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becauseofthepossibilityofparadoxicalrenalarteriolarvasoconstriction.42Othervasodilatorssuchas
dopamine (50 mcg/kg intra-arterial) and fenoldopam have been studied. IVUS for measurement of
minimal luminal area (MLA) may be considered, and this technique may help to define severity of
questionablelesionsandtolocalizethetrueostiumifthereisuncertainty.
33,53
3.Recentrecommendationsfavorthediagnosisoffunctionallysignificantrenovasculardisease(meriting
revascularization) ifoneof thefollowingcriteria is present: (1) resting ratio of distal arteryto aortic
pressure(Pd/Pa)<0.90,(2)hyperemicfractionalflowreservevalue(Pd/Pa)<0.80,(3)hyperemicmean
gradient>20mmHg,(4)hyperemicsystolicgradient>20mmHg,or(5)IVUS-derivedMLA<8.6mmsq.
42
4. Itmaybe worth considering some limitations inphysiologicmeasurements:becausefractionalflow
reserve is dependent on the degree of hyperemic flow achieved pharmacologically, greaterhyperemic
flowcreateshigherpressuregradientsandthuslowerfractionalflowreservevalues(andviceversa).
38
Consequently, because of the lesser vasodilator reserve of the renal arterial bed (as opposed to the
coronarycirculation),thedifferencebetweenbaselineandstimulatedhyperemicgradientsissmallerthan
inthe coronary circulation.Itfollowsalso that in the renalarterythe differences betweennormal and
abnormalfractionalflowreservesaresmallerandthatthepredictivevalueofrestinggradientsisnearly
equal to that of pharmacologically provoked gradients.38 Thus, investigative challenges remain in
definingtheoptimalphysiologicanalyticsforfunctionalrenovasculardisease.
5.Inadditiontoconsideringothercausesforrenalimpairmentorhypertension,kidneyviabilityshould
be evaluated beforerevascularization is attempted. Useful parameters will include kidneysize, recent
declineinrenalfunction,nuclearrenalperfusion,andrenalresistiveindexmeasurements.
4
VIII.RenalRevascularization:EarlySurgicalExperience
Early surgical methods for treatment of renovascular hypertension encompassed nephrectomy of the
pressor kidneyandtheuseofvenousconduits for aorto-renalartery bypass grafting,as well asextraanatomic hepatorenal(right)orsplenorenal(left)bypassgraftingunderselectedclinicalcircumstances.
Morerecently,becauseoftherecognitionofhighermorbidityandmortalitywithsurgeryversuscatheterbasedmethods,thelatterhavebeenpreferred.
IX.RenalRevascularization:BalloonAngioplasty
Initially described by Gruntzig in 1978, percutaneous balloon angioplasty demonstrated reasonably
durableresultsandbecameawidelyusedminimallyinvasivealternativetosurgicalrenalarterybypass.
54
Althoughsupplantedbyendoluminalstentinginrecentyears,simpleballoonangioplastymaintainsan
importantroleinthetreatmentofrenovasculardiseaseoffibromusculardysplasticorigin(Figs.8.1–8.3).
X.RenalRevascularization:EndoluminalStenting
Endoluminalstentingforrenovasculardiseasehasbeenshowntoprovidebetterproceduralandlong-term
outcomes compared against simple balloon angioplasty in a prospective randomized trial.
42,55
Observational series have confirmed a very high technical success rate for renal artery stenting (3):
overall mortality rate is low (0.8%), less than 8% risk of major complications (stroke, myocardial
infarction,hemorrhagerequiringtransfusion,renalarteryperforation,orurgentsurgery),andlessthan5%
riskofeventualneedforrenalreplacementtherapy(dialysisortransplant).4Withgoodtechnique,renal
artery stent restenosis rates are less than15%,23 and the procedure can be accomplished safely and
successfullyeven inthecontextofadvanced renalimpairment.56Renalduplex ultrasound represents a
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reasonablemethodoflongitudinalpoststentclinicalnoninvasivesurveillance.
Beforetheprocedure,aspirinandadequateprehydrationtominimizecontrastnephropathyareadvisable.
