Cardiac dysfunction from cancer and cancer therapy: new pathways for the prevention of late cardiotoxicity

AbstractLeft ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04–9.97; p = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.

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Very early detection of low dose anti-cancer therapy-related cardiotoxicity in lymphoma patients

European Heart Journal ◽

10.1093/ehjci/ehaa946.3257 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y.W Liu ◽

H.Y Chang ◽

C.H Lee ◽

W.C Tsai ◽

P.Y Liu ◽

...

Keyword(s):

Heart Failure ◽

Cancer Therapy ◽

Cardiac Dysfunction ◽

Systolic Dysfunction ◽

Multivariable Analysis ◽

Cardiopulmonary Exercise Test ◽

Left Ventricular ◽

Funding Source ◽

Anti Cancer ◽

All Cause Mortality

Abstract Background and purpose Left ventricular (LV) global peak systolic longitudinal strain (GLS) by speckle-tracking echocardiography is a sensitive modality for the detection of subclinical LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving anti-cancer therapy remains unknown. Methods We prospectively enrolled 74 patients (57.9±17.0 years old, 57% male) with lymphoma who underwent echocardiography prior to chemotherapy, post 3rd and 6th cycle and 1 year after chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) is defined as the reduction of absolute GLS value from baseline of ≥15%. All the eligible patients underwent a cardiopulmonary exercise test (CPET) upon completion of 3 cycles of anti-cancer therapy. The primary outcome was defined as a composite of all-cause mortality and heart failure events. Results Among 36 (49%) patients with CTRCD, LV GLS was significantly decreased after the 3rd cycle of chemotherapy (20.1±2.6% vs. 17.5±2.3%, p<0.001). In the multivariable analysis, male sex and anemia (hemoglobin <11 g/dL) were found to be independent risk factors of CTRCD. Objectively, patients with CTRCD had lower minute oxygen consumption/kg (VO2/kg) and lower VO2/kg value at anaerobic threshold in the CPET. The incidence of the primary composite outcome was higher in the CTRCD group than in the non-CTRCD group (hazard ratio 3.21; 95% CI, 1.04–9.97; p=0.03). Conclusion LV GLS is capable of detecting early cardiac dysfunction in lymphoma patients receiving anti-cancer therapy. Patients with CTRCD not only had a reduced exercise capacity but also a higher risk of all-cause mortality and heart failure events. Change of LVEF and GLS after cancer Tx Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Ministry of Science and Technology (MOST), Taiwan

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Cardio-oncology — elucidation of the mechanism of cardiac dysfunction caused by cancer therapy and cancer cachexia

Folia Pharmacologica Japonica ◽

10.1254/fpj.19123 ◽

2020 ◽

Vol 155 (3) ◽

pp. 165-170

Author(s):

Miki Nonaka ◽

Susumu Ueno ◽

Yasuhito Uezono

Keyword(s):

Cancer Therapy ◽

Cardiac Dysfunction ◽

Cancer Cachexia

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Cancer therapy-related cardiac dysfunction: is endothelial dysfunction at the heart of the matter?

Clinical Science ◽

10.1042/cs20210059 ◽

2021 ◽

Vol 135 (12) ◽

pp. 1487-1503

Author(s):

Crizza Ching ◽

Dakota Gustafson ◽

Paaladinesh Thavendiranathan ◽

Jason E. Fish

Keyword(s):

Cancer Therapy ◽

Cardiac Dysfunction ◽

Inflammatory Markers ◽

Cancer Survival ◽

Growth Factor Receptor ◽

Cardiovascular Effects ◽

Cardiovascular Complications ◽

Cardiac Biomarkers ◽

Cancer Therapies ◽

The Impact

Abstract Significant improvements in cancer survival have brought to light unintended long-term adverse cardiovascular effects associated with cancer treatment. Although capable of manifesting a broad range of cardiovascular complications, cancer therapy-related cardiac dysfunction (CTRCD) remains particularly common among the mainstay anthracycline-based and human epidermal growth factor receptor-targeted therapies. Unfortunately, the early asymptomatic stages of CTRCD are difficult to detect by cardiac imaging alone, and the initiating mechanisms remain incompletely understood. More recently, circulating inflammatory markers, cardiac biomarkers, microRNAs, and extracellular vesicles (EVs) have been considered as early markers of cardiovascular injury. Concomitantly, the role of the endothelium in regulating cardiac function in the context of CTRCD is starting to be understood. In this review, we highlight the impact of breast cancer therapies on the cardiovascular system with a focus on the endothelium, and examine the status of circulating biomarkers, including inflammatory markers, cardiac biomarkers, microRNAs, and endothelial cell-derived EVs. Investigation of these emerging biomarkers may uncover mechanisms of injury, detect early stages of cardiovascular damage, and elucidate novel therapeutic approaches.

