Left Axis Deviation in Brugada Syndrome: Vectorcardiographic Evaluation during Ajmaline Provocation Testing Reveals Additional Depolarization Abnormalities.

Patients with Brugada syndrome (BrS) can show a leftward deviation of the frontal QRS-axis upon provocation with sodium channel blockers. The cause of this axis change is unclear. In this study, we aimed to determine (1) the prevalence of this left axis deviation and (2) to evaluate its cause, using the insights that could be derived from vectorcardiograms. Hence, from a large cohort of patients who underwent ajmaline provocation testing (n = 1430), we selected patients in whom a type-1 BrS-ECG was evoked (n = 345). Depolarization and repolarization parameters were analyzed for reconstructed vectorcardiograms and were compared between patients with and without a >30° leftward axis shift. We found (1) that the prevalence of a left axis deviation during provocation testing was 18% and (2) that this left axis deviation was not explained by terminal conduction slowing in the right ventricular outflow tract (4th QRS-loop quartile: +17 ± 14 ms versus +13 ± 15 ms, nonsignificant) but was associated with a more proximal conduction slowing (1st QRS-loop quartile: +12[8;18] ms versus +8[4;12] ms, p < 0.001 and 3rd QRS-loop quartile: +12 ± 10 ms versus +5 ± 7 ms, p < 0.001). There was no important heterogeneity of the action potential morphology (no difference in the ventricular gradient), but a left axis deviation did result in a discordant repolarization (spatial QRS-T angle: 122[59;147]° versus 44[25;91]°, p < 0.001). Thus, although the development of the type-1 BrS-ECG is characterized by a terminal conduction delay in the right ventricle, BrS-patients with a left axis deviation upon sodium channel blocker provocation have an additional proximal conduction slowing, which is associated with a subsequent discordant repolarization. Whether this has implications for risk stratification is still undetermined.

Predicting cardiac electrical response to sodium-channel blockade and Brugada syndrome using polygenic risk scores.

AIMS: Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors of ajmaline-induced PR and QRS changes and Type I Brugada syndrome (BrS) electrocardiogram (ECG). METHODS AND RESULTS: In 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements of 26 721 ECGs, dose-response mixed modelling and genotyping. We calculated polygenic risk scores (PRS) for PR interval (PRSPR), QRS duration (PRSQRS), and Brugada syndrome (PRSBrS) derived from published genome-wide association studies and used regression analysis to identify predictors of ajmaline dose related PR change (slope) and QRS slope. We derived and validated using bootstrapping a predictive model for ajmaline-induced Type I BrS ECG. Higher PRSPR, baseline PR, and female sex are associated with more pronounced PR slope, while PRSQRS and age are positively associated with QRS slope (P < 0.01 for all). PRSBrS, baseline QRS duration, presence of Type II or III BrS ECG at baseline, and family history of BrS are independently associated with the occurrence of a Type I BrS ECG, with good predictive accuracy (optimism-corrected C-statistic 0.74). CONCLUSION: We show for the first time that genetic factors underlie the variability of cardiac electrical response to SCB. PRSBrS, family history, and a baseline ECG can predict the development of a diagnostic drug-induced Type I BrS ECG with clinically relevant accuracy. These findings could lead to the use of PRS in the diagnosis of BrS and, if confirmed in population studies, to identify patients at risk for toxicity when given SCB.

Ventricular fibrillation induction and diffuse abnormal ST-segment response to ajmaline in a patient with apparent pre-existing dynamic right bundle branch block.

