Original Article
Clinical Practice,Resource Utilization,and Outcomes of Device Closure of Patent Foramen Ovale in Pediatrics
Shaji C.Menon MD a ,*,Amanda Grove BS a ,Molly McFadden MS b ,Kent E.Korgenski MS b ,Collin G.Cowley MD a
a Division of Pediatric Cardiology,University of Utah,Salt Lake City,Utah b
Department of Pediatrics,University of Utah,Salt Lake City,Utah
abstract
BACKGROUND:There are few data on patent foramen ovale closure and its outcome in children.In this study,we
evaluated the current clinical practice,resource utilization,and outcome of device closure of patent foramen ovale in children.We hypothesized that patent foramen ovale closure would not result in a demonstrated bene fit in children.METHODS:We undertook a prospective survey of all concutive pati
ents (<20years)who underwent patent foramen ovale closure in our metropolitan area between 1995and 2010.Differences in proportions were tested using the chi-square test or Fisher ’s exact test where appropriate.Differences in group medians were tested using Wilcoxon signed-rank test.RESULTS:A total of 153patients (104girls),median age 16years (range 7-19)were studied.Indications for patent foramen ovale closure included:(1)migraine headache (104;68%),(2)nonmigraine headache (24;16%),(3)visual symptoms (110;72%),(4)transient ischemic attack symptoms (42;28%),and (5)stroke-like symptom (24;16%).Patent foramen ovale was clod with an Amplatzer ptal occluder in 115(75%)and a Helex ptal occluder in 47(30%).The mean length of hospital stay was 18Æ11hours;the mean hospital charge was $24,126Æ$5808.The median duration of follow-up was 12months,and 80patients responded to the study survey.On follow-up,symptoms improved in 143(93%),of which 29(19%)had a residual shunt.None of the patient or treatment parameters predicted lack of improvement on follow-up.CONCLUSIONS:Despite the lack of proven bene fit,children undergo closure of the patent foramen ovale for a variety of reasons,with the vast ma-jority (92%)of patients reporting signi ficant improvement in their symptoms.However,patent foramen ovale closure is an expensive procedure with rious potential complications.Symptomatic improvement even in the prence of a residual shunt suggests a strong placebo effect.
Keywords:patent foramen ovale,children,migraine,outcome,resource utilization
Pediatr Neurol 2014;50:213-217
购物车 英文
Ó2014Elvier Inc.All rights rerved.
See related editorial on page 203.
Background
A patent foramen ovale (PFO)is a normal fetal connection between the right and left atria that allows oxygen-rich职称英语考试
blood from the placenta to bypass the lungs and supply the fetal heart and brain.This hemodynamically insigni fi-cant communication between the atria clos in the major-ity of people with time.However,in approximately 25%of the adult population,the ptum primum fails to fu with the ptum cundum and the PFO remains patent allowing for interatrial communication.1A number of studies in adults have shown an association between the prence of a PFO and migraine headaches with aura.2,3Other studies have shown a signi ficant reduction in migraine symptoms after closure of PFO.4-6However,other studies have failed to show any bene fit.7,8The prence of a PFO has also been associated with cryptogenic stroke 9-12and decompression sickness in divers.
13There are few data in children regarding an association between PFO and migraine headaches.In a
Disclosure :None of the authors have any con flict of interest or disclosure.Funding:None.
Prented in part at the 2012meeting of the American Academy of Pediatrics,New Orleans,Louisiana.
Article History:
Received June 10,2013;Accepted in final form November 12,2013
*Communications should be addresd to:Dr.Shaji C Menon;Pedi-atric Cardiology;100N.Mario Capechhi Drive;Salt Lake City,UT 84113.
E-mail address:
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<@utah.edu
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Pediatric Neurology
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Pediatric Neurology 50(2014)213e 217
previous study from our center,children with migraine with aura were found to have significantly high
er prevalence of PFO(50%)compared with tho without aura(27%)or the general population.14However,there are few data on out-comes of device closure of PFO in children.Despite the lack of rigorous scientific evidence demonstrating a benefit to children undergoing device closure of PFO,we have wit-nesd an apparent increasing number of children in our metropolitan area referred for device closure of their PFO. The objective of this study was to evaluate the current clinical practice,resource utilization,and outcome of device closure of PFO in children.Bad on current published re-sults in adults,we hypothesized that PFO closure would not result in a demonstrated benefit in children.
