Human antibodies with muscarinic activity modulate ventricular repolarization: basis for electrical disturbance.
BACKGROUND
In chronic chagasic patients sudden death has been reported when QT interval dispersion is increased and antibodies with muscarinic-like activity have been demonstrated to trigger arrhythmias. The aims were to investigate, in vivo and in vitro, relation between these antibodies and heterogeneity of ventricular repolarization and to identify predictors of cardiac death in chronic chagasic patients.


RESULTS
Clinical, electrocardiograph and echocardiograph variables from 32 chronic chagasic patients with moderate to severe left ventricular dysfunction, followed-up for 10 years were analyzed. Sera from chronic chagasic patients with or without muscarinic activity were tested in isolated rabbit hearts to study ventricular repolarization. Stepwise multivariate logistic analysis was applied to identify independent predictors of cardiac death. QT interval dispersion of patients with muscarinic activity (75.9+/-5.5 ms) was larger than that of patients without muscarinic activity (51.3+/-4.0 ms, p<0.001). Maximum uncorrected and corrected QT intervals were not significantly different between groups of patients. Sera from patients with muscarinic activity significantly and reversibly increased QT interval in isolated rabbit hearts (p=0.002). This effect was abolished in the presence of the muscarinic antagonist atropine. Multivariate analysis identified maximum corrected QT intervals and left ventricular end diastolic index as independent predictors of cardiac death (p=0.03 and p=0.02, respectively).


CONCLUSIONS
Sera with muscarinic activity from chagasic patients have a strong contribution to evoke ventricular repolarization rhythm disorder. In these patients, ventricular repolarization heterogeneity is increased significantly. In vitro, muscarinic sera reversibly increased repolarization duration. Maximum corrected QT intervals and left ventricular end diastolic index are independent predictors of cardiac death.
Medei
Emiliano
E
Laboratório de Eletrofisiologia Cardíaca Antônio Paes de Carvalho, Instituto de Biofísica Carlos Chagas Filho, Brazil.
Pedrosa
Roberto C
RC
Benchimol Barbosa
Paulo Roberto
PR
Costa
Patricia C
PC
Hernández
Ciria C
CC
Chaves
Elen A
EA
Linhares
Vivian
V
Masuda
Masako O
MO
Nascimento
Jose H
JH
Campos de Carvalho
Antonio C
AC
D000368:Aged; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality*; D002908:Chronic Disease; D016757:Death, Sudden, Cardiac; D004195:Disease Models, Animal; D004452:Echocardiography; D004562:Electrocardiography; D004594:Electrophysiology; D006329:Heart Conduction System / Q000502:physiology; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008875:Middle Aged; D015999:Multivariate Analysis; D015588:Observer Variation; D011379:Prognosis; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000276:immunology / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000503:physiopathology*
D000906:Antibodies; D011976:Receptors, Muscarinic