RESUMO
Arrhythmogenic cardiomyopathy (AC) is a rare heart muscle disease with a genetic background and autosomal dominant mode of transmission. The clinical manifestation is characterized by ventricular arrhythmias (VA), heart failure (HF) and the risk of sudden cardiac death (SCD). Pregnancy in young female patients with AC represents a challenging condition for the life and family planning of young affected women. In addition to genetic mechanisms that influence the complex pathophysiology of AC, experimental and clinical data have confirmed the pathogenetic role of strenuous exercise and competitive sports in the early onset and rapid progression of AC symptoms and complications. Pregnancy and exercise share a number of physiological aspects of adaptation. In AC, both result in ventricular volume overload and myocardial stretch. Therefore, pregnancy has been postulated as a potential risk factor for HF, VA, SCD, and pregnancy-related obstetric complications in patients with AC. However, the available evidence on pregnancy in AC does not confirm this hypothesis. In most women with AC, pregnancies are well tolerated, uneventful, and follow a benign course. Pregnancy-related symptoms (VA, syncope, HF) and mortality, as well as obstetric complications, are uncommon in AC patients and range in the order of background populations and cohorts with AC and no pregnancy. The number of completed pregnancies is not associated with an acceleration of AC pathology or an increased risk of VA or HF during pregnancy and follow-up. Accordingly, there is no medical indication to advise against pregnancy in patients with AC. Preconditions include stability of rhythm and hemodynamics at baseline, as well as clinical follow-ups and the availability of multidisciplinary expert consultation during pregnancy and postpartum. Genetic counseling is recommended prior to pregnancy for all couples and their families affected by AC.
Assuntos
Displasia Arritmogênica Ventricular Direita , Cardiomiopatias , Arritmias Cardíacas , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/genética , Morte Súbita Cardíaca/prevenção & controle , Feminino , Humanos , Gravidez , Fatores de RiscoRESUMO
INTRODUCTION: The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying mechanisms in an experimental whole-heart model. METHODS AND RESULTS: Isolated and retrogradely perfused rabbit hearts underwent a standardized protocol employing atrial burst pacing-induced AF in five of 20 hearts under baseline conditions (seven episodes). Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Two monophasic action potential recordings on the left- and two on the right atrial epicardium showed a decrease in atrial action potential duration (aAPD, -25 msec, P<.05) and atrial effective refractory period (aERP; -52 msec, P<.01) after infusion of acetylcholine (1 µmol/L) and isoproterenol (1 µmol/L). This led to induction of AF in 14 of 20 hearts (145 episodes). Simultaneous infusion of ANT (20 µmol/L) led to a complete suppression of AF in all inducible hearts. Treatment with ANT also led to a significant increase in aAPD (+41 msec, P<.01) and aERP (+74 msec, P<.05), leading to a marked increase in atrial postrepolarization refractoriness (aPRR, +33 msec, P<.01). Results were compared to 13 rabbits treated with flecainide. Flecainide induced a significant increase in aPRR and resulted in induction of AF in seven of 13 hearts (51 episodes) while 11 of 13 hearts were inducible with acetylcholine and isoproterenol (93 episodes). CONCLUSION: Administration of ANT was highly effective in suppressing AF. The antiarrhythmic effect could be explained by a significant increase in postrepolarization refractoriness as a result of a more marked increase in aERP as compared with aAPD.
Assuntos
Antazolina/farmacologia , Antiarrítmicos/farmacologia , Fibrilação Atrial/prevenção & controle , Frequência Cardíaca/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Acetilcolina , Potenciais de Ação , Animais , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/fisiopatologia , Estimulação Cardíaca Artificial , Relação Dose-Resposta a Droga , Descoberta de Drogas , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Flecainida/farmacologia , Preparação de Coração Isolado , Isoproterenol , Coelhos , Período Refratário Eletrofisiológico , Fatores de TempoRESUMO
In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2µM: +47ms, 4µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic ventricular tachycardia (pVT). Application of escitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes). The results were compared to 12 rabbits treated with haloperidol which led to an increase in QT-interval (1µM:+62ms; 2µM:+96ms; P<0.01), APD and dispersion (1µM:+15ms, 2µM:+40ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes). Citalopram and escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic.
