1,721,177 research outputs found
Arrhythmogenic cardiomyopathy: electrical instability and intercalated disc abnormalities in transgenic mice
Full text linkAims: Mutations in genes encoding desmosomal proteins have been implicated in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the consequences of these mutations in early disease stages are unknown. We investigated
whether mutation-induced intercalated disc remodeling impacts on electrophysiological properties before the onset of cell death and replacement fibrosis.
Methods and Results: Transgenic mice with cardiac overexpression of mutant Desmoglein2 (Dsg2) Dsg2-N271S (Tg-NS/L) were studied before and after the onset of cell death and replacement fibrosis. Mice with cardiac overexpression of wild-type Dsg2 and wild-type
mice served as controls. Assessment by electron microscopy established that intercellular space widening at the desmosomes/adherens junctions occurred in Tg-NS/L mice before the onset of necrosis and fibrosis. At this stage, epicardial mapping in Langendorff-perfused
hearts demonstrated prolonged ventricular activation time, reduced longitudinal and transversal conduction velocities, and increased arrhythmia inducibility. A reduced action
potential upstroke velocity due to a lower Na+ current density was also observed at this stage
of the disease. Furthermore, co-immunoprecipitation demonstrated an in vivo interaction
between Dsg2 and the Na+ channel protein NaV1.5.
Conclusion: Intercellular space widening at the level of the intercalated disc (desmosomes/fascia adherens junctions) and a concomitant reduction in action potential upstroke velocity, as a consequence of lower Na+ current density, leads to slowed conduction and increased arrhythmia susceptibility at disease stages preceding the onset of necrosis and replacement
fibrosis. The demonstration of an in vivo interaction between Dsg2 and NaV1.5 provides a
molecular pathway for the observed electrical disturbances during the early ARVC stages
BICUSPID AORTIC VALVE: THE MOST FREQUENT AND NOT SO BENIGN CONGENITAL HEART DISEASE
Full text link: Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, with an incidence of approximately 1%. It can be silent and associated with normal valve function. However, a series of complications, even catastrophic, may occur with time: valve incompetence, valve stenosis by dystrophic calcification, infective endocarditis, progressive dilatation of the ascending aorta, aortic dissection, sudden death. The problem of BAV is not just about the number of semilunar cusps, but also the aortic wall. Severe non inflammatory degenerative changes (elastic fiber fragmentation, smooth muscle cells death, mucoid extracellular matrix accumulation=MEMA) is observed in the aortic wall of BAV patients, with intrinsic weakness accounting for progressive aneurysmal dilatation of the ascending aorta, valve incompetence and wall dissection. The link between valve and aortic wall pathology finds most probably an explanation in the embryology of the arterial pole, since neurocrestal cells play a role in the development of both the ascending aorta, aortic arch and semilunar valves. The frequent association of adult aortic coarctation and bicuspid aortic valve provides evidence to this hypothesis. BAV has a significant genetic component as to require screening of first degree relatives, as outlined by AHA/ACC 2022 guidelines
Cardiac arrest at rest and during sport activity: causes and prevention
No full textIn the Western Countries, cardiovascular diseases are still the most frequent cause of death, which is often sudden. Sudden death (SD) in the young population occurs at a rate of 1/100 000/year and carries a profound social impact both for the young age of the victims and the unanticipated occurrence. Physical effort is a triggering risk factor, in fact SD occurs three times more frequently in athletes than in non-athletes. The screening for sport activity fitness can identify apparently healthy subjects carrying a silent abnormality able to trigger sudden cardiac death during sport activity, thus the fitness screening could be lifesaving. The spectrum of cardiovascular conditions identified at post-mortem examination is quite extensive, and include: coronary, myocardial, valvular diseases, as well as conduction system abnormalities. In 20% of the cases, the heart is normal, and sudden cardiac death is ascribed to ionic channel disease. The diagnosis of cardiomyopathy is possible with the integration of electrocardiogram and echography, thus decreasing significantly the occurrence of SD of athletes in Italy, but early diagnosis of coronary artery disease still remains challenging. The best strategy to further decrease sudden cardiac death during sport activities consists in combining early diagnosis with widespread availability of defibrillators on site
[Sudden cardiac death in women].
No full textAlthough the incidence of sudden cardiac death (SCD) is greater in men than in women, it represents an important
mode of death also in the female gender. Sex-related differences have been identified not only in
the prevalence of the phenomenon, but also in risk factors and etiology of SCD. The peripartum period represents
a peculiar trigger of SCD in women with underlying cardiovascular substrates. Several lesions, both
congenital and acquired, may be identified at postmortem in SCD victims, including coronary artery, myocardial,
valve, and aortic diseases. While the incidence of SCD increases progressively with age in adult elderly
women to reach a 1:1 male:female ratio after the age of 80 years, mostly due to the increasing incidence
of atherosclerotic disease in the postmenopausal period, SCD in young women is a rare event and usually
associated with non-atherosclerotic disease, such as mitral valve prolapse, spontaneous coronary dissection,
myocarditis, inherited cardiomyopathies and congenital heart diseases. The heart can be found structurally
normal and inherited ion channel diseases are often implicated. Gender differences in the risk of SCD deserve
further attention, since they affect the evaluation of interventions designed to reduce the rate of female
SCD
Coronary Arteries: Normal Anatomy With Historical Notes and Embryology of Main Stems
Full text linkAnatomy of subepicardial coronary arteries became a topic of investigation at autopsy in Florence (Italy) by Banchi in the early twentieth century, with the discovery of dominant and balanced patterns. Thereafter, in the 60's of the same century Baroldi in Milan did post-mortem injection with spectacular three-dimensional casts. Later Sones at the Cleveland Clinic introduced selective coronary arteriography for in vivo visualization of coronary arteries. In the present chapter we show these patterns, as well as normal variants of origin and course with questionable risk of ischemia, like myocardial bridge as well as origin of the left circumflex coronary artery from the right sinus with retroaortic course. As far as embryology, the coronary arteries and veins are epicardial in origin and finally connect the former with the aorta, and the latter with the sinus venosus. At the time of spongy myocardium, intramural blood supply derives directly by the ventricular cavities, whereas later, at the time of myocardial compaction, vascularization originates from the subepicardial network. The connection of the subepicardial plexus with the aorta occurs with prongs of the peritruncal ring, which penetrate the facing aortic sinuses. Septation of truncus arteriosus is not responsible for the final position of the coronary orifices. Infact in transposition of the great arteries coronary ostia are regularly located within facing sinuses of the anterior aorta
The missing pieces in the puzzle of arrhythmic mitral valve prolapse: papillary muscles, mitral anulus disjunction and myocardial scarring
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