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This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li 2 CO 3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li 2 CO 3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C-group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Claudia Kusmic reports equipment, drugs, or supplies was provided by LoLi Pharma Srl. Elisa Lepore reports a relationship with LoLi Pharma Srl that includes: employment. Giampiero Forte reports a relationship with LoLi Pharma Srl that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Competing Interests: The author declares no conflict of interest with respect to the authorship and/or publication of this article. The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Competing Interests: The author declares no conflict of interest with respect to the authorship and/or publication of this article. The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Chemotherapy has markedly improved cancer outcomes, yet cancer therapy-related cardiac dysfunction (CTRCD) poses a significant challenge, affecting around 10% of patients. CTRCD can be asymptomatic or present with heart failure symptoms. Multimodality imaging, particularly echocardiography, remains pivotal for monitoring cardiac function. Potential biomarkers for CTRCD assessment include troponin and B-type natriuretic peptide. Pharmacological interventions, such as dexrazoxane, angiotensin-converting enzyme inhibitors, and statins, play a crucial role in primary prevention and mitigating cardiotoxicity alongside cardiac rehabilitation programs. Thus, a comprehensive approach is essential for optimal cardiac recovery and improved patient outcomes., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-β1) and α-smooth muscle actin (α-SMA) expressions were determined in heart tissue. The CYP group's troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-β1 and α-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-β1, FSP1 and α-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage., (© 2024 Wiley Periodicals LLC.)

Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Doxorubicin (DOX) is an effective anticancer agent, yet its clinical utility is hampered by dose-dependent cardiotoxicity. This study explores the cardioprotective potential of Marein (Mar) against DOX-induced cardiac injury and elucidates underlying molecular mechanisms. Neonatal rat cardiomyocytes (NRCMs) and murine models were employed to assess the impact of Mar on DOX-induced cardiotoxicity (DIC). In vitro, cell viability, oxidative stress were evaluated. In vivo, a chronic injection method was employed to induce a DIC mouse model, followed by eight weeks of Mar treatment. Cardiac function, histopathology, and markers of cardiotoxicity were assessed. In vitro, Mar treatment demonstrated significant cardioprotective effects in vivo, as evidenced by improved cardiac function and reduced indicators of cardiac damage. Mechanistically, Mar reduced inflammation, oxidative stress, and apoptosis in cardiomyocytes, potentially via activation of the Focal Adhesion Kinase (FAK)/AKT pathway. Mar also exhibited an anti-ferroptosis effect. Interestingly, Mar did not compromise DOX's efficacy in cancer cells, suggesting a dual benefit in onco-cardiology. Molecular docking studies suggested a potential interaction between Mar and FAK. This study demonstrates Mar's potential as a mitigator of DOX-induced cardiotoxicity, offering a translational perspective on its clinical application. By activating the FAK/AKT pathway, Mar exerts protective effects against DOX-induced cardiomyocyte damage, highlighting its promise in onco-cardiology. Further research is warranted to validate these findings and advance Mar as a potential adjunctive therapy in cancer treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D 3 , which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D 3 24 h prior to a race ( n = 16), while the other group received a placebo ( n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D 3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D 3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run.

Purpose: Studies during the past 9 years suggest that delivering radiation at dose rates exceeding 40 Gy/s, known as "FLASH" radiation therapy, enhances the therapeutic index of radiation therapy (RT) by decreasing normal tissue damage while maintaining tumor response compared with conventional (or standard) RT. This study demonstrates the cardioprotective benefits of FLASH proton RT (F-PRT) compared with standard (conventional) proton RT (S-PRT), as evidenced by reduced acute and chronic cardiac toxicities., Methods and Materials: Mice were imaged using cone beam computed tomography to precisely determine the heart's apex as the beam isocenter. Irradiation was conducted using a shoot-through technique with a 5-mm diameter circular collimator. Bulk RNA-sequencing was performed on nonirradiated samples, as well as apexes treated with F-PRT or S-PRT, at 2 weeks after a single 40 Gy dose. Inflammatory responses were assessed through multiplex cytokine/chemokine microbead assay and immunofluorescence analyses. Levels of perivascular fibrosis were quantified using Masson's Trichrome and Picrosirius red staining. Additionally, cardiac tissue functionality was evaluated by 2-dimensional echocardiograms at 8- and 30-weeks post-PRT., Results: Radiation damage was specifically localized to the heart's apex. RNA profiling of cardiac tissues treated with PRT revealed that S-PRT uniquely upregulated pathways associated with DNA damage response, induction of tumor necrosis factor superfamily, and inflammatory response, and F-PRT primarily affected cytoplasmic translation, mitochondrion organization, and adenosine triphosphate synthesis. Notably, F-PRT led to a milder inflammatory response, accompanied by significantly attenuated changes in transforming growth factor β1 and α smooth muscle actin levels. Critically, F-PRT decreased collagen deposition and better preserved cardiac functionality compared with S-PRT., Conclusions: This study demonstrated that F-PRT reduces the induction of an inflammatory environment with lower expression of inflammatory cytokines and profibrotic factors. Importantly, the results indicate that F-PRT better preserves cardiac functionality, as confirmed by echocardiography analysis, while also mitigating the development of long-term fibrosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The compounds known as flavonoids, commonly found in fruits, vegetables, legumes, medicinal herbs, chocolate, and coffee and tea beverages, have been extensively researched for their impact on cardiovascular health. Flavonoids, with their demonstrated potential, have shown promising effects in regulating blood vessel function and apoptotic processes, as well as in improving lipid profiles. While their powerful antioxidant properties were initially thought to be the main reason behind these effects, recent studies have uncovered new insights into the positive effects of flavonoids on cardiovascular health, and researchers have now identified several signaling pathways and mechanisms that also play a role. Of particular interest are the studies that have highlighted the role of autophagy in maintaining the physiological functions of cardiomyocytes and protecting them from harm. Recent publications have linked the dysregulation of autophagic processes with the development of cardiomyopathies, heart failure, and other cardiovascular diseases. This review aims to present the latest, novel findings from preclinical research regarding the potential beneficial effects of flavonoids on various heart conditions associated with altered autophagy processes.

