RESUMEN
BACKGROUND: The relationship between anti-beta-adrenergic (anti-betaR) and anti-M(2)-cholinergic (anti-M2R) receptor antibodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated. METHODS AND RESULTS: We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas' heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas' heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-beta(1)RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for beta(1),beta(2)-adrenergic receptors (cAMP increment) or M(2)-cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-betaRAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-betaRAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol. CONCLUSIONS: Our results demonstrate a strong correlation between anti-betaRAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-betaRAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.
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Arritmia Sinusal/inmunología , Arritmias Cardíacas/inmunología , Autoanticuerpos/inmunología , Receptores Adrenérgicos beta/inmunología , Receptores Colinérgicos/inmunología , Adulto , Anciano , Secuencia de Aminoácidos , Animales , Arritmia Sinusal/complicaciones , Arritmias Cardíacas/complicaciones , Atropina/farmacología , Autoanticuerpos/análisis , Células COS , Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Chagásica/complicaciones , Cardiomiopatía Chagásica/inmunología , AMP Cíclico/metabolismo , Electrocardiografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Fosfatidilinositoles/metabolismo , Propranolol/farmacología , Receptores Adrenérgicos beta/química , Receptores Adrenérgicos beta/genética , Receptores Colinérgicos/química , Receptores Colinérgicos/genética , Sistemas de Mensajero Secundario/efectos de los fármacosRESUMEN
OBJECTIVE: We sought to assess the efficacy and safety of amiodarone for restoration and maintenance of sinus rhythm in patients with chronic atrial fibrillation in a prospective, randomized, double blind trial. BACKGROUND: Restoration and preservation of sinus rhythm is difficult in patients with chronic atrial fibrillation. The efficacy of oral amiodarone has not been conclusively established. METHODS: Ninety-five patients with chronic atrial fibrillation, lasting an average of 35.6 months, were randomized to either amiodarone (600 mg/d) (47 patients) or placebo (48 patients) during four weeks. Nonresponders underwent electric cardioversion, and those who reverted continued with amiodarone (200 mg/d) or placebo. End-points were successful cardioversion and sinus rhythm maintenance. RESULTS: Sixteen patients (34.04%) in the amiodarone group reverted within 27.28 +/- 8.85 days in comparison with 0% in the placebo group (P < 0.000009). The conversion rate rose to 51.72% in patients with chronic atrial fibrillation lasting less than 12 months. Twenty-eight patients in the amiodarone group and 39 in the placebo group underwent electric cardioversion, which was successful in 19 patients (67.8%) of the amiodarone group and in 15 (38.46%) of the placebo group (P = 0.017). Altogether, conversion was obtained in 79.54% of the amiodarone group patients and in 38.46% of the placebo group patients (P < 0.0001). During follow-up, atrial fibrillation relapsed in 13 (37.14%) of 35 patients of the amiodarone group within 8.84 +/- 8.57 months and in 12 (80%; P = 0.009) of 15 patients of the placebo group within 2.74 +/- 3.41 months. CONCLUSIONS: Oral amiodarone restored sinus rhythm in one third of patients with chronic atrial fibrillation, increased the success rate of electric cardioversion, decreased the number of relapses and delayed their occurrence.
