Tromboendarterectomia pulmonar em Portugal

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www.revportcardiol.org

Revista Portuguesa de

Cardiologia

Portuguese Journal of Cardiology

ORIGINAL ARTICLE

Pulmonary thromboendarterectomy in Portugal: Initial experience

José Fragata, Helena Telles

Servic¸odeCirurgiaCardiotorácica,HospitaldeSantaMarta,CentroHospitalareUniversitáriodeLisboaCentral(CHULC),Nova MedicalSchool,Lisboa,Portugal

Received17February2020;accepted6May2020 Availableonline26August2020

KEYWORDS Chronic

thromboembolic pulmonary hypertension;

Pulmonarythrom- boendarterectomy;

Single-centerreport results;

Cardiothoracic surgery;

Pulmonary hypertension;

Treatment

Abstract

Introduction:Surgicaltreatmentforchronicthromboembolicpulmonaryhypertension(CTEPH) ischallenging.MostPortuguesepatientswithCTEPHhavebeenreferredtoforeigninstitutions fortreatment,withsigniﬁcantsocialandeconomiccosts.Tomeetthisemergingneed,thecar- diothoracicsurgerydepartmentofHospitaldeSantaMarta,Lisbon,hasdevelopedadedicated programforpulmonarythromboendarterectomy(PTE).Weherebypresenttheresultsforthe ﬁrst19patientstreated.

Methods:We conducted a retrospective analysis of all 19 patients who underwent PTE at HospitaldeSantaMartabetween2008andApril2019.

Results:Since2008,atotalof19patientshaveundergonePTEinourdepartment.Thepro- cedure wasperformed withgoodoutcomesinbothsurvivalandfunctionalrecovery. Atthe verybeginningoftheseriestwopatientsdiedperioperatively,beforealltheteamunderwent formaltrainingattheRoyalPapworthHospital,UK,withnoearlydeathssince.Postoperative complicationsweresimilartootherpublishedseries.During11yearsoffollow-up,therewere threelatedeaths,allinpatientswithresidualpulmonaryarterialhypertension.Atthelatest follow-up(October2019),allsurvivingpatients showedsignificantfunctionalrecovery,allin NYHAclassIorII,withonlyonepatientonvasodilatortherapywithsildenafil(thefirstinthe series,operatedin2008).

Conclusions: PTE isademanding procedure, inwhich outcomesarerelated to volume and accumulatedexperience,howeveritcanbeperformedsafelyandwithreproducibleresultsby aproperlyprepareddedicatedteamwithawell-controlledlearningcurve.Morepatientsand multidisciplinaryexperiencewillbeneededtofurtherimproveandstreamlineresults.

E-mailaddress:[email protected](H.Telles).

https://doi.org/10.1016/j.repc.2020.05.006

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PALAVRAS-CHAVE Doenc¸apulmonar tromboembólica crónica;

Tromboendarterectomia pulmonary;

Resultadosde relatóriodecentro único;

Cirurgia cardiotorácica;

Hipertensão pulmonar;

Tratamento

TromboendarterectomiapulmonaremPortugal:Experiênciainicial

Resumo

Introdução:Otratamentocirúrgicodahipertensãopulmonartromboembólicacrónica(CTEPH) édesafiante.Atéaopresente,amaioriadosdoentesportuguesessofrendodestapatologiatêm vindoaserreferidos paratratamentoem instituiçõesestrangeiras, comimportantescustos sociais eeconómicos.Para responderànecessidadede desenvolvimentodeum tratamento local de qualidadepara estes doentes,oServiço deCirurgia Cardiotorácicado Hospital de SantaMarta(HSM)temvindoadesenvolverumprogramadedicadodetromboendarterectomia pulmonar(PTE).Apresentamososresultadoscomosprimeiros19doentes.

Métodos: Análiseretrospetivadetodosos19doentessubmetidosaPTEnoHSMde2008aabril de2019.

Resultados: Desde2008,19doentesforamtratadosnoServic¸odeCirurgiaCardiotorácicado HSM, com bons resultados, quer a nível da sobrevivência quer da recuperac¸ão funcional.

