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BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: The purpose of this study was to assess the contemporary real-world practice approach and short and long-term outcomes of RF CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClincalTrials.gov Identifier: NCT04088071) Registry, patients undergoing RF CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2470 patients undergoing CA from January 2018 to December 2022 were included. Mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedural and total RF times of 95.4 ± 41.7 minutes and 22.1±11.8 minutes, respectively. At 1-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing pulmonary vein isolation vs pulmonary vein isolation plus ablation approaches. The complication rate was 1.9%. CONCLUSION: Refinement of RF CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows resulted in excellent short- and long-term clinical outcomes.
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Background: CONVERGE was a prospective, multicenter, randomized controlled trial that evaluated the safety of Hybrid Atrial Fibrillation Convergent (HC) and compared its effectiveness to endocardial catheter ablation (CA) for the treatment of persistent atrial fibrillation (PersAF) and longstanding PersAF (LSPAF). In 2020, we reported that CONVERGE met its primary safety and effectiveness endpoints. The primary objective of the present study is to report CONVERGE trial results for quality of life (QOL) and Class I/III anti-arrhythmic drug (AAD) utilization following HC. Methods: Eligible patients had drug-refractory symptomatic PersAF or LSPAF and a left atrium diameter ≤6.0 cm. Enrolled patients were randomized 2:1 to receive HC or CA. Atrial Fibrillation Severity Scale (AFSS) and the 36-Item Short Form Health Survey (SF-36) were assessed at baseline and 12 months; statistical comparison was performed using paired t-tests. AAD utilization at baseline through 12 and 18 months post-procedure was evaluated; statistical comparison was performed using McNemar's tests. Results: A total of 153 patients were treated with either HC (n=102) or CA (n=51). Of the 102 HC patients, 38 had LSPAF. AFSS and SF-36 Mental and Physical Component scores were significantly improved at 12 months versus baseline with HC overall and for the subset of LSPAF patients treated with either HC or CA. The proportion of HC patients (n=102) who used Class I /III AADs at 12 and 18 months was significantly less (33.3% and 36.3%, respectively) than baseline (84.3%; P<0.001). In LSPAF patients who underwent HC (n=38), AADs use was 29.0% through 18 months follow-up versus 71.1% at baseline (P<0.001). Conclusions: HC reduced AF symptoms, significantly improved QOL, and reduced AAD use in patients with PersAF and LSPAF. ClinicalTrialsgov Identifier: NCT01984346.
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Background: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA. Objective: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial. Methods: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety endpoint was major adverse event incidence through 30 days with HC. Key secondary effectiveness measures included (1) percent of patients achieving ≥90% AF burden reduction vs baseline and (2) AF freedom. Results: Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Primary effectiveness was 65.8% (95% confidence interval [CI] 50.7%-80.9%) with HC vs 37.0% (95% CI 5.1%-52.4%) with CA (P = .022). Through 18 months, these rates were 60.5% (95% CI 50.0%-76.1%) with HC vs 25.9% (95% CI 9.4%-42.5%) with CA (P = .006). Secondary effectiveness rates were higher than CA with HC at 12 and 18 months. Freedom from atrial arrhythmias off AADs was 52.6% (95% CI 36.8%-68.5%) and 47.4% (95% CI 31.5%-63.2%) with HC at 12 and 18 months vs 25.9% (95% CI 9.4%-42.5%) and 22.2% (95% CI 6.5%-37.9%) with CA, respectively (12 months: P = .031; 18 months: P = .038). Three (7.9%) major adverse events occurred within 30 days of HC. Conclusion: Post hoc analysis demonstrated effectiveness and acceptable safety of HC compared with CA in LSPAF.
