Vascular dysfunction after coarctation repair is related to the age at surgery

doi:10.1016/j.ijcard.2004.02.001

International Journal of Cardiology

Volume 99, Issue 2, 18 March 2005, Pages 295-299

https://doi.org/10.1016/j.ijcard.2004.02.001 Get rights and content

Abstract

Background: Despite repair of aortic coarctation, hypertension is frequent in adults and premature coronary and cerebrovascular disease remain of concern. Persistent impairment of arterial dilation has been suspected to contribute to abnormal blood pressure regulation. We tested the hypothesis that arterial reactivity is more likely to be impaired in patients corrected at older age. Methods: We studied changes in brachial artery diameter in response to reactive hyperemia (FMD) and to nitroglycerin (NMD) in 36 patients and 25 controls. Depending on their age at surgery, patients were divided in group A (surgery <9 years) and group B (surgery ≥9 years). Results: Cholesterol levels and percentage of smokers were similar in patients and controls, but 16 patients had arterial hypertension compared to none of the controls. Endothelium-dependent vasodilation, FMD, and endothelium-independent vasodilation, NMD, were significantly impaired in patients vs. controls (8.2±6.2% vs. 13.0±5.1%, p<0.001 and 12.9±8.0% vs. 18.8±9.2%, p<0.01, respectively), both, in hypertensives (8.3±6.0%, p<0.01 and 11.8±6.0%, p<0.05) and in normotensives (8.1±6.5% p<0.01 and 13.8±9.3%, p<0.05). However, FMD and NMD in patients of group A did not significantly differ from that in controls (10.0±6.7% n.s. and 15.0±7.6% n.s.), whereas they were lowest in patients of group B (5.5±4.3%, p<0.0001 and 9.6±7.7% p<0.001). Conclusions: Persistent impairment of FMD and NMD after repair of coarctation is more likely to be present in patients corrected at older age. It may be an important contributor to abnormal blood pressure regulation and late morbidity and mortality.

Introduction

Although surgery has dramatically improved the survival of patients with coarctation of the aorta, their life expectancy remains reduced even after successful repair [1], [2], [3], [4], [5]. Arterial hypertension has remained a frequent finding during adult life and coronary artery disease, stroke and heart failure account for the majority of premature deaths [2], [3], [4], [5], [6], [7]. The causes of late hypertension remain insufficiently explained. An increased left ventricular performance with enhanced left ventricular preload, increased stiffness and persistent narrowing of the aorta as well as abnormalities of the renin–angiotensin system have been proposed in the past [8], [9]. Persistent impairment of arterial dilation in the precoarctation vascular bed has previously been reported in young adults followed after successful coarctation repair by Gardiner et al. [10]. Coarctation is not simply a mechanical disease that imposes afterload. The para-coarctation aorta consistently harbors inherent medial abnormalities of smooth muscle and extracellular matrix, the ascending aorta harbors mural changes that result in decreased distensibility and the frequent coexistence of a bicuspid valve is accompanied by its own medial abnormalities.

Persistent vascular dysfunction has been suspected to be an important contributor to abnormal blood pressure regulation and, thus, late morbidity and mortality [10]. However, although late hypertension and cardiovascular mortality have been reported to be strongly related to age at surgery [3], [4], [5], [7], vascular responses were not related to age at repair in this previous report [10]. Thus, we sought to study arterial reactivity in adults followed after successful coarctation repair in order to test the hypothesis that vascular dysfunction in this patient group is related to the age at surgery.

