ABSTRACT

Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.

PMID:37242146 | PMC:PMC10222243 | DOI:10.3390/nu15102259

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PubMed articles on: Cardio-Oncology

Prognostic Impact of Global Longitudinal Strain and NT-proBNP on Early Development of Cardiotoxicity in Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy

Medicina (Kaunas). 2023 May 15;59(5):953. doi: 10.3390/medicina59050953.

ABSTRACT

Background. The most important anthracycline side effect is cardiotoxicity, resulting in congestive heart failure (HF). Early detection of cardiac dysfunction and appropriate treatment can improve outcomes and reduce the progression of HF. The aim of our study was to evaluate changes in clinical data, echocardiographic parameters, and NT-proBNP, as well as their associations with early anthracycline-induced cardiotoxicity (AIC) in patients treated with anthracycline-based chemotherapy. Methods and Materials. Patients with breast cancer were prospectively assessed with echocardiography, as well as NT-proBNP testing at baseline, (T0), after two cycles (T1) and four cycles (T2) of chemotherapy. AIC was defined as a new decrease in the LVEF of 10 percentage points, to a value below the lower limit of normal. Results.We evaluated 85 patients aged 54.5 ± 9.3 years. After a cumulative dose of 237.9 mg/m2 of doxorubicin, 22 patients (25.9%) met the criteria of AIC after chemotherapy. Patients who subsequently progressed to cardiotoxicity had demonstrated a significantly larger impairment in LV systolic function compared to those who did not develop cardiotoxicity (LVEF: 54.0 ± 1.6% vs. 57.1 ± 1.4% at T1, p< 0.001, and 49.9 ± 2.1% vs. 55.8 ± 1.6% at T2, p< 0.001; GLS: -17.8 ± 0.4% vs. -19.3 ± 0.9% at T1, p< 0.001, and -16.5 ± 11.1% vs. -18.5 ± 0.9% at T2, p< 0.001, respectively). The levels of NT-proBNP increased significantly from 94.8 ± 43.8 ng/L to 154.1 ± 75.6 ng/L, p< 0.001. A relative decrease in GLS ≤ -18.0% (sensitivity: 72.73%; specificity: 92.06%; AUC, 0.94; p< 0.001) and a relative increase in NT-proBNP > 125 ng/L (sensitivity: 90.0%; specificity: 56.9%; AUC, 0.78; p< 0.001) from baseline to T1 predicted subsequent LV cardiotoxicity at T2. Conclusions. Decrease in GLS and elevation in NT-proBNP were significantly associated with AIC, and these could potentially be used to predict subsequent declines in LVEF with anthracycline-based chemotherapy.

PMID:37241185 | PMC:PMC10224214 | DOI:10.3390/medicina59050953

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PubMed articles on: Cardio-Oncology

Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats

J Pers Med. 2023 Apr 27;13(5):750. doi: 10.3390/jpm13050750.

ABSTRACT

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.

PMID:37240920 | PMC:PMC10221553 | DOI:10.3390/jpm13050750

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PubMed articles on: Cardio-Oncology

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination

J Clin Med. 2023 May 12;12(10):3427. doi: 10.3390/jcm12103427.

ABSTRACT

Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter-Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of -17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m2, and the right ventricular free wall longitudinal strain (LS) was impaired in some patients but not in all. There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group (32% vs. 62.5%, p= 0.04). In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy (-19.1 ± 3.1% vs. -16.5 ± 5.1%, p= 0.04). DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter-Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment.

PMID:37240533 | PMC:PMC10219019 | DOI:10.3390/jcm12103427

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PubMed articles on: Cardio-Oncology

Primary Cardiac Schwannoma: A Meta-Analysis of Individual Case Reports

J Clin Med. 2023 May 9;12(10):3356. doi: 10.3390/jcm12103356.

ABSTRACT

Primary cardiac schwannoma (PCS) is a neurogenic tumor that arises from Schwann cells. Malignant schwannoma (MSh) is an aggressive cancer comprising 2% of all sarcomas. Information on the proper management of these tumors is limited. Four databases were searched for case reports/series of PCS. The primary outcome was overall survival (OS). Secondary outcomes included therapeutic strategies and the corresponding outcomes. Among 439 potentially eligible studies, 53 met the inclusion criteria. The patients included had 43.72 ± 17.76 years and 28.3% were males. Over 50% of patients had MSh, with 9.4% also demonstrating metastases. Schwannoma commonly occurs in the atria (66.0%). Left-sided PCS were more common than right-sided ones. Surgery was performed in almost 90% of the cases; chemotherapy and radiotherapy were used in 16.9% and 15.1% of cases, respectively. Compared to benign cases, MSh occurs at a younger age and is commonly located on the left side. OS of the entire cohort at 1 and 3 years were 60.7%, and 54.0%, respectively. Females and males OS were similar up to 2 years follow-up. Surgery was associated with higher OS (p < 0.01). Surgery is the primary treatment option for both benign and malignant cases and was the only factor associated with a relative improvement in survival.

