Congenital Heart Disease in Adults: Assessment of Functional Capacity Using Cardiopulmonary Exercise Testin

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www.revportcardiol.org

Revista

Portuguesa

de

Cardiologia

Portuguese

Journal

of

Cardiology

ORIGINAL

ARTICLE

Congenital

heart

disease

in

adults:

Assessmentof

functional

capacity

using

cardiopulmonary

exercise

testing

Sílvia

Aguiar

Rosa

a_,_∗

_,

_Ana

_Agapito

a

_,

_Rui

_M.

_Soares

a

_,

_Lídia

_Sousa

a

_,

José

Alberto

Oliveira

a

_,

_Ana

_Abreu

a

_,

_Ana

_Soﬁa

_Silva

a

_,

_Sandra

_Alves

a

_,

Helena

Aidos

b

_,

_Fátima

_F.

_Pinto

c

_,

_Rui

_Cruz

_Ferreira

a

a_Cardiology_Department,_Santa_Marta_Hospital,_Lisbon,_Portugal

b_Instituto_de_{Telecomunicac}_¸ões,_Instituto_Superior_Técnico,_Portugal_Minalytics,_Advanced_Solutions_for_Data_Mining_and

Analytics,Lisbon,Portugal

c_Paediatric_Cardiology_Department,_Santa_Marta_Hospital,_Lisbon,_Portugal

Received18January2017;accepted24September2017

KEYWORDS Adultcongenital heartdisease; Functionalcapacity; Cardiopulmonary exercisetesting Abstract

Aim: Theaimofthestudywastocomparefunctionalcapacityindifferenttypesofcongenital

heartdisease(CHD),asassessedbycardiopulmonaryexercisetesting(CPET).

Methods:AretrospectiveanalysiswasperformedofadultpatientswithCHDwhohad

under-goneCPETinasingletertiarycenter.DiagnosesweredividedintorepairedtetralogyofFallot,

transpositionofthegreatarteries(TGA)afterSenningorMustardproceduresorcongenitally

correctedTGA,complexdefects,shunts,leftheartvalvediseaseandrightventricularoutﬂow

tractobstruction.

Results:We analyzed 154 CPET cases. There were signiﬁcant differences between groups,

withthelowest peakoxygenconsumption(VO2)valuesseeninpatientswith cardiacshunts

(39%withEisenmengerphysiology)(17.2±7.1ml/kg/min,comparedto26.2±7.0ml/kg/minin

tetralogyofFallotpatients;p<0.001),thelowestpercentageofpredictedpeakVO2 in

com-plexheartdefects(50.1±13.0%)andthehighestminuteventilation/carbondioxideproduction

slope incardiacshunts (38.4_±13.4). Chronotropism was impaired inpatients with complex

defects.Eisenmengersyndrome(n=17)wasassociatedwiththelowestpeakVO2(16.9±4.8vs.

23.6±7.8ml/kg/min;p=0.001)andthehighestminuteventilation/carbondioxideproduction

slope(44.8±14.7vs.31.0±8.5;p=0.002).Age, cyanosis,CPETduration,peaksystolicblood

pressure,timetoanaerobicthresholdandheartrateatanaerobicthresholdwerepredictorsof

thecombinedoutcomeofall-causemortalityandhospitalizationforcardiaccause.

∗_{Corresponding}_author.

E-mailaddress:silviaguiarosa@gmail.com(S.AguiarRosa).

https://doi.org/10.1016/j.repc.2017.09.020

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Conclusion:AcrossthespectrumofCHD,cardiacshunts(particularlyinthosewithEisenmenger

syndrome)andcomplexdefectswereassociatedwithlowerfunctionalcapacityandattenuated

chronotropicresponsetoexercise.

reserved. PALAVRAS-CHAVE Cardiopatias congénitasdoadulto; Capacidade funcional; Provadeesforc¸o cardiorrespiratória

Cardiopatiacongénitaemadultos:avaliac¸ãodacapacidadefuncionalporprovade esforc¸ocardiorrespiratória

Resumo

Objetivo:Compararacapacidadefuncionalnascardiopatiascongénitas,avaliadaporprovade

esforc¸ocardiorrespiratória.

