Discordance between microneurographic and heart-rate spectral indices of sympathetic activity in pulmonary arterial hypertension

McGowan, Cheri L.; Swiston, John R.; Notarius, Catherine F.; Mak, Susanna; Morris, Beverley L.; Picton, Peter; Granton, John; Floras, John S.

doi:10.1136/hrt.2008.157115

Cited by 37 publications

(38 citation statements)

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“…These contradictory findings are not surprising; circulating NE plasma levels are an imperfect measure of sympathetic tone, since they are not only the result of NE release, but also uptake, metabolism, and clearance. Increases in sympathetic nerve traffic have also been described in patients with PAH (11,28,44), with recent findings suggesting that muscle sympathetic nerve activity has prognostic significance, predicting episodes of clinical deterioration (10). Finally, patients with PAH have decreased heart rate variability (21,28,45), and in patients with congenital heart disease, the reduction in heart rate variability correlates with the severity of right ventricular dysfunction (15).…”

Section: Discussionmentioning

confidence: 94%

“…However, heart rate variability is representative of the balance of vagal input and sympathetic tone directed at the sinus node and is, therefore, not a specific measure of sympathetic activity directed at the myocardium (27). Indeed, in patients with PAH, there was an inverse rather than a positive relationship between direct measures of peripheral sympathetic nerve activity and indirect (heart rate variability) estimates of sympathetic modulation of heart rate (28).…”

Section: Discussionmentioning

confidence: 98%

“…Increases in sympathetic nerve traffic have also been described in patients with PAH (11,28,44), with recent findings suggesting that muscle sympathetic nerve activity has prognostic significance, predicting episodes of clinical deterioration (10). Finally, patients with PAH have decreased heart rate variability (21,28,45), and in patients with congenital heart disease, the reduction in heart rate variability correlates with the severity of right ventricular dysfunction (15). However, heart rate variability is representative of the balance of vagal input and sympathetic tone directed at the sinus node and is, therefore, not a specific measure of sympathetic activity directed at the myocardium (27).…”

Section: Discussionmentioning

confidence: 99%

“…Some investigations have documented peripheral sympathetic activation in patients with PAH, including elevations in peripheral plasma NE, increased sympathetic activity directed to skeletal muscle, as well as changes in the autonomic regulation of heart rate. (10,11,28,31,36,44) Important, with respect to the findings presented here, is the fact that sympathetic outflow is regional and organ specific with certain organs experiencing the greatest degree of sympathetic activation (18,23,40). Therefore, although sympathetic activation to the periphery has been demonstrated in patients with PAH, the state of cardiac sympathetic activity in PAH remains an important, unanswered question.…”

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confidence: 89%

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Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Mak

Witte

Al‐Hesayen

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 Ϯ 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 Ϯ 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 Ϯ 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 Ϯ 2.2 vs. 1.5 Ϯ 0.9 pmol/ml; P Ͻ 0.01) but similar to that seen in those with CHF (3.3 Ϯ 1.4; P ϭ NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure. pulmonary hypertension; norepinephrine; hemodynamics PULMONARY HYPERTENSION IS defined as a mean pulmonary artery pressure of more than 25 mmHg at rest and is classified into five groups based upon etiology (42, 43). Idiopathic pulmonary arterial hypertension (IPAH) and other forms of pulmonary hypertension due to abnormalities in the pulmonary vasculature [pulmonary arterial hypertension (PAH)] require the exclusion of other causes, particularly abnormalities of left heart function.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 89%

See 2 more Smart Citations

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Mak

Witte

Al‐Hesayen

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We have previously summarised the pathophysiological relevance of the neurohormonal axis in PAH [10,11]. In short, in PAH patients, sympathetic nervous system activity is increased and correlates with prognosis [12][13][14][15][16][17]. In addition, local changes in β-adrenergic receptor signalling of the right ventricular myocardium of PAH patients have been demonstrated [18][19][20].…”

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confidence: 99%

β-blockers in pulmonary arterial hypertension: evolving concepts of right heart failure

