ABSTRACT

Gefitinib (GEF) may increase the risk of corrected QT prolongation (QTc). We aimed to evaluate whether gefitinib increases the risk of corrected QT interval (QTc) prolongation and analyze the associated risk factors.A total of 122 cases of advanced EGFR-mutated non-small cell lung cancer (NSCLC) who received gefitinib therapy from January 2015 to December 2020 were evaluated. The results of at least two resting 12-lead electrocardiogram before and after gefitinib treatment were obtained. The Bazett and Fridericia formulas were used to calculate the QTc interval, and the changes of QTc interval values before and after treatment were evaluated. The correlation between gefitinib and QTc interval prolongation and related risk factors were analyzed.After gefitinib-targeted therapy, 23 patients (18.9%) had a prolonged QTc interval, which increased from a mean of 446 ± 25 ms at baseline to 478 ± 18 ms (P < 0.001). Three of the patients met criteria for Grade 3 QTc prolongation in the common term V5.0 for clinical adverse events. Univariate analysis showed that age (ORR, 1.054; 95% confidence interval [CI], 1.003-1.107; P = 0.038), history of hypertension (ORR, 3.409; 95% CI, 1.334-8.713; P = 0.01), CCB medication history (ORR, 0.259; 95% CI, 0.094-0.712; P = 0.009), history of lung cancer surgery (ORR, 0.231; 95% CI, 0.064-0.829; P = 0.025), and baseline QT interval (ORR, 0.978; 95% CI, 0.964-0.993; P = 0.004) were important predictors of QTc interval prolongation in patients treated with gefitinib. The results of multivariate analysis showed that the history of lung cancer surgery and the baseline QT interval were important factors affecting QTc interval prolongation in patients treated with gefitinib.Gefitinib increases the risk of QTc prolongation in NSCLC patients, which may be more pronounced in patients with advanced age, hypertension, CCB therapy, lung cancer surgery, and a long QT interval at baseline.

PMID:37258113 | DOI:10.1536/ihj.22-583

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PubMed articles on: Cardio-Oncology

Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series

J Immunother Cancer. 2023 May;11(5):e004792. doi: 10.1136/jitc-2022-004792.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening.

METHODS: We conducted a multicenter cross-sectional retrospective study with the aim of better characterizing ICI-related myocarditis. Myocarditis diagnosis was based on the recent consensus statement of the International Cardio-Oncology Society.

RESULTS: Twenty-nine patients were identified, from six different referral centers. Most patients (55%) were treated using anti-programmed-death 1, rather than ICI combination (35%) or anti-programmed-death-ligand 1 (10%). Transthoracic echocardiography was abnormal in 52% of them, and cardiac magnetic resonance showed abnormal features in 14/24 patients (58%). Eleven patients (38%) were classified as severe. Compared with other patients, they had more frequently pre-existing systemic autoimmune disease (45% vs 6%, p=0.018), higher troponin level on admission (42-fold the upper limit vs 3.55-fold, p=0.001), and exhibited anti-acetylcholine receptor autoantibodies (p=0.001). Seven patients (24%) had myocarditis-related death, and eight more patients died from cancer progression during follow-up. Twenty-eight patients received glucocorticoids, 10 underwent plasma exchanges, 8 received intravenous immunoglobulins, and 5 other immunosuppressants. ICI rechallenge was performed in six patients, with only one myocarditis relapse.

DISCUSSION: The management of ICI-related myocarditis may be challenging and requires a multidisciplinary approach. Prognostic features are herein described and may help to allow ICI rechallenge for some patients with smoldering presentation, after an accurate evaluation of benefit-risk balance.

PMID:37258037 | DOI:10.1136/jitc-2022-004792

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PubMed articles on: Cardio-Oncology

Dapagliflozin May Protect Against Doxorubicin-Induced Cardiotoxicity

Anatol J Cardiol. 2023 Jun;27(6):339-347. doi: 10.14744/AnatolJCardiol.2023.2825.

ABSTRACT

BACKGROUND: Doxorubicin is a widely used agent in the treatment of cancer, but the cardiotoxicity associated with this drug limits its potential for use. The cardioprotective effects of dapagliflozin, an antidiabetic drug, have the potential to counteract the cardiotoxic effect of doxorubicin therapy. In our study, we aimed to investigate the protective effect of dapagliflozin from possible doxorubicin-induced cardiotoxicity.

METHODS: A total of 40 male Wistar albino rats were divided into 4 groups consisting of 10 each (control = 10, dapagliflozin = 10, doxorubicin = 10, doxorubicin + dapagliflozin = 10). Meanwhile, doxorubicin and doxorubicin + dapagliflozin groups received a total dose of 15 mg/kg doxorubicin intraperitoneally, dapagliflozin and doxorubicin + dapagliflozin groups were gavaged daily with 10 mg/kg dapagliflozin. At the sixth week of the study, rats were examined by echocardiography and electrocardiogram. Furthermore, histopathological method was used to evaluate the level of cardiotoxicity.

RESULTS: Ejection fraction decreased by 15% in the doxorubicin group, and this reduction in ejection fraction was alleviated in the doxorubicin + dapagliflozin group. In addition, a 65% increase in QRS duration was observed in the group given doxorubicin, while an increase of 7% was observed in doxorubicin + dapagliflozin group. Corrected QT duration increased by 12% in the doxorubicin group, compared to 2% in doxorubicin + dapagliflozin group. Meanwhile, sarco-myolysis, inflammatory cell infiltration, and necrotic changes were examined heavily in doxorubicin group, they were minimal in doxorubicin + dapagliflozin group.

CONCLUSION: Our study showed that dapagliflozin has the potential to reduce the effects of doxorubicin-induced cardiotoxicity.

PMID:37257007 | DOI:10.14744/AnatolJCardiol.2023.2825

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PubMed articles on: Cardio-Oncology

Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer

JAMA Cardiol. 2023 May 31. doi: 10.1001/jamacardio.2023.1229. Online ahead of print.

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

Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - a nationwide database analysis from Hungary

Diabetes Res Clin Pract. 2023 May 29:110734. doi: 10.1016/j.diabres.2023.110734. Online ahead of print.