Elevated sympathetic activity, endothelial dysfunction, and late hypertension after repair of coarctation of the aorta☆
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.
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)
- et al.
High prevalence of hypertension and end-organ damage late after Coarctation repair in normal arches
Ann. Thorac. Surg.
(2015) - et al.
Results after repair of coarctation of the aorta beyond infancy: a 10 to 28 year follow-up with particular reference to late systemic hypertension
Am. J. Cardiol.
(1983) - et al.
Coarctation of the aorta: lifelong surveillance is mandatory following surgical repair
J. Am. Coll. Cardiol.
(2013) - et al.
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology
J. Am. Soc. Echocardiogr.
(2005) - et al.
Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight
J. Am. Coll. Cardiol.
(1992) - et al.
Sympathetic reflex latencies and conduction velocities in normal man
J. Neurol. Sci.
(1980) - et al.
Ambulatory arterial stiffness index derived from 24-hour ambulatory blood pressure monitoring
Hypertension
(2006) - et al.
Coarctation of the aorta can no longer be considered a benign condition
Heart Lung Circ.
(2014) - et al.
Left ventricular hypertrophy in adults with previous repair of coarctation of the aorta; association with systolic blood pressure in the high normal range
Int. J. Cardiol.
(2016) - et al.
Evidence of vascular dysfunction in young patients with successfully repaired coarctation of aorta
Atherosclerosis
(2005)
Comparison of Candesartan versus Metoprolol for treatment of systemic hypertension after repaired aortic coarctation
Am. J. Cardiol.
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.
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.
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
Evidence for cardiovascular autonomic dysfunction in neonates with coarctation of the aorta
Circulation
Resetting of the cardiopulmonary baroreflex 10 years after surgical repair of coarctation of the aorta
Heart
Baroreflex control of sympathetic nerve activity in essential and secondary hypertension
Hypertension
Cited by (33)
Prenatal diagnosis of coarctation: Impact on early and late cardiovascular outcome
2024, International Journal of CardiologyPosterior reversible encephalopathy syndrome (PRES) after pediatric heart transplantation: A multi-institutional cohort
2023, Journal of Heart and Lung TransplantationOn-treatment blood pressure and cardiovascular mortality in adults with repaired coarctation of aorta
2023, American Heart JournalCardiac Phenotypes in Secondary Hypertension: JACC State-of-the-Art Review
2022, Journal of the American College of CardiologyCitation Excerpt :Interestingly, normotensive patients with repaired coarctation of the aorta (r-CoA) present with signs of premature arterial aging of the entire arterial tree, including endothelial dysfunction,25 increased intima-media thickness, and increased arterial stiffness. Altogether, these vascular changes, as well as reduced baroreceptor sensitivity and chronically increased sympathetic activity, are thought to be the main mechanisms involved in the pathophysiology of hypertension in patients with CoA.26 In other words, hypertension may be caused by a generalized vasculopathy from birth rather than by simple isolated aortic narrowing (Figure 1).
Arterial stiffness and pulsatile hemodynamics in congenital heart disease
2022, Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and Disease
- ☆
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
- 1
Joint senior authorship (equal contribution).