Ascomplicações pós-operatóriassãosemelhantesàsdescritasnaliteratura.Ocorreramduas mortes perioperatóriasnoiníciodaexperiência, antesde aequipaterfeito umperíodo de treinoformalnoRoyalPapworthHospital,semmortalidadeprecocedesdeentão.Duranteos 11anosdefollow-up,ocorreramtrêsmortestardias,emdoentescomalgumgraudehipertensão pulmonarresidual.Àdatadoúltimoseguimento(outubrode2019),osdoentesvivosapresen- tavamrecuperaçãofuncionalsignificativa,encontrando-setodosemclasseNYHAIouII.Apenas um(oprimeirodestasérie,operadoem2008)estavasobterapêuticavasodilatadorapulmonar comsildenafil.

Conclusões:APTEéumprocedimentoexigente,emqueosresultadosestãodependentesde volumedecasoseacumulac¸ãodeexperiência,masquepodeserrealizadacomseguranc¸ae resultadosreprodutíveisporumaequipadedicadacomumacurvadeaprendizagembemcon- trolada.Maisdoenteseexperiênciamultidisciplinarserãonecessáriosparamelhorareotimizar osresultados.

Introduction

Chronicthromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary arterial hypertension (PAH) resulting from the ﬁbrotic transformation of pulmonary artery clots causing chronic obstruction of the pulmonary arteries, leading to vascular remodeling in the microvasculature. Consequently, pulmonary arterial pres- sureandvascularresistanceincrease,leadinginexorablyto right heart failure, functional impairment and premature death.

Not all patients with CTEPH report a history of acute pulmonaryembolism(PE);theincidenceofCTEPHafterPE is around1.5% andregistry data indicatea prevalence of 3-30permillioninthegeneralpopulation.¹However,most CTEPH patients present with a previous PE. The Interna- tionalCTEPHRegistryreportsaprevious acutePEeventin 74.8%of CTEPH patients,andthe cumulativeincidenceis reportedtobe0.1-9.1%withintwoyearsofanysymptomatic pulmonaryembolicevent.

Althoughtheexact prevalenceandannualincidenceof CTEPHareunknown,somedatasuggest thatthecondition mayoccurinapproximatelyﬁvepermillionpopulationper year.Itsprevalence inEuropeancountriesis3.2casesper millionperyear,andis0.9casespermillioninSpain,²which, duetosimilaritiesinthepopulationsofthetwocountries,

meansthatareasonableestimateforPortugalwouldbenine newcasesyearly.

ThetrueincidenceandprevalenceofCTEPHinthePor- tuguese population are unknown, although according to Gouveiaetal.³theestimatedincidenceofacutepulmonary embolisminPortugalin2013was35per100000population.

In a nationwidestudy by Baptista et al.,⁴ afterexcluding patientsinWorldHealthOrganization(WHO)PAHgroups2,3 and5,CTEPHpatientscomprised41.8%ofallthosewithPAH.

Thisstudy,basedonasmallnumberofpatientsfollowedat dedicated PAH centers,remains the sole nationwide data availableforCTEPH.

Predisposing factors such as thrombophilic disorders, lupus anticoagulant and antiphospholipid antibody syn- dromes, protein S and C deﬁciency, activated protein C resistance includingfactor V Leidenmutation,thrombotic gene mutations, antithrombin III deﬁciency and elevated factorVIIIhavebeenreportedin31.9%ofpatientsandpre- vioussplenectomyin3.4%.²

Diagnosis and assessment of operability

AdiagnosisofCTEPHisbasedonﬁndingsobtainedafterat leastthreemonthsofeffectiveanticoagulation,inorderto differentiatethisconditionfromsubacuteformsofPE.²

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The clinicalcriteriafor diagnosisaccordingtothe2015 EuropeanSocietyofCardiology/EuropeanRespiratorySoci- ety (ESC/ERS) guidelines were mean pulmonary artery pressure(mPAP)≥25mmHg(revisedin2018to≥20mmHg), pulmonary artery wedge pressure ≤15 mmHg, and spe- ciﬁcdiagnostic signsfor CTEPH onimagingstudies.These includemismatchedperfusiondefectsonlungscan(anormal V/Q scaneffectivelyexcludes CTEPH witha sensitivityof 90-100%andspeciﬁcityof94-100%),andring-likestenoses, webs/slits and chronic total occlusions (pouch lesions or tapered lesions).² Imaging studies --- multidetector com- puted tomography (CT) angiography, magnetic resonance imaging(MRI),orconventionalpulmonary cineangiography --- areessentialfordiagnosisandlesioncharacterizationand toguidesurgicalintervention.Atleasttwoimagingmethods arerecommended;electivepulmonarycineangiographycan bereplacedbyMRIorCTscan.