Most procedures are performed via the femoral approach,which accommodates larger (7F) catheters,
althoughtheupperextremityapproaches(radial,brachial)maybelinkedtolessfrequenthemorrhageas
wellasallowing morefavorable geometryforcatheterseatingconsideringtheinferior angled originof
many renal arteries, as notedabove.42 Typically, 6-7F intravascular sheaths are used for renal artery
stenting.Forstenting,inadditiontoaspirin,clopidogrel300-600mgshouldbegivenorally(then75mg
orally daily for 4 weeks [some authors recommend 6 weeks] following the stenting procedure), and
intraprocedural anticoagulation may take the form of low-molecular-weight heparin, unfractionated
heparin(goalactivatedclottingtime250),bivalirudin,orargatroban.
Balloonangioplastyalonemaybeperformed viaa 5F guiding system,but stentplacement will usually
require a 6F guiding catheter or a 5F guiding sheath. Although the guiding catheter offers better
torquability(neededwiththefemoralapproach),thesmallerguidingsheathisusefulfromupperextremity
accesspointswheretorquabilityislessimportantgiventheinferiorangulationofrenalarteryorigins.
4
Toaccesstherenalarteryoriginfromthecommonfemoralarteryapproachinasafeandcoaxialmanner,
twoapproacheshavebeenwelldescribed4:theno-touchtechniqueandthedirectmethod.
A.No-TouchTechnique
The no-touchtechnique hasbeenadvocatedwhereby,usinga guiding catheter orguiding sheath, a first
guidewireisadvancedsuperiorly(cephalad)intheaortabeyondtherenalarteryeffectivelyholdingthe
guidingsystematasmall yetsafedistance awayfromthe artery origin.47Thena second guidewire is
passed into the renalarterytocross thestenosis.Thiswire will come to restinadistal renalarterial
branch.Thefirstguidewireisthenwithdrawn,permittingtheguidingsystemtobecomeseatedsafelyand
coaxiallyinthearteryorigin,minimizingthepossibilityofdamagetotheostium.33Iftheproperseatingof
aguidingsheathisdifficult,asmallercaliberdiagnosticcathetercanbetelescopedthroughtheguiding
sheath(Fig.8.1),followedbyguidewirecrossingofthestenosis,andthensubsequentadvancementofthe
guidingsheathoverthecombinedwireanddiagnosticcathetersystem.
B.DirectMethod
Thedirectmethodusesasmallcaliber(4-5F)diagnosticcatheterthatistelescopedthroughtheguiding
systemtoengagetherenalarteryorigin,followedbythepassingofaguidewireacrossthestenosis.Wire
sizeistypically0.014.Tofollow,theguidingsystemisthenadvancedoverthesmallcalibercatheterto
engagethearterysafely(Fig.8.2).Bothno-touchanddirectengagementtechniquesservetoavoidguiding
cathetertraumatothearteryorigin,frequentlythesiteofplaqueinatheroscleroticlesions.
4
C.ProcedureStepsandOptions
1.Thenextstepintheprocedureisballoonangioplastyusingadevicesize-matchedtotheartery,with
theproximalendoftheballoonlocatedintheaortatoensurecompletecoverageofanostiallesion,if
present,duringballoondilatation.Becauseballoon-expandablestentsexhibitbetterradialstrength,they
arepreferredtoself-expandingstents.Stentsaretypicallysized5-7mm,againwithproximalendofthe
stentextendingatleastminimallyoutintotheaortatoensureunambiguousostialcoverage.Atthispoint,
theguidingsystemiswithdrawnintotheaortatoavoidstentdeploymentwithintheguidingsystem.The
stent is then deployed. As the stent balloon deflates after deployment, the guiding system should be
advancedsothatthedistaltip ofthe guiding systemlies coaxiallywithinthe stent,therebyallowing a
postdilatationballoontopassintothenewlyplacedstentuneventfullydespitestentstrutsprotrudinginto
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theaorta,whilealsofacilitatingthecreationofapoststentingfollow-upangiogram4(Figs.8.4–8.6).
FIGURE8.5 Renovasculardisease.Atheroscleroticrenalarterystenosis.Thestenosiswascrossedusing
aHi-TorqueAbbottVascularSpartacoreguidewire,followedby5.0mmballoonangioplastypredilatationwith
deploymentofa6×18mmAbbottVascularHerculinkElitestent.
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FIGURE8.6 Renovasculardisease.Atheroscleroticrenalarterystenosis.Finalangiographicviewpost–
stentplacementbeforewireremovalshowsexcellentflowwithnoresidualrightrenalarterystenosis.The
subsequentclinicalcoursehasbeenremarkableforreducedfrequencyofangina,improvedbloodpressurecontrol,
andultrasound-documentedstabilizationofkidneysize.
