RESUMO
BACKGROUND: The etiology of structural heart disease in patients with life-threatening arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) may define clinical characteristics at presentation, may require that different therapies be administered, and may cause different mortality outcomes. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) registry, baseline clinical characteristics, treatments instituted, and ultimate mortality outcomes from the National Death Index were obtained on 3117 patients seen at participating institutions with VT/VF, irrespective of participation in the randomized trial. By use of these data, 2268 patients with coronary artery disease (CAD) were compared with 334 patients with dilated nonischemic cardiomyopathy (DCM). RESULTS: The CAD group was 7 years older and had a higher percentage of males. DCM patients were more likely to be African American, have severely compromised left ventricular function (52% vs 39%), and have a history of congestive heart failure symptoms (62% vs 44%). Patients with CAD were more likely to be treated with b-blockers and calcium channel blockers and less likely to be treated with angiotensin-converting enzyme inhibitors. Patients with DCM were more likely to be treated with diuretics, warfarin, and an implantable cardioverter defibrillator for VT/VF (54% vs 48% for CAD); the use of other antiarrhythmic therapies did not differ between the 2 groups. Two-year survival was not significantly different between the groups (76.6% [95% CI 74.6%-78.7%] vs 78.2% [95% CI 73.6%-82.9%]). CONCLUSIONS: In AVID registry patients with VT/VF, demographic and clinical characteristics were different between patients with CAD and those with DCM. Despite these differences, overall survival was similar in these 2 groups.
Assuntos
Cardiomiopatia Dilatada/mortalidade , Doença das Coronárias/mortalidade , Taquicardia Ventricular/mortalidade , Fibrilação Ventricular/mortalidade , Antiarrítmicos/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/terapia , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/terapia , Desfibriladores Implantáveis , Humanos , Sistema de Registros , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/terapia , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/terapiaRESUMO
The effects of left ventricular hypertrophy (LVH) on the generation of phase 2 early afterdepolarization (EAD) and transmural dispersion of repolarization (TDR) were assessed using arterially perfused rabbit ventricular wedge preparations. Transmembrane action potentials from epicardium, subendocardium, and endocardium were simultaneously recorded together with a transmural ECG. Transmural action potential duration (APD) was also mapped. LVH (renovascular hypertension model) produced significant prolongation in ventricular APD and QT interval. Preferential APD prolongation in subendocardium and endocardium was associated with a marked increase in TDR. Phase 2 EADs were generated from subendocardium or endocardium in all LVH rabbits (15 of 15) in the absence of APD prolonging agents at basic cycle lengths of 2,000-4,000 ms. Phase 2 EAD could produce "R on T" extrasystoles, initiating polymorphic ventricular tachycardia (VT). This study provides the first direct evidence from intracellular recordings that phase 2 EAD could be generated from rabbit intact hypertrophied LV wall in the absence of APD prolonging agents, resulting in R on T extrasystoles capable of initiating polymorphic VT under enhanced TDR.
Assuntos
Potenciais de Ação/fisiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Complexos Ventriculares Prematuros/fisiopatologia , Animais , Endocárdio/fisiopatologia , CoelhosRESUMO
INTRODUCTION: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND RESULTS: Included in the AVID registry were patients from all participating sites who had "out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms." In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.
Assuntos
Antiarrítmicos/uso terapêutico , Desfibriladores Implantáveis , Síncope/terapia , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Sistema de Registros , Taxa de Sobrevida , Síncope/mortalidade , Taquicardia Ventricular/mortalidade , Fibrilação Ventricular/mortalidadeRESUMO
BACKGROUND: This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl-sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. METHODS AND RESULTS: Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl-Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 micromol/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 micromol/L but shortened them at 30 micromol/L. Unlike dl-sotalol, azimilide (>3 micromol/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl-sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl-sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 micromol/L) increased APD more than dl-sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. CONCLUSIONS: This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation.
