AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741).

Background: Breast cancer (BC) survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 early-stage BC patients scheduled for AC to determine if 12-months of exercise training (ExT) could attenuate functional disability (primary endpoint), improve cardiorespiratory fitness (VO 2 peak) and prevent cardiac dysfunction. Methods: Women aged 40-75 years with stage I-III BC scheduled for AC were randomized to 3-4 days/wk of aerobic and resistance ExT for 12-months (n = 52) or usual care ([ UC ], n = 52). Functional measures were performed at baseline, 4-weeks following AC (4-months) and at 12-months comprising: 1) cardiopulmonary exercise testing to quantify VO 2 peak and functional disability (VO 2 peak ≤18.0mL/kg/min), 2) cardiac reserve (response from rest to peak exercise) quantified using exercise cardiac magnetic resonance measures to determine changes in left- and right-ventricular ejection fraction [ LVEF, RVEF ], cardiac output [ CO ], and stroke volume [ SV ]), 3) standard-of-care echocardiography-derived resting LVEF and global longitudinal strain [ GLS ], and 4) biochemistry (troponin and B-type natriuretic peptide [ BNP ]). Results: Among 104 participants randomized, greater study attrition was observed among UC participants (P=0.031) with 93 women assessed at 4-months (ExT: n=49, UC: n=44) and 87 at 12-months (ExT: n=49, UC: n=38). ExT attenuated functional disability at 4-months (OR: 0.32 [95% CI 0.11, 0.94], P=0.03), but not at 12-months (OR: 0.27, [95% CI 0.06, 1.12], P=0.07). In a per-protocol analysis, functional disability was entirely prevented at 12-months among participants adherent to ExT (ExT: 0% vs. UC: 20%, P=0.005). As compared with UC at 12-months, ExT was associated with a net +3.5 mL/kg/min improvement in VO 2 peak that coincided with greater CO, SV, LVEF and RVEF reserve (P<0.001 for all). There was no effect of ExT on resting measures of LV function. Post-chemotherapy troponin increased less in ExT than UC (8-fold vs. 16-fold increase, P=0.002). There were no changes in BNP in either group. Conclusions: In women with early-stage BC undergoing AC, 12-months of ExT did not attenuate functional disability but provided large and clinically meaningful benefits on VO2peak and cardiac reserve. Clinical Trial Registration: URL: https://www.anzctr.org.au/ Unique Identifier: ACTRN12617001408370

The SUCCOUR trial will be the first randomized controlled trial of GLS and will provide evidence to inform guidelines regarding the place of GLS for surveillance for CTRCD. (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes [SUCCOUR]; ANZ Clinical Trials ACTRN12614000341628).

Key Points• Prescribing appropriately for age and cardiovascular risk is likely to result in minimal permanent toxicity-related dasatinib cessation.• CML patients on dasatinib with pleural effusion are more likely to have achieved MR4.5 after 6-month therapy than those without effusion.Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation.Age and dose were risk factors for pleural effusion (P , .01 and .047, respectively).Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P 5 .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P 5 .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.