Man

Handoko

2015

Eur Respir J

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@ERSpublications Beta-blockers can be used safely by some PAH patients with comorbidities such as arrhythmias or hypertension http://ow.ly/P2JHgCurrent guidelines advise against the use of β-blockers in pulmonary arterial hypertension (PAH) to avoid systemic hypotension [1]. In addition, PAH patients have a fixed stroke volume, and are therefore highly dependent on heart rate to increase their cardiac output [2][3][4]. Indeed, PROVENCHER et al. [5] showed that withdrawal of β-blockers significantly improved exercise capacity in portopulmonary hypertension. PEACOCK and ROSS [6] described another case of portopulmonary hypertension, in which the use of a β-blocker to treat a supraventricular tachycardia in an already haemodynamically unstable patient was nearly fatal.Interestingly, patients with left heart failure also have a relatively fixed stroke volume [3,7]. However, in this case, β-blocker therapy (together with angiotensin-converting enzyme (ACE) inhibition) is considered the cornerstone of treatment [8]. How can we explain this discrepancy? PACKER [9] elegantly described the change in perspective on heart failure over the past 50 years. Until the 1960s, heart failure was solely regarded as an oedematous disorder, and the use of diuretics was central in the treatment. In the 1980s this view was extended with the cardiocirculatory model, in which heart failure was also viewed as a haemodynamic disorder. This led to the use of peripheral vasodilators and the development of positive inotropic agents. Although these agents effectively reduced symptoms, later it was consistently demonstrated that they increased mortality. Therefore, the conceptual view was adjusted again in the 1990s, and nowadays heart failure is also considered a neurohormonal disorder. This is the basis for the treatment with β-blockers and ACE inhibitors.We see a similar pattern emerging when looking at PAH-induced right heart failure, where more and more evidence is accumulating that might shift our conceptual framework from a solely haemodynamic to also a neurohormonal perspective. We have previously summarised the pathophysiological relevance of the neurohormonal axis in PAH [10,11]. In short, in PAH patients, sympathetic nervous system activity is increased and correlates with prognosis [12][13][14][15][16][17]. In addition, local changes in β-adrenergic receptor signalling of the right ventricular myocardium of PAH patients have been demonstrated [18][19][20]. Furthermore, in experimental PAH-models, β-blocker therapy reversed cardiac remodelling and improved outcome [21][22][23].Whereas it is much too early to advocate β-blockers treatment to reverse right heart failure in patients, signals are emerging that the dangers of β-blockers in PAH patients are much smaller than previously thought. In this issue of the European Respiratory Journal, BANDYOPADHYAY et al. [24] describe the outcomes of β-blocker use in the largest PAH cohort thus far. Most patients received β-blockers for treatment of arrhythmias, presumed congestive cardiac failu...

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Heart Rate Variability and Arrhythmic Burden in Pulmonary Hypertension

Witte

Meyer-Arend

Andrié

et al. 2016

Pulmonary Dysfunction and Disease

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A growing body of evidence indicates that sudden cardiac death constitutes a major cause of mortality in pulmonary hypertension (PH). As validated method to evaluate cardiac autonomic system dysfunction, alterations in heart rate variability (HRV) are predictive of arrhythmic events, particularly in left ventricular disease. Here, we sought to determine the clinical value of HRV assessment in PH. Sixty-four patients were allocated to different PH-subgroups in this prospectively conducted trial: 25 patients with pulmonary arterial hypertension (PAH), 11 patients with chronic thromboembolic PH (CTEPH), and 28 patients with COPD-induced PH. All patients underwent 24-h Holter electrocardiogram for HRV assessment by time- and frequency-domain analysis. Arrhythmic burden was evaluated by manual analysis and complementary automatic measurement of premature atrial and ventricular contractions. The results were compared to 31 healthy controls. The PAH patients offered a significantly higher mean heart rate (78.6 ± 10.4 bpm vs. 70.1 ± 10.3 bpm, p = 0.04), a higher burden of premature ventricular contractions (p < 0.01), and decreases in HRV (SDNN: p < 0.01; SDANN: p < 0.01; very low frequency: p < 0.01; low frequency/high frequency ratio: p < 0.01; total power: p = 0.02). In CTEPH patients, only the amount of premature ventricular contractions differed from controls (p < 0.01), whereas in COPD both premature atrial contraction count and frequency-domain-based HRV manifested significant differences. In conclusion, PAH appears to be primarily affected by HRV alterations and ventricular arrhythmic burden, indicating a high risk for malignant arrhythmic events.

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Discordance between microneurographic and heart-rate spectral indices of sympathetic activity in pulmonary arterial hypertension

Abstract: Thus, in PAH (as in patients with left ventricular systolic dysfunction) loss of PL relates inversely to gain in MSNA burst frequency. Diminished sympathetic neural heart rate modulation and increased right atrial stretch may combine to attenuate HRV, an adverse prognostic marker.

Cited by 37 publications

References 37 publications

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

β-blockers in pulmonary arterial hypertension: evolving concepts of right heart failure

Heart Rate Variability and Arrhythmic Burden in Pulmonary Hypertension

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