Section snippets

Patients

The study population consists of 36 patients (11 females and 25 males) with a mean age of 28±9 years (range, 16 to 58 years) who had successful repair of aortic coarctation at a mean age of 9±10 years. Only five patients had early surgery before the age of 5 months, the others had been operated on at ages of 2 to 55 years. According to previous studies that demonstrated significant differences in clinical outcome for patients older and younger than 9 years at surgery [3], [5], [7], the patient

Results

Echocardiographically, all patients had normal left ventricular systolic function. In 13 patients aortic valve was bicuspid and 8 of them had mild aortic regurgitation. An additional 8 patients with tricuspid aortic valve had mild regurgitation whereas the 14 patients had functionally and morphologically normal aortic valves. Mild tricuspid regurgitation was present in 4, mild mitral regurgitation in 8, and mild mitral stenosis in 1 patient. One patient had a prosthetic mitral valve and 1

Discussion

The present study demonstrates that vascular dysfunction is a frequent finding in patients after successful repair of aortic coarctation despite a good anatomical long-term result. An impaired FMD has previously been reported for young adults with cardiovascular risk factors such as hypercholesterolemia, cigarette smoking, and diabetes [16]. Reduced FMD which reflects impaired endothelium-dependent vasodilatation has also been demonstrated to be related to adverse cardiovascular outcome in

References (19)

P.M. Clarkson et al.
Results after repair of coarctation of the aorta beyond infancy: a 10 to 28 years follow-up with particular reference to late systemic hypertension
Am. J. Cardiol.
(1983)
P.A. Seirafi et al.
Repair of coarctation of the aorta during infancy minimizes the risk of late hypertension
Ann. Thorac. Surg.
(1998)
C.M. Ong et al.
Increased stiffness and persistent narrowing of the aorta after successful repair of coarctation of the aorta: relationship to left ventricular mass and blood pressure at rest and with exercise
Am. Heart J.
(1992)
ThR Kimball et al.
Persistent hyperdynamic cardiovascular state at rest and during exercise in children after successful repair of coarctation of the aorta
J. Am. Coll. Cardiol.
(1994)
D.S. Celermajer et al.
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
Lancet
(1992)
M.C. Corretti et al.
Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery
J. Am. Coll. Cardiol.
(2002)
J. Guenthard et al.
Exercise-induced hypertension in the arms due to impaired arterial reactivity after successful coarctation resection
Am. J. Cardiol.
(1995)
M. Champbell
Natural history of coarctation of the aorta
Br. Heart J.
(1970)
P. Presbitero et al.
Long term results (15–30 years) of surgery of aortic coarctation
Br. Heart J.
(1987)

There are more references available in the full text version of this article.

Cited by (46)

