Aetiology of sudden cardiac death in sport: a histopathologist's perspective.

In the UK, when a young person dies suddenly, the coroner is responsible for establishing the cause of death. They will ask a consultant pathologist to carry out an autopsy in order to ascertain when, where and how that person died. Once the cause of death is established and is due to natural causes, the coroner can issue a death certificate. Importantly, the coroner is not particularly interested in the cause of death as long as it is due to natural causes, which avoids the need for an inquest (a public hearing about the death). However, if no identifiable cause is established at the initial autopsy, the coroner can refer the heart to a cardiac pathologist, since the cause of death is usually due to heart disease in most cases. Consultant histopathologists are responsible for the analysis of human tissue from both living individuals and the dead in order to make a diagnosis of disease. With recent advancements in the management protocols for routine autopsy practice and assessment following the sudden death of a young individual, this review describes the role of the consultant histopathologist in the event of a sudden death of a young athletic individual, together with the older middle-aged 'weekend warrior' athlete. It provides concise mechanisms for the main causes of sudden cardiac death (including coronary artery disease, cardiomyopathies, valve abnormalities, major vessel ruptures and electrical conduction abnormalities) based on detailed autopsy data from our specialised cardiac pathology laboratory. Finally, the review will discuss the role of the histopathologist in the event of a 'negative' autopsy

Constrictive pericarditis and rheumatoid nodules with severe aortic incompetence.

The case of a female patient presenting with constrictive rheumatoid pericarditis and aortic incompetence secondary to valvular rheumatoid nodules is described along with a review of the literature with the aim to highlight this rare cause of aortic insufficiency

Mitral valve and left ventricular features in malignant mitral valve prolapse.

Objective: Mitral valve prolapse is a benign condition, however with occasional reports of sudden cardiac death or out-of-hospital cardiac arrest in the absence of severe mitral regurgitation or coronary artery disease, suggesting the existence of a malignant form. The objective of our study was to contribute to the characterisation of malignant mitral valve prolapse. Methods: We performed a retrospective analysis of pathology findings in 68 consecutive cases of sudden cardiac death with mitral valve prolapse as lone abnormal finding, reported as cause of death. Results: All mitral valve prolapse sudden death cases had mitral valve characteristics of Barlow disease, with extensive bileaflet multisegmental prolapse and dilatation of the annulus. The majority of cases (80.9%) had microscopic left ventricular fibrosis with associated hypertrophy and degenerative features of the myocytes, and some cases (10.9%) had right ventricular fibrosis as well. Conclusions: Malignant mitral valve prolapse is Barlow disease. Sudden cardiac death in mitral valve prolapse is due to Barlow disease, which besides the typical mitral valve degeneration may comprise a distinct Barlow disease cardiomyopathy, as suggested by myocyte degeneration and bi-ventricular involvement

Sudden unexpected death: a national programme which will establish genetic testing and cardiological screening of families in the UK.

Sudden cardiac death (SCD) in young people is due to genetic cardiac causes in the majority of cases. In UK all cases have an autopsy and results are given to the family. We now have  a national pathway with detailed programme to establish that all members of the family  are screened by cardiologists in inherited cardiac centres . Also genetic testing of material taken at autopsy will be carried out in all cases which will be a valuable addition to the pathological and clinical findings. All this will aid the family in coming to terms with the tragic death and provide genotype phenotype correlation within the family to prevent future deaths

Sudden Death in Congenital Heart Disease: The Role of the Autopsy in Determining the Actual Cause.

Congenital heart defects (CHDs) have undergone a large change in epidemiology due to prenatal screening and improved outcomes with surgery and percutaneous procedures. In patients with complex CHD there is an increased risk of sudden cardiac death (SCD) and up to 11% of all SCDs in the young occur in people with CHD. It is essential for clinicians to be aware of the risk factors, and for all patients to be followed up in specialised centres. When an SCD occurs, it is important that an autopsy is done and for the pathologist to have an in-depth knowledge of the particular defect and the corrective surgical techniques employed, as well as any complications due to these procedures. Both pathologist and cardiologist should work closely together to explain the cause of death to the family. A terminal cardiac arrhythmia explains many of the SCD cases, often with underlying cardiac fibrosis due to previous procedures. SCD may also be the first presentation of CHD, so great care is required when examining such cases and referral for a detailed expert opinion is recommended in all CHD-SCD cases

Ultra-short echo time cardiovascular magnetic resonance of atherosclerotic carotid plaque.

