HFpEF
Heart Failure with
Preserved Ejection Fraction
Heart Failure
Heart failure is a clinical syndrome characterized by the inability of the heart to pump blood more effectively to meet the body’s metabolic demands. The specific type of heart failure is diagnosed based on which part of the heart is impaired.
HEART FAILURE WITH PRESERVED EJECTION FRACTION
Heart failure with preserved ejection fraction (HFpEF) is an acquired medical condition that occurs when the left ventricle can’t relax normally because the muscle has become stiff, limiting the heart’s ability to adequately fill with blood between beats.
Approximately 6.7 million Americans over age 20 have heart failure, and it is estimated that more than 50% of these cases are attributed to HFpEF. Common symptoms of HFpEF include fatigue and shortness of breath during everyday activities such as walking, climbing stairs, or carrying groceries.
Therapeutic strategies for chronic heart failure have traditionally focused on the modification of hemodynamic alterations, helping the failing heart pump blood more effectively. However, heart failure is also associated with significant alterations in cardiac metabolism (Neubauer, 2007).
The failing heart faces an energy deficit, primarily because of a decrease in mitochondrial oxidative capacity, the powerhouses of the cell. Pharmacological targeting of the energy metabolic pathways that improve cardiac energetics has emerged as a novel therapeutic approach to improving cardiac efficiency, decreasing the energy deficit, and improving cardiac function in the failing heart.
IMPROVE-DICE
IMPROVE-DiCE (NCT04826159) was the first clinical trial utilizing multi-nuclear and state-of-the-art hyperpolarized MR spectroscopy to quantify the metabolic and energetic responses to an investigational metabolic modulator in cardiovascular disease. It was a two-part, Phase 2a clinical trial evaluating the safety, tolerability and pharmacodynamic effects of ninerafaxstat.
Part 1 enrolled pre-HFpEF patients with type 2 diabetes and obesity and demonstrated normalization of cardiac energetics, significant reduction in cardiac steatosis and improvements to the rate of diastolic filling, an important component of heart failure.
Part 2 enrolled symptomatic patients with cardiometabolic HFpEF and assessed the impact of ninerafaxstat on cardiac energetics, diastolic function, functional capacity and heart failure symptoms.