Métodos: Análiserestrospetivadosdoentesadultoscomcardiopatiacongénita,submetidosa

provadeesforc¸ocardiorrespiratória.OsdoentesforamdivididosemtetralogiadeFallot

oper-ada,transposic¸ãodegrandesartériasapóscirurgiadeSenning/Mustard,transposic¸ãodegrandes

artérias congenitamentecorrigida, defeitos complexos, shunts,doenc¸a valvular esquerdae

obstruc¸ãodotratodesaídadoventrículodireito.

Resultados: Foramavaliadas154provascardiorrespiratórias.Osvaloresmaisbaixosdeconsumo

de oxigénio no picoforam observados nosdoentes com shunt cardíaco (39%apresentavam

síndromedeEisenmenger)(17,2_±7,1ml/kg/min,emcomparac¸ãocom26,2_±7,0ml/kg/min

natetralogiadeFallot;p<0,001);ovalormaisbaixodapercentagemdeconsumodeoxigénio

nopicorelativamenteaoprevistofoiobservadonosdefeitoscomplexos(50,1_±13,0%)eomaior

valorderampaventilac¸ãominuto/produc¸ãodedióxidodecarbononosshuntscardíacos(38,4

±13,4).Ocronotropismofoimenoseﬁcaznosdoentescomdefeitoscomplexos.Asíndromede

Eisenmenger(n=17)associou-seaovalormaisbaixodeconsumodeoxigénionopico(16,9±4,8

versus23,6±7,8ml/kg/min;p=0,001)eaomaiorvalorderampaventilac¸ãominuto/produc¸ão

dedióxidodecarbono(44,8_±14,7versus31,0_±8,5;p=0,002).Idade,cianose,durac¸ãoda

prova,pressãoarterialsistólicanopico,tempoparaolimiaranaeróbioefrequênciacardíacano

limiaranaeróbioforampreditoresdooutcomecombinadocommortalidadedetodasascausas

ehospitalizac¸ãodecausacardíaca.

Conclusão:Osshuntscardíacos(particularmentecomsíndromedeEisenmenger)eosdefeitos

complexosassociaram-seamenorcapacidadefuncionalerespostacronotrópicaatenuadaao

exercício.

direitosreservados.

Introduction

Nowadaysmostpatientswithcongenitalheartdisease(CHD) areexpectedtoreachadulthood.Becauseexercise intoler-ancehasbeendocumentedatallagesofCHD,thesepatients needclosefollow-upandanobjectiveassessmentof func-tionalcapacity.1,2

Duetolong-termadaption,themajorityofadultpatients

withCHD self-reporttheir exercisecapacitystatusas

sat-isfactory, even in the presence of signiﬁcantly depressed

functionalstatus.Cardiopulmonaryexercisetesting(CPET)

is an accurate method for quantitative assessment of

exercisecapacity, including assessment of aerobic

capac-ity,chronotropicresponseandarrhythmias.1,3---6_Quantifying

exercise capacity by measuring parameters such as peak

oxygen consumption (VO2) is an established technique in

the management of patients with chronic heart failure.

However, in adult CHD patients its role has been much

less studied, and interpretation of test results remains a

challenge. Previous studies have demonstrated that CPET

datahaveanimportantinﬂuenceonthetreatmentapproach

inCHD,includingindicationforcardiactransplantation,and

onprognosis.2,7,8

Theaimofthepresentstudywastwofold:toassessand

comparefunctionalcapacityindifferentCHDgroups,

mea-sured objectively by CPET, and to investigate a possible

associationbetweenCPETparametersandoutcome.

