Abstract
Bidirectional, multilevel communication between the heart and the brain is pivotal for the beat-to-beat regulation of cardiac function and the close titration of cardiac output to meet metabolic demand. Given this bidirectional communication, it is perhaps not surprising that cardiac pathologies lead to changes in the central and peripheral autonomic nervous system, which in turn lead to further progression of cardiovascular disease. Within the CNS, structural and functional changes have been reported in the setting of hypertension and heart failure in multiple autonomic regions and nuclei, including the spinal cord, brainstem, hypothalamus and higher centres, such as the amygdala and thalamus. These alterations enhance the excitability of sympathetic neuronal populations and diminish the excitability of neurons within the parasympathetic nuclei, resulting in sympathovagal imbalance. The primary drivers of these structural and functional changes appear to be a combination of increased angiotensin signalling (both central and peripheral), neuroinflammation, oxidative stress and glial activation. Targeting the CNS in the setting of cardiovascular disease presents an exciting avenue for the field of neuromodulation.
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Acknowledgements
M.V. is supported by NIH grants R01HL148190 and R01 HL1706262. V.Y.H.v.W. is supported by the Rubicon grant from the NWO.
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M.V. has patents related to neuromodulation at University of California, Los Angeles, and has performed educational consulting for Biosense-Webster, Medtronic, Zoll Inc. and has shares in Nference and NeuCures Inc. V.Y.H.v.W. declares no competing interests.
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Glossary
- Bathmotropy
-
The degree of cardiac myocyte excitability, referring to the ease with which cardiomyocytes can be depolarized.
- Chronotropy
-
The rate at which the heart muscle is excited, expressed as heart rate.
- Dromotropy
-
The speed or velocity of cardiac electrical impulse conduction.
- HFmrEF
-
Heart failure with mildly reduced left ventricular ejection fraction of 41–49%.
- HFpEF
-
Heart failure with preserved left ventricular ejection fraction of ≥50%.
- HFrEF
-
Heart failure with reduced left ventricular ejection fraction of ≤40%.
- Inotropy
-
The force of cardiac contraction, expressed as mmHg s−1.
- Lusitropy
-
The rate of myocardial relaxation, expressed as mmHg s−1.
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van Weperen, V.Y.H., Vaseghi, M. The brain–heart axis: effects of cardiovascular disease on the CNS and opportunities for central neuromodulation. Nat. Rev. Neurosci. (2025). https://doi.org/10.1038/s41583-025-01000-6
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DOI: https://doi.org/10.1038/s41583-025-01000-6