CurrentstentsapprovedforrenalarteryuseincludetheExpressSD(BostonScientific),Formula(Cook),
andRXHerculinkElite(AbbottVascular)33(Figs.8.5–8.6).
2.Anadditionalproceduraloptionisthatofdistalembolicprotection,wherebyatheroembolicanbe
collectedusinganetlikefilterorballoonocclusionsystemdeployeddistallytopreventembolicmigration
intosmallerarterialbranches,therebytheoreticallymitigatingrenalinjury.23Thegeneralanalogywould
parallelthesuccessfuluseofsuchdevicesfortranscathetercarotidorcoronaryveingraftinterventions.
Provingbenefitforroutine renalartery usehasbeendifficult,however,partlybecauseofthe lackofa
biomarkersuchastroponinthatmeasuresend-organinjuryorfreedomthereof.23Inoneseriesevaluating
patients withchronic kidneydisease, althoughblood pressureandglomerular filtrationratesimproved
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overall,therewasnodifferenceinthesemeasuresbetweenthosereceivingstentingwithdistalembolic
protection andthose receiving stenting alone.56 Recovery of debris has been reported in most series
where distal embolic protection was used consistently, irrespective of device used.
57,58
There are
technical challenges, however, including the presence of early arterial branches, as well as the
requirement thattherebe atleasta 2-cm separationbetweenthedistal endofthe stentandthe resting
locationofthefilterdevice.4Atpresent,distalembolicprotection isnotusedroutinelyinrenalartery
stenting.
XI.MedicalVersusTranscatheterManagement:ClinicalTrial
Evidence
Over thepast decade, several prospective randomized trials haveaddressed the valueofrenal artery
revascularization versus optimal medical therapy. Each of these trials has suffered from potential
methodologicflaws.Forexample,EMMAandASTRALexcludedmanysubjectswhomayhavereceived
benefitfromstentrevascularization.
59,60
However,ameta-analysisofalltrialsofrenalrevascularization
versus medical therapy showed no overall benefit arising from revascularization on mortality,
progressiontoend-stagerenalimpairment,majoradversecardiovascularevents,orhypertensioncontrol.
61
Yetthesetrials,despitetheirlimitations,mostlyshowedtrendsfavoringmodestimprovementsinblood
pressureintherevascularizationarms.42Belowaredetailsoftheimportanttrials.
A.EMMA(EssaiMulticentriqueMedicamentsvsAngioplastie)StudyGroup
The EMMA (Essai Multicentrique Medicaments vs Angioplastie) study group found no difference in
ambulatory blood pressure between medically treated versus balloon angioplasty groups. Yet it was
underpowered,hadahighcrossoverratefrommedicaltherapytoballoonangioplasty,hadnostentoption
forsuboptimalballoonresults,enrolledmainlypatientswithmoderateratherthanseverestenoticdisease,
anddidnotincludethemostillpatients(advancedrenalimpairment,flashpulmonaryedema,malignant
hypertension).
59
B.ScottishandNewcastleRenalArteryStenosisCollaborativeGroup
The Scottish and Newcastle Renal Artery Stenosis Collaborative Group showed that balloon
revascularizationtendedtoimprovebloodpressureinthebilateraldiseasearm(althoughnotstatistically
significant)butnotintheunilateraldiseasearmcomparedagainstmedicaltherapy.
62
C.DutchRenalArteryStenosisInterventionCooperativeStudyTrial
(DRASTIC)
The Dutch Renal Artery Stenosis Intervention Cooperative Study trial (DRASTIC) compared balloon
angioplastyagainst medical therapy, withnostatistical difference inbloodpressurecontrol.However,
nearlyhalfofthemedicalpatientscrossedovertoangioplasty,andanginaandheartfailurepatientswere
excluded.Despitethestatisticallynegativeresults,bloodpressurecontrolimprovedinmostindividuals
intheballoonangioplastycohort.
63
D.STARTrial(StentPlacementinPatientsWithAtheroscleroticRenal
ArteryStenosisandImpairedRenalFunction)
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The STARTrial (Stent Placement inPatients with AtheroscleroticRenalArtery StenosisandImpaired
RenalFunction)comparedstentingtomedicaltherapyinrenovasculardiseasepatientswhoshowedrenal
impairment. Event rateswerelowoverall, with manysubjectsmanifestingmoderaterather than severe
disease.Theresultwasnotstatisticallysignificant.Threepostproceduralmortalitiesinthestentarmis
consideredmostunusual.