OBJECTIVE: ST-segment elevation in the right precordial electrocardiography (ECG) leads in Brugada syndrome (BS) can be unmasked by class I anti-arrhythmic drugs (sodium channel blockers) administration. It is still debated whether this ECG pattern is better explained by abnormal repolarization or ventricular conduction and depolarization. Conduction diseases can conceal type 1 BS-like ECG in standard V1-V3 leads. ECG alterations were found also in alternative leads. The role of electrophysiology study (EPS) in sudden cardiac death risk stratification remains controversial, and could depend on the phenotypic expression of the cardiac sodium channels disease. CASE REPORT: We describe unmasked diffuse J-point and ST-segment anomalies in peripheral and precordial ECG leads and ventricular fibrillation (VF) induction by EPS after ajmaline administration in a patient with pre-existing atypical right bundle branch block (RBBB) concealing subtle anomalies in standard V1-V3 leads. RBBB was influenced by the underlying BS-like ECG associating repolarization anomaly and pre-existing conduction disease. EPS induced VF when RBBB was associated with BS-like ECG, and failed to induce VF when RBBB was present alone. CONCLUSIONS: BS phenotype heterogeneity requires further studies to improve the knowledge of its pathophysiological mechanisms associated with conduction diseases in order to better identify an individual therapy and prognostic stratification.

Prevalence of type 1 Brugada ECG pattern after administration of Class 1C drugs in patients with type 1 myotonic dystrophy: Myotonic dystrophy as a part of the Brugada syndrome.

BACKGROUND: Both type 1 myotonic dystrophy (MD1) and Brugada syndrome (BrS) may be complicated by conduction disturbances and sudden death. Spontaneous BrS has been observed in MD1 patients, but the prevalence of drug-induced BrS in MD1 is unknown. OBJECTIVE: The purpose of this study was to prospectively assess the prevalence of type 1 ST elevation as elicited during pharmacologic challenge with Class 1C drugs in a subgroup of MD1 patients and to further establish correlations with ECG and electrophysiologic variables and prognosis. METHODS: From a group of unselected 270 MD1 patients, ajmaline or flecainide drug challenge was performed in a subgroup of 44 patients (27 men, median age 43 years) with minor depolarization/repolarization abnormalities suggestive of possible BrS. The presence of type 1 ST elevation after drug challenge was correlated to clinical, ECG, and electrophysiologic variables. RESULTS: Eight of 44 patients (18%) presented with BrS after drug challenge. BrS was seen more often in men (26% vs 6%, P = .09) and was related to younger age (35 vs 48 years, P = .07). BrS was not correlated to symptoms, baseline ECG, HV interval, results of signal-averaged ECG, or abnormalities on ambulatory recordings. MD1 patients with BrS had longer corrected QT intervals, greater increase in PR interval after drug challenge, and higher rate of inducible ventricular arrhythmias (62% vs 21%, P = .03). Twelve patients were implanted with a pacemaker and 5 with an implantable cardioverter-defibrillator. Significant bradycardia did not occur in any patients, and malignant ventricular arrhythmia never occurred during median 7-year follow-up (except 1 hypokalemia-related ventricular fibrillation). CONCLUSION: BrS is elicited by a Class 1 drug in 18% of MD1 patients presenting with minor depolarization/repolarization abnormalities at baseline, but the finding seems to be devoid of a prognostic role.

Rapid diagnostics and treatment of early complications after CABG surgery: a life saver.

Early graft failure after CABG surgery may lead to severe adverse events and death. Because the cause of the graft failure can vary, rapid diagnostic management is mandatory in order to address these complications appropriately. In the present 2 cases, patients who underwent CABG procedures showed typical electrocardiograms and serology of a perioperative myocardial ischemia shortly after surgery. In the first case, a rapidly performed coronary angiogram revealed a torqued right CABG, which was detorqued and, in order to avoid further torsion, fixated to the pericardium in a redo procedure. In the second case, the patient underwent a revascularization by means of percutaneous coronary intervention with stent implantation for severe stenosis due to a localized dissection of the vein graft, diagnosed on coronary angiogram. The further postoperative course of both patients was smooth and both could be discharged on day 8 and 11 after initial surgery, respectively.

Ajmaline attenuates electrocardiogram characteristics of inferolateral early repolarization.

