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A modified conditioning regimen based on low-dose cyclophosphamide and fludarabine for haploidentical hematopoietic stem cell transplant in severe aplastic anemia patients at risk of severe cardiotoxicity.

Severe cardiotoxicity is a fatal complication during high-dose cyclophosphamide (Cy)-based conditioning in hematopoietic stem cell transplant (HSCT) for severe aplastic anemia (SAA). This study aimed to evaluate the feasibility and efficacy of a modified conditioning regimen in haploidentical HSCT (haplo-HSCT) for severe-cardiotoxic-risk SAA patients. This BuCylow Flu conditioning utilized busulfan (Bu, 3.2 mg/kg for 2 days), low-dose Cy (100 mg/kg), fludarabine (150 mg/m2 ), and rabbit antithymocyte globulin (rATG, 10 mg/kg). Compared to BuCy conditioning using high-dose Cy of 200 mg/kg, Bu o…

GPR91 Receptor Mediates Protection against Doxorubicin-Induced Cardiotoxicity without Altering Its Anticancer Efficacy. An In Vitro Study on H9C2 Cardiomyoblasts and Breast Cancer-Derived MCF-7 Cells.

Doxorubicin (DOX) is an anticancer drug widely used in oncology, especially for breast cancer. The main limitation of DOX treatment is its cardiotoxicity due to the cumulative dose. Clinically, DOX-induced cardiomyopathy develops as a progressive heart failure caused by a progressive cardiomyocyte's death. For long, the oxidative stress induced by DOX was considered as the main toxic mechanism responsible for heart damage, but it is now controverted, and other processes are investigated to develop cardioprotective strategies. Previously, we studied DOX-induced cardiotoxicity and dexrazoxane (D…

TEMPORAL DYNAMICS OF GLOBAL LONGITUDINAL STRAIN AND NT-PROBNP IN THE EARLY DETECTION OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY: A 24-MONTH PROSPECTIVE STUDY IN POSTMENOPAUSAL WOMEN WITH BREAST CANCER.

BACKGROUND: As breast cancer survival improves, cardiovascular toxicity has emerged as a major determinant of long-term outcomes. Cancer therapy-related cardiac dysfunction is particularly prevalent among postmenopausal women with increased cardiovascular risk, highlighting the need for early cardiotoxicity detection and targeted cardio-oncology surveillance. OBJECTIVE: To assess correlations between longitudinal changes in Global longitudinal strain, conventional Left Ventricular systolic-diastolic echocardiographic parameters, and cardiac biomarkers for prediction and early detection of can…

Balancing the Risk of Cardiotoxicity Outcomes in Treatment Selection for Multiple Myeloma: A Retrospective Multicenter Evaluation of Ixazomib, Lenalidomide, and Dexamethasone (IRd) Versus Carfilzomib, Lenalidomide, and Dexamethasone (KRd).

IntroductionCarfilzomib use has been extensively associated with cardiovascular toxicity; the risk with ixazomib, a novel oral proteasome inhibitor, is underreported and no large comparative analysis is available.MethodsWe conducted a retrospective cohort study utilizing the TriNetX platform to compare toxicity outcomes among multiple myeloma patients who received lenalidomide, dexamethasone, and ixazomib (IRd) or carfilzomib (KRd).ResultsAfter propensity-score-matching 478 patients from each cohort, the onset of new heart failure (HR 0.25; p p = 0.014) at 6 months were significantly lower wit

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… Among TRAE associated with MM therapies, cardiotoxicity, diarrhea, and peripheral neuropathy have emerged as important toxicities. … As numerous MM therapies, such as immunomodulatory agents or cyclophosphamide, can induce or compound cardiotoxicity, previous attempts at comparing cardiotoxicity of ixazomib versus carfilzomib alone may not accurately represent the true risk. …

Complete amino acid sequence of an acidic, cardiotoxic phospholipase A2 from the venom of Ophiophagus hannah (King Cobra): a novel cobra venom enzyme with "pancreatic loop".

A phospholipase A2 (OHV A-PLA2) from the venom of Ophiophagus hannah (King cobra) is an acidic protein exhibiting cardiotoxicity, myotoxicity, and antiplatelet activity. The complete amino acid sequence of OHV A-PLA2 has been determined using a combination of Edman degradation and mass spectrometric techniques. OHV A-PLA2 is composed of a single chain of 124 amino acid residues with 14 cysteines and a calculated molecular weight of 13719 Da. It contains the loop of residues (62-66) found in pancreatic PLA2s and hence belongs to class IB enzymes. This pancreatic loop is between two proline resi…

Added value of serial troponin I and N-terminal pro B-type natriuretic peptide for early detection of cardiotoxicity in breast cancer: A three-year retrospective cohort study.