4,34
E.ASTRALTrial(AngioplastyandStentingforRenalArteryLesions)
TheASTRALTrial(AngioplastyandStentingforRenalArteryLesions)alsoexaminedsubjectswhohad
renalimpairmentandrenovasculardisease,thetreatmentarmsbeingstentingversusmedicaltherapy,with
anegativeresultregardingtheendpointofchangesinserumcreatinine.Therewasanonsignificanttrend
favoring stenting, however,and criticisms focused on thepresence of only moderate disease inmany
subjects,aswellastheinclusionofindividualswhohadconsiderablysmallkidneysizes.
4,64
Inaddition,
there was an unexpectedly high number ofperiproceduralcomplications38in31 of 359 patients(9%)
who received revascularization (these events included pulmonaryedema, myocardial infarction, renal
embolizations,renalarteryocclusions,renalarteryperforations,femoralarteryaneurysm,andcholesterol
embolizationsleadingtoperipheralgangreneandamputations).
64
F.CORAL(CardiovascularOutcomesinRenalAtheroscleroticLesions)
1. CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) was the largest stent versus
optimized medical therapy trial. CORAL enrolled subjects who had either (1) unilateral or bilateral
renovascular disease (angiographic stenosis >60% or peak Doppler velocity of >300 cm/s or >80%
stenosisbyMRangiography/CTangiographyor>70%ifotherevidenceofrenalischemiawaspresent)
or (2) hypertension despite two or more drugs or an estimated glomerular filtration rate of
<60 mL/min/1.73 sq m based on renovascular hypertension. Both arms received optimized medical
therapy(antiplatelettreatment,as wellas treatment for lipids, glucose,andhypertension,includingthe
angiotensinreceptorblockercandesartan).Reportedafteramedianof3.6years’follow-up,therewasno
difference between groups in the primary composite end point of cardiovascular or renal mortality,
stroke, myocardialinfarction,heartfailurehospitalization, 30%fallinglomerular filtrationrate,or the
development of end-stage renal impairment.25 Blood pressure response was nearly identical, and
revascularizationproceduralcomplicationswereinfrequent.
2.TheCORALtrialhasbeencritiquedbecauseitincludedsubjectswhohadmodestclinicalindications
(twodrughypertension),andfunctionalassessmentofstenosisforphysiologicsignificancewasnotpart
oftheprotocol.Moreover,aswiththeearlierrevascularizationversusmedicaltherapytrials,thepatients
most likely to benefit from revascularization were not included, such as those with short duration of
severe hypertension,truemultidrug-resistant hypertension (average2.1 drugsinCORAL),or recurrent
flashpulmonaryedema(excludedinCORAL).
3. Incontrast,althoughnot randomized,several prospective observationalstudiesinhigh-risk patients
showed benefit when stented. For example, when 467 such patients (some of whom had pulmonary
edema, progressive renal impairment, resistant hypertension, or both resistant hypertension and
progressiverenalimpairment)weretreatedbymedicationversusrevascularizationasselectedbypatient
andphysician preference, the revascularization arm subjects who had the above high-risk factors had
significantly better 4-year mortality and event outcomes. When high-risk factors were absent,
interestingly,therewasnodifferencebetweenthetwotreatmentarms.
65
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XII.RenalVeinThrombosis
Etiologies for renal vein thrombosis include malignancy, inferior vena cava (or vena cava filter)
thrombosis, nephrotic syndrome, connective tissue diseases, and hypercoagulable states, with some
reportsofsuccessfulcatheter-basedthrombolysisorthrombectomy.
4,66,67
Forthisprocedure,theuseofa
multipurposeorrenaldoublecurveguidingcatheterisdescribed,throughwhichaglidewireandangled
glide catheter are passed to cross the obstruction followed by rheolytic thrombectomy and catheter
infusion of thrombolytic drug therapy, if needed.
66,67
However, in the setting of chronic renal vein
occlusion,collateralvenouspathwaysmayprovideadequatedrainagetopermitlong-termviabilityunder
conservativemedicaltherapyusinganticoagulation.
