`Medtronic, Inc., Medtronic Vascular, Inc.,
`& Medtronic Corevalve, LLC
`v. Troy R. Norred, M.D.
`Case IPR2014-00395
`
`
`
`iv‘:
`
`.xx
`
`..i\\z
`
`,,:\
`\1w
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`Imaging the dissected aorta
`
`SIR,-—-I read with interest and sympathy Mr
`Treasure’s editorial on imaging the dis-
`sected aorta.‘ I agree that it is a diflicult to
`achieve a standard approach.
`I have found
`the following guidelines for acute dissection
`clinically reliable:
`(ct) Type B dissection is defined as dis-
`section confined to the descending aorta-
`that is, any part of the aorta beyond the
`origin of the left subclavian artery.
`(b) Type A dissection is any dissection
`that involves the ascending aorta, whether
`or not it also affects the descending aorta,
`and irrespective of the site of entry.
`(5) Computed tomography (CT) is a reli-
`able technique for the detection and assess-
`ment of type B dissections. It
`is certainly
`more reliable than angiography. This is
`because the flap in type B dissections is usu-
`ally static and can be reliably imaged by
`CT, despite the fact
`that the true lumen
`may have regained a smooth, circular cross
`section.
`(d) In type A dissection the flap in the
`ascending aorta is often mobile, giving a sig-
`nificant
`incidence of false negative CT
`examinations, but nevertheless .
`.
`.
`(e) the ascending aorta is always dilated
`in type A dissection. If a dissection in the
`descending aorta is accompanied by an
`ascending aorta of normal size it is reason-
`able to exclude type A origin or extension of
`the false lumen.
`In passing,
`I would like to endorse the
`efiicacy of transoesophageal sonography in
`the diagnosis of traumatic aortic tear, as
`described by de Belder et al.’ Indeed, I have
`yet to hear of a falsely negative study.
`IB PARTRIDGE
`Harefield Hospital,
`Harefield,
`Middlesex UB9 6]H
`
`l Treasure T. Imaging the dissected aorta. Br
`Heart] 1993;70:497—8.
`2 de Belder A, Thomas M, Marrinan, M.
`Traumatic rupture of the thoracic aorta
`diagnosed by transoesophageal echocardio-
`graphy. Br Heart] l993;70:393—4.
`
`This letter was sent to the author, who replies as
`follows.‘
`
`SIR,-—-Dr Partridge’s guidelines indicate his
`keen interest in this problem and that he
`has considered it carefully. I will address his
`points item by item.
`(ct and b) In the original paper on which
`the Stanford classification is based‘ type B
`is defined as dissection that does not extend
`proximally to the subclavian artery.
`In a
`subsequent paper there was a subtle but
`important
`change
`in
`detail.’ Type A
`includes any dissection that
`involves the
`ascending aorta, just as Dr Partridge writes,
`but type B includes all the rest, thus includ-
`ing some cases with arch involvement."
`No classification is perfect but the virtue
`of the current version of the classification is
`that it defines a group (type A) in which a
`challenging but achievable operation on the
`ascending aorta protects the patient from
`three lethal consequences of dissection at
`this site:
`0 Rupture into the pericardium
`0 Severe aortic valvar regurgitation
`O Occlusion of the coronary ostia
`This reduces the risk from near 100% for
`type A to a much lower figure, made up of
`the risk of the operation itself and the risk
`
`associated with any residual uncorrected
`abnormality in the arch and descending
`aorta. Classification is an interesting disci-
`pline. In this instance type A is defined by
`inclusion of the particular characteristic—
`that
`is,
`involvement of
`the
`ascending
`aorta-and type B is defined by exclusion of
`this characteristic. (5, d, and e) His observa-
`tions on the nuances of the interpretation of
`computed tomograms of the ascending and
`descending aorta are nicely observed and
`ring true.
