Identifying Therapeutic Mechanisms for Incretin-Based Treatment in Obesity-Related Heart Failure With Preserved Ejection Fraction (HFpEF)
The central hypothesis to be tested is that patients with obesity and heart failure with preserved ejection fraction (HFpEF) prescribed tirzepatide will demonstrate reductions in measured plasma volume. In conjunction with state-of-the-art body composition analysis and measures of adipokines, this will establish an important mechanism of clinical benefit and inform disease pathophysiology. To accomplish this, this study will perform a 15-month prospective cohort study in 50 patients with obesity and HFpEF who clinically qualify for treatment with tirzepatide. The investigators will serially measure plasma volume and body composition with quantitative magnetic resonance to determine changes over time with tirzepatide treatment.
• Diagnosis of heart failure (HF) per the ACC/AHA guidelines with NYHA class II-III symptoms
• Left ventricular ejection fraction \>= 45% within 6 months of recruitment
• At least one of the following: elevated N-terminal pro- B-type natriuretic peptide (NT-proBNP) \>=200 pg/ml (\>=600 pg/ml with concurrent atrial fibrillation), evidence of structural heart disease (left atrial (LA) enlargement with LA volume index \>29 mL/m2 or LA diameter \>=40 mm in males/\>38= mm in females), elevated filling pressures (resting wedge \>15 mmHg or exercise wedge \>25 mmHg, lateral E/e' ratio \>12 or septal E/e' \> 15)
• Body mass index (BMI) \>30 kg/m2
• Stable doses of HF medications within 4 weeks of screening with optimal volume control in the opinion of the investigator.