Fueling Better Outcomes in Heart Failure

A healthy heart efficiently pumps blood throughout the body to provide good circulation, stable energy, and healthy blood pressure. A diseased heart, though, struggles to keep up, which can cause shortness of breath, fatigue, irregular heart rhythms, and more. Improving heart function and symptoms remain important goals for patients with heart failure.  

Senthil Selvaraj, MD, assistant professor of medicine at Duke University School of Medicine, is helping patients do just that. By better understanding heart metabolism in both healthy individuals and those with heart diseases, he’s gaining important insights into how the heart uses fuel and the impacts that has across the body. 

Heart failure can occur at any age, but it is primarily a disease among the elderly; the incidence of heart disease in general rises sharply above age 65, and at 75 the risk of congestive heart failure is up to 10 times what it is among younger adults.  

The path to a healthy heart starts at the other end of life, in infancy. The neonatal heart mostly runs on glucose, but as it matures, it starts using other fuels, eventually running mostly on fats with some glucose and ketones. “This flexibility,” Selvaraj said, “helps the heart stay efficient.” 

In heart failure, the heart loses the flexibility to use fats and glucose efficiently.  “What we’ve found, though, is the heart likes ketones,” Selvaraj said, “but ketones aren’t typically available in high abundance.” 

Ketones are a chemical the liver produces when the body breaks down fat for energy when it doesn’t get enough glucose. Ketone bodies are mostly generated through fasting, starvation, or by eating a ketogenic diet. “When ketones are around, failing hearts readily use them,” Selvaraj said. This has led him to investigate ketones’ effects on heart function across the spectrum of cardiovascular health.  

Exercise strengthens heart muscle, which, in turn, boosts blood flow, manages weight, lowers bad cholesterol, and more — and exercise becomes increasingly important to overall health as people age. However, people with heart failure often have exercise intolerance, so they may struggle to get enough movement for the heart to become stronger. 

SGLT-2 inhibitors have become standard treatment for all types of heart failure. They may work, in part, by making ketones a more readily available fuel source for the heart. Selvaraj wanted to know if adding even more ketones could improve heart function and allow patients with heart failure to exercise more.  

A phase 1 clinical trial examined the safety of taking ketone supplements in addition to an SGLT-2 inhibitor in patients with heart failure.  

“We wanted to see if a ketone drink would be tolerated in people already on SGLT-2 inhibitors,” Selvaraj said, “and we found that that combination therapy appeared to be safe.” 

A phase 2 clinical trial investigated whether taking a ketone drink acutely would allow patients to exercise more.  

Patients were given a ketone drink and then tested for their peak VO2, or the total amount of oxygen your body can consume during exercise. “It’s an integrative measure of physical fitness,” Selvaraj said. “The more oxygen you can consume, the more your heart is pumping, the more blood the legs are getting, the more the lungs are exchanging gas, etc.”  

Most people, though, don’t push themselves to exercise to maximum capacity, so the research team also tested submaximal exercise, which is more consistent with daily activities.  

While one ketone drink did not change a patient’s ability to exercise more, Selvaraj noted the researchers did see several changes happen in the heart.  

The addition of ketones helped decrease pressure in the heart during exercise and stress, increase heart function, and shift the body’s use away from carbohydrates as fuel.  

The next step, now underway, is looking at the effects of multiple doses of ketone drinks over an eight-week period. If adding ketone drinks into the treatment plan for patients with heart failure improves the heart’s ability to pump over time, it may allow patients to exercise more. The more exercise they can safely do, the better their chances are of improving the overall function of the heart.  

“This research, we hope, could lead to more people with heart failure living healthier lives,” Selvaraj said. 

Alissa Kocer is a communication strategist in the Office of Strategic Communications at the Duke University School of Medicine. 

Eamon Queeney is assistant director multimedia and creative in the Office of Strategic Communications at the Duke University School of Medicine.