J Clin Pathol: first published as 10.1136/jcp.42.9.912 on 1 September 1989. Downloaded from

J Clin Pathol 1989;42:912-918

Postmortem audit in a paediatric cardiology unit

G A RUSSELL, P J BERRY From the Department ofPaediatric Pathology, Bristol Royal Hospitalfor Sick Children sumMARY Postmortem examinations performed on 76 children with a clinical diagnosis of congenital heart disease were reviewed retrospectively and compared with the findings before death. Both operated and unoperated cases were studied over a three year period. Despite intensive investigation during life, there was a high rate of unsuspected abnormalities at necropsy (80%): 29 cases had undiagnosed additional cardiac anomalies or surgical flaws, which contributed to death in 13 cases. Defects in surgery were uncommon but permitted modification in surgical technique to avoid recurrence. Myocardial necrosis and pulmonary foreign body were common findings, the importance ofwhich is uncertain and requires further study for their prevention. Even in the most thoroughly investigated cases postmortem examination has a high yield of clinically important pathology which is undetected during life.

The lamentable decline in the number of necropsies clinical observations, echocardiography, and performed in the United Kingdom has been the angiography recorded. Details ofsurgical intervention subject of much comment and speculation. The and other treatment were noted. A synopsis ofthe final reasons underlying this change in clinical practice are clinical diagnosis was made. The necropsy report was copyright. complex and varied. Many studies by pathologists then reviewed and the findings summarised and have shown the continued value of necropsies in compared with the clinical assessment. When available clinical audit.' We chose to study a group of children the heart was re-examined to resolve any points that with a very specific diagnostic problem by performing were unclear from the report. No major modifications, a retrospective review of 76 necropsies performed on however, were made to the necropsy accounts of the children with a clinical diagnosis of congenital heart cardiac abnormalities. The original histological disease. One of our aims was to assess the claim that preparations from each case were reviewed and the modem diagnostic techniques are sufficiently accurate findings recorded without knowledge of the original http://jcp.bmj.com/ as to negate the value of necropsy.2 The children had report. Cases were then categorised into four main been thoroughly investigated in life by both invasive groups: and non-invasive imaging. Our experience has allowed Group: A where the necropsy showed additional us to propose a protocol for this type of examination undiagnosed cardiac lesions; when performed at specialist centres. Group B: where the necropsy showed unsuspected major or minor complications of cardiac Material and methods disease or of its treatment; on September 30, 2021 by guest. Protected Group C: where the necropsy showed additional Seventy six cases from the Bristol paediatric clinically important pathology not directly cardiology unit had necropsies performed by the resulting from the cardiac condition; paediatric pathology department during a three year Group D: where the necropsy yielded no additional period, 1985-1987. All these children had a clinical information. diagnosis of congenital heart disease and were under Groups A, B, and C were not mutually exclusive; the care of the cardiology and surgical teams; we also group D formed a completely separate category. included cases who had received cardiological assess- ment under the care of neonatologists. We did not Results include cases ofcardiological malformation diagnosed antenatally and aborted as these seemed to form a Seventy six consecutive cases from the Bristol distinct group with different diagnostic problems. paediatric cardiology and cardiac surgery depart- Case notes were examined and the findings from ments were reviewed. The sex ratio was exactly equal with 38 boys and 38 girls. Forty eight (63%) of the Accepted for publication 20 April 1989 necropsies were performed for Her Majesty's Coroner, 912 J Clin Pathol: first published as 10.1136/jcp.42.9.912 on 1 September 1989. Downloaded from

