The heart on a turning planet: Clinical implications of biological clocks for heart failure

Abstract

Heart failure is an incurable condition with a low 5-year survival rate (~60%) and a significant impact on quality of life. Biological clocks, which regulate 24-hour rhythms, play a crucial role in cardiac function. In this dissertation we explore the impact of heart failure on the biological clock. In addition, we investigate the role of this clock in preventing heart failure in cancer patients. We investigated whether the biological clock is disrupted in heart failure and found that while the clock remains active in the heart itself, the day-night variation of cortisol and melatonin is reduced. These hormones are responsible for synchronizing biological clocks present in all organs of the body and are controlled by the central clock in the brain. Furthermore, we observed decreased blood pressure variability and more frequent sleep disturbances in patients with heart failure. These findings offer new perspectives for treatments aimed at strengthening the biological clock, such as lifestyle interventions (consistent sleep schedules, diet, and physical activity) and possibly melatonin supplementation, to improve quality of life. Furthermore, we examined whether heart failure caused by certain chemotherapy agents (anthracyclines) could be mitigated by adjusting the timing of administration. Previous in vitro and animal studies suggest that the heart's sensitivity to chemotherapy may be time dependent. Our analysis of electronic health record data indicates that chemotherapy administered in the afternoon may lead to greater cardiac damage. Before time-dependent chemotherapy can be implemented clinically, further research is needed to confirm the effectiveness and safety of this strategy.