Methods
We reviewed the records of all concutive patients(<20years)who underwent device closure of PFO between January1995and December 2010throughout the Intermountain Healthcare system.Intermountain Healthcare is an internationally recognized nonprofit system of22 hospitals in Utah and Idaho.The hospitals rve as the largest single referral center for children living in the Intermountain West.This study was approved by the institutional review boards of the University of Utah and Intermountain Healthcare.Parental connt and participant asnt were obtained as appropriate.
Retrospective data
The following retrospective data were collected:patient demographics,family history of PFO closure,clinical characteristics, indications for procedure,number of symptoms,preprocedural workup and evaluation,number of medications,procedural details,device ud, complications,postprocedure therapy,outcome,length of stay,and procedural charges.
Prospective survey
A survey was administered prospectively to miquantitatively evaluate the respon to therapy.Respon to treatment was graded as1, complete resolution;2,reduction in symptoms;3,no improvement;or4, worning of symptoms.
Our survey also asked who recommended device closure of PFO:(1) neurologist,(2)cardiologist,(3)family or friends,or(4)other.We also asked if the patient would recommend this procedure to a friend with similar problems(yes or no).For patients who did not respond to our survey,data regarding clinical improvement were obtained retrospec-tively from their last clinic visit note and graded in a similar fashion as described previously.
Patent Foramen Ovale
A PFO,defined as incomplete adherence of the ptum primum and ptum cundum at the level of the fossa ovalis,was diagnod by two-dimensional and Doppler transthoracic echocardiography or transophageal echocardiography and transcranial Doppler scanning. Shunting across the atrial ptum was evaluated with two-dimensional transthoracic/transophageal echocardiography using agitated saline contrast solution and by transcranial Doppler also using agitated saline contrast solution.Patients with cundum atrial ptal defects with deficiency of the atrial ptum and right heart enlargement were excluded from this study.
Statistics
Continuous variables were expresd as the meanÆstandard deviation.Dichotomous variables were expresd as a percentage fre-quency.Differences in proportions were tested using chi square test or Fisher’s exact test where appropriate.Differences between group medians were tested using Wilcoxon signed-rank test.A generalized linear regres-sion analysis was ud to test the demographic,preprocedure,procedure, or postprocedure factors associated with improvement or nonimprove-ment in symptoms for which PFO closure was performed.A P value0.05 was considered to be statistically significant.SAS,version9.3,statistical software(SAS Institute,Cary,NC)was ud for statistical analys. Results
The study cohort consisted of153patients,of which104 (68%)were girls.The median age at device closure of PFO was16years(range7-19years).All153study patients underwent a two-dimensional transthoracic echocardio-graph and agitated saline contrast study for diagnosis of PFO.Agitated saline solution transcranial Doppler scanning was performed in only41(27%)patients.A transophageal echocardiogram was performed in24(16%)and a preprocedure electrocardiogram was performed in120 (79%)patients of the study cohort.
Table1depicts the baline characteristics of the study cohort.Of the153patients included in this study,80(52%) responded to the survey questionnaires.There was no statistically significant difference in the baline charac-teristics between survey responders and survey non-responders,demonstrating survey responders being a reprentative sample of the entire cohort.Consultation with a neurologist was only performed in75(49%)of the study cohort and in the remaining patients diagnosis of the neurological condition was made by their primary care doctor or a cardiologist.Table2shows the procedural de-tails,postprocedure anticoagulation management, complications,resource utilization,and follow-up.The majority(115,75%)of PFO closures were performed by adult cardiologists in an adult facility.Amplatzer ptal occluders were ud to clo the PFO in115(75%)patients.Device-related endocarditis occurred in one patient(<1%) 4months after
device implantation and required open heart surgery to remove the device.Infive(3%)patient,bleeding TABLE1.
Baline Characteristics of Study Cohort
Variables n(%)Survey
Responders
Survey
Nonresponders Total15380(52)73(48) Females104(68)60(75)44(60)
Median age;years(range)16(7-19)16(7-18)16(8-19)
Family history of patent
foramen ovale
42(27)27(34)15(21)
On psychiatric medications19(12)10(13)9(12) Indication for patent foramen ovale closure*
Migraine104(68)53(66)51(70)
Nonmigraine headache24(16)13(16)11(15)
Visual symptoms110(72)54(68)53(73)
Transient ischemic attack
symptoms
42(28)25(31)17(23)
Symptoms suggestive
of stroke
24(16)12(15)12(16)
Preprocedure workup
Neurological consult75(49)34(43)41(56)
Neurological imaging112(73)57(71)55(75)
Lipid profile97(64)30(36)27(37)
Coagulation studies46(30)25(31)21(29)
*A single patient may have multiple symptoms.
