines-treated group when sensitivity analysis was performed. CONCLUSIONS: Higher T1 mapping and ECV values in patients exposed to anthracyclines could represent early biomarkers of CTRCD, able to detect subclinical myocardial changes present before the development of overt myocardial dysfunction. Our results highlight the need for further studies to investigate the correlation between anthracyclines-based chemotherapy and changes in CMR mapping parameters that may guide future tailored follow-up strategies in this group of patients.

Precision Cardio-oncology: Update on Omics-Based Diagnostic Methods.

OPINION STATEMENT: Cardio-oncology is an emerging interdisciplinary field dedicated to the early detection and treatment of adverse cardiovascular events associated with anticancer treatment, and current clinical management of anticancer-treatment-related cardiovascular toxicity (CTR-CVT) remains limited by a lack of detailed phenotypic data. However, the promise of diagnosing CTR-CVT using deep phenotyping has emerged with the development of precision medicine, particularly the use of omics-based methodologies to discover sensitive biomarkers of the disease. In the future, combining information produced by a variety of omics methodologies could expand the clinical practice of cardio-oncology. In this review, we demonstrate how omics approaches can improve our comprehension of CTR-CVT deep phenotyping, discuss the positive and negative aspects of available omics approaches for CTR-CVT diagnosis, and outline how to integrate multiple sets of omics data into individualized monitoring and treatment. This will offer a reliable technical route for lowering cardiovascular morbidity and mortality in cancer patients and survivors.

Artificial intelligence-enabled prediction of chemotherapy-induced cardiotoxicity from baseline electrocardiograms.

Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD) that adversely affects prognosis. Despite guideline recommendations, only half of the patients undergo surveillance echocardiograms. An AI model detecting reduced left ventricular ejection fraction from 12-lead electrocardiograms (ECG) (AI-EF model) suggests ECG features reflect left ventricular pathophysiology. We hypothesized that AI could predict CTRCD from baseline ECG, leveraging the AI-EF model's insights, and developed the AI-CTRCD model using transfer learning on the AI-EF model. In 1011 anthracycline-treated patients, 8.7% experienced CTRCD. High AI-CTRCD scores indicated elevated CTRCD risk (hazard ratio (HR), 2.66; 95% CI 1.73-4.10; log-rank p < 0.001). This remained consistent after adjusting for risk factors (adjusted HR, 2.57; 95% CI 1.62-4.10; p < 0.001). AI-CTRCD score enhanced prediction beyond known factors (time-dependent AUC for 2 years: 0.78 with AI-CTRCD score vs. 0.74 without; p = 0.005). In conclusion, the AI model robustly stratified CTRCD risk from baseline ECG.

A Comprehensive Review of Cancer Drug-Induced Cardiotoxicity in Blood Cancer Patients: Current Perspectives and Therapeutic Strategies.

OPINION STATEMENT: Cardiotoxicity has emerged as a serious outcome catalyzed by various therapeutic targets in the field of cancer treatment, which includes chemotherapy, radiation, and targeted therapies. The growing significance of cancer drug-induced cardiotoxicity (CDIC) and radiation-induced cardiotoxicity (CRIC) necessitates immediate attention. This article intricately unveils how cancer treatments cause cardiotoxicity, which is exacerbated by patient-specific risks. In particular, drugs like anthracyclines, alkylating agents, and tyrosine kinase inhibitors pose a risk, along with factors such as hypertension and diabetes. Mechanistic insights into oxidative stress and topoisomerase-II-B inhibition are crucial, while cardiac biomarkers show early damage. Timely intervention and prompt treatment, especially with specific agents like dexrazoxane and beta-blockers, are pivotal in the proactive management of CDIC.

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.

Cardiac substructures dosimetric predicts cardiac toxicity and prognosis in esophageal squamous cell cancer treated by radiotherapy.