Assuntos
Sistema de Condução Cardíaco/fisiopatologia , Imidazolidinas , Síndrome do QT Longo/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Animais , Antiarrítmicos/farmacologia , Cães , Relação Dose-Resposta a Droga , Eletrocardiografia/efeitos dos fármacos , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Hidantoínas , Imidazóis/farmacologia , Técnicas In Vitro , Síndrome do QT Longo/complicações , Contração Miocárdica/efeitos dos fármacos , Piperazinas/farmacologia , Coelhos , Sotalol/farmacologia , Especificidade da Espécie , Sístole/efeitos dos fármacos , Taquicardia Ventricular/complicações , Disfunção Ventricular Esquerda/etiologiaRESUMO
BACKGROUND: Delayed rectifier K(+) currents are critical to action potential (AP) repolarization. The present study examines the effects of left ventricular hypertrophy (LVH) on delayed rectifier K(+) currents and their contribution to AP repolarization in both epicardial (Epi) and endocardial (Endo) myocytes. METHODS AND RESULTS: VH was induced in rabbits by a 1-kidney removal, 1-kidney vascular clamping method. Slowly (I(Ks)) and rapidly (I(Kr)) activating delayed rectifier K(+) currents were recorded by the whole-cell patch-clamp technique, and APs were recorded by the microelectrode technique. In normal rabbit left ventricular myocytes, I(Ks) densities were larger in Epi than in Endo (1.1+/-0.1 versus 0.43+/-0.07 pA/pF), whereas I(Kr) density was similar between Epi and Endo (0.31+/-0.05 versus 0.36+/-0.07 pA/pF) at 20 mV. LVH reduced I(Ks) density to a similar extent (approximately 40%) in both Epi and Endo but had no significant effect on I(Kr) in either Epi or Endo. Consequently, I(Kr) was expected to contribute more to AP repolarization in LVH than in control. This was confirmed by specific I(Kr) block with dofetilide, which prolonged AP significantly more in LVH than in control (31+/-3% versus 18+/-2% in Epi; 53+/-6% versus 32+/-4% in Endo at 2 Hz). In contrast, L-768,673 (a specific I(Ks) blocker) prolonged AP less in LVH than in control. The very small I(Ks) density in Endo with LVH is consistent with the greater incidence of early afterdepolarizations induced in this region by dofetilide. CONCLUSIONS: LVH induces a decrease in I(Ks) density and increases the propensity to develop early afterdepolarizations, especially in Endo.
Assuntos
Potenciais de Ação/fisiologia , Endocárdio/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Pericárdio/fisiopatologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/metabolismo , Animais , Canais de Potássio de Retificação Tardia , Eletrofisiologia , Masculino , Miocárdio/metabolismo , CoelhosRESUMO
This was a retrospective analysis of patients who had CABG surgery at our hospital over a 12-month period to determine the intermediate-term prognosis of those who had developed PAF after their operation before hospital discharge. Of 317 patients who were operated by a single surgical group, 116 (37%) had AF postoperatively of whom 112 had the paroxysmal form. Of these, 36 were treated with class I or III antiarrhythmic drugs and rate control drugs (group 1) and 76 were treated with rate control alone (group 2). Group 3 consisted of 151 randomly selected patients who did not have AF. All patients were reevaluated at 6 weeks to determine their rhythm and clinical status. Only one patient each in groups 1 and 2 was in AF 6 weeks after discharge. There was a trend toward a higher mortality and morbidity in group 2 patients. PAF after coronary surgery appears to be a self-limited disease process. In this cohort of patients, the rate of recurrence of AF after discharge was similar in patients receiving class I or class III antiarrhythmic drugs together with rate control agents compared to those receiving rate control drugs alone.
