Treating Heart Dysfunction Related to Cancer Therapy With Sacubitril/Valsartan

The current study will test the hypothesis that among adult age survivors of cancer diagnosed at age < 39 years treatment of Stage B heart failure with sacubitril-valsartan is feasible and safe.

Inclusion criteria

• Age </= 39 years old at time of cancer diagnosis
• Clinical records adequate to determine diagnosis and treatment regimen
• Previous anthracycline chemotherapy
• Global longitudinal strain <18% and/or
• Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal but >/=40% on echocardiogram or cardiac magnetic resonance imaging (MRI)
• No symptoms of heart failure (shortness of breath, fatigue, swelling). Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).

Exclusion criteria

• -Age <18 years
• Inability to obtain consent from patient or legally authorized representative
• Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent compliance with study instructions
• Limited English or Spanish proficiency that in the opinion of the investigator may prevent understanding the content of the informed consent form or safely completing the study procedures
• Participation in another concurrent intervention study within 30 days or treatment with an investigational drug within 5 half-lives prior to randomization
• Greater than mild mitral or aortic valve regurgitation/stenosis known pre-cancer therapy
• Severe kidney disease (glomerular filtration rate (GFR) <30 milliliters (mL)/minute (min)/1.73 meters squared (m2))
• Chronic hyperkalemia (>5millimoles per liter (mmol/L))
• Evidence of Coronavirus (COVID-19) within the last 60 days or recent (21 days) exposure to close personal contact with COVID-19.
• Greater than moderate tricuspid or pulmonary valve regurgitation/stenosis known pre-cancer therapy
• Hemodynamically significant congenital heart disease in the opinion of the investigator (not including patent foramen ovale (PFO)/small atrial septal defect (ASD) or small ventricular septal defect (VSD))
• Greater than moderate pericardial effusion
• Constrictive cardiomyopathy diagnosed pre-cancer therapy
• Family history of genetic cardiomyopathy
• Evidence of infiltrative cardiomyopathy
• Symptomatic heart disease based on New York Heart Association (NYHA) classification
• Allergy to valsartan or sacubitril
• Inability to complete cardiac magnetic resonance (CMR) or 6-minute walk test
• Inability to measure non-invasive blood pressure and heart rate in the ambulatory/home setting
• Pregnant/lactating
• History of severe hypersensitivity reactions to gadolinium-based contrast agents (will perform limited cardiac imaging without contrast)
• Concomitant use of other angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), aliskiren, non-steroidal anti-inflammatories (NSAIDs) or lithium or the inability to stop these medications for the study