Assuntos
Citalopram/efeitos adversos , Haloperidol/efeitos adversos , Coração/efeitos dos fármacos , Taquicardia Ventricular/induzido quimicamente , Potenciais de Ação/efeitos dos fármacos , Animais , Coração/fisiopatologia , Coelhos , Taquicardia Ventricular/fisiopatologiaRESUMO
In several case reports a prolongation of the QT-interval and even proarrhythmic effects of fluconazole and voriconazole were reported. The aim of the present study was to investigate if application of fluconazole or voriconazole has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In female rabbits, fluconazole (10, 30 and 50 µM, n=6) and voriconazole (10, 30 and 50 µM, n=6) were infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of fluconazole as compared with baseline (10 µM:+12 ms, 30 µM:+22 ms, 50 µM:+37 ms; P<0.05) accompanied by an increase of action potential duration (APD90). Administration of voriconazole also induced QT prolongation (30 µM:+10 ms, 50 µM:+20 ms, P<0.05). Spatial dispersion of repolarization remained stable in voriconazole-treated hearts while fluconazole induced a significant increase (30 µM:+15 ms, 50 µM:+16 ms; P<0.05). Lowering of potassium concentration in bradycardic AV-blocked hearts did not provoke any early afterdepolarizations (EADs) or polymorphic ventricular tachycardia in voriconazole-treated hearts. Application of fluconazole led to the reproducible induction of EADs in 4 of 6 hearts and polymorphic ventricular tachycardia in 3 of 6 hearts (36 episodes). In the present study, voriconazole demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, fluconazole led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization. These results imply that application of fluconazole might be torsadogenic and the QT-interval should be closely monitored.
Assuntos
Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Fluconazol/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Voriconazol/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Sistema de Condução Cardíaco/efeitos dos fármacos , CoelhosRESUMO
OBJECTIVE: Catheter-based modulation of the slow pathway is the first-line therapy of atrioventricular nodal reentrant tachycardia (AVNRT), the most common supraventricular tachycardia (SVT). In patients with a typical history, in whom AVNRT is not inducible during an electrophysiological study, the current guidelines allow consideration of empirical slow pathway modulation (ESPM) under the precondition that both, dual nodal pathway physiology (DNPP) and an ECG documentation compatible with AVNRT exist. This recommendation is based on small series. Furthermore, it is unknown whether ESPM is beneficial in the presence of ECG documentation but the absence of DNPP or vice versa in the presence of DNPP but absence of ECG documentation. METHODS: Out of 3003 patients who underwent slow pathway modulation from 1993 to 2013, we included 116 patients (68 female; median age 47.0 years) with symptomatic tachycardia who had non-inducible SVT. All patients either had ECG documentation of SVT (66 %) or DNPP (89 %) or both (54 %). All patients underwent ESPM. No severe complications occurred. RESULTS: After a follow-up time of 64 ± 5.3 months, 81 % of all patients had benefited from ESPM (49 % freedom of symptoms, 32 % improvement). In patients with ECG documentation but absence of DNPP 100 % benefited (85 % freedom of symptoms; 15 % improvement). In patients with DNPP but absence of ECG documentation 75 % benefited (40 % freedom of symptoms, 35 % improvement). CONCLUSION: In a large cohort of patients, ESPM is a safe procedure that improves clinical symptoms in the majority of patients during long-term follow-up. We show for the first time that this also applies for cases where there is no DNPP but a characteristic ECG documentation, and vice versa.
Assuntos
Ablação por Cateter/estatística & dados numéricos , Sistema de Condução Cardíaco/cirurgia , Complicações Pós-Operatórias/epidemiologia , Taquicardia por Reentrada no Nó Atrioventricular/epidemiologia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Comorbidade , Eletrocardiografia/estatística & dados numéricos , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Resultado do TratamentoRESUMO
AIMS: Interaction between dronedarone and digitalis has been discussed as a possible cause for increased mortality in the presence of dronedarone observed in the PALLAS trial. The aim of this study was to assess possible proarrhythmic effects of dronedarone in combination with digitalis in an experimental whole heart model. METHODS AND RESULTS: Twenty-six female rabbits underwent chronic oral treatment with dronedarone (50 mg/kg/day for 6 weeks). Twenty-four rabbits received placebo. Heart failure was induced by rapid ventricular pacing. Sham-operated rabbits received a right-ventricular pacing lead but were not paced. Thereafter, hearts were isolated and Langendorff-perfused. Monophasic action potentials and a 12 lead electrocardiogram showed a dose-dependent decrease of QT interval, APD90, effective refractory periods, and postrepolarization refractoriness in control hearts and dronedarone-pretreated hearts after application of ouabain (0.1 and 0.2 µM). After acute application of ouabain, ventricular fibrillation (VF) was inducible by programmed ventricular stimulation in 6 of 12 untreated sham hearts (38 episodes) as compared with 7 of 11 dronedarone-pretreated sham hearts (76 episodes). In untreated failing hearts, 6 of 12 hearts were inducible (47 episodes) as compared with 7 of 15 hearts dronedarone-pretreated failing hearts (93 episodes). CONCLUSION: In this study, ouabain treatment resulted in an increased ventricular vulnerability in chronically dronedarone-pretreated control and failing hearts. Ouabain led to a significant abbreviation of ventricular repolarization. This was more marked in dronedarone-pretreated hearts and resulted in an elevated incidence of VF. This may help to interpret the results of the PALLAS trial.