Methods

Studydesign

Aretrospectiveanalysiswasperformedofconsecutiveadult

patientswithCHDwhounderwentCPETforassessment of

functionalcapacity.Thedatawerecollectedinasingle

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Thestudypopulationwasdividedaccordingtodiagnosis

or pathophysiological status: repaired tetralogy of Fallot,

transposition of the greatarteries (TGA)after Senning or

Mustard proceduresand congenitally corrected TGA(both

witha rightventriclefunctioningasasystemicventricle),

complexheartdefects(univentricularheart,Fontansurgery,

truncusarteriosus),shunts (atrial,ventricularor arterial),

leftheartvalvediseasewithstenosisorregurgitation

(bicus-pidaortic valve, subaorticstenosis), and right ventricular

outﬂowtractobstruction(RVOTO).

CPET was performed in patients with some degree of

effort intolerance,complexdefectsor signiﬁcant residual

lesions.

The combined outcome of hospitalization for cardiac

causeandall-causemortalitywasanalyzed.

Cardiopulmonaryexercisetesting

Maximal symptom-limited treadmill CPET was performed

usingthemodiﬁed Bruceprotocol.CPETandtherecovery

periodweremonitoredwithcontinuous12-lead

electrocar-diogram,bloodpressurecuff,saturation probeanda face

masktomeasurerespiratorygases.Bloodpressurewas

mea-suredat rest,at each stage,at peakexercise and at the

ﬁrst,thirdand sixthminuteof therecoveryphase.

Respi-ratorygaseswereanalyzed usingan Innocor® gas analyzer

and VO2, carbon dioxide production andventilation were

measuredonabreath-by-breathbasis.

Patientswereencouragedtoperformexerciseuntilthe

carbon dioxide production/oxygen consumption ratio was

1.15orhigher.

PeakVO2adjustedforbodymass,orforfat-freemassin

obesepatients(bodymassindex>30kg/m2_),_was_analyzed,

aswellasthepercentageofpredictedpeakVO2forageand

genderaccordingtotheWasserman/Hansenequation.The

minute ventilation (VE)/carbon dioxideproduction (VCO2)

slopewascalculatedbyautomaticlinearregressionwith

val-uesobtainedduringCPET.TheratiobetweenVE/VCO2slope

andpeakVO2wasalsocalculated.Peakcirculatorypower

wasdetermined by multiplyingpeak VO2 by peaksystolic

bloodpressure.Bothbaselineandpeakoxygensaturations

werealsocollected.

The chronotropic index was calculated as(peak heart

rate/resting heartrate)/(220-age/resting heart rate),and

considerednormalforvaluesbetween0.8and1.3.9

Statisticalanalysis

ThestatisticalanalysiswasperformedusingSPSSStatistics

version22(IBMSPSS,Chicago,IL).Continuousvariableswere

expressedasmean±standarddeviation.CPETparameters

werecomparedbetweenstudygroupsusingone-way

analy-sisofvariancebetweenmeanvaluesorthenon-parametric

Kruskal-Wallistest,andmultiplecomparisonsbetweenthe

study groups were performed with an appropriate

post-hoc test. Pearson’s chi-square or Fisher’s exact test was

applied for categorical variables. The Student’s t test or

the Wilcoxon-Mann-Whitney test for continuous variables

wasusedforgendercomparisons.Pearson’scorrelationwas

used to estimate correlation between continuous

varia-bles.Theassociation betweenvariablesandthecombined

outcome was assessed with univariate Cox proportional

hazardsanalysis(forwardstepwise).

Results

CPET data were analyzed from 154 patients, mean age

34.8±8.8years,55.8% male. The most frequent diagnosis

wascorrectedtetralogyofFallot(36%),followedbycomplex

defects(21%)(Table1).

There were signiﬁcant differences in CPET

parame-ters between the study groups. As shown in Table 1, the

lowest values for peak VO2 were seen in patients with

cardiac shunts, related to the fact that 39% of these

patientshadEisenmengersyndrome(17.2±7.1ml/kg/min,

compared to 26.2±7.0ml/kg/min in tetralogy of Fallot

patients;p<0.001).PeakVO2differedsigniﬁcantlybetween

genders only in the complex heart defect group (males

23.3±6.1ml/kg/min vs. females 16.9±4.6ml/kg/min;

p<0.001).Percentage of predicted peak VO2 adjusted for

age and gender was lower in the complex heart defect

group(50.1±13.0%)comparedtotheothergroups.

