Early changes in heart failure with preserved ejection fraction: The merit of a sex-specific approach

Abstract

More women than men have heart failure with preserved ejection fraction, but it is unclear why. This intriguing question is at the heart of this dissertation, where we explore the early changes that may lead to HFpEF, a condition that severely impacts quality of life. Unlike other forms of heart failure, HFpEF is not caused by a weakened ability of the heart to contract, but rather by its inability to relax properly. This issue of insufficient relaxation becomes more common with age, yet only a fraction of those affected, primarily wome, go on to develop heart failure symptoms. We are trying to better understand this from different perspectives. A key component of this dissertation is the HELPFulUP study, in which we follow patients with insufficient relaxation of the heart muscle over time. We make some interesting observations: In this population, women indeed develop heart failure more often than men. Surprisingly, though, the markers indicating poor relaxation of the heart muscle do not show significant changes over time. We do observe that reduced kidney function and increased blood pressure contribute to worsening over time in both men and women. Furthermore, this dissertation includes several chapters in which we examine biomarkers to better understand the underlying mechanism of reduced relaxation. For example, we discover that the protein called interferon-alpha 5 only plays a role in early changes that can lead to heart failure in women. We believe this is due to genetic differences between men and women. Additionally, we study a signal on the electrocardiogram called the TQ interval. The TQ interval correlates with the relaxation phase within a heartbeat. We observe that, as expected, the TQ interval is shorter in women than in men, and that there is a relationship with reduced heart relaxation and heart failure. This dissertation contains important new results from repeated measurements of heart relaxation and the progression to heart failure. Various underlying mechanisms are investigated through biomarker research.