ABSTRACT

IMPORTANCE: Cancer therapy-related cardiac dysfunction (CTRCD) is a potentially serious cardiotoxicity of treatments for ERBB2-positive breast cancer (formerly HER2). Identifying early biomarkers of cardiotoxicity could facilitate an individualized approach to cardiac surveillance and early pharmacologic intervention. Circulating cell-free DNA (cfDNA) of cardiomyocyte origin is present during acute cardiac injury but has not been established as a biomarker of CTRCD.

OBJECTIVE: To determine whether circulating cardiomyocyte cfDNA is associated with CTRCD in patients with ERBB2-positive breast cancer treated with anthracyclines and ERBB2-targeted therapy.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort of 80 patients with ERBB2-positive breast cancer enrolled at an academic cancer center between July 2014 and April 2016 underwent echocardiography and blood collection at baseline, after receiving anthracyclines, and at 3 months and 6 months of ERBB2-targeted therapy. Participants were treated with doxorubicin-based chemotherapy followed by trastuzumab (+/- pertuzumab). The current biomarker study includes participants with sufficient biospecimen available for analysis after anthracycline therapy. Circulating cardiomyocyte-specific cfDNA was quantified by a methylation-specific droplet digital polymerase chain reaction assay. Data for this biomarker study were collected and analyzed from June 2021 through April 2022.

MAIN OUTCOMES AND MEASURES: The outcome of interest was 1-year CTRCD, defined by symptomatic heart failure or an asymptomatic decline in left ventricular ejection fraction (≥10% from baseline to less than lower limit of normal or ≥16%). Values for cardiomyocyte cfDNA and high-sensitivity cardiac troponin I (hs-cTnI) measured after patients completed treatment with anthracyclines were compared between patients who later developed CTRCD vs patients who did not using the Wilcoxon rank sum test, and the association of post-anthracycline cardiomyocyte cfDNA level with CTRCD was estimated using logistic regression.

RESULTS: Of 71 patients included in this study, median (IQR) age was 50 (44-58) years, all were treated with dose-dense doxorubicin, and 48 patients underwent breast radiotherapy. Ten of 71 patients (14%) in this analysis developed CTRCD. The level of cardiomyocyte cfDNA at the post-anthracycline time point was higher in patients who subsequently developed CTRCD (median, 30.5 copies/mL; IQR, 24-46) than those who did not (median, 7 copies/mL; IQR, 2-22; P = .004). Higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD (hazard ratio, 1.02 per 1-copy/mL increase; 95% CI, 1.00-1.03; P = .046).

CONCLUSIONS AND RELEVANCE: This study found that higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD. Cardiomyocyte cfDNA quantification shows promise as a predictive biomarker to refine risk stratification for CTRCD among patients with breast cancer receiving cardiotoxic cancer therapy, and its use warrants further validation.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02177175.

PMID:37256614 | DOI:10.1001/jamacardio.2023.1229

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PubMed articles on: Cardio-Oncology

Natriuretic Peptides, Cardio-Oncology

Anatol J Cardiol. 2023 Jun;27(6):298. doi: 10.14744/AnatolJCardiol.2023.6.

NO ABSTRACT

PMID:37257014 | DOI:10.14744/AnatolJCardiol.2023.6

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PubMed articles on: Cardio-Oncology

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors

J Interv Card Electrophysiol. 2023 May 31. doi: 10.1007/s10840-023-01575-z. Online ahead of print.

ABSTRACT

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies.

METHODS: We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022.

RESULTS: One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32 months in the ibrutinib group vs 64 months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias.

CONCLUSIONS: In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias.

PMID:37256462 | DOI:10.1007/s10840-023-01575-z

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PubMed articles on: Cardio-Oncology

An unusual case of checkpoint-inhibitor-induced pleuropericarditis

J Oncol Pharm Pract. 2023 May 30:10781552231179369. doi: 10.1177/10781552231179369. Online ahead of print.

ABSTRACT

INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor that promotes effector T-cell functions on malignant cells by binding to programmed cell death protein 1 (PD-1). Pembrolizumab is well tolerated in most cases with an adverse event profile consisting mainly of pruritus, fatigue, and anorexia. Cardiotoxicity comprises 1% of the total adverse events.

CASE REPORT: We present a case of a 64-year-old female with non-small cell lung cancer (NSCLC) who developed pleuropericarditis following pembrolizumab therapy.