Patientswithcardiacshuntsandcongenitally corrected

TGAhadhigherVE/VCO2 slope(38.4±13.4and38.2±13.2,

respectively), for which the lowest value was in left

heartvalvedisease.Asigniﬁcant differencebetween

gen-ders was observed only in the complex defects group

(males32.3±12.4vs.females41.3±8.3;p<0.012).Theratio

betweenVE/VCO2slopeandpeakVO2washigherincomplex

defects.Peakcirculatorypowerwaslowerinpatientswith

shuntsandcomplexdefects.

Peakoxygensaturationbelow90% wasseen inpatients

withRVOTO,TGAandshunts,anditwasparticularlylowin

complexdefects(83.0±8.9%).

Chronotropism was impaired in patients with

com-plexdefects, among whom 71.9% presented chronotropic

incompetence,demonstratedbyachronotropicindex<0.8

(Table2).

Analyzing the overall population, cyanotic patients

(n=33) presented signiﬁcantly lower peak VO2 and higher

VE/VCO2 slope than non-cyanotic patients (17.8±5.4 vs.

24.3±7.9ml/kg/min;p<0.001and40.6±13.0vs.30.3±8.0;

p<0.001,respectively).Patientswithpulmonary

hyperten-sion (n=23) also presented lower peak VO2 (17.2±5.9 vs.

23.8±7.8ml/kg/min; p<0.001) and higher VE/VCO2 slope

(41.9±14.9vs.31.1±8.5;p=0.009).Eisenmengersyndrome

(n=17)wasassociatedwithevenlowerpeakVO2(16.9±4.8

vs.23.6±7.8ml/kg/min;p=0.001)andhigherVE/VCO2slope

(44.8±14.7vs.31.0±8.5;p=0.002)(Figure1).

TGA patients (after Mustard or Senning surgery)

pre-sented a negative linear correlation between time from

interventiontoCPETandpeakVO2(r=-0.564;p=0.070)and

peakcirculatorypower(r=-0.632;p=0.037),andapositive

linearPearsoncorrelationbetweentimefromintervention

toCPETandVE/VCO2slope(r=0.554;p=0.122)(Figure2).

In the overall population, 18.2% of patients (n=28)

reacheda carbon dioxideproduction/oxygen consumption

ratioof1.15orhigher.

