The effectively therapeutic approaches for Heart failure with preserved ejection fraction (HFpEF) remain limited. The PARAGON-HF trial found that Angiotensin Receptor-Neprilysin Inhibition (ARNI) has potential benefits for the management of HFpEF. Nevertheless, the role of ARNI in cardiac fibrosis in HFpEF are still unclear. We will conduct a prospective randomized controlled trial to evaluate the effect of ARNI on cardiac fibrosis in patients with HFpEF by cardiac magnetic resonance (CMR).

Heart failure with preserved ejection fraction (HFpEF) comprises approximately 50% of all heart failure. The effectively therapeutic approaches for HFpEF remain limited. The PARAGON-HF trial found that Angiotensin Receptor-Neprilysin Inhibition (ARNI) has potential benefits for the management of HFpEF. Nevertheless, the role of ARNI in cardiac fibrosis in HFpEF are still unclear. We will conduct a prospective randomized controlled trial to evaluate the effect of ARNI on cardiac fibrosis in patients with HFpEF by cardiac magnetic resonance (CMR). We will randomly assign 60 patients with HFpEF (NYHA II-IV) class, ejection fraction ≥ 50% and elevated level of natriuretic peptides to receive sacubitril-valsartan (target 100mg bid) or placebo (100mg bid). The primary endpoint is change in extracellular volume [ECV] measured by CMR. The secondary endpoints were 6-minute walking distance(6-WMD), KCCQ, hospitalizations for heart failure, myocardial infarction and death.

Inclusion Criteria:

• Signed and dated written informed consent
• Age ≥ 45 years at time of screening
• Preserved systolic left ventricular function, defined by left ventricular ejection fraction (LVEF) ≥ 50%
• NYHA classes II-IV
• H2FPEF score ≥ 6 or HFA-PEFF score ≥ 5

Exclusion Criteria:

• Patients with a known history of angioedema
• History of hypersensitivity to ARNI
• Any prior echocardiographic measurement of LVEF <45%
• Significant congenital heart disease
• Rheumatic valvular heart disease
• Acute coronary syndrome, cardiac surgery, other major cardiovascular surgery
• Probable alternative diagnoses could account for the patient's HF symptoms
• Systolic blood pressure(BP) >180 mm Hg or diastolic BP >120 mm Hg at visit
• Diastolic BP <90 mm Hg at visit 1, or symptomatic hypotension
• Patients with a cardiac pacemaker therapy device
• eGFR <30 ml/min/1.73 m2
• Serum potassium >5.2 mmol/l at visit 1
• Pregnant or nursing women