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Outcomes of percutaneous transluminal angioplasty for pediatric renovascular hypertension
Journal of Pediatric Surgery 52 (2017) 395–399
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Outcomes of percutaneous transluminal angioplasty for pediatric renovascular hypertension☆,☆☆ Angus Alexander a,e,⁎, Lara Richmond b, Denis Geary c, Joao Luis Pippi Salle a,d, Joao Amaral b, Bairbre Connolly b a
Division of Pediatric Urology, The Hospital for Sick Children, University of Toronto, Canada Breast Imaging Division, Sunnybrook Health Sciences Centre, Toronto Division of Nephrology, Department of Pediatrics, Sidra Medical and Research Center, Doha, Qatar d Division of Pediatric Urology, Sidra Medical and Research Center, Doha, Qatar e Department of Paediatric Surgery, The Sydney Children's Hospital Network at Westmead, Sydney, Australia b c
a r t i c l e
i n f o
Article history: Received 5 February 2016 Received in revised form 30 June 2016 Accepted 18 August 2016 Key words: Pediatric Hypertension Percutaneous transluminal angioplasty Renovascular Endovascular
a b s t r a c t Background: Up to 10% of hypertensive children will have renovascular disease. Where medical therapy fails to control the hypertension, endovascular techniques can improve renal perfusion. The purpose of this study was to assess the efficacy of angioplasty in controlling renovascular hypertension (RVH) in children. Methods: This is a single-center, retrospective review of patients who underwent angioplasty for RVH between 1992 and 2009. All patients were selected from the Interventional Radiology database. The primary outcome measure was clinical success as reflected by a favorable, sustained response in blood pressure for at least 1 year following the angioplasty. Results: Two hundred sixteen patients underwent diagnostic angiography for suspected RVH, of these 28 required 42 angioplasties. Ten (36%) were cured, 9 (32%) were improved and 9 (32%) failed to respond to treatment. Major complications occurred in three patients and minor complications occurred in 18 angioplasties. Fibromuscular dysplasia (FMD) was the most common diagnosis in this series and was associated with a 79% success rate. Conclusion: In our exclusively pediatric population angioplasty safely improved blood pressure control in 68% of patients, more than half of which are cured. FMD appeared to have the best clinical outcomes in our series. © 2017 Elsevier Inc. All rights reserved.
(See Figs. 1 and 2.) Hypertension affects 1%–3% of children [1–4] and of these, 5%–10% will have renovascular disease [5,6]. The latter are a small but very important group because they are potentially curable. Traditionally antihypertensive medication and surgical revascularization have formed the backbone of pediatric management. The efficacy of renal artery PTA for the reduction of blood pressure (BP) in pediatric and adult patients is highly variable with the available literature reporting a 28%–94% and 36%–100% success rate respectively, [7–11]. The purpose of this study was to assess our results using PTA for renovascular hypertension (RVH) in an exclusively pediatric practice and to add a relatively large series to the published data on the subject. 1. Materials and methods We conducted a single-center, retrospective review of all patients who underwent PTA for RVH in a tertiary pediatric center between the 1st of ☆ Compliance with Ethical Standards. ☆☆ Conflicts of Interest: The authors declare that they have no conflict of interest. ⁎ Corresponding author at: Department of Paediatric Surgery, The Sydney Children's Hospital Network at Westmead, Cnr Hawkesbury Road and Hainsworth Street, Westmead, 2145, Sydney, Australia. E-mail address: [email protected] (A. Alexander). http://dx.doi.org/10.1016/j.jpedsurg.2016.08.011 0022-3468/© 2017 Elsevier Inc. All rights reserved.
April 1992 and the 30th of April 2009. The study was approved by the hospital's research ethics board and is a collaborative work involving the departments of Interventional Radiology (IR), Urology and Nephrology.
1.1. Patients All patients who had a diagnosis of renovascular hypertension and underwent a PTA of their renal arteries were selected from the IR database. The study included patients with systemic or regional vasculopathy and renal transplant recipients who underwent PTA. All patients had at least one year of follow-up. The medical records for identified patients were reviewed for demographic data; clinical presentation; urinalysis; associated regional or systemic vasculopathy; age, weight and BP; antihypertensive medication and dose. All angiographic images that were available as an electronic record (PACS) were reviewed by the principal and senior author. Any procedures prior to this had details extracted from the IR reports. Follow-up data were sourced from medical records where possible; telephone reports were required in five patients who were not being followed at our institution. All children were referred to the interventional radiology team by local or regional nephrology services based on a strong clinical suspicion
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Fig. 1. a. Deployment and partial inflation of the angioplasty balloon in the left renal artery. The stenosis is evident as a waist in the balloon. b. Full balloon inflation with obliteration of the waist during angioplasty.
of renovascular hypertension and poor blood pressure control despite best medical management.
