The STOP-MED CTRCD Trial

Inclusion Criteria:

• Adult patients (age ≥18 years) with cancer therapy completed more than 6 monthsprior (other than hormonal therapy) and no plan for further cancer treatments withpotential risk for CTRCD.

• Prior cancer therapy with anthracyclines and/ or HER2-targeted therapy.

• Prior asymptomatic, moderate CTRCD, defined using the European Society of Cardiologycriteria (≥10% drop in LVEF from baseline to 40% to 49.9% OR <10% drop to 40-49.9%with a reduction in GLS by >15% or new abnormal Troponin I/T or NT-proBNP),diagnosed within 1 year of completing potentially cardiotoxic cancer therapy.

• Current use of ≥1 HF medication started for CTRCD for at least 6 months with LVEF ≥55% by recently performed (≤6 months) echocardiogram, normal NT-proBNP, and nosymptoms attributable to HF.

• Confirmation of LVEF ≥55% and normal volumes at baseline CMR (i.e., some patientsrecruited based on echocardiography, may be excluded if baseline CMR LVEF/volumesare not normal). This is included given that the primary outcome includes the use ofCMR LVEF.

Exclusion Criteria:

• Indication for continuation of HF medications i.e., ongoing HF symptoms, chronickidney disease (CKD), vascular disease, atrial or ventricular arrythmias, other (note: participants with hypertension will be switched to other guideline-basedantihypertensive therapy).

• Contraindications for CMR (e.g., MRI non-compatible implanted pacemakers).

• Patients with severe CTRCD defined as having a nadir LVEF <40% due to the known poorprognosis in these patients.

• Continued use of loop diuretic therapy for heart failure purposes i.e., furosemide.

• Life expectancy <1 year or metastatic disease.

• Prior history of major cardiovascular event (defined as myocardial infarction,cerebral vascular event, admission for HF) or therapeutic cardiovascular procedure (e.g., percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)).

• Issues that prevent communication, understanding or presentation for study-relatedvisits and inability to provide informed consent.