Assuntos
Fibrilação Atrial/epidemiologia , Ponte de Artéria Coronária , Complicações Pós-Operatórias/epidemiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Casos e Controles , Digoxina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Complicações Pós-Operatórias/tratamento farmacológico , Prognóstico , Distribuição Aleatória , Recidiva , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: More than 200,000 permanent pacemakers will be implanted in the United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome (SSS) will likely account for approximately half of all cases necessitating implantation. Pacemaker technology permits the selection of ventricular (single-chamber) or dual-chamber devices. However, clinical and outcomes data are inadequate to support a clear recommendation that one or the other type of device be used. METHODS: The Mode Selection Trial (MOST) is a single-blind study supported by the National Heart, Lung, and Blood Institute designed to enroll 2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to VVIR or DDDR before implantation. The average time of follow-up will be 3 years. MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end points will include health-related quality of life and cost effectiveness, atrial fibrillation, and development of pacemaker syndrome. Prespecified subgroups for analysis will include women and the elderly. Enrollment was completed in October 1999, with a total of 2010 patients. RESULTS: The median age of the first 1000 enrolled patients is 74 years, with 25% of patients 80 years or older. Women comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker implantation, 22% of patients reported a history of congestive heart failure, 11% coronary angioplasty, and 25% coronary bypass surgery. Supraventricular tachycardia including atrial fibrillation was present in 53% of patients. A prior stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients. CONCLUSIONS: MOST will fill the clinical need for carefully designed prospective studies to define the benefits of dual-chamber versus single-chamber ventricular pacing in patients with SSS. The MOST population is typical of the overall pacemaker population in the United States. Thus the final results of MOST should be clinically generalizable.
Assuntos
Estimulação Cardíaca Artificial , Síndrome do Nó Sinusal/terapia , Idoso , Idoso de 80 Anos ou mais , Estimulação Cardíaca Artificial/economia , Estimulação Cardíaca Artificial/mortalidade , Análise Custo-Benefício , Eletrocardiografia , Feminino , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Síndrome do Nó Sinusal/economia , Síndrome do Nó Sinusal/mortalidade , Método Simples-Cego , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
Despite the emergence of several forms of nonpharmacologic therapy for cardiac arrhythmias, antiarrhythmic drugs continue to play an important role in the management of patients with this common clinical problem. The key to the proper use of antiarrhythmic drugs is a thorough knowledge of their mode of action and pharmacology. The pharmacology of antiarrhythmic drugs is particularly important because patients with cardiac arrhythmias frequently have multiorgan disease, which may influence the metabolism and elimination of antiarrhythmic drugs. The accumulation of toxic amounts of these agents can lead to dire effects including, but not limited to, ventricular proarrhythmia and malignant bradycardia. The goals of pharmacologic therapy of cardiac arrhythmia are to provide the maximum benefit in terms of arrhythmia suppression while maintaining patient safety. To accomplish these goals, a knowledge of the pharmacology of several antiarrhythmic drugs is mandatory.
Assuntos
Antiarrítmicos/classificação , Antiarrítmicos/farmacologia , Idoso , Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Patients with inducible sustained ventricular tachycardia (VT) sometimes receive intravenous procainamide during electrophysiologic testing. Unfortunately, the responses to intravenous and subsequent oral drug therapy are variable and may be discordant. HYPOTHESIS: It was the aim of this study to determine whether this variability might be explained by heterogeneity in the electropharmacologic response, even in a homogeneous population. METHODS: We studied 42 patients who had spontaneous malignant ventricular arrhythmia and were inducible to sustained monomorphous VT during electrophysiologic testing. Each received 15 mg/kg of intravenous procainamide followed by a 2 mg/min infusion. Serum levels were drawn immediately following programmed stimulation. The mean procainamide level was 6.7 +/- 1.4 mcg/ml with an N-acetyl procainamide level of 1.0 +/- 0.5 mcg/ml. The 14 procainamide responders (5 of whom were noninducible and 9 whose VT cycle length increased > 100 ms) and the 28 nonresponders had similar procainamide and NAPA levels (6.5 +/- 1.4 vs. 6.7 +/- 1.4 mcg/ml). RESULTS: There was no significant difference in baseline clinical parameters, His to ventricular electrogram (HV) interval, effective refractory period, or VT cycle length. Prolongation of the effective refractory period and infra His conduction time occurred to a similar extent in responders and nonresponders. CONCLUSION: We conclude that procainamide has a consistent dose-response relationship with respect to refractoriness and conduction in patients with malignant arrhythmias. However, acute antiarrhythmic efficacy of procainamide cannot be predicted by clinical factors, drug levels, or drug-induced changes in common electrophysiologic parameters.