`Although I had no data or experience on
`which to base a comment,
`I was worried
`when de Belder et al advocated trans-
`oesophageal echocardiography to diagnose a
`traumatic
`aortic
`tear.’ Dissection
`has
`length, so any cross sectional
`image will
`detect it. Traumatic aortic transection is a
`tear with an adjacent haematoma; it is not a
`propagating dissection. Because there are
`other sources of blood (rib and vertebral
`fractures)
`to cause
`the haematoma
`in
`trauma, it is visualisation of aortic wall dis-
`continuity that is critical. High specificity,
`that is confidently excluding the diagnosis
`when it
`is absent,
`is
`required. We have
`argued elsewhere‘ that the cross sectional
`image of CT cannot prove or exclude trau-
`matic
`aortic dissection.
`In a
`critically
`injured patient this makes CT an unneces-
`sary waste of time. The fact
`that
`trans-
`oesophageal echocardiography can be used
`at the bedside makes it attractive, provided
`a negative test is convincing and that any
`induced hypertension and local interference
`do not make the aorta go “pop”.
`TOM TREASURE
`Cardiac Department,
`St George ’s Hospital,
`Blacleshaw Road,
`London S W1 7 OQT
`
`1 Daily PO, Trueblood HW, Stinson EB,
`Wuerflein RD, Shumway NE. Management
`of acute aortic dissections. Ann Tlrorac Surg
`l970;10:237—47.
`.,
`t
`2 Miller DC, Stinson EB, Oyer PE, Rossiter S],
`Reitz BA, Griepp RB, Shumway NE.
`Operative treatment of aortic dissections. ]
`Thorac Cardiovasc Surg l979;781365—82.
`3 de Belder A, Thomas M, Marrinan M.
`Traumatic rupture of the thoracic aorta
`diagnosed by transoesophageal echocardio-
`graphy. Br Heart] l993;70:393—4.
`4 Unsworth-White M], Buckenliam T, Treasure
`T. Traumatic
`rupture of
`the
`thoracic
`aorta——computed tomography may be a
`dangerous waste of time. Ann R Coll Surg
`Engl (in press).
`
`Anthracyclines and the heart
`
`SIR,—I thank Dr Rhoden, Dr Hasleton, and
`Dr Brooks for an excellent review of anthra-
`cyclines and the heart.’
`I would like to point out an error. The
`evidence for doxorubicin-related cardiotoxi-
`city
`involving myocardial
`adrenergic
`derangement comes
`from ‘”I-meta-iodo-
`benzyl-guanidine (MIBG) rather than from
`ml-methoxy-isobutyl
`isonitrile
`(MIBI)!
`These radiopharrnaceuticals are quite dis-
`‘ similar. MIBG shares similar uptake mecha-
`nisms into sympathetic nerve endings as
`noradrenaline. It is therefore ideally suited
`to imaging both the "distribution of sympa-
`thetic nerve endings in the heart as well as
`neuroendocrine tumours such as pheochro-
`mocytomas." MIBI is a myocardial perfu-
`sion agent available in cold kit form that is
`labelled with technetium-99m rather than
`with iodine-123. MIBI is a lipophilic agent
`taken up into myocytes independently of
`
`Letters
`
`the sympathetic nerve endings but roughly
`proportionally to myocardial blood flow.
`MIBI is therefore used to assess the patency
`of coronary arteries rather than the status of
`the sympathetic nervous system.’
`PAUL THOMAS
`Department of Nuclear Medicine,
`]ohn Hunter Hospital,
`Locked Bag l,
`Newcastle /Wail Centnz,
`NSW 2310,
`Australia
`
`We thank Dr Thomas for drawing attention to this
`error and we apologise to the authors of the review for
`introducing this mistake when the technical editor
`mistook the abbreviation IWIBG for MIBI. Authors
`can help us to avoid such mistakes by spelling out
`all
`abbreviations
`and
`acronyms
`at
`the
`firs!
`mention——EDITOR
`
`Brooks N.