BACKGROUND: Cardiotoxicity remains a major limitation in breast cancer treatment, especially with anthracyclines and radiotherapy. Early biomarkers may improve risk stratification. METHODS: This retrospective cohort study included breast cancer patients treated between 2020 and 2023 with chemotherapy and/or radiotherapy. Troponin I (TPI) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured at baseline and at three, six, 12, 18, 24, 30, and 36 months. Cardiotoxicity was defined per European Society of Cardiology (ESC) guidelines as a ≥10% drop in left ventricular ejection fr…

Myocardial Strain Measurements Obtained with Fast-Strain-Encoded Cardiac Magnetic Resonance for the Risk Prediction and Early Detection of Chemotherapy-Related Cardiotoxicity Compared to Left Ventricular Ejection Fraction.

Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and tailored to reverse cardiac dysfunction and prevent the discontinuation of essential cancer treatments. Objectives: The PRoactive Evaluation of Function to Evade Cardio Toxicity (PREFECT) study sought to evaluate the ability of fast-strain-encoded (F-SENC) cardiac magnetic resonanc…

Evaluation of the protective effect of aqueous-methanolic leaf extract of Jatropha mollissima (Pohl.) Baill. on doxorubicin-induced cardiotoxicity in rats via modulating inflammatory markers and oxidative stress.

INTRODUCTION: Jatropha mollissima (Pohl.) Baill is a traditional medicinal plant reputed for its hepatoprotective and nephroprotective properties. However, its potential cardioprotective and anti-inflammatory effects, both in vitro and in vivo, remain underexplored. AIM OF THE STUDY: This study conducted a series of in vitro, in vivo, and ex vivo experiments to determine the cardioprotective properties and anti-inflammatory effect of the aqueous-methanolic leaf extract of J. mollissima. Doxorubicin-induced cardiotoxicity, thrombolytic, anticoagulant, antioxidant, vasorelaxant, anti-inflammato…

Attenuation of NF-κB/NLRP3 inflammasome axis and oxidative stress, and upregulation of Nrf2/HO-1 signaling mediate the protective effect of S-carboxymethylcysteine against cyclophosphamide-induced cardiotoxicity.

Cyclophosphamide (CP) is a potent chemotherapeutic and immunosuppressant agent used in the management of lymphoproliferative disorders and solid tumors. However, it induces cardiotoxicity and other severe adverse effects, thereby limiting its clinical application, highlighting the need for safe and effective cardioprotective agents. This study investigates the cardioprotective potential of carbocysteine (S-carboxymethylcysteine (SCMC)), a mucolytic agent with emerging pleiotropic properties, against CP-induced toxicity. The study explores the effect of SCMC on oxidative stress, NF-κB/NLRP3 inf…

Combined diosmin and bisoprolol attenuate cobalt chloride-induced cardiotoxicity and endothelial dysfunction through modulating miR-143-3P/MAPK/MCP-1, ERK5/CXCR4, Orai-1/STIM-1 signaling pathways.

Even while accelerated cardiomyocyte apoptosis is one of the primary causes of cardiac damage, the underlying mechanism is still mostly unknown. In addition to examining potential protective effects of bisoprolol and diosmin against CoCl2-induced cardiac injury, the goal of this study was to identify potential mechanisms regulating the hypoxic cardiac damage caused by cobalt chloride (CoCl2). For a period of 21 days except Cocl2 14 days from the first day of the experiment, rats were split into the following groups: Normal control group, rats received vehicle only (2 ml/kg/day, p.o.), (Cocl2,

Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer.

PURPOSE: Trastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates [left ventricular ejection fraction (LVEF) decline, congestive heart failure (CHF), cardiac death or trastuzumab discontinuation] and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice. METHODS: Patients receiving curative trastuzumab between 2011 and 2018 wer…

A Novel Conditioning Regimen Incorporating Low-Dose Cyclophosphamide and Thiotepa for Haploidentical Hematopoietic Stem Cell Transplantation in Pediatric Patients with Severe Aplastic Anemia at High Risk of Cardiotoxicity.

High-dose cyclophosphamide (Cy)-related cardiotoxicity (CT) during transplant conditioning in patients with severe aplastic anemia (SAA) is a life-threatening complication. To evaluate the efficacy and safety of a modified conditioning regimen to reduce CT in pediatric SAA. We conducted a prospective, single-arm clinical trial. The regimen was as follows: busulfan (Bu) 3.2 mg/kg/d on days -8 and -7, thiotepa (TT) 10 mg/kg/d on day -6, Cy 20 mg/kg/d on days -5 to -2, and antithymocyte globulin 2.5 mg/kg on days -5 to -2. Patients with high-risk SAA in a historical cohort who received the tradit…

Protective effects of Allium sativum essential oil against lead nitrate-induced cardiotoxicity: Modulation of lipid metabolism, nitric oxide dynamics, inflammatory mediators, and histological profiles in Swiss albino mice.

