Cost-Effectiveness of Rate- and Rhythm-Control Drugs for Treating Atrial Fibrillation in Korea

PURPOSE: Although the economic and mortality burden of atrial fibrillation (AF) is substantial, it remains unclear which treatment strategies for rate and rhythm control are most cost-effective. Consequently, economic factors can play an adjunctive role in guiding treatment selection. MATERIALS AND METHODS: We built a Markov chain Monte Carlo model using the Korean Health Insurance Review & Assessment Service database. Drugs for rate control and rhythm control in AF were analyzed. Cost-effective therapies were selected using a cost-effectiveness ratio, calculated by net cost and quality-adjusted life years (QALY). RESULTS: In the National Health Insurance Service data, 268149 patients with prevalent AF (age ≥18 years) were identified between January 1, 2013 and December 31, 2015. Among them, 212459 and 55690 patients were taking drugs for rate and rhythm control, respectively. Atenolol cost $714/QALY. Among the rate-control medications, the cost of propranolol was lowest at $487/QALY, while that of carvedilol was highest at $1363/QALY. Among the rhythm-control medications, the cost of pilsicainide was lowest at $638/QALY, while that of amiodarone was highest at $986/QALY. Flecainide and propafenone cost $834 and $830/QALY, respectively. The cost-effectiveness threshold of all drugs was lower than $30000/QALY. Compared with atenolol, the rate-control drugs propranolol, betaxolol, bevantolol, bisoprolol, diltiazem, and verapamil, as well as the rhythm-control drugs sotalol, pilsicainide, flecainide, propafenone, and dronedarone, showed better incremental cost-effectiveness ratios. CONCLUSION: Propranolol and pilsicainide appear to be cost-effective in patients with AF in Korea assuming that drug usage or compliance is the same.

Medidas profiláticas para fibrilação atrial no pós-operatório de cirurgia cardíaca / Prevention of atrial fibrillation after cardiac surgery

A fibrilação atrial é a arritmia mais frequentemente encontrada após cirurgia cardíaca. Embora geralmente autolimitada, representa um importante preditor de aumento de morbimortalidade e de custos aos sistemas de saúde. Numerosos estudos tentaram determinar os mecanismos associados à fibrilação atrial no pós-operatório com resultados variados. Uma fisiopatologia multifatorial é sugerida, sendo o processo inflamatório e a ativação simpática adrenérgica do período pós-operatório reconhecidos como importantes fatores de contribuição. O tratamento é dificultado pela escassez de dados relativos aos resultados de diferentes intervenções terapêuticas nessa população. Este artigo analisa a literatura cujo foco sejam as intervenções para prevenir a fibrilação atrial no pós-operatório

Atrial fibrillation is the most commonly found arrhythmia after cardiac surgery. Although usually self-limiting, it represents an important predictor of increased patient morbidity, mortality, and health care costs. Numerous studies have attempted to determine the underlying mechanisms of postoperative atrial fibrillation with different results. A multifactorial pathophysiology is suggested, with inflammation and postoperative adrenergic activation recognized as important contributing factors. The management is complicated by a lack of data on the outcomes of different therapeutic interventions in this population. This article reviews the literature focusing on interventions to prevent postoperative atrial fibrillation

A Prospective Survey of Atrial Fibrillation Management for Real-world Guideline Adherence: COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) Registry

BACKGROUND AND OBJECTIVES: The aging population is rapidly increasing, and atrial fibrillation (AF) is becoming a significant public health burden in Asia, including Korea. This study evaluated current treatment patterns and guideline adherence of AF treatment. METHODS: In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were consecutively enrolled between June 2016 and April 2017 from 10 tertiary hospitals in Korea. RESULTS: The AF type was paroxysmal, persistent, and permanent in 65.3%, 30.0%, and 2.9% of patients, respectively. Underlying structural heart disease was present in 11.9%. Mean CHA2DS2-VASc was 2.7±1.7. Oral anticoagulation (OAC), rate control, and rhythm control were used in 70.1%, 53.9%, and 54.4% of patients, respectively. OAC was performed in 82.7% of patients with a high stroke risk. However, antithrombotic therapy was inadequately used in 53.4% of patients with a low stroke risk. For rate control in 192 patients with low ejection fraction (< 40%), β-blocker (65.6%), digoxin (5.2%), or both (19.3%) were adequately used in 90.1% of patients; however, a calcium channel blocker was inadequately used in 9.9%. A rhythm control strategy was chosen in 54.4% of patients. The prescribing rate of class Ic antiarrythmics, dronedarone, and sotalol was 16.9% of patients with low ejection fraction. CONCLUSION: This study shows how successfully guidelines can be applied in the real world. The nonadherence rate was 17.2%, 9.9%, and 22.4% for stroke prevention, rate control, and rhythm control, respectively.

