1,720,981 research outputs found
[Molecular investigation of sudden death].
No full textJuvenile sudden death and sudden infant death syndrome exert a deep social impact, due to the young age of the victims and the unexpected occurrence of death. Recently, genetically determined ion channel diseases have been demonstrated to account for many forms of juvenile sudden death sine materia and also for some cases of sudden infant death syndrome (Brugada syndrome, long QT and short QT syndromes and catecholaminergic polymorphic ventricular tachycardia). Moreover, a not negligible amount of juvenile sudden deaths are due to myocarditis as a consequence of cardiotropic viruses. Thus, it is now becoming mandatory to apply molecular pathology techniques also to the post mortem study of sudden death. In general, a long interval between death and post mortem exam and inadequate tissue sampling and preservation may increase the poor results of molecular investigation. The aim of this review was to provide evidence of the need to develop a molecular pathology investigation protocol to be used at post mortem
Sudden cardiac death, borderline myocarditis and molecular diagnosis: evidence or assumption?
No full textPURPOSE:
Sudden unexpected death autopsy is sometimes non-conclusive both from a macroscopic and from a histological point of view, even if carried out according to the guidelines for sudden cardiac death examination. Molecular biology techniques are required in this setting and may play a crucial role in reaching the final diagnosis. A
CASE REPORT:
The postmortem examination and toxicology findings of the body of a young monk found dead in his cell were negative. Rare focal myocardial lymphocytic infiltrates were seen microscopically, associated with interstitial oedema. The findings were not sufficient to diagnose a myocarditis as the certain final cause of cardiac arrest. According to the recent guidelines for sudden cardiac death, a molecular investigation by polymerase chain reaction analysis was performed on samples of myocardium and spleen, with detection of parvovirus B19 DNA in the myocardium. Accordingly, a diagnosis of parvovirus B19 borderline acute myocarditis was put forward as the possible cause of sudden cardiac death.
CONCLUSION:
In sudden death cases in which there is lack of a cause-effect relationship with the postmortem findings, the final report should be expressed as a descriptive association of evidence, not providing unreliable certainty, as the Association for European Cardiovascular Pathology recommends
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
Classification and histological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease.
Full text linkIn 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. According to Dallas criteria, myocarditis is diagnosed in the setting of an "inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes, not typical of ischemic damage associated with coronary artery disease". The majority of experts in the field agree that an actual increase in sensitivity of EMB has now been reached by using immunohistochemistry together with histology. A value of >14 leukocytes/mm(2) with the presence of T lymphocytes >7 cells/mm(2) has been considered a realistic cut off to reach a diagnosis of myocarditis. The development of molecular biological techniques, particularly amplification methods like polymerase chain reaction (PCR) or nested-PCR, allows the detection of low copy viral genomes even from an extremely small amount of tissue such as in EMB specimens. Positive PCR results obtained on EMB should always be accompanied by a parallel investigation on blood samples collected at the time of the EMB. According to the recent Association for European Cardiovascular Pathology guidelines, optimal specimen procurement and triage indicates at least three, preferably four, EMB fragments, each 1-2 mm in size, that should immediately be fixed in 10 % buffered formalin at room temperature for light microscopic examination. In expected focal myocardial lesions, additional sampling is recommended. Moreover, one or two specimens should be snap-frozen in liquid nitrogen and stored at -80 °C or alternatively stored in RNA-later for possible molecular tests or specific stains. A sample of peripheral blood (5-10 ml) in EDTA or citrate from patients with suspected myocarditis allows molecular testing for the same viral genomes sought in the myocardial tissue
Arrhytmogenic right ventricular cardiomyopathy/displasia: is there a role for viruses?
