Dissertação/Tese VALOR PROGNÓSTICO DA PRESSÃO EXPIRADA E DIÓXIDO DE CARBONO DURANTE O TESTE DE ESFORÇO CARDIOPULMONAR EM PACIENTES COM CARDIOMIOPATIA CHAGÁSICA - PPGREAB

Introdução: Pacientes com cardiomiopatia chagásica (CCh), forma cardíaca da doença de Chagas, geralmente apresentam pior prognóstico quando comparados à outras cardiopatias. O comprometimento funcional pode ser detectado desde o início da cardiopatia e o valor prognóstico das variáveis avaliadas durante o esforço deve ser investigado. Na insuficiência cardíaca, a pressão parcial de dióxido de carbono expirado no pico do exercício (PETCO2 pico) apresentou-se como bom preditor de sobrevida. Entretanto, sua acurácia na identificação dos pacientes com pior desfecho ainda é desconhecida na CCh. Objetivo: Avaliar o valor prognóstico do PETCO2 pico e das principais variáveis funcionais em pacientes com CCh. Métodos: Setenta e seis pacientes com CCh (49,2±9,8 anos, 39,5% mulheres, NYHA I-III) foram avaliados por ecocardiografia e Teste de Esforço Cardiopulmonar (TECP). Os pacientes foram acompanhados por quatro anos e o desfecho foi definido como morte cardíaca, eventos cerebrovasculares ou transplante cardíaco. A análise de sobrevida e os pontos de corte foram verificados pela curva ROC, regressão uni e multivariada de Cox e diagrama de Kaplan-Meier. Resultados: No final do período de seguimento (29,0±16,0 meses), 16 pacientes (21%) apresentaram eventos adversos. No modelo univariado, sexo feminino, classe funcional da New York Heart Association, frequência cardíaca máxima atingida ao esforço, pico do consumo de oxigênio (VO2pico), ventilação minuto/produção de dióxido de carbono, PETCO2 pico, tempo de esforço durante o TECP, a fração de ejeção do ventrículo esquerdo e o diâmetro diastólico do ventrículo esquerdo estavam associados a um desfecho ruim no final do período de acompanhamento. No modelo multivariado final, apenas a PETCO2 pico (HR 0,849; IC 95%: 0,758 a 0,951, p = 0,005) e VO2pico (HR 0,877; IC 95%: 0,781 a 0,984, p = 0,026) permaneceram como preditores independentes de prognóstico desfavorável em pacientes com CCh. As áreas sob a curva ROC demonstraram a acurácia do VO2pico (AUC = 0,85; IC 95%: 0,75 a 0,95) e PETCO2 pico (AUC = 0,83; IC 95%: 0,69 a 0,97) na predição de eventos adversos. Os pontos de corte com a melhor combinação de sensibilidade e especificidade do VO2pico e PETCO2 pico foram 20 mL.kg.min (valor preditivo negativo de 80%) e 32 mmHg (valor preditivo positivo de 91%), respectivamente. No diagrama de Kaplan-Meier, houve diferenças significativas (p <0,001) entre os pacientes com menor VO2pico (≤20 mL.kg.min; n = 28) e maior VO2pico (> 20 mL.kg.min; n = 48) bem como entre os pacientes com PETCO2 pico menor (≤32 mmHg; n = 20) e maior (> 32 mmHg; n = 54). Conclusão: O VO2pico e PETCO2 pico tiveram valor prognóstico adequados em pacientes com CCh, podendo ser utilizados como variáveis do TECP na estratificação de risco e auxiliar na resposta terapêutica em pacientes com CCh.

