ABSTRACT

PURPOSE OF REVIEW: Although mortality rates have declined significantly in recent years, breast cancer remains the second most common cause of cancer death in women, with rates significantly higher among women with metastatic disease. New therapeutic agents have improved the prognosis of patients with metastatic breast cancer but raise concerns around the risk of cardiovascular disease. This review aims to discuss the oncologic treatment of the different subtypes of breast cancer along with the cardiac complications associated with each therapy.

RECENT FINDINGS: This article emphasizes human epidermal growth factor receptor targeted therapies with a focus on incidence of cardiotoxicity, reversibility, long-term outcomes, and management in high-risk patients. This review will address the use of cardiac biomarkers to monitor for toxicity, as well as the utility of cardiac imaging, including global longitudinal strain as a prognostic factor. We will also include recent findings on tyrosine kinase inhibitors, cyclin dependent kinase 4/6, and immune checkpoint inhibitors. Cardiotoxicity may lead to premature discontinuation of novel cancer therapies; optimizing cardiovascular risk factors and close monitoring for cardiotoxicity allow patients to maximize their oncologic and cardiovascular outcomes.

PMID:37249834 | DOI:10.1007/s11912-023-01427-z

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PubMed articles on: Cardio-Oncology

Cardio-Oncology for the Primary Care Provider

Rom J Intern Med. 2023 May 30. doi: 10.2478/rjim-2023-0012. Online ahead of print.

ABSTRACT

Cardiovascular disease is a major cause of mortality among oncologic patients. As cancer therapies continue to evolve and advance, cancer survival rates have been increasing and so has the burden of cardiovascular disease within this population. For this reason, cardio-oncology plays an important role in promoting multidisciplinary care with the primary care provider, oncology, and cardiology. In this review, we discuss the roles of different providers, strategies to monitor patients receiving cardiotoxic therapies, and summarize cancer therapy class-specific toxicities. Continued collaboration among providers and ongoing research related to cardiotoxic cancer therapies will enable patients to receive maximal, evidence-based, comprehensive care.

PMID:37249550 | DOI:10.2478/rjim-2023-0012

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PubMed articles on: Cardio-Oncology

The incidence rate of allergic reactions induced by oxaliplatin is higher in patients with rectal cancer compared with colon cancer

Drug Chem Toxicol. 2023 May 29:1-7. doi: 10.1080/01480545.2023.2217700. Online ahead of print.

ABSTRACT

AIM: To explore the diverse profiles of adverse reactions caused by oxaliplatin between colon and rectal cancer, we investigated the toxicity of oxaliplatin in patients with colon and rectal cancer.

METHODS: From January 2017 to December 2021, 200 cases of sporadic CRC patients with adverse reactions after oxaliplatin were collected from Harbin Medical University Cancer Hospital, Harbin, China. All patients received a chemotherapy regimen containing oxaliplatin (100 colon cancer and 100 rectal cancer). We reviewed the adverse reactions induced by oxaliplatin in patients with colon and rectal cancer.

RESULTS: We found there was no significant difference in gastrointestinal toxicity, hematotoxicity, neurotoxicity, hepatotoxicity, respiratory toxicity, and cardiotoxicity caused by oxaliplatin between patients with colon cancer and patients with rectal cancer, but patients with rectal cancer were more prone to allergic reactions than patients with colon cancer after oxaliplatin. In addition, we found neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) were higher in patients with colon cancer than in patients with rectal cancer. This may reflect differences in immune status and inflammatory responses between colon cancer and rectal cancer, which might be the reason for more allergic reactions caused by oxaliplatin in colon cancer patients compared to rectal cancer patients.

CONCLUSION: Except for a higher incidence of allergic reactions in patients with rectal cancer, no significant difference in the incidence of adverse drug reactions associated with oxaliplatin was noted between patients with colon cancer and rectal cancer. Our results suggested more attention should be paid to the allergic reaction caused by oxaliplatin in patients with colon cancer.

PMID:37246950 | DOI:10.1080/01480545.2023.2217700

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PubMed articles on: Cardio-Oncology

Hyperoside prevents doxorubicin-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway

Phytother Res. 2023 May 28. doi: 10.1002/ptr.7900. Online ahead of print.

ABSTRACT

Clinical application of doxorubicin (Dox) in cancer chemotherapy is limited by its cardiotoxicity. Present study aimed to demonstrate the effect and mechanism of hyperoside in Dox-induced cardiotoxicity. C57BL/6 mice were injected with 12 mg/kg of Dox, and 1 μM Dox was exposed to primary cardiomyocytes. Cardiac function was evaluated by echocardiographic and myocardial enzyme levels. Cardiomyocyts apoptosis was analyzed by TUNEL staining and flow cytometry. Network pharmacology and molecular docking were utilized to explore potential targets of hyperoside. Protein expressions were detected by western blot and enzyme activities were determined by colorimetry. Cardiac dysfunction and cardiomyocyte apoptosis induced by Dox were attenuated by hyperoside. Mechanism of hyperoside was mainly related to "oxidative stress" pathway. Hyperoside exhibited strong binding activities with nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs, the main source of ROS in cardiomyocytes) and cyclooxygenases (COXs). Experiments proved that hyperoside suppressed the ROS generation and the elevated activities of NOXs and COXs induced by Dox. Dox also triggered the activation of NLRP3 inflammasome, which was reversed by hyperoside. Hyperoside bound to NOXs and COXs, which prevents Dox-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway. Hyperoside holds promise as a therapeutic strategy for Dox-induced cardiotoxicity.

