[Use-dependence of propafenone. Clinical demonstration of the hypothesis of modulated receptors]. / Uso-dependencia con propafenona. Demonstración clínica de la hipótesis de los receptores modulados.

UNLABELLED: The aim of this study was to assess use-dependence in patients with ventricular premature contractions (VPC's) treated with propafenone, by means of the increase in heart rate using transesophageal atrial pacing. It was also analyzed whether this phenomenon was related to the antiarrhythmic effect. Fifteen patients with more than 30 symptomatic VPC's/sour were evaluated. Esophageal pacing was performed with cycles of 600 and 400 msec during periods of 1 min and with simultaneous recording of 2 or 3 EKG leads with a paper speed of 100 mm/sec. Holter monitoring (HM) was carried out in all patients. Propafenone was administered in doses of 450 and 900 mg/day, during 5-7 days, at which moment another HM and esophageal stimulation were repeated. The QRS duration (pre-treatment) was 82.6 +/- 13.5 msec (basal) and 82.4 +/- 13 msec during pacing with 600 msec cycle length (p: NS). The QRS duration with P (900 mg/day) was 96.6 +/- 20 msec (basal) (p:NS vs. pre-treatment) but during atrial pacing with 600 msec cycle length it increased to 109.3 +/- 23 msec (p < 0.0004). This use-dependence was also observed with pacing at 600 msec in patients receiving doses of 450 mg/day: 95.3 +/- 13 msec (p < 0.0001 vs. baseline QRS) (Table 1). IN CONCLUSION: 1) there was no significant increase in the QRS duration with P without pacing; 2) propafenone showed use-dependence during atrial stimulation, even with cycle length of 600 msec and with the lower doses.

Uso dependencia con propafenona: demostracion clinica de la hipotesis de los receptores modulados / Use dependence of prepafenone: clinical demonstration of the hypothesis modulated receptors

Mediante sestimulación auricular esofágica se evaluó un aspecto de la hipótesis de los receptores modulados, denominado "uso-dependencia". Esta consiste en el enlentecimiento de la conducción intraventricular, con el aumento de la frecuencia cardíaca en presencia de antiarrítmicos de clase I. Se estudiaron 15 pacientes con > 30 extrasístoles ventriculares sintomáticas/hora tratados con propafenona por vía oral. El marcapaseo auricular mostró incremento en la duración del complejo QRS con ciclos de estimulación de 600 mseg y aun con dosis de 450 mg/día. Se correlacionaron los hallazgos con la variación en la actividad ectópica observada por Holter

Uso dependencia con propafenona: demostracion clinica de la hipotesis de los receptores modulados / Use dependence of prepafenone: clinical demonstration of the hypothesis modulated receptors

Mediante sestimulación auricular esofágica se evaluó un aspecto de la hipótesis de los receptores modulados, denominado "uso-dependencia". Esta consiste en el enlentecimiento de la conducción intraventricular, con el aumento de la frecuencia cardíaca en presencia de antiarrítmicos de clase I. Se estudiaron 15 pacientes con > 30 extrasístoles ventriculares sintomáticas/hora tratados con propafenona por vía oral. El marcapaseo auricular mostró incremento en la duración del complejo QRS con ciclos de estimulación de 600 mseg y aun con dosis de 450 mg/día. Se correlacionaron los hallazgos con la variación en la actividad ectópica observada por Holter (AU)

[Ventricular extrasystole and coronary disease: to treat or not to treat?]. / Extrasistolia ventricular y enfermedad coronaria: tratar o no tratar?

The prognostic significance of ventricular premature beats (VPB) and their proper management are still a subject of controversy, particularly since during the last few years a number of publications have raised doubts as to the effectiveness and safety of antiarrhythmic drugs. An appropriate assessment of the VPB must consider: 1) electrocardiographic characteristics. 2) Associated symptoms. 3) Presence or absence of underlying disease, and 4) Ventricular function (VF). On this basis VPB may be classified as "Benign" (isolated; asymptomatic; mild or absent cardiopathy, and preserved VF); "Hazardous" (presence of complex VPB; with or without symptoms, and recognized organic heart disease), and "Malignant" (complex VPB and ventricular tachyarrhythmias; symptomatic cardiac disease, and compromised VF). Antiarrhythmic drugs are indicated for "Hazardous" and "Malignant" VPB. However, selection and efficacy must be documented by objective testing (Holter, stress, plasma levels). When utilized in well defined groups of patients, with reduction in the hourly number of VPB (more than 50-70%) and mainly of complex forms, there is clear benefit in terms of long-term survival, including coronary disease and congestive heart failure.

