Despite significant advances in therapies, heart failure (HF) remains a progressive
disease that, once advanced, is associated with significant death and disability.
Cardiac replacement therapies with left ventricular assist device (LVAD) and heart
transplantation (HT) are the only treatment options for advanced HF, while lifesaving
they can also be lifespan limiting due to the associated complications. Systemic inflammation
is mechanistically important in HF pathophysiology and progression. However, directly
targeting inflammation in HF has not been beneficial thus far. These failed attempts
at therapeutics might be related to our limited understanding of the factors that
cause inflammation in HF, and, therefore, to our inability to investigate these triggers
in interventional studies. Observational studies have consistently demonstrated associations
between alterations in the digestive (gut and oral) microbiome, inflammation and HF
risk and progression. Additionally, recent data indicate that these microbial perturbations
persist following LVAD and HT, along with residual inflammation and oxidative stress.
Furthermore, there is rising recognition of the critical contribution of the microbiome
to the metabolism of immunosuppressive drugs after HT. Cumulatively, these findings
might posit a mechanistic link between microbiome alterations, systemic inflammation,
and adverse outcomes in HF patients before and after cardiac replacement therapies.
This review (1) provides an update on available data linking changes in digestive
tract microbiota, inflammation, and oxidative stress, to HF pathogenesis and progression;
(2) describes evolution of these relationships following LVAD and HT; and (3) outlines
present and future intervention strategies that can manipulate the microbiome and
possibly modify HF disease trajectory.
KEYWORDS
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Published online: December 14, 2022
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