1.2. Technique 1.2.1. Angiography All renal angiograms were performed under general anesthetic and systemic heparinization (100 U/kg). Initial assessment in the early series included routine renal vein renin sampling prior to any endovascular intervention. PTA was either performed during the same anesthetic or at a subsequent procedure depending on the patient's condition and the certainty of the diagnosis. In later years, renal vein renin samples were taken less often. The contralateral femoral artery was catheterized for diagnostic angiography with a 4 French sheath. A flush aortogram was performed followed by selective renal angiography.
1.2.2. Percutaneous transluminal angioplasty Balloon size was chosen according to the estimated normal renal artery size (range 3–6 mm) [Image 1a and 1b]. A post procedure angiogram was performed to assess the response, residual stenosis, and any complications. Because of the size of the pediatric vasculature and the limitations of early pressure monitors post-PTA, trans-lesional pressures were not routinely recorded. Following angioplasty, the patients were kept overnight for routine procedure specific observations and blood pressure management. 1.3. Definitions Hypertension was defined as an average systolic blood pressure (sBP) and/or diastolic blood pressure (dBP) that was ≥95th percentile for age, sex and height on three separate occasions. [12]. Renal artery stenosis was defined as any narrowing of the renal artery: Ostial stenoses were defined by lesions that involved the renal ostium and did not extend beyond 5 mm from the aortic origin. Truncal stenoses were defined as those lesions confined to the main renal artery that did not involve the ostium or the divisional branches. Branch stenoses were defined as those lesions confined to branch vessels or by a component of the stenosis extending into the divisional or segmental branches [13]. Outcomes were defined in terms of both anatomical and clinical results: 1.3.1. Anatomical outcomes Success was achieved if the post-PTA aortogram demonstrated a b 30% residual stenosis in the renal artery [14]. Failure was defined as those angioplasties that failed to achieve a b 30% residual stenosis. Clinical outcomes defined at 1 year post PTA in one of three ways: 1. Cured: A normotensive child off all anti-hypertensive medication. 2. Improved: One of the following three criteria had to be met:
Fig. 2. A false aneurysm with intraluminal clot requiring surgical revascularization.
• A sustained post-PTA decrease in number of antihypertensive medications without an increase in dosage of any of the medications, • A sustained post-PTA decrease in dosage of the medications without any change in type/number of medications, • A sustained decrease in BP by at least one major percentile division with no increase in dose or number of medications.
A. Alexander et al. / Journal of Pediatric Surgery 52 (2017) 395–399
3. Failure: No improvement in hypertension and no reduction in the dose or number of blood pressure medications
397
Table 1 Patient exclusion algorithm.
Clinical success: A positive clinical outcome. Either an improvement or cure. 1.3.2. Complications Complications were defined and classified as either minor or major, based on outcome and occurring within 30 days of the procedure, as per the Society for Interventional Radiology's standards of practice committee [14]. 1.4. Measurements and calculations The length of the stenosis was a measure of the distance between the proximal and distal shoulders of the stenosis. The percentage stenosis was calculated by measuring the ratio between the diameter of the narrowest segment of the renal artery and the diameter of the reference segment. Where there was a pre-stenotic segment of artery present, this was taken as the reference segment. Where there was no pre-stenotic segment present, then the segment of distal vessel beyond any perceived post-stenotic dilation was measured. 1.5. Follow-up Patients who underwent PTA had at least 1 year of follow-up BP monitoring. Anti-hypertensive medication, dose, and height were recorded. Data were extracted from clinic notes, or were captured telephonically from referring pediatric centers and adult hospitals where transition to adult care had taken place. 1.6. Outcomes reporting The primary outcome measure was clinical success as reflected by a favorable, measurable and sustained clinical response in blood pressure following renal angioplasty.
respective 95th percentile (range of 18–72 mmHg). The mean diastolic BP was 20 mmHg for boys and 33 mmHg for girls above their respective 95th percentile (range of 13–50 mmHg). The mean number of antihypertensive medications taken by this group was 2. At diagnosis 7 patients had renal impairment, 3 of whom had pre-existing nephropathy. Urinalysis revealed proteinuria and hematuria in 6 patients with isolated proteinuria in 1. Eight patients had ventricular hypertrophy evident on ECG or echo cardiogram.
