ABSTRACT

BACKGROUND: This study aimed to investigate the prevalence, clinical characteristics and outcomes of type 2 myocardial infarction (T2AMI) in patients with versus without cancer.

METHODS: All hospitalizations with a primary discharge diagnosis of T2AMI were stratified according to cancer status (secondary diagnosis of any-cancer vs cancer-free) using data from the US National Inpatient Sample (2016-2019). The primary outcome was in-hospital all-cause mortality while secondary outcomes were in-hospital major adverse cardiovascular and cerebrovascular events (MACCE).

RESULTS: Among 61,305 included hospitalizations with primary diagnosis of T2AMI, 3745 (6.1%) were associated with a diagnosis of cancer. Patients with T2AMI and cancer presented more frequently with acute respiratory failure (23.2% vs 18.1%), acute pulmonary embolism (3.7% v 1.3%), major bleeding (6.8% vs 4.1%) and renal failure (51.0% vs 46.8%), compared to patients without. On adjusted analysis, diagnosis of cancer was associated with lower odds of invasive coronary angiography (aOR 0.75, 95% CI 0.60 to 0.93, p = 0.009) but greater odds of mortality (aOR 1.95, 95% C.I. 1.26-2.99 p = 0.002). Among the different types of cancer, adjusted risk of all-cause mortality was higher in patients with colorectal (aOR 4.17 95% CI 1.68-10.32, p = 0.002), lung (aOR 3.63, 95% CI 1.83-7.18, p < 0.001) and haematologic (aOR 2.48, 95% CI 1.22-5.05, p = 0.001) cancer.

CONCLUSIONS: Patients with cancer presenting with T2AMI have lower odds of management with invasive diagnostic coronary angiography and have higher rates of in-hospital all-cause death. Further studies are warranted to improve overall care and outcomes of cancer patients and cardiovascular diseases.

PMID:37442352 | DOI:10.1016/j.ijcard.2023.131154

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PubMed articles on: Cardio-Oncology

Penpulimab-induced complete atrioventricular block in a patient with metastatic renal cancer

HeartRhythm Case Rep. 2023 Apr 23;9(7):451-455. doi: 10.1016/j.hrcr.2023.04.007. eCollection 2023 Jul.

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PMID:37492041 | PMC:PMC10363469 | DOI:10.1016/j.hrcr.2023.04.007

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PubMed articles on: Cardio-Oncology

Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer

Curr Cardiol Rep. 2023 Jul 25. doi: 10.1007/s11886-023-01909-3. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy.

RECENT FINDINGS: While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.

PMID:37490155 | DOI:10.1007/s11886-023-01909-3

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PubMed articles on: Cardio-Oncology

Identification and protection of early cardiotoxicity in acute myeloid leukemia patients undergoing transplantation

Hematology. 2023 Dec;28(1):2239569. doi: 10.1080/16078454.2023.2239569.

ABSTRACT

Cardiotoxicity of antitumor therapy results in declining survival rates. More specifically, cardiotoxicity is positively correlated with cumulative dose of anthracyclines and eventually develops from reversible to irreversible. In this context, early monitoring methods should be explored for the timely detection of cardiotoxicity and cardioprotective therapy should be performed in patients under consideration for potentially cardiotoxic therapy. This paper reports a 22-year-old male patient with acute myeloid leukemia who underwent whole-course cardiac monitoring after receiving antileukemia therapy. After the early detection of an asymptomatic decrease in left ventricular ejection fraction (LVEF), along with a significant decrease in global longitudinal strain (GLS), the patient was treated with sacubitril/valsartan (Sac/Val). Finally, the patient completed four courses of chemotherapy and subsequent hematopoietic stem cell transplantation as planned. The measurements of LVEF and GLS also recovered after 2 months treatment of Sac/Val. Therefore, the early identification and protection of patients with cardiotoxicity are of paramount importance and future prospective studies are expected to develop the management and treatment of cancer treatment-related cardiac dysfunction.

PMID:37489927 | DOI:10.1080/16078454.2023.2239569

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PubMed articles on: Cardio-Oncology

Therapeutic potential of extracellular vesicles derived from cardiac progenitor cells in rodent models of chemotherapy-induced cardiomyopathy

Front Cardiovasc Med. 2023 Jul 7;10:1206279. doi: 10.3389/fcvm.2023.1206279. eCollection 2023.

