The 24-hour rhythm is important for the functioning of our bodies, both when we are healthy and when we are sick. Researchers at UMC Utrecht wondered if the 24-hour rhythm changes in patients with heart failure. They found that despite disruptions in hormone levels and body functions, the molecular clock in the heart remained intact.

The researchers published their results in Ebiomedicine, the translational journal of Lancet.

In the Netherlands, there are about 250,000 people who suffer from heart failure. In heart failure, the heart does not pump blood around as well as it should. Linda van Laake, a cardiologist at UMC Utrecht, has wondered for years about the day and night rhythm of patients with heart failure. “We know that the 24-hour rhythm is important (link in Dutch) for the proper functioning of our body. But what about when you’re sick with heart failure?” She has now investigated that in collaboration with other researchers at UMC Utrecht and with support from the Heart Foundation.

Body functions

Fifty patients with heart failure participated in the study. Over a 24-hour period, hormone levels and various bodily functions were determined several times. The researchers saw that the hormones melatonin (also known as the sleep hormone) and cortisol (often referred to as the stress hormone) showed smaller spikes compared to people without heart failure. PhD student Markella Printezi explains, “We saw that patients with heart failure showed 30-50% less variation in their melatonin and cortisol fluctuations than people without heart failure. That means that the rhythm still fluctuated, but there was less difference between the day and night values.” The researchers also looked at blood pressure and heart rate: both bodily functions had disturbed rhythms. Linda: “When you sleep, blood pressure and heart rate should drop. We saw in the patients with heart failure that there were fewer fluctuations in those body functions. ”

The molecular clock

The researchers also looked at the molecular clock of the heart itself. Markella: “Every cell in our body has its own molecular clock. To ensure that all those individual clocks within an organ are in sync, they are synchronized by input from the 24-hour rhythm. For example, by hormone signals, such as melatonin and cortisol.” That molecular clock of an organ can be examined in humans and in animal models. In humans, they are looking at substances specifically present in heart muscle cells, including troponin. The researchers found that the pattern of these values looked normal in patients with heart failure. The molecular clock of the heart in the animals was also intact, with the researchers looking at specific genes being expressed. Says Markella, “Based on our findings, we can assume that in patients with heart failure, the molecular clock of the heart is intact. That’s an interesting finding.” Linda explains, “It is an unexpectedly special result. It shows how important such a clock is for a person. Even if the heart is very sick, a 24-hour rhythm remains present.”

Future prospects

With the results of this study, follow-up steps can be taken immediately. Such as tracking when measurements are taken in patients with heart failure. Says Markella, “Now that we know that the hormonal fluctuations of the 24-hour rhythm are attenuated, but the molecular clock of the heart still seems to be intact, we can take into account the possible influence of time on treatments such as surgery or drugs.” The researchers would advise anyone doing heart failure research to keep track of when patients receive treatments from now on. Markella: “That way, it will be possible to see in retrospect whether there is a connection between the time of administration and the effectiveness of the treatment.” With this, the researchers hope to be able to increase the effectiveness of treatment in the future.

Changes in activity patterns or lifestyle interventions can also help patients with heart failure. Linda: “An example of this is moving more in the morning. That is good for the melatonin peak later in the day, which may help heart failure patients sleep better in the evening. In addition, the distribution of meals throughout the day can be looked at to improve the disturbed metabolism of heart muscle.” It is now known that the 24-hour rhythm is disturbed in patients with heart failure. Linda: “With this knowledge, we can do further research to improve the quality of life of patients.”