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UK study could be a breakthrough in autopsy practice

EDAutopsyFor most sudden natural adult deaths investigated by British coroners, postmortem computing tomography, enhanced with targeted coronary angiography (PMCTA) could be used to avoid invasive autopsy.

The ground-breaking UK  study could represent a breakthrough in how autopsy practice is conducted in the UK and around the world, the authors say.

The research was led by Professors Guy Rutty at East Midlands forensic pathology unit, CSMM and Bruno Morgan at University Radiology Unit, CSMM in collaboration with other University of Leicester, and University Hospitals of Leicester employees past and present. It was funded by the National Institute for Health Research (NIHR).

Rutty explained: "Over the years there have been several attempts to develop alternative approaches to the invasive autopsy to limit the extent to which the cadaver is dissected. Although these techniques have been published, the invasive examination remains the standard adopted approach."

A previous study of PMCT showed promise for using medical imaging to investigate the cause of natural death, but with a major weakness: the inability to diagnose coronary artery disease, the most common cause of natural death. Morgan explained: "In clinical CT scanning, a contrast agent is injected into a vein and circulation delivers it around the body. This allows the CT scan to show the state of blood vessels anywhere in the body. However, the lack of circulation in cadavers means these techniques cannot be used."

This has been overcome by developing a novel minimally invasive coronary artery angiography technique. A variety of these techniques have been developed around the world over the last few years, but this is the first large-scale fully autopsy-controlled trial to demonstrate their efficacy in adult natural death. Rutty explained: "Here at the University of Leicester we developed a quick and minimally invasive approach to improve diagnostic accuracy. This uniquely uses a combination of standard contrast agent (positive) and air (negative) to show the coronary artery lumens and ventricular cavities."

Morgan explained: "By 'minimally invasive' we mean that we use a catheter inserted into an artery to perform the angiography. The insertion techniques are like those we use on patients every day in our clinics, with just the use of local anaesthetic to numb the skin."

The Leicester team applied their PMCTA technique to a cohort of 240 deaths investigated by the HM coroner. They show that a cause of death could be given in 92% of cases, based on "the balance of probabilities," the burden of proof required by the HM Coroner. Comparison with independently generated autopsy results showed that PMCTA had a similar accuracy to autopsy, did not miss autopsy-identifiable unnatural or "reportable" causes of death, and would also not significantly change population "cause of death" statistics.

Morgan added: "We have shown that PMCT enhanced by targeted coronary angiography can diagnose the cause of death in up to 90% of HM Coronial investigations for suspected natural death. This is the most successful application of PMCT and PMCTA to-date in natural death, and shows that a significant number of deaths could be investigated without the need for an invasive autopsy."

PMCTA was found to be superior at identifying trauma and haemorrhage, whereas autopsy was superior at identifying pulmonary thromboembolism. Both tests had different strengths and weaknesses in heart and lung disease.

Rutty cautioned: "Both autopsy and PMCTA have different strengths and weaknesses as investigative approaches. When a higher burden of proof is required the 'gold standard' of death investigation should include both PMCT and invasive autopsy."

The findings of the study are unique from an international perspective as it focuses on natural death. In the study a small number of unnatural deaths were also examined, showing PMCTA was also useful in these cases.

Rutty concludes: "There is already great interest in providing PMCTA as an alternative to autopsy in the UK with several centres, including Leicester, recently initiating services. These data now provide strong evidence to validate these services, especially where they use angiography techniques. We therefore expect these results to have a major influence on the future of autopsy practice in the UK, and across the world."

Rutty and Morgan are internationally recognised as pioneers, researchers and practitioners within the field of post mortem computed tomography. They are the authors of the largest body of scientific publications in this field within the UK, including research studies and educational papers and book chapters.

The team believes adopting PMCTA as the standard first-line test in natural death would have a positive and profound effect on the public and religious groups within the UK and potentially beyond.

Background: England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations.
Methods: In this single-centre (Leicester, UK), prospective, controlled study, we selected cases of natural and non-suspicious unnatural death referred to Her Majesty's (HM) Coroners. We excluded cases younger than 18 years, known to have had a transmittable disease, or who weighed more than 125 kg. Each case was assessed by PMCTA, followed by autopsy. Pathologists were masked to the PMCTA findings, unless a potential risk was shown. The primary endpoint was the accuracy of the cause of death diagnosis from PMCTA against a gold standard of autopsy findings, modified by PMCTA findings only if additional substantially incontrovertible findings were identified.
Findings: Between Jan 20, 2010, and Sept 13, 2012, we selected 241 cases, for which PMCTA was successful in 204 (85%). Seven cases were excluded from the analysis because of procedural unmasking or no autopsy data, as were 24 cases with a clear diagnosis of traumatic death before investigation; 210 cases were included. In 40 (19%) cases, predictable toxicology or histology testing accessible by PMCT informed the result. PMCTA provided a cause of death in 193 (92%) cases. A major discrepancy with the gold standard was noted in 12 (6%) cases identified by PMCTA, and in nine (5%) cases identified by autopsy (because of specific findings on PMCTA). The frequency of autopsy and PMCTA discrepancies were not significantly different (p=0·65 for major discrepancies and p=0·21 for minor discrepancies). Cause of death given by PMCTA did not overlook clinically significant trauma, occupational lung disease, or reportable disease, and did not significantly affect the overall population data for cause of death (p≥0·31). PMCTA was better at identifying trauma and haemorrhage (p=0·008), whereas autopsy was better at identifying pulmonary thromboembolism (p=0·004).
Interpretation: For most sudden natural adult deaths investigated by HM Coroners, PMCTA could be used to avoid invasive autopsy. The gold standard of post-mortem investigations should include both PMCT and invasive autopsy.

Guy N Rutty, Bruno Morgan, Claire Robinson, Vimal Raj, Mini Pakkal, Jasmin Amoroso, Theresa Visser, Sarah Saunders, Mike Biggs, Frances Hollingbury, Angus McGregor, Kevin West, Cathy Richards, Laurence Brown, Rebecca Harrison, Roger Hew

[link url=""]University of Leicester material[/link]
[link url=""]The Lancet article summary[/link]

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