Assuntos
Antiarrítmicos/farmacologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Procainamida/farmacologia , Taquicardia Ventricular/tratamento farmacológico , Idoso , Antiarrítmicos/administração & dosagem , Antiarrítmicos/sangue , Antiarrítmicos/uso terapêutico , Fascículo Atrioventricular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletrofisiologia , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Procainamida/administração & dosagem , Procainamida/sangue , Procainamida/uso terapêuticoRESUMO
BACKGROUND: The prognosis of patients with sustained ventricular tachyarrhythmias varies according to clinical characteristics. We sought to identify predictors of survival in a large population of patients with documented sustained ventricular tachyarrhythmias not related to reversible or correctable causes included in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Registry. METHODS AND RESULTS: We analyzed the impact of 36 demographic, clinical, and discharge treatment variables on the outcome for 3559 patients. Survival status was assessed with the use of the National Death Index. Multivariate analyses were performed with the use of the Cox proportional hazards model. After a mean follow-up of 17 +/- 12 months, 631 patients died. Actuarial survival was 0.86 (95% confidence interval [CI] 0.85 to 0.88), 0.79 (95% CI 0.78 to 0.81), and 0.72 (95% CI 0.70 to 0.74) at 1, 2, and 3 years. Multivariate predictors of worse survival included older age, severe left ventricular dysfunction, lower systolic blood pressure, history of congestive heart failure, diabetes, smoking or atrial fibrillation, and preexistent pacemaker. The hemodynamic impact of the qualifying arrhythmia was not a predictor of outcome. Defibrillator implantation and hospital discharge while the patient was taking a beta-blocker or an angiotensin-converting enzyme inhibitor were associated with better prognosis. CONCLUSIONS: Despite therapeutic advances, the mortality rates of patients with sustained ventricular tachyarrhythmias remain high. Prognosis depends on the severity of underlying heart disease, as reflected by the extent of left ventricular dysfunction and the presence of heart failure. Well-tolerated ventricular tachycardia in patients with structural heart disease does not carry a significantly better prognosis than ventricular tachyarrhythmia with more severe hemodynamic consequences.
Assuntos
Antiarrítmicos/uso terapêutico , Desfibriladores Implantáveis , Sistema de Registros , Taquicardia Ventricular/terapia , Idoso , Amiodarona/efeitos adversos , Amiodarona/uso terapêutico , Antiarrítmicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Prognóstico , Estudos Prospectivos , Sotalol/efeitos adversos , Sotalol/uso terapêutico , Taxa de Sobrevida , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidadeRESUMO
Recurrent ventricular fibrillation was observed in a 29-year-old Vietnamese man who did not exhibit structural heart disease. The patient's ECG showed prominent J (Osborn) waves and ST segment elevation in the inferior leads that were not associated with hypothermia, serum electrolyte disturbance, or myocardial ischemia. Rate-dependent change in the amplitude of J waves and ST segment elevation also were observed. An implantable cardioverter defibrillator (ICD) was implanted. Adjunctive treatment with amiodarone reduced J wave amplitude, preventing ventricular fibrillation and ICD shocks. Prominent J waves and ST segment elevation in the inferior leads may serve as an important diagnostic sign to detect high-risk individuals with a history of unexplained syncope. ICD implantation plus amiodarone is the treatment of choice.
