Hypertension, infection and non-ischemic cardiomyopathy

Co-author: Siyavash Hosseinzadeh

Understanding the development of non-ischemic cardiomyopathy (NICM) remains a major unmet global challenge. The differential development of NICM in patients with single risk factors suggests a multifactorial etiology.

Hypertension

Hypertension is the leading cause of NICM and on top of that is a primary cause of heart failure with preserved ejection fraction (HFpEF) – which itself puts patients at risk of NICM. As it stands today, there are no approved treatment options for HFpEF, despite the stark fact that patients with this form of heart failure account for approximately half of all heart failure hospital admissions.

Hypertension can be a trigger for cardiac hypertrophy, tissue fibrosis, diastolic dysfunction and, over time, chamber dilation and impaired systolic function. Interestingly, not all patients with poorly controlled hypertension develop HFpEF or NICM. Traditional risk factors account for only 50% of the risk for heart failure development, suggesting that additional mechanisms promote susceptibility.

Viral infection

Another risk factor for NICM is viral infection – for which we also have few, if any, effective treatment options. Viral genomes can be detected within the myocardium of ~67% of patients with NICM, suggesting a high prevalence of infection.

We believe cardiac immune cell composition is altered by both forms of cardiac stress (viral, hypertension) which increases the susceptibility to develop NICM. To make therapeutic progress we must understand how immune cells drive this process. Yet a major limitation in the field is the inability to differentiate between immune cells such as monocytes, macrophages, and dendritic cells, which either enhance or impair the myocardium’s ability to withstand hypertension as well as the presence of a virus.

Meeting a global challenge head-on

This lab’s current and previous work in these areas is paving the way to understanding the complexities of non-ischemic cardiomyopathy. The ultimate question here: does the combination of viral infection and hypertension predispose the heart to amplified immune cell driven development of heart failure?

Treatment of non-ischemic cardiomyopathy remains a global challenge because of its multifactorial etiology. Current treatment options, which are limited at best, focus on treating only a single factor contributing to heart failure. Our preliminary data show that immune cells are affected by many different types of cardiac insults. Focusing on how the immune cell composition is altered by these different stresses will reveal novel therapeutic targets for more comprehensive treatment options for non-ischemic cardiomyopathy.

 

Dr. Slava Epelman earned a Ted Rogers Centre Innovation Award for the work described here.
The image above is of dendritic cells and macrophages.