A la luz de la evidencia, es el paciente con enfermedad de Chagas sin patología demostrada, de bajo riesgo?

Transcription

1 Federacion Argentina de Cardiologia (FAC) XXIX Congreso Nacional de Cardiología 20 al 22 de Mayo de 2011, Córdoba, Argentina A la luz de la evidencia, es el paciente con enfermedad de Chagas sin patología demostrada, de bajo riesgo? Anis Rassi Junior, MD, PhD, FACP, FACC, FAHA Director Científico del Anis Rassi Hospital Goiânia (GO) BRASIL arassijr@terra.com.br NO CONFLICTO DE INTERESES

2 Chagas Disease INDETERMINATE FORM Term first used by Carlos Chagas in 1916: In order to better define the cases of this kind we shall make of them the undeterminate chronic form, to indicate the absence of any dominant clinical syndrome Chagas C. Pathogenic processes of American Trypanosomiasis. Mem Inst Oswaldo Cruz 1916;8:334

3 Chagas Disease INDETERMINATE FORM (asymptomatic, latent, subclinical or nonapparent) Positive serological and/or parasitological tests No signs/symptoms Normal ECG Normal chest xray Indeterminate form Normal esophagus xray (barium swallow) Normal colon xray (barium enema) 50% 10% 30% 10% Cardiac form Digestive form Cardiodigestive form First Annual Meeting of Applied Research in Chagas` Disease. Araxá (MG) Rev Soc Bras Med Trop 1985;18:46

4 DEFINITION OF INDETERMINATE FORM PARAMETERS CLASSIC NONCLASSIC Cardiac symptoms* Absent Absent Absent Absent Absent Digestive symptoms+ Absent Absent Absent Absent Absent Physical examination Normal Normal Normal Normal Normal ECG changes Absent Absent Absent Absent Absent Heart size (Xrays) Normal Normal Normal Not done Normal/not done Barium swallow Normal Normal Not done Not done Normal/not done Barium enema Normal Not done Not done Not done Not done Echocardiogram Not needed Not done Not done Not done Normal *dyspnea, presyncope, syncope, severe palpitations +dysphagia, retroesternal pain, regurgitation, loss of weight, severe constipation ARJr

5 Indeterminate Form x Healthy Controls 103 patients with the IF of Chagas`disease: normal ECG, and normal radiological examination of chest, esophagus and colon (50% men; mean age = 42 years) 20 controls (healthy individuals 50% men; mean age = 45 years) Undergoing 24h Holter monitoring, exercise testing and 2D echocardiography Complex VA* Systolic Dysfunction + GROUP N Holter Exercise testing 2D ECHO Indeterminate form % 4% 0% Normals (control) 20 10% 5% 0% *complex ventricular arrhythmias: polimorphic PVCs, couplets or runs + systolic dysfunction: abnormal EF or segmental wall motion abnormalities Rassi Jr. A et al. Arq Bras Cardiol 1991; 57 (supl C): C140

6 Indeterminate Form of Chagas` Disease and More Sensitive Tests Classic definition Nonclassic definition Exercise stress test 24h Holter monitoring LV systolic function LV diastolic function Perfusion defects RV biopsy Autonomic function BNP measurement Prognosis/death Normal* Normal* Normal??? Abnormal in few? = normal population Abnormal in few (arrhythmias/chronotropic deficit) Abnormal in few (complex arrhytmias) Mild segmental abnormalities in few Mild abnormalities in few Present in few Abnormal in few Abnormal in few Normal = normal population *When compared to healthy controls (matched for age and sex ) Adapted and expanded from MarinNeto JA et al. Chagas` heart disease. Arq Bras Cardiol 1999;72:24780

7 Prognosis of the Indeterminate Form (any definition) = Normal population regarding death ARJr

8 Followup=18 years (baseline) N=387

9 Chagas` disease (chronic phase) Prognosis of patients with a normal ECG Longitudinal study n = 5710 patients (Argentina) 4335 patientes (76%) with normal ECG age: 15 to 50 years follow up: yearly evaluation of serology, clinical examination, chest radiography, and ECG average follow up: 5.3 years Annual sudden death rate: 0.004% or 4/ per year Manzullo EC, 1982 In: Mem Inst Oswaldo Cruz. 1999;94 Suppl 1:31720

10 Rev Pat Trop 1975;4:5778 Bambui (MG) N = N=885 N=911 1) La forme indeterminée est stable; son pronostic est excellent (survie à dix ans: 97,44 pour cent ± 1,34 pour l`ensemble de l`échantillon).

