Desmin mutations and arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias, associated with mutations in the desmosomal genes. Only a missense mutation in the DES gene coding for desmin, the intermediate filament protein expressed by cardiac and skeletal muscle cells, has been recently associated with ARVC. We screened 91 ARVC index cases (53 negative for mutations in desmosomal genes and an additional 38 carrying desmosomal gene mutations) for DES mutations.

Mutations in the area composita protein αT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy.

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of juvenile sudden death and is characterized by fibro-fatty replacement of the right ventricle. Mutations in several genes encoding desmosomal proteins have been identified in ARVC. We speculated that αT-catenin, encoded by CTNNA3, might also carry mutations in ARVC patients.

Classification and histological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease.

In the WHO 1996 classification of cardiomyopathies, myocarditis is defined as an "inflammatory disease of the myocardium associated with cardiac dysfunction" and is listed among "specific cardiomyopathies". Myocarditis is diagnosed on endomyocardial biopsy (EMB) by established histological, immunological, and immunohistochemical criteria, and molecular techniques are recommended to identify viral etiology. Infectious, autoimmune, and idiopathic forms of inflammatory cardiomyopathy are recognized that may lead to dilated cardiomyopathy.

Three-dimensional molecular reconstruction of rat heart with mass spectrometry imaging.

Cardiovascular diseases are the world's number one cause of death, accounting for 17.1 million deaths a year. New high-resolution molecular and structural imaging strategies are needed to understand underlying pathophysiological mechanism.

Lipid insudation as a cause of structural failure of a stentless pericardial bioprosthesis.

The Sorin Pericarbon Freedom (SPF) valve is a stentless bioprosthesis made from bovine pericardium, with a peculiar design aimed at preventing the mechanical failures observed with old models of stented pericardial bioprostheses. Herein, the case is described of a patient who presented with severe regurgitation of a SPF six years after aortic valve replacement, caused by commissural dehiscence. Both, microradiographic and histologic investigations, revealed mild calcific deposits and massive lipid infiltration, thus confirming that a patient-related mechanism such as 'atheromasia' can account for structural valve deterioration also in recipients of pericardial bioprostheses.

Arrhythmogenic right ventricular cardiomyopathy. What is needed for a cure?

There have been major advances in recent years in the clinical setting of arrhythmogenic right ventricular cardiomyopathy, including new diagnostic criteria, a changing spectrum of the disease with even left dominant forms, the role of cardiac magnetic resonance and electroanatomic mapping, the expanding use of genetic screening and the existence of overlapping phenotypes. Moreover, early diagnosis at pre-participation screening with sports disqualification and risk stratification for the indication of ICD have been shown to be life-saving. In addition to traditional therapies targeting arrhythmias and congestive heart failure, an effective treatment of the disease could be based on the discovery of the molecular mechanisms involved in the pathobiology of the disease in order to block the onset and progression of cell death.

Extracellular matrix graft for vascular reconstructive surgery: evidence of autologous regeneration of the neoaorta in a murine model.

Objectives: The study aimed to evaluate the efficacy of the porcine small intestine submucosa extracellular matrix (SIS-ECM) in a murine model, as a possible vascular patch for clinical use in reconstructive vascular and potentially cardiac surgery.

Methods: Fifteen adult male Sprague Dawley rats and five green fluorescent protein (GFP) rats were enrolled in this study. The SIS-ECM graft (6 mm long, 4 mm wide) was implanted for patch plasty on the abdominal aorta of the animal, after excising part of its anterior wall.

Criteria for histopathologic diagnosis of aortic disease consensus statement from the SIAPEC-IAP study group of "cardiovascular pathology" in collaboration with the association for Italian cardiovascular pathology.

Nowadays, the histopathological study of surgical specimens is an essential part of the diagnostic work-up in aortic disease, and not only in characterizing the neoplastic forms. Despite increasing clinico-therapeutic complexity of aortic pathology, the criteria for histopathological diagnosis have not been properly updated over the years, with the result that we find inconsistent terminology and little standardization of diagnostic criteria. In light of this consideration, the SIAPeC-IAP Study Group of "Cardiovascular Pathology", in collaboration with the Association for Italian Cardiovascular Pathology, has created this consensus document, with the aim of defining the features of histopathological substrates in the main non-neoplastic aortopathies (atherosclerotic, "degenerative"/non inflammatory, and inflammatory) and of systematizing diagnostic criteria even for the rare tumours of the aorta and pulmonary artery.

Intercalated disc abnormalities, reduced Na(+) current density, and conduction slowing in desmoglein-2 mutant mice prior to cardiomyopathic changes.

Aims: 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 remodelling impacts on electrophysiological properties before the onset of cell death and replacement fibrosis.

The pathology of TRI-Tech valve leaflet escape.

Background And Aim Of The Study: The study aim was to investigate leaflet escape in the TRI-Tech mechanical valve, as reported in three patients.

Methods: Among the three patients, one patient with a mitral prosthesis from which leaflet escape occurred underwent a successful reoperation. However, two patients with an aortic prosthesis from which leaflet escape occurred died suddenly.

[Sudden cardiac death in women].

Although 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.

The changing spectrum of arrhythmogenic (right ventricular) cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a clinically and genetically heterogeneous heart muscle disorder associated with ventricular arrhythmias and risk of sudden death. The disease is heredo-familial, and mutations in desmosomal genes have been identified in about half of patients. Recent experimental models confirm this disease develops after birth due to progressive myocardial dystrophy.

