Effects of Sacubitril/Valsartan in Patients with High Arrhythmic Risk and an ICD: A Longitudinal Study



Patients affected by heart failure with reduced ejection fraction (HFrEF) receive clinical and functional beneficial effects from treatment with sacubitril/valsartan. However previous studies have shown that patients with an implantable cardioverter defibrillator (ICD) could obtain even greater benefit, but only make up a only a small proportion of patients. In the current study we evaluated the effect of sacubitril/valsartan in patients with an ICD.


Thirty-five outpatients with HFrEF (aged 60 ± 11 years, 28 were males), on optimal medical therapy were studied. All patients received an ICD at least 6 months before enrollment or were non-responders to ICD plus resynchronization (CRT-D). An open-label sacubitril/valsartan treatment was established at the maximum tolerated dose. Clinical assessment, 6-min walk test (6MWT) and echocardiography, were performed during follow-up at 90, 180, and 360 days. Quality of life score and perceived fatigue on exercise were assessed.


Clinical conditions dramatically improved in most patients, especially within the first 6 months of therapy (76 % were in NYHA-I and 24 % in NYHA-II at the end of study vs 71 % NYHA-II and 29 % NYHA III at enrollment, p < 0.001). Quality of life and exercise performance significantly improved according to N-terminal pro-brain natriuretic peptide (NT-proBNP) serum levels lowering. Walking distance at 6MWT increased from 274 ± 97 to 389 ± 53 m and walking speed from 0.74 ± 0.27 to 1.07 ± 0.15 m/s (p < 0.001), while oxygen saturation did not differ significantly (from 90 ± 1 % to 91 ± 2 %). More gradual was left ventricular reverse remodeling. Ejection fraction improved mildly (+ 5 points %, p < 0.001). Global longitudinal strain and diastolic function were also assessed over time.


Sacubitril/valsartan therapy for HFrEF may lead to significant clinical and functional improvements even in patients with ICD at greater arrhythmic risk. Clinical improvement is obtained within the first 6 months of treatment while reverse remodeling needs more time.

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Corresponding author

Correspondence to Michele Correale.

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This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

Author contributions

Conceptualization, GD and CG; methodology, GD and CG; formal analysis, MC and GD; investigation, GL, VV, CM; data curation, MC and MC; writing—original draft preparation, MC and MC; writing—review and editing, MC and MC; visualization, SSS, FL and NK; supervision, FL; project administration, GD and CG. All authors have read and agreed to the published version of the manuscript.

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Casale, M., Correale, M., Laterra, G. et al. Effects of Sacubitril/Valsartan in Patients with High Arrhythmic Risk and an ICD: A Longitudinal Study. Clin Drug Investig 41, 169–176 (2021). https://doi.org/10.1007/s40261-020-00995-3

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