1.7. Statistical analysis Descriptive statistics were performed using EpiCalc2000. Results have been described using means medians and ranges. 2. Results Between April 1992 and April 2009, 216 patients underwent diagnostic angiography for suspected renovascular hypertension. Of these, 34 patients had renal artery stenosis identified. Twenty-nine subsequently underwent PTA. Of the 5 that did not have an angioplasty, 2 opted for ongoing medical management and 3 went on to have surgical revascularization as the lesions were not amenable to PTA. One patient was lost to follow-up (at nine months, normotensive and off all medication). The remaining 28 pediatric patients were included in this study. [Table 1]. The median age at first PTA was 8.25 years (range 7 months– 17.3 years). The male to female ratio was 1.6:1. 2.1. Clinical features Of the 23 patients who had documentation of the circumstances surrounding their initial diagnosis of hypertension, the majority 19 (83%) were clinically asymptomatic. Fibromuscular dysplasia accounted for 14/28 (50%) of the patients with an underlying vascular pathology in our group. The remaining 14 patients had underlying diagnoses of neurofibromatosis (n = 5), renal transplantation (n = 4) Takayasu's (n = 3), nonspecific vasculitis (n = 1) and William's syndrome (n = 1). The sole indication for referral to the interventional radiology service for diagnostic angiogram was poorly controlled hypertension. The mean systolic BP was 36 mmHg for boys and 44 mmHg for girls above their
2.2. Angiographic features In our series 4 patients had transplant vessel stenosis. In the remaining 24 the renal artery stenosis was bilateral in 5 patients (20%), on the right in 12 (50%) and on the left in 7 (30%). The median percentage stenosis was 66% (range 25% to 95%). The median length of the lesion was 5.3 mm (range 1 mm–19.9 mm). Trunk vessel stenoses were present in 12 (50%), ostial lesions were evident in 4 (17%) and branch stenoses in 3 (13%) of the patients. Diffuse proximal disease involving the ostium and trunk was seen in 2 patients, diffuse distal disease of trunk and branch vessels was seen in 2 and diffuse disease involving the entire vascular tree was seen in 1 patient. 2.3. Angioplasty results Twenty-eight patients underwent 42 renal PTA's. Anatomical success, as defined above, was achieved following 24/42 angioplasties with complete obliteration of stenosis in 9 patients, b 30% residual stenosis in 15. Anatomical failure, as defined above, occurred in 18/24 with N 30% residual stenosis in 15 and complete non-response in 3. Ten patients had more than one angioplasty. Median time between repeated angioplasties in the same patient was 209 days (range 63–1155 days). In 3/10 patients the stenosis appeared more severe on their repeat imaging, than after their first angioplasty, suggesting restricturing and recurrence. The remaining 7 patients showed sustained improvement in the angiographic appearance, but the lesion remained clinically significant. In addition to standard balloon dilation a cutting balloon was used in 2 patients, a wire passed alongside the balloon
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Table 2 Complications of angioplasty. Major Complications
Number
SIR grade(18)
Renal loss, transient self-limiting limb ischemia and a groin hematoma in one patient False aneurysm requiring elective surgical revascularization (cutting balloon) Hypoglycemic seizure and a burst balloon with fragmentation of a guide-wire requiring alternate access for retrieval
1 1 1
E D C
Minor Complications Groin hematomas (self-limiting, no treatment) Burst balloon Renal artery spasm (self-limiting, no treatment) Luminal thrombus extracted during the procedure Hospitalization N24 h, prolonged bleeding, decreased Hb (not transfused), burst balloon Mild transient foot pain (self-limiting, no treatment) Prolonged bleeding from femoral site (pressure applied) Perforation of renal artery (transient, sealed spontaneously) Retroperitoneal hematoma not requiring treatment Intimal flap created without compromised flow
(“focused force angioplasty”) was used in 1, and one patient had a combination of “focused force angioplasty” and cutting techniques employed. No patient in this group had renal artery stenting. Three patients suffered a major complication as a result of PTA [Image 2]. Minor complications occurred in 18 angiograms [Table 2]. 2.4. Clinical results Of the 28 patients, 10 (35.8%) were cured, 9 (32.1%) were improved and 9 (32.1%) failed after a minimum of one year of follow-up. [Table 3] Cure was achieved after one PTA in 6 patients, two PTAs in 3 patients and four PTAs in 1 patient. Fibromuscular dysplasia was the most likely cause for the underlying vasculopathy in 14 patients in this series (50%) and was associated with a PTA success rate of 78.5%. Despite small numbers, Takayasu's, neurofibromatosis and transplant stenosis were associated with reasonable success (70, 60 and 50% respectively). Of those angioplasties that demonstrated anatomical success, only 15/24 (63%) correlated with clinical success. Conversely anatomical failure correlated with clinical failure in 12/18 (67%). 2.5. Follow-up Median follow-up for each angiogram was 3.8 years [range 1.0–9.9 years]. 3. Discussion This series documents the outcomes of PTA in an exclusively pediatric population of 28 patients that underwent 42 angiograms. In our
Table 3 The clinical results of 28 patients.