Asunto(s)
Amiodarona/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Adulto , Anciano , Amiodarona/efectos adversos , Enfermedad Crónica , Método Doble Ciego , Cardioversión Eléctrica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: The goal of this study was to report a variety of atrial tachycardia that might be caused by an unusual electrophysiologic substrate. BACKGROUND: The mechanism of atrial tachycardias is attributed to re-entry, abnormal automaticity or triggered activity, based on their electropharmacological responses. A rate-related and lidocaine-sensitive atrial tachycardia has not been reported. METHODS: Eight patients (3 women and 5 men, aged 14 to 60 years) with repetitive, uniform atrial tachycardias were studied. In six patients the arrhythmia had been refractory to at least three antiarrhythmic agents (class 1A and C sodium channel blockers, amiodarone, beta-adrenergic blocking agents, verapamil, digoxin). Conventional electrocardiograms, Holter recordings and B mode echocardiograms were performed in each patient. Intravenous lidocaine and verapamil were tested in the eight patients. Six patients underwent an electrophysiologic study. RESULTS: The baseline electrocardiogram showed nearly incessant runs of atrial tachycardia in all patients. The mean atrial ectopic cycle length ranged from 376 to 502 ms. In seven patients a progressive prolongation of the cycle length from the beginning to the end of the salvos was documented. The arrhythmia was suppressed by increments of sinus node rate and by atrial pacing at cycle lengths longer than that of the atrial tachycardia. In all patients the arrhythmia was abolished by intravenous lidocaine, whereas intravenous verapamil was ineffective. Four symptomatic patients were successfully treated with radiofrequency ablation of the ectopic focus, and two patients were treated with oral mexiletine. CONCLUSIONS: The peculiar electropharmacological responses of this arrhythmia suggest an uncommon underlying mechanism that remains to be elucidated.
Asunto(s)
Antiarrítmicos/uso terapéutico , Lidocaína/uso terapéutico , Taquicardia/tratamiento farmacológico , Adolescente , Adulto , Electrocardiografía , Femenino , Atrios Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Taquicardia/fisiopatologíaRESUMEN
Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the beta1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the beta1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-beta1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.
Asunto(s)
Anticuerpos Antiprotozoarios/inmunología , Autoanticuerpos/inmunología , Cardiomiopatía Chagásica/inmunología , Lupus Eritematoso Sistémico/inmunología , Miocardio/inmunología , Proteínas Protozoarias , Proteínas Ribosómicas/inmunología , Trypanosoma cruzi/inmunología , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos , Humanos , Datos de Secuencia MolecularRESUMEN
OBJECTIVES: This study sought to determine the prevalence of autoantibodies directed against the beta-adrenoceptors in patients with primary electrical cardiac abnormalities, including atrial arrhythmias, ventricular arrhythmias and conduction disturbances, in the absence of any other cardiac abnormality. BACKGROUND: Using synthetic peptides corresponding to the predicted sequences for the second extracellular loop of the human beta 1- and beta 2-adrenoceptors as antigenic targets, autoantibodies directed against the beta-adrenoceptors were recently shown to occur in patients with idiopathic dilated cardiomyopathy and Chagas' heart disease. METHODS: Eighty-six patients (57 with primary electrical abnormalities, 29 with idiopathic dilated cardiomyopathy) and 101 healthy and cardiopathic control subjects were studied. Antibodies against the beta 1- and beta 2-peptides were detected with an enzyme immunoassay performed in blinded manner. In nine selected (seropositive) cases, the immunoglobulin G (IgG) fraction was tested for functional effects on the rate of beating of cultured neonatal rat cardiomyocytes. RESULTS: Antibodies recognizing the beta 1- and beta 2-peptides were found in 11 (52.3%) of 21 patients with ventricular arrhythmias (p < 0.01), 5 (35.7%) of 14 patients with conduction disturbances (p < 0.05), 3 (13.6%) of 22 patients with atrial arrhythmias (p > 0.05) and 11 (37.9%) of 29 patients with dilated cardiomyopathy (p < 0.05) compared with 15 (14.8%) of 101 control subjects. A rapid increase in the rate of beating of the cultured cardiomyocytes was induced by IgG from a selected group of patients, suggesting an agonist-like interaction with a functional epitope. This response was mediated by stimulation of both the beta 1- and beta 2-adrenoceptors in the patients with primary ventricular arrhythmias but only the beta 1-adrenoceptors in the patients with idiopathic dilated cardiomyopathy. CONCLUSIONS: Primary ventricular arrhythmias and conduction disturbances, like idiopathic cardiomyopathy, show a high prevalence of antibodies interacting with functional epitopes of the beta-adrenoceptors, suggesting a common or similar abnormal immunoregulatory process.
