Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity

Goel, Shom; Liu, Jia; Guo, Hao; Barry, William T.; Bell, Richard H.; Murray, Bronwyn; Lynch, Jodi; Bastick, Patricia; Chantrill, Lorraine A.; Kiely, Belinda E; Abdi, Ehtesham; Rutovitz, J.; Asghari, Ray; Sullivan, A.; Harrison, Michelle; Kohonen‐Corish, Maija; Beith, Jane

doi:10.1016/j.jchf.2019.04.014

Cited by 34 publications

(56 citation statements)

References 29 publications

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“…In the initial trastuzumab studies, heart failure and LV dysfunction were observed in up to 30% of patients [126]. Due to improvements in the selection of patients, optimised therapy modalities and cardiac monitoring during therapy, event frequencies of less than 10% for trastuzumab [48] and even lower frequencies in the case of pertuzumab, emtansine and lapatinib are observed today [61]. The most important risk factors for trastuzumab-associated cardiotoxicity are prior or concurrent anthracycline therapy or a pre-existing reduced LVEF [104].…”

Section: Her2 Inhibitors/egf2-dependent Therapeuticsmentioning

confidence: 99%

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology

et al. 2020

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The acute and long-lasting side effects of modern multimodal tumour therapy significantly impair quality of life and survival of patients afflicted with malignancies. The key components of this therapy include radiotherapy, conventional chemotherapy, immunotherapy and targeted therapies. In addition to established tumour therapy strategies, up to 30 new therapies are approved each year with only incompletely characterised side effects. This consensus paper discusses the risk factors that contribute to the development of a potentially adverse reaction to tumour therapy and, in addition, defines specific side effect profiles for different treatment groups. The focus is on novel therapeutics and recommendations for the surveillance and treatment of specific patient groups.

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Section: Her2 Inhibitors/egf2-dependent Therapeuticsmentioning

confidence: 99%

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology

et al. 2020

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“…Recently, Rocco et al reported that standard troponin values in younger patients and women were much lower compared with older patients and men [59]. This may be especially significant in breast cancer patients as it affects women of all ages (including the young) where high-dose protocols and combination chemotherapy treatments are used [38,45,60]. Moreover, it has also been postulated that sex hormones, specifically estrogen, could influence the pathophysiological mechanisms involved in anthracycline-induced cardiotoxicity [61].…”

Section: Ctns Assays and Considerationsmentioning

confidence: 99%

Cardiac Biomarkers in Patients with Cancer: Considerations, Clinical Implications, and Future Avenues

et al. 2020

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Purpose of the Review As the number of cancer survivors increases due to early screening and modern (antineoplastic) treatments, cancer treatment associated cardiotoxicity (CTAC) is becoming an increasing health burden that affects survival and quality of life among cancer survivors. Thus, clinicians need to identify adverse events early, in an effort to take suitable measures before the occurrence of permanent or irreversible cardiac dysfunction. Recent Findings Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) have been proven to detect subclinical cardiotoxicity during antineoplastic treatment. As such, these cardio-specific biomarkers could predict which patients are at risk of developing CTAC even before the start of therapy. Nevertheless, there are inconsistent data from published studies, and the recommendations regarding the use of these biomarkers and their validity are mostly based on expert consensus opinion. Summary In this review, we summarize available literature that evaluates biomarkers of CTAC, and we encourage strategies that integrate circulating biomarkers and cardiac imaging in identifying cancer patients that are at high risk.

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“…It has been widely demonstrated that NT-proBNP and hs-TnT levels increase during cancer therapy, although their utility for cardiotoxicity prediction has been recently questioned [19,[23][24][25]. In this study,…”

Section: Discussionmentioning

confidence: 87%

“…Early subclinical cardiotoxicity was de ned as a relative decrease in 2D global longitudinal strain (GLS, as assessed by speckle-tracking analysis) > 15% versus baseline [18], and established cardiotoxicity as an asymptomatic decrease in LVEF > 15% or an asymptomatic decrease of LVEF > 10% to an absolute value < 53% versus baseline [18,19].…”

Section: Study Protocolmentioning

confidence: 99%

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

Adl

Santisteban

Lupón

et al. 2020

Preprint

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Background Anthracycline-based cancer chemotherapy (ACC) has been related to myocardial interstitial fibrosis (MIF), a lesion contributing to left ventricular dysfunction (LVD). We investigated whether biomarker-assessed MIF was associated with LVD in patients with breast cancer receiving ACC and in patients with ACC-induced heart failure (ACC-HF). Moreover, chemotherapy agent’s pro-fibrotic activity was evaluated in human cardiac fibroblasts (HCFs). Methods Echocardiography, serum biomarkers of collagen deposition (procollagen type-I C-terminal-propeptide [PICP]) and crosslinking (collagen type-I C-terminal-telopeptide/matrix metalloproteinase-1 ratio), and biomarkers of myocardial and vascular stress (galectin-3, sST2, amino-terminal pro-brain natriuretic peptide [NT-proBNP], hs-troponin-T and vascular cell adhesion molecule-1 [VCAM-1]) were assessed in 70 breast cancer patients at baseline, and during ACC at 3 and 6 months. Subclinical cardiotoxicity was defined as global longitudinal strain (GLS) relative reduction>15%. In addition, PICP and NT-proBNP were determined in 347 patients with different HF etiologies, 37 with ACC-HF (of whom 65% had been diagnosed with breast cancer) and 12-month-follow-up LVEF assessment. HCFs activation was examined after incubation with doxorubicin, cyclophosphamide, paclitaxel and trastuzumab for 24 hours. Results In patients with breast cancer, six-months-ACC reduced GLS and upregulated PICP, hs-troponin-T, NT-proBNP and VCAM-1 (P<0.01) versus baseline. At 6 months, elevation of PICP was higher in patients with subclinical cardiotoxicity versus the remaining patients (P for interaction<0.001). PICP levels were directly and independently associated with a relative reduction in GLS (P<0.001). In ACC-HF patients, baseline LVEF was inversely associated with PICP and NT-proBNP (P<0.01). After 12 months, LVEF did not change in patients with higher basal PICP (3rd tertile) but improved in the remaining patients (P<0.001). Doxorubicin, cyclophosphamide and trastuzumab stimulated collagen synthesis in HCFs. Conclusion These results indicate that biomarker-assessed MIF associates with early LVD in ACC-treated patients with breast cancer. In addition, these findings suggest that MIF may be associated with established LVD in ACC-HF patients, hindering LV functional improvement after 12 months. Finally, chemotherapy can directly activate collagen metabolism in HCFs.

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Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity

Cited by 34 publications

References 29 publications

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology

Cardiac Biomarkers in Patients with Cancer: Considerations, Clinical Implications, and Future Avenues

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

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