68
XIII.RenalSympatheticDenervationforResistant
Hypertension:TheoryandEarlyExperience
A.Theprevalenceoftruemedication-resistanthypertensionhasbeendifficulttoquantify,partlybecause
of variations in the denominators of populations examined. When resistant hypertension is defined
generallyasbloodpressurethatremains>140/90mmHgdespiteadherence tofull-dosetherapyforan
adequatetimeintervalusingatleastthreedrugsincludingadiuretic,thisconditionmaybepresentina
spectrumof3%-18%ofpatientsdependingonwhetherprimarycarepracticesversustertiaryclinicsare
considered.
1,69
Inlargeclinicaltrialsofhypertensiontreatmentwheredrugtherapywasactivelytitrated
to prespecified targets, diastolic blood pressure <90 mm Hg was attained in 90% of instances, yet
systolicbloodpressure<140mmHginonly60%.
1,70,71
In onespecialtyuniversity hypertensionclinic,
only 59%ofpatients reachedgoalvaluesof<140/90 mm Hgdespiteintensive titration efforts.72 The
most recently published large-scale US population data indicate that the overall prevalence of
hypertensionis31%(68million),ofwhom8.9%metcriteriaforresistanthypertension.
32,73
B. Early surgical experience using operative lumbar sympathectomy for uncontrollable hypertension
created the theoretical basis for catheter-guided renal denervation. Initial surgical series documented
improved blood pressure and survival compared against medical therapy, with enhanced diuresis and
natriuresis,reducedreninrelease,unchangedrenalbloodflow,andstableglomerularfiltrationrate.74Yet
orthostatic, dermatologic,pulmonary, gastrointestinal,andgenitourinaryadverse effects proved vexing,
andtheeventualextinctionofthe surgicalapproachwascausedbytheadvent ofthiazidediureticsand
othereffectiveandwell-toleratedoralagents.
C.However,catheter-baseddenervationmayprovidebenefitsinresistanthypertensionwithoutsimilar
side effects and is founded upon the presence of both efferent and afferentsympathetic nerves in the
adventitial regions surrounding the renal arteries. The efferent nerves constitute postganglionic fibers
arising from the hypothalamus andtravel to the renal arteries via pre- and paravertebral sympathetic
ganglia T10 through L2. The afferent nerves originate in the wall of the renal pelvis (chemo- and
mechanoreceptors)andcourseviadorsalrootgangliaL4throughT6tocentralnervoussystemautonomic
centers as well as the contralateral kidney. Increased afferent signal traffic may arise from elevated
vascularpressure,renalischemia,orrenalarterystenosis.Inturn,efferentsympatheticresponsefromthe
central nervous system can promote direct renal vasoconstriction andaugmented renin release.75 The
consequent activation of the renin-angiotensin system will manifest several actions: (1) systemic
vasoconstriction,(2)augmentedbloodvolume,(3)vascularsmoothmusclehypertrophy,(4)myocardial
hypertrophy, (5) salt and water retention in the kidney, and (6) overall intensification of systemic
sympathetic activity. Further renal consequences can include reduced renal blood flow, increased
proteinuria,andresistancetothediureticeffectsofB-typenatriureticpeptide.Longerrangeeffectsmay
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encompass increased insulin resistance, impaired glucose metabolism, heart failure, generalized
atherosclerosis,myocardialischemia,increasedcardiacinotropicandchronotropicresponses,aswellas
atrialandventriculararrhythmias.
75
D.Intermsofphysiology,humanstudieshaveshownloweredbloodpressure,improvedrenalresistive
index, and lessening of proteinuria without change in glomerular filtration rate.76 Yet it is worth
considering theoretical objections to renal denervation: long-term effects are unknown, andthere is a
concern that treated individuals may forfeit necessary sympathetic responses to future illnesses such
sepsis with distributive vasodilatory shock, allergic anaphylaxis, or life-threatening hemorrhage. For
example,inanovinemodel(normotensiveaswellashypertensivesheepwithchronickidneydisease),
renaldenervationversusashamprocedurewasperformed.Hypertensionandrenalfunctionimprovedin
thedenervationkidneydisease group. Experimentalhemorrhage was theninduced inall subjects,with
greater fall in blood pressure in all denervated subjects, with attenuated heart rate and renin release
responsesinthedenervatedversusthenondenervatedsubjects.Theseresponsesweresimilarat2months
and 5 months postprocedure, suggesting that sympathetic responses do not return over time.77 The
potentialsignificanceofthesefindingsinhumansisunknown.