Abordagem das arritmias na Doença de Chagas Crônica / Approach of arrhythmias in chronic Chagas Disease

As arritmias na cardiopatia chagásica (CCH) são responsáveis por incapacitação física e morte em indivíduos adultos em faixa etária precoce e produtiva, decorrendo daí a necessidade de sua abordagem criteriosa e, às vezes, mais agressiva para se obter controle completo. As arritmias cardíacas mais encontradas na CCH são as bradiarritmias e as taquicardias. Entre as bradicardias estão as alterações sinoatriais e os bloqueios atrioventriculares, cujo tratamento padrão é o emprego de implante de marcapasso definitivo. Entre as taquiarritmias, encontram-se as supraventriculares ­ extrassístoles atriais, taquicardia atrial ectópica, "flutter" atrial e fibrilação atrial ­ que provocam morbidades como progressão para disfunção ventricular esquerda e fenômenos tromboembólicos, e as ventriculares, cujo desfecho pode ser a morte súbita instantânea. A abordagem deve ser, inicialmente, por meio de eletrocardiograma de 12 derivações, pela gravação ambulatorial (Holter), ecocardiograma, teste ergométrico, e por fim, o estudo eletrofisiológico e a ressonância nuclear magnética. O tratamento farmacológico pode ser conduzido com o uso dos fármacos existentes em nosso mercado, como amiodarona, propafenona e sotalol. O tratamento invasivo, pode consistir em ablação por cateter, embora com resultados ainda abaixo de índices confortadores, devido à possibilidade de recidivas. O uso de cardiodesfibrilador implantável é a última alternativa, que também tem suas limitações

Arrhythmias in Chagas cardiomyopathy (CCM) are responsible for physical disability and death in adults in early and productive age group, from which arises the need for a judicious and sometimes more aggressive approach to achieve the complete control. The arrhythmias most common in CCM are bradyarrhythmias and tachycardias. Among the bradycardias are the sinoatrial changes and atrioventricular blocks, whose standard treatment is the use of permanent pacemaker implantation. Among tachyarrhythmias are the supraventricular ones - atrial extrasystoles, ectopic atrial tachycardia, atrial flutter and atrial fibrillation - causing morbidity and progression of left ventricular dysfunction and thromboembolic events, and the ventricular ones, whose outcome can be the instantaneous sudden death. The approach should be initially through 12-lead electrocardiogram, by ambulatory ECG recording (Holter), echocardiogram, stress testing, and finally the electrophysiological study and magnetic resonance imaging. Pharmacological treatment can be conducted with the use of marketed drugs such as amiodarone, propafenone and sotalol. The invasive treatment may consist of catheter ablation, although the results are still below comforting rates due to the possibility of recurrence. The use of implantable cardioverter defibrillator is the last alternative, which also has its limitations

Arritmias genéticas: como investigar e como tratar? / Inherited arrhythmias: how to investigate and how to treat?

As arritmias hereditárias são responsáveis por uma proporção significante de mortes cardíacas súbitas em indivíduos jovens aparentemente saudáveis. As canalopatias, como síndrome de Brugada, síndrome do QT longo/curto e taquicardia ventricular polimórfica catecolaminérgica, contribuem com essa incidência e não são marcadas por anomalias estruturais. A cardiomiopatia genética, como cardiomiopatia arritmogênica doventrículo direito e cardiomiopatia hipertrófica, também são causas de morte súbita por arritmia. Novos consensos têm sido publicados para orientar melhor as ferramentas dediagnóstico, os escores de estratificação e o tratamento. Os testes genéticos têm papel importante no diagnóstico, na estratificação de risco e no tratamento de pacientes e de suas famílias. Os avanços da genética molecular nas duas últimas décadas revelaram a base genética subjacente da doença, e podem levar a tratamentos mais personalizados...