In additiontoimagingstudies, patientsshouldundergo right heart catheterization, an echocardiogram, and car- diorespiratoryfunctionaltestingsuchasthe6-minwalktest ortreadmillexercisetesting.^6,7

Acceptance criteria

Pulmonarythromboendarterectomy(PTE)isthetreatment of choice for patients withCTEPH, both for symptomatic reliefandforimprovementor normalizationofpulmonary hemodynamics.

There is general agreement in the literature that PTE shouldbeofferedtoeveryoperablepatientwithCTEPHif theriskisacceptable,sincethisprovidessurvivalbeneﬁt.

Accordingtotheguidelines,operabilityisdeterminedby multiple factors that arenot easily standardized. Certain featuressuchasthedegreeofpulmonaryvascularresistance (PVR)andlocationofthromboticlesionsarestronglyrelated tooutcomes.^8,9

Tobeconsideredoperable,apatientmusthavesufﬁcient surgically accessible thromboembolic material, and more importantly,agoodcorrelationbetweentheextentofdis- easeandthedegreeofPVR.Extensivesecondaryperipheral vasculopathyshouldbeexcluded.^1,6,9

Patientsofadvancedage,frailorinpoorgeneralcondi- tion,or withserious comorbidities,aregenerallydeemed tobeinoperableduetotheiroverallsurgicalrisk.Operabil- ityisbestestablishedbasedonacase-by-caseanalysis,and borderlinecaseswillcertainlyneedasecondopinion.

Althoughregistrydatasuggestthatinthepastmorethan onethirdofpatientsdiagnosedwithCTEPHdidnotproceed toPTE surgery, PTE shouldbe offered tothe majority of patients.^1,6,9,10

AlthoughPTEisthetreatmentofchoiceforCTEPH,itis stillnotwidelyavailabletothePortuguesepopulation,with onlyasmallnumberofpatientsbeingreferredtointerna- tionalcenters,atconsiderablepersonalandsocietalcost.¹¹ Since 2008, the cardiothoracic surgery department of Hospital de Santa Marta in Lisbon has been operating a PTE program, providing surgical treatment to Portuguese patients with CTEPH. The department provides the full rangeofservicesneededtoperformandsupportthistype ofsurgery,includingcardiothoracicsurgery,structuralcar- diology,cardiacandthoracicanesthesiology,extracorporeal

Table1 Clinicalcharacteristicsofthestudypopulationat diagnosis(n=19).

Demographics

Age,years 54.8±14.8

Malegender 36.8(7)

BMI,kg/m² 26.8±5.1

Genetics(conﬁrmed) 21(4)

Preoperative

Creatinine,mg/dl 0.76±0.23

Systemichypertension 68.42(13)

Diabetes 15.8(3)

Smokinghistory 26.3(5)

COPD 15.8(3)

PreviousMI 5(1)

Previousacuteevent 31.6(7)

Clinical

NYHAI/II 5(1)

NYHA≥III 94.7(18)

Useofpulmonaryvasodilators 21(4)

SupplementaryO2 36.8(7)

Echocardiography

PASP,mmHg 100.5±14.84

TAPSE,mm 14.5±0.7

TRgrade>III 47.4(9)

Hemodynamics

mPAP,mmHg 45.6±13.4

PASP,mmHg 81.4±24.3

PVR,WU 22.8±6.8

PVR,dyn.s.cm⁵ 1821.6±575.1

PVR>12.5WU/1000dyn.s.cm⁵ 42(8)

CI,l/min/m² 2.02±0.68

Valuesarepercentage(n)ormean±standarddeviation.

Onepatienthadapreviousmyocardialinfarctiontreatedwith percutaneouscoronaryinterventionoftheleftanteriordescend- ingartery.