XIV.RenalSympatheticDenervationforResistant
Hypertension:RandomizedProspectiveData
A.EarlyCatheter-BasedTrials:SymplicityHTN-1Study
Theearliestcatheter-basedtrialsofrenaldenervationutilizedtheMedtronicsystem,whichconsistedofa
6Fhelicalradiofrequencyablatingsystem,andwhichrequiredablationrunsof2minutesdurationeach,
usingamaximalenergyof8Wwithattainmentofatemperatureof70-90°C.78Arteriesofinterestneeded
to be at least 4.0 mm in diameter and >20 mm in length. Subjects were excluded if they exhibited
calcification,fibromuscular dysplasia, orobstructiveatherosclerotic disease (need foradequateblood
flowtodisperseheatandavoid thermaldamagetotherenalartery).Usingthissysteminapreliminary
pilottrial(the SymplicityHTN-1 Study),50subjectswerefollowedfor12months,showingincreasing
overall improvements in blood pressure regulation after the procedure (−14/−10 mm Hg at 1 mo,
advancingto−27/−17mmHgat12mo).79Currentlythereisnobiomarkeravailabletoprovesuccessful
denervation.
78
B.SymplicityHTN-2Trial
1. The SymplicityHTN-2 Trial tested 190 subjects with resistant hypertension, of whom 106 were
randomized tothe renal denervationarmversus control with12-monthtotal follow-upduration.80 At
6 months,control patientswere permittedtocrossover torenaldenervation. At the6-monthpoint, the
denervation arm showed blood pressure change of −32/−12 mm Hg versus control −1/0 mm Hg. At
12 months, the original denervation armexhibited blood pressure change of −28/−10 mm Hg and the
crossovergroup−24/−8mmHg.
2. Yet the SymplicityHTN-2 Trial was critiqued because the most dramatic improvements in blood
pressurewerewitnessedinacohortofsubjectswhohadofficebloodpressureevaluationversusamuch
less impressive response in subjects who were assayed using a 24-hour ambulatory blood pressure
monitor. The latter ambulatory technique (1) provides more data, (2) encompasses physiologic (or
pathologic)diurnalvariation,(3)eliminatestransientofficehypertension,(4)avoidshumansubjectivity
in measurement, and (5) is considered a standard optimal techniquefor contemporary blood pressure
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research.
3.Inadditiontothequestionofambulatorymonitoring,otherdeficienciescitedincludedlackofasham
procedure,failuretotrackchangesinantihypertensivemedicationsduringthefollow-upperiod,andthe
relativelyminimal roleoftherapeuticaldosterone inhibitors,showninresistanthypertensioncohortsto
have nearlyidentical bloodpressure–loweringeffects asobservedinthe renaldenervationarmover a
similartimeinterval(forspironolactone,−21/−10mmHgat6wk,−25/−12mmHgat6mo).
81
C.SymplicityHTN-3Trial
1. The SymplicityHTN-3 Trial successfully addressed the above objections regarding consistent
ambulatorymonitoringandthe inclusion ofasham proceduresasthecontrol,emphasizedfulldosesof
three antihypertensive medications for both denervation and control arms, and prohibited medication
changes for the first six months postprocedure.82 Nonetheless the trial was negative, showing a
nonsignificant systolic blood pressure difference betweendenervation and sham procedurearms using
office(−14vs−12mmHg)aswellambulatory(−7vs−5mmHg)measurementtechniques.
2. There may bevariousdiverse factors that explainthenegative resultofwhathadappeared to be a
promising novel transcatheter method: (1) whether disorders that have strong lifestyle component can
trulybestudiedinarandomizedfashion,(2)whetherthecontemporaryexcellenceofmedicaltherapycan
be matched by any interventional technique, (3) whether much of what appears to be resistant
hypertension is not truly so when subjected to ambulatory monitoring, (4) whether operator-based
variationscontaminatedthetrial,(5)whethertheinitialtrialresultsunderscoredaplaceboeffectrather
than an objective physiologic improvement, (6) whether anatomic factors were influential, such as a
potential need to perform ablation more distally in the renal arterial tree, (7) whether there was
differential postprocedure medication adherence between the two arms, and (8) finally, whether this
resultreflectsa device-specificfailurethatisremediablethrough newcatheter designs.Regarding (8),
there are a multitude of novel devices in development that use diverse methods including ultrasound,
alcohol ablation,andcenteringballoonsthatoptimize symmetryofcircumferential treatmentexposure.
