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Medication to treat diabetes helps with heart failure
German researchers were able to show for the first time that a particular diabetes medication affects the human heart muscle and improves heart function. Now there is hope for a therapy of cardiac insufficiency with preserved pump function. There is currently no treatment for this disease that addresses the causes.
Around two million Germans suffer from heart failure
According to health experts, chronic heart failure (heart muscle weakness or heart weakness) is an increasing challenge in Western society due to its frequency, mortality and hospital admission. It is associated with a long course of the disease, high suffering and poor prognosis for the patients. According to experts, almost two million people are affected in Germany alone. As a result of this disease, the heart is no longer able to provide the body with sufficient blood and oxygen. Researchers have now found that diabetes medication could help people with diabetes.
What can help those affected
In recent years, new approaches to treating heart failure have been reported.
For example, researchers at the Hannover Medical School (MHH) found that more iron could help some patients because it makes the heart more resilient.
And scientists from the German Center for Cardiovascular Research (DZHK) have now been able to show that a diabetes medication can be beneficial for those affected.
The researchers' results were published in the "European Journal of Heart Failure".
Drug reduced the death rate
As the DZKH writes in a communication, the active ingredient empaglifozin is approved in Germany for the treatment of type II diabetes mellitus in adults.
The EMPA-REG OUTCOME study has now investigated the effect of empaglifozin in diabetes patients who also had cardiovascular disease.
Surprisingly, the drug in this study reduced both the overall death rate and the number of deaths caused by cardiovascular diseases by more than 30 percent each.
In addition, the number of hospital stays decreased due to heart failure by 35 percent.
These positive effects became apparent after just two months and were grounds for Professor Samuel Sossalla from the University Medical Center Göttingen and the University Hospital Regensburg to believe that something was happening directly on the heart muscle and to take a closer look at it.
"If empagliflozin had an indirect effect and influenced secondary risk factors, such as blood pressure or cholesterol levels, it would take years to see an effect," said DZHK scientist Sossalla.
Researchers worked with explanted hearts
Sossalla and his staff have reportedly worked with explanted human hearts that were taken from heart failure patients when they received a donor heart.
More precisely, on the muscle strips prepared from it, which can be imagined as a beating heart in the laboratory.
"When we treated these heart muscle strips with empagliflozin, the cardiac muscle's ability to relax improved," said Dr. Steffen Pabel, postdoc in the Sossalla group.
"However, the heart's power, that is, its ability to contract, remained unchanged." The effect of empagliflozin on the ability to relax was independent of whether there was an additional diabetes or not.
No causal therapy is currently available
As explained in the communication, the heart's ability to relax is impaired in patients with cardiac insufficiency who maintain pump function. Half of all heart failure patients therefore suffer from this form of heart failure.
The left ventricle is so thick and stiff that it can no longer expand sufficiently in the so-called diastolic phase and fill with blood.
This causes insufficient oxygen-rich blood to enter the body during the subsequent contraction of the heart, the systolic phase.
There are currently no therapies for this heart weakness that fight the causes of the disease. Medicines can only alleviate the symptoms of the patient.
Effects on the human heart muscle strip
Sossalla's work group focuses on translational projects, i.e. work that helps ensure that results from the laboratory actually reach the patient.
"Here we are dealing with the opposite path," said Sossalla. "Results from the clinic lead back to the laboratory in order to understand the observed effect at all."
The advantage of in vitro investigations compared to clinical studies with patients is clear to him:
“With isolated heart muscle cells, we can see whether the heart muscle is directly affected. Heart effects that are observed in patients could always be indirect effects. "
The scientists were also able to confirm the effects of empagliflozin on the human heart muscle strips in the hearts of mice with and without diabetes.
Mechanism for increased cardiac muscle relaxation
In the case of cardiac insufficiency with preserved pump function, significantly fewer phosphate groups are attached to certain contractile proteins of the heart muscle than in a healthy heart.
In their investigation of the mechanism of action, the researchers were able to show that immediately after the administration of empagliflozin, the phosphorylation of precisely these contractile proteins increased again significantly.
"This effect of empagliflozin, which has been demonstrated for the first time, explains why the cardiac muscle relaxes again," said Pabel.
Experts were able to experimentally rule out another conceivable mechanism for increased relaxation, the change in the concentration of calcium ions in the heart muscle.
Because after the administration of empagliflozin, this concentration did not change in isolated human cardiac muscle cells.
The group now wants to find out more about the mechanism of action and so how empagliflozin works in the long term on so-called stem cell heart muscle cells, which can be cultivated for months in the laboratory.
Until now, they have only observed the acute effect - isolated heart muscle cells do not survive in the laboratory for more than 48 hours. (ad)