Assuntos
Amiodarona/análogos & derivados , Glicosídeos Digitálicos/administração & dosagem , Glicosídeos Digitálicos/efeitos adversos , Fibrilação Ventricular/induzido quimicamente , Fibrilação Ventricular/prevenção & controle , Amiodarona/administração & dosagem , Amiodarona/efeitos adversos , Animais , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Dronedarona , Interações Medicamentosas , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Coelhos , Fibrilação Ventricular/diagnósticoRESUMO
Owing to increased life expectancy, patients with grown-up congenital heart disease nowadays present various types of arrhythmias. We report treatment of a 27-year-old patient with tricuspid and pulmonary atresia who was referred to our department with symptomatic tachycardia. During electrophysiologic study, a diagnosis of typical AV-nodal re-entrant tachycardia was made, and he was successfully treated despite the described anatomic malformation.
Assuntos
Nó Atrioventricular/fisiopatologia , Ablação por Cateter/métodos , Sistema de Condução Cardíaco/cirurgia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Atresia Tricúspide/complicações , Adulto , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Seguimentos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Taquicardia por Reentrada no Nó Atrioventricular/etiologia , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Atresia Tricúspide/fisiopatologia , Atresia Tricúspide/cirurgiaRESUMO
BACKGROUND: The present ESC guidelines on atrial fibrillation have introduced vernakalant (VER) for pharmacologic cardioversion of atrial fibrillation. The aim of the present study was to investigate possible proarrhythmic effects of vernakalant in an experimental model of heart failure (HF). METHODS AND RESULTS: In 12 female rabbits, HF was induced with the use of 4 weeks of rapid ventricular pacing. Twelve rabbits were sham operated. Isolated hearts demonstrated a significant prolongation of myocardial repolarization after induction of HF. Vernakalant caused a concentration-dependent (10 µmol/L and 30 µmol/L) increase of action potential duration (APD90) and QT interval without affecting spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period resulting in a significant increase in post-repolarization refractoriness. In control conditions, programmed ventricular stimulation and burst pacing led to ventricular fibrillation (VF) in 2 of the 12 sham (4 episodes) and in 3 of the 12 HF (24 episodes) subjects. In the presence of 30 µmol/L vernakalant, VF was no longer inducible in both groups (0 episodes). In the presence of low K+ concentration, neither sham nor HF vernakalant-treated subjects developed early after-depolarizations or ventricular tachyarrhythmias. CONCLUSION: In the present study, application of vernakalant led to a significant prolongation of myocardial repolarization and increased post-repolarization refractoriness but did not induce early after-depolarization and therefore did not cause proarrhythmia in failing hearts.
Assuntos
Anisóis/farmacologia , Fibrilação Atrial/tratamento farmacológico , Terapia de Ressincronização Cardíaca/efeitos adversos , Insuficiência Cardíaca/fisiopatologia , Pirrolidinas/farmacologia , Animais , Antiarrítmicos/farmacologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Modelos Animais de Doenças , Eletrocardiografia , Feminino , Sistema de Condução Cardíaco/efeitos dos fármacos , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Modelos Cardiovasculares , CoelhosRESUMO
AIM: The most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety profile of VER in a sensitive model of proarrhythmia. METHODS AND RESULTS: In 36 Langendorff-perfused rabbit hearts, VER (10, 30 µM, n = 12); ranolazine (RAN, 10, 30 µM, n = 12), or sotalol (SOT, 50; 100 µM, n = 12) were infused after obtaining baseline data. Monophasic action potentials and a 12-lead electrocardiogram showed a significant QT prolongation after application of VER as compared with baseline (10 µM: +25 ms, 30 µM: +50 ms, P < 0.05) accompanied by an increase of action potential duration (APD). The increase in APD90 was accompanied by a more marked increase in effective refractory period (ERP) leading to a significant increase in post-repolarization refractoriness (PRR, 10 µM: +30 ms, 30 µM: +36 ms, P < 0.05). Vernakalant did not affect the dispersion of repolarization. Lowered potassium concentration in bradycardic hearts did not provoke early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT). Comparable results were obtained with RAN. Hundred micromolars of SOT led to an increase in QT interval (+49 ms) and APD90 combined with an increased ERP and PRR (+23 ms). In contrast to VER, 100 µM SOT led to a significant increase in dispersion of repolarization and to the occurrence of EAD in 10 of 12 and pVT in 8 of 12 hearts. CONCLUSION: In the present study, application of VER and SOT led to a comparable prolongation of myocardial repolarization. Both drugs increased the PRR. However, VER neither affect the dispersion of repolarization nor induce EAD and therefore did not cause proarrhythmia.