Inherited arrhythmias account for a significant proportion of sudden cardiac deaths in apparently healthy and young individuals. Ion channelopathies such as Brugada syndrome, long/short QT syndrome and catecholaminergic polymorphic ventricular tachycardiacontribute to this incidence and are marked by no structural abnormalities. Genetic cardiomyopathy such as Right Ventricular Arrhythmogenic Cardiomyopathy and HypertrophicCardiomyopathy are also causes of arrhythmogenic sudden death. New consensuses are published to better guide the diagnostic tools, stratification scores and treatment. Genetic testing plays somehow an important role in the diagnosis, risk-stratification and treatment of patients and family members. Molecular genetic advances in the last 2 decades have revealed the underlying genetic basis and these may lead to a personalized medicine...

Quais as medicações antiarrítmicas indicadas para o tratamento da taquicardia ventricular no paciente com cardiopatia estrutural? / Which antiarrhythmic drugs are indicated for the management of ventricular tachycardia in patients with structural heart disease?

As taquicardias ventriculares são as arritmias cardíacas com maior potencial de instabilidade clínica e mortalidade cardíaca. Embora possam ocorrer no contexto de pacientes sem cardiopatia estrutural demonstrável, quase sempre ocorrem em coração estruturalmente alterado, com substrato anatômico para reentradas. As alterações cardíacas podem ser isquêmicas e não isquêmica. A distinção entre as etiologias é importante por terem diferentes mecanismos e origens de taquicardia ventricular, que irá determinar a escolha do tratamento adequado das arritmias ventriculares e prevenção de morte súbita. Os principais objetivos no manejo destes pacientes são: a reversão imediata da taquicardia, a prevençãode recorrências e a redução da mortalidade cardiovascular. Atualmente os fármacos com eficácia e perfil de segurança mais utilizados para tratamento de taquicardia ventricular em pacientes com cardiopatia estrutural são os betabloqueadores, amiodarona e sotalol. Com exceção dos betabloqueadores, os antiarrítmicos não possuem a eficácia em manejo primário ou na prevenção de morte súbita demonstrada em estudos clínicos randomizados atuais de forma consistente. Em portadores de cardiodesfibrilador implantável, os antiarrítmicos podem atuar na supressão das taquicardias ventriculares não sustentadas e sustentadas, na lentificação das taquicardias ventriculares com intuito de facilitar a reversão por antitachycardia pacing e prevenir sincopes, além de controlas as taquicardias supraventriculares. Devido aos efeitos colaterais e potencial efeito pró-arrítmico, devem ser utilizados com precaução e com controle adequado...

Ventricular tachycardia is the cardiac arrhythmia with the most potential to result in clinical instability and cardiac mortality. Although it can occur in patients without structural heart disease, it tends to occur where there is underlying heart disease, with anatomical substrate for reentry. It can be subdivided into ischemic and non-ischemic. This is an important distinction, because the mechanisms and origins of ventricular tachycardia may differ between the two, which will determine the choice of treatment for the ventricular arrhythmia and help prevent sudden death. The objective in clinical management of these patients includes: immediate reversal of tachycardia, prevention of relapses, and reducing cardiovascular mortality. The beta-blockers amiodarone and sotalol are currently the most commonly used antiarrhythmic agents, with the best efficacy and safety profile for treating ventricular tachycardia in patients with structural heart disease. With the exception of beta-blockers, currently available antiarrhythmic drugs have not been shown, in randomized clinical trials, to be effective in the primary management of patients with life-threatening ventricular arrhythmias or in the prevention of sudden cardiac death. Inpatients with implantable cardioverter-defibrillators, the potential beneficial effects of antiarrhythmic drugs may be the suppression of non-sustained and sustained ventricular tachycardias, slowing of ventricular tachycardia rate to facilitate pace termination or prevent syncope, and control of atrial tachyarrhythmias. Due to potential adverse effects of antiarrhythmic drugs and the risk of proarrhythmia, close monitoring of the patient is recommended...

