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.
Amiodarone ; Atenolol ; Atrial Fibrillation ; Betaxolol ; Bisoprolol ; Compliance ; Cost-Benefit Analysis ; Diltiazem ; Flecainide ; Humans ; Insurance, Health ; Korea ; Markov Chains ; Mortality ; National Health Programs ; Propafenone ; Propranolol ; Quality-Adjusted Life Years ; Sotalol ; Verapamil

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.
Aging ; Asia ; Atrial Fibrillation* ; Calcium Channels ; Digoxin ; Guideline Adherence* ; Heart Diseases ; Humans ; Korea ; Prospective Studies* ; Public Health ; Sotalol ; Stroke ; Tertiary Care Centers

OBJECTIVEEctopic 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.

METHODA 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.

RESULTThe 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.

CONCLUSIONEAT 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.

Amiodarone ; Anti-Arrhythmia Agents ; Cardiomyopathies ; Catheter Ablation ; Child ; Child, Preschool ; Echocardiography ; Electrocardiography ; Humans ; Infant ; Retrospective Studies ; Sotalol ; Tachycardia, Ectopic Atrial ; drug therapy ; physiopathology ; Tachycardia, Supraventricular ; drug therapy ; Ventricular Function, Left

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.
Acyclovir ; Adenosine ; Administration, Intravenous ; Animals ; Child ; Electrocardiography ; Enterovirus ; Fever ; Foot ; Foot-and-Mouth Disease ; Glucocorticoids ; Hand ; Heart Rate ; Hospitalization ; Humans ; Immunoglobulins ; Infant ; Male ; Mouth ; Mouth Diseases ; Mucous Membrane ; Pharynx ; Physical Examination ; Skin ; Sotalol ; Tachycardia, Supraventricular ; Tachypnea ; Viruses ; Vomiting

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.
Arrhythmias, Cardiac ; Atrial Fibrillation ; Digoxin ; Electrocardiography ; Electrodes ; Heart ; Heart Rate ; Humans ; Infant, Newborn ; Propranolol ; Sotalol ; Tachycardia

Anti-Arrhythmia Agents ; therapeutic use ; Arrhythmias, Cardiac ; drug therapy ; Child ; Humans ; Sotalol ; therapeutic use

BACKGROUND AND OBJECTIVES: The action potential duration (APD) restitution kinetics has been known to play a crucial role in the initiation and maintenance of ventricular tachycardia (VT)/fibrillation (VF). We hypothesized that "the anti-arrhythmic and proarrhythmic effects of d,l-sotalol are mediated by changing the APD restitution (APDR) kinetics". MATERIALS AND METHODS: The purposes of this study were: 1) to assess the effects of d,l-sotalol on the APDR kinetics, and 2) to correlate the anti-arrhythmic and proarrhythmic action using the APDR kinetics. We recorded the transmembrane potentials (TMPs), using the microelectrode technique, in seven isolated perfused swine right ventricles, at the baseline, and with 1, 5, 10 and 20 mg/L of d,l-sotalol, with a washout period of 1 hour. The ventricular effective refractory periods (VERP), APD at 90% repolarization (APD90), spontaneous defibrillation rate and VF inducibility were measured at each concentration. We plotted APDR curves of S1-S2 pacing against VF, and calculated the maximal slopes (Smax) of the APDR. RESULTS: Sotalol (10 mg/L) prolonged the APD90 (p<0.001) by reducing the Smax of the APDR (by S1-S2 pacing, p<0.01; during VF, p<0.05). Accordingly, 41.7% of the VT/VF was terminated spontaneously, and VT/VF inducibility reduced from 91.1% at the baseline to 25% with 10 mg/L sotalol. A higher dose of sotalol (20 mg/L) increased the Smax, despite continuous prolongation of the VERP and APD90, resulting in the increase in the VT/VF inducibility (36.4%). CONCLUSION: Sotalol produces its anti-fibrillatory effect by APD prolongation in parallel with a flattening of the Smax at therapeutic doses. However, a higher concentration of sotalol increased the Smax and VF inducibility in isolated swine ventricular tissue.
Action Potentials* ; Heart Ventricles ; Kinetics* ; Membrane Potentials ; Microelectrodes ; Sotalol ; Swine ; Tachycardia, Ventricular ; Ventricular Fibrillation

OBJECTIVEAlthough 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.