Assuntos
Anisóis/toxicidade , Antiarrítmicos/toxicidade , Arritmias Cardíacas/induzido quimicamente , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/efeitos dos fármacos , Pirrolidinas/toxicidade , Acetanilidas/toxicidade , Potenciais de Ação , Animais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Técnicas In Vitro , Modelos Animais , Perfusão , Piperazinas/toxicidade , Bloqueadores dos Canais de Potássio/toxicidade , Coelhos , Ranolazina , Medição de Risco , Fatores de Risco , Bloqueadores dos Canais de Sódio/toxicidade , Sotalol/toxicidade , Fatores de TempoAssuntos
Nó Atrioventricular/fisiopatologia , Eletrocardiografia Ambulatorial , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia Supraventricular/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia Supraventricular/fisiopatologiaRESUMO
AIMS: Phased radiofrequency (RF) ablation for atrial fibrillation is associated with an increased number of silent cerebral lesions on magnetic resonance imaging and cerebral microembolic signals (MESs) on transcranial Doppler ultrasound imaging compared with irrigated RF. The increased rate of embolic events may be due to a specific electrical interference of ablation electrodes attributed to the catheter design. The purpose of this study was to elucidate the effect of deactivating the culprit electrodes on cerebral MESs. METHODS AND RESULTS: Twenty-nine consecutive patients (60 ± 11 years, 10 female) underwent their first pulmonary vein isolation using phased RF energy. Electrode pairs 1 or 5 were deactivated to avoid electrical interference between electrodes 1 and 10 ('modified'). Detection of MESs by transcranial Doppler ultrasound was performed throughout the procedure to assess cerebral microembolism. Results were compared with the numbers of MESs in 31 patients ablated using all available electrodes ('conventional') and to 30 patients undergoing irrigated RF ablation of a previous randomized study. Ablation with 'modified' phased RF was associated with a marked decrease in MESs when compared with 'conventional' phased RF (566 ± 332 vs. 1530 ± 980; P < 0.001). This difference was mainly triggered by the reduction of MES during delivery of phased RF energy, resulting in MES numbers comparable to irrigated RF ablation (646 ± 449; P = 0.7). Total procedure duration as well as time of RF delivery was comparable between phased RF groups. Both times, however, were significantly shorter compared with the irrigated RF group (123 ± 28 vs. 195 ± 38; 15 ± 4 vs. 30 ± 9; P < 0.001, respectively). CONCLUSION: Pulmonary vein isolation with 'modified' phased RF is associated with a decreased number of cerebral microembolism especially during the delivery of ablation impulses, supporting the significance of electrical interference between ablation electrodes 1 and 10. Deactivation of electrode pairs 1 or 5 might increase the safety of this approach without an increase in procedure duration or RF delivery time.
Assuntos
Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Embolia Intracraniana/etiologia , Embolia Intracraniana/prevenção & controle , Veias Pulmonares/cirurgia , Fibrilação Atrial/diagnóstico , Feminino , Humanos , Embolia Intracraniana/diagnóstico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Early repolarization, involving infero-lateral ST segment elevation and prominent J waves at the QRS-ST junction has been considered a normal ECG variant for more than 80 years. More recent studies suggest that this phenomenon is not as benign as earlier believed and may represent a risk for subsequent ventricular fibrillation in patients with and without structural heart disease. However, based on current data it seems unjustified to consider these often accidental ECG findings a marker for high risk of sudden cardiac death. The concept of a reduced repolarization reserve developed for the Long QT syndrome can be transformed to early repolarization syndrome. In general a "fibrillation reserve" is relatively high but if triggers such as a genetic background, age, gender, influences of the autonomous nervous system, changes in body temperature, or an acute coronary syndrome act together ventricular fibrillation may occur. A combination of an "early repolarization ECG" with syncope and/or a positive family history of sudden cardiac death may justify defibrillator therapy just on an individual basis. This review intends to summarize actual aspects of early repolarizations syndrome and focuses on the dilemma of risk stratification.