Duringa mean follow-upof 31.9 months (minimumsix

months;maximum 79 months), the combinedoutcome of

all-causemortalityandhospitalizationforcardiaccausewas

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T able 1 Cardiopulmonary exercise testing data. Diagnosis n Age (years) Male (%) P eak VO 2 (ml/kg/min) % predicted peak VO 2 VE/VCO 2 slope VE/VCO 2 slope/VO 2 PCP (mmHg/ml/kg/min) Baseline OS (%) P eak OS (%) CPET duration (min) To F 5 5 35.0 ± 8.4 64.8 26.2 ± 7.0 a,b 68.9 ± 15.3 a,b 27.5 ± 5.3 a,b 1.2 ± 0.6 4195.6 ± 1484.7 a,b 95.2 ± 3.4 a 91.1 ± 4.5 b 14.0 ± 3.3 a TGA 15 30.1 ± 4.5 88.5 22.0 ± 5.0 55.2 ± 11.7 34.0 ± 9.5 1.7 ± 1.1 3388.2 ± 1023.7 93.3 ± 3.6 88.4 ± 6.0 13.3 ± 1.9 ccTGA 6 34.4 ± 8.3 83.3 24.3 ± 3.1 57.0 ± 11.7 38.2 ± 13.2 1.6 ± 0.7 3917.3 ± 540.3 93.5 ± 7.8 No data 14.8 ± 1.4 Complex defects 33 32.4 ± 7.5 50.0 20.1 ± 6.2 b 50.1 ± 13.0 b 36.6 ± 11.4 b 1.8 ± 1.0 2958.0 ± 1029.7 b 89.5 ± 4.4 a,b,c 83.0 ± 8.9 a,b 12.1 ± 3.1 Shunts d 24 38.4 ± 11.9 43.5 17.2 ± 7.1 a 54.4 ± 17.9 a 38.4 ± 13.4 a 1.6 ± 1.3 2680.9 ± 1259.9 a 95.1 ± 4.6 b 89.8 ± 11.0 a 10.8 ± 4.3 a,b Left heart valve disease 8 31.5 ± 8.9 50.0 28.1 ± 13.4 65.8 ± 12.8 26.7 ± 4.2 1.2 ± 0.6 4612.2 ± 1910.2 94.2 ± 4.2 92.8 ± 3.9 16.1 ± 3.1 b R VOT O 13 39.7 ± 7.9 30.8 22.8 ± 8.8 64.3 ± 18.0 33.3 ± 8.4 1.4 ± 0.7 4181.5 ± 1857.5 96.0 ± 2.6 c 86.2 ± 8.0 12.6 ± 4.7 ap<0.001 bp=0.004 ap=0.005 bp<0.001 ap<0.001 b p=0.004 ap=0.028 bp=0.006 ap<0.001 b p=0.001 cp=0.005 ap=0.020 bp=0.015 ap=0.030 bp=0.046 d 39% had Eisenmenger syndrome. % predicted peak VO 2 : percentage of predicted peak oxygen consumption; ccTGA: congenitally corrected transposition of the great arteries; CPET : cardiopulmonary exercise testing; OS: oxygen saturation; PCP: peak circulatory power; R VOT O: right ventricular outﬂow tract obstruction; TGA: transposition of the great arteries after Senning or Mustard procedure; ToF: tetralogy of Fallot; VE/VCO 2 : minute ventilation/carbon dioxide production; VO 2 : oxygen consumption.

Table2 Assessmentofchronostropism.

Diagnosis Peakheart

rate(bpm) Chronotropic index<0.8(%) Patientsunder Beta-blockers (%) ToF 156.7±23.5 46.3 18.5 TGA 151.5_±34.8 26.9 3.8 ccTGA 147.0±17.0 66.7 50.0 Complex defects 143.8_±29.1 71.9 40.6 Shunts 138.7±23.7 69.9 13.0 Leftheart valve disease 168.5±27.5 37.5 12.5 RVOTO 157.7±23.7 46.2 30.8

ccTGA:congenitallycorrectedtranspositionofthegreat arter-ies; HR: heart rate; RVOTO: right ventricular outﬂow tract obstruction;TGA:transpositionofthegreatarteriesafter Sen-ningorMustardprocedure;ToF:tetralogyofFallot.

age,cyanosis,CPETduration,peaksystolicbloodpressure, time to anaerobic threshold and heart rate at anaero-bic threshold were predictors of the combined outcome (Table3).PeakVO2wasnotapredictorofthecombined

out-come(hazardratio0.995;conﬁdenceinterval0.949-1.043;

p=0.829).

Discussion

AlthoughanincreasingnumberofCHDpatientsreach

adult-hood,theirexercisecapacityisoftensigniﬁcantlyimpaired.

CPETenablesmoredetailedassessmentoffunctional

capac-itybymeasuringrespiratorygases.PeakVO2,whichreﬂects

VO2intissuesanddependsoncardiacoutput,arterial

oxy-genandtheoxygenextractioncapacityofmuscletissue,is

anaccuratemeasureofexercisecapacity.10

In line with previous research,1,10---13 _our _study _showed

markedlydepressedfunctionalcapacityinCHDpatients,as

shownbythefactthatallstudygroupspresentedpeakVO2

valuesbelow70%ofthosepredicted.Regardlessofthetype

ofCHD,thepeakVO2valuesreachedbythestudypopulation

were substantially lower thanthose expected for healthy

subjectsofthesameageandgender.

