Prevention, Detection, and Management of Heart Failure in Patients Treated for Breast Cancer.

PURPOSE OF REVIEW: Long-term survival has increased significantly in breast cancer patients, and cardiovascular side effects are surpassing cancer-related mortality. We summarize risk factors, prevention strategies, detection, and management of cardiotoxicity, with focus on left ventricular dysfunction and heart failure, during breast cancer treatment. RECENT FINDINGS: Baseline treatment of cardiovascular risk factors is recommended. Anthracycline and trastuzumab treatment constitute a substantial risk of developing cardiotoxicity. There is growing evidence that this can be treated with beta blockers and angiotensin antagonists. Early detection of cardiotoxicity with cardiac imaging and circulating cardiovascular biomarkers is currently evaluated in clinical trials. Chest wall irradiation accelerates atherosclerotic processes and induces fibrosis. Immune checkpoint inhibitors require consideration for surveillance due to a small risk of severe myocarditis. Cyclin-dependent kinases4/6 inhibitors, cyclophosphamide, taxanes, tyrosine kinase inhibitors, and endocrine therapy have a lower-risk profile for cardiotoxicity. Preventive and management strategies to counteract cancer treatment-related left ventricular dysfunction or heart failure in breast cancer patients should include a comprehensive cardiovascular risk assessment and individual clinical evaluation. This should include both patient and treatment-related factors. Further clinical trials especially on early detection, cardioprevention, and management are urgently needed.

Longitudinal strain analysis for assessment of early cardiotoxicity during anthracycline treatment in childhood sarcoma: A single center experience.

BACKGROUND: The growing population of long-term childhood cancer survivors encounter a substantial burden of cardiovascular complications. The highest risk of cardiovascular complications is associated with exposure to anthracyclines and chest radiation. Longitudinal cardiovascular surveillance is recommended for childhood cancer patients; however, the optimal methods and timing are yet to be elucidated. AIMS: We aimed to investigate the feasibility of different echocardiographic methods to evaluate left ventricular systolic function in retrospective datasets, including left ventricular ejection fraction (LVEF), fractional shortening (FS), global longitudinal strain (GLS) and longitudinal strain (LS) as well as the incidence and timing of subclinical left ventricular dysfunction detected by these methods. METHODS AND RESULTS: A retrospective longitudinal study was performed with re-analysis of longitudinal echocardiographic data, acquired during treatment and early follow-up, including 41 pediatric sarcoma patients, aged 2.1-17.8 years at diagnosis, treated at Astrid Lindgren Children's Hospital, Stockholm, Sweden, during the period 2010-2021. All patients had received treatment according to protocols including high cumulative doxorubicin equivalent doses (≥250 mg/m2 ). In 68% of all 366 echocardiograms, LS analysis was feasible. Impaired LS values (<17%) was demonstrated in >40%, with concomitant impairment of either LVEF or FS in 20% and combined impairment of both LVEF and FS in <10%. Importantly, there were no cases of abnormal LVEF and FS without concomitant LS impairment. CONCLUSION: Our findings demonstrate feasibility of LS in a majority of echocardiograms and a high incidence of impaired LS during anthracycline treatment for childhood sarcoma. We propose inclusion of LS in pediatric echocardiographic surveillance protocols.

Estrogen receptors do not influence angiogenesis after myocardial infarction.

BACKGROUND: There is controversy on whether estrogen receptors are present and functioning in the myocardium. Aims. To explore if after myocardial infarction (MI) estrogen receptors α (ERα) and ß (ERß) are upregulated in myocardial tissue and to explore if the presence/ absence of ERα or ERß influences angiogenesis after MI. METHODS: MI was induced by ligation of the left anterior descending artery in knockout (KO) mice, ERαKO and ERßKO, respectively, and non-KO littermate-controls, C57Bl/6 mice. The hearts were harvested after 12 days. A part of the periinfarct tissue was collected for ERα and ERß mRNA expression determination by real-time polymerase chain reaction. Using immunohistochemistry, ERα and ERß protein expression and capillary and arteriolar densities were blindly determined in the periinfarct area. RESULTS: In myocardium disrupted mRNA was upregulated in both ERαKO and ERßKO, (p < 0.005) and did not change after MI. There was no change in mRNA expression of ERα or ERß in wild type mice after MI. Expression of ERß in ERαKO and of ERα in ERßKO did not change. Following MI ERα or ERß could not be demonstrated by immunohistochemistry in either wild type or ERαKO or ERßKO. The capillary and arteriolar densities after MI did not differ between the groups in the periinfarct area. CONCLUSIONS: Although disrupted ER mRNA is upregulated in myocardium of ER knockout mice, no change in these or native receptors occurs following MI. At least in this model ER therefore seems not to have a role in myocardial arteriogenesis and angiogenesis after MI.

Erythropoietin has an antiapoptotic effect after myocardial infarction and stimulates in vitro aortic ring sprouting.

Aims were to explore if darbepoietin-alpha in mouse can induce angiogenesis and if moderate doses after myocardial infarction stimulates periinfarct capillary and arteriolar densities, cell proliferation, and apoptosis. Myocardial infarction was induced by ligation of LAD. Mouse aortic rings (0.8mm) were cultured in matrigel and the angiogenic sprouting was studied after addition of darbepoietin-alpha with and without VEGF-165. After 12 days the hemoglobin concentration was 25% higher in the darbepoietin-alpha treated mice than in the control group. No difference in capillary densities in the periinfarct or noninfarcted areas was seen with darbepoietin-alpha. Cell proliferation was about 10 times higher in the periinfarct area than in the noninfarcted wall. Darbepoietin-alpha treatment led to a decrease of cell proliferation (BrdU, (p<0.02)) and apoptosis (TUNEL, p<0.005) with about 30% in the periinfarct area. Darbepoietin-alpha and VEGF-165 both independently induced sprouting from aortic rings. The results suggest that darbepoietin-alpha can induce angiogenesis but that moderate doses after myocardial infarction are not angiogenic but antiapoptotic.