Assuntos
Estimulação Cardíaca Artificial , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia/métodos , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/prevenção & controle , Diagnóstico Diferencial , Humanos , Medição de RiscoRESUMO
BACKGROUND: Ranolazine is evaluated for antiarrhythmic therapy of atrial fibrillation (AF). The electrophysiologic mechanisms of ranolazine in combination with class III drugs were studied in an isolated whole-heart model of stretch-related AF. METHODS AND RESULTS: Thirty rabbits were fed with amiodarone (50 mg/kg/day, n = 10), dronedarone (50 mg/kg/day, n = 10), or placebo (n = 10) for 6 weeks. Subsequently, in isolated hearts, AF was induced by high-rate atrial pacing and acute atrial dilatation. In placebo-treated hearts, d,l-sotalol (50 µM) was acutely administered. Ranolazine (10 µM) was additionally infused in all groups. Chronic amiodarone (+26 ± 7 ms, P < 0.05) or dronedarone (+22 ± 4 ms, P < 0.05) as well as acute application of d,l-sotalol (+20 ± 3 ms, P < 0.05) increased atrial action potential duration (aAPD90 ). Additional treatment with ranolazine did not significantly change aAPD90 (P = ns). Class III drugs did not affect interatrial conduction time, while ranolazine significantly increased it (amiodarone group: +15 ± 3 ms, dronedarone group: +11 ± 3 ms, sotalol group: +15 ± 6 ms; P < 0.05 each). Ranolazine led to an additional increase in atrial effective refractory period (aERP), thus leading to an enhanced atrial postrepolarization refractoriness (aPRR, +17 ± 6 ms, +21 ± 4 ms and +16 ± 8 ms, P < 0.05, respectively). Acute atrial dilatation increased AF incidence compared with baseline. Amiodarone-pretreated hearts showed a lower incidence of AF. Additional infusion of ranolazine further diminished AF. Dronedarone or acute infusion of sotalol did not significantly suppress AF, while additional treatment with ranolazine in these groups also reduced AF incidence. CONCLUSION: In this study, ranolazine on top of class III antiarrhythmic therapy had a beneficial effect. The increase in interatrial conduction time and marked atrial aPRR suppressed AF. These results shed further light on a potential therapeutic benefit of ranolazine on top of conventional antiarrhythmic therapy for rhythm control in AF.
Assuntos
Acetanilidas/farmacologia , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Piperazinas/farmacologia , Potenciais de Ação/efeitos dos fármacos , Amiodarona/administração & dosagem , Amiodarona/análogos & derivados , Animais , Modelos Animais de Doenças , Dronedarona , Quimioterapia Combinada , Feminino , Coelhos , Ranolazina , Período Refratário Eletrofisiológico/efeitos dos fármacos , Sotalol/administração & dosagemRESUMO
OBJECTIVES: The purpose of this study was to evaluate clinical and electrophysiologic characteristics of AT in patients after surgical ASD repair as well as outcome after ablation. BACKGROUND: Atrial tachycardias (AT) are a common complication after surgical closure of an atrial septal defect (ASD). METHODS: From a prospective ablation database we analyzed data of patients with a history of ASD repair who presented to our institution for AT ablation. We investigated ECG characteristics and the electrophysiologic mechanism of AT in this collective and analyzed follow-up data. RESULTS: Data of 54 patients (47.3 ± 14.5 years, 35 females) were included. In 30 patients (55.6%) ASD had been closed by direct suture, 24 patients (44.4%) had a patch for ASD repair without significant difference in terms of gender and age at the time of the procedure (p=0.234, p=0.231). In 42 patients (77.8%), electrophysiological studies were performed in AT. All patients had right atrial macro-reentrant AT. The leading mechanism was isthmus-dependent right atrial flutter in 29 patients (69.0%) with clockwise atrial activation in 41%. The mechanism of AT (typical atrial flutter (n=29), atriotomy-dependent flutter (n=7), and double loop flutter (n=5)) did not differ with regard to type of surgery. Only 70.6% of patients with proven isthmus dependent counter-clockwise atrial flutter presented with an ECG morphology typical for this mechanism. However, all clockwise typical atrial flutter patients showed the characteristic positive P-waves in the inferior leads. Of note, 83.3% of clockwise typical flutter ECGs had long isoelectric lines (mean 74.5 ms). Follow-up was complete in 45 of 54 patients. During a mean follow-up of 7.7 ± 3.7 years, 27 patients (60%) remained free of any arrhythmia, two patients had AT recurrence with different mechanisms compared to the first procedure and underwent successful ablation. Five patients (11%) developed atrial fibrillation. CONCLUSION: Isthmus dependent right atrial flutter is the leading AT mechanism in patients with a history of ASD repair. The mechanism of atrial flutter did not differ in relation to the mode of ASD closure (direct suture versus patch closure). ECG characteristics of the tachycardia may be misleading as they are more often atypical in patients after ASD repair.