Clinical course and treatment of ectopic atrial tachycardia in 144 children / 中华儿科杂志

<p><b>OBJECTIVE</b>Ectopic atrial tachycardia (EAT) is a common type of supraventricular tachycardia in pediatric population, and it can be resistant to antiarrhythmic drugs and lead to tachycardia induced cardiomyopathy (TIC) if not properly managed. This study assessed the clinical course and response to treatment of EAT in children.</p><p><b>METHOD</b>A retrospective review included 144 children at the First Hospital of Tsinghua University diagnosed with EAT from January 2009 to April 2014. The clinical detailed history, 12 lead ECG, 24-h Holter recording, echocardiography, response to therapy and follow-up were analyzed.</p><p><b>RESULT</b>The onset of EAT occurred at any age with a distribution with positive skewness, 57 children ≤1 years, 22 children > 1 - 3 years, 25 children > 3 - 6 years and 40 children ≥ 6 years of age. The percentages of the three tachycardia types were 36. 1% (n = 52) for incessant EAT, 52. 8% (n = 76) for paroxysmal EAT and 11. 1% (n = 16) for sporadic EAT, respectively. There were 115 patients received drug therapy in our hospital and in 72 cases the EAT was completely controlled. Antiarrhythmic therapy had been discontinued in 35 children with complete control. Normal sinus rhythm was observed by telemetry or Holter within 4 to 90 days and the mean duration of medical therapy was 310 days (range 15 to 608 days) in these children. The combination of sotalol and propafenone showed better effectiveness for control of children with EAT (54%, 41/76), compared with single sotalol (36%, 24/66) and the combination of amiodarone and metoprolol (30%, 7/23) (χ2 = 6. 296, P = 0. 043). Tachycardia type was able to predict the response to antiarrhythmic drugs for children with EAT, sporadic tachycardia had best control rate on pharmacological therapy compared with paroxysmal tachycardia and incessant tachycardia (94% (15/16) vs. 67% (42/63) vs. 42% (15/36), χ2 = 17. 925, P = 0. 000) . Acute success of radiofrequency ablation (RFA) in children who showed poor response to antiarrhythmic drugs was achieved in 45 of 49 (92%), ultimate success was achieved in 33 of 49 (67%). The incidence of TIC secondary to EAT was 18. 1% (n =26), and left ventricular ejection-fraction (LVEF) returned to normal in 23 children after successful control of EAT ((61 ± 4) % vs. (43 ± 5) %, t = - 10. 036, P = 0. 000). Side effects including abnormal thyroid function (in 3) and abnormal liver function (in 1) occurred in 4 (17%) of 23 children who received amiodarone and disappeared when amiodarone was discontinued.</p><p><b>CONCLUSION</b>EAT in children predominantly occurred in young infants and children. Incessant EAT comprised a great percentage. The combination of sotalol and propafenone provided the best results for control of children with EAT. RFA should be considered as a preferred treatment for older children who displayed poor response to medical therapy.</p>

Sotalol: A rescue drug in the face of life-threatening refractory ventricular tachycardia.

We describe postoperative refractory ventricular tachycardia (VT) in a patient following aortic and mitral valve replacement. Following an uneventful separation from cardiopulmonary bypass with dobutamine, the patient developed recurrent VT, 4 hours into the postoperative period. The VT did not respond to standard doses of xylocard, magnesium and amiodarone. Electrolyte and acid base parameters were normal. Multiple cardioversions failed to revert back to a stable rhythm. Intra‑aortic balloon pumping was instituted and overdrive right ventricular pacing was unsuccessful. Following intravenous sotalol 80 mg, the VT came under control and reverted to a nodal rhythm, which required atrial pacing for the next 8 hours. Oral sotalol therapy was continued at 40 mg daily. The VT did not recur.