Another useful parameter is VE/VCO2 slope, which

expressesventilatoryefﬁciencyandhasbeen showntobe

anindependentpredictorofoutcome.14_The_ratio_between

VE/VCO2 slope and peakVO2 integrates theseparameters

andalsohasprognosticvalue.15_By_integrating_the

hemody-namicvaluesmonitoredinthistestitispossibletocompute

peakcirculatorypower. Alltheseparameterswere

consis-tentlyabnormalinallgroups.

AcrosstheCHDspectrum,patientswithleftheartvalve

disease and repaired tetralogy of Fallotpresented better

exercisecapacity.Ontheotherhand,TGA(afterMustardor

Senningsurgery,orcongenitallycorrected),complexheart

defects and shunts were associated with more severely

impairedfunctionalcapacity.

It should also be noted that 39% of patients with

shunts presented Eisenmenger physiology, which explains

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Cyanotic patients P eak V O2 (ml/kg/min) VE/VCO 2 slope Non-cy anotic patients Cyanotic patients Non-cy anotic patients Pulmonar y hyper tension Without pulmonar y hyper tension Pulmonar y hyper tension Without pulmonar y hyper tension Einsenmenger syndrome Without Einsenmenger syndrome

Einsenmenger syndrome Without Einsenmenger syndrome

25 50 45 40 35 30 25 23 21 p<0.001 p<0.001 p=0.001 p<0.001 p=0.009 p=0.002 19 17 15

Figure1 Peakoxygenconsumption(VO2)andminuteventilation/carbondioxideproduction(VE/VCO2)slopeincyanoticpatients

andinpatientswithpulmonaryhypertensionandEisenmengersyndrome.

30,0

A

P eak V O2 VE/VCO 2 slope

B

_60,00 50,00 40,00 30,00 20,00 25,0 20,0 15,0 10,0 20,00 25,00 30,00 35,00

Time to CPET (years) Time to CPET (years)

40,00 45,00 20,00 25,00 30,00 35,00 40,00 45,00

Figure2 Transpositionofthegreat arteries.(A)Negative linearPearson correlationbetween timefrom MustardorSenning

surgerytoCPETandpeakoxygenconsumption(VO2)(r=-0.564);(B)positivelinearPearsoncorrelationbetweentimefromMustard

orSenningsurgerytoCPETandVE/VCO2slope(r=0.554).

Table3 Predictorsofthecombinedoutcome

(hospitaliza-tionforcardiaccauseandall-causemortality)byunivariate

Coxregression.

Predictors HR 95%CI p

Age 1.065 1.019-1.113 0.005

Cyanosis 3.584 1.094-11.737 0.035

CPETduration 0.907 0.826-0.995 0.040

Peaksystolicblood

pressure 0.982 0.967-0.998 0.029 Timetoanaerobic threshold 0.819 0.717-0.935 0.003 Heartrateat anaerobicthreshold 0.973 0.955-0.993 0.007

CI:conﬁdenceinterval;CPET:cardiopulmonaryexercisetesting; HR:hazardratio.

Irrespective of the baseline defect, cyanosis and pul-monary hypertension were associated with poor exercise

tolerance,particularlywhenthetwowerecombined,which wasassociated with lower peak VO2 and higher VE/VCO2

slope.AccordingtoDilleretal.,2_patients_with_Eisenmenger

physiology have the most severe impairment in exercise

capacity,reﬂectedinthelowestpeakVO2andthehighest

VE/VCO2slope.

