Focus area
HFrEF Heart failure with reduced ejection fraction
In HFrEF, a weakened heart muscle pumps less blood. Despite guideline-directed medical therapy, residual risks for pump failure and serious cardiac arrhythmias remain. The focus of the ASPIRE-HF study is to investigate the safety and efficacy of SGK1 inhibition to reduce these risks.
Understanding heart failure
Heart failure describes a condition where the heart is not pumping enough blood to meet the body's needs. Heart failure can also affect the heart's electrical function and lead to abnormal heart rhythms, called arrhythmias.
More than 7 million adults in the United States live with heart failure.
Source: Heart Failure Society of America
Signs and symptoms
What Heart Failure Patients Experience
Shortness of breath
Rapid or irregular heartbeat
Fatigue
Reduced ability to exercise
Swelling in legs, ankles or feet
Persistent cough or wheezing
Focus of ASPIRE-HF study
HFrEF
Heart failure with reduced ejection fraction
< 40%
left ventricular ejection fraction (LVEF)
The heart pumps less forcefully and ejects less blood volume. A normal LVEF is >50%.
HFpEF
Heart failure with preserved ejection fraction
≥ 50%
left ventricular ejection fraction (LVEF)
Although the LVEF is in a normal range, the heart is stiff and does not relax well to fill with blood between beats.
The unmet need
Progress, but risk remains
Guideline-directed medical therapy (GDMT) has improved outcomes, but patients continue to be at risk of worsening heart failure, hospitalization and potentially lethal arrhythmias.
No current therapy addresses the underlying electrical remodeling and instability of heart failure.
~40%
of recently hospitalized patients on quadruple GDMT die or are re-hospitalized for heart failure within 12 months.1
~1 in 2
patients with advanced heart failure have QTc prolongation, a marker of arrhythmia risk.2
6×
higher rate of sudden cardiac death at 6 months with prolonged QTc (12% vs 2%).2
9×
higher rate of pump-failure death at 6 months with prolonged QTc (18% vs 2%).2
1. Greene SJ, et al. JAMA Cardiol. 2026;11(3):293-297.
2. Vrtovec B, et al. Circulation. 2003;107(13):1764-1769. Advanced heart failure cohort (n=241), QTc >440 ms vs ≤440 ms.
Thryv's approach
Serum- and glucocorticoid-regulated kinase 1 (SGK1) drives parallel electrical and structural remodeling
SGK1 is a genetically validated, stress-activated kinase. It is a node at the intersection of electrical and structural remodeling, the drivers of residual risk that GDMT leaves inadequately addressed.
Human genetic validation
Lower ventricular SGK1 expression is associated with reduced heart failure risk.
In the UK Biobank, a rare SGK1 variant was significantly associated with heart failure.
These human genetic findings validate SGK1 as a core disease node to target persistent electrical, functional, and structural disease abnormalities in heart failure and cardiomyopathies.
Electrical remodeling
Inflammation
Electrical instability
Delayed repolarization and QTc prolongation on the ECG, increasing the risk of potentially lethal ventricular arrhythmias.
Fibrosis (Structural remodeling)
Heart Metabolism (Function)
Inflammation & fibrosis
SGK1 activation triggers an inflammatory and fibrosis cascade in the heart.
Adverse structural remodeling
Continued dysfunction in contractility, relaxation, and structural remodeling
ASPIRE-HF at a glance
Addressing residual risk in HFrEF with SGK1-inhibition
ASPIRE-HF: Addressing SGK1-driven Prolonged QT and Impaired REmodeling in Heart Failure.