Asunto(s)
Arritmias Cardíacas/inmunología , Autoanticuerpos/análisis , Cardiomiopatía Dilatada/inmunología , Receptores Adrenérgicos beta 1/inmunología , Receptores Adrenérgicos beta 2/inmunología , Adulto , Animales , Autoanticuerpos/farmacología , Estudios de Casos y Controles , Células Cultivadas , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Miocardio/patología , Prevalencia , RatasRESUMEN
Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.
Asunto(s)
Antígenos de Protozoos/inmunología , Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunología , Cardiomiopatía Chagásica/inmunología , Epítopos Inmunodominantes/inmunología , Imitación Molecular , Fosfoproteínas/inmunología , Receptores Adrenérgicos beta 1/inmunología , Proteínas Ribosómicas , Trypanosoma cruzi/inmunología , Secuencia de Aminoácidos , Animales , Animales Recién Nacidos , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/química , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoantígenos/química , Enfermedades Autoinmunes/etiología , Bisoprolol/farmacología , Células Cultivadas , Cardiomiopatía Chagásica/etiología , Enfermedad de Chagas/sangre , Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/inmunología , Reacciones Cruzadas , Epítopos Inmunodominantes/química , Leishmania donovani/inmunología , Leishmaniasis/inmunología , Leishmaniasis Visceral/inmunología , Datos de Secuencia Molecular , Contracción Miocárdica/efectos de los fármacos , Miocardio/citología , Fosfoproteínas/química , Ratas , Receptores Adrenérgicos beta 1/química , Proteínas Recombinantes/inmunología , Alineación de Secuencia , Homología de Secuencia de AminoácidoAsunto(s)
Electrocardiografía , Función Ventricular , Animales , Bloqueo de Rama/fisiopatología , Estimulación Cardíaca Artificial , Bloqueo Cardíaco/fisiopatología , Humanos , Taquicardia Ventricular/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Derecha , Complejos Prematuros Ventriculares/fisiopatologíaRESUMEN
Recent studies confirm the existence of antibodies (Abs) to beta-adrenoceptors in patients with idiopathic dilated cardiomyopathy and Chagas' heart disease. These Abs can be shown to exert both stimulatory and inhibitory effects, which may play a role in the development of the cardiac abnormalities known to occur in these diseases, including advanced heart failure. The hypothesis is advanced that Chagas' heart disease and some forms of idiopathic dilated cardiomyopathy may represent, at least partially, a form of "adrenergic cardiomyopathy."
Asunto(s)
Anticuerpos/análisis , Anticuerpos/fisiología , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Chagásica/inmunología , Receptores Adrenérgicos beta/inmunología , Animales , Cardiomiopatías/inmunología , Cardiomiopatía Dilatada/complicaciones , Insuficiencia Cardíaca/etiología , HumanosRESUMEN
OBJECTIVES: The aim of this study was to assess the response of refractoriness in normal and diseased human bundle branches to changes in cycle length, as well as during a long period of continuous overdrive pacing. BACKGROUND: The anterograde refractory period of the bundle branches in patients with functional bundle branch block shortens as the rate is increased. The rate-dependent response of refractoriness in diseased bundle branches is quite different. However, this difference has not been precisely delineated, and its physiologic meaning is uncertain. METHODS: Refractoriness of the bundle branches was measured by the extrastimulus technique in 16 patients with tachycardia-dependent bundle branch block and 10 patients with functional bundle branch block, both after basic trains of 8 atrial-paced impulses at different cycle lengths and during a 10-min period of continuous overdrive pacing. RESULTS: The baseline refractory period in the bundle branches of patients with functional bundle branch block measured 430 +/- 32 ms (mean +/- SD) and shortened to 368 +/- 30 ms at the shortest cycle length. The maximal effect was reached within the 1st min of overdrive pacing. The baseline refractory period of the bundle branches was significantly longer in patients with tachycardia-dependent bundle branch block (611 +/- 184 ms) and demonstrated a cumulative overdrive prolongation in 15 (83%) of 18 studies with typical manifestations of fatigue. In two other studies, this occurred only after ajmaline administration. CONCLUSIONS: A rate- and time-dependent prolongation of refractoriness frequently occurs in diseased human bundle branches. When absent, this response may be induced under the effects of sodium channel blockers. This would suggest that an abnormality in the recovery from inactivation of the sodium channel might underlie the early stages of bundle branch disease.
