Predicting Reversibility of Anticancer Drugs‐Related Cardiac Dysfunction: A New Piece to the Routine Use of Deformation Imaging

Cancer and cardiovascular diseases are the leading causes of death in the Western world. Newer cancer therapies have improved the survival of patients with cancer but, in some cases, turned cancer into a chronic cardiovascular disease. Indeed, millions of patients in the world are now surviving long enough to develop adverse cardiovascular effects of some cancer therapies to become the main determinant of quality of life, and in some cases the cause of premature mortality. This is particularly true for breast cancer, even when detected at an early stage, the most common cancer in women. The introduction of adjuvant therapy (endocrine therapy, anthracyclines, taxanes and, for patients with human epidermal growth factor receptor 2 (HER2)-positive disease, trastuzumab) remarkably improved both diseasefree survival and overall mortality. In patients with breast cancer, trastuzumab is often used sequentially after anthracycline therapy completion. However, anthracyclines and trastuzumab act synergistically when coprescribed to damage the heart. The incidence of heart failure ranges from 2% to 7% when trastuzumab is used as monotherapy and may be as high as 27% when it is used concurrently with anthracyclines plus cyclophosphamide. Cardiotoxicity seems to be much higher in the real world compared with the incidence reported in clinical trials in particular in patients aged over 60 years old as shown by the data from SEERMedicare and the Texas Cancer Registry-Medicare databases. Chavez-MacGregor et al. reported that the risk of congestive heart failure was 29.4% for the 2203 patients receiving trastuzumab (of a total of 9535 patients with breast cancer) compared with 18.9% in the nontrastuzumab users. Adequate monitoring of cardiotoxicity was identified in only 36.0% of the patients receiving trastuzumab. Type I damage from anthracyclines generally produces irreversible, dose-dependent death to heart muscle cells, which increases over time, taking months to years to manifest, but may be reversible when caught early. Risk factors for anthracycline-related damage include prior use of these drugs, arterial systemic hypertension, and age. The cardiotoxic effects of anthracyclines can be potentiated by adjunctive chest irradiation. Advanced age has also been associated with an increased risk of trastuzumab-induced cardiotoxicity. Trastuzumab significantly alters the expression of myocardial genes for DNA repair, which is associated with ultrastructural alterations in cardiomyocytes, and also promotes cell apoptosis and oxidative stress in the myocardium. Type II heart damage from trastuzumab varies substantially from patient to patient, is unpredictable, does not appear to be dose dependent, and seems more reversible than anthracycline damage. Beyond the risk of clinical heart failure, a substantial fraction of patients experience asymptomatic changes in LV ejection fraction with chemotherapy. These clinically silent but measurable drops in LV ejection fraction have been observed in patients receiving anthracyclines or trastuzumab. Although they have been considered to be largely benign and reversible within a period of 3 months after discontinuation of trasAddress for correspondence and reprint requests: Prof. Patrizio Lancellotti, Department of Cardiology, University Hospital, Universit e de Li ege, CHU du Sart Tilman, Avenue de l’hôpital, n1, 4000 Li ege, Belgium. Fax: +(32-4) 366 71 95; E-mail: plancellotti@chu.ulg.ac.be