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Coarctation of the Aorta can no Longer be Considered a Benign Condition
EDITORIAL
Heart, Lung and Circulation (2014) 23, 297–298 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2014.03.001
Coarctation of the Aorta can no Longer be Considered a Benign Condition Melissa G.Y. Lee, MBBS, Yves d’Udekem, MD, PhD* Department of Cardiac Surgery, The Royal Children’s Hospital, Department of Paediatrics, University of Melbourne; and the Murdoch Childrens Research Institute, Melbourne, Australia
Keywords
Aortic arch Aortic arch hypoplasia Coarctation of the aorta Congenital heart defect Hypertension Outcome studies
Surgical repair of coarctation of the aorta has been described for more than 65 years. It is one of the smallest operations in paediatric cardiac surgery but it can no longer be regarded as a benign procedure. There has been renewed interest in the late outcomes after coarctation repair because rates of late arch reobstruction and late hypertension have recently been demonstrated to be much higher than initially expected [1,2]. Of particular concern is the finding that hypertension will be responsible for the death of close to 20% of these patients within three decades of the initial repair when compared to an age and gender-matched population [3]. This is why the two articles on outcomes after coarctation repair in this issue by Tong et al. and Padang et al. are so important [4,5]. A close look at the current literature will show large variations in the rate of complications observed. The two articles in this issue reported late reobstruction to be present in 20-48% and late hypertension to be present in 21-42% of patients, yet others have described these rates to be as high as 41% and 75% respectively [6,7]. The reader should be aware that the large variation reported in the rates of adverse outcomes after coarctation repair is often related to the way these outcomes are defined and the techniques used to collect these events. There seems to be no term as poorly defined as hypoplasia of the aortic arch. Today, describing arch size by z-scores should be the gold standard but these measurements are still rarely reported. An arch is commonly considered to be hypoplastic if its size deviates from normal values. The most common way to diagnose arch hypoplasia has been to calculate the ratio between the diameter of the arch and the diameter of the ascending aorta as in the study by Tong et al
[4]. The cut-off of 0.5 for a normal arch was derived from autopsy studies [8], while others have advanced on echocardiography and magnetic resonance imaging (MRI) data that this ratio should be above 0.9 [9]. Others have opted to compare the arch to the descending aorta [10]. Whatever the value chosen, arch hypoplasia has been repeatedly demonstrated to be predictive of adverse outcomes, and it is likely that hypoplasia of the arch should be defined as the size under which late complications will occur, but this value is not yet known. The definition of arch reobstruction seems to be equally arbitrary. There is a general consensus that the arch is obstructed if echocardiography demonstrates a pressure gradient through the coarctation repair site. Echocardiography seems to be far more sensitive in detecting arch obstruction than clinical gradient, and a study analyzing only clinical parameters will underestimate the prevalence of arch obstruction [10]. It is interesting to note that Padang et al. used a ratio of the actual diameter of the residual coarctation segment to the diameter of the descending aorta as the definition of reobstruction [5]. Whatever quantification method for obstruction is chosen is likely to be of little value if the procured measurements are not correlated to the only crucial clinical outcome, namely the development of hypertension. Today, the most sensitive method to detect hypertension is the use of 24-hour ambulatory blood pressure monitoring. One should be aware that any studies, such as those presented in this issue, using resting blood pressure measurements alone will underestimate the prevalence of hypertension [1,7]. In an ongoing investigation we have found that, when screened by 24-hour ambulatory blood
*Corresponding author. Department of Cardiac Surgery, The Royal Children’s Hospital, Flemington Road, Parkville, Melbourne 3052, Victoria, Australia. Tel.: +61 3 9345 5200 (business); fax: +61 3 9345 6386., Email: [email protected] © 2014 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
298
pressure monitoring, 60% of patients develop hypertension in the two decades following coarctation repair [1]. Tong et al. demonstrated an improvement in left ventricular hypertrophy after coarctation repair in the short-term, but their finding that roughly a third of patients maintained this hypertrophy after several years is concerning because it might affect the longevity of these patients [4]. It supports our finding that after two decades a third of our patients who had a coarctation repair were still found to have left ventricular hypertrophy [1]. We could not correlate the development of hypertrophy with the co-existence of arch obstruction, and it is likely that other factors such as the presence of suboptimal arch geometry played a role in the genesis of this hypertrophy, as hypothesized by Padang et al [5]. It should also be highlighted that the patients included in the two studies are likely a