Competing Interests: The author declares no conflict of interest with respect to the authorship and/or publication of this article. The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1β), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1β, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1β, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Radiation-induced heart disease (RIHD) is one of the most serious complications in patients receiving chest radiotherapy, partially offsetting its benefits. At present, there is a lack of effective treatments for RIHD. Ferroptosis is a newly discovered type of cell death that results from iron-dependent lipid peroxide accumulation. It was recently shown that irradiation generates severe ferroptosis, providing new insights for the treatment of RIHD. Abelmoschus manihot (L.) possesses excellent pharmacological properties and is widely used in treating various ischemic heart and brain diseases; however, its efficacy and mechanism in treating RIHD are unknown., Aim: This study aimed to investigate the efficacy and mechanism of total extracts from A. manihot (L.) (TEA) in treating RIHD., Materials and Methods: C57BL/6 mice and H9C2 cells were exposed to irradiation to induce RIHD in vivo and in vitro, respectively. In vivo, we evaluated the protective effects of TEA (150 and 300 mg/kg) on RIHD. Body and heart weight changes of mice were calculated in each group, and malondialdehyde (MDA) level, glutathione/oxidized glutathione (GSH/GSSH) and nicotinamide adenine dinucleotide phosphate (NADPH/NADP + ) ratios, western blot, heart histology, and immunohistochemistry were used to evaluate TEA effectiveness. We identified the potential mechanism of radiation-induced cardiomyocyte injury in H9C2 cells treated with small interfering RNA. We determined the effective dose of TEA (0.6 mg/mL) using a Cell Counting Kit-8 assay. Intracellular Fe 2+ and lipid peroxidation levels were detected by Phen Green™ SK diacetate probe, BODIPY 581/591 C11 staining, and MDA, GSH, and NADPH kits, and the level of target protein was evaluated by immunofluorescence and western blot., Results: Radiation inhibited system Xc-cystine (xCT)/glutathione peroxidase 4 (GPX4) expression and activity in cardiomyocytes in a time and dose-dependent manner. After silencing xCT/GPX4, MDA significantly increased and GSH/GSSH and NADPH/NADP +  ratios were reduced. xCT/GPX4 inhibition drove ferroptosis in radiation-induced H9C2 injury. Oxidative stress in H9C2 was significantly enhanced by irradiation, which also significantly increased NADPH oxidase 4 (NOX4) expression and inhibited nuclear factor E2-related factor 2 (Nrf2) expression in vivo and in vitro. Inhibition of xCT/GPX4 drove ferroptosis in radiation-induced H9C2 injury, which was aggravated by inactivation of Nrf2 and alleviated by inhibition of NOX4. Compared with the ionizing radiation-only group, TEA improved body weight loss, MDA levels, and histological changes induced by irradiation in mice hearts, and increased the ratio of GSH/GSSH and NADPH/NADP + in vivo; it also reduced lipid peroxidation and intracellular Fe 2+ accumulation, restored MDA levels, and elevated the ratios of GSH/GSSH and NADPH/NADP + in irradiation-injured H9C2 cells. TEA up-regulated Nrf2, xCT, and GPX4 expression and inhibited NOX4 expression in vivo and in vitro., Conclusions: Ferroptosis induced by redox imbalance mediated through the NOX4/xCT/GPX4 axis is a potential mechanism behind radiation-induced cardiomyocyte injury, and can be prevented by TEA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Doxorubicin (DOX) is a highly effective chemotherapeutic agent whose clinical use is hindered by the onset of cardiotoxic effects, resulting in reduced ejection fraction within the first year from treatment initiation. Recently it has been demonstrated that DOX accumulates within mitochondria, leading to disruption of metabolic processes and energetic imbalance. We previously described that phosphoinositide 3-kinase γ (PI3Kγ) contributes to DOX-induced cardiotoxicity, causing autophagy inhibition and accumulation of damaged mitochondria. Here we intend to describe the maladaptive metabolic rewiring occurring in DOX-treated hearts and the contribution of PI3Kγ signalling to this process. Metabolomic analysis of DOX-treated WT hearts revealed an accumulation of TCA cycle metabolites due to a cycle slowdown, with reduced levels of pyruvate, unchanged abundance of lactate and increased Acetyl-CoA production. Moreover, the activity of glycolytic enzymes was upregulated, and fatty acid oxidation downregulated, after DOX, indicative of increased glucose oxidation. In agreement, oxygen consumption was increased in after pyruvate supplementation, with the formation of cytotoxic ROS rather than energy production. These metabolic changes were fully prevented in KD hearts. Interestingly, they failed to increase glucose oxidation in response to DOX even with autophagy inhibition, indicating that PI3Kγ likely controls the fuel preference after DOX through an autophagy-independent mechanism. In vitro experiments showed that inhibition of PI3Kγ inhibits pyruvate dehydrogenase (PDH), the key enzyme of Randle cycle regulating the switch from fatty acids to glucose usage, while decreasing DOX-induced mobilization of GLUT-4-carrying vesicles to the plasma membrane and limiting the ensuing glucose uptake. These results demonstrate that PI3Kγ promotes a maladaptive metabolic rewiring in DOX-treated hearts, through a two-pronged mechanism controlling PDH activation and GLUT-4-mediated glucose uptake., (Copyright © 2024.)

