Adverse consequences of high sympathetic nervous activity in the failing human heart

Kaye, David M.; Lefkovits, Jeffrey; Jennings, Garry; Bergin, Peter; Broughton, Archer; Esler, Murray

doi:10.1016/0735-1097(95)00332-0

Cited by 622 publications

(423 citation statements)

References 29 publications

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“…High dose sildenafil was associated with a 20% reduction in cardiac norepinephrine spillover, a variable that is an independent predictor of mortality [15]. Three possible mechanisms for this observation can be suggested.…”

Section: Discussionmentioning

confidence: 86%

“…Finally, this selective cardiac sympathoinhibitory effect could be related to the cardiopulmonary baroreceptor unloading that occurred in response to sildenafil infusion. Multiple lines of evidence suggest that reductions in cardiac filling pressure in patients with heart failure secondary to dilated cardiomyopathy can lead to cardiac specific reductions in sympathetic activity [15,19,20]. Although the methods we employed do not allow us to determine the mechanism with certainty, it is reasonable to hypothesize that both the prejunctional sympathoinhibitory effects of NO and the indirect sympatholytic effects related to the unloading of cardiopulmonary receptors could explain the observed reduction in cardiac norepinephrine spillover.…”

Section: Discussionmentioning

confidence: 96%

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The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Al‐Hesayen

Floras

Parker

2006

European J of Heart Fail

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Background: Erectile dysfunction is common in patients with chronic heart failure and sildenafil is an effective treatment option in this population. Sildenafil has been reported to increase sympathetic outflow in normal volunteers. To date, experience with sildenafil in patients with congestive heart failure is limited and the impact of phosphodiesterase-5 inhibition on sympathetic activity in this population has not been evaluated. Methods and results: 10 patients with heart failure (ejection fraction 23 T 3%) were studied. Generalized and cardiac sympathetic activity responses to an intravenous infusion of sildenafil were measured by the norepinephrine spillover method. In response to sildenafil, there was a significant reduction in mean pulmonary artery (À 26 T 5%, P < 0.01) and mean arterial pressures (À 8 T 1%, P < 0.01). These hemodynamic responses were accompanied by a 22 T 5% reduction in cardiac norepinephrine spillover ( P < 0.02) but no change in total body norepinephrine spillover. Conclusions: The acute administration of sildenafil is associated with a modest reduction in systemic arterial blood pressure and a more substantial reduction in pulmonary arterial pressure. These hemodynamic changes are observed in the absence of systemic sympathetic activation and are associated with a reduction in cardiac norepinephrine spillover in patients with chronic heart failure. These observations are relevant given the high prevalence of erectile dysfunction in this patient population.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 96%

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Al‐Hesayen

Floras

Parker

2006

European J of Heart Fail

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“…We have not demonstrated how well ΔHR reflects established measures of autonomic tone in HF, including HR variability,4 HR recovery,3 norepinephrine spillover,2 baroreflex sensitivity, or muscle sympathetic nerve activity 8. Further studies will be required to better define the pathophysiological correlates of ΔHR.…”

Section: Discussionmentioning

confidence: 87%

“…Measures of more advanced autonomic dysfunction are indicators of the severity of HF and adverse prognosis 2, 3, 4, 5, 6. They may include heart rate variability,4, 7 heart rate recovery,3 baroreflex sensitivity,5 measurement of norepinephrine spillover,2, 7 and muscle nerve sympathetic activity 8. However, the techniques needed to identify these are complex, and their application requires considerable infrastructure and time and are, therefore, not well suited for serial testing in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of the Change in Heart Rate From the Supine to the Upright Position in Patients With Chronic Heart Failure

Maeder

Zurek

Rickli

et al. 2016

JAHA

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BackgroundThe prognostic value of the change in heart rate from the supine to upright position (∆HR) in patients with chronic heart failure (HF) is unknown.Methods and Results∆HR was measured in patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME‐CHF) who were in sinus rhythm and had no pacemaker throughout the trial (n=321). The impact of ∆HR on 18‐month outcome (HF hospitalization‐free survival) was assessed. In addition, the prognostic effect of changes in ∆HR between baseline and month 6 on outcomes in the following 12 months was determined. A lower ∆HR was associated with a higher risk of death or HF hospitalization (hazard ratio 1.79 [95% confidence interval {95% CI} 1.19‐2.75] if ∆HR ≤3 beats/min [bpm], P=0.004). In the multivariate analysis, lower ∆HR remained an independent predictor of death or HF hospitalization (hazard ratio 1.75 [95% CI, 1.18‐2.61] if ∆HR ≤3 bpm, P=0.004) along with ischemic HF etiology, lower estimated glomerular filtration rate, presence and extent of rales, and no baseline β‐blocker use. In patients without event during the first 6 months, the change in ∆HR from baseline to month 6 predicted death or HF hospitalization during the following 12 months (hazard ratio=2.13 [95% CI 1.12–5.00] if rise in ∆HR <2 bpm; P=0.027).Conclusions∆HR as a simple bedside test is an independent prognostic predictor in patients with chronic HF. ∆HR is modifiable, and changes in ∆HR also provide prognostic information, which raises the possibility that ∆HR may help to guide treatment.Clinical Trial Registration Information URL: www.isrctn.org. Unique identifier: ISRCTN43596477.

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“…Plasma norepinephrine is a systemic prognostic marker,4, 5 but cardiac uptake of the norepinephrine analogue iodine‐123–labelled meta ‐iodobenzylguanidine ( 123 I‐ m IBG) allows more direct assessment of cardiac denervation which has a greater prognostic value in HF patients 6, 7…”

Section: Introductionmentioning

confidence: 99%

Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance

2017

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AimsExtent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients.Methods and resultsA post hoc analysis of 858 heart failure subjects in the ADMIRE‐HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123I‐mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all‐cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b‐type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all‐cause and cardiac mortality were baseline heart rate (χ 2 = 4.5, P = 0.029 and χ 2 = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ 2 = 8.9, P = 0.0006 and χ 2 = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P < 0.0001 and χ 2 = 17.8, P < 0.0001, respectively). In multivariate analyses, carvedilol‐equivalent dose (P = 0.017), plasma norepinephrine (P = 0.002), and H/M (P = 0.0001) were significant predictors of all‐cause mortality. In separate analyses using multiple measurements of heart rate, mean heart rate >67 b.p.m. was associated with significantly higher cardiac mortality.ConclusionsHigher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123I‐mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death.

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Adverse consequences of high sympathetic nervous activity in the failing human heart

Cited by 622 publications

References 29 publications

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Prognostic Value of the Change in Heart Rate From the Supine to the Upright Position in Patients With Chronic Heart Failure

Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance

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