selected group of patients. Although the MRI study by Padang et al. emphasized that the prevalence of late outcomes is high in patients after coarctation repair, one can suspect that their patients were more likely to be investigated if they presented clinical issues prompting MRI referral, and therefore did not represent a cross-sectional study [5]. In the study by Tong et al., half of the patients in Group A, the ‘‘simple’’ coarctation group, had a patent ductus arteriosus (PDA) and they were operated at a median of 9 months, perhaps indicating that these patients might have been older survivors of coarctation [4]. In Australia our patients tend to present at a much younger age at operation, which is the likely reason why so many of the patients in their study still had a PDA. The study from the Beijing team beautifully illustrates evidence for a recent theory. They demonstrate that patients who have intra-cardiac shunting are less prone to developing hypertension following coarctation repair despite their increased complexity [4]. This finding supports the idea that increased pressure load on the proximal aortic arch in utero or in the early neonatal period causes activation of a cascade of events leading to endothelial dysfunction and vascular remodeling of the proximal aorta, resulting in irremediable hypertensive changes [11,12]. Patients with intra-cardiac shunting would not apply pressure on their proximal arch and therefore avoid this cascade of events. In conclusion, there are more long-term issues after coarctation repair than previously believed. These issues are predominantly related to the development of hypertension. The prevalence of persistent arch hypoplasia and arch reobstruction should not be underestimated. In this issue, Padang et al. demonstrate that MRI is ideally suited to detect morphological issues which develop after coarctation repair [5]. Twenty-four hour ambulatory blood pressure monitoring is a cost-effective and sensitive method to detect hypertension. There is no doubt that these two investigations should be performed more systematically in our patients
MGY. Lee, Y. d’Udekem
if we want to detect anomalies of the repaired arch and identify the minimal size of the arch required to prevent hypertension. The ideal timing of this screening remains unclear and there is no doubt that more studies, such as those presented in this issue, will be necessary before we can start to answer these important questions.
Acknowledgements This work was supported by the Victorian Government’s Operational Infrastructure Support Program and by a HeartKids Grant-In-Aid grant. Yves d’Udekem is a Career Development Fellow of The National Heart Foundation of Australia [CR 10 M 5339].
References [1] Lee MG, Kowalski R, Galati JC, Cheung MM, Jones B, Koleff J, et al. Twenty-four-hour ambulatory blood pressure monitoring detects a high prevalence of hypertension late after coarctation repair in patients with hypoplastic arches. The Journal of Thoracic and Cardiovascular Surgery 2012;144(5):1110–6. [2] Pedersen TA, Munk K, Andersen NH, Lundorf E, Pedersen EB, Hjortdal VE, et al. High long-term morbidity in repaired aortic coarctation: weak association with residual arch obstruction. Congenital Heart Disease 2011;6(6):573–82. [3] Brown ML, Burkhart HM, Connolly HM, Dearani JA, Cetta F, Li Z, et al. Coarctation of the aorta: lifelong surveillance is mandatory following surgical repair. Journal of the American College of Cardiology 2013;62(11):1020–5. [4] Tong F, Li ZQ, Li L, Chong M, Zhu YB, Su JW, et al. The Follow-up Surgical Results of Coarctation of the Aorta Procedures in a Cohort of Chinese Children from a Single Institution. Heart Lung & Circulation 2013. [5] Padang R, Dennis M, Semsarian C, Bannon PG, Tanous DJ, Celermajer DS, et al. Detection of Serious Complications by MR Imaging in Asymptomatic Young Adults with Repaired Coarctation of the Aorta. Heart Lung & Circulation 2013. [6] Clarkson PM, Nicholson MR, Barratt-Boyes BG, Neutze JM, Whitlock RM. Results after repair of coarctation of the aorta beyond infancy: a 10 to 28 year follow-up with particular reference to late systemic hypertension. The American Journal of Cardiology 1983;51(9):1481–8. [7] O’Sullivan JJ, Derrick G, Darnell R. 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;88(2):163–6. [8] Moulaert AJ, Bruins CC, Oppenheimer-Dekker A. Anomalies of the aortic arch and ventricular septal defects. Circulation 1976;53(6):1011–5. [9] Clarkson PM, Brandt PW. Aortic diameters in infants and young children: normative angiographic data. Pediatric Cardiology 1985;6(1): 3–6. [10] Smith Maia MM, Cortes TM, Parga JR, De Avila LF, Aiello VD, BarberoMarcial M, et al. Evolutional aspects of children and adolescents with surgically corrected aortic coarctation: clinical, echocardiographic, and magnetic resonance image analysis of 113 patients. The Journal of Thoracic and Cardiovascular Surgery 2004;127(3):712–20. [11] de Divitiis M, Pilla C, Kattenhorn M, Zadinello M, Donald A, Leeson P, et al. Vascular dysfunction after repair of coarctation of the aorta: impact of early surgery. Circulation 2001;104(12 Suppl 1):I165–70. [12] Vogt M, Kuhn A, Baumgartner D, Baumgartner C, Busch R, Kostolny M, et al. Impaired elastic properties of the ascending aorta in newborns before and early after successful coarctation repair: proof of a systemic vascular disease of the prestenotic arteries? Circulation 2005;111(24): 3269–73.