MANAGEMENT & OUTCOME: The patient was successfully managed with colchicine, furosemide, and timely initiation of methylprednisolone with the improvement of her symptoms. The decision to discontinue pembrolizumab was made, and six months after this intervention, the patient has remained asymptomatic.

DISCUSSION: Clinicians should recognize these potential immune-mediated adverse effects to provide effective and timely management and optimize patient care.

PMID:37254508 | DOI:10.1177/10781552231179369

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PubMed articles on: Cardio-Oncology

Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients

PLoS One. 2023 May 30;18(5):e0286364. doi: 10.1371/journal.pone.0286364. eCollection 2023.

ABSTRACT

BACKGROUND: Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes.

OBJECTIVES: To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy.

METHODS: Breast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed.

RESULTS: 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease.

CONCLUSIONS: In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

PMID:37252927 | PMC:PMC10228774 | DOI:10.1371/journal.pone.0286364

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PubMed articles on: Cardio-Oncology

Cardiotoxicities of Non-Chemotherapeutic Metastatic Breast Cancer Treatments

Curr Oncol Rep. 2023 May 30. doi: 10.1007/s11912-023-01427-z. Online ahead of print.

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

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

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

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

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: Cancer & VTE/PE

Thrombosis in the Neonatal Intensive Care Unit

Neoreviews. 2023 Jun 1;24(6):e356-e369. doi: 10.1542/neo.24-6-e356.

ABSTRACT

Neonates, particularly critically ill and premature infants, have one of the highest risks of thromboembolic complications, particularly venous thromboembolism (VTE), in the pediatric population. Recent data suggest that the incidence of VTE has significantly increased in neonates over the last few decades. Critically ill and premature infants exhibit multiple risk factors that place them at a high risk for thromboembolic events including developmental hemostasis, propensity to infections, and frequent need for central venous access. The clinical presentation, diagnostic modalities, and treatment strategies for thromboembolic complications in neonates vary based on several factors, including the etiology of the thromboembolic event, the anatomic site affected, and the patient's underlying comorbidities. Although guidelines for management are available, they are mostly based on consensus recommendations and on extrapolation from adult data due to a lack of high-quality data in the neonatal population. Current guidelines recommend anticoagulation for specific scenarios. More studies are necessary to elucidate optimal management strategies for newborns with thromboembolic complications.

PMID:37258498 | DOI:10.1542/neo.24-6-e356

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PubMed articles on: Cancer & VTE/PE

Disparities in the Outcomes of Acute Pulmonary Embolism in Hospitalized Patients with Hematologic Malignancy and Solid Tumor

Int Heart J. 2023;64(3):432-441. doi: 10.1536/ihj.22-704.

ABSTRACT

This study aimed to compare the clinical burden and healthcare utilization outcomes of hematologic versus solid malignancies in patients hospitalized with acute pulmonary embolism (PE). This population-based, retrospective study extracted and analyzed the discharge data from the 2016-2018 US National Inpatient Sample (NIS) of hospitalized patients with a primary diagnosis of acute PE and a subsequent diagnosis of hematologic malignancies or solid tumors. Prolonged length-of-stay (LOS) was defined as ≥75th percentile LOS of the study cohort. Unfavorable discharge was defined as discharged to nursing home or long-term facility. Univariate and multivariate regression analyses were conducted to determine associations between cancer type, presence of unstable PE, and in-hospital outcomes in acute PE patients. Patients with acute PE with solid tumors had higher rates of in-hospital deaths and unfavorable discharge than those with hematologic malignancies (6.4% versus 3.2%, P < 0.001; 14.0% versus 11.2%, P = 0.01, respectively). Acute PE patients with hematologic malignancies had a lower risk of in-hospital death (aOR: 0.43, 95% CI: 0.31-0.60), unfavorable discharge (aOR: 0.76, 95% CI: 0.63-0.92), and prolonged LOS (aOR: 0.83, 95% CI: 0.71-0.98) than those with solid tumors. Stratified analysis showed that male patients aged <60

PMID:37258119 | DOI:10.1536/ihj.22-704

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PubMed articles on: Cancer & VTE/PE

Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor

Thromb Haemost. 2023 May 31. doi: 10.1055/s-0043-1769609. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancers. The risk factors and pathophysiological mechanisms of venous thromboembolic events (VTEs) of this new therapeutic class are still to be specified.

METHODS: The included patients had to have cancer and should be treated with ICI. Data analyzed included demographic data, biological data, and immune-related adverse events (IRAEs). We studied the prevalence of VTEs and the factors associated with VTEs.