6 3 2 1 1 1 1 1 1 1
A B A B B A A A B B
series right sided and truncal stenosis dominated. Clinical success was achieved in 68% of our patients at one year of follow-up. In our hands the procedure has an acceptable complication profile with major complications occurring in 7% and minor complications in 43% of angioplasties. This compares very favorably with other reports in children [11]. With respect to the distribution of renal vascular disease, this series with its 54% prevalence of truncal disease, differs from the experience of Vo who reported that divisional branches were involved in 50% of their patients [15]. The results of the balloon angioplasty are in-line with the outcomes of Tyagi and Schroff in curing about one third, improving blood pressure control in one third and failure of the intervention being reported in one third [11,16]. We were unable to identify features of the diagnosis, stenosis or response to PTA that could predict, with statistical significance, the clinical outcome in our patients. FMD with its 79% success rate for PTA suggests that this disease is amenable to the intervention but as a predictor of success it failed to reach statistical significance when compared with pooled data (p = 0.22). Anatomical outcome as a predictor of clinical outcome also failed to reach statistical significance (p = 0.06). Neither length of the stenosis nor degree of narrowing predicted outcome in our series. A single repeat PTA appears to have a similar result distribution as a primary procedure. Attempts beyond this would intuitively be met with less success and the results for two such PTAs were in keeping with this expectation, both having failed. However, we had a single patient that had three failed interventions including the use of a cutting balloon, and yet achieved success after the fourth procedure. It appears that there was no increased risk of complications beyond that inherent in each individual procedure. Given the above results it seems prudent to attempt a second angioplasty in those children who have experienced an initial failure. The decision to perform subsequent angioplasties should be individualized. The experience with cutting balloons in this series is very limited. They were used with mixed success in three patients, one of whom required surgical intervention for the development of a renal artery aneurysm. We did not stent any of the patients in this study period. This study highlights some of the difficulties of applying established adult reporting standards to pediatric interventions. For example, antihypertensive medicine dose is a marker of outcome in adults and yet doses are constantly increased with increasing weight as the pediatric patient grows. Length of the stenosis is another important reporting criteria when comparing results in adult series but in pediatric patients the renal vessels are expected to lengthen as the child grows making absolute lengths vary considerably with age. Prospective trials with standard medication regimes and alteration protocols could offset the problems with drug dosing. Similarly ratios of the length of the stenosis to a relatively constant variable such as vertebral body height could
A. Alexander et al. / Journal of Pediatric Surgery 52 (2017) 395–399
possibly be a more accurate reporting tool. In addition, comparison of results from pediatric trials and adult trials (ASTRAL or CORAL) is very difficult. Adult patients are generally much older, atherosclerosis is the predominant etiology, end organ dysfunction is more prevalent and primary outcome measures are different, focusing on death and organ dysfunction. To compete with the available adult literature, prospective multi-institutional studies and registries are required. It is important to standardize measurements, outcomes and reporting if we are going to meaningfully pool pediatric institutional experience. There are several limitations to this study. It is a single-center study with relatively small numbers. Data collection for this study highlights many inherent limitations of a retrospective chart review. BP measurements were readings taken in a variety of specialist clinics using different methods of measurement. Antihypertensive medication regimens were not standardized as our patients came from different referring nephrologists with a highly variable prescribing practice. In addition, medication reduction following intervention did not follow any specific protocols. The angioplasty technique was not standardized and there were no set criteria for intervention. At least two patients had a b 50% stenosis, a degree of stenosis less than this is thought not to be hemodynamically significant in the adult literature. The catheters, balloons and techniques varied as experience increased and equipment improved through the years of the study. In future cohorts, use of fine pressure measuring wires and intravascular ultrasound may play important roles in establishing anatomical and hemodynamic results. Follow-up of more than one year appears to be a reasonable measure of short and intermediate term outcomes but long-term data are essential to ascertain the durability of the procedure. This is especially true in the pediatric population where growth and an increased demand on the renal supply are expected.
4. Conclusion We believe PTA for renovascular hypertension is a worthwhile initial intervention in centers that have the necessary expertise, equipment and experience. Angioplasty for renovascular hypertension in our exclusively pediatric population is curative in 36% of patients and improves blood pressure control in a further 32% of patients. The intervention is far less invasive than open surgery and has a favorable side effect profile. Of all the underlying causes of stenosis, FMD appeared to have a better response to PTA in our series.
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5. Abbreviations
BP FMD IR PTA RVH
Blood Pressure Fibromuscular Dysplasia Interventional Radiology Percutaneous Transluminal Angioplasty Renovascular Hypertension
