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Sympathetic nerve activity during non-sustained ventricular tachycardia in chronic heart failure
International Journal of Cardiology 165 (2013) e15–e17
Contents lists available at SciVerse ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Sympathetic nerve activity during non-sustained ventricular tachycardia in chronic heart failure☆,☆☆ Ahmed M. Adlan a, Gregory Y.H. Lip b, Paul J. Fadel c, d, James P. Fisher a,⁎ a
College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK University of Birmingham Centre of Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, UK Department of Medical Pharmacology and Physiology, University of Missouri, Colombia, MO, 65212, USA d Dalton Cardiovascular Research Center, University of Missouri, Colombia, MO, 65212, USA b c
a r t i c l e
i n f o
Article history: Received 28 September 2012 Accepted 28 October 2012 Available online 22 November 2012 Keywords: Arrhythmias Autonomic function Chronic heart failure Non-sustained ventricular tachycardia Sympathetic nerve activity
Ventricular arrhythmias are strongly associated with hemodynamic collapse, syncope and sudden cardiac death, and occur commonly in the presence of structural heart disease (i.e. chronic heart failure) [1]. Heightened sympathetic adrenergic drive is implicated in the genesis of arrhythmias, while an inappropriate sympatheticvascular response to arrhythmia may further compound the hemodynamic compromise. However, the sympathetic response to ventricular arrhythmias is incompletely understood. In fact much of the research has involved models of stimulated ventricular tachycardia (VT) [2], which may not fully represent spontaneous VT. We report the results of the first direct recording of sympathetic neural activity during spontaneous non-sustained VT (NSVT) in chronic heart failure. The patient is a 67 year old male with non-ischemic chronic heart failure (left ventricular ejection fraction 15–20%) who was studied in our neural cardiovascular control research laboratory. In accordance with the Declaration of Helsinki, written informed consent for participation was provided, and all protocols were approved by the local ethics committee. The patient was on optimal medical therapy (angiotensin II receptor blocker, β-blocker, aldosterone antagonist, lanoxin, statin, and vitamin K antagonist) as well as cardiac resynchronization/defibrillator device
☆ The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ☆☆ Funding: This research was supported by the NIH grant no. HL 038690-22 and by a University of Missouri Research Board Grant (#3301). ⁎ Corresponding author. Tel.: +44 121 4148011; fax: +44 121 4144121. E-mail address: j.p.fi[email protected] (J.P. Fisher). 0167-5273/$ – see front matter © 2012 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.ijcard.2012.10.088
therapy. While resting supine, the patient developed an unprovoked episode of NSVT. Intra-neural recordings of muscle sympathetic nerve activity were made using peroneal nerve microneurography, while electrocardiogram and arterial blood pressure (Finometer) were monitored (Fig. 1). As shown in Fig. 1B, ~15 s prior to the NSVT a premature ventricular complex evoked a large burst of sympathetic nerve activity (*). The patient subsequently developed ventricular bigeminy, during which blood pressure diminished. A further burst of sympathetic nerve activity (○) was observed coinciding with the onset of NSVT (6 beats at a rate of 160 b.min−1). During NSVT the blood pressure dramatically fell to ~50 mm Hg evoking multiple large broad bursts of sympathetic nerve activity (●; Fig. 1C). Following termination of NSVT, blood pressure began to recover and was normalized after ~15 s. No sympathetic nerve activity was seen for ~30 s after termination of the NSVT (sympathetic silence). The patient remained asymptomatic throughout. The sympathetic response to VT is likely the net result of conflicting inputs from cardiopulmonary and arterial baroreceptor afferents to the brainstem. The fall in blood pressure unloads the arterial baroreceptors eliciting sympatho-excitation, while the elevation in cardiac filling pressure loads the cardiopulmonary baroreceptors promoting sympathoinhibition [2]. The sympatho-excitation during NSVT suggests the arterial baroreceptors have the predominant effect. However, during NSVT the sympathetic burst morphology is remarkably altered (Fig. 1C). At baseline sympathetic bursts are symmetrical and coupled to the cardiac cycle, while during NSVT the bursts are broader, lack symmetry and cardiac rhythmicity is lost. A similar pattern of sympathetic activity is observed during arterial baroreceptor denervation [3], perhaps indicating that the pattern of sympathetic activity during NSVT results from the reduced blood pressure pulsatility and the concomitant cyclic loading and unloading of the arterial baroreceptors. Following termination of NSVT there is a prolonged “sympathetic silence” lasting ~30 s. Although, a brief sympathetic silence has been reported following premature ventricular contractions in CHF [4], this is not observed after stimulated VT [2]. This sympathetic silence occurs despite blood pressure returning to baseline levels, perhaps indicating a transient alteration in the generator properties of sympathetic motor nuclei. While this may serve to protect the heart from pro-arrhythmogenic effects of further adrenergic stimulation, it could lead to poor hemodynamic tolerance during subsequent VT and may help explain why CHF patients have poor survival from VT [5]. In summary, hemodynamic compromise during NSVT caused brief sympatho-excitation different in character to baseline activity,
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A.M. Adlan et al. / International Journal of Cardiology 165 (2013) e15–e17
Fig. 1. Integrated muscle sympathetic nerve activity (obtained using the microneurography technique at the peroneal nerve), electrocardiogram (ECG), and arterial blood pressure (ABP) traces before (panel A) and during an episode of non-sustained ventricular tachycardia (NSVT; panel B). Baseline heart rate was 80 b.min−1 (paced) and ABP was 132/78 mm Hg. Approximately 15 s prior to NSVT a premature ventricular beat (indicated by an arrow) evoked a large burst of sympathetic activity (indicated by an *). The patient subsequently developed ventricular bigeminy (indicated by a solid line) during which the ABP waveform began to diminish. A further burst of sympathetic nerve activity (indicated by an open circle) coincided with the onset of NSVT (6 beats at a rate of 160 b.min−1; indicated by a dashed line). During NSVT, ABP dramatically fell to ~50 mm Hg evoking broader bursts of sympathetic nerve activity (indicated by a black circle). Following termination of NSVT, ABP began to rise and was normalized after ~15 s, however sympathetic nerve activity was suppressed, and it was not until after ~30 s that a normal sympathetic burst pattern resumed. Panel C highlights the normal sympathetic burst morphology and the wider asymmetrical bursts during NSVT (indicated by a black circle).
