The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF: A Randomized Controlled Trial

Conditions
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Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Drug: Angiotensin Receptor-Neprilysin Inhibition
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HFpEF with ARNI treatment<br>Sacubitril/valsartan (ARNI, 100mg bid) | Drug: Angiotensin Receptor-Neprilysin Inhibition<br>* Sacubitril/valsartan [100 mg] bid). Continuous treatment was maintained for at least three months.<br>* Other names: Sacubitril/valsartan;|
| Placebo Comparator: Control group<br>placebo (100mg bid) | Drug: Placebo<br>* Placebo [100 mg] bid). Continuous treatment was maintained for at least three months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extracellular volume [ECV] | Extracellular volume [ECV] assessment by CMR | Before ARNI or placebo treatment and after 3 months of continuous ANRI or palcebo treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myocardial infarction, hospitalization for heart failure and death | myocardial infarction, hospitalization for heart failure and all-cause death | After 3 months of continuous ANRI or palcebo treatment |