Assuntos
Flutter Atrial/complicações , Ablação por Cateter , Comunicação Interatrial/cirurgia , Complicações Pós-Operatórias/etiologia , Taquicardia/etiologia , Adulto , Idoso , Feminino , Átrios do Coração , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Symptomatic, premature ventricular contractions (PVCs) frequently originate in the right ventricular outflow tract, less frequently in the left ventricular outflow tract, aortic root, or mitral annulus (MA). Little is known about the patient population presenting with MA PVC and/or ventricular tachycardia (VT). OBJECTIVE: To characterize the subgroup of ventricular arrhythmias arising from the MA. METHODS: Among 404 consecutive patients who presented for catheter ablation of idiopathic PVC/VT over a period of 9 years, patients who were found to have an ablation site at the MA were analyzed for clinical and electrophysiological parameters. RESULTS: Twenty-two (5%) patients (mean age 45 ± 18 years; range 16-76 years; 14 [64%] men) had PVC/VT arising from the MA. History of PVC ranged from 2 days in a case with suspected focal myocarditis to 19 years. No patient had severely depressed left ventricular function or significant heart disease, which was determined by echocardiogram, magnetic resonance imaging, and/or coronary angiogram. Sites of origin were distributed around the MA with no preferential area. Ablation was successful in 13 of 16 (81%) patients. One 28-year-old female patient with normal magnetic resonance imaging and no structural heart disease died suddenly 3 months after ablation. CONCLUSIONS: Ventricular arrhythmias from the MA represent a rare subgroup of idiopathic PVC/VT. They appear to occur at any age and do not indicate underlying structural heart disease. Catheter ablation has a success rate comparable to that of outflow tract tachycardia. Prognosis remains unclear.
Assuntos
Ablação por Cateter , Valva Mitral , Taquicardia Ventricular/cirurgia , Complexos Ventriculares Prematuros/cirurgia , Adolescente , Adulto , Idoso , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Prognóstico , Taquicardia Ventricular/fisiopatologia , Complexos Ventriculares Prematuros/fisiopatologia , Adulto JovemRESUMO
AIMS: In several clinical and pre-clinical studies, application of ranolazine (RAN) led to suppression of atrial fibrillation (AF). The aim of the present study was to investigate whether RAN can suppress AF in an experimental rabbit whole heart model, in which acute haemodynamic changes trigger AF. Ranolazine was compared with flecainide and sotalol as established antiarrhythmic agents. METHODS AND RESULTS: In 60 Langendorff-perfused, isolated rabbit hearts, AF episodes were evoked by burst pacing with a fixed number of stimuli at baseline and following acute atrial stretch. Data were obtained in the absence and presence of acute dilatation of the left atrium (20 mmHg) at baseline and after drug application (RAN 10 µM, n = 10; flecainide 2 µM, n = 10; sotalol 50 µM, n = 10). Application of sotalol, but not RAN or flecainide increased the atrial action potential duration at 90% repolarization (aAPD90); however, both RAN (+8 ms) and flecainide (+13 ms) increased interatrial conduction time. All three drugs caused a significant increase in atrial effective refractory period (aERP) and, thus, an increase in atrial post-repolarization refractoriness (aPRR: +11 ms each, P < 0.05). Acute dilatation of the left atrium reduced aAPD90 and aERP. The described drug effects were preserved in the setting of acute atrial dilatation. Acute atrial dilatation significantly increased the incidence of AF. Ranolazine and flecainide, but not sotalol, decreased the number of responses. CONCLUSION: Ranolazine-related sodium channel block is preserved upon acute atrial stretch. Ranolazine suppresses stretch-induced AF by increasing interatrial conduction time and aPRR. These results shed further evidence on the potential role of RAN in the prevention of AF. This might also apply to clinical conditions that are associated with haemodynamic or mechanical disorders, leading to acute dilatation of the atria.
