BackgroundThe epithelial growth factor receptor family of tyrosine kinases modulates embryonic formation of semilunar valves. We hypothesized that mice heterozygous for a dominant loss‐of‐function mutation in epithelial growth factor receptor, which are Egfr
Vel/+ mice, would develop anomalous aortic valves, valve dysfunction, and valvular cardiomyopathy.Methods and ResultsAortic valves from Egfr
Vel/+ mice and control mice were examined by light microscopy at 2.5 to 4 months of age. Additional Egfr
Vel/+ and control mice underwent echocardiography at 2.5, 4.5, 8, and 12 months of age, followed by histologic examination. In young mice, microscopy revealed anatomic anomalies in 79% of Egfr
Vel/+ aortic valves, which resembled human unicuspid aortic valves. Anomalies were not observed in control mice. At 12 months of age, histologic architecture was grossly distorted in Egfr
Vel/+ aortic valves. Echocardiography detected moderate or severe aortic regurgitation, or aortic stenosis was present in 38% of Egfr
Vel/+ mice at 2.5 months of age (N=24) and in 74% by 8 months of age. Left ventricular enlargement, hypertrophy, and reversion to a fetal myocardial gene expression program occurred in Egfr
Vel/+ mice with aortic valve dysfunction, but not in Egfr
Vel/+ mice with near‐normal aortic valve function. Myocardial fibrosis was minimal or absent in all groups.ConclusionsA new mouse model uniquely recapitulates salient functional, structural, and histologic features of human unicuspid aortic valve disease, which are phenotypically distinct from other forms of congenital aortic valve disease. The new model may be useful for elucidating mechanisms by which congenitally anomalous aortic valves become critically dysfunctional.
Bundle branch reentrant ventricular tachycardia (BBR-VT) is an uncommon form of macro-reentrant ventricular tachycardia (VT) characterized by a fast (200-300 beats/min) wide complex tachycardia involving the His-Purkinje system. It can present with syncope, hemodynamic instability, or cardiac arrest. Diagnosis is challenging and is based on electrophysiological findings. Radiofrequency catheter ablation is currently regarded as the first-line therapy.CASE PRESENTATION: 56-year-old male with a history of morbid obesity (BMI 70), HTN, type 2 DM, and atrial tachycardia on Sotalol was admitted for acute hypoxemic respiratory failure. Baseline ECG had intraventricular conduction delay (IVCD) with PVCs. He developed persistent atrial tachycardia in the setting of respiratory failure, so Flecainide was initiated. After 2 doses, he developed wide complex tachycardia with HR above 200s. Flecainide was discontinued, and he was started on Amiodarone. Arrhythmia recurred the next day with HR 210, successfully treated with Lidocaine. However, patient developed atrial tachycardia that degenerated to VT storm despite Amiodarone, Lidocaine, Adenosine, and 3 unsuccessful attempts at defibrillation. Thus, Procainamide was initiated, and he stabilized after 1 hour. He continued to have recurrences of VT which were felt to be BBR-VT. The use of fluoroscopic imaging and electrophysiologic mapping was limited due to patient size. A dual-chamber pacemaker was implanted with an unsuccessful attempt at ablation in OR. Arrhythmias recurred, and pacemaker interrogation demonstrated atrial tachycardia with 1:1, 2:1, and Wenckebach conduction with HR 130s. Procainamide was stopped on day 10 without further VT until day 13, but PVCs noted. The patient then developed atrial tachycardia that transitioned into BBRVT with HR 200s.AV node and right bundle ablation with mapping technology were performed on day 14 after finding bed accommodation. Postablation, his pacemaker was reprogrammed to non-tracking mode. No further ventricular arrhythmias were observed.DISCUSSION: Atrial tachycardia initiated this patient's BBR-VT. Anti-arrhythmic therapy used may have further delayed conduction in the His-Purkinje system and promoted BBR-VT. His QRS morphology during BBR-VT was of typical right bundle block with AV dissociation. BBR-VT was suspected due to underlying IVCD with atrial tachycardia and PVCs. The diagnosis was ultimately confirmed in the EP lab. It is important to recognize BBR-VT and understand its associations, as pharmacologic antiarrhythmic therapy is usually ineffective and may worsen the condition. Radiofrequency catheter ablation of either bundle branch will treat BBR-VT definitively, as observed in this patient.CONCLUSIONS: BBR-VT has a high risk for morbidity and mortality and is difficult to treat with pharmacologic interventions or cardioversion. Treat definitively with radiofrequency catheter ablation.
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