RESULTS: Of 374 patients on ICI, over a median follow-up period of 15.2 months, the number of VTE was 50 (13.4%). The majority of patients were treated for metastatic melanoma or nonsmall cell lung cancer. There was no difference in prevalence or survival between cancer types. Patients with combined therapy composed of nivolumab and ipilimumab had higher 1-year cumulative VTE occurrence (29.3% [95% confidence interval [CI]: 9.7; 44.6]) than patients with pembrolizumab (14.9%, [95%CI: 2.5; 25.8], p= 0.03) or nivolumab (9.1%, [95% CI: 5.0; 12.9], p< 0.01). The presence of IRAE was associated with a higher risk of VTE occurrence compared with patients without any IRAE (1-year VTE cumulative incidence: 17.42% [95% CI: 9.5; 24.65] vs. 9.46% [95% CI: 5.18; 13.55], p= 0.04). There was a higher risk of VTE in patients treated with the combination of nivolumab and ipilimumab (adjusted subdistribution hazard ratio [SHR]: 3.71 [95% CI: 1.74; 7.90], p< 0.001) and in patients with IRAE (adjusted SHR: 2.14 [95% CI: 1.22; 3.75], p< 0.01).

CONCLUSION: The prevalence of VTE was 14.2% under ICIs. IRAE and combine treatment of nivolumab and ipilimumab were associated with VTE. The pathophysiological mechanisms are multiple and complex with a possible link to aberrant activation of the immune system.

PMID:37257835 | DOI:10.1055/s-0043-1769609

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PubMed articles on: Cancer & VTE/PE

A systemic review and meta-analysis of Aflibercept plus FOLFIRI regimen as a second-line treatment for metastatic colorectal cancer: A PRISMA compliant pooled analysis of randomized controlled trials and single arm studies to assess efficacy and safety

Crit Rev Oncol Hematol. 2023 May 29:104034. doi: 10.1016/j.critrevonc.2023.104034. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium, fluorouracil, irinotecan hydrochloride) chemotherapy regime, was FDA approved in 2012 as second-line salvage chemotherapy for metastatic colorectal cancer (mCRC). This is the first systematic review, and meta-analysis-based evidence to determine the efficacy and safety of Aflibercept plus FOLFIRI regimen pooling randomized controlled trials and single-arm studies.

METHOD: PubMed, Cochrane library, Embase, and Clinical trial.gov were systematically searched for published randomized controlled trials, single-arm studies, and national patient programs on aflibercept plus FOLFIRI chemotherapy for the treatment of mCRC till 11/10/2022.

RESULT: Ten studies met the inclusion criteria comprising 1075 patients for efficacy studies and 2027 patients for safety studies. The pooled prevalences were 18% (95% CI, 5%-37%, p = 0.00) for 12m PFS and 61% (95% CI, 53% - 68%, p = 0.00) for 12m OS. The pooled prevalences were 69% (95% CI, 55% - 82%, p = 0.00) for any grade 3-4 toxicities, 10% (95% CI, 5% - 16%, p = 0.00) for grade 3-4 diarrhea, 13% (95% CI, 5% - 24%, p = 0.00) for grade 3-4 hypertension, 31% (95% CI, 22% - 40%, p = 0.00) for grade 3-4 neutropenia and 5% (95% CI, 2% - 7%, p = 0.00) for grade 3-4 venous thromboembolic event.

CONCLUSION: Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events.

PMID:37257732 | DOI:10.1016/j.critrevonc.2023.104034

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PubMed articles on: Cancer & VTE/PE

Thrombotic Risk Assessment in Patients with Lymphoid Neoplasm seen at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State

West Afr J Med. 2023 May 27;40(5):533-540. ABSTRACTBACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated.

OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer.

METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23.

RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001).

CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events.

CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d’évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d’une thromboprophylaxie. Les scores de risque des patients dans notre environnement n’ont pas été étudiés de manière adéquate.

OBJECTIF: L’étude évalue l’association des scores d’évaluation du risque thrombotique (en utilisant l’outil modifié d’évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d’un cancer lymphoïde.

MÉTHODES: Il s’agit d’une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d’Anambra). Quarante-cinq patients atteints d’un cancer lymphoïde et 45 sujets apparemment sains ont participé à l’étude. Le score modifié d’évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l’estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23.

RÉSULTATS: L’âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que l[...]

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PubMed articles on: Cancer & VTE/PE

Evaluation of Patient Characteristics Linked to Major Bleeding Events in Patients Prescribed Direct Oral Anticoagulants

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231172765. doi: 10.1177/10760296231172765.