11 . BA 82% 96 (24%) Jornal Brasileiro de Medicina 1980;38:3440

12 Virgem da Lapa MG IguatamaPains FI = ECG e RX tórax (PA e perfil com esôfago contrastado) normais

13 A folowup period of 13 years prospective study in 190 chagasic patients of Mambaí, Goiás, State, Brazil Cleudson Castro, Aluizio Prata e Vanize Macêdo Median age: 41,5 years Rev Soc Bras Med Trop 2001; 34:

14 Castro Alves (BA) Circulation 1987;75:

15 Percent Survival SURVIVAL OF 775 CHAGASIC PATIENTS ACCORDING TO THE PRESENCE OF CONGESTIVE HEART FAILURE (San Juan de Los Morros, Roscio County, north Venezuela) Acquatella et al. Circulation 1987; 76: % 64%:normal 87% 38% p < 0,05 p < 0, Years of follow up Asymptomatic (n = 614) NYHA class I/II (n = 99) NYHA class III/IV (n = 62) ECG 12%:borderline 27%:abnormal. Venezuela Mean age 45±14yrs San Juan de Los Morros

16 Prognostic implications of clinical, electrocardiographic and hemodynamic findings in chronic Chagas' disease. Hugo A. Carrasco, Henry Parada, Lourdes Guerrero, Miguel Duque, Dumar Durán, César Molina Mérida, Venezuela IA: normal clinical and ECG findings; normal left cineventriculogram (n=110) IB: normal clinical and ECG findings; abnormal left cineventriculogram (n=87) Mean age: 41 years II: abnormal clinical and ECG findings; abnormal left cineventriculogram; no CHF (n=185) III: abnormal ECG and abnormal left cineventriculogram; CHF (n=104) Int J Cardiol 1994;43:2738

17 856 patients (mean age at entry 43.7 yrs) Median followup: 8 years Patients monitored and followed according to a specific protocol Group I (n=731): normal ECG, no LV Group II (n=35): abnormal ECG, no LV Group III (n=90): abnormal ECG, LV, no CHF Progression of disease: appearance of an ECG abnormality, enlargement of the LV, the appearance of heart failure, or death 6/ per year

18 FIOCRUZ, RJ (idade média:46±12a) A: ECG abn; Eco normal B1: ECG e Eco abn; FE>45% B2: ECG e Eco abn; FE<45% C: IC compensada D: IC refratária N=1.167 Revista da SOCERJ 2007;20:133139

19 Development of Clinical Disease: from Indeterminate to Determinate Forms Analysis of Longitudial Studies Authors,yr Laranja, 1956 Moleiro, 1974 Nava Rhode, 1974 Macedo, 1980 Carrasco, 1983 Espinosa, 1985 Coura, 1985 Manzullo, 1985 Maguire, 1987 Pereira, 1990 Madoery, 1992 Storino, 1992 Ianni, 2001 Castro, 2001 Viotti, 2006 N years 15.0% 33.0% 10.4% 25.0% Percentage of progression 78 years 22.4% 7,5% 20.0% 21.3% 10 years 13 years 22.7% 10.0% 24.0% 34.5% 48.0% 25.0% 7.2% 32.5% Evolution depends: duration of followup, mean age of the population (time interval from the acute phase), parasite strain, region of the study, concept of progression, regularity of followup assessments etc Adapted and expanded from Storino R, Milei J. Estudios de seguimiento evolutivo de la enfermedad de Chagas. In Madoery RJ, Madoery C, Cámera MI. Actualizaciones en la enfermedad de Chagas, Argentina 1993.

20 160 patients with the indeterminate form of Chagas` disease Studied from 1979 until 1994 Mean followup: 8.2 ± 2.5 years ECG repeated at 6mo intervals and echo at 12mo intervals ECG EVOLUTION: Group I (125 patients): maintained normal ECGs Group IIA (9 patients): ECG changes (permanent) Group IIB (14 patients): ECG changes (transitory) Group IIC (11 patients): ECG changes (only in the final ECG) inicial ECG alt. final

21 CHAGAS DISEASE EVOLUTION MEGAESOPHAGUS MEGACOLON Indeterminate form ECG alterations Segmental LV dysfunction Global LV dysfunction Heart failure Pump failure death No deaths due to CD Sudden Cardiac Death ARJr

22 Sociedad Interamericana de Cardiología, 2010 Comité de Enfermedad de Chagas de FAC, 2010

23 Comité de Enfermedad de Chagas de FAC, 2010

24 Criteria Considered Important For a Screening Program To Be Valid in Chagasic Patients With a Normal ECG The natural history of the condition, including development from latent to declared disease, should be adequately understood There should be a suitable test(s) with sufficient sensitivity and specificity to identify important disease in early stage Early diagnosis should improve outcomes There should be an accepted treatment for patients with recognized disease. If there is no treatment, it is premature to institute screening The costbenefit analysis of casefinding should be economically attractive ARJr

