Elsevier

International Journal of Cardiology

Volume 243, 15 September 2017, Pages 185-190
International Journal of Cardiology

Elevated sympathetic activity, endothelial dysfunction, and late hypertension after repair of coarctation of the aorta

https://doi.org/10.1016/j.ijcard.2017.05.075Get rights and content

Abstract

Background

There is a high prevalence of late hypertension after coarctation repair. The relative contribution of elevated sympathetic tone and endothelial dysfunction to its development is unknown. This study aims to investigate the neural profile of coarctation patients including muscle sympathetic nerve activity testing to directly measure sympathetic nervous activity.

Methods

Twenty-three patients aged ≥ 18 years with a coarctation repair underwent measurements of clinic and 24-h blood pressures, muscle sympathetic nerve activity, sympathetic and cardiac baroreflex functions, digital endothelial function, and ambulatory arterial stiffness index. Median age at repair was 1.2 months (interquartile range: 0–9 months). Patients were compared to 17 healthy matched controls.

Results

After 26 ± 5 years, 6% (1/18) and 44% (8/18) suffered clinic hypertension and prehypertension, respectively. On 24-h blood pressure monitoring, 15% (3/20) and 20% (4/20) had hypertension and prehypertension, respectively. Coarctation patients had elevated muscle sympathetic nerve activity compared with controls (49.6 ± 24.9 vs. 29.9 ± 14.0 bursts/100 heartbeats, p = 0.02), dampened sympathetic baroreflex function (− 2.2 ± 2.1 vs. − 7.0 ± 5.6 bursts/100 heartbeats·mm·Hg 1, p = 0.007), normal cardiac baroreflex function (41.9 ± 30.4 vs. 35.7 ± 21.1 ms·mm·Hg 1, p = 0.6), endothelial dysfunction (pulse amplitude tonometry ratio: 0.39 ± 0.32 vs. 0.81 ± 0.50, p = 0.004), and increased ambulatory arterial stiffness index (0.46 ± 0.15 vs. 0.29 ± 0.17, p = 0.008).

Conclusion

After coarctation repair patients have increased muscle sympathetic nerve activity, dampened sympathetic baroreflex response, endothelial dysfunction, and increased ambulatory arterial stiffness index, all of which may contribute to the development of late hypertension.

Introduction

Hypertension is a major determinant of mortality after repair of coarctation of the aorta and may be present in up to 75% of patients by early adulthood [1], [2], [3], [4], [5]. Studies of survival after coarctation repair suggest that up to 20% of patients may be deceased within three decades after repair compared to a matched population due to the accelerated effects of hypertension [6]. Unfortunately, this late hypertension is often resistant to conventional antihypertensive therapies [3]. Although arch reobstruction intuitively seems the most likely cause, contemporary studies have demonstrated that it may account for only a small proportion of patients with late hypertension [1], [2], [3]. Consequently, the mechanisms underpinning the development of late hypertension after coarctation repair remain unclear.

It has been hypothesized that neural factors such as elevated sympathetic tone may contribute to the development of this late hypertension. However, current studies examining sympathetic activity in the repaired coarctation population have only used indirect methods of assessment such as heart rate variability [7], [8]. Muscle sympathetic nerve activity testing (MSNA) is a direct measure of sympathetic activity of muscle vasoconstrictor nerve fibers and has been linked to chronic elevated blood pressure (BP) [9]. MSNA has not been performed in the coarctation population before.

This study aims to investigate the neural, hemodynamic, and vascular profile of coarctation patients including the use of MSNA testing to directly measure sympathetic nervous activity, and to compare them to a healthy matched population.

Section snippets

Study population

The study protocol was approved by the Human Research and Ethics Committees of The Royal Children's Hospital and The Alfred Hospital, Melbourne. Written informed consent was obtained from each patient. All patients were recruited from a cohort of 142 patients who had previously undergone 24-h BP monitoring after coarctation repair at The Royal Children's Hospital, Melbourne, who were living in the state of Victoria, and did not have univentricular physiology or intellectual disability [1], [2].

Clinical outcomes

Clinic resting hypertension and prehypertension was present in 6% (1/18) and 44% (8/18), respectively. Results of 24-h BP monitoring are presented in Supplemental Table 1. Hypertension and prehypertension on 24-h BP monitoring were present in 15% (3/20) and 20% (4/20), respectively. Only one of the patients with hypertension on 24-h BP monitoring had clinic hypertension. All controls were normotensive on 24-h BP monitoring. There was no significant difference in mean 24-h SBP or DBP between

Comment

Coarctation of the aorta is often considered a benign condition [20]. However, up to 75% of patients may develop hypertension after coarctation repair [1], [2], [3], [4], [5]. We demonstrated elevated muscle sympathetic nerve activity and impaired endothelial function to be present in coarctation patients with elevated BP compared to those with normal BP, adding to the growing evidence that these patients are predisposed to the development and consequences of hypertension even as young adults

Conclusion

After coarctation repair patients have increased muscle sympathetic nerve activity, dampened sympathetic baroreflex response, endothelial dysfunction, and increased ambulatory arterial stiffness index, all of which may contribute to the development of late hypertension.

The following is the supplementary data related to this article.

. Comparison of 24-h BP results between coarctation patients and controls.

Grant support

This project was supported by the Victorian Government's Operational Infrastructure Support Program and a HeartKids Grant-in-Aid research grant. Melissa Lee was supported by a National Health and Medical Research Council (NHMRC) Medical Research Postgraduate Scholarship (1134274), a National Heart Foundation Health Professional Scholarship supported by The Noel and Imelda Foster Research Award (100681), an Avant Doctors-in-Training research scholarship, and an Australian Government Research

Disclosures

Christian Brizard is a consultant for Admedus. Gavin Lambert's laboratory has received funding from Medtronic, Abbott Pharmaceuticals, Servier Australia, and Allergan. Gavin Lambert has received honoraria or travel support for presentations from Pfizer, Wyeth Pharmaceuticals, Servier and Medtronic, and was a consultant for Medtronic. Yves d'Udekem is a consultant for Actelion and MSD.

References (34)

  • E. Moltzer et al.

    Comparison of Candesartan versus Metoprolol for treatment of systemic hypertension after repaired aortic coarctation

    Am. J. Cardiol.

    (2010)
  • M.G. Lee et al.

    Twenty-four-hour ambulatory blood pressure monitoring detects a high prevalence of hypertension late after coarctation repair in patients with hypoplastic arches

    J. Thorac. Cardiovasc. Surg.

    (2012)
  • A. Hager et al.

    Coarctation long-term assessment (COALA): significance of arterial hypertension in a cohort of 404 patients up to 27 years after surgical repair of isolated coarctation of the aorta, even in the absence of restenosis and prosthetic material

    J. Thorac. Cardiovasc. Surg.

    (2007)
  • J.J. O'Sullivan et al.

    Prevalence of hypertension in children after early repair of coarctation of the aorta: a cohort study using casual and 24 hour blood pressure measurement

    Heart

    (2002)
  • J.W. Polson et al.

    Evidence for cardiovascular autonomic dysfunction in neonates with coarctation of the aorta

    Circulation

    (2006)
  • D. Johnson et al.

    Resetting of the cardiopulmonary baroreflex 10 years after surgical repair of coarctation of the aorta

    Heart

    (2001)
  • G. Grassi et al.

    Baroreflex control of sympathetic nerve activity in essential and secondary hypertension

    Hypertension

    (1998)
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