No full textArrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a primary heart muscle disease characterized structurally by progressive fibrofatty replacement of the right ventricle and clinically by life-threatening ventricular arrhythmias with left bundle branch block morphology. Recently, there has been a great deal of interest on ARVC/D as a cause of sudden death in young people, and it has been reported as the most common cause of exercise-related sudden death among competitive athletes in Italy. An autosomic dominant familial occurrence has been recognized, and four disease-causing genes have been recently identified in the dominant forms: ryanodinic cardiac receptor 2, desmoplakin, plakophilin 2, and transforming growth factor (TGF)-beta3. Furthermore, plakoglobin has been identified as the first gene responsible for the recessive variant of ARVC/D associated with palmoplantar keratosis and woolly hair (Naxos disease). However, although much progress has been made in molecular genetics, up to today, the pathogenesis of the disease is still unclear. The occurrence of myocyte apoptosis has been documented, suggesting that recurrent bouts of apoptosis may account for progressive atrophy of the myocardium, which is then replaced by fibrofatty tissue. Considering the frequent finding of myocarditis at histology, an inflammatory theory has been advanced, and infective mechanisms have been postulated to contribute to the onset and the progression of the disease. Cardiotropic viruses have been detected in some ARVC/D cases, and they have been proposed as possible etiologic agents. Several etiopathogenetic theories are herein presented in detail with particular attention to the inflammatory/infective one and its possible links between this and the genetic/dystrophic theories are discussed
Myocarditis and dilated cardiomyopathy in athletes: Diagnosis, management, and recommendations for sport activity
No full textIF JCR 2007: 0.96
Prevention of sudden cardiac deathin the young and in athletes: dream or reality?
No full textCardiovascular diseases account for 40% of all deaths in the Western countries, and nearly two thirds of them occur suddenly. Young people (<35 years) are not spared from sudden death (SD) with a rate of 1/100,000 per year. Effort is a trigger with a threefold risk in athletes vs. nonathletes, and sports disqualification is by itself life-saving in people with underlying concealed cardiovascular diseases. Several culprits of cardiac SD may be identified at postmortem and atherosclerotic coronary artery disease is the leading cause (25% of SD cases in the young), mostly consisting of a single obstructive plaque with fibrocellular intimal proliferation. However, the spectrum of cardiovascular substrates is wide and include also congenital diseases of the coronary arteries (mainly anomalous origin), myocardium (arrhythmogenic and hypertrophic cardiomyopathies, myocarditis), valves (aortic stenosis and mitral valve prolapse), and conduction system (ventricular preexcitation, accelerated atrioventricular conduction and block). In up to 20% of cases, the heart is grossly and histologically normal at autopsy (unexplained SD or "mors sine materia"), and inherited ion channel diseases have been implicated (long and short QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia). Targets to treat and prevent SD in the young consist of the following: (a) avoid triggers like effort or emotion, (b) inhibit the onset of arrhythmias with drugs or ablation, (c) switch off arrhythmias with defibrillator, and (d) hinder the recurrence of the disease with genetic counseling and/or therapy. In vivo detection of cardiomyopathies is nowadays feasible by electrocardiogram and/or echocardiography, which resulted in a sharp decline of SD in the athletes in Italy, thanks to obligatory preparticipation screening for sport activity. Genetic screening could play a pivotal role in early detection of asymptomatic mutation carriers of cardiovascular diseases at risk of SD
Postmortem genetic testing for conventional autopsy-negative sudden unexplained death - An evaluation of different DNA extraction protocols and the feasibility of mutational analysis from archival paraffin-embedded heart tissue
No full textIF JCR 2007: 2.62
Sudden cardiac death with normal heart Molecular autopsy.
No full textSeveral culprits may be identified at postmortem in sudden death (SD) victims, including coronary artery, myocardial, valve, conduction system, and congenital heart diseases. However, particularly in young people, the heart can be found grossly and histologically normal in a not-so-minor amount of cases (the so-called unexplained SD or "mors sine materia") and inherited ion channel diseases are implicated (long and short QT syndromes, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia). These channelopathies are due to defective genes encoding for proteins of sodium and potassium ion channels at the sarcolemma level or for receptors regulating intracellular calcium release at the sarcoplasmic reticulum level. Postmortem investigation may still represent the first opportunity to make the proper diagnosis also in the setting of a structurally normal heart and the employment of molecular biology techniques is of help to solve the puzzle of such "silent" autopsies. For these reasons, autopsy investigation of cardiac SD should always include sampling for genetic testing to search for the invisible inherited arrhythmogenic disorders, as recommended in the recent guidelines by the Association for European Cardiovascular Pathology
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