Paroxysmal Supraventricular Tachycardia in an Infant with Hand, Foot, and Mouth Disease

An 11-month-old male infant was admitted to our hospital with fever, fussiness, poor feeding, vomiting, and tachypnea for two days prior. Physical examination revealed sporadic papules and vesicles occurring on his hands, feet, face, and perianal mucosa. Enterovirus 71 was identified from both throat swab and vesicle fluid using virus isolation techniques. The patient's heart rate fluctuated in a very narrow range from 180~210/beats/min regardless of his physiologic state. An electrocardiogram showed P-waves buried within or occurring just after regular, narrow, QRS complexes. The patient was diagnosed as having hand, foot, and mouth disease in combination with paroxysmal supraventricular tachycardia (PSVT). The child recovered well with symptomatic treatment, including intravenous administration of acyclovir, glucocorticoids, immunoglobulin, adenosine, and sotalol. PSVT was terminated within 36 hours of hospitalization. The skin lesions became crusted on the third day, and then proceeded to heal spontaneously. Here we report on this unusual case and review the associated literature.

Prenatal management with digoxin and sotalol combination for fetal supraventricular tachycardia : Case report and review of literature.

Sustained fetal supraventricular tachycardia (SVT) with a heart rate of approximately 210 bpm may lead to increased atrial and venous pressures and congestive heart failure. There is no clear consensus regarding the best drug-treatment regimens for fetal SVT. However, considerable nonrandomized experience in the transmaternal treatment of fetal SVT is available with a number of antiarrhythmic agents. We report a case of fetal supraventricular tachyarrhythmia with hydrops detected at 32 weeks that was managed with combination of oral digoxin and sotalol and review management guidelines available in the literature.

Effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes.</p><p><b>METHODS</b>Healthy rabbits (1.6-1.8 kg) were treated with amiodarone (80 mg x kg(-1) x d(-1)) for four weeks. Action potential duration (APD) was recorded under isolated arterially perfused left ventricular wedge preparation, then single myocytes were isolated using enzyme digestion. L-type calcium current recovery (time constant, tau) were determined by fitting data with monoexponential. Tau/APD90 were compared in cells treated with saline, amiodarone and sotalol (3 x 10(-5) mmol/L).</p><p><b>RESULTS</b>In chronic amiodarone treated myocytes, tau [(164 +/- 8) ms vs. (98 +/- 8) ms, P<0.05], APD90 [(321 +/- 12) ms vs. (220 +/- 10) ms, P<0.05] and tau/APD90 (0.51 +/- 0.03 vs. 0.44 +/- 0.03, P<0.05) were significantly increased than those in control myocytes. Sotalol significantly increased tau [(128 +/- 7) ms vs. (98 +/- 8) ms, P<0.05] and ADP90 [(405 +/- 13) ms vs. (220 +/- 10) ms, P<0.05] while reduced the tau/APD90 (0.32 +/- 0.05 vs. 0.44 +/- 0.03, P<0.05) compared to control myocytes.</p><p><b>CONCLUSION</b>The differential effect of amiodarone and sotalol on ventricular myocytes tau/APD90 ratio might be responsible for the safety profile of these two drugs.</p>

Multifocal Atrial Tachycardia in a Newborn

Multifocal atrial tachycardia (MAT) is a rare arrhythmia in the newborn. MAT can be difficult to diagnose; it is frequently confused with atrial fibrillation. MAT is difficult to treat but often resolves spontaneously within the first year of life. A newborn with a rapid and irregular pulse rate was diagnosed with multifocal atrial tachycardia by eletrocardiography (ECG) using a hand-made transesophageal electrode. Treatment with propranolol was attempted but ineffective. Treatment with digoxin and sotalol was attempted. The heart rhythm gradually reverted to a sinus rhythm with this treatment. We report our experience managing a neonate with MAT diagnosed by ECG using a hand-made transesophageal electrode.

Arritmias en el embarazo: cómo y cuándo tratar? / Arrhythmias in pregnancy: how and when to treat?