Competing Interests: Funding Support and Author Disclosures Dr Catanzaro has received research funding from Circa Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

NaAsO 2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO 2 -contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO 2 )-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO 2 (50 ppm); and (IV) NaAsO 2  + BET. NaAsO 2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO 2 -intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The survival of pediatric cancer patients has significantly increased thanks to the improvement of oncological treatments. Therefore, it is of utmost importance to manage short- and long-term cardiovascular complications. In pediatric cardio-oncology, there are no recognized guidelines as in adults. Several recommendations and many indications have been derived from the data obtained in the adult cancer population, resulting in greater discrepancies in the clinical management of patients. The aim of this position paper of the Italian Society of Pediatric Cardiology (SICP) is to collect the main evidence regarding the diagnosis, prevention, treatment and follow-up of cardiotoxicity in children, to provide useful indications for clinical practice, and to promote a network between pediatric centers.

Objectives Cardiac rehabilitation (CR) provides evidence-based secondary prevention for people with heart disease (HD) (clients). Despite HD being the leading cause of mortality and morbidity, CR is under-utilised in Australia. This research investigated healthcare systems required to improve access to CR in rural and remote areas of North Queensland (NQ). Methods A qualitatively dominant case study series to review management systems for CR in rural and remote areas of NQ was undertaken. Data collection was via semi-structured interviews in four tertiary hospitals and four rural or remote communities. An audit of discharge planning and CR referral, plus a review of community-based health services, was completed. An iterative and co-design process including consultation with healthcare staff and community members culminated in a systems-based model for improving access to CR in rural and remote areas. Results Poorly organised CR systems, poor client/staff understanding of discharge planning and low referral rates for secondary prevention, resulted in the majority of clients not accessing secondary prevention, despite resources being available. Revised health systems and management processes were recommended for the proposed Heart: Road to health model, and given common chronic diseases risk factors it was recommended to be broadened into Chronic disease: Road to health . Conclusion A Chronic disease: Road to health model could provide effective and efficient secondary prevention for people with chronic diseases in rural and remote areas. It is proposed that this approach could reduce gaps and duplication in current healthcare services and provide flexible, client-centred, holistic, culturally responsive services, and improve client outcomes.

COVID-19 vaccination has been shown to prevent and reduce the severity of COVID-19 disease. The aim of this study was to explore the cardioprotective effect of COVID-19 vaccination in hospitalized COVID-19 patients. In this retrospective, single-center cohort study, we included hospitalized COVID-19 patients with confirmed vaccination status from July 2021 to February 2022. We assessed outcomes such as acute cardiac events and cardiac biomarker levels through clinical and laboratory data. Our analysis covered 167 patients (69% male, mean age 58 years, 42% being fully vaccinated). After adjustment for confounders, vaccinated hospitalized COVID-19 patients displayed a reduced relative risk for acute cardiac events (RR: 0.33, 95% CI [0.07; 0.75]) and showed diminished troponin T levels (Cohen's d: - 0.52, 95% CI [- 1.01; - 0.14]), compared to their non-vaccinated peers. Type 2 diabetes (OR: 2.99, 95% CI [1.22; 7.35]) and existing cardiac diseases (OR: 4.31, 95% CI [1.83; 10.74]) were identified as significant risk factors for the emergence of acute cardiac events. Our findings suggest that COVID-19 vaccination may confer both direct and indirect cardioprotective effects in hospitalized COVID-19 patients., (© 2024. The Author(s).)

