Fibrosis, Connexin-43, and Conduction Abnormalities in the Brugada Syndrome.

Background: The right ventricular outflow tract (RVOT) is acknowledged to be responsible for arrhythmogenesis in Brugada syndrome (BrS), but the pathophysiology remains controversial.

Objectives: This study assessed the substrate underlying BrS at post-mortem and in vivo, and the role for open thoracotomy ablation.

Methods: Six whole hearts from male post-mortem cases of unexplained sudden death (mean age 23.

iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death.

Desmosomes are anchoring junctions that exist in cells that endure physical stress such as cardiac myocytes. The importance of desmosomes in maintaining the homeostasis of the myocardium is underscored by frequent mutations of desmosome components found in human patients and animal models. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a phenotype caused by mutations in desmosomal components in ∼ 50% of patients, however, the causes in the remaining 50% of patients still remain unknown.

Clinical characteristics and circumstances of death in the sudden arrhythmic death syndrome.

Background: Sudden cardiac death (SCD) is a devastating event in the young. Referral to a specialist cardiac pathologist is recommended. Age, sex, and circumstances of death may reflect underlying diagnoses.

Calibration of myocardial T2 and T1 against iron concentration.

Background: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.

Methods: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading.

The importance of specialist cardiac histopathological examination in the investigation of young sudden cardiac deaths.

Aims: Post-mortem examination of the heart in young sudden cardiac death (SCD) is vital as the underlying aetiology is often an inherited cardiac disease with implications for surviving relatives. Our aim is to demonstrate the improvement in diagnostic quality offered by a specialist cardiac pathology service established to investigate SCD with fast-track reporting on hearts sent by pathologists in cases of SCD.

Methods And Results: A tertiary centre prospective observational study was conducted.

Sudden cardiac death with autopsy findings of uncertain significance: potential for erroneous interpretation.

Background: The sudden death of young individuals is commonly attributed to inherited cardiac disorders, and familial evaluation is advocated. The identification of pathognomonic histopathologic findings, or the absence of cardiac pathology (sudden arrhythmic death syndrome [SADS]) at postmortem, directs familial evaluation targeting structural disorders or primary arrhythmogenic syndromes, respectively. In a proportion of autopsies, structural abnormalities of uncertain significance are reported.

Myocardial infarction with normal coronaries: an autopsy perspective.

Aim: To analyse postmortem cases of myocardial infarction (MI) with normal coronary arteries in terms of patient characteristics, features of the MI and risk factors.

Methods: This retrospective non-case controlled study was carried out at a specialist cardiac pathology department at a tertiary cardiac referral centre. Cases of histologically confirmed MI and normal coronary arteries during the period 1996-2010 were identified and analysed for the presence of risk factors.

Sudden cardiac death caused by coronary vasculitis.

Coronary vasculitis is a rare and diagnostically challenging cause of sudden cardiac death (SCD). There are currently no large-scale series on this rare entity. A retrospective non-case-control observational study of SCD with coronary vasculitis referred to a tertiary cardiac pathology referral centre at the National Heart and Lung Institute at the Royal Brompton Hospital between 1996 and 2010 was completed.

On T2* magnetic resonance and cardiac iron.

Background: Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically via its reciprocal, T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans are limited.

Methods And Results: Twelve human hearts were studied from transfusion-dependent patients after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure (n=4).