Ivabradine in a 15-day-old male neonate with refractory focal atrial tachycardia.

Ivabradine is used to reduce heart rate in children with chronic heart failure and dilated cardiomyopathy, it has recently been used off-label to treat tachyarrhythmias such as ectopic atrial tachycardia and junctional ectopic tachycardia (JET) in children. We report a successful ivabradine experience in a male neonate with refractory focal atrial tachycardia (FAT).

Successful treatment of the focal ectopic atrial tachycardia in an infant with a single dose of ivabradin.

We report on a 12-month-old boy with an ectopic atrial tachycardia successfully treated with the ivabradine that acts on cardiac pacemaker cells by selectively inhibiting the If channel. The patient was diagnosed with supraventricular tachycardia in another centre, and multi-drug therapy was unsuccessful to restore sinus ryhthm, so he was sent to our hospital for catheter ablation. We stopped the medications the patient was taking and started using ivabradine. Sinus rhythm was restored 2 hours after ivabradine treatment was started.

Ivabradine as a stabilising anti-arrhythmic agent for multifocal atrial tachycardia.

Multifocal atrial tachycardia has certain electrocardiographic similarities to atrial fibrillation. The mechanism of atrial fibrillation is heterogenous but in some cases may arise from a single ectopic driver with fibrillatory conduction to the rest of the atria. This has led to the speculation that multifocal atrial tachycardia may have a similar mechanistic unifocal site that disperses through the atrium in a fibrillatory pattern. Ivabradine has been reported to be efficacious in an adult with paroxysmal atrial fibrillation as well as in children with junctional or ectopic atrial tachycardias. This is the first report of successfully using ivabradine, a novel anti-arrhythmic If blocking agent, to convert multifocal atrial tachycardia in a 5-month-old critically ill infant to a pattern indicating a single ectopic atrial focus. This allowed the patient's single atrial focus to be ablated with return to sinus rhythm and decannulation from ventriculoarterial extracorporeal membrane oxygenation. This case suggests that multifocal atrial tachycardia may arise from a single automatic focus with downstream fibrillatory conduction to the atria.

Severe congenital RYR1-associated myopathy complicated with atrial tachycardia and sinus node dysfunction: a case report.

BACKGROUND: Cardiac arrhythmias are sometimes encountered in patients with hereditary myopathies and muscular dystrophies. Description of arrhythmias in myopathies and muscular dystrophies is very important, because arrhythmias have a strong impact on the outcomes for these patients and are potentially treatable. CASE PRESENTATION: A girl with severe congenital RYR1-related myopathy exhibited atrial tachycardia and sinus node dysfunction during infancy. She was born after uncomplicated caesarian delivery. She showed no breathing, complete ophthalmoplegia, complete bulbar paralysis, complete facial muscle paralysis, and extreme floppiness. At 5 months old, she developed persistent tachycardia around 200-210 beats per minutes. Holter monitoring revealed ectopic atrial tachycardia during tachyarrhythmia and occasional sinus pauses with junctional escape beats. Propranolol effectively alleviated tachyarrhythmia but was discontinued due to increased frequency and duration of the sinus pauses that led to bradyarrhythmia. There was no evidence of structural heart diseases or heart failure. The arrhythmia gradually resolved spontaneously and at 11 months old, she showed complete sinus rhythm. CONCLUSIONS: Although supraventricular arrhythmia is sometimes encountered in congenital myopathies, this is the first report of cardiac arrhythmia requiring drug intervention in RYR1-associated myopathy.

Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients.

Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first-line supraventricular tachycardia anti-arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti-arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4-month-old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.

Efficacy of Intravenous Sotalol for Treatment of Incessant Tachyarrhythmias in Children.

Our objective was to evaluate the efficacy and safety of intravenous (IV) sotalol in the treatment of incessant tachyarrhythmias in children with normal cardiac function. Eighty-three children admitted to hospital from October 2011 to December 2014 were treated with IV sotalol or IV sotalol plus IV propafenone. The time to conversion to sinus rhythm and maintaining sinus rhythm were evaluated. Blood pressure, heart rate, QTc, PR intervals, and rhythm were monitored; 50 patients (60%) were converted to sinus rhythm with IV sotalol; time to conversion was 12.0 ± 18.0 hours; 12 additional patients (15%) were converted with IV sotalol combined with IV propafenone; time to conversion was 13.1 ± 17.6 hours. A total of 62 patients (75%) were converted. Success rates of IV sotalol for different tachycardias were similar, whereas the time to conversion differed. The time to conversion for atrioventricular reentrant tachycardia was shorter than atrial tachycardia or atrial flutter (p <0.05). QTc prolongation (from 253 to 486 ms and from 398 ms to 500 ms) was seen in 2 patients (2%) within 48 hours after conversion. The QTc reverted to normal range at 48 and 144 hours, respectively, after withdrawal of IV sotalol. A 1 month old with atrial flutter developed bradycardia (7:1 atrioventricular conduction) 5 minutes after IV sotalol, and heart rate increased gradually after drug withdrawal. No other adverse effects were observed. In conclusion, IV sotalol can be safely and effectively used to terminate pediatric tachycardias in patients with normal cardiac function. No proarrhythmic or significant toxicities were detected. Close monitoring of QTc and heart rate is required after IV sotalol. Adding IV propafenone to IV sotalol in resistant cases enhance conversion.