BACKGROUND: Lead (Pb²⁺) is a toxic metal known to induce oxidative stress and inflammation, contributing to cardiovascular diseases such as hypertension and atherosclerosis. Natural compounds like Allium sativum essential oil (ASEO) offer potential therapeutic benefits against lead-induced damage, but their cardioprotective effects remain underexplored. This study investigates the efficacy of ASEO in mitigating cardiovascular toxicity induced by lead nitrate in male Swiss albino mice. METHODS: Thirty-six male mice were divided into six groups: Control, Lead Nitrate (50 mg/kg), Lead Nitrate + 

Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.

BACKGROUND: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy. METHODS: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitiv…

The impact of CBR3 (rs1056892) and ABCC1 (rs45511401) genetic polymorphisms on doxorubicin-induced cardiotoxicity and the potential role of brain natriuretic peptide as an early cardiac biomarker in breast cancer patients.

BACKGROUND: Doxorubicin (DOX), a potent antineoplastic drug, can induce cardiotoxicity through its cardiotoxic metabolites catalyzed by CBR 3 and its accumulation in cardiac tissue via the ABCC1 transporter. Here, we investigated CBR3 and ABCC1 genetic polymorphisms affecting doxorubicin cardiotoxicity in breast cancer patients and explored the potential role of brain natriuretic peptide (BNP) as an early cardiac biomarker. METHODS: One hundred Breast cancer patients are receiving DOX treatment. Blood samples were analyzed for CBR3 and ABCC1 gene polymorphisms and echocardiography and BNP bio…

Assessment of the neutralizing potency of antisera raised against native and γ-irradiated Naja nigricollis (black-necked spitting cobra) venom in rabbits, concerning its cardiotoxic effect.

The present study was designed to prepare a specific safe antiserum for Naja nigricollis using γ-irradiated (1.5KGy and3KGy) venoms. Rabbits were used for active immunization using irradiated venoms (1.5 and 3 kGy) as a toxoid, mice were used for determination of LD50 post immunization and the rats were used for neutralization of the cardiotoxic effect of venom. Results of the immunodiffusion test indicated that the sera of rabbits raised against non-irradiated, 1.5- and 3-kGy γ-irradiated venom, had the same results of precipitin bands. A significant inhibition of phospholipase A2 activities

SGLT2i Dapagliflozin in primary prevention of chemotherapy induced cardiotoxicity in breast cancer patients treated with neo-adjuvant anthracycline-based chemotherapy +/- trastuzumab: rationale and design of the multicenter PROTECT trial.

BACKGROUND: SGLT2i exerts several cardiometabolic benefits in heart failure with reduced and preserved ejection fraction through the systemic reduction of insulin, visceral fat, chemokines and growth factors involved in cardiovascular diseases. Anthracyclines are considered the principal culprit drugs behind chemotherapy-induced cardiotoxicity. The pathognomonic manifestation of anthracycline-induced cardiotoxicity is a hypokinetic cardiomyopathy progressively leading to heart failure. Anthracycline-induced cardiotoxicity is still a significant problem that compromises the quality of life and …

Sacubitril-Valsartan for the Prevention of Anthracycline Cardiotoxicity in Patients With Elevated Cardiac Troponin I Concentration During Chemotherapy: A Double-Blind Randomized Placebo-Controlled Clinical Trial: The SARAH Trial.

BACKGROUND: The clinical effects of sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, on anthracycline-induced cardiotoxicity remain unknown. Experimental evidence suggests cardioprotective properties. This study evaluated the efficacy of sacubitril-valsartan in reducing cardiotoxicity in patients with increased cardiac troponin I concentrations during anthracycline chemotherapy. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 114 patients with elevated cardiac troponin I levels during anthracycline treatment. Participants were randomized 1:1 to rec…

Heart-Type Fatty Acid-Binding Protein (H-FABP) as a Candidate Adjunctive Biomarker for Immune Checkpoint Inhibitor-Related Cardiotoxicity: Linking Early Immune-Metabolic Myocardial Injury with Translational Cardio-Oncology.

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of oncology but are increasingly associated with cardiovascular immune-related adverse events (irAEs), including myocarditis, heart failure, arrhythmias, and vascular complications. Among these, ICI-associated myocarditis represents the most severe manifestation, often characterized by high mortality and challenging early diagnosis. Detecting subclinical myocardial injury before irreversible cardiomyocyte necrosis occurs remains a major unmet need in contemporary cardio-oncology. This narrative expert review critica