Conflicts of interest The authors declare that they have no conflict of interest. References [1] Moore WE, Stephens A, Wilson T, et al. Body mass index and blood pressure screening in a rural public school system: the Healthy Kids Project. Prev Chronic Dis 2006;3(4): A114. [2] Sinaiko AR. Hypertension in children. N Engl J Med 1996;335(26):1968–73. [3] Sorof JM, Lai D, Turner J, et al. Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004;113(3 Pt 1):475–82. [4] Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and adolescents. JAMA 2007;298(8):874–9. [5] Gill DG, Mendes de Costa B, Cameron JS, et al. Analysis of 100 children with severe and persistent hypertension. Arch Dis Child 1976;51(12):951–6. [6] Wyszynska T, Cichocka E, Wieteska-Klimczak A, et al. A single pediatric center experience with 1025 children with hypertension. Acta Paediatr 1992;81(3):244–6. [7] Kidney D, Deutsch LS. The indication and results of percutaneous transluminal angioplasty and stenting in renal artery stenosis. Semin Vasc Surg 1996;9:188–97. [8] Martin LG, Rees CR, O'Bryant T. In: D.E.S Jr, Breda Av, editors. Percutaneous angioplasty of the renal arteries, in Vascular Disease: Surgical and interventional therapy. Churchill Livingstone; 1994. p. 721–41. [9] Sos TA, Pickering TG, Saddekni S, et al. The current role of renal angioplasty in the treatment of renovascular hypertension. Urol Clin North Am 1984;11:503–13. [10] Safian RD. Renal artery stenosis. N Engl J Med 2001;344(6):431–42. [11] Shroff R, Roebuck DJ, Gordon I, et al. Angioplasty for renovascular hypertension in children: 20-year experience. Pediatrics 2006;118(1):268–75. [12] National High Blood Pressure Education Program Working Group on High Blood Pressure in, C. and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004; 114(2 Suppl 4th Report):555–76. [13] Rundback JH, Sacks D, Kent KC, et al. Guidelines for the reporting of renal artery revascularization in clinical trials. J Vasc Interv Radiol 2003;14(9 Pt 2):S477–92. [14] Martin LG, Rundback JH, Wallace MJ, et al. Quality improvement guidelines for angiography, angioplasty, and stent placement for the diagnosis and treatment of renal artery stenosis in adults. J Vasc Interv Radiol 2010;21(4):421–30 [quiz 230]. [15] Vo NJ, Hammelman BD, Racadio JM, et al. Anatomic distribution of renal artery stenosis in children: implications for imaging. Pediatr Radiol 2006;36(10):1032–6. [16] Tyagi S, Kaul AU, Satsangi DK, et al. Percutaneous transluminal angioplasty for renovascular hypertension in children: initial and long-term results. Pediatrics 1997; 99(1):44–9.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Outcomes of percutaneous transluminal angioplasty for pediatric renovascular hypertension☆,☆☆ Angus Alexander a,e,⁎, Lara Richmond b, Denis Geary c, Joao Luis Pippi Salle a,d, Joao Amaral b, Bairbre Connolly b a
Division of Pediatric Urology, The Hospital for Sick Children, University of Toronto, Canada Breast Imaging Division, Sunnybrook Health Sciences Centre, Toronto Division of Nephrology, Department of Pediatrics, Sidra Medical and Research Center, Doha, Qatar d Division of Pediatric Urology, Sidra Medical and Research Center, Doha, Qatar e Department of Paediatric Surgery, The Sydney Children's Hospital Network at Westmead, Sydney, Australia b c
a r t i c l e
i n f o
Article history: Received 5 February 2016 Received in revised form 30 June 2016 Accepted 18 August 2016 Key words: Pediatric Hypertension Percutaneous transluminal angioplasty Renovascular Endovascular
a b s t r a c t Background: Up to 10% of hypertensive children will have renovascular disease. Where medical therapy fails to control the hypertension, endovascular techniques can improve renal perfusion. The purpose of this study was to assess the efficacy of angioplasty in controlling renovascular hypertension (RVH) in children. Methods: This is a single-center, retrospective review of patients who underwent angioplasty for RVH between 1992 and 2009. All patients were selected from the Interventional Radiology database. The primary outcome measure was clinical success as reflected by a favorable, sustained response in blood pressure for at least 1 year following the angioplasty. Results: Two hundred sixteen patients underwent diagnostic angiography for suspected RVH, of these 28 required 42 angioplasties. Ten (36%) were cured, 9 (32%) were improved and 9 (32%) failed to respond to treatment. Major complications occurred in three patients and minor complications occurred in 18 angioplasties. Fibromuscular dysplasia (FMD) was the most common diagnosis in this series and was associated with a 79% success rate. Conclusion: In our exclusively pediatric population angioplasty safely improved blood pressure control in 68% of patients, more than half of which are cured. FMD appeared to have the best clinical outcomes in our series. © 2017 Elsevier Inc. All rights reserved.
(See Figs. 1 and 2.) Hypertension affects 1%–3% of children [1–4] and of these, 5%–10% will have renovascular disease [5,6]. The latter are a small but very important group because they are potentially curable. Traditionally antihypertensive medication and surgical revascularization have formed the backbone of pediatric management. The efficacy of renal artery PTA for the reduction of blood pressure (BP) in pediatric and adult patients is highly variable with the available literature reporting a 28%–94% and 36%–100% success rate respectively, [7–11]. The purpose of this study was to assess our results using PTA for renovascular hypertension (RVH) in an exclusively pediatric practice and to add a relatively large series to the published data on the subject. 1. Materials and methods We conducted a single-center, retrospective review of all patients who underwent PTA for RVH in a tertiary pediatric center between the 1st of ☆ Compliance with Ethical Standards. ☆☆ Conflicts of Interest: The authors declare that they have no conflict of interest. ⁎ Corresponding author at: Department of Paediatric Surgery, The Sydney Children's Hospital Network at Westmead, Cnr Hawkesbury Road and Hainsworth Street, Westmead, 2145, Sydney, Australia. E-mail address: [email protected] (A. Alexander). http://dx.doi.org/10.1016/j.jpedsurg.2016.08.011 0022-3468/© 2017 Elsevier Inc. All rights reserved.
April 1992 and the 30th of April 2009. The study was approved by the hospital's research ethics board and is a collaborative work involving the departments of Interventional Radiology (IR), Urology and Nephrology.