PMID:37246409 | DOI:10.1002/ptr.7900

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PubMed articles on: Cardio-Oncology

Alternate-day fasting exacerbates doxorubicin cardiotoxicity in cancer chemotherapy

Trends Endocrinol Metab. 2023 May 26:S1043-2760(23)00093-0. doi: 10.1016/j.tem.2023.05.003. Online ahead of print.

ABSTRACT

Doxorubicin (Dox) is a highly potent chemotherapy drug. Despite its efficacy, Dox's clinical application is limited due to its association with significant complications, namely cardiotoxicity and the risk of heart failure. Recent intriguing findings by Ozcan et al. indicate that alternate-day fasting (ADF) significantly exacerbates the cardiotoxicity of Dox.

PMID:37246117 | DOI:10.1016/j.tem.2023.05.003

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PubMed articles on: Cardio-Oncology

Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice

Nutrients. 2023 May 12;15(10):2287. doi: 10.3390/nu15102287.

ABSTRACT

BACKGROUND: Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage.

METHODS: Using transmission electron microscopy, we evaluated cells' morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1/3), inflammation (TNFα, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase).

RESULTS: Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival.

CONCLUSION: Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.

PMID:37242170 | PMC:PMC10222879 | DOI:10.3390/nu15102287

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PubMed articles on: Cardio-Oncology

p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

Nutrients. 2023 May 10;15(10):2259. doi: 10.3390/nu15102259.

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

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

Association of atrial fibrillation and outcomes in patients undergoing bone marrow transplantation

Europace. 2023 May 19;25(5):euad129. doi: 10.1093/europace/euad129.

ABSTRACT

AIMS: Haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant haematologic conditions. Patients undergoing HSCT are at an increased risk of developing atrial fibrillation (AF). We hypothesized that a diagnosis of AF would be associated with poor outcomes in patients undergoing HSCT.

METHODS AND RESULTS: The National Inpatient Sample (2016-19) was queried with ICD-10 codes to identify patients aged >50 years undergoing HSCT. Clinical outcomes were compared between patients with and without AF. A multivariable regression model adjusting for demographics and comorbidities was used to calculate the adjusted odds ratio (aOR) and regression coefficients with corresponding 95% confidence intervals and P-values. A total of 50 570 weighted hospitalizations for HSCT were identified, out of which 5820 (11.5%) had AF. Atrial fibrillation was found to be independently associated with higher inpatient mortality (aOR 2.75; 1.9-3.98; P < 0.001), cardiac arrest (aOR 2.86; 1.55-5.26; P = 0.001), acute kidney injury (aOR 1.89; 1.6-2.23; P < 0.001), acute heart failure exacerbation (aOR 5.01; 3.54-7.1; P < 0.001), cardiogenic shock (aOR 7.73; 3.17-18.8; P < 0.001), and acute respiratory failure (aOR 3.24; 2.56-4.1; P < 0.001) as well as higher mean length of stay (LOS) (+2.67; 1.79-3.55; P < 0.001) and cost of care (+67 529; 36 630-98 427; P < 0.001).

CONCLUSION: Among patients undergoing HSCT, AF was independently associated with poor in-hospital outcomes, higher LOS, and cost of care.

PMID:37208304 | PMC:PMC10198774 | DOI:10.1093/europace/euad129

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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.

ABSTRACT

OBJECTIVE: To investigate the association between stages of QTc prolongation and the risk of cardiac events among patients on TKIs.

METHODS: This was a retrospective cohort study performed at an academic tertiary care center of cancer patients who were taking TKIs or not taking TKIs. Patients with two recorded ECGs between January 1, 2009, and December 31, 2019, were selected from an electronic database. The QTc duration > 450ms was determined as prolonged. The association between QTc prolongation progression and events of cardiovascular disease were compared.

RESULTS: This study included a total of 451 patients with 41.2% of patients taking TKIs. During a median follow up period of 3.1 years, 49.5% subjects developed CVD and 5.4% subjects suffered cardiac death in patient using TKIs (n = 186); the corresponding rates are 64.2% and 1.2% for patients not on TKIs (n = 265), respectively. Among patient on TKIs, 4.8% of subjects developed stroke, 20.4% of subjects suffered from heart failure (HF) and 24.2% of subjects had myocardial infarction (MI); corresponding incidence are 6.8%, 26.8% and 30.6% in non-TKIs. When patients were regrouped to TKIs versus non-TKIs with and without diabetes, there was no significant difference in the incidence of cardiac events among all groups. Adjusted Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). There is a significant increased risk of HF events (HR, 95% CI: 2.12, 1.36-3.32) and MI events (HR, 95% CI: 1.78, 1.16-2.73) during the 1st visit. There are also trends for an increased incidence of cardiac adverse events associated with QTc prolongation among patient with QTc > 450ms, however the difference is not statistically significant. Increased cardiac adverse events in patients with QTc prolongation were reproduced during the 2nd visit and the incidence of heart failure was significantly associated with QTc prolongation(HR, 95% CI: 2.94, 1.73-5.0).

CONCLUSION: There is a significant increased QTc prolongation in patients taking TKIs. QTc prolongation caused by TKIs is associated with an increased risk of cardiac events.

PMID:37208762 | PMC:PMC10197472 | DOI:10.1186/s40959-023-00178-x

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PubMed articles on: Cardio-Oncology

Modelling cardiac mechanics in doxorubicin-induced cardiotoxicity following childhood acute lymphoblastic leukemia using a combination of cardiac magnetic resonance imaging, cardiopulmonary exercise testing and the CircAdapt model

J Biomech. 2023 Jun;154:111616. doi: 10.1016/j.jbiomech.2023.111616. Epub 2023 May 5.