Heart, Lung and Circulation (2014) 23, 297–298 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2014.03.001
Coarctation of the Aorta can no Longer be Considered a Benign Condition Melissa G.Y. Lee, MBBS, Yves d’Udekem, MD, PhD* Department of Cardiac Surgery, The Royal Children’s Hospital, Department of Paediatrics, University of Melbourne; and the Murdoch Childrens Research Institute, Melbourne, Australia
Keywords
Aortic arch Aortic arch hypoplasia Coarctation of the aorta Congenital heart defect Hypertension Outcome studies
Surgical repair of coarctation of the aorta has been described for more than 65 years. It is one of the smallest operations in paediatric cardiac surgery but it can no longer be regarded as a benign procedure. There has been renewed interest in the late outcomes after coarctation repair because rates of late arch reobstruction and late hypertension have recently been demonstrated to be much higher than initially expected [1,2]. Of particular concern is the finding that hypertension will be responsible for the death of close to 20% of these patients within three decades of the initial repair when compared to an age and gender-matched population [3]. This is why the two articles on outcomes after coarctation repair in this issue by Tong et al. and Padang et al. are so important [4,5]. A close look at the current literature will show large variations in the rate of complications observed. The two articles in this issue reported late reobstruction to be present in 20-48% and late hypertension to be present in 21-42% of patients, yet others have described these rates to be as high as 41% and 75% respectively [6,7]. The reader should be aware that the large variation reported in the rates of adverse outcomes after coarctation repair is often related to the way these outcomes are defined and the techniques used to collect these events. There seems to be no term as poorly defined as hypoplasia of the aortic arch. Today, describing arch size by z-scores should be the gold standard but these measurements are still rarely reported. An arch is commonly considered to be hypoplastic if its size deviates from normal values. The most common way to diagnose arch hypoplasia has been to calculate the ratio between the diameter of the arch and the diameter of the ascending aorta as in the study by Tong et al
[4]. The cut-off of 0.5 for a normal arch was derived from autopsy studies [8], while others have advanced on echocardiography and magnetic resonance imaging (MRI) data that this ratio should be above 0.9 [9]. Others have opted to compare the arch to the descending aorta [10]. Whatever the value chosen, arch hypoplasia has been repeatedly demonstrated to be predictive of adverse outcomes, and it is likely that hypoplasia of the arch should be defined as the size under which late complications will occur, but this value is not yet known. The definition of arch reobstruction seems to be equally arbitrary. There is a general consensus that the arch is obstructed if echocardiography demonstrates a pressure gradient through the coarctation repair site. Echocardiography seems to be far more sensitive in detecting arch obstruction than clinical gradient, and a study analyzing only clinical parameters will underestimate the prevalence of arch obstruction [10]. It is interesting to note that Padang et al. used a ratio of the actual diameter of the residual coarctation segment to the diameter of the descending aorta as the definition of reobstruction [5]. Whatever quantification method for obstruction is chosen is likely to be of little value if the procured measurements are not correlated to the only crucial clinical outcome, namely the development of hypertension. Today, the most sensitive method to detect hypertension is the use of 24-hour ambulatory blood pressure monitoring. One should be aware that any studies, such as those presented in this issue, using resting blood pressure measurements alone will underestimate the prevalence of hypertension [1,7]. In an ongoing investigation we have found that, when screened by 24-hour ambulatory blood
*Corresponding author. Department of Cardiac Surgery, The Royal Children’s Hospital, Flemington Road, Parkville, Melbourne 3052, Victoria, Australia. Tel.: +61 3 9345 5200 (business); fax: +61 3 9345 6386., Email: [email protected] © 2014 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
298
pressure monitoring, 60% of patients develop hypertension in the two decades following coarctation repair [1]. Tong et al. demonstrated an improvement in left ventricular hypertrophy after coarctation repair in the short-term, but their finding that roughly a third of patients maintained this hypertrophy after several years is concerning because it might affect the longevity of these patients [4]. It supports our finding that after two decades a third of our patients who had a coarctation repair were still found to have left ventricular hypertrophy [1]. We could not correlate the development of hypertrophy with the co-existence of arch obstruction, and it is likely that other factors such as the presence of suboptimal arch geometry played a role in the genesis of this hypertrophy, as hypothesized by Padang et al [5]. It should also be highlighted that the patients included in the two studies are likely a selected group of patients. Although the MRI study by Padang et