Arterial Stiffness in Congenital Heart Disease
2021, Heart Lung and Circulation
Transposition of the great arteries (TGA), coarctation of the aorta (CoA), single ventricle (SV) and tetralogy of Fallot (ToF) are forms of congenital heart disease (CHD). Despite advances in treatment, cardiovascular and cerebrovascular complications in patients with repaired CHD occur earlier in life compared to healthy subjects. A factor that may contribute to this increased risk is elevated arterial stiffness. This systematic review provides a critical assessment of current evidence on central arterial stiffness in patients with CHD compared to healthy controls. In July 2020, Medline OVID, EMBASE and Scopus were searched using keywords and MeSH terms. Articles were included if they reported indices of aortic or carotid artery stiffness in patients with TGA, CoA, SV or ToF, and compared these to controls. Additional studies were screened from the reference lists of included articles. Of 1,033 studies identified, 43 were included in the final review. Most studies identified at least one index of central arterial stiffness, commonly in the aortic root or ascending aorta, that was higher in patients with CHD compared to controls. The commonly reported surrogate markers of stiffness were pulse wave velocity, aortic distensibility and the β stiffness index. There was a relatively small number of original studies, and synthesis of data was limited by methodological heterogeneity, highlighting the need for further studies with standardised methods. However, there was consistent evidence of early and/or accelerated arterial stiffening in CHD patients, which may contribute to the increased risk of adverse cardiovascular and cerebrovascular events in this population.
Carotid atherosclerosis, changes in tissue remodeling and repair in patients with aortic coarctation
2021, Atherosclerosis
Citation Excerpt :
However, 3-year treatment with atorvastatin in 80 CoA patients (36.3 ± 11.8 years) did not lead to a reduction of carotid IMT, mortality or morbidity due to cardiovascular disease, despite a decrease in total cholesterol and LDL levels [8]. Early atherosclerotic changes in normotensive patients after CoA repair have been observed [9–11], suggesting that other mechanisms might also be involved. Atherosclerosis is known to be an inflammatory disease.
After aortic coarctation (CoA) repair, patients still suffer from cardiovascular complications. The aim of this study was to measure cardiovascular markers, intima-media thickness (IMT) and plaques in controls and patients with CoA.
Sixty-four patients with CoA (66% male, mean age 48 ± 15 years) and controls (54% men, mean age 47 ± 16 years) underwent ultrasound of their arteries. A multiplex platform to analyze circulating blood levels biomarkers reflecting inflammation, tissue remodeling and repair was used.
In men following CoA repair, a significantly increased carotid bulb IMT was observed in comparison to the control group (1.05 [0.72–1.24] vs. 0.67 [0.59–0.95] mm; p = 0.003). Median common carotid artery (CCA) IMT was increased in men compared to controls (0.82 [0.61–0.97] mm vs. 0.58 [0.53–0.76] mm, p < 0.003) and in women compared to controls (0.83 [0.70–0.92] vs. 0.60 [0.55–0.69], p < 0.004). CoA demonstrated an independent association with IMT in both men and women. Men with CoA were also more likely to have a plaque in their carotid arteries (p = 0.010). In women with CoA, we observed significantly lower levels of stem cell factor (SCF, p = 0.004) while in men with CoA we observed significantly lower levels of matrix metalloproteinase-3 (MMP-3, p = 0.048), tumor necrosis factor receptor 1 (TNF-R1, p = 0.032), tumor necrosis factor receptor superfamily member 10B (TRAIL-R2, p = 0.019) and monocyte chemotactic protein 1 (MCP-1, p = 0.015).
This is the first study to show that despite successful CoA repair, patients have more carotid atherosclerosis than can be explained by changes in tissue remodeling and repair.
Hemodynamic Management in Aortic Root Replacement in a Patient With Coarctation of the Aorta
2018, Journal of Cardiothoracic and Vascular Anesthesia
Low plasma renalase concentration in hypertensive patients after surgical repair of coarctation of aorta
2014, Journal of the American Society of Hypertension
The study aimed to evaluate plasma renalase level, a recently discovered kidney-derived catecholamine-metabolizing enzyme in patients after successful repair of aortic coarctation, with special consideration of arterial hypertension in the context of underlying process of arterial remodeling. This case–control study covered 50 consecutive patients after Dacron patch repair of aortic coarctation (31 men; median age 33 [26; 40]; age at surgery 10 [5; 16] years), matched in terms of age and gender with 50 controls. Both groups were stratified depending on the presence of hypertension and assessed in terms of renalase, C-reactive protein, and carotid intima-media thickness. Additionally ultrasound and tonometric markers of vascular remodeling were obtained in the study group. Hypertension was found in 21 patients (42%) in the study group and 29 (58%) in the control group (P = .11). Renalase level was significantly lower in patients in the study than control group (5825.1 vs. 6592.7 ng/mL; P = .041). Significant difference in terms of renalase concentration between hypertensive and normotensive patients was confirmed both in subjects with coarctation of aorta (P = .027) and in control group (P < .0001). Renalase level inversely correlated with serum creatinine (r = −0.36) and arterial blood pressure in the whole population, and with central systolic (r = −0.29) and diastolic pressure (r = −0.35) in study group. Multivariate regression revealed that serum creatinine and pulse pressure were independent predictors of renalase. Surgical intervention >7 years was linked to lower renalase (P = .018) and unfavorable vascular parameters. Renalase level <4958 ng/mL accurately predicted presence of hypertension in patients after coarctation of aorta repair (odds ratio, 3.8; P = .032). Renalase deficiency is associated with the presence of hypertension in both patients after surgical repair of aortic coarctation and the control group. In coarctation of aorta, its action is probably parallel to underlying arterial remodeling.