ABSTRACT

BACKGROUND: Current treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy. We assessed whether repeated intravenous injections of human extracellular vesicles from cardiac progenitor cells (EV-CPC) could represent a new therapeutic option and whether EV manufacturing according to a Good Manufacturing Practices (GMP)-compatible process did not impair their bioactivity.

METHODS: Immuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4 mg/kg each; cumulative dose: 12 mg/kg) and were then intravenously (IV) injected three times with EV-CPC (total dose: 30 billion). Cardiac function was assessed 9-11 weeks later by cardiac magnetic resonance imaging (CMR) using strain as the primary end point. Then, immuno-competent rats received 5 IP injections of DOX (3 mg/kg each; cumulative dose 15 mg/kg) followed by 3 equal IV injections of GMP-EV (total dose: 100 billion). Cardiac function was assessed by two dimensional-echocardiography.

RESULTS: In the chronic mouse model of CCM, DOX + placebo-injected hearts incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with sham DOX-untreated mice (p = 0.043, p= 0.042, p= 0.048 respectively) while EV-CPC preserved these indices. Global longitudinal strain followed a similar pattern. In the rat model, IV injections of GMP-EV also preserved left ventricular end-systolic and end-diastolic volumes compared with untreated controls.

CONCLUSIONS: Intravenously-injected extracellular vesicles derived from CPC have cardio-protective effects which may make them an attractive user-friendly option for the treatment of CCM.

PMID:37485274 | PMC:PMC10360184 | DOI:10.3389/fcvm.2023.1206279

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PubMed articles on: Cardio-Oncology

DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes

Noncoding RNA. 2023 Jul 13;9(4):39. doi: 10.3390/ncrna9040039.

ABSTRACT

Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called cardio-oncology. Doxorubicin is a chemotherapy drug widely used to treat cancer, such as bladder and breast cancer. However, this drug causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. Based on this evidence, we hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. To test this hypothesis, we analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. To confirm these findings, we treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB.

PMID:37489459 | PMC:PMC10366827 | DOI:10.3390/ncrna9040039

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PubMed articles on: Cardio-Oncology

Clinical characteristics of patients referred to cardio-oncology clinic

Zhonghua Yi Xue Za Zhi. 2023 Jul 25;103(28):2183-2186. doi: 10.3760/cma.j.cn112137-20221108-02348.

ABSTRACT

To explore characteristics of outpatients in a single cardio-oncology clinic, patients visiting cardio-oncology clinic of Fuwai Hospital CAMS&PUMC (Beijing, China) from January 2020 to December 2021 were analyzed retrospectively. In total, 330 patients were included, the median age (Q1, Q3) was 58(46, 66) years, and there were 192 females (58.2%). The purposes for visit included an evaluation and treatment of cardiovascular adverse reactions (n=247, 74.8%), pre-antitumor therapy assessment (n=51, 15.5%), and management of primary or metastatic cardiac tumors (n=32, 9.7%). For patients with cardiovascular adverse reactions, the most common tumor type was breast cancer (n=88, 29.5%), followed by gastrointestinal cancer (n=70, 23.5%), and hematological cancers (n=62, 20.8%). Among them, 236 cases (95.5%) had received antitumor drugs in the past; 38 cases (15.4%) had a history of chest radiotherapy; some cases were complicated with hypertension (n=69, 23.2%) and/or hyperlipidemia (n=69, 23.2%); 42 cases (14.1%) had a history of coronary heart disease; and 16 cases (5.4%) were complicated with atrial fibrillation or flutter. Among 32 patients with cardiac tumors, 11 cases (34.4%) had primary malignant tumors; 6 cases (18.8%) had benign tumors; 2 cases (6.3%) had metastatic tumors; and 13 (40.6%) had unknown pathological types. This study explores the epidemiology of cardio-oncology in China and provides clinical insights for the future development of cardio-oncology. In the future, it is still necessary to study the benefits of cardio-oncology clinics and develop standardized indicators to evaluate their benefits.

PMID:37482731 | DOI:10.3760/cma.j.cn112137-20221108-02348

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PubMed articles on: Cardio-Oncology

Acetylcholine receptor agonists effectively attenuated multiple program cell death pathways and improved left ventricular function in trastuzumab-induced cardiotoxicity in rats

Life Sci. 2023 Jul 22;329:121971. doi: 10.1016/j.lfs.2023.121971. Online ahead of print.

