Lumacaftor Yields Reversal of Impaired Cerebral Blood Flow in Heart Failure Patients

Cognitive impairment (CI) is highly prevalent in patients with heart failure with reduced ejection fraction (HFrEF), which has significant implications for disease management, quality of life and clinical outcomes. Currently, there are no specific treatments for CI aside from the current standard of care therapy for HF, making this a high unmet medical need. Impaired cerebral autoregulation is a proposed mechanistic factor that leads to cerebral hypoperfusion, ischemic damage and the development for CI. Preclinical data indicates that restoring CFTR-protein expression normalizes cerebral microvascular function and cerebral blood flow (CBF) in models of HF. The purpose of this study is to investigate whether CFTR-targeting therapy enhances cerebral perfusion and cognitive function in heart failure patients using the CFTR-corrector Lumacaftor.

Inclusion Criteria Participants screened for enrolment must meet all of the following criteria to be eligible for study participation: 1. Provide written informed consent 2. Aged 18 years or older with stable heart failure NYHA class II-III, with reduced cardiac output and an EF of \3 x the upper limit of normal (ULN) or total bilirubin \>2 x ULN 7. Resting heart rate of \>100 bpm 8. Symptomatic blood pressure \