Sacubitril/ Valsartan in Advanced Heart Failure: Is it Just a Matter of Contractility or are there Effects on the Pulmonary Circulation? A Real Life Monocentric Experience

Background: Sacubitril/valsartan (S/V), an angiotensin receptor neprilysin inhibitor (ARNI), is the first drug to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction. S/v had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, compared with subjects receiving enalapril. However, the mechanisms are not clear. The aim of this prospective, non-randomized study was to assess the clinical and instrumental effects of this agent in patients with HFrEF and pulmonary hypertension.

Methods: To investigate the effects of S/V in HFrEF, we selected 40 consecutive patients (31 males, 9 females, mean age 64±19 years) in the NYHA class II-III, because they had left ventricular ejection fraction ≤35% at echocardiography. Etiology: 22 CHD, 3 Myocarditis, 15 IDCM.

Results: 2 patients took the maximum dose of 97/103 mg, 2 stopped the therapy due to a creatinine increase, all the others took the dose of 49/52 mg. During a mean ± SD follow-up of 24±6 months, no patients died. PASP decreased from 42.71 to 36 mm/Hg (p <0.0001); 6MWT improved from 402 m to 453 m (p <0.0001). Mean LVEF increased from 28.9% to 31.5% p <0.005); NYHA mean class improved from 1.95 to 1.70. An AICD was implanted in 20 patients.

Conclusion: These preliminary data suggest that in patients with severe heart failure, S/V is able to improve 6MWT and PASP, even in the absence of a significant improvement of ventricular contractility. S/v may reduce the fluid retention and pulmonary vasoconstriction that contribute to heart failure symptoms.