Background: Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract., Methods and Results: HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function., Conclusions: These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.

To accept the toxic side effects of any treatment, whether medical, surgical or radiotherapeutic, cannot be avoided but implies to evaluate them taking into account the severity and prognosis of the disease that is concerned. Screening, preventing and treatment of these side effects are an integral aspect of the treatment of cancers. We will here review the contribution of the cardio-oncology, a recently emerged medical specialty. Cardiac irradiation cannot be avoided when treating several cancers, most frequently left sided breast cancer. As soon as radiotherapy is considered, it is of prime importance to evaluate each patient's risk factors and to handle them. If technical progresses have led to the complete disappearance of acute side effects of radiotherapy, this is not true for the delayed ones that may occur many years after the irradiation. Hence the need for «red flags» and for a systematic follow-up. Cardiac complications of left breast irradiation concern all aspects of cardiology: diseases of cardiac rhythm, valvulopathies, heart failure, coronary and pericardial disorders.

Transport stress (TS) not only weakens poultry performance but also affects animal welfare. Additionally, TS can evoke cardiac damage by triggering sterile inflammation in chicks, but the underlying mechanism is not fully understood. Here, we aimed to elucidate how TS induces sterile inflammation and heart injury and to clarify the antagonism effect of astragalus polysaccharides (APS). We randomly divided 60 chicks (one-day-old female) into 5 groups (n = 12): Control&#95;0h (Con&#95;0h) group (chicks were slaughtered at initiation), Control group (stress-free control), TS group (simulated TS exposure for 8 h), TS plus water (TS+W) group, and TS plus APS (TS+APS) group. Before simulation transport, the chicks of TS+W and TS+APS groups were, respectively, dietary with 100 μL of water or APS (250 μg/mL). H&E staining was employed for cardiac histopathological observation. ELISA assay was used to measure oxidative stress marker levels (GSH, GPX, GST, and MDA). A commercial kit was used to isolate the mitochondrial portion, and qRT-PCR was employed to measure the mitochondrial DNA (mtDNA) levels. Furthermore, we evaluated the activity of mtDNA-mediated NF-κB, NLRP3 inflammasome, and cGAS-STING inflammatory pathways and the expression of downstream inflammatory factors by Western Blotting or qRT-PCR. Our findings revealed that APS notably relieved TS-induced myocardial histopathological lesions and infiltrations. Likewise, the decrease in proinflammatory factors (TNF-α, IL-1β, and IL-6) and IFN-β by APS further supported this result. Meanwhile, TS caused severe oxidative stress in the chick heart, as evidenced by decreased antioxidant enzymes and increased MDA. Importantly, APS prevented mtDNA stress and leakage by reducing oxidative stress. Interestingly, TS-induced mtDNA leakage caused a series of inflammation events via mtDNA-PRRs pathways, including TLR21-NF-κB, NLRP3 inflammasome, and cGAS-STING signaling. Encouragingly, all these adverse changes related to inflammation events induced by mtDNA-PRRs activation were all relieved by APS treatment. In summary, our findings provide the first evidence that inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by APS could protect against TS-induced cardiac damage in chicks., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The translation of evidence-based interventions into practice settings remains challenging. Implementation science aims to bridge the evidence-to-practice gap by understanding multilevel contexts and tailoring evidence-based interventions accordingly. Engaging community partners who possess timely, local knowledge is crucial for this process to be successful. The Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance aims to address cardiopulmonary health disparities by engaging diverse community partners to improve the implementation of evidence-based interventions. The goal of the Community Engagement Subcommittee is to strengthen community engagement practice across DECIPHeR. This paper presents the subcommittee's "Why We Engage Communities" statement that outlines why community engagement is critical for implementation science. The paper also provides case examples of DECIPHeR community engagement activities., Methods: To develop the "Why We Engage Communities" statement, we conducted a literature review, surveyed subcommittee members to assess the importance of community engagement in their work, and integrated community partner feedback. We synthesize the findings into three key themes and present examples of community engagement activities and their impact across DECIPHeR projects., Results: The statement presents three themes that illustrate why community engagement increases the impact of implementation and health equity research. Community engagement (1) engages local knowledge and expertise, (2) promotes authentic relationships, and (3) builds community and researcher capacity. The statement provides a guiding framework for strengthening DECIPHeR research and enhancing community partnerships., Conclusion: Community engagement can improve the implementation of evidence-based interventions across diverse settings, improving intervention effectiveness in underserved communities and furthering health equity., Competing Interests: Conflict of Interest: All authors have no conflicts of interest to report.