Postmortem audit in a paediatric cardiology unit 913 Bristol. The usual reason for referral to the Coroner Table 1 Missed cardiac lesions that would have influenced was that recent surgery had been performed. Twenty management had they been detected two children had died within 24 hours of their operation. The methods used by the pathologist were Additional necropsyfinding Clinical diagnoses confirmed the same for both types of case. Sixty nine of the Aortopulmonary window Interrupted aortic arch postmortem examinations were performed by the two Unilateral partial anomalous authors, the rest were done by other members of the pulmonary venous drainage Ventncular septal defect Atrioventricular septal defect and Transposition of great pathology department under supervision. The age cleft mitral valve cusp vessels range of cases was between a few hours and 11 years: Closed secundum ASD Pulmonary atresia, mitral + patent Blalock shunt atresia, univentricular <24 hours (n = 3) (4%); 24 hours-7 days (n = 12) (closed on echocardiogram) heart (16%); 7 days-l month (n = 7) (9%); 1 month-l year Mitral valve dysplasia Aortic stenosis Secundum ASD Fallot's tetralogy (n = 28) (37%); > 1 year (n = 26) (34%). (misinterpreted as dilated All the children had echocardiographic imaging of coronary sinus) the heart and multiple examinations had often been Aortopulmonary window Interrupted aortic arch made. In 16 cases echocardiography had been the only ASD = ; VSD = ventricular septal defect. mode of examination; this was often because invasive catheterisation was contraindicated due to the child's of other complex cardiac lesions. Aortopulmonary poor clinical condition. Sixty cases had had both window was missed twice in children with interrupted cardiac catheterisation and echocardiography. aortic arches. In four of these seven cases diagnosis Cardiac surgery had been performed on 60 children, had been based solely on echocardiography. 37 on cardiopulmonary bypass. Sixteen children had In seven cases surgical flaws were found at necropsy died within 24 hours of open heart surgery and six (subgroup III, table 2). In five of these the surgical within the same time following closed operations. problem was probably a contributing factor in the patient's death; the flaws were of more doubtful GROUP A clinical importance in the other cases. Twenty nine (38%) cases had additional cardiac The largest number ofcases were in subgroup IV (18 copyright. lesions found at necropsy. These were subdivided into cases, 24%). This included many minor cardiac abnor- four subgroups to reflect the implications of the extra malities such as small muscular ventricular septal lesions found: defects. We included some major abnormalities ifthey subgroup I where the cardiac diagnosis before death were present in the setting ofother correctly diagnosed was completely wrong. severe malformations and where the diagnosis of the subgroup II where the diagnosis before death was missed anomaly would not have affected outcome. only partly correct and additional The cases are listed in table 3.

lesions were missed that might have http://jcp.bmj.com/ influenced the management. GROUP B subgroup III cases where cardiac surgery was imper- Undiagnosed complications of the congenital heart fect or inappropriate to the lesion found. disease or of its treatment were common at necropsy subgroup IV cases where the cardiac diagnosis before (51 cases, 67%) (table 4). The most common undiag- death was substantially correct but nosed abnormality was myocardial necrosis, present additional lesions were found at in 30 (40%) cases. Typically this affected the suben- necropsy that would not have affected docardial portion of the left ventricular myocardium, the management had they been diag- on September 30, 2021 by guest. Protected nosed in life. Table 2 Surgical imperfections detected at necropsy Four cases appeared in more than one subgroup but these were counted only once in the total of 29 cases. Surgical imperfection Clinical diagnoses confirmed Only one case appeared in subgroup I. This was a child who died at 4 hours of age in heart failure. A Small defect in atrial suture Transposition ofgreat line in Senning repair vessels clinical diagnosis ofEbstein's anomaly ofthe tricuspid Aberrant atrial pathway, Senning repairTransposition of great valve was based on a single echocardiographic (misinterpreted anatomy)* vessels Residual infundibular stenosis Fallot's tetralogy examination. Postmortem examination showed a Failure to close secundum ASD* Fallot's tetralogy fistula between the left coronary artery and the Failure to close ventricular* Double outlet right coronary sinus; the tricuspid valve was normal. The septal defect ventricle Trauma to atrioventricular bundle* Fallot's tetralogy child also had severely hypoplastic lungs. Failed Blalock Hanlon septectomy* Double outlet right Subgroup II contained seven (9%) cases where ventricle with intact important cardiac anomalies had been missed (table ventricular septum 1). These included a range of anomalies in the setting *Cases where surgical flaw probably contributed to death. J Clin Pathol: first published as 10.1136/jcp.42.9.912 on 1 September 1989. Downloaded from