1.1. Patients All patients who had a diagnosis of renovascular hypertension and underwent a PTA of their renal arteries were selected from the IR database. The study included patients with systemic or regional vasculopathy and renal transplant recipients who underwent PTA. All patients had at least one year of follow-up. The medical records for identified patients were reviewed for demographic data; clinical presentation; urinalysis; associated regional or systemic vasculopathy; age, weight and BP; antihypertensive medication and dose. All angiographic images that were available as an electronic record (PACS) were reviewed by the principal and senior author. Any procedures prior to this had details extracted from the IR reports. Follow-up data were sourced from medical records where possible; telephone reports were required in five patients who were not being followed at our institution. All children were referred to the interventional radiology team by local or regional nephrology services based on a strong clinical suspicion
396
A. Alexander et al. / Journal of Pediatric Surgery 52 (2017) 395–399
Fig. 1. a. Deployment and partial inflation of the angioplasty balloon in the left renal artery. The stenosis is evident as a waist in the balloon. b. Full balloon inflation with obliteration of the waist during angioplasty.
of renovascular hypertension and poor blood pressure control despite best medical management.
1.2. Technique 1.2.1. Angiography All renal angiograms were performed under general anesthetic and systemic heparinization (100 U/kg). Initial assessment in the early series included routine renal vein renin sampling prior to any endovascular intervention. PTA was either performed during the same anesthetic or at a subsequent procedure depending on the patient's condition and the certainty of the diagnosis. In later years, renal vein renin samples were taken less often. The contralateral femoral artery was catheterized for diagnostic angiography with a 4 French sheath. A flush aortogram was performed followed by selective renal angiography.
1.2.2. Percutaneous transluminal angioplasty Balloon size was chosen according to the estimated normal renal artery size (range 3–6 mm) [Image 1a and 1b]. A post procedure angiogram was performed to assess the response, residual stenosis, and any complications. Because of the size of the pediatric vasculature and the limitations of early pressure monitors post-PTA, trans-lesional pressures were not routinely recorded. Following angioplasty, the patients were kept overnight for routine procedure specific observations and blood pressure management. 1.3. Definitions Hypertension was defined as an average systolic blood pressure (sBP) and/or diastolic blood pressure (dBP) that was ≥95th percentile for age, sex and height on three separate occasions. [12]. Renal artery stenosis was defined as any narrowing of the renal artery: Ostial stenoses were defined by lesions that involved the renal ostium and did not extend beyond 5 mm from the aortic origin. Truncal stenoses were defined as those lesions confined to the main renal artery that did not involve the ostium or the divisional branches. Branch stenoses were defined as those lesions confined to branch vessels or by a component of the stenosis extending into the divisional or segmental branches [13]. Outcomes were defined in terms of both anatomical and clinical results: 1.3.1. Anatomical outcomes Success was achieved if the post-PTA aortogram demonstrated a b 30% residual stenosis in the renal artery [14]. Failure was defined as those angioplasties that failed to achieve a b 30% residual stenosis. Clinical outcomes defined at 1 year post PTA in one of three ways: 1. Cured: A normotensive child off all anti-hypertensive medication. 2. Improved: One of the following three criteria had to be met:
Fig. 2. A false aneurysm with intraluminal clot requiring surgical revascularization.
• A sustained post-PTA decrease in number of antihypertensive medications without an increase in dosage of any of the medications, • A sustained post-PTA decrease in dosage of the medications without any change in type/number of medications, • A sustained decrease in BP by at least one major percentile division with no increase in dose or number of medications.
A. Alexander et al. / Journal of Pediatric Surgery 52 (2017) 395–399
3. Failure: No improvement in hypertension and no reduction in the dose or number of blood pressure medications
397
Table 1 Patient exclusion algorithm.
Clinical success: A positive clinical outcome. Either an improvement or cure. 1.3.2. Complications Complications were defined and classified as either minor or major, based on outcome and occurring within 30 days of the procedure, as per the Society for Interventional Radiology's standards of practice committee [14]. 1.4. Measurements and calculations The length of the stenosis was a measure of the distance between the proximal and distal shoulders of the stenosis. The percentage stenosis was calculated by measuring the ratio between the diameter of the narrowest segment of the renal artery and the diameter of the reference segment. Where there was a pre-stenotic segment of artery present, this was taken as the reference segment. Where there was no pre-stenotic segment present, then the segment of distal vessel beyond any perceived post-stenotic dilation was measured. 1.5. Follow-up Patients who underwent PTA had at least 1 year of follow-up BP monitoring. Anti-hypertensive medication, dose, and height were recorded. Data were extracted from clinic notes, or were captured telephonically from referring pediatric centers and adult hospitals where transition to adult care had taken place. 1.6. Outcomes reporting The primary outcome measure was clinical success as reflected by a favorable, measurable and sustained clinical response in blood pressure following renal angioplasty.
respective 95th percentile (range of 18–72 mmHg). The mean diastolic BP was 20 mmHg for boys and 33 mmHg for girls above their respective 95th percentile (range of 13–50 mmHg). The mean number of antihypertensive medications taken by this group was 2. At diagnosis 7 patients had renal impairment, 3 of whom had pre-existing nephropathy. Urinalysis revealed proteinuria and hematuria in 6 patients with isolated proteinuria in 1. Eight patients had ventricular hypertrophy evident on ECG or echo cardiogram.