[Spontaneous variability of ventricular extrasystole in chronic Chagas cardiopathy]. / Variabilidade espontânea da extra-sistolia ventricular na cardiopatia chagásica crônica.

PURPOSE: To study the spontaneous variability of single (VPCs) and coupled (CVPCs) in patients with chronic Chagas' disease (CCD). PATIENTS AND METHODS: Twenty patients with CCD, 14 male, in class I and II NYHA, with frequent VPCs and VCPCs, free of drug therapy were studied. 21 hour Holter monitoring was done for 4 subsequent days. The data analysis assessed the variation in the frequency of VPCs and CVPCs between patients, seven hour periods one hour periods in a hierarchical model by a Poisson process. RESULTS: a) the frequency of VPCs follows a circadian rhythm, closely related to the hourly variations of the mean heart rate; b) disregarding the heart rate influence on the variability of the ventricular arrhythmia, its behavior was at random and unpredictable; c) the minimal percentual reduction in VPCs/h that discriminated between antiarrhythmic effect and spontaneous between antiarrhythmic effect and spontaneous between antiarrhythmic effect and spontaneous variability was 121.86% for seven-hour, 58.42% for 21-hour and 38.45% for 42-hour electrocardiographic monitoring periods; d) the same approach for the VCPCs revealed values of 133.6%, 63.21% and 41.3% respectively. CONCLUSION: The large variability of ventricular arrhythmia in CCD during a 24 hour period makes necessary observations always longer. The minimal percentual reduction in VPCs/h that discriminated between antiarrhythmic effect and spontaneous variability might be 58.42% for two 21-hour electrocardiography monitoring periods.

Variabilidade espontânea da extra-sistolia ventricular na cardiopatia chagásica crônica / Spontaneous variabitity of ventricular extrasystole in chronic Chagas cardiopathy

Purpose - To study the spontaneous variability of single (VPCs) and coupled (CVPCs) in patients with chronic Chagas' disease (CCD). Patients and Methods - Twenty patients with CCD, 14 male, in class I and III NYHA, with frequent VPCs and VCPCs, free of drug therapy were studied.21 hour Holter monitoring was done for 4 subsequent days. The data analysis assessed the variation in the frequency of VPCs and CVPCs between patients, seven hour periods one hour periods in a hierarchical model by a Poisson process. Results - a) the frequency of VPCs follows a circadian rhythm, closely related to the hourly variations of the mean heart rate; b) disregarding the heart rate influence on the variability of the ventricular arrhythmia, its behavior was at random and unpredictable; c) the minimal percentual reduction in VPCs/h that discriminated between antiarrhythmic effect and spontaneous between antiarrhythmic effect and spontaneous variability was 121.86% for sevenhour, 58.42% for 21-hour and 38.45% for 42-hour electrocardiographic monitoring periods; d) the same approch for the VCPCs revealed values of 133,8%, 63.21% and 41.3% respectively

[Optic neuropathy caused by amiodarone]. / Neuropatía óptica por amiodarona.

Amiodarone has been used for the last 20 years, initially as antianginal and then as antiarrhythmic agent. To the collateral effects described, the optic neuropathy must be added as a complication, not so frequent, caused apparently by the prolonged ingestion of it. Two patients treated with MDD of 250 mg of amiodarone, for a mean of 17 months, are reported. They presented a decrease of the visual acuity. After proposing the possible differential diagnosis, the relation between the use of amiodarone and the optic alteration observed is briefly exposed, relating it with the demyelination neuropathy induced by this drug. This presumption is corroborated by the ultrastructural alterations registered in the optic nerve of animals in which amiodarone was used, similar to those of the peripheral nerves, as an expression of a disorder of the lipidic metabolism, which allow it to be integrated to the so called iatrogenic lipidoses.

[Pneumonitis induced by amiodarone]. / Pneumonite por amiodarona.

Fifteen patients, eleven males and four females, with amiodarone induced pulmonary disease were studied. Their ages ranged between 52 and 79 (mean = 64.0) years. 66% of the patients were taking a daily dose of 200 mg of amiodarone. The time elapsed between the initial dose and the diagnosis of the pneumonitis varied from 2 to 84 (mean = 23.3) months. Premature ventricular beats and recurrent episodes of paroxistic supra ventricular tachycardia were the most common indications for the use of the drug. The most frequent clinical complaints were progressive dyspnea and cough. Weight loss was observed in five patients, fever in six and chest pain in two. The most habitual thoracic physical sign was diffuse crepitation. Chest roentgenograms disclosed bilateral interstitial infiltrates in all patients, associated to pleural effusions in two. An increased diffuse uptake of 67 gallium citrate was observed in the nine patients to whom it was done. Lung function tests showed a pattern of restrictive ventilatory respiratory insufficiency and hypoxemia. Lung tissue specimens were obtained in ten patients, bronchoalveolar lavage in one and pleural fluid in one. The material was examined by light and electron microscopy. Amiodarone was discontinued in all patients and corticosteroids were introduced in thirteen. Five patients (33.3%) died, eight improved and two remained with radiographic scars.