Assuntos
Acetanilidas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacos , Piperazinas/administração & dosagem , Período Refratário Eletrofisiológico/efeitos dos fármacos , Administração Oral , Animais , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/diagnóstico , Feminino , Flecainida/administração & dosagem , Sistema de Condução Cardíaco/efeitos dos fármacos , Técnicas In Vitro , Coelhos , Ranolazina , Bloqueadores dos Canais de Sódio/administração & dosagem , Sotalol/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The risk of developing a stroke or systemic embolus due to a left atrial (LA) thrombus in patients with atrial fibrillation (AF) and/or atrial flutter (AFL) is estimated by the CHADS(2) score and more recently the CHA(2)DS(2)-VASc score. We aimed to further characterize AF/AFL patients who were found to have a LA thrombus on a transesophageal echocardiogram (TEE). METHODS AND RESULTS: Of 3,165 TEE between 2005 and 2011 for a broad spectrum of indications, we detected 65 AF patients with LA thrombus (2 %). There were 40 men and 25 women, mean age was 65 ± 13 years (range 36-88 years). Mean CHADS(2) score was 1.8 ± 1.1 and mean CHA(2)DS(2)-VASc score was 3.0 ± 1.6. 11 patients (17 %) had a CHADS(2) score of 0, 12 patients (18 %) of 1, 28 patients (43 %) of 2 and 12 patients (18 %) of 3. Hypertension was the most frequent risk factor (72 %), followed by congestive heart failure (32 %), diabetes (23 %) and age ≥75 years (23 %). Mean difference between CHADS(2) and CHA(2)DS(2)-VASc was 1.25 ± 0.91. Of the 11 patients (17 %) with a LA thrombus despite a CHADS(2) score of 0, five had a CHA(2)DS(2)-VASc score of 0, four a CHA(2)DS(2)-VASc score of 1 and two a CHA(2)DS(2)-VASc score of 2. CONCLUSION: In an unselected TEE population with newly detected LA thrombus about one-third of patients fell into the low-risk group when classified based on the CHADS(2) score, while a much lower population fell in the same low-risk group when classified according to the CHA(2)DS(2)-VASc score. However, this does not prove clinical superiority of the CHA(2)DS(2)-VASc score over the established CHADS(2) score. Whether our observation has clinical implications (e.g. TEE prior to LA ablation irrespective of CHADS(2) score), or argues for use of the CHA(2)DS(2)-VASc score needs to be evaluated in prospective studies.
Assuntos
Fibrilação Atrial/complicações , Flutter Atrial/complicações , Técnicas de Apoio para a Decisão , Embolia/etiologia , Acidente Vascular Cerebral/etiologia , Trombose/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Flutter Atrial/diagnóstico , Complicações do Diabetes/etiologia , Ecocardiografia Transesofagiana , Feminino , Insuficiência Cardíaca/complicações , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose/diagnóstico por imagemRESUMO
BACKGROUND: Ranolazine inhibits late Na(+) and K(+) currents. Earlier studies have reported an antiarrhythmic effect. The aim of the present study was to understand whether ranolazine could still preserve its antiarrhythmic properties in the settings of chronic heart failure (CHF). METHODS AND RESULTS: In 12 female rabbits, CHF was induced by 4 weeks of rapid ventricular pacing leading to a decrease in ejection fraction. Twelve rabbits underwent sham operation. Isolated hearts were Langendorff perfused and demonstrated a significant QT prolongation after induction of heart failure. Ranolazine caused a concentration-dependent (10 and 30 µmol/L) increase of action potential duration (APD(90)) in sham-operated and failing hearts. Eight endo- and epicardial monophasic action potentials revealed a nonsignificant increase in spatial and temporal dispersion of repolarization. The increase in APD(90) was accompanied by a greater increase in refractory period, resulting in a significant increase in postrepolarization refractoriness in sham-operated (+29 ms and +55 ms; P < .01) and failing (+22 ms and +30 ms; P < .05) hearts. In control conditions, programmed ventricular stimulation and a burst pacing protocol led to ventricular fibrillation (VF) in 5 of the 12 sham-operated (6 episodes) and in 7 of the 12 failing (18 episodes) hearts. In the presence of ranolazine, VF was inducible in only 2 of 12 failing hearts (5 episodes). In the presence of low [K(+)], only 1 ranolazine-treated sham-operated heart developed early afterdepolarizations and ventricular tachyarrhythmias despite significant QT prolongation. CONCLUSIONS: Ranolazine decreases inducibility of VF in the presence of a significant increase in postrepolarization refractoriness. This antiarrhythmic effect in the intact heart is preserved in CHF and is not associated with drug-induced proarrhythmia.