`P,
`l Rhodcn. W, Hasleton
`Anthracyclines and the heart. Br Heart _'I
`l993;70:499——502.
`2 Valdes—Olmos RA, Ten Bokkel-Huinuk WW,
`Greve JC,
`I-Ioefnagel CA. "31-MIBG and
`serial
`radionuclide
`angiocardiography in
`doxorubicin-related cardiotoxicity. Clin Nucl
`Med l992;l7:l63-7.
`3 Dae M. Scintigraphic assessment of cardiac
`innervation using iodine-123 metaiodoben-
`zylguanidine.
`In: Ernst E van der Wall,
`Sochor I-I, Righetti A, Niemeyer MG, eds.
`What’s new in cardiac imaging? Dordrecht:
`Kluwer Academic Publishers, 1992;377—85.
`4 Gross MD, Shapiro B, Thrall JH. Adrenal
`scintigraphy. In: Gottschalk A, Hofier PB,
`Potchen E], eds. Diagnostic nuclear medi-
`cine, Baltimore Wflliam and Wilkins,
`l988;826—7.
`5 Rigo P, Larock M, Braat SI-I. Myocardial per-
`fusion imaging with teclmetium-99m isoni-
`triles: Attractive thallium substitutes? In:
`Ernst E van der Wall, et al eds. What’s new
`in cardiac
`imaging? Dordrecht: Kluwer
`Academic Publishers, 1992;69—85.
`
`Balloon dilatation (valvoplasty) as first
`line treatment for severe stenosis of the
`aortic valve in early infancy: median
`term results and determinants of sur-
`vrval
`
`SIR,--In their otherwise excellent article
`Bu’Lock and her colleagues’ do not give
`any details of the morphology of the aortic
`valve
`itself,
`specifically the number of
`leaflets. This matter
`is of
`importance
`because in the so-called unicommissural
`and unicuspid variant of aortic valvar steno-
`sis recent studies have shown that the leaflet
`tissue is attached within the aortic root in a
`circular rather than a semilunar fashion.’
`This arrangement would seem, on morpho-
`logical grounds, to militate against success-
`ful balloon dilatation: but morphologists are
`constantly wary of predicting outcomes in
`life from their observations on cadaveric
`hearts. For this reason it would be invalu-
`able to know whether Bu’Lock and her col-
`leagues had information on the number of
`leaflets present in the valves dilated in their
`patients?
`ROBERT H ANDERSON
`Department of Paediamcs,
`Royal Brampton National Heart and
`Lung Institute, Dovehouse Street,
`London S W3 6LY
`
`l Bu’Lock FA, Iofife HS, Jordan SC, Martin RP.
`Balloon dilatation (valvoplasty) as first
`line
`treatment for severe stenosis of the aortic
`valve in early infancy: medium term results
`and determinants of survival. Br Heart ]
`l993;70:546—53.
`2 McKay R, Smith A, Leung MP, Arnold R,
`Anderson RH. Morphology of the venn'icu-
`loaortic junction in critical aortic stenosis. ]
`Thorac Cardiovasc Surg l992;l04:434—42.
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`
`Letters
`
`This letter was shown [0 the authors, who reply
`as follows:
`
`Familial atrioventricular septal defect:
`possible genetic mechanism
`
`SIR,———We thank Professor Anderson for his
`pertinent
`reminder of the importance of
`morphological
`factors in congenital heart
`disease and their potential relevance to the
`treatment of patients with aortic stenosis.
`The reason that data on valve morphology
`were not included in our report is that we
`believe it is often diflicult to be certain of
`leaflet morphology based solely on echocar-
`diography in neonates with severe aortic
`stenosis. The poor correlation between
`echocardiographic predictions and observed
`morphology at the time of surgery was well
`described in the paper by Leung and
`Anderson.‘
`In
`their
`study,
`echocardio-
`graphic examination of 20 infants with criti-
`cal
`aortic
`stenosis
`identified
`16 with
`bicuspid valves, four with tricuspid valves,
`and no unicuspid valves. This contrasts
`with the surgical
`findings
`in the same
`infants where six valves were described as
`unicuspid, 13 bicuspid, and 1 tricuspid.