BACKGROUND: Multi-contrast weighted cardiovascular magnetic resonance (CMR) allows detailed plaque characterisation and assessment of plaque vulnerability. The aim of this preliminary study was to show the potential of Ultra-short Echo Time (UTE) subtraction MR in detecting calcification. METHODS: 14 ex-vivo human carotid arteries were scanned using CMR and CT, prior to histological slide preparation. Two images were acquired using a double-echo 3D UTE pulse, one with a long TE and the second with an ultra-short TE, with the same TR. An UTE subtraction (DeltaUTE) image containing only ultra-short T2 (and T2*) signals was obtained by post-processing subtraction of the 2 UTE images. The DeltaUTE image was compared to the conventional 3D T1-weighted sequence and CT scan of the carotid arteries. RESULTS: In atheromatous carotid arteries, there was a 71% agreement between the high signal intensity areas on DeltaUTE images and CT scan. The same areas were represented as low signal intensity on T1W and areas of void on histology, indicating focal calcification. However, in 15% of all the scans there were some incongruent regions of high intensity on DeltaUTE that did not correspond with a high intensity signal on CT, and histology confirmed the absence of calcification. CONCLUSIONS: We have demonstrated that the UTE sequence has potential to identify calcified plaque. Further work is needed to fully understand the UTE findings

Sudden unexplained death in alcohol misuse (SUDAM) patients have different characteristics to those who died from sudden arrhythmic death syndrome (SADS).

There is growing awareness of sudden unexplained death in alcohol misuse (SUDAM) in which there is no obvious cause of death, no evidence of acute alcohol toxicity or alcoholic ketoacidosis, and the heart is morphologically normal. This study describes the characteristics of a cohort with SUDAM from a tertiary cardiovascular referral center and compares the findings with those of individuals who died from sudden arrhythmic death syndrome (SADS). Cases in this retrospective cross-sectional study were identified from a database of referrals to our center spanning approximately 40 years. Cases with recorded heavy use of alcohol and non-alcohol users were selected, then limited to those with SUDAM or SADS aged 16 to 64 years. 62 cases of SUDAM and 41 cases of SADS were identified. The SUDAM group were older than the SADS group; mean age 35.8 years and 27.7 years respectively (P=0.0002). There was also a higher incidence of significant psychiatric illness in SUDAM (19.7%) than SADS (2.4%) cases. Post mortem liver examination was more likely to reveal heavy livers in SUDAM than SADS (2196.1g and 1572.4g respectively; P=0.0033) and more fatty liver change (24.2% and 2.4%). SUDAM tends to occur in individuals who are older and have heavier livers than those with SADS. Psychiatric illness is also more common. SADS, unlike SUDAM, is often associated with heritable channelopathies that may affect surviving family members. Therefore, differentiating between SUDAM and SADS identifies families likely to benefit from screening for these mutations, thus preventing further sudden arrhythmic deaths

Pulmonary capillary haemangiomatosis - An unusual cause of hypoxia.

We describe the case of a 58-year-old man who presented with progressive dyspnoea on exertion and severe exertional hypoxia. There was a paucity of radiological findings, mild pulmonary hypertension, and no demonstrable anatomical shunt. Post mortem examination of lung tissue suggested a diagnosis of pulmonary capillary haemangiomatosis. The case is unusual in displaying few radiological findings. We postulate that the severe hypoxia was due to shunting through the abnormal capillary proliferations

Gold- and Silver-Catalyzed Reactions of Propargylic Alcohols in the Presence of Protic Additives

A wide range of primary, secondary and tertiary propargylic alcohols undergo a Meyer–Schuster rearrangement to give enones at room temperature in the presence of a gold(I) catalyst and small quantities of MeOH or 4-methoxyphenylboronic acid. The syntheses of the enone natural products isoegomaketone and daphenone were achieved using this reaction as the key step. The rearrangement of primary propargylic alcohols can readily be combined in a one-pot procedure with the addition of a nucleophile to the resulting terminal enone, to give β-aryl, β-alkoxy, β-amino or β-sulfido ketones. Propargylic alcohols bearing an adjacent electron-rich aryl group can also undergo silver-catalyzed substitution of the alcohol with oxygen, nitrogen and carbon nucleophiles. This latter reaction was initially observed with a batch of gold catalyst that was probably contaminated with small quantities of silver salt