METHODSThirty-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.

RESULTSSotalol 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.

CONCLUSIONSThese 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.

Adult ; Exercise ; physiology ; Exercise Test ; Female ; Heart ; drug effects ; physiopathology ; Heart Rate ; drug effects ; physiology ; Humans ; Male ; Sotalol ; pharmacology

OBJECTIVETo evaluate the effects of W-7, a calmodulin inhibitor, on transmural dispersion of repolarization (TDR), early after depolarization (EAD) and torsade de pointes (TdP) induction after administration of d-sotalol in isolated rabbit heart.

METHODSTdP was induced by d-sotalol (30 micromol/L), bradycardia, and hypokalemic (1.5 mmol/L)/hypomagnesaemic (0.35 mmol/L) solution in isolated female rabbit hearts. Thirty six rabbit hearts were divided into 4 groups (n = 9 each): d-sotalol alone, d-sotalol + W-7 (20 micromol/L), d-sotalol + W-7 (50 micromol/L), and d-sotalol + W-7 (100 micromol/L). Monophasic action potentials (MAPs) of the left ventricular epimyocardium (Epi), midmyocardium (M), and endomyocardium (Endo) were recorded simultaneously with ECG. The incidence of EAD and TdP were observed as well.

RESULTSTreatment with d-sotalol alone prolonged ventricular MAP duration and QT interval, increased TDR, and evoked high incidence of EAD (9/9) and spontaneous TdP (7/9) in hypokalemic/hypomagnesaemic solution in female rabbit heart. W-7 concentration-dependently decreased incidence of TdP (4/9 in 20 micromol/L; 2/9 in 50 micromol/L; 1/9 in 100 micromol/L). This effect of W-7 coincided with the decreased incidence of EAD (5/9 in 20 micromol/L; 4/9 in 50 micromol/L; 1/9 in 100 micromol/L). However, the d-sotalol-induced prolongation of QT interval and TDR was not significantly altered by W-7 at the three concentration used.

CONCLUSIONSIn isolated female rabbit hearts, calmodulin antagonist W-7 suppresses d-sotalol-induced TdP without altering TDR but does suppress EAD. The effects observed with W-7 also suggest a possible important role for calmodulin-activated enzymes in the induction of TdP.

Animals ; Calmodulin ; antagonists & inhibitors ; Enzyme Inhibitors ; therapeutic use ; Female ; In Vitro Techniques ; Rabbits ; Sotalol ; adverse effects ; Sulfonamides ; therapeutic use ; Torsades de Pointes ; chemically induced ; prevention & control

BACKGROUNDTorsade de pointes (TdP) is a form of polymorphic ventricular tachycardia featuring prolonged QT intervals. Female gender is associated with an increased risk of TdP. However, the causes of the sex difference in risk are poorly understood. Recently, transmural dispersion of repolarization (TDR) has been implicated in the genesis of TdP. Consequently, we compared TdP incidence and TDR between male and female rabbit hearts in order to investigate the mechanism of sex difference in TdP risk in rabbits in vitro.

METHODSBy means of monophasic action potential recording techniques, the monophasic action potential of the epicardium, midmyocardium, and endocardium were simultaneously recorded using specially designed plunge-needle electrodes placed across the left ventricular free wall of both female (n = 8) and male (n = 8) rabbit hearts purfused by the Langendorff method. TdP was induced by bradycardia, d-sotalol, and low-K+, Mg2+ Tyrode solution.

RESULTSTDR measurements in all three myocardial layers of male and female rabbit hearts were (18 +/- 2) ms and (21 +/- 2) ms, respectively (n = 8, P > 0.05). After perfusion with d-sotalol, the 90% monophasic action potential duration was prolonged in both male and female rabbits. TDR in male and female rabbit hearts increased to (29 +/- 2) ms and (61 +/- 2) ms, respectively, a difference that is significant. Eight female rabbit hearts had early afterdepolarization and 7 of them developed TdP. Seven male rabbit hearts had early after depolarization, but only one of these hearts developed TdP.

CONCLUSIONGreater TDR may play an important role in the higher incidence of TdP in female rabbit hearts.

Action Potentials ; Animals ; Electrocardiography ; Female ; Male ; Rabbits ; Risk ; Sex Characteristics ; Sotalol ; Torsades de Pointes ; etiology ; physiopathology