IntroductionIntroductionIntroduction IntroductionIntroductionIntroduction : PatientsPatientsPatientsPatientsPatientsPatients Patients withwithwithwith Chagas ChagasChagas Chagas cardiomyopathycardiomyopathycardiomyopathy cardiomyopathy cardiomyopathy cardiomyopathycardiomyopathycardiomyopathy (ChC) , thethe cardiaccardiaccardiac cardiaccardiaccardiac form of Chagas ChagasChagas disease, disease,disease,disease,disease,disease, generally generallygenerallygenerally generallygenerallygenerally have have a worseworse worse prognosis prognosisprognosis whenwhen when comparedcomparedcomparedcompared compared to other other other cardiopathies.cardiopathies.cardiopathies. cardiopathies.cardiopathies. cardiopathies.cardiopathies.cardiopathies.cardiopathies.cardiopathies.cardiopathies. FunctionalFunctional FunctionalFunctionalFunctional Functional impairmentimpairmentimpairment impairmentimpairmentimpairmentimpairment can be detected detecteddetecteddetecteddetecteddetecteddetected from thethe onset onsetonset of heartheartheartheart disease diseasediseasediseasediseasedisease andand thethe prognostic prognosticprognosticprognostic value valuevalue of thethethe variables variablesvariables variablesvariables evaluatedevaluated evaluatedevaluated evaluatedevaluatedevaluated during during thethethe efforteffort effort shouldshould should be investigated.investigated. investigated.investigated.investigated.investigated. investigated.investigated.investigated. In heartheartheartheart failure, failure,failure,failure, failure, endend -tidaltidaltidaltidaltidal carboncarboncarbon carbon dioxide dioxide at peak peakpeak exerciseexercise exercise exerciseexerciseexercise (PETCO2 (PETCO2(PETCO2(PETCO2 (PETCO2 peak) peak) waswaswas a good predictor predictor predictorpredictorpredictor of survival.survival. survival. survival.survival. However,However, However,However, However, its accuracyaccuracyaccuracyaccuracy accuracyaccuracyaccuracy in identifyingidentifying identifying identifyingidentifying identifyingidentifying patients patientspatientspatientspatients patients withwithwithwith worseworse worseworse outcomes outcomesoutcomes outcomesoutcomes is stillstillstillstillstill unknown unknown unknown unknown in ChC . ObjectiveObjectiveObjective ObjectiveObjective Objective : To assessassessassessassessassessassess thethe prognostic prognosticprognosticprognostic valu valuvalue of peakpeakpeakpeak PETCO2PETCO2PETCO2PETCO2 PETCO2 andand key key functional functionalfunctionalfunctional functional variables variablesvariablesvariablesvariables variablesvariables in patientspatientspatientspatientspatientspatients patients withwithwithwith ChC . MethodsMethodsMethods Methods Methods: SeventySeventySeventy Seventy Seventy-sixsixsix patients patientspatientspatientspatientspatientspatients withwithwithwith ChC (49.2 ±9.8 years, years,years, years, 39.5% women,women, women,women, NYHA I-III) werewerewere evaluatedevaluated evaluated evaluatedevaluatedevaluated by echocardiographyechocardiographyechocardiography echocardiographyechocardiography echocardiographyechocardiography echocardiography andand Cardiopulmonaryardiopulmonary ardiopulmonaryardiopulmonary ardiopulmonary ardiopulmonaryardiopulmonary ardiopulmonaryardiopulmonaryardiopulmonary Exercise xercise xercisexercisexercise Testingestingestingestingesting (CPET) (CPET)(CPET)(CPET). PatientsPatientsPatientsPatientsPatientsPatients Patients werewerewere followed followedfollowedfollowed followedfollowed for four yearsyearsyearsyears andand thethe endend -point point waswaswas defined defined defined defined as cardiovascularcardiovascularcardiovascular cardiovascular cardiovascularcardiovascularcardiovascularcardiovascular cardiovascularcardiovascular