ABSTRACT

AIMS: Cardiotoxicity is a seriously debilitating complication of trastuzumab (TRZ) therapy in patients with cancer as a consequence of overexpression of the human epidermal growth factor receptor 2. Although most TRZ-induced cardiotoxicity (TIC) cases are reversible, some patients experience chronic cardiac dysfunction, and these irreversible concepts may be associated with cardiomyocyte death. Acetylcholine receptor (AChR) activation has been shown to exert cardioprotection in several heart diseases, but the effects of AChR agonists against TIC have not been investigated.

MAIN METHOD: Forty adult male Wistar rats were randomized into 5 groups: (i) CON (0.9 % normal saline), (ii) TRZ (4 mg/kg/day), (iii) TRZ + α7nAChR agonist (PNU-282987: 3 mg/kg/day), (iv) TRZ + mAChR agonists (bethanechol: 12 mg/kg/day), and (v) TRZ + combined treatment (Combined PNU-282987 and bethanechol).

KEY FINDINGS: The progression of TIC was driven by mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including by pyroptosis, ferroptosis, and apoptosis, which were significantly alleviated by α7nAChR and mAChR agonists. Interestingly, necroptosis was not associated with development of TIC. More importantly, the in vitro study validated the cytoprotective effects of AChR activation in TRZ-treated H9c2 cells, while not interfering with the anticancer properties of TRZ. All of these findings indicated that TRZ induced mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including pyroptosis, ferroptosis, and apoptosis, leading to impaired cardiac function. These pathological alterations were attenuated by α7nAChR and mAChR agonists.

SIGNIFICANCE: α7nAChR and mAChR agonists might be used as a future therapeutic target in the mitigation of TIC.

PMID:37482212 | DOI:10.1016/j.lfs.2023.121971

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PubMed articles on: Cardio-Oncology

Interventional cardiology in cancer patients: A position paper from the Portuguese Cardiovascular Intervention Association and the Portuguese Cardio-Oncology Study Group of the Portuguese Society of Cardiology

Rev Port Cardiol. 2023 Jul 21:S0870-2551(23)00382-7. doi: 10.1016/j.repc.2023.04.013. Online ahead of print.

ABSTRACT

The field of Cardio-Oncology has grown significantly, especially during the last decade. While the awareness for cardiotoxicity due to cancer disease and/or therapies has greatly increased, much of the attention has focused on myocardial systolic disfunction and heart failure. However, coronary and structural heart disease are also a common issue in cancer patients, and encompass the full spectrum of cardiotoxicity. While invasive intervention, either percutaneous or surgical, is often needed or considered in cancer patients, limited evidence or guidelines are available for dealing with coronary or structural heart disease. The Society for Cardiovascular Angiography and Interventions consensus document published in 2016 is the most comprehensive document regarding this particular issue, but relevant evidence has emerged since, which render some of its considerations outdated. In addition to that, the recent 2022 ESC Guidelines on Cardio-Oncology only briefly discuss this topic.As a result, the Portuguese Association of Cardiovascular Intervention and the Cardio-Oncology Study Group of the Portuguese Society of Cardiology have partnered to produce a Position Paper to address the issue of Cardiac Intervention in cancer patients, focusing on percutaneous techniques. A brief review of available evidence is provided, followed by practical considerations. These are based both on the literature as well as accumulated experience with these types of patients, as the authors are either interventional cardiologists, cardiologists with experience in the field of Cardio-Oncology, or both.

PMID:37482119 | DOI:10.1016/j.repc.2023.04.013

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Incidence of interstitial lung disease and cardiotoxicity with trastuzumab deruxtecan in breast cancer patients: a systematic review and single-arm meta-analysis

ESMO Open. 2023 Jul 21;8(4):101613. doi: 10.1016/j.esmoop.2023.101613. Online ahead of print.

ABSTRACT

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd.

MATERIALS AND METHODS: We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software.

RESULTS: We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%).

CONCLUSIONS: In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.

PMID:37481956 | DOI:10.1016/j.esmoop.2023.101613

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PubMed articles on: Cardio-Oncology

Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies

Cardiovasc Toxicol. 2023 Jul 21. doi: 10.1007/s12012-023-09800-x. Online ahead of print.