Assuntos
Acetanilidas/farmacologia , Antiarrítmicos/farmacologia , Piperazinas/farmacologia , Período Refratário Eletrofisiológico/efeitos dos fármacos , Fibrilação Ventricular/prevenção & controle , Potenciais de Ação/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Eletrocardiografia , Insuficiência Cardíaca/tratamento farmacológico , Coelhos , Ranolazina , Sotalol/farmacologiaRESUMO
BACKGROUND: Ranolazine exhibits a synergistic effect in combination with class III drugs to suppress atrial fibrillation. OBJECTIVE: To investigate whether a combination therapy affects repolarization and provokes ventricular tachyarrhythmias (VT) in a sensitive model of proarrhythmia. METHODS: Thirty-seven rabbits were assigned to 3 groups and fed with amiodarone (50 mg/kg/d; n = 10) or dronedarone (50 mg/kg/d; n = 10) over a period of 6 weeks. A third group was used as control (n = 17). After obtaining baseline data in Langendorff-perfused control hearts, sotalol (100 µM) was administered in this group. Thereafter, ranolazine (10 µM) was additionally infused on top of amiodarone, dronedarone, or sotalol. RESULTS: Chronic treatment with amiodarone or dronedarone as well as sotalol significantly increased action potential duration at 90% repolarization (APD(90)). Additional treatment with ranolazine further increased APD(90) in amiodarone- and dronedarone-pretreated hearts but not in sotalol-treated hearts. Ranolazine increased postrepolarization refractoriness as compared with amiodarone or dronedarone alone owing to a marked effect on the refractory period. In contrast to amiodarone and dronedarone, acute application of sotalol increased dispersion of repolarization (P < .05). Additional treatment with ranolazine did not further increase spatial or temporal dispersion. After lowering extracellular [K(+)] in bradycardic hearts, no proarrhythmia occurred in amiodarone- or dronedarone-treated hearts whereas 11 of 17 sotalol-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with ranolazine reduced the number of VT episodes in sotalol-treated hearts and did not cause proarrhythmia in combination with amiodarone or dronedarone. CONCLUSIONS: Application of ranolazine on top of class III drugs does not cause proarrhythmia despite a marked effect on ventricular repolarization. The effect of ranolazine on the repolarization reserve is associated with the lack of effect on early afterdepolarizations and dispersion of repolarization.
Assuntos
Eletrocardiografia/efeitos dos fármacos , Sistema de Condução Cardíaco/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Taquicardia Ventricular/tratamento farmacológico , Acetanilidas , Potenciais de Ação/efeitos dos fármacos , Animais , Antiarrítmicos , Modelos Animais de Doenças , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Piperazinas , Coelhos , Ranolazina , Taquicardia Ventricular/fisiopatologiaRESUMO
AIMS: Ranolazine (RAN) was reported to be effective and safe in converting atrial fibrillation (AF) to sinus rhythm by administration of a single dose ('pill in the pocket') to patients with structural heart disease. This study examines the underlying mechanisms for the antiarrhythmic benefit of RAN application in chronic heart failure (CHF). METHODS AND RESULTS: In 10 female rabbits, CHF was induced by rapid ventricular pacing, leading to a significant decrease in ejection fraction in the presence of a dilated left ventricle and atrial enlargement. Twelve rabbits were sham-operated and served as controls. Isolated hearts were perfused using the Langendorff method. Burst pacing was used to induce AF. Monophasic action potential recordings showed an increase of atrial action potential duration (aAPD) and effective refractory period (aERP) in CHF hearts compared with sham hearts. Infusion of acetylcholine (1 µM) and isoproterenol (1 µM) led to AF in all failing hearts and in 11 sham hearts. Simultaneous infusion of RAN (10 µM) remarkably reduced inducibility of AF in 50% of sham and 50% of failing hearts. RAN had no effect on aAPD but significantly increased aERP, leading to a marked increase in atrial post-repolarization refractoriness. Moreover, RAN application moderately increased interatrial conduction time. CONCLUSION: RAN has been shown to be effective in reducing the inducibility of AF in an experimental model of AF. The antiarrhythmic effect is mainly due to development of atrial post-repolarization refractoriness and a moderate increase in conduction time. The described electrophysiological mechanisms remain preserved in the setting of CHF.