Asunto(s)
Fascículo Atrioventricular/fisiopatología , Bloqueo de Rama/fisiopatología , Estimulación Cardíaca Artificial/métodos , Adulto , Anciano , Ajmalina , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Taquicardia Paroxística/fisiopatología , Taquicardia Supraventricular/fisiopatologíaRESUMEN
Chagas' disease is a chronic parasitosis affecting most Latin American countries. Its most important clinical manifestation is a late developing chronic myocarditis and, much less frequently, an early acute myocarditis. Chagasic myocardial damage is microfocal and disseminated throughout the heart. In most cases, the coexistence of areas of myocytic degeneration, inflammatory infiltration, and fibrosis suggests a permanent evolving process. Commonly, chronic chagasic myocarditis resembles a dilated cardiomyopathy, with characteristic ECG abnormalities (atrial and ventricular extrasystoles, intraventricular and/or AV conduction disturbances, and primary ST-T wave changes). Since myocardial damage is scattered throughout the heart, the ECG abnormalities (arrhythmias, conduction disturbances, and repolarization changes) are also representative of the widespread cardiac involvement. Thus, sick sinus syndrome, atrial extrasystoles, intraatrial conduction disturbances, and atrial fibrillation or flutter are common findings in different stages of the disease. At the ventricular level, both conduction disturbances and arrhythmias are conspicuous expressions of the myocardial damage. Right bundle branch block alone or in combination with left anterior hemiblock are the most common conduction defects. Further compromise of the conduction system can lead to different degrees of AV block. Chagas' disease is the main cause of bundle branch block and AV block in endemic areas. In advanced cases of Chagas' heart disease, ventricular premature contractions are extremely frequent, multiform, and repetitive (couplets and runs of ventricular tachycardia), and show R on T phenomenon. These arrhythmias are usually aggravated by increased sympathetic tone, implying an enhanced risk of cardiac sudden death among chagasic patients, which is sometimes the first manifestation of the illness. Chronic chagasic myocarditis is the leading cause of cardiovascular death, mostly as a consequence of heart failure and sudden death, in areas where the disease is endemic.
Asunto(s)
Arritmias Cardíacas/fisiopatología , Cardiomiopatía Chagásica/fisiopatología , Arritmias Cardíacas/etiología , Nodo Atrioventricular/fisiopatología , Sistema Nervioso Autónomo/fisiología , Cardiomiopatía Chagásica/etiología , Electrocardiografía , HumanosAsunto(s)
Arritmias Cardíacas/diagnóstico , Nodo Atrioventricular/fisiopatología , Bloqueo de Rama/diagnóstico , Fibras Nerviosas/fisiología , Función Ventricular Derecha , Adolescente , Arritmias Cardíacas/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Vías Nerviosas/fisiopatologíaAsunto(s)
Animales , Antígenos de Protozoos/inmunología , Autoanticuerpos/inmunología , Cardiomiopatía Chagásica/inmunología , Trypanosoma cruzi/inmunología , Antígenos de Protozoos/química , Autoanticuerpos/química , Epítopos/inmunología , Biomarcadores , Datos de Secuencia Molecular , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/química , Homología de Secuencia de AminoácidoAsunto(s)
Anticuerpos Antiprotozoarios/inmunología , Autoanticuerpos/inmunología , Cardiomiopatía Chagásica/inmunología , Trypanosoma cruzi/inmunología , Animales , Anticuerpos Antiprotozoarios/química , Autoanticuerpos/química , Biomarcadores , Epítopos/inmunología , Humanos , Datos de Secuencia Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunología , Homología de Secuencia de AminoácidoRESUMEN