BACKGROUND: J waves are the hallmark of both inferolateral early repolarization (ER) and Brugada syndrome. While ajmaline, a class 1a antiarrhythmic drug, accentuates the J wave in Brugada syndrome, its effect on ER is unreported. OBJECTIVE: To describe the effect of ajmaline on the electrocardiogram in ER. METHODS: We analyzed electrocardiograms before and after the administration of intravenous ajmaline (1 mg/kg) in 31 patients with ER, 21 patients with Brugada type 1 electrocardiogram (Br), and 22 controls. ER was defined as J-point elevation of ≥1 mm with QRS slurring or notching in ≥2 inferolateral leads (I, aVL, II, III, aVF, V4-V6). RESULTS: Ajmaline decreased mean J-wave amplitude in the ER group from 0.2 ± 0.15 mV at baseline to 0.08 ± 0.09 mV (P < .001). The QRS width prolonged significantly in all 3 groups, but the prolongation was significantly less in the ER group (+21 ms) than in the Br group (+36 ms; P < .001) or controls (+28 ms; P = .010). Decrease in mean inferolateral R-wave amplitude was similar in all the groups (ER group -0.14 mV; Br group -0.11 mV; controls -0.13 mV; P = ns), but mean inferolateral S-wave amplitude increased significantly less in the ER group (ER group +0.14 mV; Br group +16 mV; controls +0.20 mV; P < .001). CONCLUSIONS: Ajmaline significantly decreases the J-wave amplitude in ER and prolongs the QRS width significantly less than in patients with Br. This indicates a different pathogenesis for both disorders. The altered terminal QRS vector probably is responsible for the decrease in the J-wave amplitude in ER, although a specific effect of ajmaline on J waves cannot be excluded.

[Life-threatening brady- and tachyarrhythmias]. / Vital bedrohliche brady- und tachykarde Herzrhythmusstörungen.

Bradycardic (heart rate<50/min) and tachycardic heart rhythm disturbances (100/min) require rapid therapeutic strategies. Supraventricular tachycardias (SVT) are sinus tachycardia, atrial tachycardia, AV-nodal reentrant tachycardia and tachycardia due to accessory pathways. Mostly SVT are characterized by small QRS complexes (QRS width<0.12 ms). It is essential to evaluate the arrhythmia history, to perform a good physical examination and to exactly analyze the 12-lead electrocardiogram. An exact diagnosis is then possible in >90% of SVT patients. Ventricular tachycardias have a broad QRS complex (>or=0.12 s), ventricular flutter and ventricular fibrillation are associated with chaotic electrophysiologic findings. For acute therapy, we will present the new concept of the "5A" that includes adenosine, adrenaline, ajmaline, amiodarone and atropine. Additional "B, C and D strategies" include betablocking agents, cardioversion as well as defibrillation. The "5A" concept allows a safe and effective antiarrhythmic treatment of all bradycardic and tachycardic arrhythmias as well as asystolia.

[Arrhythmias during pregnancy]. / Herzrhythmusstörungen in der Schwangerschaft.

Cardiovascular emergencies are rare during pregnancy with an incidence of 0,2-4,0%. Emergencies include arrhythmias, acute coronary syndrome, peripartum cardiomyopathy and hypertensive disorders. Electrical DC-cardioversion with 50-100 Joules is indicated in the acute treatment of arrhythmias in all patients in an unstable hemodynamic state. If 100 J fails higher energies (up to 360 J) will be necessary. In stable supraventricular tachycardia intravenous adenosine is the first choice drug and may safely terminate the arrhythmia. Ventricular premature beats are frequently present during pregnancy and benign in most patients. However, life-threatening ventricular tachyarrhythmias (sustained ventricular tachycardia [VT], ventricular flutter [VFlt], ventricular fibrillation [VF]) were observed less frequently. Electrical DC-cardioversion is necessary in all pregnant women who are in a hemodynamically unstable state and have a life-threatening ventricular tachyarrhythmias. In hemodynamically stable pregnant women the initial therapy with ajmaline, procainamide or lidocaine is indicated. Implantation of a cardioverter-defibrillator is indicated in patients with syncope caused by VT, VF, VFlt or aborted sudden death.

Combination of cardiac conduction disease and long QT syndrome caused by mutation T1620K in the cardiac sodium channel.

