ajmaline and Myotonic-Dystrophy

Myotonic dystrophy type 1 (DM1) generates missplicing of the SCN5A gene, encoding the cardiac sodium channel (Nav 1.5). Brugada syndrome, which partly results from Nav 1.5 dysfunction and causes increased VF occurrence, can be unmasked by ajmaline. We aimed to investigate the response to ajmaline challenge in DM1 patients and its potential impact on their sudden cardiac death risk stratification.. Among 36 adult DM1 patients referred to our institution, electrophysiological study and ajmaline challenge were performed in 12 patients fulfilling the following criteria: (1) PR interval >200 ms or QRS duration >100 ms; (2) absence of complete left bundle branch block; (3) absence of permanent ventricular pacing; (4) absence of implantable cardioverter-defibrillator (ICD); (5) preserved left-ventricular ejection fraction >50%; and (6) absence of severe muscular impairment. Of note, DM1 patients with ajmaline-induced Brugada pattern (BrP) were screened for SCN5A.. In all the 12 patients studied, the HV interval was <70 ms. A BrP was unmasked in three patients but none carried an SCN5A mutation. Ajmaline-induced sustained ventricular tachycardia occurred in one patient with BrP, who finally received an ICD. The other patients did not present any cardiac event during the entire follow-up (15 ± 4 months).. Our study is the first to describe a high prevalence of ajmaline-induced BrP in DM1 patients. The indications, the safety, and the implications of ajmaline challenge in this particular setting need to be determined by larger prospective studies.

Topics: Adolescent; Adult; Aged; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myotonic Dystrophy; Prospective Studies

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.. 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.. 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.. 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).. 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.

Topics: Adult; Ajmaline; Brugada Syndrome; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Flecainide; Follow-Up Studies; France; Humans; Incidence; Male; Myotonic Dystrophy; Prevalence; Prognosis; Prospective Studies; Survival Rate; Voltage-Gated Sodium Channel Blockers

Twelve patients with dystrophia myotonica had cardiac electrphysiological study for conduction disturbances (five cases) or for syncope (seven cases). Conduction disturbances were found in each case, being intranodal in two cases, intra-Hisian in three cases, or diffuse in seven cases. These findings are in agreement with those previously reported, and may be related to the high incidence of sudden death in these patients. Pacemakers are advocated in symptomatic patients, and in some asymptomatic patients with severe and diffuse lesions.

Topics: Adolescent; Adult; Aged; Ajmaline; Electrocardiography; Female; Heart Conduction System; Humans; Male; Middle Aged; Myotonic Dystrophy

Six patients with congenital myotonia and 4 patients with myotonic dystrophy have been examined clinically before and after the administration of N-propyl-ajmalin, an alkaloid frequently used as a cardiac antiarrhythmic drug. All patients but one reported a good to moderate improvement of their myotonic muscle stiffness. This was verified by measuring the time the patients needed to ascend a flight of stairs and by recording the speed of opening the hand. The amplitude of the compound muscle action potential decreased during repetitive nerve stimulation in myotonic patients. This decrease was not influenced by N-propyl-ajmalin. It seems to be due to the increased after-depolarization observed in myotonic fibres which causes partial inactivation of the Na-carrying system. From one patient a muscle biopsy was taken and intracellular potentials were measured with a microelectrode. Almost all muscle cells investigated showed myotonic activity which was completely abolished by addition of 10(-5) g/ml N-propyl-ajmalin to the bathing fluid. The development and duration of "warm-up" is illustrated and a possible electrophysiological basis is discussed.

Topics: Action Potentials; Ajmaline; Female; Humans; Locomotion; Male; Muscle Contraction; Muscles; Myotonia; Myotonia Congenita; Myotonic Dystrophy