death, death,death,death, cerebrovascularcerebrovascularcerebrovascularcerebrovascularcerebrovascular cerebrovascularcerebrovascularcerebrovascular cerebrovascularcerebrovascular eventsevents events or cardiaccardiaccardiac cardiaccardiac transplantationtransplantation transplantation transplantation transplantationtransplantation transplantationtransplantationtransplantationtransplantation . SurvivalSurvival SurvivalSurvivalSurvival analysisanalysis analysisanalysis analysisanalysis andand cutoffcutoff cutoff points pointspoints points werewerewere verifiedverifiedverified verified verifiedverified by ROC ROC curve,curve, curve, Cox uni - andand multivariatemultivariate multivariatemultivariatemultivariate multivariate multivariatemultivariatemultivariate regression regression regressionregressionregressionregressionregression , andand KaplanKaplanKaplan KaplanKaplan-MeierMeierMeierMeierMeier diagram. diagram.diagram. diagram.diagram. ResultsResultsResultsResultsResultsResults : At thethe endend of thethe follow followfollow -up period period period (29.0 16.0 monthsmonths months ), 16 patients patientspatientspatientspatients patients (2 1%) had had experiencedexperienced experienced experiencedexperienced experiencedexperienced adverseadverse adverseadverse adverse eventsevents events. TheThe female femalefemalefemalefemale sex,sex,sex, NewNewNew YorkYork HeartHeartHeartHeart AssociationAssociationAssociationAssociation AssociationAssociationAssociationAssociationAssociation functional functionalfunctionalfunctional functional class,class,class,class,class,class, peak peakpeak heart heartheartheart rate rate achieved,achieved,achieved,achieved,achieved,achieved, achieved, peak peakpeak oxygen oxygen oxygenoxygen uptake uptakeuptakeuptake (VO (VO2peak 2peak2peak), minuteminuteminute minute ventilation/carbon ventilation/carbonventilation/carbonventilation/carbonventilation/carbonventilation/carbonventilation/carbonventilation/carbonventilation/carbon ventilation/carbonventilation/carbonventilation/carbonventilation/carbon dioxidedioxidedioxide dioxide production productionproductionproductionproduction (VE/VCO (VE/VCO(VE/VCO(VE/VCO(VE/VCO 2 slope),slope),slope), slope), endend -tidaltidaltidal carboncarboncarbon dioxide dioxide dioxidedioxide at peak peakpeak exerciseexercise exercise exerciseexerciseexercise (PETCO (PETCO(PETCO(PETCO 2 peak),peak),peak),peak), timetimetimetime of efforteffort during during CPET, CPET,CPET,CPET, leftleftleft ventricular ventricular ventricularventricularventricularventricular ejectionejectionejectionejectionejectionejectionejection fraction fractionfractionfractionfraction (LVEF)(LVEF)(LVEF)(LVEF)(LVEF)(LVEF) andand leftleftleft ventricular ventricular ventricularventricularventricularventricular ventricularventricular endend -diastolic diastolicdiastolicdiastolicdiastolicdiastolicdiastolicdiastolic diameter diameterdiameterdiameterdiameterdiameterdiameter (LVDd) (LVDd)(LVDd)(LVDd) werewerewere associatedassociatedassociatedassociated associatedassociatedassociatedassociated withwithwithwith poor outcome outcomeoutcomeoutcome outcome at thethethe endend of follow followfollow -up period period period . In thethe finalfinalfinal final multivariatemultivariate multivariatemultivariatemultivariate multivariatemultivariatemultivariatemultivariate model,model, model,model,model, only onlyonly PETCOPETCOPETCOPETCO 2 peak peakpeak (HR (HR 0.849 0.849 ; 95% CI: 0.758 to 0.951 0.9510.951, p=0.0 05 ) andand VO2 peak peakpeak (HR(HR(HR 0. 877 ; 95% CI: 0. 