S.C.Menon et al./Pediatric Neurology50(2014)213e217 214
at the cardiac catheterization site resulted in extended obrvation after the procedure.None of the patients required blood transfusion.The mean length of hospital stay was less than1day(18hours)and the mean hospital charges were approximately$24,000/procedure.The tech-nical charge for the procedure was an additional$4203/ procedure.Intermountain Healthcare typically accepts
reimburment at approximately60%of charges for the patients for a charge to cost ratio of0.6.Table3depicts the symptomatic outcomes of patients who underwent device closure of their PFO.After PFO closure,the majority of patients reported complete resolution(112,72%)or reduc-tion(31,20%)in their symptoms.No improvement or worning symptoms were reported by few patie
nts(10, 7%)in the study cohort.Interestingly,29(19%)patients with a residual atrial level shunt by echocardiogram on follow-up also reported complete resolution or improvement in their symptoms.There was no statistically significant difference in the outcomes reported by survey non-responders(median follow-up:16months)and survey responders(median follow-up:30months).
Table4depicts the key differences between patients who reported improvement in symptoms and tho who reported no change or worning of symptoms.There were no statistically significant differences between the two cohorts except that patients with no improvement in symptoms were less likely to recommend PFO closure to family and friends.On univariate regression analysis,none of the tested demographic,preprocedure-,procedure-,or postprocedure-related factors was associated with improvement or nonimprovement in symptoms for which PFO closure was performed.
Discussion
招聘广告范文PFO,a usually hemodynamically insignificant communi-cation between the right and left atria,is postulated to allow passage of vasoactive metabolites or microemboli to the systemic circulation,resulting in a variety of ailments including migraine headaches,cryptogenic stroke,or deco
mpression illness.14An increasing number of studies in both adults and children report an association between PFO and migraine,especially migraine with aura.4-6,8,14-18Simi-larly,in30%of young stroke survivors,no clear cau for stroke is identified even after a thorough evaluation.19In half of young patients with cryptogenic stroke,a PFO is found on transophageal echocardiograph as compared with25%in general population.20Despite the reports,the association between PFO and migraine and cryptogenic stroke remains controversial.21Regardless,we have witnesd an increasing incidence of children with migraine,stroke,and miscella-neous other nonspecific neurological symptoms to be referred for device closure of their PFO.
In adults,there are independent reports of resolution or improvement in migraine headache symptoms following
TABLE2.
Procedure,Complications,Resource Utilization,and Follow-up of the Entire Cohort
n(%) Procedure performed by
Adult cardiologist115(75)
Pediatric cardiologist38(25)
Device ud
Amplatzer ptal occluder106(69)
Helex ptal occluder47(30)
Multiple Amplatzer devices9(6) Postprocedure anticoagulation
Aspirin104(68)
Aspirinþclopidogrel38(25)
Clopidogrel11(7) Complications
Bleeding5(3)
Endocarditis1(0.7) Resource utilization
Mean length of hospital stay(hr)
(meanÆstandard deviation)
18Æ11 Mean hospital charges($)
(meanÆmeanÆstandard deviation)
24,126Æ5808 Follow-up
Median follow-up duration for entire
group in months(range)
12(6-24) Median follow-up duration for survey
responders in months(range)
30(12-60)
TABLE3.
Symptomatic Outcomes Following Device Closure of Patent Foramen Ovale
Survey Responders 80(52%)Survey
Nonresponders
73(48%)
Residual Shunt
29(19%)
Complete resolution62(78)50(69)24(83) Reduction in symptom13(16)18(25)5(17) No improvement1(1)4(5)0 Worning of symptom4(5)1(1)0TABLE4.