BMI:bodymassindex;CI:cardiacindex;COPD:chronicobstructivepulmonarydisease;MI:myocardialinfarction;mPAP:mean pulmonary arterypressure;NYHA:NewYorkHeartAssociation class;PASP:pulmonaryarterysystolicpressure;PVR:pulmonary vascular resistance; TAPSE: tricuspid annular plane systolic excursion;TR:tricuspidregurgitation;WU:Woodunits.

membrane oxygenation (ECMO) and lung transplantation programs.Weherebypresenttheinitialexperiencewiththis ongoingprogram.

Methods

We retrospectively analyzed data from all patients who underwentPTEatourcenter.Thesepatientswerereferred byourlocalPAHteam,aswellasbyotherexpertPAHteams inthecountry.

All patients were diagnosed andassessed according to theESC/ERSguidelines,atleasttwoimagingtests(CTscan and pulmonary angiography) being required to determine thediagnosisandestablishoperability.

BaselinepatientcharacteristicsaredescribedinTable1.

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Figure1 Typicalsurgicalspecimenofmoldedcasts.

Figure2 Surgicalspecimenofpredominantwebs.

Surgical protocol

Allpatientswereoperatedelectively,bythesamesurgical team,followingthesamestandardperioperativeprotocol.

All procedureswere performed withaortic anddouble venouscannulation,rightsuperiorpulmonaryveinandmain pulmonaryarteryventing,single-shotcoldbloodcardiople- giaandstandardcirculatoryarrestperiodsof20minat18^◦C nasopharyngeal temperature. If circulatory arrest periods longerthan20minwereneeded,10-minreperfusionperiods weremandatorybetweenarrestperiods.

Standardmodiﬁedultraﬁltrationandcerebralprotection measureswereroutinelyused.

Thecentralpulmonaryarteriesweremobilizeduptothe hilum,takingcarenottoopenthepleurae,then,underperi- ods of complete hypothermiccirculatory arrestand total exsanguination,pulmonaryendarterectomieswerecarried outsequentially,ﬁrstontheright,thenontheleftside.

The critical step is the development of the correct dissection plane, followed by meticulous circumferential dissection,extendingdistallytothesegmentalandsubseg- mentalbranches.Thisenablestheremovaloffullcastsand webs,leadingtoeffectivereliefofobstruction(Figures1-3).

After direct closure of the pulmonary arteriotomies with 5-0 nylon sutures, patients are fully rewarmed and weaned off cardiopulmonary bypass. Inotropic support is usedaccordingtoourprotocol,typicallyinlowtomoderate dosages.Meticuloushemostasisisachieved.

Figure3 Surgicalspecimen frompatient 3. Notethelarge quantityofclotcastsandwebsremoved,which,togetherwith thereductioninpulmonaryarterypressureconﬁrmedimmedi- atelyaftersurgery,ledustoexpectagoodoutcome.However, thepatientdidnotsurvive.

Table2 Surgicaltimes.

Durationofsurgery,min 256.9±58.0

Bypasstime,min 185.5±66.7

Cross-clamptime,min 48.3±11.9

Cumulativecirculatoryarresttime (separatedbyreperfusion),min

31.6±21.1 Valuesaremean±standarddeviation.

Onlytheﬁrstpatient(in2008)underwenttricuspidannu- loplasty; none of the other patients had their functional tricuspidregurgitationaddressedatsurgery,sincerecovery is expected after removing right ventricular afterload,as statedintheliterature.¹²

Operative specimens are systematically documented (Figures1-3).

Meansurgical times aredisplayedin Table 2and some operativespecimensareshowninFigures1and2.

Postoperative management

Postoperative care is conducted according to published protocols, paying particular attention to prevention and managementofreperfusionedema.

Inotropicsupportuse wasdeterminedby hemodynamic and echocardiographic monitoring. Low-dose dobutamine andnoradrenalinearemostfrequentlyused,otherinotropes or vasodilators being added according to clinical circum- stances.

Negative fluid balance (by fluid restriction and intra- venous furosemide)iscrucialin themanagementofthese patients, as is early adequate anticoagulation. Anticoag- ulant therapy consists of low molecular weight heparin (1mg/kg,twicedaily),startedasearlyaspossible(ideally in thefirst 24hoursif surgicalbleedingis <50 cc/h),and switchedovertooralanticoagulationwithvitaminKantago- nists,untiltherapeuticinternationalnormalizedratiolevels (around3)areachieved.