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BACKGROUND: Cardiac implantable electronic device (CIED) implantation is increasingly performed worldwide with improving safety. Outpatient CIED implantation has similar complication rates compared to those implants which are hospitalized. Here, we analyze patient preferences on discharge timing after CIED implantation. OBJECTIVE: To identify and understand the factors contributing to patient preferences towards same-day or next-day discharge after CIED implantation. METHODS: One hundred and two patients undergoing new CIED implants were included in the study at two separate hospitals in CT (CT group) and FL (FL group) from 2018-2019. A 7-question survey was administered to the patients after the procedure. Survey responses and demographic data were statistically analyzed. RESULTS: Seventy-four percent of CT group and 58% of the FL group responded with a 10 score (0-10) that they were ready to be discharged home the same day (p=0.09). Both groups reported a low number of patients feeling safer by having a remote monitor provided at the time of discharge (44% CT group, 28% FL group; p=0.123). The mean distance of patients living from the hospital in CT group (21.6 miles) was significantly lower than that for the FL group (35.5 miles); p=0.01. Hypertension (86% vs 52%; p=0.0002) and Diabetes mellitus (44% vs 21%; p=0.013) were more prevalent in the FL group compared to the CT group. CONCLUSION: Despite the influence of local practices, the majority of patients preferred same-day discharge after CIED implantation. Improved patient education regarding the ability of remote monitors to provide real-time response to acute events is needed.
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BACKGROUND: The limited effectiveness of endocardial catheter ablation (CA) for persistent and long-standing persistent atrial fibrillation (AF) treatment led to the development of a minimally invasive epicardial/endocardial ablation approach (Hybrid Convergent) to achieve a more comprehensive lesion set with durable transmural lesions. The multicenter randomized controlled CONVERGE trial (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent AF) evaluated the safety of Hybrid Convergent and compared its effectiveness to CA for persistent and long-standing persistent AF treatment. METHODS: One-hundred fifty-three patients were randomized 2:1 to Hybrid Convergent versus CA. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia absent new/increased dosage of previously failed/intolerant class I/III antiarrhythmic drugs through 12 months. Primary safety was major adverse events through 30 days. CONVERGE permitted left atrium size up to 6 cm and imposed no limits on AF duration, making it the only ablation trial to substantially include long-standing persistent-AF, that is, 42% patients with long-standing persistent-AF. RESULTS: Of 149 evaluable patients at 12 months, primary effectiveness was achieved in 67.7% (67/99) patients with Hybrid Convergent and 50.0% (25/50) with CA (P=0.036) on/off previously failed antiarrhythmic drugs and in 53.5% (53/99) versus 32.0% (16/50; P=0.0128) respectively off antiarrhythmic drugs. At 18 months using 7-day Holter, 74.0% (53/72) Hybrid Convergent and 55% (23/42) CA patients experienced ≥90% AF burden reduction. A total of 2.9% (3/102) patients had primary safety events within 7 days, and 4.9% (5/102) between 8 and 30 days postprocedure. No deaths, cardiac perforations, or atrioesophageal fistulas occurred. All but one primary safety event resolved. CONCLUSIONS: The Hybrid Convergent procedure has superior effectiveness compared to the CA for the treatment of persistent and long-standing persistent atrial fibrillation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01984346.
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Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Venas Pulmonares/cirugía , Anciano , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Ablación por Catéter/efectos adversos , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Venas Pulmonares/fisiopatología , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Estados UnidosRESUMEN
INTRODUCTION: Catecholamines are known to affect cardiac repolarization, and provocation with either isoproterenol or epinephrine has been proposed as a tool for uncovering latent repolarization abnormalities. This study systematically compares the effects of isoproterenol and epinephrine infusions on QT interval (QT), T waves and U waves in normal subjects. METHODS AND RESULTS: Twenty-four normal subjects (29 +/- 8 years) were evaluated during graded infusions of up to 0.30 microg/kg/minute epinephrine and 5.0 microg/minute isoproterenol. Heart rates at peak doses were 81 +/- 13 bpm at 0.28 +/- 0.04 microg/kg/minute epinephrine and 104 +/- 5 bpm at 2.4 microg/minute isoproterenol. The longest absolute QT increase was 4 +/- 5 msec above baseline during isoproterenol (P < 0.001) and 12 +/- 23 msec during epinephrine (P = 0.07), while the longest corrected QT interval (QTc) increase was 67 +/- 28 msec (P < 0.0001) and 79 +/- 40 msec (P < 0.0001) above baseline during isoproterenol and epinephrine, respectively (P = 0.12 for difference). There was a 2-fold increase in U-wave amplitude during each intervention (P < 0.001). The specificity of paradoxical QT prolongation (>or=30 msec at 0.05 microg/kg/minute or >or=35 msec at 0.10 microg/kg/minute epinephrine) and an increase in QTc >or=600 msec at any dose epinephrine were 100%. However, the specificity of other proposed criteria that utilized QTc measurement (>or=30 msec at 0.10 microg/kg/minute or >or=65 msec at any dose) was poor whether all leads or only lead II were assessed. CONCLUSION: Both epinephrine and isoproterenol are associated with QTc prolongation and amplification of the U wave in normal subjects. The specificity of proposed criteria for epinephrine provocation in diagnosis of the long-QT syndrome is variable; however, paradoxical QT prolongation at low-dose epinephrine or a QTc >or=600 msec is highly specific.