The mechanisms responsible for intermittent bundle branch block are still under debate. The role of the time-dependent behavior of the slow calcium channel has recently been emphasized. To test this hypothesis and ascertain the possible involvement of the fast sodium channel, the effects of the slow calcium channel blocker verapamil and the fast sodium channel blocker procainamide were compared in 10 patients with intermittent bundle branch block. All 10 patients showed bundle branch block during spontaneous sinus rhythm. Maneuvers to slow cardiac rate (that is, carotid sinus massage, Valsalva maneuver) were performed to identify normal conduction as well as phase 4 bundle branch block. Thus, the ranges of diastolic intervals (RR) resulting in phase 3 (tachycardia-dependent) bundle branch block, phase 4 (bradycardia-dependent) bundle branch block and normal conduction were measured in two control studies performed before intravenous administration of verapamil (control 1) and procainamide (control 2) and at the peak effect of both drugs. In the control studies, all 10 patients showed phase 3 bundle branch block, whereas phase 4 bundle branch block occurred in only 4 patients. The ranges of phase 3 bundle branch block, phase 4 bundle branch block and normal conduction were very similar in control studies 1 and 2. The phase 3 bundle branch block range was slightly shortened by verapamil (983 +/- 83.5 ms in control 1; 930 +/- 69.4 ms at the peak effect of verapamil), whereas phase 4 bundle branch block remained unchanged. In contrast, conduction was systematically worsened by procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Bloqueo de Rama/fisiopatología , Procainamida/farmacología , Canales de Sodio/efectos de los fármacos , Verapamilo/farmacología , Adulto , Anciano , Bloqueo de Rama/tratamiento farmacológico , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco/efectos de los fármacos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
To identify Trypanosoma cruzi target antigens in overt Chagas' heart disease, a parasite lambda gt11 cDNA library was screened with the serum of a patient with a severe chagasic heart involvement (JL). Using a phage dot array immunoassay, 5 highly antigenic clones, JL1, JL5, JL7, JL8, and JL9, were probed with sera from clinically characterized T. cruzi infected subjects. The correlation of cloned T. cruzi antigen recognition with the clinical status of the subjects led to the identification of a recombinant antigen, JL5, that reacted predominantly with sera from patients with Chagas' heart disease. The antigenic determinant of the JL5 recombinant was a small 35 amino acid peptide. The nucleotide and the deduced amino acid sequence, together with other experimental data, allowed identification as the C-terminal portion of a T. cruzi P ribosomal protein. The C-terminal undecapeptide in JL5, EDDDMGFGLFD, was highly homologous to the same region of the human P protein SD(D/E)DMGFGLFD. The latter sequence has been identified as the P protein epitope in systemic lupus erythematosus (SLE). Positive SLE sera reacted with the JL5 recombinant phage, suggesting that the T. cruzi P protein might induce antibodies with a similar specificity to that of P antibodies in SLE.
Asunto(s)
Antígenos de Protozoos/inmunología , Cardiomiopatía Chagásica/inmunología , Proteínas Protozoarias/inmunología , Proteínas Ribosómicas/inmunología , Trypanosoma cruzi/inmunología , Adulto , Anciano , Secuencia de Aminoácidos , Animales , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/genética , Secuencia de Bases , Enfermedad Crónica , Clonación Molecular , ADN/genética , Epítopos/análisis , Epítopos/inmunología , Humanos , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
A 22-year-old female, asymptomatic and without any evidence of cardiac disease, was found to have a persistent idioventricular tachycardia (IVT). Sinus rhythm and IVT rates were similar and showed parallel changes in successive resting electrocardiograms. Both IVT and sinus rhythm were transiently slowed or suppressed by vagal stimulation and accelerated by sympathetic stimulation. Long periods of atrial overdrive pacing, at a rate 62% faster than the spontaneous rate of IVT, depressed both ectopic and sinus activity. Fast channel blocking agents (lidocaine, disopyramide), and digoxin and amiodarone failed to modify IVT significantly. Verapamil, a calcium channel blocking drug, allowed total control of the arrhythmia. These electrophysiologic and pharmacologic responses suggest that the IVT may relate to the automatic activity of a ventricular focus of the "slow response" type, functionally resembling an "additional" sinus node with preserved innervation. During an 88-month follow-up, the patient continued to be asymptomatic, warning arrhythmias were never found and the features of IVT remained unmodified.