Despite several ambitious national health initiatives to eliminate health disparities, spanning more than 4 decades, health disparities remain pervasive in the United States. In an attempt to bend the curve in disparities elimination, the National Heart, Lung, and Blood Institute (NHLBI) issued a funding opportunity on Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) in March 2019. Seven implementation research centers and 1 research coordinating center were funded in September 2020 to plan, develop, and test effective implementation strategies for eliminating disparities in heart and lung disease risk. In the 16 articles presented in this issue of Ethnicity & Disease , the DECIPHeR Alliance investigators and their NHLBI program staff address the work accomplished in the first phase of this biphasic research endeavor. Included in the collection are an article on important lessons learned during technical assistance sessions designed to ensure scientific rigor in clinical study designs, and 2 examples of clinical study process articles. Several articles show the diversity of clinical and public health settings addressed including schools, faith-based settings, federally qualified health centers, and other safety net clinics. All strategies for eliminating disparities tackle a cardiovascular or pulmonary disease and related risk factors. In an additional article, NHLBI program staff address expectations in phase 2 of the DECIPHeR program, strategies to ensure feasibility of scaling and spreading promising strategies identified, and opportunities for translating the DECIPHeR research model to other chronic diseases for the elimination of related health disparities., Competing Interests: Conflict of Interest: No conflicts of interest reported by authors.

Clinical practice guidelines from the American Heart Association recommend consideration of prophylactic anticoagulation to prevent left ventricular thrombus (LVT) formation in patients with anterior ST-elevation myocardial infarction. These guidelines were given a low certainty of evidence (class IIb, level C), relying primarily on case studies and expert consensus to inform practice. Our objective was to compare the safety and efficacy of prophylactic anticoagulation, in addition to dual antiplatelet therapy, in the current era of timely primary percutaneous coronary intervention. Electronic databases, including EMBASE, MEDLINE, and Cochrane Library, were systematically searched from January 2012 through June 2022. A total of 7,378 publications were screened, and 5 publications were eventually included in this review: 1 randomized control trial and 4 retrospective studies involving 1,461 patients. Data were pooled using a fixed-effects model and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome of interest was the rate of LVT formation, and the secondary outcomes were the rate of major bleeding and systemic embolism. Pooled analysis showed a significantly lower rate of LVT formation (OR 0.28, 95% CI 0.11 to 0.73, p <0.01) and significantly higher rates of bleeding (OR 2.85, 95% CI 1.13 to 7.24, p = 0.03) in the triple therapy group compared with dual antiplatelet therapy. No significant difference was observed in the rate of systemic embolism between the groups (OR 0.37, 95% CI 0.12 to 1.13, p = 0.08). In this meta-analysis, there is no conclusive evidence to either support or oppose the use of triple therapy for LVT prevention in patients with anterior ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Appropriately powered randomized controlled trials are warranted to further evaluate the benefits of LVT prevention against the risks of major bleeding in this population., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Preimplantation genetic testing (PGT) is a reproductive technology that selects embryos without (familial) genetic variants. PGT has been applied in inherited cardiac disease and is included in the latest American Heart Association/American College of Cardiology guidelines. However, guidelines selecting eligible couples who will have the strongest risk reduction most from PGT are lacking. We developed an objective decision model to select eligibility for PGT and compared its results with those from a multidisciplinary team., Methods: All couples with an inherited cardiac disease referred to the national PGT center were included. A multidisciplinary team approved or rejected the indication based on clinical and genetic information. We developed a decision model based on published risk prediction models and literature, to evaluate the severity of the cardiac phenotype and the penetrance of the familial variant in referred patients. The outcomes of the model and the multidisciplinary team were compared in a blinded fashion., Results: Eighty-three couples were referred for PGT (1997-2022), comprising 19 different genes for 8 different inherited cardiac diseases (cardiomyopathies and arrhythmias). Using our model and proposed cutoff values, a definitive decision was reached for 76 (92%) couples, aligning with 95% of the multidisciplinary team decisions. In a prospective cohort of 11 couples, we showed the clinical applicability of the model to select couples most eligible for PGT., Conclusions: The number of PGT requests for inherited cardiac diseases increases rapidly, without the availability of specific guidelines. We propose a 2-step decision model that helps select couples with the highest risk reduction for cardiac disease in their offspring after PGT., Competing Interests: Disclosures None.