`In the patients we studied,’ the aortic
`valve was considered to be bicuspid in six,
`tricuspid in five, and one may have had a
`Because
`few of
`these
`unicuspid valve.
`patients had visual inspection of the aortic
`valve (either surgically or at necropsy) we
`are unable to comment on the validity of
`the echocardiographic findings. There did
`not seem to be any correlation between
`echocardiographically
`determined
`valve
`morphology and outcome. The principal
`determinants of survival being left ventricu— .
`lar
`(rather than aortic valve) dimensions
`and presence and severity of associated
`lesions. The patient with the apparently
`unicuspid valve had an excellent response to
`balloon valvoplasty.
`It does, however, seem logical to believe
`that aortic valve morphology may have an
`important influence on the degree of relief
`of valve obstruction obtained,
`on
`the
`propensity for early re-stenosis, and on the
`maintenance of longer term valve compe-
`tence. Studies of the relation between valve
`morphology and the outcome of balloon
`dilatation might be of considerable interest.
`Precordial echocardiography may not be
`adequate
`for
`such cases, where
`trans-
`oesophageal echocardiography or intravas-
`cular ultrasound may be of additional value.
`F A BU’LOCK
`on behalf of
`H S ]o_/ffe
`S C jordan
`R P Martin
`Bristol Royal Hospital
`for Sick Children,
`St Michael’: Hill,
`Bristol BS2 8B]
`
`1 Leung MP, McKay R, Smith A, Anderson
`RH, Arnold R. Critical aortic stenosis in
`early infancy. J Thorac Cardiovasc Surg
`l99l;101:526—35.
`2 Bu’Lock FA, Jol‘fe I-IS, Jordan SC, Matin RP.
`Balloon dilatation (valvoplasty) as fi.l’SI line
`treatment for severe stenosis of the aortic
`valve in early infancy: medium term results
`and determinants of survival Br Heart ]
`l993;70:546—53.
`
`the report of
`S1R,——We read with interest
`Kumar et al describing a family in which the
`mother and her two daughters by different
`fathers had atrioventricular septal defects
`not associated with trisomy 21.‘ They sug-
`gest that an autosomal dominant pattern of
`inheritance may be involved in this pedi-
`gree, although a multifactorial or cytoplas-
`mic mechanism cannot be ruled out.
`in
`We recently described five families
`which two or more members had isolated
`atrioventricular septal defect. Parent-to—son
`transmission of concordant cardiac defect
`was documented in four cases. The mother
`was affected in three cases and the father in
`one.’
`Lately we found an additional example of
`atrioventricular septal defect in four mem-
`bers in two generations of the same family
`(figure). None of
`the
`family members
`showed phenotypic anomalies and all had a
`normal karyotype. They were examined by
`electrocardiography and echocardiography.
`A partial atrioventricular septal defect was
`diagnosed in one case (II S) and a complete
`defect in two cases (III
`1 and III 2). The
`daughter of a patient with atrioventricular
`septal defect had an isolated cleft of the
`mitral valve (III 3).
`Anatomical differences between isolated
`mitral" clefts and clefts associated with an
`atrioventricular
`septal defect have been
`described.’ The high frequency of isolated
`mitral cleft in families with atrioventricular
`septal defects," including our family, and
`its prevalence in patients with Down’s syn-
`drome (4/420 22 3/S200 in our experience),
`however, suggests that
`this malfortnation
`should be included in the spectrum of atrio-
`ventricular septal defects.