Assuntos
Eletrocardiografia , Parada Cardíaca/etiologia , Fibrilação Ventricular/complicações , Fibrilação Ventricular/fisiopatologia , Adulto , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Ritmo Circadiano , Desfibriladores Implantáveis , Parada Cardíaca/terapia , Humanos , Masculino , Ressuscitação , Fibrilação Ventricular/prevenção & controle , Fibrilação Ventricular/terapiaRESUMO
beta-Adrenergic stimulation of cardiac L-type Ca(2+) channels is severely impaired in hypertrophied and failing hearts of both experimental animals and humans. The aim of this study was to test the hypothesis that chronic treatment of renovascular hypertension with captopril restores normal beta-adrenergic responsiveness of L-type Ca(2+) channels in cardiac myocytes. Left ventricular hypertrophy was induced in rabbits by unilateral renal artery banding and contralateral nephrectomy. Beginning at 3 months after banding, hypertensive rabbits were treated with captopril for 3 months. The responsiveness of L-type Ca(2+) current (I(Ca,L)) to (+/-)-isoproterenol was investigated with the whole-cell patch-clamp technique. (+/-)-Isoproterenol (1 microM) induced an increase of I(Ca,L) at 0 mV of 126 +/- 20% (n = 13) in control myocytes versus 69 +/- 11% (n = 18) in hypertrophied myocytes from rabbits 3 months after banding. The half-maximal activation concentration of (+/-)-isoproterenol was similar between control and hypertrophied myocytes. Forskolin (10 microM) induced a similar percentage of increase of I(Ca,L) in control and hypertrophied myocytes, 109 +/- 13% (n = 12) versus 120 +/- 14% (n = 11) at 0 mV. The responsiveness of I(Ca,L) to (+/-)-isoproterenol remained depressed in untreated hypertensive rabbits. (+/-)-Isoproterenol (1 microM) increased I(Ca, L) at 0 mV by 64 +/- 8% (n = 14) in myocytes isolated from rabbits 6 months after banding versus 111 +/- 15% (n = 16) in age-matched controls. In captopril-treated rabbits, 1 microM (+/-)-isoproterenol increased I(Ca,L) by 110 +/- 11% (n = 17). We conclude that the maximal response of I(Ca,L) to (+/-)-isoproterenol was severely depressed in hypertrophied myocytes. Chronic treatment of renovascular hypertension with captopril can restore normal responsiveness of I(Ca,L) to (+/-)-isoproterenol in cardiac myocytes.
Assuntos
Canais de Cálcio/efeitos dos fármacos , Captopril/farmacologia , Coração/efeitos dos fármacos , Hipertensão Renovascular/tratamento farmacológico , Receptores Adrenérgicos beta/efeitos dos fármacos , Animais , Captopril/uso terapêutico , Colforsina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Hipertensão Renovascular/fisiopatologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/fisiopatologia , Isoproterenol/farmacologia , Nefrectomia , Técnicas de Patch-Clamp , Coelhos , Distribuição Aleatória , Receptores Adrenérgicos beta/fisiologia , Artéria Renal/cirurgia , Fatores de TempoRESUMO
Ventricular tachycardia, which causes hemodynamic instability, and ventricular fibrillation do not occur frequently in any hospital. However, they usually occur in patients who have severe underlying cardiovascular disease such as myocardial ischemia/infarction or congestive heart failure, and they are associated with high mortality. Most of those deaths are due to an intractable arrhythmia, not suppressible with even the most potent antiarrhythmic drugs. Fortunately, during the last few years, our ability to suppress highly lethal ventricular arrhythmia has been enhanced by the approval of intravenous amiodarone. When used in appropriate patient populations, intravenous amiodarone has been successful in suppressing the most malignant arrhythmia, thus permitting aggressive and successful treatment of severe underlying cardiac conditions. This article reviews data on the use of parenteral antiarrhythmic drugs for the control of ventricular arrhythmia in patients in hospital, and will attempt to provide some guidance as to how these antiarrhythmic drugs may be used in specific patient populations to maximize their efficacy and safety. We will also make recommendations on the sequence of therapy for specific arrhythmias to optimize the chances of patient survival.