PMID:37240461 | PMC:PMC10219427 | DOI:10.3390/jcm12103356

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PubMed articles on: Cardio-Oncology

Recurrent cardiotoxicity in a fluoropyrimidine treated cancer patient - case report and practical recommendations

Arch Clin Cases. 2023 May 18;10(2):55-60. doi: 10.22551/2023.39.1002.10241. eCollection 2023.

ABSTRACT

Fluoropyrimidines remain some of the most used chemotherapeutics, despite the appearance in the therapeutic arsenal of targeted therapy and immunotherapy. Fluropyrimidines related cardiotoxicity is an undesirable adverse event and affects almost 20% of patients. The mechanisms of fluoropyrimidine toxicity are closely related to deficient allelic variants of DPYD, but considering the low penetrance and interindividual variability, not all adverse reactions are explained by their presence. In this case, we report a patient with recurrent fluoropyrimidine toxicity without a deficient allelic variant and how this case was managed by the oncologist and cardiologist, considering the need to use fluoropyrimidine in the treatment.

PMID:37215066 | PMC:PMC10194170 | DOI:10.22551/2023.39.1002.10241

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PubMed articles on: Cardio-Oncology

Will nanomedicine become a good solution for the cardiotoxicity of chemotherapy drugs?

Front Pharmacol. 2023 May 4;14:1143361. doi: 10.3389/fphar.2023.1143361. eCollection 2023.

ABSTRACT

Cancer is one of the leading causes of death worldwide, and with the continuous development of life sciences and pharmaceutical technology, more and more antitumor drugs are being used in clinics to benefit cancer patients. However, the incidence of chemotherapy-induced cardiotoxicity has been continuously increasing, threatening patients' long-term survival. Cardio-oncology has become a research hot spot, and the combination of nanotechnology and biomedicine has brought about an unprecedented technological revolution. Nanomaterials have the potential to maximize the efficacy and reduce the side effects of chemotherapeutic drugs when used as their carriers, and several nano-formulations of frequently used chemotherapeutic drugs have already been approved for marketing. In this review, we summarize chemotherapeutic drugs that are highly associated with cardiotoxicity and evaluate the role of nano-delivery systems in reducing cardiotoxicity based on studies of their marketed or R&D nano-formulations. Some of the marketed chemotherapy drugs are combined with nano-delivery systems that can effectively deliver chemotherapy drugs to tumors and cannot easily penetrate the endothelial barrier of the heart, thus decreasing their distribution in the heart and reducing the cardiotoxicity to some extent. However, many chemotherapy nanomedicines that are marketed or in R&D have not received enough attention in determining their cardiotoxicity. In general, nanomedicine is an effective method to reduce the cardiotoxicity of traditional chemotherapy drugs. However, cardiovascular complications in cancer treatment are very complex diseases, requiring the application of multiple measures to achieve effective management and prevention.

PMID:37214453 | PMC:PMC10194942 | DOI:10.3389/fphar.2023.1143361

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PubMed articles on: Cardio-Oncology

Poorer Survival after Out-of-Hospital Cardiac Arrest among Cancer Patients - A Population-Based Register Study

Eur Heart J Acute Cardiovasc Care. 2023 May 20:zuad053. doi: 10.1093/ehjacc/zuad053. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The association between cancer and survival after out-of-hospital cardiac arrest (OHCA) has not been thoroughly investigated. We aimed to address this knowledge gap using national, population-based registries.

METHODS: For this study, 30,163 OHCA patients (≥18 years) were included from the Swedish Register of Cardiopulmonary Resuscitation. Via linkage to the National Patient Registry, 2,894 patients (10%) with cancer diagnosed within 5 years prior to OHCA were identified. Differences in 30-day survival between cancer patients and controls (defined as OHCA patients without previous cancer diagnosis) were assessed related to cancer stage (locoregional vs metastasized cancer) and cancer site (i.e. lung cancer, breast cancer etc.) using logistic regression adjusted for prognostic factors. Long-term survival is presented as a Kaplan-Meier curve.

RESULTS: For locoregional cancer no statistically significant difference in return of spontaneous circulation (ROSC) was seen compared to controls, metastasized disease was associated with poorer chance of ROSC. Cancer was associated with lower 30-day survival for all cancers (Adjusted odds ratio, OR, 0.57, CI 0.49-0.66), locoregional cancer (Adjusted OR 0.68, CI 0.57-0.82) and metastasized cancer (Adjusted OR 0.24, CI 0.14-0.40) compared to controls. Lower 30-day survival compared to controls was seen for lung cancer, gynaecological and haematological cancers.

CONCLUSION: Cancer is associated with poorer 30-day survival after OHCA. This study suggests that cancer site and disease stage are more relevant factors than cancer in general with regard to its effect on survival after OHCA.