PURPOSE: To look into the relationship between cardiac substructures (CS) dosimetric parameters and cardiac events (CE) or overall survival (OS) in patients undergoing radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: A retrospective study included 350 patients with ESCC receiving definitive chemoradiotherapy or radiotherapy (d-CRT/d-RT) or neoadjuvant chemoradiotherapy (NCRT) from March 2013 to May 2022. Our study examined the adverse cardiac events of any grade or G3+, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Competing risk analysis and Cox regression analysis were used to assess the relationship between CS doses and CEs or OS. RESULTS: 201 (57.4 %) patients received any grade CEs over a median follow-up time of 22.50 months (IQR, 12.40-45.60), and 24 (6.86 %) patients suffered G3+ CEs. On landmark analysis, patients with any grade CEs had significantly lower OS (P = 0.003). Multivariable analysis revealed that any grade CEs were predicted by the dose of CSs in all populations. In addition, for G3+ cardiac events, arrhythmic and small probability of cardiac events, LAD V20 ((HR: 1.02, 95 % CI: 1.00-1.03, P = 0.012; HR: 1.01, 95 % CI: 1.00-1.02, P = 0.005; HR; 1.01, 95 % CI: 1.00-1.02, P = 0.012) was also an independent predictive factor. LAD V50 (HR: 1.07, 95 % CI: 1.03-1.10, P <0.001) predicted pericardium effusion events. Moreover, the multivariable analysis revealed that OS was predicted by LAD V30 (HR: 1.03; 95 % CI, 1.01-1.05, P = 0.015). CONCLUSIONS: In the population of ESCC patients receiving RT, we showed that the CS factors had a substantial predictive value for the various types and grades of CEs. The elevated radiation dose of LAD was a significant contributor to a higher rate of cardiac events and a worse prognosis.

Mechanisms of Cardiovascular Toxicities Induced by Cancer Therapies and Promising Biomarkers for Their Prediction: A Scoping Review.

AIM: With the advancement of anti-cancer medicine, cardiovascular toxicities due to cancer therapies are common in oncology patients, resulting in increased mortality and economic burden. Cardiovascular toxicities caused by cancer therapies include different severities of cardiomyopathy, arrhythmia, myocardial ischaemia, hypertension, and thrombosis, which may lead to left ventricular dysfunction and heart failure. This scoping review aimed to summarise the mechanisms of cardiovascular toxicities following various anti-cancer treatments and potential predictive biomarkers for early detection. METHODS: PubMed, Cochrane, Embase, Web of Science, Scopus, and CINAHL databases were searched for original studies written in English related to the mechanisms of cardiovascular toxicity induced by anti-cancer therapies, including chemotherapy, targeted therapy, immunotherapy, radiation therapy, and relevant biomarkers. The search and title/abstract screening were conducted independently by two reviewers, and the final analysed full texts achieved the consensus of the two reviewers. RESULTS: A total of 240 studies were identified based on their titles and abstracts. In total, 107 full-text articles were included in the analysis. Cardiomyocyte and endothelial cell apoptosis caused by oxidative stress injury, activation of cell apoptosis, blocking of normal cardiovascular protection signalling pathways, overactivation of immune cells, and myocardial remodelling were the main mechanisms. Promising biomarkers for anti-cancer therapies related to cardiovascular toxicity included placental growth factor, microRNAs, galectin-3, and myeloperoxidase for the early detection of cardiovascular toxicity. CONCLUSION: Understanding the mechanisms of cardiovascular toxicity following various anti-cancer treatments could provide implications for future personalised treatment methods to protect cardiovascular function. Furthermore, specific early sensitive and stable biomarkers of cardiovascular system damage need to be identified to predict reversible damage to the cardiovascular system and improve the effects of anti-cancer agents.

Heartbreaker: Detection and prevention of cardiotoxicity in hematological malignancies.

Cancer survivors are at significant risk of cardiovascular (CV) morbidity and mortality; patients with hematologic malignancies have a higher rate of death due to heart failure compared to all other cancer subtypes. The majority of conventional hematologic cancer treatments is associated with increased risk of acute and long-term CV toxicity. The incidence of cancer therapy induced CV toxicity depends on the combination of patient characteristics and on the type, dose, and duration of the therapy. Early diagnosis of CV toxicity, appropriate referral, more specific cardiac monitoring follow-up and timely interventions in target patients can decrease the risk of CV adverse events, the interruption of oncological therapy, and improve the patient's prognosis. Herein, we summarize the CV effects of conventional treatments used in hematologic malignancies with a focus on definitions and incidence of the most common CV toxicities, guideline recommended early detection approaches, and preventive strategies before and during cancer treatments.

