Adverse consequences of high sympathetic nervous activity in the failing human heart
Open accessAbstract
Objectives In view of previous experimental evidence relating sympathetic nervous overactivity in the heart to myocardial necrosis and ventricular arrhythmias, we prospectively examined the hypothesis that heightened cardiac sympathetic nervous activity is associated with an adverse outcome in patients with moderate to severe heart failure.Background Despite recent therapeutic advances, patients with heart failure continue to have high mortality from progressive hemodynamic decompensation and lethal ventricular arrhythmias. It is believed that initially compensatory increases in sympathetic nervous system activity may ultimately be maladaptive, potentially contributing to subsequent adverse events.Methods Sixty patients with moderate to severe heart failure (left ventricular ejection fraction 18.9 +/- 0.9% [mean +/- SE]) were studied prospectively. In addition to the compilation of a hemodynamic, biochemical and electrocardiographic profile for each patient, whole-body and cardiac sympathetic activity were determined by isotope dilution. The relation of these variables to outcome was determined by Cox proportional hazards analysis.Results The mean follow-up period of the study group was 7 +/- 1 months (range 1 to 24) with a 12-month actuarial survival of 75%. Deaths (14 in all) were accounted for either by sudden death or progressive heart failure in equal numbers. The rate of release of norepinephrine from the heart was significantly higher in patients with heart failure than in healthy subjects (402 +/- 37 vs. 105 +/- 19 pmol/min, p < 0.01), although the values for heart failure ranged widely from normal to 10 times normal. By univariate Cox proportional hazards analysis, pulmonary capillary wedge pressure (p < 0.01), mean pulmonary artery pressure (p < 0.001), serum sodium levels (p < 0.01) and cardiac norepinephrine spill-over rate (p < 0.001) were identified as significant prognostic markers. In a multivariate analysis, cardiac norepinephrine spillover rate was identified as the most powerful prognostic marker (p = 0.0006) of those evaluated in this study.Conclusions These results suggest that activation of the sympathetic nervous system in patients with heart failure, specifically the cardiac sympathetic nerves, may contribute to the poor prognosis associated with severe heart failure. The data therefore provide a rationale for the use of drugs such as beta-adrenergic blocking agents in the management of patients with heart failure.
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In heart failure, patients with the highest cardiac sympathetic activity, measured by cardiac norepinephrine spillover, fared worst.
“When sympathetic activity in heart failure was prospectively measured specifically in the heart using cardiac norepinephrine spillover measurements, patients with the highest cardiac sympathetic activity clearly fared worst.19”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [19]
For cardiac sympathetic activation, the ranking is cardiac failure > normal-weight essential hypertension > depressive illness > aging.
“The ranking is as follows: for cardiac sympathetic activation, cardiac failure>normal-weight essential hypertension>depressive ill ness>aging.19,22,24,42,44,45,49,78”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [19]
Cardiac sympathetic activation in heart failure, more extreme than in the other conditions, is a proven lethality factor.
“Cardiac sympathetic activation in heart failure, more extreme than in the other conditions, is a proven lethality factor.19”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [19]
Ongoing systemic sympathetic activation has long been thought to be noxious in heart failure and renal failure.
“Ongoing systemic sympathetic activation has long been thought to be noxious, in heart failure 18,19 and renal failure.113”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [19]
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Self-citation
- Authors
- Kaye, D. M., Lefkovits, J., Jennings, G. L., Bergin, P., Broughton, A., & Esler, M. D.
- Affiliations
- The Alfred Hospital (AU)
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 1995-11
- Volume
- 26
- Issue
- 5
- Pages
- 1257-1263
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2061689246
- Cited by
- 665
- References
- 33
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 5 · 2023: 16 · 2022: 19 · 2021: 21 · 2020: 22 · 2019: 23 · 2018: 31 · 2017: 21 · 2016: 26 · 2015: 27 · 2014: 22 · 2013: 28 · 2012: 36
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- heart failure, norepinephrine spillover, sympathetic hyperactivity, prognosis, mortality, sudden death, hemodynamic decompensation, beta-adrenergic blocking agents, prognostic factors, pulmonary capillary wedge pressure, serum sodium
- MeSH terms
- Adult, Female, Follow-Up Studies, Heart Failure, Hemodynamics, Humans, Male, Middle Aged, Norepinephrine, Prospective Studies, Risk Factors, Sympathetic Nervous System, Survival Analysis
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