PMID:37210580 | DOI:10.1093/ehjacc/zuad053

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PubMed articles on: Cardio-Oncology

Cardiac AL amyloidosis presenting as recurrent dyspnoea in a patient with cancer: an important clinical clue to an early diagnosis

BMJ Case Rep. 2022 Sep 2;15(9):e245969. doi: 10.1136/bcr-2021-245969.

ABSTRACT

Cardiac amyloidosis (CA) is challenging to diagnose due to its non-specific clinical manifestations early in the disease process. We report the case of a patient who presented with dyspnoea, abdominal distension and leg swelling. Medical history was notable for hypertension, recurrent vulvar squamous cell carcinoma and polysubstance abuse. Over 1 year before the official diagnosis of CA, the patient had multiple hospital readmissions for dyspnoea. Our case illustrates the importance of having a high index of clinical suspicion for an early diagnosis of CA. Furthermore, it highlights the need to re-evaluate a presumed diagnosis when a patient's symptoms recur or do not respond to appropriate treatment and to consider the influence of social factors on diagnostic processes.

PMID:37209004 | PMC:PMC9442486 | DOI:10.1136/bcr-2021-245969

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PubMed articles on: Cardio-Oncology

Development of cardiac risk prediction model in patients with HER-2 positive breast cancer on trastuzumab therapy

Cardiooncology. 2023 May 19;9(1):26. doi: 10.1186/s40959-023-00177-y.

ABSTRACT

BACKGROUND: 25% of all breast cancer patients have HER-2 overexpression. Breast Cancer patients with HER-2 overexpression are typically treated with HER-2 inhibitors such as Trastuzumab. Trastuzumab is known to cause a decrease in left ventricular ejection fraction. The aim of this study is to create a cardiac risk prediction tool among women with Her-2 positive breast cancer to predict cardiotoxicity.

METHOD: Using a split sample design, we created a risk prediction tool using patient level data from electronic medical records. The study included women 18 years of age and older diagnosed with HER-2 positive breast cancer who received Trastuzumab. Outcome measure was defined as a drop in LVEF by more than 10% to less than 53% at any time in the 1-year study period. Logistic regression was used to test predictors.

RESULTS: The cumulative incidence of cardiac dysfunction in our study was 9.4%. The sensitivity and specificity of the model are 46% and 84%, respectively. Given a cumulative incidence of cardiotoxicity of 9%, the negative predictive value of the test was 94%. This suggests that in a low-risk population, the interval of screening for cardiotoxicity may be performed less frequently.

CONCLUSION: Cardiac risk prediction tool can be used to identify Her-2 positive breast cancer patients at risk of developing cardiac dysfunction. Also, test characteristics in addition to disease prevalence may inform a rational strategy in performing cardiac ultrasound in Her-2 breast cancer patients. We have developed a cardiac risk prediction model with high NPV in a low-risk population which has an appealing cost-effectiveness profile.

PMID:37208775 | PMC:PMC10197831 | DOI:10.1186/s40959-023-00177-y

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PubMed articles on: Cardio-Oncology

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies

Blood Cancer J. 2023 May 19;13(1):83. doi: 10.1038/s41408-023-00849-z.

ABSTRACT

With the continuous improvement in survival of cancer patients, including those with multiple myeloma, related to the novel treatment agents and therapeutic approaches, the probability for patients to develop cardiovascular disease has significantly increased, especially in elderly patients and those with additional risk factors. Multiple myeloma is indeed a disease of the elderly population and so these patients are, solely by age, at an increased risk of cardiovascular disease. Risk factors for these events can be patient-, disease- and/or therapy-related, and they have been shown to adversely impact survival. Cardiovascular events affect around 7.5% of patients with multiple myeloma and the risk for different toxicities has considerably varied across trials depending on patients' characteristics and treatment utilized. High grade cardiac toxicity has been reported with immunomodulatory drugs (odds ratio [OR] around 2), proteasome inhibitors (OR 1.67-2.68 depending on the specific agent, and generally higher with carfilzomib), as well as other agents. Cardiac arrhythmias have also been reported with various therapies and drug interaction plays a significant role in that setting. Comprehensive cardiac evaluation before, during and after various anti-myeloma therapy is recommended and the incorporation of surveillance strategies allows early detection and management resulting in improved outcomes of these patients. Multidisciplinary interaction including hematologists and cardio-oncologists is critical for optimal patient care.

PMID:37208317 | PMC:PMC10199017 | DOI:10.1038/s41408-023-00849-z

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PubMed articles on: Cardio-Oncology

The association of QTc prolongation with cardiovascular events in cancer patients taking tyrosine kinase inhibitors (TKIs)

Cardiooncology. 2023 May 19;9(1):25. doi: 10.1186/s40959-023-00178-x.