PostoperativedataaresummarizedinTable3.

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Table3 Postoperativedata.

Hospitalstay

ICUstay,days 9.2±8.5

Totalstay,days 21.5±12.9 Complications

Pulmonarysteal 31.6(n=6) Reperfusionedema 5(n=1)

ARDS 5(n=1)

Renaldysfunction 5.26(n=1) Inotropes>24h 52(n=10) Bleeding>10mg/kg/24

hand/ortransfusion

57.9(n=10)

Discharge

Home 73.68(n=14)

Otherhospital 26.31(n=5;three patientslaterdischarged home,twodiedin referringhospital)^a Mortality

In-hospitalmortality (<30days)

10.5(n=2)^a

Latemortality 15.78(n=3)^b

a Atthebeginningofthestudyperiod.

b Overthe11yearsofthestudyperiod.

Valuesarepercentage(n)ormean±standarddeviation.

ARDS:acuterespiratorydistresssyndrome;ICU:intensivecare unit.

Results

Preoperativedata

The meanage of thepatients was54.8±14.8years.They werepredominantlyfemale(63.2%),hadahistoryofapre- viousacuteeventin31.6%ofcases,andin21%ofcasesthere wereconﬁrmedgeneticprocoagulantconditions.

Asexpected,mostpatients(91.7%,n=14)presentedwith signiﬁcantclinicalandfunctionalimpairment,inNewYork HeartAssociation(NYHA)classIIIorIV.Oxygensupplementa- tionwasneededin36.8%and21%wereonchronicpulmonary vasodilatortherapy.

Echocardiography showed severe pulmonary hyperten- sionandrightventriculardysfunctioninallpatients,47.4%

ofpatientspresentingwithsevere(gradeIIIorIV)tricuspid regurgitation. Hemodynamicdata confirmed the echocar- diographicfindings,withasignificantproportionofpatients (42%) presenting withseverely elevated PVR (>12.5 Wood units/1000dyn.s.cm⁵).Cardiacoutputwasuniformlylow.

BaselinepatientcharacteristicsaredescribedinTable1.

Operativedata

Giventhenatureofthissurgicaltechnique,surgical times tendtobelong,particularlyduetothecoolingandrewarm- ingphases. Cross-clampandcirculatoryarresttimes were withintherecommendedlimits.

NopatientsneededoperativeECMOsupport.

OperativedataaresummarizedinTable2andsomeoper- ativespecimensareshowninFigures1and2.

Postoperativecourseandcomplications

Postoperativecoursewasfrequentlyprolonged,withamean intensivecareunitstayof9.2±8.5daysandtotallengthof stayof21.5±12.9days.

Pulmonarycomplicationswerethemostcommon,occur- ringineightpatients.Ofthese,six(31.6%)presentedwith some form of pulmonary steal syndrome with persistent hypoxemia,requiringprolonged ventilationor supplemen- tary oxygen postoperatively. One patient presented with frank pulmonary reperfusion edema and one patient had full-blownacuterespiratorydistresssyndrome.Renal dysfunction occurred in one patient,without need for renal replacementtherapy.

Central nervoussystem complications wererare andif presentweremild,presentingasmoodchangesand/oragi- tation.

Need for inotropes for more than 48 h was frequent, albeitatlowdosages.

Transfusion was frequent, due to a relatively lib- eral transfusion strategy (transfusion threshold ≤8 g/dl hemoglobin),butnopatientsneededreoperationforbleed- ing.

ECMOsupportwasnotneededpostoperatively.

Mostpatients(73.68%,n=14)weredischargedhome,with asmallnumber(26.31%,n=5)beingtransferredtotherefer- ring hospitals due to delayed recovery. Of these, three patientswerelaterdischargedhomehavingmadeanade- quaterecoveryandtwodiedatthereferringhospital.

Duetothesmallsamplenumber,thesedelayedrecover- iesweighedheavilyinthelengthofstaynumbers.

Follow-up

Completefollow-upwasachievedinallpatients.