[Electrophysiological changes of the excitoconduction system in patients with Chagas cardiomyopathy and their modification by flecainide]. / Estudio de las alteraciones electrofisiológicas del sistema excitoconductor en pacientes con miocardiopatía Chagásica y las modificaciones determinadas por la flecainida.

We studied 20 patients with a confirmed diagnosis of Chagas heart disease. Clinical and electrocardiography examinations at baseline documented that all patients had chronic PVC's and that 40% of them also had supraventricular extrasystoles. Also 80% of the patients had RBBB's, 70% had LBBB's and 35% had 1st. degree AV blocks. Flecainide (F) completely suppressed the arrhythmias in 85% of the patients and did partially so in 98% of the patients. Flecainide did not affect sinus node function except in one patient who developed a sinus node atrial block. PR and QRS intervals were prolonged after F but there no 2nd or 3rd degree AV blocks. Flecainide demonstrated to be highly effective with a comfortable margin of safety in the management of these patients with marked alterations of their pace-making and conduction functions.

[Comparative multicenter clinical study of flecainide and amiodarone in the treatment of ventricular arrhythmias associated with chronic Chagas cardiopathy]. / Estudio clínico multicéntrico comparativeo de la flecainida y la amiodarona en el tratamiento de las arritmias ventriculares asociadas a la cardiopatía chagásica cronica.

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.

Análisis de las arritmias ventriculares con Holter y su tratamiento con propafenona / Analysis of ventricular arrhythmias with Holter and its treatment of propafenone

Con el objeto de valorar la eficacia antiarrítmica de la propafenona se estudiaron en total 20 pacientes con edades que fluctuaron entre los 27 y 93 años, quienes presentaban extrasístoles ventriculares sintomáticas o extrasístoles ventriculares complejas potencialmente letales. Todos los casos fueron evaluados con registro electrocardiográfico ambulatorio continuo durante 16 a 24 h, antes y durante el tratamiento con propafenona a dosis promedio de 600 mg diarios por vía oral. Se obtuvo el 100% de supresión de las extrasístoles en dos casos y se logró una importante redución tanto en el número como en la complejidad de la arritmia en el resto de los pacientes. Las extrasístoles ventriculares multiformes (tipo 3 de Lown) fueron suprimidas en el 50% de los pacientes y los pares ventriculares, así como el único caso en el que se identificaron salvas de taquicardia ventricular (tipo 4A y 4B de Lown) se suprimieron en el 100% de los casos. Para el total del grupo estudiado se obtuvo un 86.15% de supresión de la extrasistolia ventricular. No se obtuvieron modificaciones significativas en la frecuencia cardíaca o en la tensión arterial. Se documentó alargamiento del intervalo P-R de 0.22" en un caso, y en otro más se observó prolongación del intervalo Q-T a 0.41". En un paciente se observó incremento de la duración del QRS a 0.11" como máximo. La tolerancia al medicamento fue excelente y no se identificaron efectos colaterales o tóxicos significativos. Consideramos que la propafenona es un potente agente antiarrítmico, seguro y bien tolerado, que se ha convertido en un fármaco de primera elección en el tratamiento por vía oral de los trastornos de ritmo ventricular

Pneumonite e fibrose pulmonar por amiodarona: relato de dois casos com microscopia óptica e eletrônica / Pneumonitis and pulmonary fibrosis due to amiodarone: report of 2 cases with optic and electronic microscopy