al. emphasized that the prevalence of late outcomes is high in patients after coarctation repair, one can suspect that their patients were more likely to be investigated if they presented clinical issues prompting MRI referral, and therefore did not represent a cross-sectional study [5]. In the study by Tong et al., half of the patients in Group A, the ‘‘simple’’ coarctation group, had a patent ductus arteriosus (PDA) and they were operated at a median of 9 months, perhaps indicating that these patients might have been older survivors of coarctation [4]. In Australia our patients tend to present at a much younger age at operation, which is the likely reason why so many of the patients in their study still had a PDA. The study from the Beijing team beautifully illustrates evidence for a recent theory. They demonstrate that patients who have intra-cardiac shunting are less prone to developing hypertension following coarctation repair despite their increased complexity [4]. This finding supports the idea that increased pressure load on the proximal aortic arch in utero or in the early neonatal period causes activation of a cascade of events leading to endothelial dysfunction and vascular remodeling of the proximal aorta, resulting in irremediable hypertensive changes [11,12]. Patients with intra-cardiac shunting would not apply pressure on their proximal arch and therefore avoid this cascade of events. In conclusion, there are more long-term issues after coarctation repair than previously believed. These issues are predominantly related to the development of hypertension. The prevalence of persistent arch hypoplasia and arch reobstruction should not be underestimated. In this issue, Padang et al. demonstrate that MRI is ideally suited to detect morphological issues which develop after coarctation repair [5]. Twenty-four hour ambulatory blood pressure monitoring is a cost-effective and sensitive method to detect hypertension. There is no doubt that these two investigations should be performed more systematically in our patients
MGY. Lee, Y. d’Udekem
if we want to detect anomalies of the repaired arch and identify the minimal size of the arch required to prevent hypertension. The ideal timing of this screening remains unclear and there is no doubt that more studies, such as those presented in this issue, will be necessary before we can start to answer these important questions.
Acknowledgements This work was supported by the Victorian Government’s Operational Infrastructure Support Program and by a HeartKids Grant-In-Aid grant. Yves d’Udekem is a Career Development Fellow of The National Heart Foundation of Australia [CR 10 M 5339].
References [1] Lee MG, Kowalski R, Galati JC, Cheung MM, Jones B, Koleff J, et al. Twenty-four-hour ambulatory blood pressure monitoring detects a high prevalence of hypertension late after coarctation repair in patients with hypoplastic arches. The Journal of Thoracic and Cardiovascular Surgery 2012;144(5):1110–6. [2] Pedersen TA, Munk K, Andersen NH, Lundorf E, Pedersen EB, Hjortdal VE, et al. High long-term morbidity in repaired aortic coarctation: weak association with residual arch obstruction. Congenital Heart Disease 2011;6(6):573–82. [3] Brown ML, Burkhart HM, Connolly HM, Dearani JA, Cetta F, Li Z, et al. Coarctation of the aorta: lifelong surveillance is mandatory following surgical repair. Journal of the American College of Cardiology 2013;62(11):1020–5. [4] Tong F, Li ZQ, Li L, Chong M, Zhu YB, Su JW, et al. The Follow-up Surgical Results of Coarctation of the Aorta Procedures in a Cohort of Chinese Children from a Single Institution. Heart Lung & Circulation 2013. [5] Padang R, Dennis M, Semsarian C, Bannon PG, Tanous DJ, Celermajer DS, et al. Detection of Serious Complications by MR Imaging in Asymptomatic Young Adults with Repaired Coarctation of the Aorta. Heart Lung & Circulation 2013. [6] Clarkson PM, Nicholson MR, Barratt-Boyes BG, Neutze JM, Whitlock RM. Results after repair of coarctation of the aorta beyond infancy: a 10 to 28 year follow-up with particular reference to late systemic hypertension. The American Journal of Cardiology 1983;51(9):1481–8. [7] O’Sullivan JJ, Derrick G, Darnell R. 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;88(2):163–6. [8] Moulaert AJ, Bruins CC, Oppenheimer-Dekker A. Anomalies of the aortic arch and ventricular septal defects. Circulation 1976;53(6):1011–5. [9] Clarkson PM, Brandt PW. Aortic diameters in infants and young children: normative angiographic data. Pediatric Cardiology 1985;6(1): 3–6. [10] Smith Maia MM, Cortes TM, Parga JR, De Avila LF, Aiello VD, BarberoMarcial M, et al. Evolutional aspects of children and adolescents with surgically corrected aortic coarctation: clinical, echocardiographic, and magnetic resonance image analysis of 113 patients. The Journal of Thoracic and Cardiovascular Surgery 2004;127(3):712–20. [11] de Divitiis M, Pilla C, Kattenhorn M, Zadinello M, Donald A, Leeson P, et al. Vascular dysfunction after repair of coarctation of the aorta: impact of early surgery. Circulation 2001;104(12 Suppl 1):I165–70. [12] Vogt M, Kuhn A, Baumgartner D, Baumgartner C, Busch R, Kostolny M, et al. Impaired elastic properties of the ascending aorta in newborns before and early after successful coarctation repair: proof of a systemic vascular disease of the prestenotic arteries? Circulation 2005;111(24): 3269–73.