An unusual ectopic ventricular rhythm in a young woman.

A case of a 22-year-old young pregnant woman with palpitations and near syncope is presented. Holter monitoring showed very frequent premature beats and runs of wide complex tachycardia, refractory to antiarrhythmic drugs. Electrophysiologic evaluation disclosed spontaneous automatism arising in an atriofascicular pathway. Differential diagnosis is discussed.

Human γ2-AMPK Mutations.

In humans, dominant mutations in the gene encoding the regulatory γ2-subunit of AMP-activated protein kinase (PRKAG2) result in a highly penetrant phenotype dominated by cardiac features: left ventricular hypertrophy, ventricular pre-excitation, atrial tachyarrhythmia, cardiac conduction disease, and myocardial glycogen storage. The discovery of a link between the cell's fundamental energy sensor, AMPK, and inherited cardiac disease catalyzed intense interest into the biological role of AMPK in the heart. In this chapter, we provide an introduction to the spectrum of human disease resulting from pathogenic variants in PRKAG2, outlining its discovery, clinical genetics, and current perspectives on its pathogenesis and highlighting mechanistic insights derived through the evaluation of disease models. We also present a clinical perspective on the major components of the cardiomyopathy associated with mutations in PRKAG2, together with less commonly described extracardiac features, its prognosis, and principles of management.

Chronic Activation of γ2 AMPK Induces Obesity and Reduces ß Cell Function.

Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.

Characterization of the distal insertion of atriofascicular accessory pathways and mechanisms of QRS patterns in atriofascicular antidromic tachycardia.

BACKGROUND: The distal insertion of right atriofascicular pathways remains a source of debate. Moreover, there are various morphologies of preexcited QRS complexes involving atriofascicular pathways that have been poorly characterized. OBJECTIVE: To characterize the distal insertion of atriofascicular accessory pathways and to provide a mechanism for the change in QRS morphology observed between short and long ventriculo-His (V-H) antidromic atrioventricular reentrant tachycardias (AVRTs) in the same patient. METHODS: Thirteen patients with atriofascicular pathways and preexcited AVRT with short V-H and long V-H intervals were studied. For each patient, the tachycardia cycle length, V-H interval, QRS width, and axis were compared. A baseline His-ventricular interval was also recorded. RESULTS: The baseline His-ventricular interval was significantly longer than the V-H interval during antidromic AVRT (median 50 ms vs. 10 ms; P < .0001). Retrograde right bundle branch block increased the V-H interval (median 10 ms vs. 85 ms; P < .0001), the tachycardia cycle length (median of 302.5 ms vs. 350 ms; P < .0001), and the QRS width (median 120 ms vs. 140 ms; P < .0002). At least subtle changes in QRS morphology, axis, or QRS width were seen in all patients. CONCLUSIONS: The distal insertion of right atriofascicular pathways fuses with the right bundle branch. The various QRS morphologies seen during the change from short V-H to long V-H antidromic AVRT can be explained by fusion, particularly over the left anterior fascicle.

Epilepsy or syncope? An analysis of 55 consecutive patients with loss of consciousness, convulsions, falls, and no EEG abnormalities.

BACKGROUND: Patients with loss of consciousness and convulsion often have the diagnosis of epilepsy despite normal electroencephalograms (EEGs). OBJECTIVE: To evaluate the proportion of patients referred to neurologists with presumed epilepsy and normal EEGs who have an alternative cause of syncope. METHODS: It was a cross-sectional study of 55 consecutive patients aged 6-85 (41 +/- 24) years presenting with faints, falls, convulsions, and normal EEGs, who were referred to neurologists before going to cardiologists. All patients underwent clinical examination, electrocardiogram, and echocardiogram. Head-up tilt table testing (HUT), 24-hour-Holter, and carotid sinus massage was offered as needed. Electrophysiological studies were undertaken in patients with structural heart disease or severe palpitations. RESULTS: Anticonvulsant agents had been prescribed to 35 patients (64%) before entering the study. Vasovagal syncope was found in 22 (40%) patients, life-threatening arrhythmias in seven (13%), carotid sinus hypersensitivity in six (11%), orthostatic hypotension in three (5%), and aortic stenosis in one (2%). Etiology of syncope could not be found in 16 (29%) patients. Arrhythmias comprised two complete atrioventricular blocks, one sustained monomorphic ventricular tachycardia, one ventricular fibrillation, one atrial tachycardia, and two atrioventricular node reentrant tachycardias. Two patients developed a prolonged asystole during HUT. Presumptive diagnosis of syncope was found in 39 patients (71%). Patients on or off anticonvulsant drugs had 64% and 84% diagnosis of syncope, respectively (odds ratio = 0.33; 95% confidence interval 0.08-1.36; P = 0.13). CONCLUSIONS: Life-threatening arrhythmias and syncope can be present in patients with presumed epilepsy and normal EEG. Prescription of anticonvulsant agents in these patients should wait for a cardiovascular assessment.

Effects of right bundle branch block on the antidromic circus movement tachycardia in patients with presumed atriofascicular pathways.

BACKGROUND: The typical and most common tachycardia in patients with atriofascicular pathways is a macro reentrant tachycardia, with anterograde conduction over the decrementally conducting bypass tract and retrograde conduction over the right bundle branch-His-AV node axis resulting in a short V-right bundle branch and short V-H interval. OBJECTIVES: To report on changes in rate and QRS configuration when right bundle branch block (RBBB) develops spontaneously during antidromic tachycardia using an atriofascicular fiber. METHODS: Three of 25 patients with an antidromic circus movement tachycardia using a right-sided atriofascicular pathway showed episodes of right bundle branch block (RBBB) during ventriculo-atrial conduction. Effect of retrograde RBBB on tachycardia rate and QRS configuration was studied using intracardiac and extracardiac recordings. RESULTS: All 3 patients showed prolongation of their V-A interval when retrograde RBBB occurred during tachycardia, resulting in a longer tachycardia cycle length. The VA time increase ranged from 85 to 100 msec, with a mean 346 +/- 5 msec. Two of the 3 patients also showed a change in QRS configuration due to a more leftward shift of the frontal plane QRS axis. CONCLUSION: Rate changes in antidromic tachycardia in patients with atriofascicular fibers can be based on a shift in VA conduction from one bundle branch to the other. This may be accompanied by changes in the frontal plane QRS axis because of a change in ventricular activation sequence.