Cardiac arrhythmias can develop during pregnancy. The risk of arrhythmias is relatively higher during labor and delivery. Potential factors that can promote arrhythmias in pregnancy or during labor and delivery, include the direct cardiac electrophysiological effects of hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia, and underlying heart disease. In this review, the basis for treatment of supraventricular and ventricular tachycardias are described. No drug therapy is usually needed for the management of supraventricular or ventricular premature beats, but potential stimulants, such as smoking, caffeine, and alcohol should be eliminated. In paroxysmal supraventricular tachycardia, vagal stimulation maneuvers should be attempted first. In pregnant women with atrial fibrillation, the goal of treatment is conversion to sinus rhythm by electrical cardioversion. Rate control can be achieved by a cardioselective beta-adrenergic blocker drug and/ or digoxin. Ventricular arrhythmias may occur in the pregnant women, specially when cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse exists. Electrical cardioversion or treatment with sotalol may be used (amiodarone is not safe for the fetus). Finally, in women with congenital long QT syndrome, beta-blocker therapy must be continued during pregnancy and postpartum period.

Antiarrhythmic drugs: present and future.

The treatment of cardiac arrhythmias has undergone a sea change with the advent of catheter ablative procedures (radiofrequency ablation) and use of implantable cardioverter defibrillator (ICD). The antiarrhythmic drugs at times are used to prevent device related arrhythmia rather than being used for primary treatment of arrhythmias. Antiarrhythmic drugs are grouped according to their drug action as proposed by Vaughan William or by their action on ion channels. Currently amiodarone is the most commonly used drug followed by sotalol, class II, class IV and other class III drugs. It is now well known that amiodarone has several non-cardiac toxic effects particularly on long term therapy. Efforts are on to develop newer drugs which have efficacy of amiodarone without complex pharmacokinetics and toxicity. Newer drugs like azimilide with class III action are also being developed.

Propanolol: una alternativa cercana para el tratamiento de la taquicardia supraventricular del feto / Propanolol: a close alternative for the treatment of fetal supraventricular tachycardia

Las taquiarritmias son las alteraciones del ritmo cardiaco más comunes en el feto que pueden generar complicaciones fatales. En general, se recomienda tratamiento cuando son persistentes. Los medicamentos más usados para el tratamiento de esta arritmia en los fetos son digoxina, flecainida, sotalol y amiodarona. Si bien son efectivos, su aplicación en los fetos se fundamenta en las características mecánicas y no electrofisiológicas, con riesgo de generar arritmias fatales o de más difícil control. El fenómeno pro-arritmogénico y los efectos secundarios, comprometen también a las gestantes. La hipotensión y arritmias como el flutter auricular, exigen una vigilancia comprometida. Es importante considerar un medicamento más seguro que pueda ser útil en las formas más simples y comunes de taquiarritmias del feto...

Tachyarrhythmias are common alterations of cardiac rhythm in the fetus that may generate fatal complications. In general, when they are persistent, treatment is advised. The more used drugs for the treatment of this arrhythmia in fetuses are digoxin, flecainide, sotalol and amiodarone. Even though they are effective, its use in fetuses is based on mechanical and not in electrophysiological characteristics, with the risk of generating fatal arrhythmias or some of more difficult control. The pro-arrhythmogenic phenomenon and the secondary effects involve also the pregnant women. Hypotension and arrhythmias such as auricular flutter demand a compromised vigilance. It is important to consider a safer drug that may be useful in the simpler and more common forms of fetal tachyarrhythmias. Objetivo: to show by means of a clinical case and by revision of relevant articles, that propanolol can be part of the group of drugs for the treatment of fetal supraventricular tachycardia. A series of alternatives have been imposed with adequate results; nevertheless, these are exigent in its knowledge and control and definitely not exempt of risks. Our objective is to show that propanolol is still an alternative for specific cases of tachyarrhythmias in fetuses, isolated or combined with other drugs.

The effects of sotalol on ventricular repolarization during exercise / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>Although after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise.</p><p><b>METHODS</b>Thirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo.</p><p><b>RESULTS</b>Sotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo.</p><p><b>CONCLUSIONS</b>These results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.</p>