Ourdatademonstratedanegativecorrelation between

time from Mustard or Senning surgery to CPET and peak

VO2 and peak circulatory power, and a positive

correla-tion between time from surgery to exercise testing and

VE/VCO2slope.Thisdeleteriousevolutionandongoing

mor-biditycouldbeexplainedbyprogressivefailureofasystemic

rightventricleandalsobychronotropicincompetence.16

Furthermore, chronotropic response to exercise is an

important determinantof functional capacity, and

dimin-ished heart rate during exercise may contribute to

reductionsinpeakVO2.12,17

Exerciseintolerancehasbeenassociatedwithincreased

riskofhospitalizationandmortality.2,7,18,19_However,_unlike

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VO2 or VE/VCO2 slope andthe combinedoutcome of

hos-pitalizationfor cardiaccauseandall-causemortality.This

couldbeduetothesmallsamplesizeandthe

heterogene-ityofthestudypopulation.Instead,ourdatashowedlower

valuesofCPETduration,peaksystolicbloodpressure,time

toanaerobicthresholdandheartrateatanaerobic

thresh-oldasbenchmarksoflowerfunctionalcapacitycorrelated

withpoorprognosis.OurresultsareinlinewithDilleretal.’s

studyof321Fontanpatients,inwhomchronotropic

capac-itywasstronglyrelatedtosurvival,contrastingwithalack

ofassociationbetweenpeakVO2orratiobetweenVE/VCO2

slopeandsurvivalorcardiactransplantation.8_The_relation

betweenchronotropicincompetenceandall-causemortality

inCHDpatientscouldbesecondarytounderlyingautonomic

dysfunction,neurohormonalactivationandarrhythmias.4,7

Wealsoestablishedanassociationbetweencyanosisand

poor outcome, with a 3.6-fold increase in mortality and

hospitalizationcomparedtonon-cyanoticpatients.Similar

datawere reportedbyDimopoulos etal., whoalso

inter-estinglydemonstratedthatinadultCHDtheVE/VCO2slope

isa strong predictorof mortalityonly inpatients without

cyanosis,suggestingthat cyanoticpatients differ

substan-tiallyinpathophysiologicalprocessesandinthesepatients

theprognosticvalueoftheVE/VCO2slopeisweaker.19

Age was also related to worse prognosis in our study,

reﬂecting progressive impairment in left and/or right

ventricular function, increasing prevalence of pulmonary

hypertensionand occurrence of arrhythmiasin older CHD

patients.

Tothebestofourknowledge,thisistheﬁrstPortuguese

publicationonCPETinadultCHDpatients.Weconsiderthat

thereportofourinitialexperienceisofinterest,

highlight-ingtheimportanceofCPETinthispopulation.

Study

limitations

ThiswasaretrospectivestudyatatertiaryadultCHDcenter

that reﬂects daily clinical practice. There was thus

cer-tainlyabiasinpatientselection,favoringmoresymptomatic

patientsandthoseinwhichitisimportantnottorelyonly

onself-reportedfunctionalcapacity.Thiscouldexplainthe

severityseen inthe shuntsubgroup,inwhich therewasa

largeproportionofEisenmengersyndrome.

Thestudypopulationsizeinevitablyreﬂectsthe

limita-tionsofasingle-centerexperience.ConsideringthatCPETis

extremelyimportantintheassessmentofCHDpatientsand

shouldbeperformedroutinely,infutureweintendtostudy

morepatients,withdifferentclinicalsituations.

Conclusion

Our sample of adult CHD patients who underwent CPET

presentedexerciseintolerance,whichdifferedsigniﬁcantly

acrossthespectrumofCHD.Thesedataillustratethemore

severe impairment in functional capacity and attenuated

chronotropicresponsetoexerciseinEisenmengersyndrome

andcomplexdefects.

Inthisstudy,age,cyanosisandworsefunctionalcapacity

were,asexpected,associatedwiththecombinedoutcome

ofall-causemortalityandhospitalizationforcardiaccause.

Increasing the number of patients and the variety of

defectsandperformingserialassessmentsineach patient

willenableustoobtainmorerobustresultsinthefuture.

Conﬂicts

of

interest

Theauthorshavenoconﬂictsofinteresttodeclare.

References

1.FredriksenPM,VeldtmanG,HechterS,etal.Aerobiccapacity inadultswithvariouscongenitalheartdiseases.AmJCardiol. 2001Feb1;87:310---4.

