A clinical study at Karolinska Institutet and Karolinska University Hospital shows that the hunger hormone ghrelin can increase the heart’s pumping capacity in heart failure. The results have been published in the European Heart Journal.

Around 200,000 Swedes are estimated to live with heart failure, which is a condition where the heart’s pumping ability is impaired, for example after a heart attack or angina pectoris. In heart failure, the heart muscle is weakened and cannot pump as much blood as is needed to provide the body with enough oxygen and nutrients. There are treatments that slow down the process, but there are no methods to directly increase the heart’s pumping ability.

Ghrelin is a hormone that is found naturally in the body with many receptor cells in the heart muscle. It stimulates appetite and releases growth hormones, and the researchers believe that its receptor may be a good target for stimulating the heart’s pumping ability.

– Heart failure is the most common cause of hospitalization among the elderly and linked to poor quality of life and high mortality. If we can find ways to increase the heart’s pumping capacity, we can potentially improve both the quality of life and prognosis for these patients, says Lars Lund , who led the study and is a professor at the Department of Medicine, Solna , Karolinska Institutet, and senior physician at Karolinska University Hospital.

In the study, 30 heart failure patients at ME Cardiology at Karolinska University Hospital were randomly assigned to either active treatment with ghrelin or a placebo given in drip form for two hours. Neither the patients nor the doctors knew who received the active substance. The participants were followed up after two to five days.

Increased pumping capacity by 28 percent

After two hours’ treatment, the cardiac output (i.e. the volume of blood pumped by the heart in one minute) had increased by an average of 28 percent in the ghrelin group, which can be compared with a small reduction in the placebo group. The reason for the increase was that more blood was pumped from the heart per beat, as the heart rate remained unchanged or was even slightly slower. At the two- to five-day follow-up, the pump capacity was 10 percent higher in the ghrelin group compared to in the placebo group.

The researchers noted no serious side effects. For an unknown reason, the ghrelin group had slightly increased levels of a heart failure biomarker, but more studies are needed to find out whether or not there is a real connection. In the current study, a small patient group was examined and the follow-up was short, which makes it difficult to know how the treatment works in larger patient groups over a longer period of time.

To study the underlying mechanisms behind the increase in pump function, the researchers also studied mouse heart cells in the laboratory. They observed that treatment with ghrelin increased the contractile function of heart cells, and they identified a new molecular mechanism for this increase.

Now the research group wants to continue with larger clinical studies and, with the help of KI’s incubator, KI Innovations, has started a company, AnaCardio, which develops molecules with the aim of activating the ghrelin receptor and increasing the heart’s pumping capacity.

Several of the researchers have reported potential conflicts of interest, including compensation from various pharmaceutical companies for consulting and lectures. Lars Lund is the founder of AnaCardio, which develops ghrelin treatment for heart failure.

Publication

” Acyl ghrelin improves cardiac function in heart failure and increases fractional shortening in cardiomyocytes without calcium mobilization. ” Lars H. Lund, Camilla Hage, Gianluigi Pironti, Tonje Thorvaldsen, Ulrika Ljung-Faxén, Stanislava Zabarovskaja, Kambiz Shahgaldi, Dominic-Luc Webb, Per M. Hellström, Daniel C. Andersson, Marcus Ståhlberg. European Heart Journal (Eur Heart J), online March 14, 2023, doi: 10.1093/eurheartj/ehad100