Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction

Exclusion Criteria

• •Cardiovascular-related:
• •Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.
• •Systolic blood pressure \> 160 mmHg at screening.
• •Planned coronary, carotid or peripheral artery revascularization.
• •Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, primary pulmonary arterial hypertension, chronic obstructive pulmonary disease, right heart failure due to pulmonary disease, complex congenital heart disease, anemia, or more than moderate mitral or aortic heart valve disease).
• •* Amyloid cardiomyopathy may be present in 5-15% of patients presenting with the clinical syndrome of HFpEF,60-62 and patients with amyloid may respond differently to WL intervention. To enhance the scientific rigor of the trial by ensuring a homogenous population of true primary HFpEF, we will carefully evaluate for the presence of amyloid using the approach outlined in a recent scientific statement from the AHA,63 which is also consistent with our current clinical practice.
• •* Specifically, potential participants will be evaluated for clues or risk factors for underlying cardiac amyloid including intolerance to antihypertensives, hypotension, orthostatic intolerance, persistent low-grade elevation in troponin, low QRS voltage on ECG, unexplained AV block or prior pacemaker, unexplained LV or RV wall thickening, impaired LV global longitudinal strain with apical sparing by echocardiography, family history of cardiomyopathy, neuropathy, autonomic dysfunction, carpal tunnel syndrome, lumbar spinal stenosis, family history of polyneuropathy, or black race. Patients with these risk factors will undergo screening evaluation for amyloid prior to consent in CAMEO-SEMA as part of best clinical practice. This includes screening for monoclonal light chain as first step, followed by hematology consultation if the screen is positive. Patients with risk factors but no monoclonal light chain will then undergo Tc-99m-PYP scan to rule out cardiac amyloid.
• •Obesity-related:
• •Bariatric surgery prior to screening within 5 years of screening or planned bariatric surgery within the trial time course.
• •A self-reported change in body weight \> 5 kg (11 lbs) within 90 days before screening irrespective of medical records.
• •Glycemia-related:
• •HbA1c ≥ 10.0% based on latest available value from medical records, not older than 3 months
• •History of type 1 diabetes (history of gestational diabetes is allowed).
• •Treatment with any GLP-1 receptor agonist within 90 days prior to the day of screening.
• •General health and safety:
• •Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
• •Presence of acute pancreatitis within the last 180 days prior to screening.
• •History or presence of chronic pancreatitis.
• •End-stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis.
• •Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell cancer and any carcinoma in-situ are allowed.
• •Known or suspected hypersensitivity to trial product(s) or related products.
• •Participation in any clinical trial of an approved or non-approved device for the treatment of heart failure or obesity within 30 days before screening.
• •Receipt of any investigational medicinal product within 30 days before screening.
• •Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• •Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.
• •Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.