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Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

European Heart Journal ◽

10.1093/eurheartj/ehw022 ◽

2016 ◽

Vol 37 (21) ◽

pp. 1671-1680 ◽

Cited By ~ 274

Author(s):

Geeta Gulati ◽

Siri Lagethon Heck ◽

Anne Hansen Ree ◽

Pavel Hoffmann ◽

Jeanette Schulz-Menger ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Cancer Therapy ◽

Cardiac Dysfunction ◽

Breast Cancer Therapy ◽

Double Blind ◽

Double Blind Clinical Trial ◽

Adjuvant Breast Cancer

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MAKING SURVIVORSHIP MATTER: PREDICTING CANCER THERAPY-RELATED CARDIAC DYSFUNCTION IN WOMEN WITH HER2+ BREAST CANCER THROUGH INTEGRATIVE DIAGNOSTIC APPROACHES

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(20)31297-3 ◽

2020 ◽

Vol 75 (11) ◽

pp. 670

Author(s):

Dakota Gustafson ◽

Crizza Ching ◽

Faisal Alibhai ◽

Natalie Galant ◽

Jason Fish ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Cardiac Dysfunction ◽

Her2 Breast Cancer ◽

Diagnostic Approaches

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Machine Learning–Based Risk Assessment for Cancer Therapy–Related Cardiac Dysfunction in 4300 Longitudinal Oncology Patients

Journal of the American Heart Association ◽

10.1161/jaha.120.019628 ◽

2020 ◽

Vol 9 (23) ◽

Author(s):

Yadi Zhou ◽

Yuan Hou ◽

Muzna Hussain ◽

Sherry‐Ann Brown ◽

Thomas Budd ◽

...

Keyword(s):

Machine Learning ◽

Cancer Therapy ◽

Cancer Patients ◽

Cardiac Dysfunction ◽

De Novo ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Oncology Patients ◽

Relevant Variables ◽

After Cancer

Background The growing awareness of cardiovascular toxicity from cancer therapies has led to the emerging field of cardio‐oncology, which centers on preventing, detecting, and treating patients with cardiac dysfunction before, during, or after cancer treatment. Early detection and prevention of cancer therapy–related cardiac dysfunction (CTRCD) play important roles in precision cardio‐oncology. Methods and Results This retrospective study included 4309 cancer patients between 1997 and 2018 whose laboratory tests and cardiovascular echocardiographic variables were collected from the Cleveland Clinic institutional electronic medical record database (Epic Systems). Among these patients, 1560 (36%) were diagnosed with at least 1 type of CTRCD, and 838 (19%) developed CTRCD after cancer therapy (de novo). We posited that machine learning algorithms can be implemented to predict CTRCDs in cancer patients according to clinically relevant variables. Classification models were trained and evaluated for 6 types of cardiovascular outcomes, including coronary artery disease (area under the receiver operating characteristic curve [AUROC], 0.821; 95% CI, 0.815–0.826), atrial fibrillation (AUROC, 0.787; 95% CI, 0.782–0.792), heart failure (AUROC, 0.882; 95% CI, 0.878–0.887), stroke (AUROC, 0.660; 95% CI, 0.650–0.670), myocardial infarction (AUROC, 0.807; 95% CI, 0.799–0.816), and de novo CTRCD (AUROC, 0.802; 95% CI, 0.797–0.807). Model generalizability was further confirmed using time‐split data. Model inspection revealed several clinically relevant variables significantly associated with CTRCDs, including age, hypertension, glucose levels, left ventricular ejection fraction, creatinine, and aspartate aminotransferase levels. Conclusions This study suggests that machine learning approaches offer powerful tools for cardiac risk stratification in oncology patients by utilizing large‐scale, longitudinal patient data from healthcare systems.

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