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Epinefrina/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Isoproterenol/administración & dosificación , Adulto , Electrocardiografía/efectos de los fármacos , Epinefrina/efectos adversos , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Infusiones Intravenosas , Isoproterenol/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/fisiopatología , Masculino , Persona de Mediana Edad , Simpatomiméticos/administración & dosificación , Simpatomiméticos/efectos adversosRESUMEN
The proarrhythmic effects of cocaine may be mediated in part by its effects on cardiac repolarization properties. This study evaluated the acute effects of smoking cocaine 25 mg on the electrocardiograms of 14 habitual cocaine users during a 12-minute observation period. After cocaine administration, heart rate increased by a mean of 22 beats/min (p <0.0001). One patient developed accelerated junctional rhythm, and 5 had nonspecific ST-T-wave abnormalities. The electrocardiograms revealed significant prolongation of the QTc interval (p <0.001) after cocaine administration. In addition, T-wave amplitude decreased and U-wave amplitude increased in response to cocaine use (p <0.05). QRS duration was unchanged by cocaine, whereas the PR interval shortened slightly. The repolarization changes observed after cocaine use were similar to those reported for other sympathomimetic agents and may be a contributing factor in the association between cocaine use and ventricular arrhythmias.
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Trastornos Relacionados con Cocaína/fisiopatología , Cocaína/efectos adversos , Inhibidores de Captación de Dopamina/efectos adversos , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Adulto , Nodo Atrioventricular/efectos de los fármacos , Nodo Atrioventricular/fisiopatología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Femenino , Sistema de Conducción Cardíaco/efectos de los fármacos , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , MasculinoRESUMEN
INTRODUCTION: Typical and atypical atrial flutters (AFLs) and atrial tachycardias (ATs) have been reported in patients with prior surgical atrial fibrillation ablation. The underlying mechanisms for this group of atrial tachyarrhythmias have not been well characterized and the efficacy of catheter ablation in their treatment is unknown. METHODS AND RESULTS: Twenty patients (6 females) with a surface ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation underwent 26 electrophysiology studies. Patients manifesting sustained, organized, and beat-by-beat reproducible atrial electrical activity underwent complete right and left atrial catheter mapping and catheter ablation. One patient had no inducible tachyarrhythmia, while 5 patients had nonmappable arrhythmias. Nineteen of the 31 potentially mappable atrial tachyarrhythmias were completely characterized in 14 patients. The underlying mechanisms were macro-reentrant left AFL (n = 9), focal left AT (n = 3), typical right AFL (n = 6), and atypical right AFL (n = 1). Of the 19 completely characterized atrial arrhythmias, catheter ablation was performed for 18, and the procedure was successful for 13 of these. After a mean follow-up of 15 +/- 10 months, 15 of 20 patients (75%) were in sinus rhythm including 10 of 13 patients (77%) with AT/flutter ablation. Ten patients, including 6 following ablation, were maintaining sinus rhythm without antiarrhythmic medications. CONCLUSIONS: Patients with an ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation may have multiple tachycardia mechanisms with the right or left atrium as the site of origin. Many of these rhythms may resolve with further maturation of surgical atrial fibrillation ablation (SAFA) lesions or be treatable with antiarrhythmic medication. However, persistent tachyarrhythmias can often be treated successfully with catheter mapping and ablation.