Clozapine metabolism and cardiotoxicity: A prospective longitudinal study.

BACKGROUND: Clozapine-induced myocarditis and cardiomyopathy are difficult to detect clinically and may be fatal if not detected early. The current/routine biomarkers for clozapine-induced myocarditis are non-specific indicators of inflammation (C-reactive protein) or cardiomyocyte damage (troponins I and T) that lack sensitivity, and for which changes often arise too late to be clinically useful. METHODS: The Clozapine Safety Study was a prospective, longitudinal, observational study to determine what, if any, the plasma concentrations of clozapine, N-desmethylclozapine, and clozapine-N-oxide in patients contribute to cardiotoxicity. Samples were collected and analysed using liquid chromatography mass spectrometry over a 41-month period from patients in the Auckland District Health Board. RESULTS: Sixty-seven patients were included. Six patients were diagnosed with myocarditis; none were diagnosed with cardiomyopathy in the study period. In patients not undergoing dose titration, clozapine biotransformation may shift to the N-oxide pathway rather than the N-desmethyl pathway with increasing dose. During dose titration, the timeframe in which myocarditis occurs, the rate of increase in the plasma concentration of clozapine-N-oxide, as well as the ratio of N-oxidation relative to N-desmethylation, were significantly higher in patients diagnosed with myocarditis. CONCLUSIONS: The assessment of clozapine-N-oxide formation, and N-oxidation relative to N-desmethylation ratios during treatment, may help identify a biomarker to aid the early detection of patients at risk of developing clozapine-induced cardiotoxicity.

[Update cardio-oncology : Immune checkpoint inhibitor therapy]. / Update Kardioonkologie : Immuncheckpoint-Inhibitor-Therapie.

Cardiovascular diseases and cancer are the most common causes of death in Germany. Cancer treatment can lead to significant cardiovascular side effects and thus form a link between the two disease groups. The focus of cardio-oncology is on the best possible prevention, diagnostics and treatment of cardiovascular complications caused by cancer treatment. It is crucial for cardio-oncology to adapt to the continuous development of new forms of oncological treatment with previously unknown cardiovascular side effects. One such new form of treatment is immune checkpoint inhibitor (ICI) therapy, which is regarded as the most important oncological milestone of the last decade due to its excellent oncological efficacy; however, the growing use has revealed a high risk of diverse cardiovascular side effects with high morbidity and mortality, so that cardio-oncological care of affected patients is of particular importance. This review summarizes the current scientific and clinical state of the pathophysiology, incidence, diagnosis and treatment of cardiovascular side effects of ICI therapy.

Risk Stratification for Cardiotoxicity in Breast Cancer Patients: Predicting Early Decline of LVEF After Treatment.

This study introduces AI-based models in prediction and risk assessment of early cardiac dysfunction in older breast cancer patients, as a side-effect of their cancer treatment. Using only features extracted during the baseline evaluation of each patient the proposed methodology could predict a decline in LVEF values in 4 different follow-up intervals during the first year after treatment initiation (i.e. months 3-12), with a mean accuracy of 66.67% and up to 73.55%. Selected baseline predictive factors were ranked according to their prevalence in the evaluation experiments, replicating the importance of various cardiac disorders at baseline, LVEF value and a higher age, which are all previously reported, while introducing Diabetes as an important risk factor.Clinical Relevance- Healthcare providers can better assess cardiovascular health status and risk of cardiotoxicity in the cancer treatment continuum. This will enable timely intervention and close monitoring on high risk patients while saving resources for low risk patients.

Methods to assess radiation-induced cardiotoxicity in rodent models.