Targeted therapy, such as tyrosine kinase inhibitors (TKIs), has been approved to manage various cancer types. However, TKI-induced cardiotoxicity is a limiting factor for their use. This issue has raised the need for investigating potential cardioprotective techniques to be combined with TKIs. Ribosomal S6-kinases (RSKs) are a downstream effector of the mitogen-activated-protein-kinase (MAPK) pathway; specific RSK isoforms, such as RSK1 and RSK2, have been expressed in cancer cells, in which they increase tumour proliferation. Selective targeting of those isoforms would result in tumour suppression. Moreover, activation of RSKs expressed in the heart has resulted in cardiac hypertrophy and arrhythmia; thus, inhibiting RSKs would result in cardio-protection. This review article presents an overview of the usefulness of RSK inhibitors that can be novel agents to be assessed in future research for their effect in reducing cancer proliferation, as well as protecting the heart from cardiotoxicity induced by TKIs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recent advances in the treatment of breast cancer have resulted in improved overall cancer survival; however, cancer therapy related cardiac dysfunction is considered a major adverse effect of several chemotherapeutic agents, particularly anthracyclines. Hence, there is a need to develop proper cardioprotective strategies to limit myocardial injury following chemotherapy., Objective: To evaluate the effect of statin therapy on prevention of anthracycline- induced cardiotoxicity in female patients with breast cancer., Patients and Methods: The current study is a prospective, randomized, single-blind, placebo-controlled trial in which we enrolled a total of 110 female patients with newly diagnosed breast cancer who received anthracycline based chemotherapy. Patients were randomly assigned in 1:1 ratio into two groups, study group in which patients received 40 mg of oral atorvastatin and control group in which patients received placebo. A comprehensive echocardiographic examination was performed to all patients prior to receiving the chemotherapy and after 6 months, assessment of LV ejection fraction was done by 3D-echocardiography. All echocardiographers were blinded to all the patients' characteristics and assignment to either group., Results: The mean age of patients assigned to the control group was 49.8±10.51 years old, while patients assigned to the intervention group had mean age of 47.84± 9.16 years old, both the control group and the intervention group were similar in demographic data and baseline clinical characteristics. There was a highly significant difference between the two groups regarding both the absolute LVEF assessed by 3D- echocardiography at 6 months and the percentage of change compared to baseline values, patients assigned to the control group had mean LVEF of 52.92% at 6 months with percentage of change reaching -7.06%, while those assigned to the intervention group had mean LVEF reaching 56.22% at 6 months with a percentage of change reaching -3.64% (P-value: 0.008 and 0.004 for the absolute value and percentage of change respectively). There was a significant difference between the two groups regarding incidence of development of cancer therapy related cardiac dysfunction (CTRCD); defined as drop in LVEF more than 10% and to a value below 53% assessed by 3D echocardiography, among the control group 15 patients (30%) developed CTRCD after 6 months from starting Anthracyclines based chemotherapy, while, among the intervention group only 6 patients (12%) developed CTRCD. (P-value= 0.027) CONCLUSION: Prophylactic use of atorvastatin may prevent the development of cancer therapy related cardiac dysfunction in breast cancer patients receiving anthracycline based chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Dose to heart substructures is a better predictor for major adverse cardiac events (MACE) than mean heart dose (MHD). We propose an avoidance planning strategy for important cardiac substructures., Material and Methods: Two plans, clinical and cardiac substructure-avoidance plan, were generated for twenty patients. Five dose-sensitive substructures, including left ventricle, pulmonary artery, left anterior descending branch, left circumflex branch and the coronary artery were chosen. The avoidance plan aims to meet the target criteria and organ-at-risk (OARs) constraints while minimizing the dose parameters of the above five substructures. The dosimetric assessments included the mean dose and the maximum dose of cardiac substructures and several volume parameters. In addition, we also evaluated the relative risk of coronary artery disease (CAD), chronic heart failure (CHF), and radiation pneumonia (RP)., Results: Pearson correlation coefficient and R 2 value of linear regression fitting demonstrated that MHD had poor prediction ability for the mean dose of the cardiac substructures. Compared to clinical plans, an avoidance plan is able to statistically significantly decrease the dose to key substructures. Meanwhile, the dose to OARs and the coverage of the target are comparable in the two plans. In addition, it can be observed that the avoidance plan statistically decreases the relative risks of CAD, CHF, and RP., Conclusions: The substructure-avoidance planning strategy that incorporates the cardiac substructures into optimization process, can protect the important heart substructures, such as left ventricle, left anterior descending branch and pulmonary artery, achieving the substantive sparing of dose-sensitive cardiac structures, and have the potential to decrease the relative risks of CAD, CHF, and RP., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Cardiovascular diseases are the second leading cause of death among breast cancer (BC) patients. Prediction of cardiovascular toxicity (CT) is an important part of the successful treatment and survival of patients., Objective: to develop a risk score model for cardiovascular toxicity (CT) predicting, based on cardiovascular risk factors (RFs), RFs associated with cancer therapy, and troponin levels., Material and Methods: The study included 76 BC patients with a prospective analysis of their clinical and treatment data, RFs, echocardiographic indicators before the start of treatment and after 6 months, and an increase in troponin level. Among all RFs, the most significant RFs of CT were: radiation therapy, treatment with anthracyclines, and cardiovascular diseases. Based on the obtained results, a combined CT risk score was developed and proposed.According to the sum of points, patients were divided into groups: group 1 - with a low risk of CT development, the sum of points < 5; group 2 - moderate risk, 6-7 points; group 3 - high risk, > 8 points., Results: In a pilot prospective study, an analysis of the RFs of CT was provided, compared to echocardiography data and the degree of troponin increase in dynamic observation; the risk score model for the CT prediction was developed for BC patients stratification. According to the developed score, BC patients with a total of > 8 points are considered to have a high risk of CT complications., Conclusions: The use of the proposed risk model score with calculation of the RFs of CT along with high-sensitivity troponin increase during cancer treatment allows predicting the risk of CT developing at the early stages - before the onset of clinical manifestations. Accordingly, these BC patients have a high risk of CT, and the use of personalized cardiac monitoring together with cardioprotective therapy can prevent cardiovascular complications., (N. V. Dovganych, S. M. Kozhukhov, I. I. Smolanka, O. F. Lygyrda, О. Ye. Bazyka, S. A. Lyalkin, О. A. Yarynkina.)