Astolong-termoutcomes,byOctober2019,14patients were alive and all had experienced signiﬁcant functional recovery,beingin NYHA classI or II, and therehad been consistentimprovementinhemodynamicparameters(con- ﬁrmedin somepatients byright heart recatheterization).

Onlyone patientis onvasodilator therapy, withsildenafil (the first in the series, operated in 2008). Although on sildenafil,thispatientiscurrentlyinNYHAclassII.Present numbersarestilltoosmallforanymeaningfulsurvivalanal- ysis.

Mortality

Twopatientsdiedperioperatively,in2011and2012,before alloftheteamunderwentformaltrainingintheexperienced centerattheRoyalPapworthHospital,UK.Onepatientdied fromintraoperativepulmonaryarteryruptureandtheother fromfulminanthemoptysisonthesixthpostoperativeday.

Thesetwoearlydeaths wereprobablyrelatedtothefact thattheywereoperatedearlyinourlearningcurve.

At11yearsoffollow-up,threelatedeathshadoccurred, allpatientshavingincommonmoderateresidualpulmonary

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J.Fragata,H.Telles Table4 Latemortality:detailedanalysis.

Patient Age, years

Genderand medicalhistory

Preoperativestatus Surgery Dis Disto D TOD

PE O2 Rioc mPAP, mmHg

PASP, mmHg

PVR, dyn.s.cm⁵

CI,l/

min/m² NT- proBNP>

1000 pg/ml

1 72 Male

PreviousCADwith PCIoftheLAD

>70%in-stent lesion LVEF40%

Y N N 35 60 571 2.2 Y PTE+LIMA

toLAD

PO$24 Home H1N1

infection andseptic shock,renal failure

PO70

2 76 Female

COPD

N N N 60 98 1281 1.89 Y PTE PO10 Referring

hospital

Respiratory infection andfailure

PO60

3 48 Female

COPD Activesmoker (120pack/years) Stroke

Bipolardisease SevereRV dysfunction

Y Y Y 55 89 2581 1.77 Y PTE PO20 Referring

hospital

Respiratory failureand infection

PO36

CAD:coronaryarterydisease;CI:cardiacindex;COPD:chronicobstructivepulmonarydisease;D:causeofdeath;Dis:timeofdischarge;Distto:dischargedto;LAD:leftanteriordescending artery;LIMA:leftinternalmammaryartery;LVEF:leftventricularejectionfraction;mPAP:meanpulmonaryarterypressure;N:no;O₂:supplementaryoxygen;PASP:pulmonaryartery systolicpressure;PCI:percutaneouscoronaryintervention;PE:pulmonaryembolism;PO:postoperativeday;PTE:pulmonarythromboendarterectomy;PVR:pulmonaryvascularresistance;

Rioc:preoperativeriociguat;RV:rightventricular;PASP:pulmonaryarterysystolicpressure;TOD:timeofdeath;Y:yes.

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hypertension.One patient,withischemic cardiomyopathy and left ventricular dysfunction (left ventricular ejection fraction40%)diedtwomonthspostoperatively,fromdocu- mentedH1N1infectionfollowedbysepsisandrenalfailure.

The other two patients were considered high risk, with severefunctionallimitationandextensivedisease.Despite relief of pulmonary arterial obstruction, one of these patientsdiedthreemonthspostoperativelyfromrespiratory infectionand failure.The third patient,withpre-existing severelungparenchymaldisease,sufferedrethrombosisof theright pulmonary arterydespiteappropriateanticoagu- lation,anddiedfrompneumoniaandrespiratoryfailureon postoperativeday36inthereferralhospital.

Assuggestedintheliterature,latedeathsmayoccurdue tounrelated causes in up to49% of patients, particularly thosewithsomeresidualpulmonary hypertensionandele- vatedPVR(≥425dyn.s.cm⁵).Thiscutoffhasbeenshownto correlatewithworsesurvival¹⁰ andis inlinewiththelate mortalityinourseries.InTable4andFigure3,wereview ourlatemortalitycasesindetail.

Discussion

ThispaperpresentsdataontheinitialexperiencewithPTE performedatasinglecenterinPortugal.

Results achievedso far byour center showacceptable survival andcomplicationrates, well withinthe expected range,giventhelevelofourpresentexperience.