Why and how to support screening strategies to prevent sudden death in athletes.

Sudden death in athletes occurs because of the existence of hidden cardiovascular disorders which, during effort, may jeopardize the electrical stability of the heart, triggering ventricular tachycardia and/or fibrillation. Apart from rare conditions of ion channel diseases in the setting of a structurally normal heart, in which the disorder may be easily diagnosed on basal or stress test ECG, cardiac abnormalities at risk of causing sudden death may affect the aorta (Marfan syndrome), the coronary arteries (congenital coronary artery anomalies, premature coronary atherosclerosis), the myocardium (hypertrophic and arrhythmogenic cardiomyopathy), the valves (bicuspid aortic valve, mitral valve prolapse) and the conduction system (pre-excitation syndromes). These structural heart disorders may be detected by ECG and/or echo.

The peritoneum as a natural scaffold for vascular regeneration.

Objective: The peritoneum has the same developmental origin as blood vessels, is highly reactive and poorly thrombogenic. We hypothesize that parietal peritoneum can sustain development and regeneration of new vessels.

Methods And Results: The study comprised two experimental approaches.

Long-term durability of a St. Jude medical X-cell bioprosthesis.

An 82-year-old female had undergone aortic valve replacement with a 23-mm St. Jude Medical X-Cell porcine bioprosthesis (XCB), a glutaraldehyde-fixed valve subjected to a decellularization process. More than 13 years later, she required a repeated operation because of XCB structural failure.

Should all individuals with a nondiagnostic Brugada-electrocardiogram undergo sodium-channel blocker test?

Background: The diagnostic Brugada-electrocardiogram (Br-ECG) is characterized by "coved-type" ST-segment elevation (type 1) in V(1) to V(2)/V(3). The sodium-channel blocker test is clinically used to unmask diagnostic Br-ECG in patients with nondiagnostic "saddle-back" Br-ECG (type 2 and type 3).

Objective: To assess the prognostic value of the sodium-channel blockers test in individuals with a nondiagnostic Br-ECG.

[Bicuspid aortic valve].

Bicuspid aortic valve (BAV) is the most common congenital heart disease, whose natural history is characterized by the incidence of clinically relevant valvular (stenosis, regurgitation, endocarditis) and/or vascular complications regarding the thoracic aorta (dilation, aneurysm, dissection) and, rarely, intracranial and epiaortic arteries. BAV may be heritable, with an autosomal dominant pattern of inheritance with reduced penetrance; moreover, some data suggest that BAV and thoracic aorta aneurysm are independent manifestations of a single gene defect. The prevalence of BAV and its susceptibility to valvular and aortic complications during the whole life result into the need of strict clinical follow-up and appropriate therapies (medical as well as surgical) to be addressed according to guidelines specifically designed for these patients.

The effects of basic fibroblast growth factor in an animal model of acute mechanically induced right ventricular hypertrophy.

Objective: To evaluate the effect of a continuous infusion of basic fibroblast growth factor on the adaptive potential of the right ventricular myocardium after 30 days of mechanically induced overload in rats. Materials and methods We banded the pulmonary trunk, so as to increase the systolic workload of the right ventricle, in six Lewis/HanHsd rats at the age of 11 weeks, using six adult rats as controls. The six adult rats were also banded and received an additional continuous infusion of basic fibroblastic growth factor, using six rats with a continuous infusion of basic fibroblastic growth factor only as controls.

Recent developments on coronary microvasculopathy after heart transplantation: a new target in the therapy of cardiac allograft vasculopathy.

Heart transplantation (HTx) is the treatment of choice for patients with refractory end-stage heart diseases. Although the procedure is considered effective in extending and improving quality of life, the onset of cardiac allograft vasculopathy (CAV) continues to limit the long-term success of HTx. Emerging data indicate that the endothelium plays a significant role in the onset, progression and complication of this multifactorial disease, with both immunologic and nonimmunologic risk factors contributing to its development.

Follow-up with exercise test of effort-induced ventricular arrhythmias linked to ryanodine receptor type 2 gene mutations.

The aim of this study was to assess exercise test results and efficacy of therapy with a β blocker (acebutolol) in ryanodine receptor type 2 (RyR2) mutation carriers with documented ventricular arrhythmias (VAs) and long-term follow-up. Twenty RyR2 mutation carriers belonging to 8 families and regularly followed at our center were analyzed using a study protocol involving electrocardiography, exercise tests off and on β-blocker therapy, 2-dimensional echocardiography, and signal-averaged electrocardiography. Off-therapy exercise testing triggered the onset of VAs at different heart rates (mean 132 ± 13 beats/min) with various patterns that worsened while exercising and disappeared immediately after stopping.

Prevalence of cardiomyopathy in Italian asymptomatic children with electrocardiographic T-wave inversion at preparticipation screening.

Background: T-wave inversion on a 12-lead ECG is usually dismissed in young people as normal persistence of the juvenile pattern of repolarization. However, T-wave inversion is a common ECG abnormality of cardiomyopathies such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, which are leading causes of sudden cardiac death in athletes. We prospectively assessed the prevalence, age relation, and underlying cardiomyopathy of T-wave inversion in children undergoing preparticipation screening.