Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease

Abstract

OBJECTIVES The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. BACKGROUND Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. METHODS A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. RESULTS At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (β = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 - ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. CONCLUSIONS A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036) (J Am Coll Cardiol Img 2018;11:1045–55) © 2018 by the American College of Cardiology Foundation.

Rapid atrophy of cardiac left ventricular mass in patients with non‐small cell carcinoma of the lung

“…However, there is a literature on cardiotoxic chemotherapy to draw on, especially anthracyclines, which are among the most prominent of the cardiotoxic agents. Anthracyclines cause clinically important reduction in LVEF and cardiac atrophy . We tried to choose a treatment regimen with minimal cardiotoxicity (carboplatin‐based); however, there is always a possibility of some cardiotoxicity.…”

“…Anthracyclines cause clinically important reduction in LVEF and cardiac atrophy. [8][9][10] We tried to choose a treatment regimen with minimal cardiotoxicity (carboplatin-based); however, there is always a possibility of some cardiotoxicity. All patients in our sample received the same carboplatin dose; however, while there was variation in the second agent (gemcitabine, pemetrexed, vinorelbine, or paclitaxel) neither loss of LVM not decline in GLS associated with these different agents (P=0.7) (data not shown).…”

“…bed rest and use of ventricular assist devices) and in anorexia nervosa . There are a few studies showing cardiac atrophy in cancer patients receiving highly cardiotoxic chemotherapy . There have been no prospective longitudinal studies designed to determine whether human cancer cachexia is associated with cardiac atrophy over time.…”

Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18F-Labeled Lipophilic Cations

“…Another possibility is a reduction in blood flow due to cardiac atrophy, which has been shown in humans and rodents after prolonged exposure to DOX. 35,36 While we cannot definitively rule this out as a contributor, a similar DOX study showed no response in perfusion tracer 99m Tc-NOET, implying no alteration in perfusion, but observing significant decrease in 99m Tc-Sestamibi (also a lipophilic cation). 18 The lack of comparison to other perfusion tracers is, however, a limitation of the study.…”

Cardiooncology. Basic principles of prevention and treatment of cardiotoxicity in cancer patients

“…В недавнем исследовании также показано, что химиотерапия антрациклинами у пациенток с раком груди, по данным МРТ сердца, вызывает снижение массы миокарда в отсутствии клинических проявлений, что требует дальнейшего изучения в плане начала превентивных мероприятий [27].…”