Damage to the mitochondria may lead to serious conditions that are difficult to treat. Doxorubicin is one of the most widely used chemotherapeutic drugs for the treatment of malignancies in children and adults, and reportedly causes damage to the mitochondria. Unfortunately, the dangerous cardiac side effects of doxorubicin appear when the patient is in the midst of a vigorous fight against the disease, either by taking doxorubicin alone or in combination with other drugs. This study aimed to determine whether exogenous healthy and functional mitochondria are internalized by cells, can it help the survival of these cells, and can reduce cardiotoxicity. For this purpose, isolated, pure, and functional exogenous mitochondria were injected into the tail vein of a rat model of doxorubicin-induced cardiotoxicity. After that, the heart function of the rats and their antioxidant status, inflammatory markers, and histopathological examination were investigated. Our findings show that intravenous mitochondrial transplantation provided efficient mitochondrial uptake and reduced cardiotoxicity by reducing ROS production, lipid peroxidation, and inflammation. In addition, the levels of ATP and antioxidant enzymes increased after mitochondrial transplantation; therefore all of these complex processes resulted in the reduction of apoptosis and necrosis in rat heart tissue. These promising results open the way to more effective cancer treatment without the side effects of related drugs. Transplanting exogenous mitochondria probably enhances the cell's mitochondrial network, potentially treating mitochondria-related disorders such as cardiovascular and neurodegenerative diseases, although the exact relationship between mitochondrial damage and these conditions remains unclear., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Radiation-induced heart disease (RIHD) is a common radiotherapy complication. Reducing radiation exposure and post-irradiation antioxidant therapy are promising approaches. Here, a liquid metal-based core-shell nanomedicine (LMN) composed of a gallium core and a multifunctional polymeric shell with radiopaque, X-ray shielding, and X-ray-responsive antioxidation properties for preventive therapy of RIHD is developed. The liquid metal provides radiopaque properties to enhance X-ray and computed tomography imaging and attenuate radiation to prevent primary myocardial damage. Under X-ray radiation, cleavage of the diselenide bond on the polymeric shell results in the release of LMN and controlled antioxidation. In vitro and in vivo experiments have demonstrated that LMN significantly reduces myocardial injury and impaired cardiac function, stabilizes mitochondrial function, and inhibits myocardial fibrosis. This nanomedicine with radiographic contrast, radiation shielding, and responsive features provides a new strategy for the prevention of radiation-related diseases., (© 2023 Wiley-VCH GmbH.)

Competing Interests: Declaration of Competing Interest E.H.Y: Research funding from CSL Behring, Boehringer Ingelheim, and Eli and Lilly Company. Consulting fees from Pfizer. A.G. is supported by American Heart Association-Strategically Focused Research Network Grant in Disparities in Cardio-Oncology (#847740, #863620) and the Department of Defense Prostate Cancer Research Program's Physician Research Award (#HT94252310158). D.A. is supported by Robert Wood Johnson Foundation (Harold Amos)- American Heart Association, and NIH K23-HL155890 grants. None of the other authors have disclosures or conflicts of interest related to this manuscript.