Salient Characteristics of Patients With Improved Symptoms and Tho Reporting No Improvementfather day
None or Fewer
Symptoms
(n¼143)
Same,Wor,
cute是什么意思
or New Symptoms
(n¼10)
Age(yr)15.8(Æ3.2)16.2(Æ2.8)
Female95(66)9(90) Psychiatric medication18(26)1(20)
Family history41(29)1(10)
Migraine97(68)7(70) Nonmigraine headache22(15)2(20)
Devices ud
Amplatzer108(76)7(70)
Helex44(31)3(30) Complications6(42)0
Aspirin96(67)8(80)
Aspirinþclopidogrel37(26)1(10) Clopidogrel10(7)1(10)
Residual shunting29(19)0
Survey responders(n¼80)
报考会计从业资格证的条件None or fewer
symptomsbpd是什么意思
(n¼75:94%)
Same,wor
or new symptoms
(n¼5:6%) Procedure
recommended by
Neurologist15(17)1(20)
Cardiologist45(60)2(40)
Family and friends7(9)1(20)
Others8(11)1(20)
Will not recommend
similar procedure to
family and friends
2(3)3(60)*
*P¼0.001.
S.C.Menon et al./Pediatric Neurology50(2014)213e217215
PFO closure.4-6,16,22However,the Migraine Intervention with STARFlex Technology trial,a prospective,blinded (sham device control arm),randomized trial,failed to show effectiveness of PFO closure on headache relief in adults with migraine with aura.8The STARFlex Technology study, however,was plagued byflaws in study design,technical issues,and study endpoints.23More recently,
results of the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT)24and the Clinical Trial Comparing Percutaneous Closure of the Patent Foramen Ovale Using the Amplatzer PFO Occluder with Medical Treatment in Patients with Cryptogenic Embolism(the PC Trial)25were published. Neither RESPECT nor the PC Trial showed a significantly lower rate of the primary end points with closure than with medical therapy in their intention-to-treat analys.In a recent meta-analysis,the overall pairwi associations between PFO,cryptogenic ischemic stroke,and migraine did not strongly suggest a causal role for PFO.21 Despite the controversies and the lack of an approved PFO closure device,PFOs are clod in children for a variety of reasons.We found an overwhelming majority of pediatric patients reported complete resolution(72%,112of153)or reduction(20%,31of153)in symptoms.No improvement or symptomatic worning was reported by few(7%,10of153) of our patients.Interestingly,19%(29)of patients with a re-sidual atrial level shunt by echocardiographic imaging also reported complete resolution or improvement in their symptoms.It is possible in this tting that the device may have reduced the degree of shunting or the shunts may have clod completely on follow-up,explaining some of the reported improvement.Alternatively,much of the improvement may be due to psychosocial factors and a placebo effect.There were no statistically significant differ-ences between the patients who symptoms improved and patients who sympto
ms did not improve.In addition,on univariate regression analysis,none of the demographic, preprocedure-,procedure-,or postprocedure-related factors were associated with improvement or nonimprovement in symptoms for which PFO closure was performed.
Similar to adult studies,PFO device closure was safe in the majority of pediatric patients.However,this procedure is expensive,with unknown long-term effects,especially in growing children.The estimated procedural charge of PFO closure in the153pediatric patients in our study cohort was approximately$4.2million,with additional costs to be encountered over time during follow-up.An important consideration not captured in this analysis is the cost associated with parental time away from work.Although this was not a prospective or randomized study,we wanted to explore the current clinical practice and outcomes of pediatric patients undergoing PFO closure for a variety of neurological symptoms.This study is limited by its retro-spective design and that consultation with a neurologist occurred in only approximately half of the patients.The possibility that the initial neurological diagnosis was inaccurate might affect the underlying physiology and respon to treatment.
Despite the fact that large studies of adults undergoing PFO closure for migraines or cryptogenic stroke have failed to demonstrate clear benefit,20,21this procedure has been performed on a fairly la
rge group of children in our patients in our metropolitan area,reflecting practice patterns over a large and diver geographic area including22individual hospitals.That75%of the pediatric patients in this cohort were treated by adult cardiologists in adult hospitals underscores the lack of rigorous standards in the evaluation and treatment of PFO in children.Nevertheless,this study demonstrates symptomatic relief in the majority of patients (92%),but does not address the possible underlying mech-anisms or exclude a significant placebo effect.Rigorous, prospective analysis is likely to be the only means of asssing the efficacy and underlying mechanisms of this unproven but emingly common medical therapy in pediatric patients.
This investigation was supported by the University of Utah Study Design and Biostatistics Center,with funding in part from the National Center for Rearch Resources and the National Center for Advancing Translational Sciences,National Institutes of Health,through Grant8UL1TR000105(formerly UL1RR025764).The content is solely the responsibility of the authors and does not necessarily reprent the official views of the NIH.
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It is afine thing to have ability,but the ability to discover ability in others is the true test.
Lou Holtz
S.C.Menon et al./Pediatric Neurology50(2014)213e217217