Cancer survivors who have received thoracic radiation as part of their primary treatment are at risk for developing radiation-induced cardiotoxicity (RICT) due to incidental radiation delivered to the heart. In recent decades, advancements in radiation delivery have dramatically improved the therapeutic ratio of radiation therapy (RT)-efficiently targeting malignancies while sparing the heart; yet, in many patients, incidental radiation to the heart cannot be fully avoided. Cardiac radiation exposure can cause long-term morbidity and contribute to poorer survival in cancer patients. Severe cardiac effects can occur within 2years of treatment. Currently, there is no way to predict who is at higher or lower risk of developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. The overarching aim of this chapter is to provide researchers with foundational and technical knowledge in the use of mice and rats for RICT investigations. After a brief overview of RICT pathophysiology and clinical manifestations, we discuss important considerations of RICT study design, including animal selection and radiation planning. We then provide example protocols for murine tissue harvesting and processing that can support use in downstream applications of the reader's choosing.

Circulating Cardiovascular Biomarkers in Cancer Therapeutics-Related Cardiotoxicity: Review of Critical Challenges, Solutions, and Future Directions.

Cardiotoxicity is a growing concern in the oncology population. Transthoracic echocardiography and multigated acquisition scans have been used for surveillance but are relatively insensitive and resource intensive. Innovative imaging techniques are constrained by cost and availability. More sensitive, cost-effective cardiotoxicity surveillance strategies are needed. Circulating cardiovascular biomarkers could provide a sensitive, low-cost solution. Biomarkers such as troponins, natriuretic peptides (NPs), novel upstream signals of oxidative stress, inflammation, and fibrosis as well as panomic technologies have shown substantial promise, and guidelines recommend baseline measurement of troponins and NPs in all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain to be examined in depth. This review provides comprehensive assessment of critical challenges and solutions in this field, with focus on analytical issues relating to biomarker measurement and interpretation. Examination of evidence pertaining to common and serious forms of cardiotoxicity reveals that improved study designs incorporating larger, more diverse populations, registry-based approaches, and refinement of current definitions are key. Further efforts to harmonize biomarker methodologies including centralized biobanking and analyses, novel decision limits, and head-to-head comparisons are needed. Multimarker algorithms incorporating machine learning may allow rapid, personalized risk assessment. These improvements will not only augment the predictive value of circulating biomarkers in cardiotoxicity but may elucidate both direct and indirect relationships between cardiovascular disease and cancer, allowing biomarkers a greater role in the development and success of novel anticancer therapies.

Non-coding RNAs, cancer treatment and cardiotoxicity: A triad of new hope.

The global health landscape has experienced a shift towards non-communicable diseases, with cardiovascular diseases and cancer as leading causes of mortality. Although advancements in healthcare have led to an increase in life expectancy, they have concurrently resulted in a greater burden of chronic health conditions. Unintended consequences of anticancer therapies on various tissues, particularly the cardiovascular system, contribute to elevated morbidity and mortality rates that are not directly attributable to cancer. Consequently, the field of cardio-oncology has emerged to address the prevalence of CVD in cancer survivors and the cardiovascular toxicity associated with cancer therapies. Non-coding RNAs (ncRNAs) have been found to play a crucial role in early diagnosis, prognosis, and therapeutics within the realm of cardio-oncology. This comprehensive review evaluates the risk assessment of cancer survivors concerning the acquisition of adverse cardiovascular consequences, investigates the association of ncRNAs with CVD in patients undergoing cancer treatment, and delves into the role of ncRNAs in the diagnosis, treatment, and prevention of CVD in patients with a history of anti-cancer therapy. A thorough understanding of the pathogenesis of cancer therapy-related cardiovascular disease and the involvement of ncRNAs in cardio-oncology will enable healthcare professionals to provide anticancer treatment with minimized cardiovascular side effects, thereby improving patient outcomes. Ultimately, this comprehensive analysis aims to provide valuable insights into the complex interplay between cancer and cardiovascular diseases, facilitating the development of more effective diagnostic, therapeutic, and preventive strategies in the burgeoning field of cardio-oncology.