1.7. Statistical analysis Descriptive statistics were performed using EpiCalc2000. Results have been described using means medians and ranges. 2. Results Between April 1992 and April 2009, 216 patients underwent diagnostic angiography for suspected renovascular hypertension. Of these, 34 patients had renal artery stenosis identified. Twenty-nine subsequently underwent PTA. Of the 5 that did not have an angioplasty, 2 opted for ongoing medical management and 3 went on to have surgical revascularization as the lesions were not amenable to PTA. One patient was lost to follow-up (at nine months, normotensive and off all medication). The remaining 28 pediatric patients were included in this study. [Table 1]. The median age at first PTA was 8.25 years (range 7 months– 17.3 years). The male to female ratio was 1.6:1. 2.1. Clinical features Of the 23 patients who had documentation of the circumstances surrounding their initial diagnosis of hypertension, the majority 19 (83%) were clinically asymptomatic. Fibromuscular dysplasia accounted for 14/28 (50%) of the patients with an underlying vascular pathology in our group. The remaining 14 patients had underlying diagnoses of neurofibromatosis (n = 5), renal transplantation (n = 4) Takayasu's (n = 3), nonspecific vasculitis (n = 1) and William's syndrome (n = 1). The sole indication for referral to the interventional radiology service for diagnostic angiogram was poorly controlled hypertension. The mean systolic BP was 36 mmHg for boys and 44 mmHg for girls above their
2.2. Angiographic features In our series 4 patients had transplant vessel stenosis. In the remaining 24 the renal artery stenosis was bilateral in 5 patients (20%), on the right in 12 (50%) and on the left in 7 (30%). The median percentage stenosis was 66% (range 25% to 95%). The median length of the lesion was 5.3 mm (range 1 mm–19.9 mm). Trunk vessel stenoses were present in 12 (50%), ostial lesions were evident in 4 (17%) and branch stenoses in 3 (13%) of the patients. Diffuse proximal disease involving the ostium and trunk was seen in 2 patients, diffuse distal disease of trunk and branch vessels was seen in 2 and diffuse disease involving the entire vascular tree was seen in 1 patient. 2.3. Angioplasty results Twenty-eight patients underwent 42 renal PTA's. Anatomical success, as defined above, was achieved following 24/42 angioplasties with complete obliteration of stenosis in 9 patients, b 30% residual stenosis in 15. Anatomical failure, as defined above, occurred in 18/24 with N 30% residual stenosis in 15 and complete non-response in 3. Ten patients had more than one angioplasty. Median time between repeated angioplasties in the same patient was 209 days (range 63–1155 days). In 3/10 patients the stenosis appeared more severe on their repeat imaging, than after their first angioplasty, suggesting restricturing and recurrence. The remaining 7 patients showed sustained improvement in the angiographic appearance, but the lesion remained clinically significant. In addition to standard balloon dilation a cutting balloon was used in 2 patients, a wire passed alongside the balloon
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Table 2 Complications of angioplasty. Major Complications
Number
SIR grade(18)
Renal loss, transient self-limiting limb ischemia and a groin hematoma in one patient False aneurysm requiring elective surgical revascularization (cutting balloon) Hypoglycemic seizure and a burst balloon with fragmentation of a guide-wire requiring alternate access for retrieval
1 1 1
E D C
Minor Complications Groin hematomas (self-limiting, no treatment) Burst balloon Renal artery spasm (self-limiting, no treatment) Luminal thrombus extracted during the procedure Hospitalization N24 h, prolonged bleeding, decreased Hb (not transfused), burst balloon Mild transient foot pain (self-limiting, no treatment) Prolonged bleeding from femoral site (pressure applied) Perforation of renal artery (transient, sealed spontaneously) Retroperitoneal hematoma not requiring treatment Intimal flap created without compromised flow
(“focused force angioplasty”) was used in 1, and one patient had a combination of “focused force angioplasty” and cutting techniques employed. No patient in this group had renal artery stenting. Three patients suffered a major complication as a result of PTA [Image 2]. Minor complications occurred in 18 angiograms [Table 2]. 2.4. Clinical results Of the 28 patients, 10 (35.8%) were cured, 9 (32.1%) were improved and 9 (32.1%) failed after a minimum of one year of follow-up. [Table 3] Cure was achieved after one PTA in 6 patients, two PTAs in 3 patients and four PTAs in 1 patient. Fibromuscular dysplasia was the most likely cause for the underlying vasculopathy in 14 patients in this series (50%) and was associated with a PTA success rate of 78.5%. Despite small numbers, Takayasu's, neurofibromatosis and transplant stenosis were associated with reasonable success (70, 60 and 50% respectively). Of those angioplasties that demonstrated anatomical success, only 15/24 (63%) correlated with clinical success. Conversely anatomical failure correlated with clinical failure in 12/18 (67%). 2.5. Follow-up Median follow-up for each angiogram was 3.8 years [range 1.0–9.9 years]. 3. Discussion This series documents the outcomes of PTA in an exclusively pediatric population of 28 patients that underwent 42 angiograms. In our
Table 3 The clinical results of 28 patients.