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Fibrilación Atrial/cirugía , Aleteo Atrial/etiología , Ablación por Catéter/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Aleteo Atrial/diagnóstico , Aleteo Atrial/fisiopatología , Diagnóstico Diferencial , Electrocardiografía , Femenino , Estudios de Seguimiento , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
The etiology of U waves on the electrocardiogram is uncertain. We previously found that U waves could be amplified by isoproterenol infusion. Whether other autonomic interventions modify U-wave amplitude is unknown. Twenty-five healthy subjects underwent graded infusions of esmolol and phenylephrine. Heart rate, T-wave amplitude, U-wave amplitude, and QT and QU intervals were measured using interactive computerized electrocardiogram software. Heart rate decreased with both interventions ( P < .001), though to a greater degree with phenylephrine. U-wave amplitude increased by 16.3% during phenylephrine ( P < .001) but decreased by 14.5% during esmolol ( P < .001). The change in U-wave amplitude was strongly dose-dependent for both phenylephrine ( P < .001) and esmolol ( P < .001). T-wave amplitude increased with phenylephrine (597-692 microV, P < .001) but decreased with esmolol (632-568 microV, P < .001). QT and QU intervals increased with both interventions ( P < .001). We conclude that sympathetic and parasympathetic activities are important determinants of U-wave timing and amplitude.
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Agonistas alfa-Adrenérgicos/administración & dosificación , Electrocardiografía/efectos de los fármacos , Fenilefrina/administración & dosificación , Propanolaminas/administración & dosificación , Agonistas alfa-Adrenérgicos/farmacología , Adulto , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Masculino , Fenilefrina/farmacología , Propanolaminas/farmacologíaRESUMEN
OBJECTIVES: In a retrospective study, we sought to evaluate the effect of left ventricular assist device (LVAD) therapy on ventricular tachyarrhythmias in patients with advanced congestive heart failure. BACKGROUND: Despite the increasing use of LVAD as a bridge to cardiac transplantation, our knowledge regarding its effect on ventricular arrhythmias is currently limited to small series. Little is known about the prevalence, predictors, and clinical consequences of ventricular arrhythmias in LVAD recipients. METHODS: We reviewed the pre- and post-LVAD course of the last 100 consecutive adult patients to receive a HeartMate LVAD (Thoratec Laboratories Corp., Pleasanton, California) at our institution. All ventricular arrhythmias sustained for at least 30 s or requiring defibrillation were analyzed. All documented pre- and post-LVAD sustained ventricular arrhythmias were classified either as monomorphic ventricular tachycardia (MVT) or polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF). RESULTS: Our population had an average age of 51 years, had predominately ischemic cardiomyopathy (63%), and a mean left ventricular ejection fraction of 20 +/- 10%. New-onset MVT was observed in 18 patients who did not have MVT before LVAD placement. After LVAD, new-onset MVT was 4.5 times more likely than elimination of previously present MVT (p = 0.001), whereas the effect of LVAD on incidence of PVT/VF was not significant. In a multivariate Cox proportional hazards regression analysis, serum electrolyte abnormality was an independent predictor of post-LVAD ventricular arrhythmias. Preoperative MVT did not predict postoperative MVT. CONCLUSIONS: After LVAD placement, there is a significant rise in the incidence of de novo MVT. By contrast, the incidence of PVT/VF was unaffected by LVAD placement.
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Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Taquicardia Ventricular/epidemiología , Electrocardiografía , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Taquicardia Ventricular/etiología , Taquicardia Ventricular/mortalidadRESUMEN
Prolonged repolarization time, an important contributor to the pathogenesis of ventricular arrhythmias, is usually identified by a long QT interval (QT) on the ECG but is frequently confounded by the presence of a U wave. The physiological basis and clinical relevance of the U wave is unresolved. To better understand the relationship between the T and U waves, this study examined their behavior during nonresting autonomic conditions. Twenty-five healthy subjects were evaluated during sympathomimetic infusion with isoproterenol and vagal inhibition with atropine. As heart rate (HR) increased in response to isoproterenol, the QU interval (QU) decreased by an eightfold greater extent than QT. Furthermore, a marked increase in U wave amplitude and decrease in T wave amplitude were observed with T and U wave fusion at higher HRs. During atropine, QU decreased by only a threefold greater extent than QT, T and U wave amplitudes were affected only minimally, and T-U wave fusion was not observed. These results demonstrate that sympathomimetic stimulation causes striking alterations in the timing and amplitude of U waves that differ from effects on the T wave. These effects are not observed during vagal inhibition. Thus, the U wave represents a component of cardiac repolarization that is electrocardiographically and physiologically distinct from the T wave with a unique response to sympathomimetic stimulation.