Asunto(s)
Electrocardiografía , Ventrículos Cardíacos/fisiopatología , Taquicardia/fisiopatología , Adulto , Bloqueo de Rama/fisiopatología , Estimulación Cardíaca Artificial , Femenino , Estudios de Seguimiento , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Monitoreo Fisiológico , Taquicardia/terapia , Nervio Vago/fisiopatología , Verapamilo/uso terapéuticoRESUMEN
En 81 pacientes con miocarditis crónica chagásica (MCC) y arritmias ventriculares (AV) pertenecientes a 4 centros cardiológicos se evaluó comparativamente la eficacia y seguridad de flecainida (F) y amiodarona (A) utilizando un protocolo abierto, randomizado y paralelo. Fueron incluídos pacientes con un número de extrasístoles ventriculares (EV) no inferior a 1200/24 hs y/o formas repetitivas. Los pacientes fueron tratados durante 60 días con una de las drogas (F: 200 a 400 mg/día; A: 800 a 400 mg/día; dosis ajustada según respuesta) y evaluados clínicamente con exámenes de laboratorio, ECG en reposo y ECG ambulatorios continuos de 24 hs (H) días - 7; - 1; 8/9; 15/16; y 59/60). Los porcentajes de reducción de EV obtenidos a los 9, 16 y 60 días con F fueron 73.1%; 82.9% y 92.4% y con A77.6%; 90.1% y 90.7%. Después de 60 días de tratamiento, la Fredujo las duplas en 92.5% y los episodios de taquicardia ventricular en 96.5% y la A, 95.2% y 92.6%, respectivamente. El tratamiento debió ser interrumpido en 6 pacientes; 3 con F (2 por bradicardia sinusal extrema y 1 por TV iterativa), y 3 con A (1 por TV sostenida y 2 por fotodermatosis severa). Aunque existieron algunas diferencias llamativas en los resultados de los distintos centros, El análisis estadísticos en conjunto sugiere una similar eficacia de F y A en el tratamiento de las AV de la MCC
Asunto(s)
Adolescente , Adulto , Persona de Mediana Edad , Humanos , Masculino , Femenino , Amiodarona/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Cardiomiopatía Chagásica/tratamiento farmacológico , Flecainida/uso terapéutico , Ensayos Clínicos como Asunto , Electrocardiografía , Frecuencia CardíacaRESUMEN
Eighty one patients with ventricular arrhythmias associated with chronic Chagas disease participated in this multi-clinic study. Treatment with Amiodarone and Flecainide were compared using an open, parallel, randomized experimental design. Inclusion criteria required the selected patients to have 1,200 premature ventricular contractions per 24 hours and/or repetitive ventricular arrhythmias. Patients received 60 days of treatment with either Flecainide at 200 to 400 mg per day or Amiodarone 800 to 400 mg per day. This dosage was adjusted to the therapeutic response. Clinical and laboratory evaluations, electrocardiogram and 24 hour Holters were performed at study days: -7, -1, 8/9, 15/16 and 59/60. The percentage reduction of premature ventricular contractions at days 9, 16 and 60 were: 73.1%, 82.9% and 92.4% with Flecainide and 77.6%, 90.1% and 90.7% with Amiodarone. At the end of the study, Flecainide had induced a 92.5% reduction in couplets and 96.5% reduction in ventricular tachycardia. For the same parameters the percentages following Amiodarone were 95.2% and 92.6% respectively. Treatment was discontinued in three patients in the Flecainide group (two because of prolonged sinus node bradycardia and one because of sustained ventricular tachycardia). In the Amiodarone group, treatment was discontinued also in three patients (one because of sustained ventricular tachycardia and two because of severe photosensitive dermatosis). Although there were some differences in the results form center to center, the conclusions from the overall data indicate a similar, therapeutic effect with both drugs.