AIMS: The aim of the present study was to elucidate the molecular mechanism underlying the concomitant occurrence of cardiac conduction disease and long QT syndrome (LQT3), two SCN5A channelopathies that are explained by loss-of-function and gain-of-function, respectively, in the cardiac Na+ channel. METHODS AND RESULTS: A Caucasian family with prolonged QT interval, intermittent bundle-branch block, sudden cardiac death, and syncope was investigated. Lidocaine (1 mg/kg i.v.) normalized the prolonged QT interval and rescued bundle-branch block. An SCN5A mutation analysis was performed that revealed a C-to-A mutation at position 4859 (exon 28), predicted to change a highly conserved threonine for a lysine at position 1620. Mutant channels were characterized both in Xenopus oocytes and HEK293 cells. The T1620K mutation remarkably altered the properties of Nav1.5 channels. In particular, the voltage-dependence of the current decay time constants was largely lost. As a consequence, mutant channels inactivated faster than wild-type channels at potentials negative to -30 mV, resulting in less Na+ inward current (loss-of-function), but significantly slower at potentials positive to -30 mV, resulting in an increased Na+ inward current (gain-of-function). Moreover, we found a hyperpolarized shift of steady-state activation and an accelerated recovery from inactivation (gain-of-function). At the same time, channel availability was significantly reduced at the resting membrane potential (loss-of-function). CONCLUSION: We conclude that lysine at position 1620 leads to both loss-of-function and gain-of-function properties in hNav1.5 channels, which may consequently cause in the same individuals impaired impulse propagation in the conduction system and prolonged QTc intervals, respectively.

Effects of ajmaline on rate-dependent atrioventricular node properties. Potential role in experimental atrioventricular re-entrant tachycardia.

Ajmaline is a well-known atrioventricular (AV) node depressant agent, but its effects on functional properties of the AV node and on experimental AV re-entrant tachycardia have not been explored. The aims of the present study were (1) to determine whether ajmaline administration modifies the rate-dependent properties of the AV node and (2) to correlate these changes with the actions of ajmaline on an in vitro model of AV re-entrant tachycardia. Selective stimulation protocols and mathematical formulations were used to quantify independently AV node recovery, facilitation, and fatigue in 10 isolated rabbit AV nodes. Ajmaline decreased facilitation and fatigue and had no significant effect on AV node recovery. The most important effect of ajmaline was rate-induced prolongation of AV node effective refractory period, resulting in a greater increase in tachycardia cycle length. AV re-entrant tachycardia was sustained when AV effective refractory period divided to tachycardia cycle length was less than 1, ajmaline suppressed AV re-entrant tachycardia by increasing the slope of the AV effective refractory period divided to tachycardia cycle length versus tachycardia rate relation, causing the critical ratio of 1 to be attained at a slower rate. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for changes in nodal conduction time, AV effective refractory period, tachycardia cycle length, and AV effective refractory period divided to tachycardia cycle length under all conditions. It can be concluded that (1) ajmaline increases AV conduction time, decreases AV node fatigue, and facilitation, without altering AV node recovery. (2) Ajmaline significantly prolongs AV effective refractory period in a rate-dependent manner. (3) These changes play a role in ajmaline's actions on experimental AV re-entrant tachycardia. Ajmaline's ability to terminate re-entrant supraventricular tachycardia may be due, at least in part, to its ability to amplify the rate-induced prolongation of the nodal refractory period.

Muerte súbita: Síndrome de Brugada / Death sudden: Brugada syndrome

Se comunica el diagnóstico y tratamiento efectivo de un caso de muerte súbita con Síndrome de Brugada, efectuándose una revisión de la literatura existente al respecto. Para ello se describe el caso de una mujer de 39 años que fue recuperada de una muerte súbita, documentándose un registro ECG de fibrilación ventricular, y en quien la evaluación cardiológica muestra en ECG en ritmo sinusal con bloqueo de rama derecha y elevación del segmento S-T de V1-V3. Se descartaron todas las causas reversibles de muerte súbita arrítmica. Durante el estudio electrofisiológico se indujo con facilidad una taquicardia ventricular polimórfica-fibrilación ventricular. La administración de ajmalina incrementa las alteraciones del segmento S-T en las precordiales derechas. La paciente fue tratada con un cardiodefibrilador implantable, sin el uso de drogas antiarrítmicas y se encuentra bien al mes de seguimiento