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Sistema Nervioso Autónomo/efectos de los fármacos , Electrocardiografía/efectos de los fármacos , Simpatomiméticos/farmacología , Nervio Vago/efectos de los fármacos , Adulto , Atropina/farmacología , Sistema Nervioso Autónomo/fisiología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Isoproterenol/farmacología , Masculino , Persona de Mediana Edad , Parasimpatolíticos/farmacología , Factores de TiempoRESUMEN
In light of the significant morbidity and mortality from atrial fibrillation (AF), there has been significant interest in the development of percutaneous catheter ablation procedures for the suppression of AF. Given the success of the surgical Maze procedure, initial catheter-based approaches involved creation of linear atrial lesions. Success rates were low and utility was limited by a high complication rate and long procedural times. The recent discovery that AF is often initiated by atrial ectopic beats has resulted in therapies designed to target the ectopic sources, particularly those within the pulmonary veins. Experience and technological advances have improved the efficacy and safety of such procedures. This article will review catheter ablation procedures for the maintenance of sinus rhythm in patients with AF.
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Fibrilación Atrial/cirugía , Ablación por Catéter , Aleteo Atrial/cirugía , Ablación por Catéter/tendencias , Sistema de Conducción Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/cirugía , Humanos , Venas Pulmonares/cirugíaRESUMEN
Clinically important supraventricular arrhythmias are occasionally encountered in patients following cardiac transplantation and the use of catheter ablation as a treatment has been reported. The following three cases are described: (1) atrial flutter, including electroanatomic mapping of the donor and recipient components of the right atrium, (2) a mid-septal accessory pathway, and (3) atrioventricular nodal reentrant tachycardia (AVNRT). A Medline database search was performed and articles addressing catheter ablation following cardiac transplantation were reviewed. The efficacy of RFA for treating various arrhythmia mechanisms was evaluated based on a summary of published case reports.
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Ablación por Catéter , Trasplante de Corazón , Taquicardia Supraventricular/cirugía , Anciano , Aleteo Atrial/epidemiología , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Taquicardia por Reentrada en el Nodo Atrioventricular/epidemiología , Taquicardia Supraventricular/epidemiología , Taquicardia Supraventricular/fisiopatologíaAsunto(s)
Electrocardiografía , Técnicas Electrofisiológicas Cardíacas/métodos , Prueba de Esfuerzo , Insuficiencia Cardíaca/diagnóstico , Adulto , Umbral Anaerobio/fisiología , Presión Sanguínea/fisiología , Femenino , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico/fisiologíaAsunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico , Hipotensión/diagnóstico , Feocromocitoma/diagnóstico , Taquicardia/diagnóstico , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Hipotensión/fisiopatología , Masculino , Persona de Mediana Edad , Feocromocitoma/diagnóstico por imagen , Cintigrafía , Taquicardia/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: We sought to determine whether the relationship between heart rate (HR) and QT interval (QT) differs as HR increases in response to exercise, atropine and isoproterenol. BACKGROUND: Autonomic nervous system influences on repolarization are poorly understood and may complicate the interpretation of QT measurements. METHODS: Twenty-five normal subjects sequentially underwent graded-intensity bicycle exercise, atropine injection and isoproterenol infusion. Serial 12-lead electrocardiograms were recorded at steady state during each condition and analyzed using interactive computer software. The HR-QT data were modeled linearly and the slopes (quantifying QT adaptation to HR) as well as the QT intervals at 100 beats/min for each intervention were compared by repeated-measures analysis of variance. RESULTS: As HR increased, QT was longer for isoproterenol in comparison to exercise or atropine, which were similar. The HR-QT slope (ms/beats/min) was less steep for isoproterenol (-0.83 +/- 0.53) than for atropine (-1.45 +/- 0.21) or exercise (-1.37 +/- 0.23) (p < 0.0001). In comparison to men, women had more negative HR-QT slopes during all interventions. At 100 beats/min, the QT was 364 ms during isoproterenol, which was significantly longer than that during exercise (330 ms) or atropine (339 ms) (p < 0.0001). Isoproterenol produced a dose-dependent increase in U-wave amplitude that was not observed during exercise or atropine. CONCLUSIONS: In comparison to exercise and atropine, isoproterenol is associated with much less QT shortening for a given increase in HR and, therefore, greater absolute QT intervals. Our findings demonstrate that autonomic conditions directly affect the ventricular myocardium of healthy subjects, causing differences in QT that are independent of HR.