The importance of a comprehensive multidisciplinary approachcannotbe overestimated.Suchan approachhas undoubtedlyhelped tosmooththeeffects ofthe learning curve,keepingpatientssafeandwithinexpectedfunctional outcomes.

Asforanycomplexsurgicalprocedure,PTErequireshigh surgical volumesandaccumulation ofexperience inorder toachievereproducibleresultsandclinicalexcellence,as stated in the updated recommendations from the 2018 CologneConsensusConference.¹³ In-hospitalfatalitiescor- relateinverselywiththenumberofcasesperformedyearly.

Specialized centers(thoseperforming over 50PTE proce- dures/year)showcasefatalityratesof≤3.5%.Forcenters performingbetween11and50PTEprocedures/year,mortal- ityaverages4.7%,andforcentersthatperformfewerthan 11PTE/yearitaverages7.4%.Ourcenterispresentlyinthe lattergroup.

The recommendedminimumnumberofPTEprocedures to be performed annually is 20; an expert center should performatleast20PTEoperationsperyearwithlessthan 10%mortality.⁶Alsoinlinewiththeserecommendations,an experiencedsurgeonisdeﬁnedasonewhoperformedover 20PTEs intheyear theywereﬁrstassessed,andcumula- tivelyover40proceduresinthepreviousthreeyears.^6,10

ForPortugal,ayearlycaseloadof20PTEscouldeasily beachieved,allowingfor reproducibleresults andmaking HospitaldeSantaMartaanexpertcenter.

Webelievethatbyincreasingreferrals,wearenowbuild- ingupasolidexperiencewithPTE.Nevertheless,wemight stilloccasionallyhavetorefermorecomplexandchalleng- ingcasesforsurgeryabroad,particularlythosewithsevere associatedcomorbiditiesormoresevereperipheraldisease,

in ordertoprovide patients with thebest possible treatment.

The recognition of our center asa national reference centerforadultPAHandPTE,followinganationwideopen contest,wouldenableus,inclosecollaborationwithevery PAHunitinPortugal,tobuilduparobustnationalPTEcenter.

OnlybyincreasingthePTEcaseloadandcloselymonitoring ourresultsandauditingourdatainatransparentwaywill thisaimbeachieved.

Conclusions

ThisisabriefreportofaninitialseriesofPTEprocedures, performedatasinglecenter.Thenumbersarestillsmall,but resultsareencouraging,reﬂectingarapidlyrisinglearning curve,withoutunduecomplicationsormortality.

Complication ratesare consistentwiththosepublished intheliterature,includingtransientpulmonarydysfunction, whichoccurredinlessthanhalfofcases.

Long-termoutcomesshowedaconsistentimprovementin NYHAclassandhemodynamicparameters,withallpatients inNYHAclassIorII.

Latemortalityoccurredinafewpatients,duetoacombi- nationofpre-existingclinicalseverityandresidual,though moderate,pulmonaryhypertension.

Presentnumbers are stilltoosmallfor any meaningful long-termsurvivalanalysis.

Weconcludethat,withamultidisciplinaryteam,itispos- sibletostart alocal program for PTEand tomanagethe learningcurve,withreproducibleresults.

Undoubtedly, more patients will be needed tofurther improveresults,butwefeelourinitialﬁndingsareencour- aging.

Authorship

JoséFragata:Surgeonperformingthecases,criticalrevision andﬁnalapprovaloftheversiontobesubmitted.

HelenaTelles:acquisition,analysisandinterpretationof data,draftingthearticleandrevisingitcriticallyforimpor- tantintellectualcontent.

The authorsagreetobe accountablefor all aspectsof the work in ensuring that questions related to the accu- racyorintegrityofanypartoftheworkareappropriately investigatedandresolved.

Funding

Thisresearchdidnotreceiveanyspeciﬁcgrantfromfunding agenciesinthepublic,commercialornot-for-proﬁtsectors.

Conﬂicts of interest

Theauthorshavenoconﬂictsofinteresttodeclare.

Acknowledgments

Wethankallthoseinvolved inthecare ofthesepatients, fromreferralcenterstoourownteam,andDr.JorgePinheiro Santosforeditingthemanuscript.

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