Relatam-se dois casos de pacientes medicados com amiodarona para controle de extrasístoles ventriculares que desenvolveram dispnéia, tosse seca, posteriormente produtiva, hipoxemia acentuada, aumento da velocidade de hemossedimentaçäo e dos níveis séricos da mucoproteína. O 1.- paciente, que também apresentou inapetência, emagrecimento e febrícula, fez inicialmente uso de 400 mg/dia durante 14 meses e de 200 mg/dia (5 dias/semana) nos últimos 5 meses. O 2.- paciente recebeu 200 mg/dia durante 5 anos. Ambos exibiam níveis séricos da amiodarona e de seu metabólito, N-desetil amiodarona, em níveis aceitos como terapêuticos. A radiogragia de tórax revelou infiltrado intersticial, difuso, bilateral e a cintilografia pulmonar com citrato de gálio 67, realizada em um dos pacientes, evidenciou hipercaptaçäo difusa. A biopsia de pulmäo nos dois pacientes foi compatível com pneumonite e fibrose pulmonar, observando-se, pela microscopia eletrônica, inclusöes citoplasmáticas lamelares. Os corpos de inclusäo foram também detectados em neutrófilos do sangue periférico nos dois pacientes e no fígado do 2.- paciente, que foi submetido a necropsia. Os pacientes apresentaram rapidamente insuficiência respiratória severa apesar da suspensäo do medicamento e o tratamento com corticosteróide foi ineficaz. Ambos os pacientes faleceram

[Holter analysis of ventricular arrhythmias and its treatment with propafenone]. / Analisis de las arritmias ventriculares con Holter y su tratamiento con propafenona.

We studied 20 patients with ventricular premature beats. All of them underwent 16-24 hs Holter monitoring before and during propafenone treatment at an average dosage of 600 mgs P.O. We observed 86% decrease in the ectopic beats. In two cases there was a complete abolition of the ventricular beats. The Lown's type 3 ventricular beats had a 50% reduction. The were not significant modifications of the heart rate of blood pressure. There were not significant side effects. We consider propafenone as a potent agent for the treatment of ventricular ectopic beats.

Tratamiento de la extrasistolia ventricular en pacientes chagásicos ambulatorios con tocainida por via oral / Treatment of ventricular extrasystole in ambulatory chagasic patients with tocainide by oral administration

Se seleccionaron 10 pacientes con serologia positiva para la enfermedad de Chagas, sin signos ni sintomas de insuficiencia cardíaca, sín cardiomegalia, con diversos trastornos electrocardiográficos. Estos pacientes tenían E.V. complejas y frecuentes. Se les realizó a cada uno un E.C.G. y una E.C.G. dinámico sin medicación; después se les suministró placebo durante una semana repitiéndose al final de la misma E.C.G. y E.C.G. dinámico. Luego se les administro comprimidos de 400 mg de tocainida cada 6 horas por via oral durante 14 dias consecutivos y se repitieron estos estudios. Se evaluo la eficacia del fármaco para disminuir las arritmias ventriculares en cada caso en particular y en todo el grupo en general, sirviendo cada paciente como testigo de si mismo. Cuatro de los 10 pacientes presentaron efectos colaterales con tocainida debiendo dos de ellos abandonar el tratamiento. En los 8 pacientes restantes hubo una reducción del número de E.V. por paciente por hora superior al 78% (P < 0,05). En 7 de ellos la reducción fue mayor al 98% (P < 0,01). Hubo desaparición de episodios de T. V. y disminución del número de fenómenos de pareo ventricular, E. V. bigeminadas y E. V. polifocales (P < 0,05). No hubo cambios significativos en el automatismo sinusal, conducción A-V o I-V con la tocainida por via oral

Tratamiento de la extrasistolia ventricular en pacientes chagásicos ambulatorios con tocainida por via oral / Treatment of ventricular extrasystole in ambulatory chagasic patients with tocainide by oral administration

Se seleccionaron 10 pacientes con serologia positiva para la enfermedad de Chagas, sin signos ni sintomas de insuficiencia cardíaca, sín cardiomegalia, con diversos trastornos electrocardiográficos. Estos pacientes tenían E.V. complejas y frecuentes. Se les realizó a cada uno un E.C.G. y una E.C.G. dinámico sin medicación; después se les suministró placebo durante una semana repitiéndose al final de la misma E.C.G. y E.C.G. dinámico. Luego se les administro comprimidos de 400 mg de tocainida cada 6 horas por via oral durante 14 dias consecutivos y se repitieron estos estudios. Se evaluo la eficacia del fármaco para disminuir las arritmias ventriculares en cada caso en particular y en todo el grupo en general, sirviendo cada paciente como testigo de si mismo. Cuatro de los 10 pacientes presentaron efectos colaterales con tocainida debiendo dos de ellos abandonar el tratamiento. En los 8 pacientes restantes hubo una reducción del número de E.V. por paciente por hora superior al 78% (P < 0,05). En 7 de ellos la reducción fue mayor al 98% (P < 0,01). Hubo desaparición de episodios de T. V. y disminución del número de fenómenos de pareo ventricular, E. V. bigeminadas y E. V. polifocales (P < 0,05). No hubo cambios significativos en el automatismo sinusal, conducción A-V o I-V con la tocainida por via oral (AU)