Desmoplakin Mutant Murine Model
Desmoplakin (DSP), localized to chromosome 6p24, was initially identified as the mutant gene causing autosomal recessive Carvajal syndrome 20,21 and later shown to cause autosomal dominant ARVD8 14 . Desmoplakin is a major component of desmosomes, complex intercellular junctions assembled through cooperative interactions between multiple proteins 22,23 . The majority of patients with DSP have the classic form of ARVC D, although a substantial number of affected individuals have associated LV...
References
Fox PR, Sisson D, Moise N, eds (1999) Textbook of canine and feline cardiology, 2nd edn. WB Saunders, Philadelphia 2. Maron BJ, Towbin JA, Thiene G et al (2006) Contemporary definitions and classification of the cardiomyopathies. An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee Quality of care and outcomes research and functional ge-nomics and translational biology interdisciplinary working groups, and...
Electrical Coupling at Gap Junctions in the Heart
Cardiac muscle is not a true electrical syncytium. Rather, it is composed of individual cells, each in vested with a continuous lipid bilayer which provides a considerable degree of electrical insulation. Electrical activation of the heart requires intercellular transfer of current, a process that can only occur at gap junctions 2 . Thus, the number, size, and distribution of gap junctions are important determinants of impulse propagation in cardiac muscle. Furthermore, alterations in the...
Voltage Mapping Differential Diagnosis Between ARVCD and Idiopathic RVOT Tachycardia
Idiopathic RVOT tachycardia refers to nonfamilial tachycardias, either paroxysmal or repetitive mono-morphic, with a left bundle brunch block and inferior axis QRS pattern that are characteristically triggered by physical exercise or by catecholamine infusion in young individuals without clinically detectable structural heart disease. Although RVOT tachycardia is considered benign and not progressive, it may cause syncope and, rarely, sudden cardiac death 44-46 . These malignant events are most...
Task Force Criteria
In many of these individuals, the clinical findings were more subtle than those reported by Marcus et al. 1 , and yet they appeared to be affected by a variant of the same condition. In some of those identified at postmortem, clinical findings antemortem had perhaps not been recognized or interpreted appropriately, and opportunities to institute potentially life-saving measures were missed. The gold standard for making a diagnosis of ARVC D is accepted as the demonstration of transmural...
Gross and Histologic Diagnosis
The pathologic diagnosis of ARVC D in autopsy hearts or those explanted at the time of cardiac transplantation has been traditionally based upon gross and histologic evidence of transmural fatty or fibrofatty myocardial replacement of the right ventricular free wall. This could be considered a myocardial dystrophy, extending from the epicardium towards the endocardium, sparing only the trabecular myocardium 3-8 . Table 4.1 summarizes the main pathologic features as observed in the original...
Voltage Mapping Methods and Equipment
Three-dimensional electroanatomic voltage mapping technique is performed using the CARTO system Biosense-Webster 20-26 . In brief, the magnetic mapping system includes a magnetic sensor in the catheter tip that can be localized in 3D using ultralow magnetic field generators placed under the fluoro-scopic table. A 7F Navi-Star catheter, with a 4 mm distal tip electrode and a 2 mm ring electrode with an interelectrode distance of 1mm, is introduced into the RV under fluoroscopic guidance and used...
Pure Fatty Infiltration of the Right Ventricle vs ARVCD
At present, considerable importance is given to the finding of fatty infiltration of the myocardium, since cardiac magnetic resonance imaging has the ability to identify adipose tissue in vivo with consequent diagnostic and therapeutic implications. It is still a matter of debate whether fatty infiltration of the right ventricle per se should be considered a morphologic hallmark of ARVC D 19 . We must recognize that the original distinction in two histologic variants, i.e., fatty and...
ARVCD vs Idiopathic RVOT Ventricular Tachycardia Differential Diagnosis
VT associated with ARVC D may be localized in the outflow tract mimicking idiopathic RVOT tachycardia. Discrimination between the two entities is mandatory for prognostic and therapeutic reasons as well as for genetic implication 80, 81 . Standardized diagnostic criteria for the diagnosis of ARVC D have been proposed and are known as the Task Force criteria 32 . According to these Task Force guidelines, the diagnosis of ARVC D is based on the presence of major and minor criteria including ECG,...
Angiographic Features of Wall Structure and Wall Motion in ARVCD
A variety of morphological and structural RV an-giographic features have been reported to be suggestive of ARVC D. These include global and regional dilatation, dilatation of the outflow tract, localized akinetic or dyskinetic bulges and outpouchings, polycyclic contours cauliflower aspect , and tra-becular hypertrophy and or disarray with deep horizontal fissures pile d'assiettes as well as dye persistence due to delayed contrast evacuation. In the first publications on RV angiography in ARVC...
Abnormal SAECG
The presence of late potentials and delayed activation of ventricular myocardium detected in the SAECG is considered to represent slowed ventricular conduction, which is a substrate for reentrant tachyarrhyth mias Fig. 13.4 . In the first reported series of patients with this disease, late potentials were recorded in 81 of patients by Marcus, Fontaine et al. 1 . In the 151 patients described by Wichter et al. 17 ,late potentials were found in 41 . Kinoshita et al. 25 analyzed the SAECG in 28...
Ventricular Tachyarrhythmias in Normal Hearts Overview and Classification
VT is usually associated with structural cardiac disease. The most common anatomic substrate of ventricular arrhythmias is chronic ischemic heart disease. Other structural disorders associated with VT are valvular and congenital heart disease, cardiac tumors, myocarditis, and cardiomyopathies. Only approximately 10 of arrhythmias occur in the absence of structural heart disease assessed by clinical examination and imaging studies. Some of them may be caused by inherited cardiac diseases such as...
Intercalated Disc Junctions
The ID is the area of end-to-end connections between cardiomyocytes, and consists of three junc-tional complexes desmosomes, fascia adherens, and gap junction also called the nexus . The desmosome is composed of a cytoplasmic electron-dense plaque of intracellular filaments containing desmoplakin, plakoglobin, plakophilin, and transmembrane calcium-sensitive proteins, i.e., desmoglein and desmo-collin. In addition to cell-to-cell adhesion, this type of junction provides a structural connection...