Baseline Troponin Level and Cardiac Toxicity in HER2-positive Early Breast Cancer Patients Receiving Trastuzumab.

BACKGROUND/AIM: There is controversy around the use of high-sensitive troponin T (hs-TnT) as an early biomarker of cardiac toxicity in patients with breast cancer on trastuzumab (T). PATIENTS AND METHODS: Patients receiving adjuvant or neo-adjuvant T for early HER2-positive breast cancer were prospectively included. Transthoracic echocardiograms and matched hs-TnT before T and at 3, 6, and 9 months were performed on all patients. Congestive heart failure, cardiac death, a decline in left ventricular ejection fraction (LVEF) of more than 10% from baseline even if it is still within the normal range, or a drop in LVEF below 55% were all considered signs of cardiac toxicity. RESULTS: In total, 24 patients (median age: 57; range=39-79 years) were enrolled. Anthracyclines were administered to all patients but three as part of neo/adjuvant treatment before T. Cardiovascular toxicity was observed in 3 out of 24 (12.5%) patients: two non-symptomatic LVEF declines (8.3%) and one heart failure episode (4.2%). In the entire population, the mean baseline hs-TnT level was 10.1±8.8 pg/ml, and after 3, 6, and 12 months, no appreciable change was observed. Patients with cardiac toxicity had mean hs-TnT levels higher than those without (18.3±12.3 vs. 8.2±7.2 pg/ml; p=0.049). A definite trend was evident in the chi-square test (chi2=3.52; p=0.06). CONCLUSION: In anthracycline-exposed patients with early breast cancer, hs-TnT may be able to identify those at risk of developing cardiac toxicity during neo/adjuvant T treatment.

Role of Cardiac Biomarkers in Monitoring Cardiotoxicity in Chemotherapy Patients.

PURPOSE: This review aims to highlight the different types of chemotherapy-induced cardiotoxicity and will discuss the evidence base behind the use of different cardiac biomarkers to predict cardiovascular complications. Additionally, we will review the use of cardiac biomarkers to monitor cardiac outcomes and the role of cardioprotective medications in reducing cardiovascular side effects. RECENT FINDINGS: Chemotherapy has been linked to an increased risk of cardiotoxicity and heart failure. Currently, patients receiving chemotherapy undergo echocardiogram before starting chemotherapy and every 6 months to monitor for any decline in cardiac function. We reviewed the current evidence and practice guidelines of monitoring chemotherapy cardiotoxicity. SUMMARY: Cardio-oncology is a rapidly evolving subspecialty in cardiology, especially with the advent of new chemotherapeutic agents, which have cardiovascular side effects. Early detection of these effects is crucial to prevent life-threatening and irreversible cardiovascular outcomes. Monitoring troponin, pro-brain natriuretic peptide, and other cardiac biomarkers during chemotherapy will help to early detect cardiotoxicity.

The diagnostic value of global longitudinal strain combined with cardiac biomarkers on early detection of anthracycline-related cardiac dysfunction.

BACKGROUND: Cardiac dysfunction associated with anthracyclines is a significant side effect of chemotherapy, and early detection is crucial. We aimed to assess the diagnostic value of combining global longitudinal strain (GLS) with biomarkers for the early detection of anthracycline-related cardiac dysfunction. METHODS: In a prospective cohort study, 80 consecutive adult patients (mean age 51 ± 11 years; 68.8% females) were screened and underwent 2D echocardiographic assessments and biomarker assessments [high-sensitivity troponin-I (hs-Troponin-I) and NT-pro brain natriuretic peptide (NT-proBNP)] before and after anthracycline-based chemotherapy's initial regimen. The patients were followed up for 12 weeks to monitor for the development of cardiotoxicity. RESULTS: Ten patients (12.5%) developed cardiotoxicity at the end of the 12-week follow-up. Baseline values of hs-Troponin-I and NT-proBNP were significantly higher in patients who developed cardiotoxicity compared to those who did not, with a similar pattern observed at the 3-week follow-up. Receiver operating characteristic (ROC) curve analysis demonstrated that a cutoff value of baseline hs-Troponin-I > 11 ng/L, NT-proBNP > 90.1 pg/mL, 3-week left ventricular ejection fraction (LVEF) ≤ 52%, 3-week GLS ≥ - 14.5%, 3-week hs-Troponin-I > 13.1 ng/L, and 3-week NT-proBNP > 118.1 pg/mL predicted the occurrence of cardiotoxicity with high sensitivity (range 83-94%) and specificity (range 77-92%). CONCLUSION: Combination of GLS with biomarkers had a high diagnostic value in early identification of anthracycline-related cardiac dysfunction, with an estimated diagnostic accuracy of over 85%. This information could potentially help in the identification of patients at high risk of developing cardiac dysfunction, allowing for earlier management.