Assuntos
Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Hospitalização , Taquicardia Ventricular/tratamento farmacológico , Fibrilação Ventricular/tratamento farmacológico , Amiodarona/efeitos adversos , Amiodarona/farmacocinética , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Taquicardia Ventricular/sangue , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/sangue , Fibrilação Ventricular/etiologiaRESUMO
In freshly-isolated, single, smooth muscle cells of rabbit coronary arteries, an inward rectifier K+ current [IK(IR)] was identified using the whole-cell voltage-clamp technique. The current/voltage (I/V) relationship of IK(IR) showed strong inward rectification with a very small outward current when the smooth muscle cells were dialyzed with a pipette solution containing Mg2+. However, dialyzing the cells with a nominally Mg2+-free pipette solution revealed a significant outward current hump in the I/V relation of IK(IR), suggesting that the strong inward rectification of IK(IR) is partly due to the inhibitory effects of internal Mg2+. IK(IR) was unaffected by tetraethylammonium (1 mM), 4-aminopyridine (1 mM), or glibenclamide (1 microM), but was inhibited by extracellular Ba2+ with a concentration of 0.87 microM eliciting half-maximal inhibition at -120 mV. IK(IR) induced in rabbit coronary smooth muscle cells declined during very negative hyperpolarizing steps, due largely to a block by external Na+. IK(IR) was inhibited by alpha1-adrenergic stimuli. Methoxamine, an alpha1-adrenergic agonist, concentration dependently inhibited IK(IR) in the presence of the beta-adrenergic antagonist propranolol. The methoxamine concentration required for half-maximal inhibition was 205 microM. We conclude that inward rectifier K+ current is present in rabbit coronary smooth muscle cells and that it shares many properties with the inward rectifier K+ current described for other cell types.
Assuntos
Vasos Coronários/fisiologia , Músculo Liso Vascular/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/fisiologia , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Eletrofisiologia , Técnicas In Vitro , Magnésio/metabolismo , Masculino , Metoxamina/farmacologia , Norepinefrina/farmacologia , Bloqueadores dos Canais de Potássio , Coelhos , Receptores Adrenérgicos alfa 1/metabolismoRESUMO
Atrial fibrillation (AF) has captured the imagination of clinical investigators who have initiated trials to examine several aspects of this multifaceted arrhythmia. We will review the protocol designs of ongoing trials that are examining the relative value of rhythm versus rate control, new methods for pharmacologic restoration and maintenance of sinus rhythm (including prophylaxis after cardiac surgery), and nonpharmacologic interventions such as pacing and atrial defibrillation. We antic ipate that the results of these studies will have a major impact on the care of patients with AF in the new millennium.
Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Flutter Atrial/terapia , Estimulação Cardíaca Artificial , Cardioversão Elétrica , Ensaios Clínicos como Assunto , Humanos , Projetos de PesquisaAssuntos
Cardiopatias/etiologia , Ventriculografia com Radionuclídeos , Idoso , Eletrocardiografia , Feminino , HumanosRESUMO
Recent studies indicate that regression of left ventricular hypertrophy (LVH) normalizes the in situ electrophysiological abnormalities of the left ventricle. This study was designed to determine whether regression of LVH also normalizes the abnormalities of individual membrane currents. LVH was induced in rabbits by renal artery banding. Single ventricular myocytes from rabbits with LVH at 3 mo after renal artery banding demonstrated increased cell membrane capacitance, prolonged action potential duration, decreased inward rectifier K+ current density, and increased transient outward K+ current density compared with myocytes from age-matched controls. Additional rabbits were randomized at 3 mo after banding to treatment with either vehicle or captopril for an additional 3 mo. Myocytes from LVH rabbits treated with vehicle showed persistent membrane current abnormalities. However, myocytes isolated from LVH rabbits treated with captopril had normal cell membrane capacitance, action potential duration, and membrane current densities. Captopril had no direct effect on membrane currents of either control or LVH myocytes. These data support the hypothesis that the action potential prolongation and membrane current abnormalities of LVH are reversed by regression. Normalization of membrane currents probably explains the reduced vulnerability to ventricular arrhythmia observed in this LVH model after treatment with captopril.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Captopril/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/fisiopatologia , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Células Cultivadas , Coração/efeitos dos fármacos , Coração/fisiologia , Coração/fisiopatologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Nefrectomia , Tamanho do Órgão/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Coelhos , Artéria Renal/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Standard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes. METHODS: The Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dual-chamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey. RESULT: The average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemaker implantation (P<0.001), but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes (including cardiovascular events or death). However, 53 patients assigned to ventricular pacing (26 percent) were crossed over to dual-chamber pacing because of symptoms related to the pacemaker syndrome. Patients with sinus-node dysfunction, but not those with atrioventricular block, had moderately better quality of life and cardiovascular functional status with dual-chamber pacing than with ventricular pacing. Trends of borderline statistical significance in clinical end points favoring dual-chamber pacing were observed in patients with sinus-node dysfunction, but not in those with atrioventricular block. CONCLUSION: The implantation of a permanent pacemaker improves health-related quality of life. However, the quality-of-life benefits associated with dual-chamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction.
Assuntos
Bradicardia/terapia , Estimulação Cardíaca Artificial/métodos , Marca-Passo Artificial , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Bradicardia/prevenção & controle , Desenho de Equipamento , Feminino , Bloqueio Cardíaco/mortalidade , Bloqueio Cardíaco/terapia , Humanos , Masculino , Método Simples-Cego , Análise de Sobrevida , Resultado do TratamentoRESUMO
Atrial fibrillation (AFib) is a common clinical entity, responsible for significant morbidity and mortality, but it also accounts for a large percentage of healthcare dollar expenditures. Efforts to treat this arrhythmia in the past have focused on subacute antithrombotic therapy and eventually use of antiarrhythmic drugs for maintenance of sinus rhythm. However, there has been a growing interest in the concept of acute electrical and pharmacologic conversion. This treatment strategy has a number of benefits, including immediate alleviation of patient symptoms, avoidance of antithrombotic therapy, and prevention of electrophysiologic remodeling, which is thought to contribute to the perpetuation of the arrhythmia. There is also increasing evidence that this is a cost-effective strategy in that it may obviate admission to the hospital and the cost of long-term therapy. This article represents a summary of the treatments that may be used acutely to control the ventricular response to AFib, prevent thromboembolic events, and provide for acute conversion either pharmacologically or electrically. It includes information on modalities that are currently available and those that are under active development. We anticipate that an active, acute treatment approach to AFib and atrial flutter will become the therapeutic norm in the next few years, especially as the benefits of these interventions are demonstrated in clinical trials.
Assuntos
Fibrilação Atrial/terapia , Antiarrítmicos/efeitos adversos , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Cardioversão Elétrica/efeitos adversos , Humanos , Tromboembolia/etiologia , Tromboembolia/prevenção & controleRESUMO
Nonsustained ventricular tachycardia (NSVT) continues to remain a subject of controversy. This is true despite a wealth of epidemiologic and basic/clinical laboratory findings that have accumulated during the past 2 decades. However, these data not only generate the impetus to conduct further research, but also provide compelling arguments against continued adherence to time honored precepts about NSVT that evolved since the inception of the "PVC Hypothesis," although never substantiated by rigorous scientific inquiry. This paper discusses the "top ten" fallacies of NSVT and details the data that support abandonment of them.