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BACKGROUND: Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. OBJECTIVES: To assess the effect of female sex on the development of incident heart failure (HF) in adult patients treated with anthracyclines. METHODS: This was a retrospective cohort study of 1525 adult patients with no prior history of HF or cardiomyopathy who were treated with anthracyclines between 1992 and 2019. The primary outcome was new HF within 5 years of the first dose of anthracyclines. The effect of sex was assessed using Cox proportional hazards and competing risk models. RESULTS: Over a median (IQR) follow-up of 1.02 (0.30-3.01) years, 4.78% of patients developed HF (44 men and 29 women). Female sex was not associated with the primary outcome in a multivariable Cox proportional hazards model (HR 0.87; 95% CI 0.53-1.43; Pâ¯=â¯0.58). Similar results were observed in a multivariable model accounting for the competing risk of death (HR 0.94; 95% CI 0.39-2.25; Pâ¯=â¯0.88). Age, coronary artery disease and hematopoietic stem cell transplant were associated with the primary outcome in a multivariable Cox proportional hazards model. Age and body mass index were associated with the primary outcome in a multivariable competing risk model. CONCLUSIONS: In this large, single-center, retrospective cohort study, female sex was not associated with incident HF in adult patients treated with anthracyclines. CONDENSED ABSTRACT: Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. In this retrospective cohort study, we assessed the effect of female sex on the development of incident heart failure in adult patients treated with anthracyclines. Using Cox proportional hazards and competing risk regression models, we found that there was no association between female sex and heart failure after treatment with anthracyclines.
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Background: Anthracyclines are effective chemotherapies that are limited by cardiotoxicity. The spatial ventricular gradient (SVG) is a marker of electrical heterogeneity linked to adverse cardiovascular outcomes, including sudden cardiac death and heart failure (HF). Objectives: The purpose of this study was to assess if SVG values before chemotherapy are associated with the risk of anthracycline-associated HF or cardiomyopathy (CM). Methods: We analyzed 12-lead electrocardiograms obtained within 6 months before initiation of anthracyclines in a retrospective cohort treated for cancer between 1992 and 2019 at a single academic medical center. Incident HF and CM were defined by ICD-9/10 codes and confirmed by chart review. Vectorcardiograms were constructed from baseline electrocardiograms, and the SVG was calculated. The cumulative incidence of anthracycline-associated HF or CM was regressed on SVG vector orientation and magnitude with death as a competing risk. Results: In 889 patients (47% male; mean age 58 ± 16 years; 71% hematologic malignancies), larger SVG magnitude prechemotherapy was associated with decreased risk of HF or CM after multivariable adjustment, with a subhazard ratio of 0.76 per 1 SD increase (95% CI: 0.59-0.96; P = 0.024). SVG vector orientation, specifically a more leftward oriented VGx, was associated with decreased risk of HF or CM with a subhazard ratio of 0.77 per 1 SD increase (95% CI: 0.61-0.96; P = 0.023). Conclusions: Larger SVG magnitude and more leftward SVG orientation were associated with a decreased risk of anthracycline cardiotoxicity in a large retrospective cohort. Improved cardiac risk stratification algorithms incorporating the SVG could personalize both cancer and cardioprotective therapy.
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BACKGROUND: The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS: In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS: We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p < .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION: Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity.
