Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease. While desmosomal gene mutations are considered major causes of ARVC, LMNA mutations have ...been reported to be possible causes of ARVC. In this study, we performed extensive genetic screening for LMNA mutations in our Japanese ARVC cohort to assess the prevalence and characteristics of LMNA mutation-positive ARVC cases. Methods Our study cohort consisted of 57 ARVC probands. Genetic analyses were performed by using direct sequencing and targeted sequencing of LMNA and four desmosomal genes. We compared clinical features of probands with desmosomal gene mutations to those of probands with LMNA mutations. Results Among 57 clinically diagnosed ARVC probands, we identified desmosomal gene mutations in 26 probands (45.6%) and two LMNA mutations in two probands. The first LMNA mutation p.M1K was detected in a 62-year-old male proband, while the second mutation p.W514X was found in a 70-year-old male proband. Compared to the 26 probands with desmosomal gene mutations, in the two probands with LMNA mutations, the mean age at diagnosis was significantly higher, and their heart rate at the diagnosis was significantly slower. While both probands with LMNA mutations underwent pacemaker implantation, only one proband with desmosomal mutations received this treatment (2/2 vs. 1/26). Conclusion Genetic screening for LMNA gene is important for ARVC patients, particularly in patients with bradycardia.
Long-QT syndrome (LQTS) is an inherited arrhythmia characterized by prolonged ventricular repolarization and malignant tachyarrhythmias. LQT1, LQT2, and LQT3 are caused by mutations in KCNQ1 (LQT1), ...KCNH2 (LQT2), and SCN5A (LQT3), which account for approximately 90% of genotyped LQTS patients. Most cardiac events in LQT1 patients occur during exercise, whereas patients with LQT3 tend to have arrhythmic events during rest or asleep.
The study aimed to identify a genetic mutation in a Japanese man who presented with sinus node dysfunction and prolonged QT interval on exercise and epinephrine stress tests, as well as to clarify the electrophysiological properties of mutant channels.
LQTS-related genes were screened in this patient. Electrophysiological functional assays were conducted with a heterologous expression system.
We identified a heterozygous missense SCN5A mutation, V2016M, which changes the last amino acid of the cardiac sodium channel. Electrophysiological analyses revealed that the mutant channels exhibited a loss-of-function feature, decreased peak sodium current densities (wild type 175.2 ± 17.6 pA/pF; V2016M 97.2 ± 16.0 pA/pF; P < .01). In addition, the mutant channels showed gain-of-function features: increased late sodium currents by protein kinase A activation (wild type 0.07 ± 0.01%; V2016M 0.17 ± 0.03%; P < .05) and impaired inactivation of sodium channels by protein kinase A or C activation.
We identified an SCN5A mutation in a patient with sinus node dysfunction and epinephrine-induced QT prolongation, which was an atypical phenotype for LQT3. The electrophysiological properties of the mutant channels might be associated with the overlapping clinical features of the patient.
Abstract Objectives This study sought to demonstrate the prevalence, mechanism, and electrocardiographic and electrophysiological characteristics of upper septal idiopathic left fascicular ...ventricular tachycardia (US-ILVT). Background ILVT is classified into left anterior and posterior types with no clear data about US-ILVT. Methods Among 193 ILVT patients, we identified 12 patients (6.2%; age 41 ± 22 years, 7 men) with US-ILVT. Results Of 12 patients with US-ILVT, 6 patients (50%) had previous history of radiofrequency catheter ablation for common ILVT. Sustained VT (cycle length: 349 ± 53 ms) was seen in all patients with a QRS interval slightly wider (104 ± 18 ms) than that during sinus rhythm (90 ± 19 ms). The VT exhibited an identical QRS configuration as sinus rhythm in 6 (50%) and incomplete right bundle branch block configuration in another 6. His-ventricular interval during VT was always shorter than that during sinus rhythm (27 ± 5 ms vs. 47 ± 10 ms). Purkinje potentials were activated in a reverse direction to that of common ILVT; namely, the diastolic potential (P1 ) was activated retrogradely but the pre-systolic potential (P2 ) was activated antegradely. At the left upper-middle ventricular septum, P1 potential was recorded during VT, preceding the QRS by 54 ± 20 ms. Radiofrequency catheter ablation at that site eliminated the VT with no recurrence during a 58 ± 35 months of follow-up. Conclusions US-ILVT is an identifiable VT that shares common criteria with ILVT and has a narrow QRS interval. Some US-ILVT cases appeared after common ILVT ablation. It is a reverse type of common ILVT (orthodromic form) with baseline morphological abnormalities that might provide a potential substrate for such VT.
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