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 to severe CTRCD, defined using the ESC/ICOS criteria (MODERATE: ≥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 or SEVERE:new LVEF reduction to <40% from normal baseline LVEF), diagnosed within 1 year ofcompleting 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 sex and age adjustedNT-proBNP or BNP ≤97.5th Centile, and no symptoms attributable to HF.

• Reference ranges for NT-proBNP and BNP by age and sex:

<30 years: Female: NT-proBNP ≤196 pg/ml, BNP ≤55 pg/ml Male: NT-proBNP ≤104 pg/ml, BNP ≤29 pg/ml

30-39 years: Female: NT-proBNP ≤209 pg/ml, BNP ≤59 pg/ml Male: NT-proBNP ≤102 pg/ml, BNP ≤29 pg/ml

40-49 years: Female: NT-proBNP ≤233 pg/ml, BNP ≤65 pg/ml Male: NT-proBNP ≤137 pg/ml, BNP ≤38 pg/ml

50-59 years: Female: NT-proBNP ≤299 pg/ml, BNP ≤84 pg/ml Male: NT-proBNP ≤195 pg/ml, BNP ≤55 pg/ml

60-69 years: Female: NT-proBNP ≤399 pg/ml, BNP ≤112 pg/ml Male: NT-proBNP ≤333 pg/ml, BNP ≤93 pg/ml

70-79 years: Female: NT-proBNP ≤743 pg/ml, BNP ≤208 pg/ml Male: NT-proBNP ≤763 pg/ml, BNP ≤214 pg/ml

≥80 years: Female: NT-proBNP ≤2,704 pg/ml, BNP ≤757 pg/ml Male: NT-proBNP ≤6,792 pg/ml, BNP ≤1,902 pg/ml

• 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 cardiac devices i.e. defibrillator, CRT, pacemaker, etc.

• 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.