Successful use of sirolimus for refractory atrial ectopic tachycardia in a child with cardiac rhabdomyoma.

Cardiac rhabdomyomas are common in tuberous sclerosis. We report a child who developed rhabdomyoma related arrhythmia refractory to antiarrhythmic drug therapy. Reversion of the atrial ectopic tachycardia was achieved with mammalian target of rapamycin pathway (mTOR) inhibitor sirolimus. As per our knowledge, this is the first time that sirolimus has been successfully used in this setting.

Predictors of Pharmacological Therapy of Ectopic Atrial Tachycardia in Children.

Ectopic atrial tachycardia (EAT) is a relatively common type of supraventricular tachycardia in the pediatric population, and it can be resistant to antiarrhythmic drugs and lead to tachycardia-induced cardiomyopathy (TIC) if not properly managed. The purpose of this study was to determine the predictors of the response to pharmacological therapy in children with EAT. From January 2009 to April 2014, 115 children were admitted to our hospital with a diagnosis of EAT and placed on antiarrhythmic drugs. We examined the clinical history, response to therapy, and follow-up of the children. The incidence of TIC secondary to EAT was 22.6% (n = 26) in children. Incessant EAT accounted for 44.3% of all patients. Control of EAT with antiarrhythmic therapy was achieved in 73.9% (n = 85) of the children. The combination of sotalol and propafenone performed well in controlling EAT in children [complete control in 35 (49.3%) of 71]. The mean time of conversion to sinus rhythm was 24 days, and the mean duration of therapy was 11 months in children with resolution. Multivariate predictors of the control of EAT were age at presentation (OR 0.289, P = 0.038) and tachycardia type (OR 0.276, P = 0.006). TIC occurs in 22.6% of children with EAT. Incessant EAT is more frequently complicated by TIC. Independent factors associated with a good response to pharmacological therapy include a younger age at presentation and non-incessant tachycardia in children with EAT.

[Perinatal Presentation and Complicated Course of a Multifocal Atrial Tachycardia]. / Polymorphes und komplexes klinisches Bild einer multifokal-ektopen Vorhoftachykardie mit perinataler Manifestation.

We report a male newborn who became symptomatic with supraventricular tachycardia on the first day of life. Neither adenosine nor electric cardioversion could terminate the tachycardia, therefore intravenous esmolol (ß-receptor blocker) was initiated. Inspite of subsequent administration of various antiarrhythmic medications in increasingly higher doses, repeated supraventricular tachycardic episodes occurred. The electrocardiogram showed typical findings of a multifocal atrial tachycardia as the underlying cause. When tachycardic episodes occurred, they also presented as atrial flutter at 460 bpm and a 2:1 block. Finally, high dosage of amiodarone (10 mg/kgbw/d) led to continuous control of the heart rate without tachycardic episodes. To date our patient is mostly in sinus rhythm but without tachycardic episodes and doing well.

[Clinical course and treatment of ectopic atrial tachycardia in 144 children].

OBJECTIVE: 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. METHOD: 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. RESULT: 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. CONCLUSION: 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.

Utility of Routine Exercise Testing to Detect Rate-Related QRS Widening in Patients Without Structural Heart Disease on Class Ic Antiarrhythmic Agents (Flecainide and Propafenone).

Class Ic antiarrhythmic agents are effective in the treatment of various atrial tachyarrhythmias. They are known to cause rate-related QRS widening in the presence of structural heart disease, which can lead to life-threatening arrhythmias. The role of routine exercise electrocardiography in patients without structural heart disease is unknown. All patients initiated on class Ic antiarrhythmic agents and who had exercise electrocardiography performed from June 2009 to June 2013 were included. Symptom-limited treadmill electrocardiography was performed to detect significant QRS widening at peak exercise (defined as an increase of >25% of baseline QRS). Fifty-six patients were included in the study. All patients were screened for structural heart disease before initiation of the medication. Significant QRS widening and atrial tachycardia occurred in a single patient, which terminated with cessation of exercise. This patient had a history of tachycardia-mediated cardiomyopathy with normalization of ejection fraction 3 years before being placed on flecainide. In conclusion, routine exercise testing to detect QRS widening is not warranted in patients with no structural heart disease.

