LCZ696 in Advanced LV Hypertrophy and HFpEF
LCZ696 in Advanced LV Hypertrophy and HFpEF
Patients with advanced LVH and HFpEF will be randomly assigned in open-label fashion to
 receive LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily,
 and will be treated for 24 weeks.
Heart failure with preserved ejection fraction (HFpEF) has a signiﬁcant morbidity and
 mortality, and therapies that have proven effective in HF with reduced EF have not been shown
 to improve long-term prognosis in HFpEF. Inhibition of circulating neprilysin could augment
 deficient NP-receptor GC signaling and therefore be beneficial in HFpEF, as suggested by the
 decrease in NP following administration of valsartan/sacubitril in the phase 2 (PARAMOUNT
 study). Use of valsartan/sacubitril is currently being tested in the multicenter PARAGON-HF
 trial with HFpEF patients. The investigators suppose the best candidates for LCZ696 therapy
 will be patients with HFpEF and advanced concentric LV hypertrophy and obesity, i.e. having
 the lowest BNP bioavailability.
Inclusion Criteria:

 1. Moderate/severe hypertensive left ventricular (LV) hypertrophy (LVMi ≥109 g/m² in
 women and ≥132 g/m² in men);

 2. New York Heart Association (NYHA) class II-III heart failure;

 3. Left ventricular ejection fraction > 50%;

 4. Increased LV filling pressures assessed at rest or at peak exercise by
 echocardiography

 5. Body mass index (BMI) > 30 kg/m²

 6. Signed and data informed consent

 Exclusion Criteria:

 1. Age ≤ 18 years;

 2. Evidence of myocardial ischemia during stress echocardiography;

 3. Chronic atrial flutter or atrial fibrillation;

 4. Alternative cause of left ventricular hypertrophy and impaired diastolic function
 (hypertrophic/restictive cardiomyopathy, aortic stenosis, constrictive pericarditis
 and etc.);

 5. NYHA classification I or decompensated heart failure at screening;

 6. Systolic blood pressure < 110 mmHg or > 180 mmHg;

 7. Diastolic blood pressure < 40 mmHg or > 100 mmHg;

 8. Anemia (Hb < 100 g/l);

 9. Significant left sided structural valve disease;

 10. Secondary hypertension;

 11. Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity,
 primary valvular, or myocardial diseases;

 12. Myocardial infarction or myocardial revascularization within the last 3 months of
 screening;

 13. Stroke or TIA within the last 3 months of screening;

 14. Autoimmunic and oncological diseases;

 15. Impaired renal function, defined as eGFR < 30 ml/min/1.73 m²;

 16. Impaired liver function;

 17. Potassium concentration >5.2 mmol/L.