Activation recovery interval as an electrocardiographic repolarization index to detect doxorubicin-induced cardiotoxicity.

BACKGROUND: It has been reported that early detection and treatment of cancer therapy- related cardiac dysfunction (CTRCD) improves its prognosis. The detailed relationships between electrocardiographic repolarization indices and decreased left ventricular function in CTRCD have not been elucidated. We closely assessed such relationships in patients with doxorubicin (DOX)-induced CTRCD. METHODS: This retrospective, single-center, cohort study included 471 consecutive patients with malignant lymphoma who received chemotherapy including DOX. Of them, 17 patients with CTRCD and 68 patients without CTRCD who underwent 12­lead electrocardiogram and an echocardiogram before and after chemotherapy were eventually analyzed. The fluctuations of the following electrocardiographic repolarization indices were evaluated in lead V5: QT, JT, T peak to T end interval (Tp-e), and activation recovery interval (ARI). These indices were corrected by heart rate with the Fridericia formula. RESULTS: The median period from the end of chemotherapy to the diagnosis of the CTRCD group was 346 days (IQR 170-1283 days). After chemotherapy, the QT interval was significantly prolonged in both with and without CTRCD groups compared with that before chemotherapy (pre QTc vs. post QTc in CTRCD group, 386 ±â€¯27 ms vs. 411 ±â€¯37 ms, p = 0.03, pre QTc vs. post QTc in non-CTRCD group, 388 ±â€¯24 ms vs. 395 ±â€¯25 ms, p = 0.04, respectively). ARIc after chemotherapy was characteristically observed only in the CTRCD group (pre ARIc vs. post ARIc in CTRCD group, 258 ±â€¯53 ms vs. 211 ±â€¯28 ms, p = 0.03, pre ARIc vs. post ARIc in non-CTRCD group, 221 ±â€¯19 ms vs. 225 ±â€¯23 ms, NS, respectively) and had negative correlations with left ventricular ejection fraction (r = -0.56, p < 0.001). Using the receiver-operating characteristic curve, the relationship between ARIc and CTRCD morbidity was examined. The optimal cut-off point of ARIc prolongation between before and after chemotherapy was 18 ms (sensitivity 75 %, specificity 79 %, area under the curve 0.76). CONCLUSIONS: ARIc prolongation may be useful in the early detection of developing late-onset chronic DOX-induced CTRCD and lead to early treatment for cardiac protection.

Cardio-oncology for Pediatric and Adolescent/Young Adult Patients.

OPINION STATEMENT: As chemotherapy continues to improve the lives of patients with cancer, understanding the effects of these drugs on other organ systems, and the cardiovascular system in particular, has become increasingly important. The effects of chemotherapy on the cardiovascular system are a major determinant of morbidity and mortality in these survivors. Although echocardiography continues to be the most widely used modality for assessing cardiotoxicity, newer imaging modalities and biomarker concentrations may detect subclinical cardiotoxicity earlier. Dexrazoxane continues to be the most effective therapy for preventing anthracycline-induced cardiomyopathy. Neurohormonal modulating drugs have not prevented cardiotoxicity, so their widespread, long-term use for all patients is currently not recommended. Advanced cardiac therapies, including heart transplant, have been successful in cancer survivors with end-stage HF and should be considered for these patients. Research on new targets, especially genetic associations, may produce treatments that help reduce cardiovascular morbidity and mortality.