Muerte súbita: Síndrome de Brugada / Death sudden: Brugada syndrome

Se comunica el diagnóstico y tratamiento efectivo de un caso de muerte súbita con Síndrome de Brugada, efectuándose una revisión de la literatura existente al respecto. Para ello se describe el caso de una mujer de 39 años que fue recuperada de una muerte súbita, documentándose un registro ECG de fibrilación ventricular, y en quien la evaluación cardiológica muestra en ECG en ritmo sinusal con bloqueo de rama derecha y elevación del segmento S-T de V1-V3. Se descartaron todas las causas reversibles de muerte súbita arrítmica. Durante el estudio electrofisiológico se indujo con facilidad una taquicardia ventricular polimórfica-fibrilación ventricular. La administración de ajmalina incrementa las alteraciones del segmento S-T en las precordiales derechas. La paciente fue tratada con un cardiodefibrilador implantable, sin el uso de drogas antiarrítmicas y se encuentra bien al mes de seguimiento (AU)

Detección no invasiva de lesiones miocárdicas subclínicas en pacientes con infección chagásica crónica / Non-invasive detection of subclinical myocardial involvement in patients with chronic Chagas' infection

La detección de compromiso miocárdico precoz en la enfermedad de Chagas es muy importante para la elaboración de estrategias terapéuticas y/o preventivas. Para ello se utilizaron diferentes procedimientos de diagnóstico no invasivo. Con el propósito de evaluar en forma comparativa la capacidad de detectar anormalidades miocárdicas subclínicas se analizaron hallazgos en el ecocardiograma bidimensional, la prueba ergométrica graduada, la prueba de ajmalina y el electrocardiograma ambulatorio de 24 horas con sistema Holter. Se estudiaron 140 pacientes (78 varones y 62 mujeres) con serología positiva para la enfermedad de Chagas. Los resultados de este estudio muestran que la prueba de ajmalina es un marcador más sensible de daño miocárdico que el ecocardiograma bidimensional, el Holter o la prueba ergométrica y permite detectar el compromiso miocárdico chagásico en etapas más tempranas, aunque en algunos pacientes es posible demostrar anormalidades ecocardiográficas en presencia de una prueba de ajmalina negativa

Detección no invasiva de lesiones miocárdicas subclínicas en pacientes con infección chagásica crónica / Non-invasive detection of subclinical myocardial involvement in patients with chronic Chagas infection

La detección de compromiso miocárdico precoz en la enfermedad de Chagas es muy importante para la elaboración de estrategias terapéuticas y/o preventivas. Para ello se utilizaron diferentes procedimientos de diagnóstico no invasivo. Con el propósito de evaluar en forma comparativa la capacidad de detectar anormalidades miocárdicas subclínicas se analizaron hallazgos en el ecocardiograma bidimensional, la prueba ergométrica graduada, la prueba de ajmalina y el electrocardiograma ambulatorio de 24 horas con sistema Holter. Se estudiaron 140 pacientes (78 varones y 62 mujeres) con serología positiva para la enfermedad de Chagas. Los resultados de este estudio muestran que la prueba de ajmalina es un marcador más sensible de daño miocárdico que el ecocardiograma bidimensional, el Holter o la prueba ergométrica y permite detectar el compromiso miocárdico chagásico en etapas más tempranas, aunque en algunos pacientes es posible demostrar anormalidades ecocardiográficas en presencia de una prueba de ajmalina negativa (AU)

Effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy requirements in isolated rabbit heart.

The majority of patients with implanted cardioverter defibrillators (ICD) require antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements. This study investigated the effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and 80% successful defibrillation energy (ED50, ED80) was calculated in four phases: predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n = 6) with only Tyrode's solution infusion indicated that the preparation was stable over time. Defibrillation energy requirements significantly (p < 0.05) increased with all ARs. Low, medium, and high lidocaine concentrations increased ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively. Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%, respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158, 212, and 286%, respectively. The results of this study demonstrate a dose-dependent increase in defibrillation energy requirements by using lidocaine, diltiazem, and ajmaline. In patients with ICDs, administration of these drugs might cause a critical increase in defibrillation energy requirements, resulting in device failure.