The primary purpose of this protocol amendment was to extend the duration of the study. The original protocol was expected to end as early as May-2022 and no later than Dec-2022. In this amendment, the duration of the study was extended to ensure that study participants continued to receive age-appropriate study drug treatment (especially those requiring the pediatric formulations not currently available outside investigational use) and safety follow-up until the expected time when pediatric use of sacubitril/valsartan received local marketing authorization and became commercially available to participants.

On 26-Oct-2021, an urgent safety measure (USM) was implemented by Novartis in the PANORAMA-HF core study due to a quality issue with enalapril, the active comparator. The USM included the following: • Investigational medicinal product (IMP) dispensation was blocked in the IRT system by Novartis • All participants who were receiving study medication at the time the USM was initiated, had to discontinue study treatment by 31-Oct-2021 and change to local standard of care, respecting any required washout periods. These participants were to attend an unscheduled visit at the site by 31-Oct-2021, or as soon as possible thereafter, for safety and efficacy assessments. • It was requested for all patients to return IMP in their possession by 31-Oct-2021. • All IMP is to be removed from the sites for destruction per local practices. As a result, not all the participants were on study drug treatment at PANORAMAHF Part 2 EOS visit (Visit 416). The purpose of the second protocol amendment was to amend the inclusion and exclusion criteria to allow participants impacted by the USM to enroll into this OLE study.