2.Diller GP, Dimopoulos K, Okonko D, et al. Exercise intol-erance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation. 2005;112:828---35.

3.BhattAB,FosterE,KuehlK,etal.AmericanHeartAssociation CouncilonClinicalCardiology.Congenitalheartdiseaseinthe olderadult: a scientiﬁcstatement from theAmerican Heart Association.Circulation.2015;131:1884---931.

4.DillerGP,DimopoulosK,OkonkoD,etal.Heartrateresponse duringexercisepredictssurvivalinadultswithcongenitalheart disease.JAmCollCardiol.2006;48:1250---6.

5.TakkenT,BlankAC,HulzebosEH,etal.Cardiopulmonary exer-cisetestingin congenitalheartdisease: equipment and test protocols.NethHeartJ.2009;17:339---44.

6.PriromprintrB,RhodesJ,SilkaMJ,etal.Prevalenceof arrhyth-miasduringexercisestresstestinginpatientswithcongenital heartdiseaseandsevererightventricularconduitdysfunction. AmJCardiol.2014;114:468---72.

7.InuzukaR,DillerGP,BorgiaF,etal.Comprehensiveuseof car-diopulmonaryexercisetestingidentiﬁesadultswithcongenital heartdiseaseatincreasedmortalityriskinthemediumterm. Circulation.2012;125:250---9.

8.DillerGP,GiardiniA,DimopoulosK,etal.Predictorsof morbid-ityandmortalityincontemporaryFontanpatients:resultsfrom amulticenterstudyincludingcardiopulmonaryexercisetesting in321patients.EurHeartJ.2010;31:3073---83.

9.Wilkoff BL,Corey J,Blackburn G. A mathematicalmodel of cardiac chronotropic response to exercise. J Electrophysiol. 1989;3:176---80.

10.FredriksenPM,TherrienJ,VeldtmanG,etal.Aerobiccapacity inadultswithtetralogyofFallot.CardiolYoung.2002;12:554---9. 11.HechterSJ,WebbG,FredriksenPM,BensonL,etal. Cardiopul-monaryexerciseperformanceinadultsurvivorsoftheMustard procedure.CardiolYoung.2001;11:407---14.

12.FredriksenPM,ChenA,VeldtmanG,etal.Exercisecapacityin adultpatientswithcongenitallycorrectedtranspositionofthe greatarteries.Heart.2001;85:191---5.

13.HarrisonDA,LiuP,WaltersJE,etal.Cardiopulmonaryfunction inadultpatientslateafterFontanrepair.JAmCollCardiol. 1995;26:1016---21.

14.ArenaR,MyersJ,AslamSS,etal.PeakVO2andVE/VCO2slope in patientswith heartfailure: a prognosticcomparison. Am HeartJ.2004;147:354---60.

15.GuazziM,DeVitaS,CardanoP,etal.Normalizationforpeak oxygenuptakeincreasestheprognosticpoweroftheventilatory responsetoexerciseinpatientswithchronicheartfailure.Am HeartJ.2003;146:542---8.

16.KempnyA,DimopoulosK,UebingA,etal.Referencevaluesfor exerciselimitationsamongadultswithcongenitalheartdisease. Relationtoactivitiesofdailylife–singlecentreexperienceand reviewofpublisheddata.EurHeartJ.2012;33:1386---96.

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17.Schulze-NeickIM,WesselHU,PaulMH.Heartrateandoxygen uptakeresponsetoexerciseinchildrenwithlowpeakexercise heartrate.EurJPediatr.1992;151:160---6.

18.GiardiniA,HagerA,LammersAE,etal.Ventilatoryefﬁciency andaerobiccapacitypredictevent-freesurvivalinadultswith atrialrepairforcompletetranspositionofthegreatarteries.J AmCollCardiol.2009;53:1548---55.

19.Dimopoulos K, Okonko DO, Diller GP,et al. Abnormal venti-latory response to exercise in adults with congenital heart diseaserelatestocyanosisand predictssurvival.Circulation. 2006;113:2796---802.