A.M. Adlan et al. / International Journal of Cardiology 165 (2013) e15–e17
followed by prolonged sympathetic silence. The disrupted burst morphology and ensuing sympathetic silence warrants further investigation to determine the precise mechanisms, as well as the clinical and prognostic significance. Conflicts of interest None. Acknowledgments The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
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References [1] Luu M, Stevenson WG, Stevenson LW, Baron K, Walden J. Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 1989;80:1675-80. [2] Smith ML, Joglar J, Wasmund SL, et al. Reflex control of sympathetic activity during stimulated ventricular tachycardia in dogs. Circulation 1999;100:628-34. [3] Fagius J, Wallin BG, Sundlof G, Nerhed C, Englesson S. Sympathetic outflow in man after anaesthesia of the glossopharyngeal and vagus nerves. Brain 1985;108: 423-38. [4] Welch WJ, Smith ML, Rea RF, Bauernfeind RA, Eckberg DL. Enhancement of sympathetic nerve activity by single premature ventricular beats in humans. JACC 1989: 69-75. [5] Bigger Jr JT. Why patients with congestive heart failure die: arrhythmias and sudden cardiac death. Circulation 1987;75(Suppl. IV):IV-28-35.
Contents lists available at SciVerse ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Sympathetic nerve activity during non-sustained ventricular tachycardia in chronic heart failure☆,☆☆ Ahmed M. Adlan a, Gregory Y.H. Lip b, Paul J. Fadel c, d, James P. Fisher a,⁎ a
College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK University of Birmingham Centre of Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, UK Department of Medical Pharmacology and Physiology, University of Missouri, Colombia, MO, 65212, USA d Dalton Cardiovascular Research Center, University of Missouri, Colombia, MO, 65212, USA b c
a r t i c l e
i n f o
Article history: Received 28 September 2012 Accepted 28 October 2012 Available online 22 November 2012 Keywords: Arrhythmias Autonomic function Chronic heart failure Non-sustained ventricular tachycardia Sympathetic nerve activity
Ventricular arrhythmias are strongly associated with hemodynamic collapse, syncope and sudden cardiac death, and occur commonly in the presence of structural heart disease (i.e. chronic heart failure) [1]. Heightened sympathetic adrenergic drive is implicated in the genesis of arrhythmias, while an inappropriate sympatheticvascular response to arrhythmia may further compound the hemodynamic compromise. However, the sympathetic response to ventricular arrhythmias is incompletely understood. In fact much of the research has involved models of stimulated ventricular tachycardia (VT) [2], which may not fully represent spontaneous VT. We report the results of the first direct recording of sympathetic neural activity during spontaneous non-sustained VT (NSVT) in chronic heart failure. The patient is a 67 year old male with non-ischemic chronic heart failure (left ventricular ejection fraction 15–20%) who was studied in our neural cardiovascular control research laboratory. In accordance with the Declaration of Helsinki, written informed consent for participation was provided, and all protocols were approved by the local ethics committee. The patient was on optimal medical therapy (angiotensin II receptor blocker, β-blocker, aldosterone antagonist, lanoxin, statin, and vitamin K antagonist) as well as cardiac resynchronization/defibrillator device
☆ The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ☆☆ Funding: This research was supported by the NIH grant no. HL 038690-22 and by a University of Missouri Research Board Grant (#3301). ⁎ Corresponding author. Tel.: +44 121 4148011; fax: +44 121 4144121. E-mail address: j.p.fi[email protected] (J.P. Fisher). 0167-5273/$ – see front matter © 2012 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.ijcard.2012.10.088
therapy. While resting supine, the patient developed an unprovoked episode of NSVT. Intra-neural recordings of muscle sympathetic nerve activity were made using peroneal nerve microneurography, while electrocardiogram and arterial blood pressure (Finometer) were monitored (Fig. 1). As shown in Fig. 1B, ~15 s prior to the NSVT a premature ventricular complex evoked a large burst of sympathetic nerve activity (*). The patient subsequently developed ventricular bigeminy, during which blood pressure diminished. A further burst of sympathetic nerve activity (○) was observed coinciding with the onset of NSVT (6 beats at a rate of 160 b.min−1). During NSVT the blood pressure dramatically fell to ~50 mm Hg evoking multiple large broad bursts of sympathetic