25 Foro de Foro Enfermedad de Chagas, 2010 [ChagasPCVC] "Bajo Riesgo" de Rassi = ExIndeterminados? Si en nuestro país se acepta que hay de parasitados por T. cruzi; si continuamos afirmando que hay un 70% de pacientes que antes del consenso denominábamos indeterminados (para Rassi, aprox 65%), esto es pacientes "de bajo riesgo" Si en este grupo dentro de los próximos 10 años morirá el 10%, estamos hablando de muertes por año. Edgardo Schapachnik

26 Normal ECG = 12 patients (2,8%)

27 Chagas Heart Disease: Risk of Death Multivariate analysis RISK FACTORS 1) Male gender 2) Low QRS voltage (ECG) 3) NSVT (24h Holter monitoring) 4) LV dysfunction (Echo) 5) Cardiomegaly (chest xray) 6) NYHA class III/IV Female RBBB + LAFB NYHA class I Couplets (Holter) POINTS % Prevalence 20% High Risk (1220 points) Mortality (10 years) 84% Intermediate risk (711 points) 44% 0 points NEJM 2006; 355: % Low risk (06 points) 10%

28 Chagas` Disease: Phases, Forms, and Stages (Groups) Acute phase Apparent form Inaparent form Chagas` disease Chronic phase Indeterminate form PREDICTORS? Determinate form Cardiac Mixed Digestive Chagas` heart disease Megacolon Stage A Stage B Stage C Stage D Megaesophagus PREDICTORS PREDICTORS Group I Group II Group III Group IV D E A T H Adapted from MarinNeto JA, Rassi Jr A, Maciel BC et al. Chapter 51: Chagas Heart Disease. In: Yusuf S, Cairns J (eds). Evidence Based Cardiology 3rd edition, 2010

29 INDETERMINATE FORM: Conclusion The strict definition of the indeterminate form requires positive serologic (or parasitologic) results, no symptoms or physical signs of disease, normal 12lead ECG, and normal findings on radiological examination of the chest, oesophagus, and colon. This classical concept should be maintained (epidemiological surveys, research). In order to avoid misunderstandings, different definitions should always be mentioned and described in detail in every study. Consenso Brasileiro em Doença de Chagas, 2011 (in press)

30 Indeterminate Form* (practical and simplified definition, with prognostic information) Positive serological and/or parasitological tests No signs/symptoms of cardiac and digestive disease Normal ECG Normal chest xray Normal esophagus xray (barium swallow) Normal colon xray (barium enema) *Chronic form without apparent cardiac or digestive alterations Consenso Brasileiro em Doença de Chagas, 2011 (in press)

31 Recommendations for evaluation: rationale Cardiac Persons with negative history, normal physical examination, and normal ECG rarely experience progression to disease requiring therapy in one year s time Additional cardiac studies (echocardiogram, 24 hour ambulatory ECG, stress test, etc): May show minor abnormalities that have little or no prognostic significance Expensive Simple guidelines at primary care level Consenso Brasileiro em Doença de Chagas, 2011 (in press)

32 Recommendations for evaluation: rationale Gastrointestinal Persons with no symptoms or signs of esophageal or colonic disease unlikely to have disease requiring therapy Barium contrast radiography (barium swallow, barium enema) expensive and uncomfortable Simple guidelines at primary care level Consenso Brasileiro em Doença de Chagas, 2011 (in press)

33 Evaluation: T. cruzi infection confirmed Medical history Physical examination 12lead ECG with 30 sec rhythm strip Normal No further cardiac/gastrointestinal evaluation Yearly followup: Medical history Physical examination, ECG Counsel Evaluate for specific (antiparasite) treatment Bern C et al JAMA 2007;298: Rassi Jr A et al. Lancet 2010;375:

34 INDETERMINATE FORM ETIOLOGIC TREATMENT Antitrypanosomal treatment is recommended for all cases of indeterminate form of Chagas` disease in individuals 18 years or younger. Class I, Level A (<12 years) / Level C (1318 years) In adults aged 19 to 50 years etiologic treatment should generally be offered. Class IIa, Level B For those older than 50 years treatment is considered optional. Class IIb, Level C Bern C et al JAMA 2007;298: Rassi Jr A et al. Lancet 2010;375:

35 A la luz de la evidencia, es el paciente con enfermedad de Chagas sin patología demostrada, de bajo riesgo? A la luz de la evidencia, pacientes con enfermedad de Chagas e ECG normal son de bajo riesgo! ARJr