Advances in interventional and hybrid therapy in neonatal congenital heart disease
2013, Seminars in Fetal and Neonatal Medicine
In addition to the considerable surgical advances in treating congenital heart diseases, hybrid and transcatheter therapies have become a cornerstone of neonatal cardiology within the last decade. Approaches to the care of cyanotic newborns with congenital heart disease focused on manipulations of the inter-atrial septum, right ventricular outflow tract obstructions, and on the arterial duct as the source for pulmonary blood flow. Currently, fewer interventional procedures are used in newborns and small infants to treat excessive pulmonary blood flow caused by shunt lesions, but transcatheter techniques and hybrid strategies have been developed to treat newborns suffering from inadequate systemic perfusion. However, transcatheter techniques are still not available to treat failing systemic ventricles without obvious structural disorders of the myocardium or dilated cardiomyopathies in newborns and infancy, despite new surgical-interventional strategies are already developed to avoid or to delay early heart transplantation. In conclusion, material and technical improvements have enabled transcatheter techniques to replace medical-based therapies to solve structurally dependent cardiovascular diseases. However, evidence-based and long-term follow-up data are required.
Hypertension, obesity, and coronary artery disease in the survivors of congenital heart disease
2013, Canadian Journal of Cardiology
Citation Excerpt :
These data suggest that even after successful early surgical repair, the life expectancy of patients with coarctation is significantly reduced from the general population, and that premature cardiovascular death is the primary cause.11,12 Age at time of repair and the presence of postoperative hypertension are the most important risk factors for late mortality,11,12 and because delayed repair of coarctation is associated with both a longer period of hypertension and increased risk postoperative hypertension, it is likely that these risk factors are interrelated.11,13 Hypertension often begins early after coarctation repair with prevalence as high as 30% among adolescents who underwent successful repair in infancy.14
Obesity, hypertension, and coronary artery disease are prevalent in the general population and well recognized as contributors to cardiac morbidity and mortality. With surgical and medical advances, there is a growing and aging population with congenital heart disease who are also at risk of developing these comorbidities. In addition, some congenital cardiac lesions predispose patients to conditions such as hypertension or coronary artery disease. The effect of these comorbidities on the structurally abnormal heart is not well understood, but might be very important, especially in those with residual abnormalities. Thus, in addition to surveillance for and treatment of late complications it is important for the congenital cardiologist to consider and aggressively manage acquired comorbidities. In this review we explore the prevalence of hypertension, obesity, and coronary artery disease, discuss congenital lesions that predispose to these conditions and review management strategies for this unique population.
L’obésité, l’hypertension et la coronaropathie sont répandues dans la population générale et bien connues comme étant des facteurs contribuant à la morbidité et à la mortalité cardiaques. Grâce aux avancées chirurgicales et médicales, une population de plus en plus grande et vieillissante ayant une cardiopathie congénitale est également exposée à un risque de développer ces comorbidités. De plus, certaines lésions cardiaques congénitales prédisposent les patients à des affections comme l’hypertension ou la coronaropathie. L’effet de ces comorbidités sur le cœur structurellement anormal n’est pas bien compris, mais pourrait être très important, particulièrement chez ceux ayant des anomalies résiduelles. Par conséquent, en plus de la surveillance et du traitement des complications tardives, il est important pour le cardiologue spécialisé en cardiopathie congénitale de considérer et de prendre en charge de façon vigoureuse les comorbidités acquises. Dans cette revue, nous explorons la prévalence de l’hypertension, de l’obésité et de la coronaropathie, discutons des lésions congénitales qui prédisposent à ces affections, et passons en revue les stratégies de prise en charge de cette population propre.

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Vascular dysfunction after coarctation repair is related to the age at surgery

Abstract

Introduction

Section snippets

Patients

Results

Discussion

Am. J. Cardiol.

Ann. Thorac. Surg.

Am. Heart J.

J. Am. Coll. Cardiol.

Lancet

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Natural history of coarctation of the aorta

Br. Heart J.

Long term results (15–30 years) of surgery of aortic coarctation

Br. Heart J.