Background Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects. Objective We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ–mediated cardiotoxicity in a chronic in vivo female murine model. Methods Wild-type C57BL/6 female mice (10–12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures. Results In the RC + DOX + TRZ–treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an ∼68% increase in LVEF compared with the RC + DOX + TRZ–treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor κB), apoptosis [poly (ADP-ribose) polymerase–1 and the ratio of BCL2-associated X protein to B-cell lymphoma–extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways. Conclusion In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ–mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.

Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received: 1) 0.9% saline, 2) BVZ (10 mg·kg−1·wk−1), or 3) SNT (40 mg·kg−1·day−1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.

Background: Marathon participation is becoming increasingly popular among individuals !40 years of age. Little is known about the prevalence of subclinical coronary artery disease (CAD) and corresponding ischemia in this patient population. The study objectives are: (1) to characterize the prevalence of silent CAD in marathoners ! 40 years old using cardiac computed tomography angiography (CCT); and (2) if subclinical CAD was detected, to determine the functional significance of occult lesions by stress echocardiography (SE). Methods: Marathoners aged ! 40 years who completed a full marathon between 2018 and 2019 were recruited to undergo a prospective CJC Open -(2021) 1e8

Objective Anorexia nervosa (AN) patients are at an increased risk of developing cardiac complications including bradyarrhythmias, systolic dysfunction, pericardial effusions, and sudden cardiac death. Although previous echocardiographic studies in AN patients have demonstrated a reduction in overall left ventricular (LV) mass, systolic dysfunction, and silent pericardial effusions, little is known about the role of cardiac magnetic resonance imaging (CMR) in assessing this patient population. The objective of this study was to assess cardiac indices and the presence of myocardial fibrosis in AN patients. Methods Between 2014 and 2015, a cross-sectional pilot study of 16 female patients who met the Diagnostic and Statistics Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN was conducted at a single tertiary care center. Baseline characteristics including age, weight, food restriction behavior, over-exercise, self-induced vomiting, and laxative abuse were collected in the study population. Electrocardiography, transthoracic echocardiography (TTE), and CMR were performed. Results The mean age was 17 years (range: 13-22 years). There were no conduction abnormalities as the average PR interval was 152 ms (range: 130-190 ms) and QTc was 413 ms (range: 360-450 ms). Using TTE, the left ventricular ejection fraction (LVEF) was 54 ± 4% with a lower LV mass/body surface area (BSA) of 56 ± 7g/m 2 in AN patients as compared to controls. Using CMR, both the mean LVEF of 52 ± 9% and LV mass/BSA of 45 ± 4g/m 2 were lower in AN patients as compared to controls. Using CMR, both right ventricular ejection fraction (RVEF) of 50 ± 10% and a right ventricular (RV) mass/BSA of 18 ± 3g/m 2 were smaller in AN patients as compared to controls. There was no evidence of late gadolinium enhancement (LGE) in the study population. Conclusions Young patients with AN have lower cardiac mass and volumes with no evidence of myocardial fibrosis.