6 3 2 1 1 1 1 1 1 1
A B A B B A A A B B
series right sided and truncal stenosis dominated. Clinical success was achieved in 68% of our patients at one year of follow-up. In our hands the procedure has an acceptable complication profile with major complications occurring in 7% and minor complications in 43% of angioplasties. This compares very favorably with other reports in children [11]. With respect to the distribution of renal vascular disease, this series with its 54% prevalence of truncal disease, differs from the experience of Vo who reported that divisional branches were involved in 50% of their patients [15]. The results of the balloon angioplasty are in-line with the outcomes of Tyagi and Schroff in curing about one third, improving blood pressure control in one third and failure of the intervention being reported in one third [11,16]. We were unable to identify features of the diagnosis, stenosis or response to PTA that could predict, with statistical significance, the clinical outcome in our patients. FMD with its 79% success rate for PTA suggests that this disease is amenable to the intervention but as a predictor of success it failed to reach statistical significance when compared with pooled data (p = 0.22). Anatomical outcome as a predictor of clinical outcome also failed to reach statistical significance (p = 0.06). Neither length of the stenosis nor degree of narrowing predicted outcome in our series. A single repeat PTA appears to have a similar result distribution as a primary procedure. Attempts beyond this would intuitively be met with less success and the results for two such PTAs were in keeping with this expectation, both having failed. However, we had a single patient that had three failed interventions including the use of a cutting balloon, and yet achieved success after the fourth procedure. It appears that there was no increased risk of complications beyond that inherent in each individual procedure. Given the above results it seems prudent to attempt a second angioplasty in those children who have experienced an initial failure. The decision to perform subsequent angioplasties should be individualized. The experience with cutting balloons in this series is very limited. They were used with mixed success in three patients, one of whom required surgical intervention for the development of a renal artery aneurysm. We did not stent any of the patients in this study period. This study highlights some of the difficulties of applying established adult reporting standards to pediatric interventions. For example, antihypertensive medicine dose is a marker of outcome in adults and yet doses are constantly increased with increasing weight as the pediatric patient grows. Length of the stenosis is another important reporting criteria when comparing results in adult series but in pediatric patients the renal vessels are expected to lengthen as the child grows making absolute lengths vary considerably with age. Prospective trials with standard medication regimes and alteration protocols could offset the problems with drug dosing. Similarly ratios of the length of the stenosis to a relatively constant variable such as vertebral body height could
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possibly be a more accurate reporting tool. In addition, comparison of results from pediatric trials and adult trials (ASTRAL or CORAL) is very difficult. Adult patients are generally much older, atherosclerosis is the predominant etiology, end organ dysfunction is more prevalent and primary outcome measures are different, focusing on death and organ dysfunction. To compete with the available adult literature, prospective multi-institutional studies and registries are required. It is important to standardize measurements, outcomes and reporting if we are going to meaningfully pool pediatric institutional experience. There are several limitations to this study. It is a single-center study with relatively small numbers. Data collection for this study highlights many inherent limitations of a retrospective chart review. BP measurements were readings taken in a variety of specialist clinics using different methods of measurement. Antihypertensive medication regimens were not standardized as our patients came from different referring nephrologists with a highly variable prescribing practice. In addition, medication reduction following intervention did not follow any specific protocols. The angioplasty technique was not standardized and there were no set criteria for intervention. At least two patients had a b 50% stenosis, a degree of stenosis less than this is thought not to be hemodynamically significant in the adult literature. The catheters, balloons and techniques varied as experience increased and equipment improved through the years of the study. In future cohorts, use of fine pressure measuring wires and intravascular ultrasound may play important roles in establishing anatomical and hemodynamic results. Follow-up of more than one year appears to be a reasonable measure of short and intermediate term outcomes but long-term data are essential to ascertain the durability of the procedure. This is especially true in the pediatric population where growth and an increased demand on the renal supply are expected.
4. Conclusion We believe PTA for renovascular hypertension is a worthwhile initial intervention in centers that have the necessary expertise, equipment and experience. Angioplasty for renovascular hypertension in our exclusively pediatric population is curative in 36% of patients and improves blood pressure control in a further 32% of patients. The intervention is far less invasive than open surgery and has a favorable side effect profile. Of all the underlying causes of stenosis, FMD appeared to have a better response to PTA in our series.
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5. Abbreviations
BP FMD IR PTA RVH
Blood Pressure Fibromuscular Dysplasia Interventional Radiology Percutaneous Transluminal Angioplasty Renovascular Hypertension
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