{'fraction_non_alphanumeric': 0.029649595687331536, 'fraction_numerical': 0.014076070679844266, 'mean_word_length': 5.640159045725646, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Fasciculoventricular Pathways Responsible for Ventricular Preexcitation in Patients With Danon Disease

September 2018 1 Danon disease, caused by the mutations in the gene of LAMP2 (lysosome-associated membrane protein 2), is an X-linked dominant disorder classically characterized by the triad of cardiomyopathy, skeletal myopathy, and mental retardation.1,2 Cardiomyopathy typically manifests a hypertrophic phenotype; ventricular preexcitation is the most frequently encountered ECG abnormality in such patients and occurs in 68.2% of men and 26.7% of women.3 The pathological hallmark of Danon disease is intracytoplasmic vacuole accumulation containing glycogen granules and autophagic materials which lead to cardiac hypertrophy,1 but the underlying mechanism responsible for ventricular preexcitation continues to be a perplexing conundrum. The objective of this study was to determine the mechanism of ventricular preexcitation in patients with Danon disease. We enrolled 197 patients with unexplained left ventricular hypertrophy, and ventricular preexcitation was present in 10 (10 of 197; 5%) unrelated patients in whom genetic testing identified 3 (3 of 10; 30%) Danon disease patients with different LAMP2 mutations. Of the 3 patients, all were men aged 17 to 23 years at diagnosis, and electrophysiological study was performed in 2 patients. Intracardiac recordings in patient 1 demonstrated a slightly short His-ventricular (HV) interval of 30 ms, and local ventricular activation recorded at the His bundle area significantly earlier than the right ventricular apex during sinus rhythm (see the first beat in the Figure [A]). During ventricular overdrive stimulation, ventriculoatrial (VA) conduction was decremental and concentric with the earliest atrial retrograde activation at the His bundle, and the activation sequence of His bundle and right bundle (RB) was noted to be similar to sinus activation with H-RB sequence (Figure [A]). The deflections of the RB electrogram during sinus rhythm and ventricular pacing were −/+ and +/−, respectively; the deflection of the His bundle electrogram was −/+/− during both sinus rhythm and ventricular pacing, suggesting that the His activation during ventricular pacing was orthodromic, while the RB potential was activated retrograde. Atrial programmed stimulation resulted in prolongation of the atrio-His (AH) and atrioventricular (AV) intervals without changing QRS morphologies and HV intervals (Figure [B]), thereby excluding the presence of antegrade conduction over an accessory pathway connecting the atrium to the ventricle. These findings favor the diagnosis of a fasciculoventricular (FV) pathway with bidirectional conduction which takes off from the proximal part of the His bundle, bypasses conduction over the distal portion of the His bundle, the bundle branches, and Purkinje system and hence, is responsible for ventricular preexcitation and early local ventricular activation at the His bundle region during sinus rhythm, as well as the H-RB activation sequence during ventricular pacing (Figure [C] and [D]). In patient 2, the baseline HV intervals measured 22 ms during sinus rhythm. With programmed atrial stimulation, AV conduction was decremental with evidence of dual AV node physiology, but the HV intervals and degree of ventricular RESEARCH LETTER