781 to 0.9 84 , p=0.0 26 ) remained remainedremainedremainedremainedremainedremained as independentindependent independentindependentindependentindependent independent predictor predictor predictorpredictorpredictor s of poor outcome outcomeoutcomeoutcomeoutcome in ChC patients patientspatientspatientspatientspatientspatients. TheThe areasareas areasareas under underunder thethethe ROC ROC curvecurve curve demonstrated demonstrateddemonstrated demonstrateddemonstrated demonstrateddemonstrateddemonstrated thethethe accuracyaccuracyaccuracyaccuracy accuracyaccuracy of thethethe VO 2peak 2peak2peak2peak (AUC (AUC(AUC = 0. 85 ; 95% CI: 0. 75 to 0. 95 ) andand PETCOPETCOPETCOPETCO 2 peak peakpeak (AUC (AUC(AUC = 0. 83 ; 95% CI: 0. 69 to 0. 97 ) in thethe prediction predictionprediction predictionpredictionprediction of adverseadverse adverse adverse events.events. events.events.events.events. TheThe cutoffcutoffcutoffcutoff points points points withwithwithwith thethe best bestbest combinationcombination combination combinationcombinationcombinationcombinationcombination of sensitivitysensitivitysensitivity sensitivitysensitivitysensitivitysensitivitysensitivitysensitivitysensitivity andand spespe cificitycificitycificity cificitycificitycificitycificity by VO 2peak 2peak2peak andand PETCOPETCOPETCOPETCO 2 peak peakpeak werewerewerewere 20 mL.kg.minmL.kg.minmL.kg.minmL.kg.min mL.kg.minmL.kg.min (negative (negative (negative(negative(negative predictive predictivepredictive predictivepredictivepredictivepredictive valuevaluevaluevalue of 80%) andand 32 mmHgmmHgmmHgmmHg (positive (positive(positive(positive(positive predictive predictivepredictive predictivepredictivepredictivepredictive value valuevaluevalue of 91%), respectively. respectively.respectively. respectively.respectively.respectively.respectively. respectively.respectively. In thethe KaplanKaplanKaplan KaplanKaplan-MeierMeierMeierMeierMeier diagram,diagram,diagram,diagram, diagram,diagram, therethere werewerewere significantsignificantsignificant significantsignificant significantsignificantsignificant differences differences differencesdifferences differences differencesdifferences (p<0.001) (p<0.001) (p<0.001) (p<0.001) between betweenbetweenbetweenbetweenbetween patients patientspatientspatientspatientspatientspatients withwithwithwith lowerlower lowerlower VO 2peak peakpeak (≤ 20 mL.kg.minmL.kg.minmL.kg.min mL.kg.min mL.kg.minmL.kg.minmL.kg.min; n=2 8) andand highhighhigh er VO 2peak 2peak2peak (> 20 mL.kg.minmL.kg.minmL.kg.min mL.kg.minmL.kg.min; n= 48 ) as weelweelweelweel as between betweenbetweenbetweenbetweenbetween patients patientspatientspatientspatients patients withwithwithwith lowerlower lowerlower (≤ 32 mmHgmmHgmmHgmmHg; n=2 0) andand highhighhigh er PETCOPETCOPETCOPETCO 2 peakpeakpeakpeak (> 32 mmHgmmHgmmHgmmHg; n= 54 ). ConclusionConclusion ConclusionConclusionConclusionConclusionConclusionConclusion : VO2peakVO2peakVO2peak VO2peakVO2peak andand PETCO2PETCO2PETCO2PETCO2 PETCO2 peak peakpeak hadhadhad adequateadequate adequate adequateadequateadequate prognostic prognostic prognosticprognosticprognostic valuevaluevaluevalue in patients patientspatientspatientspatientspatientspatients withwithwithwith ChC . TheThe cutoffcutoffcutoffcutoff points points points of VO2peakVO2peakVO2peak VO2peakVO2peakVO2peak andand PETCPETCPETCPETCO2 peak peakpeak of 20 mL.kg.minmL.kg.minmL.kg.min mL.kg.minmL.kg.min andand 32 mmHg,mmHg,mmHg,mmHg, respectively, respectively, respectively,respectively,respectively, respectively,respectively, can be used usedused in risk riskrisk stratificationstratificationstratification stratificationstratification stratificationstratificationstratificationstratificationstratification andand help helphelp in thethethe therapeutictherapeutic therapeutic therapeutictherapeutictherapeutic therapeutictherapeutic response responseresponse response in ChC patients patientspatientspatientspatientspatientspatients.