A case of atrial tachycardia treated with ivabradine as bridge to ablation.

Ivabradine is indicated in cardiac failure and ischemia to reduce sinus rate by inhibition of the pacemaker I(f) current in sinoatrial node. We report a case of an 18-year-old woman with left atrial tachyarrhythmia resistant to several antiarrhythmic drugs and to electric cardioversion who responded only to ivabradine, which significantly reduced heart rate without abolishing the arrhythmia itself. An ectopic focus in the ostium of left pulmonary veins was found and the patient was successfully ablated. We suggest that ivabradine might be therefore useful in the treatment of supraventricular tachyarrhythmias due to an enhanced automaticity.

Efficiency of individual dosage of digoxin with calculated concentration.

BACKGROUND: Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4-1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8-2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC. METHODS: The study subjects comprised 72 patients with cardiac failure or/and atrial tachyarrhythmia seen at our hospital from January 2012 to December 2013. The patients were divided into five groups according to Kidney Diseases Outcome Quality Initiative guidelines. SDCs were measured using the Abbott Architect i1000 immunology analyzer. The correlations between measured SDCs and calculated SDCs and between clearance of digoxin and creatinine clearance rate were assessed retrospectively. RESULTS: The correlation between measured and predicted SDC calculated by the Konishi equation was significant (r=0.655, P<0.001) for the 72 patients overall; however, correlations within the different stages of renal function were nonsignificant, with a correlation found only in patients with stage 3 (30 mL per minute < creatinine clearance <60 mL per minute). With regard to the correlation between clearance of digoxin and creatinine clearance, our results show that although there was a significant correlation between clearance of digoxin and creatinine clearance in the group overall, correlations were not evident within the different stages of renal function. CONCLUSION: The results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease. Further research in larger numbers of patients across all stages of renal function will be required in the future to verify the original Konishi model.

Unifying mechanism of sustained idiopathic atrial and ventricular annular tachycardia.

BACKGROUND: Based on the current understanding of cardiac conduction system development and the observation that arrhythmogenic foci can originate in areas near the atrioventricular annuli, we hypothesized that focal annular tachycardias, whether atrial or ventricular, share a common mechanism. We, therefore, prospectively evaluated this hypothesis in patients with sustained atrial and ventricular tachycardia originating from the peri-tricuspid and mitral annuli. METHODS AND RESULTS: Forty-nine consecutive patients with sustained, focal annular tachycardia comprised the study group. All underwent electrophysiological evaluation and the mode of tachycardia initiation, termination, sensitivity to catecholamine infusion, and response to adenosine/verapamil were evaluated. Electroanatomical activation maps identified the sites of arrhythmia origin. Tachycardias could be initiated or terminated or both with programmed stimulation in 46 of 46 patients and most (70%) were catecholamine facilitated. Of the 9 patients with sustained annular ventricular tachycardia, 3 were localized to the tricuspid annulus, and 6 to the mitral annulus. All the 9 ventricular tachycardias (100%) terminated with adenosine, 2 of 2 terminated with verapamil, and 2 of 2 terminated with Valsalva. Of the 40 patients with annular atrial tachycardia, 4 tachycardias were localized to the mitral annulus and 37 to the tricuspid annulus (including 9 para-Hisian), and all were adenosine sensitive. CONCLUSIONS: Peri-annular atrial and ventricular tissue correspond to a region enriched with arrhythmogenic foci, which may reflect a common developmental origin. Furthermore, the sensitivity of these tachycardias to adenosine provides evidence for a shared arrhythmia mechanism, consistent with intracellular calcium overload and triggered activity.

Magnesium adjunctive therapy in atrial arrhythmias.

Magnesium (Mg) is an important intracellular ion with cardiac metabolism and electrophysiologic properties. A large percentage of patients with arrhythmias have an intracellular Mg deficiency, which is out of line with serum Mg concentrations, and this may explain the rationale for Mg's benefits as an atrial antiarrhythmic agent. A current limitation of antiarrhythmic therapy is that the potential for cardiac risk offsets some of the benefits of therapy. Mg enhances the balance of benefits to harms by enhancing atrial antiarrhythmic efficacy and reducing antiarrhythmic proarrhythmia potential as well as providing direct antiarrhythmic efficacy when used as monotherapy in patients undergoing cardiothoracic surgery.