nerve activity (●; Fig. 1C). Following termination of NSVT, blood pressure began to recover and was normalized after ~15 s. No sympathetic nerve activity was seen for ~30 s after termination of the NSVT (sympathetic silence). The patient remained asymptomatic throughout. The sympathetic response to VT is likely the net result of conflicting inputs from cardiopulmonary and arterial baroreceptor afferents to the brainstem. The fall in blood pressure unloads the arterial baroreceptors eliciting sympatho-excitation, while the elevation in cardiac filling pressure loads the cardiopulmonary baroreceptors promoting sympathoinhibition [2]. The sympatho-excitation during NSVT suggests the arterial baroreceptors have the predominant effect. However, during NSVT the sympathetic burst morphology is remarkably altered (Fig. 1C). At baseline sympathetic bursts are symmetrical and coupled to the cardiac cycle, while during NSVT the bursts are broader, lack symmetry and cardiac rhythmicity is lost. A similar pattern of sympathetic activity is observed during arterial baroreceptor denervation [3], perhaps indicating that the pattern of sympathetic activity during NSVT results from the reduced blood pressure pulsatility and the concomitant cyclic loading and unloading of the arterial baroreceptors. Following termination of NSVT there is a prolonged “sympathetic silence” lasting ~30 s. Although, a brief sympathetic silence has been reported following premature ventricular contractions in CHF [4], this is not observed after stimulated VT [2]. This sympathetic silence occurs despite blood pressure returning to baseline levels, perhaps indicating a transient alteration in the generator properties of sympathetic motor nuclei. While this may serve to protect the heart from pro-arrhythmogenic effects of further adrenergic stimulation, it could lead to poor hemodynamic tolerance during subsequent VT and may help explain why CHF patients have poor survival from VT [5]. In summary, hemodynamic compromise during NSVT caused brief sympatho-excitation different in character to baseline activity,
e16
A.M. Adlan et al. / International Journal of Cardiology 165 (2013) e15–e17
Fig. 1. Integrated muscle sympathetic nerve activity (obtained using the microneurography technique at the peroneal nerve), electrocardiogram (ECG), and arterial blood pressure (ABP) traces before (panel A) and during an episode of non-sustained ventricular tachycardia (NSVT; panel B). Baseline heart rate was 80 b.min−1 (paced) and ABP was 132/78 mm Hg. Approximately 15 s prior to NSVT a premature ventricular beat (indicated by an arrow) evoked a large burst of sympathetic activity (indicated by an *). The patient subsequently developed ventricular bigeminy (indicated by a solid line) during which the ABP waveform began to diminish. A further burst of sympathetic nerve activity (indicated by an open circle) coincided with the onset of NSVT (6 beats at a rate of 160 b.min−1; indicated by a dashed line). During NSVT, ABP dramatically fell to ~50 mm Hg evoking broader bursts of sympathetic nerve activity (indicated by a black circle). Following termination of NSVT, ABP began to rise and was normalized after ~15 s, however sympathetic nerve activity was suppressed, and it was not until after ~30 s that a normal sympathetic burst pattern resumed. Panel C highlights the normal sympathetic burst morphology and the wider asymmetrical bursts during NSVT (indicated by a black circle).
A.M. Adlan et al. / International Journal of Cardiology 165 (2013) e15–e17
followed by prolonged sympathetic silence. The disrupted burst morphology and ensuing sympathetic silence warrants further investigation to determine the precise mechanisms, as well as the clinical and prognostic significance. Conflicts of interest None. Acknowledgments The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
e17
References [1] Luu M, Stevenson WG, Stevenson LW, Baron K, Walden J. Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 1989;80:1675-80. [2] Smith ML, Joglar J, Wasmund SL, et al. Reflex control of sympathetic activity during stimulated ventricular tachycardia in dogs. Circulation 1999;100:628-34. [3] Fagius J, Wallin BG, Sundlof G, Nerhed C, Englesson S. Sympathetic outflow in man after anaesthesia of the glossopharyngeal and vagus nerves. Brain 1985;108: 423-38. [4] Welch WJ, Smith ML, Rea RF, Bauernfeind RA, Eckberg DL. Enhancement of sympathetic nerve activity by single premature ventricular beats in humans. JACC 1989: 69-75. [5] Bigger Jr JT. Why patients with congestive heart failure die: arrhythmias and sudden cardiac death. Circulation 1987;75(Suppl. IV):IV-28-35.