78,83
D.SPYRALHTN-OFFMEDTrial
1.Morerecently,theSPYRALHTN-OFFMEDtrialwaspresentedandpublishedonline.
84
Thisstudy
answeredsomeoftheconcernslistedabove,85showingmodestyetstatisticallysignificantbloodpressure
loweringusingrenaldenervationasaproofofconceptexercise,wherenoantihypertensivemedications
werepermittedineitherrenaldenervationorsham-procedurecontrolarms(denervationarmversussham
showeda difference of−5/−4 mm Hgsystolic/diastolic by ambulatory monitoring, and adifference of
−8/−5systolic/diastolicbyofficereadings,bothstatisticallysignificant).84Althoughtheproofofconcept
isscientificallyinteresting,itisacknowledgedthatthismodestdegreeofbloodpressureloweringinan
untreated patient would be readily available through the simplest of medication (or even lifestyle)
measures.Moreover,itisstillnotclearinwhichhypertensiveclinicalsubsetsrenaldenervationwould
bebestapplied.
29
2.Ofmajortechnicalinterest,thisstudybroughtintoplayanewgenerationdevice,theSymplicitySpyral
catheter.Thisiterationisnotableforamultielectrodesystemthatiscapableofsimultaneousquadrantal
therapyinthe mainrenal arteryinadditionto arterialbranches and accessoryarteries, provided these
vessels are 3.0-8.0 mm in diameter. The value of branch ablation is supported by emerging data
suggesting that the renal sympathetic nerves may lie closer to the vessel lumens inthese more distal
locations,creatingheightenedopportunityforablativebenefit.
86-88
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XV.RenalSympatheticDenervationforExtrarenalCirculatory
Disorders
The well-established observation that sympathetic overactivity underlies many cardiovascular and
metabolic conditions, and thatchemical antiadrenergictherapies(beta-adrenergicblockers, andothers)
haveproventherapeuticallyuseful,hasgivenrisetoseveralpresentlyenrolling(orcompleted)studiesof
renalsympatheticdenervation(Table8.2).Theseconditions(andtrials)encompassresistanthypertension
(SymplicityHTN-1,2,3;SPYRALHTN-OFFMED),atrialfibrillation(Symplicity-AF),sleepapnea,
89,90
leftventricularhypertrophy, metabolic syndromewith insulinresistance (DREAMS-Denervationofthe
Renal Artery in Metabolic Syndrome), and congestive heart failure (Symplicity-HF). A recent report
describing an experimentalmodel haslinked renal sympathetic denervationwithimprovement inheart
failureviatheinhibitionofneprilysinactivityinthekidney.91Althoughthereareplausibleandattractive
theoreticalmechanismsbywhichrenaldenervationmaybenefitthesedisorders,asisevidentfromrecent
experience,thescientificcommunitymustawaittheresultsofwell-constructedclinicaltrialstodetermine
theincrementalvalueofrenaldenervationbeyondpresentlyexistingtherapies.
Table8.2
ClinicalConditionsforWhichRenalDenervationhasBeenProposedasTherapy
Resistanthypertension(SymplicityHTN-1,2,3)
Congestiveheartfailure(Symplicity-HF)
Atrialfibrillation(Symplicity-AF)
Sleepapnea
Leftventricularhypertrophy
Metabolicsyndromeandinsulinresistance(DREAMS)
XVI.ContemporaryManagementofRenovascularDiseaseand
FutureDirections
A.InterventionalTherapies
Interventional therapies for obstructive renovascular disease as well as hypertension (and other
cardiovascularandmetabolicconditions)havematuredfromatechnicalanddeviceviewpointoverthe
past decades. However,more critically, there has beena refinement in the clinical diagnostic sphere:
emerginginvestigativeandpracticeexperienceisinformingthe communityofvascularspecialistswith
greater specificity regarding whom to treat(as well as whom notto treat) when considering evolving
technologiessuchasrenalarterystentingordenervation.
Severalpoints,however,are clear.Forindividuals whohaveatherosclerotic renovasculardisease, all
shouldreceiveoptimalmedicationandlifestyletherapy(Table8.3).Futureinvestigations maycombine
physiologic measurements with angiographic findings in testing strategies of revascularization versus
optimalmedicaltherapy.
Table8.3
SuggestedOptimalMedicalandLifestyleTherapyforManagementofRenovascularDisease
Aspirin
Clopidogrel(orothernovelantiplateletcompounds)
Statin
Antihyperglycemic
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана