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Published on: December 11, 2017

Effect of Sacubitril/Valsartan on Functional and Structural Cardiac Parameters in Adults With Nonobstructive

Milena Petranovic1, Elke Platz2, Anke Schneider3

  • 1Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA; Novartis, Cambridge, Massachusetts, USA.

JACC. Heart Failure
|August 19, 2026
PubMed

Insights

Sacubitril/valsartan did not improve exercise capacity in nonobstructive hypertrophic cardiomyopathy (nHCM) patients. However, the drug demonstrated favorable cardiac structural remodeling, suggesting potential benefits for nHCM treatment.

Area of Science:

  • Cardiology
  • Pharmacology
  • Clinical Trials

Background:

  • Symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM) presents a significant unmet therapeutic need.
  • Sacubitril/valsartan (LCZ696), a novel angiotensin II receptor-neprilysin inhibitor, has shown efficacy in heart failure but remains unevaluated in nHCM.

Purpose of the Study:

  • To assess the safety, tolerability, and efficacy of sacubitril/valsartan (LCZ696) in enhancing exercise capacity in patients diagnosed with nHCM.
  • This phase II, multicenter, randomized, double-blinded, placebo-controlled trial aimed to provide critical insights into LCZ696's potential for nHCM management.

Main Methods:

  • Adult patients with nHCM and reduced exercise capacity (≤80% predicted peak oxygen consumption) were randomized to receive either placebo or LCZ696, uptitrated to 200 mg twice daily.
  • The primary efficacy endpoint was the change in peak oxygen uptake (pVO2) after 50 weeks, measured via cardiopulmonary exercise testing.
  • Secondary endpoints included echocardiographic changes, heart failure serum biomarkers, and a composite z-score of key nHCM parameters.

Main Results:

  • The study randomized 40 participants; LCZ696 did not significantly improve peak oxygen uptake (pVO2) compared to placebo (P = 0.55).
  • Significant reductions were observed in interventricular septal thickness (-4.7 mm, P = 0.0001) and left ventricular mass index (-22.5 g/m2, P = 0.02) in the LCZ696 group.
  • A composite z-score improved in the LCZ696 group (P = 0.015), driven by favorable changes in cardiac structure and troponin levels. Safety profile was consistent with prior heart failure studies.

Conclusions:

  • While sacubitril/valsartan (LCZ696) did not enhance peak oxygen uptake in nHCM patients after 50 weeks, it induced significant favorable cardiac structural remodeling.
  • These findings suggest a potential therapeutic benefit of LCZ696 in nHCM, warranting further investigation into its impact on cardiac structure and long-term outcomes.
Abstract

Keywords:
angiotensin-receptor neprilysin inhibitorhypertrophic cardiomyopathy

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