Principles and Applications of Cardio-immunology in Heart Failure

Cardio-immunology is an emerging field at the intersection of cardiology and immunology, focusing on the role of the immune system in cardiovascular disease. Heart failure (HF), in particular, is considered an immunologic phenomenon. However, attempts to modulate the immune system for treating HF have been largely unsuccessful. In this thesis we examined various aspects of immune activation in HF.

In Chapter 2 we summarized the immunomodulatory properties of current treatments for HF, we summarized previous and ongoing clinical studies of immunomodulatory treatments for HF and discussed potential future applications. In Chapters 3 and 4, the association between circulating interleukin-6 and clinical characteristics and prognosis in patients with HF was evaluated. Elevated interleukin-6 levels were associated with a worse prognosis, as well as specific clinical characteristics and blood measurements. In Chapter 5, biomarker analyses identified processes related to interferon-γ signaling and T cell co-stimulation as having the most consistent associations with all-cause mortality in patients with HF. Chapter 6 revealed that autoantibodies against autonomic nervous system receptors had limited prognostic value in patients with HF, although anti-β1 seropositivity was independently associated with a higher likelihood of hospitalization for HF. In Chapter 7, white blood cell profiling in patients with HF provided prognostic and pathophysiologic information, suggesting its potential use for risk stratification and patient selection for immunomodulatory treatments.

Overall, this thesis contributes to the understanding of immune activation in HF and lays the foundation for further research in cardio-immunology for preventive, diagnostic/prognostic, and therapeutic applications.