Heart Failure

Heart failure, also known as congestive heart failure, occurs when the heart does not pump enough blood for the body's needs. “Heart failure” is different than a heart attack – with heart failure, the heart has not stopped pumping, but the volume of blood that the heart pumps with each beat has decreased.

Heart Failure with Preserved Ejection Fraction (HFpEF)

In some cases of heart failure, the heart squeezes or contracts normally but is stiff and does not fill well with blood. This lack of relaxation leads to elevated filling pressure in the heart and a reduced blood volume. This is called “heart failure with preserved ejection fraction” (HFpEF), or diastolic heart failure. Although the percentage of blood in the heart ejected during one contraction (the “ejection fraction”) is in the normal range, the heart does not hold enough blood to meet the body’s demands during exertion, leading to shortness of breath with exercise or with basic activities. HFpEF can be caused by chronic medical conditions such as hypertension, diabetes, coronary artery disease, physical inactivity, obesity, or by other underlying conditions of the lungs, kidney or immune system.

Heart Failure with Reduced Ejection Fraction (HFrEF)

In contrast, when the heart holds enough blood, but cannot pump properly, this is called “heart failure with reduced ejection fraction” (HFrEF), or systolic heart failure. The syndrome of HFrEF is caused by conditions that damage or weaken the heart muscle over time. Common causes include coronary artery disease, heart attack, high blood pressure, valve disease, diabetes, persistent arrhythmia, and infection of the heart muscle. A healthy heart’s ejection fraction is around 70 percent, which means that 70 percent of the blood in the left ventricle is pushed out with each heartbeat. An ejection fraction below 40 percent is considered HFrEF. In both HFpEF and HFrEF, the body does not receive enough blood. Despite several approved medical and device therapies for HFrEF, prognosis is poor, and a considerable unmet need remains.

Prevalence of Heart Failure

According to the Centers for Disease Control and Prevention, more than 6 million adults in the United States have heart failure. Heart failure cost the nation an estimated $30.7 billion in 2012. This total includes the cost of health care services, medicines to treat heart failure, and missed days of work. (Source: The Centers for Disease Control and Prevention)

The prevalence of heart failure with preserved ejection fraction (HFpEF) among heart failure patients is significant, and a substantial proportion of these individuals are overweight or obese.

  • Prevalence of HFpEF: Approximately 50% of heart failure patients are diagnosed with HFpEF. (Source: The British Medical Journal)

  • Obesity Among HFpEF Patients in the U.S.: In the United States, over 80% of patients with HFpEF are overweight or obese. (Source: AHA Journals)

Signs and Symptoms of Heart Failure

  • Shortness of breath with activity or when lying down

  • Fatigue and weakness

  • Swelling in the legs, ankles and feet

  • Rapid or irregular heartbeat

  • Reduced ability to exercise

  • Wheezing, a persistent cough, or a cough that brings up white or pink mucus with spots of blood

Heart Failure & SGK1

We are investigating our novel SGKI inhibitors for the treatment of heart failure. One of our novel compounds (THRV-1268) has demonstrated efficacy in models of heart failure, including models of both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). These data demonstrate the broad potential of SGK1 inhibition in these indications. Prior to the initiation of clinical studies, necessary safety pharmacology studies have also been successfully completed. In 2025, we plan to initiate a Phase 2 proof-of-concept clinical study in patients with heart failure to further evaluate the therapeutic potential of THRV-1268 on aspects of electrical, structural, and metabolic derangements.

If you are concerned about your personal health, please speak to a specialist or your healthcare provider urgently.