`Monogenic autosomal dominant inheri-
`tance with incomplete penetrance could
`explain the atrioventricular septal defects in
`the families we studied and those reported
`by other workers. Normal parents of
`affected children could be obligate carriers
`of the gene involved in familial atrioventric-
`ular septal defects. The father-to—daughter
`transmission of cardiac malfonnation in two
`cases excludes cytoplasmic inheritance in
`these families. Moreover, atrioventricular
`septal defects in patients with and without
`Down’s syndrome differ not only in terms
`of the prevalence of partial or complete
`forms“ but also in tenns of the distribution
`of
`associated
`cardiac malformations.”
`These
`anatomical
`differences
`and
`the
`absence of linkage in the molecular analysis
`of chromosome 21 in families with atrioven-
`tricular septal defect’‘’‘‘‘ suggest
`that
`the
`gene or genes involved in the pathogenesis
`of atrioventricular septal defect in “nomual”
`children are different from those in patients
`with Down’s syndrome.
`MARIA CRISTINA DIGILIO
`BRUNO MARINO
`ALDO GIANNOTTI[
`BRUNO DALLAPICCOLA
`Paediatric Cardiology and Genetics,
`Otpedale Bambino Gert),
`00165 Rome, Italy
`
`
`
`O Female
`
`l:l Male H Dead
`
`E Atrioventricular septal defect
`
`0 Isolated cleft mitral valve
`
`Pedigree
`
`1 Kumar A, Williams CA, Victorica BE.
`Familial atrioventricular septal defect: possi-
`ble genetic mechanisms. Br Heart ] 1994;
`71:79-81.
`2 Digilio MC, Marino B, Cicini MP, Giannotti
`A, Formigari R, Dallapiccola B. Risk of con-
`genital heart defects in relatives of patients
`with atrioventricular canal. Am ] Dis Child
`l993;147:l295—7.
`3 Smallhorn JF, DeLeval M, Stark J, Somerville
`J, Tylor JFN, Anderson RH, et al. Isolated
`anterior mitral
`cleft:
`two
`dimensional
`echocardiographic assessment and differen-
`tiation from “clefts” associated with atrio-
`ventricular
`septal
`defect. Br Heart ]
`1982;48:109—16.
`4 Disegni E, Pierpont MEM, Bass JL, Kaplinksy
`E. Two dimensional echocardiography in
`detection of endocardial cushion defect
`in
`families. Am _7 Cardiol l985;55:l6/19-52.
`5 Cousineau AJ, Lauer RM, Pierpont ME,
`Burns TL, Ardingcr RH, et al. Linkage
`analysis of autosomal dominant atn'ovent_ric-
`ular canal defects: exclusion of chromosome
`21. Hmn Genet 1994;93:l03—8.
`6 Marine B, Vairo U, Como A, Nava S,
`Guccione P, Calabro R, Marcelletti C.
`Atrioventricular canal in Down’s syndrome.
`Am]Dis Child 1990;144:1 120-2.
`JA.
`7 Carmi R,
`Ferencz C, Boughrnan
`Endocardial cushion defect: further studies
`of “Isolated” versus “syndromic” occur-
`rence. Am]Med Genet 1992;43:569-75.
`8 De Biase L, Di Ciommo L, Ballerini L,
`Bevilacqua M, Marcelletti C, Marino B.
`Prevalence of left-sided obstruction lesion in
`patient with atrioventricular canal without
`Down’s syndrome. ] Thorac Cardiovasc Surg
`1986;91:467—70.
`9 Wilson L, Curtis A, Korenberg JR, Schipper
`RD, Allan L, Chenevix-Trench G, er al. A
`large, dominant pedigree of atrioventricular
`septal defect (AVSD): exclusion from the
`Down’s syndrome critical region on chro-
`mosome 21. Am ] Hum Genet 1994,53:
`1262-8.
`S, Digilio MC, Marino B,
`10 Melchionda
`Giannotti A, Mingarelli R, Dallapiccola B.
`Analisi di linkage con marcatori delle regioni
`Zlq ed 8p in una famiglia con canale atrio-
`ventricolare. G Ital Cardiol 1993;23:7.
`
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