Exercise training is an encouraging approach to treat cardiac dysfunction in type 2 diabetes (T2DM), but the impact of its intensity is not understood. We aim to investigate whether and, if so, how moderate-intensity training (MIT) and high-intensity interval training (HIIT) alleviate adverse cardiac remodeling and dysfunction in rats with T2DM. Male rats received standard chow (n = 10) or Western diet (WD) to induce T2DM. Hereafter, WD rats were subjected to a 12-week sedentary lifestyle (n = 8), running MIT (n = 7) or HIIT (n = 7). Insulin resistance and glucose tolerance were assessed during the oral glucose tolerance test. Plasma advanced glycation end-products (AGEs) were evaluated. Echocardiography and hemodynamic measurements evaluated cardiac function. Underlying cardiac mechanisms were investigated by histology, western blot and colorimetry. We found that MIT and HIIT lowered insulin resistance and blood glucose levels compared to sedentary WD rats. MIT decreased harmful plasma AGE levels. In the heart, MIT and HIIT lowered end-diastolic pressure, left ventricular wall thickness and interstitial collagen deposition. Cardiac citrate synthase activity, mitochondrial oxidative capacity marker, raised after both exercise training modalities. We conclude that MIT and HIIT are effective in alleviating diastolic dysfunction and pathological cardiac remodeling in T2DM, by lowering fibrosis and optimizing mitochondrial capacity.

Introduction: Anthracycline-based chemotherapy increases the risk of cancer therapeutics-related cardiac dysfunction. Recently, evidences from in vitro experiments and animal studies have shown that ginsenosides may exert cardiovascular protection against cancer therapeutics-related cardiac dysfunction. Here, we aimed to evaluate this effect in a clinical situation., Methods: In this randomized, double-blind, placebo-controlled clinical trial, women with non-metastatic breast cancer whose left ventricular ejection fraction was ≥ 50% were randomly assigned in 1:1 ratio to receive ginseng (1 g/day) or placebo besides standard chemotherapy. Echocardiographic measurements were performed at baseline, after the fourth, and eighth chemotherapy cycles. High-sensitive cardiac troponin I was assessed at baseline and after the 4th cycle. The primary endpoint of the study was change in left ventricular ejection fraction. Cancer therapeutics-related cardiac dysfunction was defined as a drop in left ventricular ejection fraction of ≥ 10% from baseline., Results: Results from 30 patients were included in the final analysis (15 patients in each group). In the intervention and control groups, left ventricular ejection fraction was dropped from 62.0 ± 0.9% to 60.7 ± 1.0% (difference = -1.3 ± 1.1%) and from 63.27 ± 1.1% to 58.0 ± 1.3% (difference = -5.27 ± 0.8%), respectively (difference = 3.97%, p  = 0.006) at the end of the fourth cycle of chemotherapy. After the eighth cycle of chemotherapy, the mean left ventricular ejection fraction was increased by 0.8 ± 1.3% from baseline in the intervention group, whereas the placebo group experienced a reduction of -7.3 ± 1.4% (difference = 8.1%, p -value < 0.001). None of the patients in the ginseng group in comparison to 1(6.7%, p -value = 0.5) and 5 (33.3%, p -value = 0.02) patients in the placebo group developed cancer therapeutics-related cardiac dysfunction after the fourth and eighth cycles, respectively. High-sensitive cardiac troponin I levels were not significantly different between groups., Conclusions: Prophylactic ginseng supplementation may protect against doxorubicin-induced early cancer therapeutics-related cardiac dysfunction and early decline in left ventricular ejection fraction in breast cancer patients.

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use., Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction., Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022., Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months., Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months., Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups., Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use., Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.

In folk medicine, the almond nut ( Terminalia catappa ) and orange peel ( Citrus sinensis ) are cost-effective sources of nutraceutical utilized in the treatment of degenerative diseases. Hyperlipidemia and hypertension are two pathological conditions implicated in cardiovascular disorders. This study sought to evaluate the cardiomodulatory effect of almond-citrus peel fortified shortbread in hyperlipidemic-hypertensive rats induced by high fat diet and N ω-nitro-l-arginine methyl ester. The experimental animals were divided into eight groups. The experimental rats were fed with shortbread supplemented with almond and citrus peel at varying inclusions of 0.2% citrus, 50% almond, and almond (50%)- citrus (0.2%) for 21 days. The mean arterial blood pressure (MABP), systolic blood pressure (SBP), and lipid profile of the experimental rats were measured. Thereafter, the activities of angiotensin-1-converting enzyme (ACE), arginase, malondialdehyde (MDA), phosphodiesterase-5, nitric oxide (NO), and antioxidant indices were evaluated. The result showed significant elevation in SBP, MABP, blood cholesterol, triglyceride, ACE, arginase, activities, and MDA levels in the heart tissue of the untreated rats. In contrast, the antioxidant status and NO level were significantly decreased in the untreated groups. Remarkably, the treatment with almond-citrus peel fortified shortbread and the individual effect of almond (50%) and citrus peel (0.2%) all reversed these trends in the hyperlipidemic-hypertensive rats. Intriguingly, the blend of almond (50%)-citrus peel (0.2%) fortified shortbread showed the best antioxidative and cardioprotective effect. The results suggest that almond and citrus peel offer potentials as therapeutic agent in the prevention and management of hyperlipidemia and hypertension.