914 Russell, Berry the mitral papillary muscles being particularly vul- Table 4 Group B: where necropsy showed minor or major nerable. Twenty six of these 30 died following recent complications ofcongenital heart disease or ofits treatment cardiac surgery, 12 within 24 hours ofoperation; 19 of the 26 had had open heart surgery. Myocardial necrosis 30 Myocardial necrosis had more varied appearances Foreign body emboli 19 Pulmonary emboli 6 than in adults. Occasionally the areas ofnecrosis were Cerebral and necrosis 5 visible as dusky irregular subendocardial patches. Less Small intestinal necrosis 4 Pulmonary hypertension 3 commonly these patches were visible as green stained Birth asphyxia 3 areas in jaundiced children (fig 1), or creamy yellow Renal infarction 3 calcified (fig 2). In Splenic infarction 2 speckled areas when extensively Haemopericardium (resuscitation injury) most cases, however, necrosis was only apparent on Haemothorax histological examination. When children had died Superior vena cava obstruction Duodenal ulcers within 24 hours of operation, zones of eosinophilic Renal vein necrosis, cytoplasmic coagulation, and loss of nuclear Acute pancreatitis Adrenal infarction staining were seen. Calcification was common and Aspergillus 1 often extensive (fig 3). It was sometimes present in Systemic aspergillosis l children in whom the duration ofmyocardial necrosis inclusions in lung and kidney Adenovirus type 1I cultured from lung was presumed to have been short (those dying within Streptococcus pneumoniae septicaemia 24 hours of operation), suggesting a very rapid onset. Haemophilus influenzae pericarditis Older lesions showed fibrosis and calcification, inflammation was uncommon. The size of necrotic areas varied from small islands around the lumen of extending transmurally or affecting the right ventricle the left ventricle to confluent geographical zones or atria. We were surprised at the prevalence offoreign body embolism in this series. Nineteen children had Table 3 Additional undiagnosed anomalies ofless fragments of foreign material within small arteries of importance their lungs. In only one case were foreign bodies found copyright. in organs other than the lungs. At least three different Additional necropsy finding Clinical diagnoses confirmed materials could be distinguished by their light Secundum ASD Patent ductus arteriosus Hypoplastic tricuspid valve Pulmonary atresia with (atretic on echocardiogram) intact ventricular septum Left atrial isomerism, aortic Hypoplastic left ventricle atresia, hypoplastic mitral valve (atretic on scan)

Left superior vena cava Fallot's tetralogy http://jcp.bmj.com/ draining into coronary sinus Right atrial isomerism Mitral atresia, univentricular heart Right sided aortic arch Truncus arteriosus Double inlet left ventricle Transposition of great (tricuspid valve thought to vessels univentricular be atretic) heart Left ventricular myxoma, Right atrial myxoma, abnormal mitral valve insertion double chamber right left atrial isomerism ventricle atrioventricular septal defect on September 30, 2021 by guest. Protected Small perimembranous VSD Total anomalous pulmonary venous drainage Double orifice mitral valve Atrioventricular septal bicuspid aortic valve defect (complete) small muscular VSDs Aneurysm of fossa ovalis Muscular VSDs Double orifice mitral valve Atrioventricular septal defect (complete) Aortic atresia Aortic stenosis Complete atrioventricular septal Pulmonary stenosis defect + failed to confirm aortopulmonary window Small muscular VSDs Transposition of great vessels Hypoplastic mitral valve Hypoplastic left ventricle, (interpreted as mitral atresia) double outlet right Fig I Green stained areas ofmyocardial necrosisfrom a ventricle intact child of8 months ofage who becamejaundiced and died six ventricular septum days after surgeryfor repair ofan atrioventricular septal Small perimembranous VSD Interrupted aortic arch defect. J Clin Pathol: first published as 10.1136/jcp.42.9.912 on 1 September 1989. Downloaded from

Postmortem audit in a paediatric cardiology unit 915

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Fig 2 Calcified subendocardial necrosis in a 12 week old child with severe aortic valve stenosis. microscopic appearance. The fragments were often surrounded by multinucleated foreign body giant cells. Changes in the adjacent blood vessel wall were rare, an exception being one child who died three copyright. months after repair of transposition of the great vessels (fig 4). The source of embolism in these 19 Fig 4 Foreign body microemboli exciting a destructive giant children was uncertain; 18 children had had previous cell reaction in a pulmonary artery ofa 14 month old child cardiac surgery, 11 on cardiopulmonary bypass. Six- who died eight weeks after repair ofa complete transposition. teen cases had had invasive cardiac angiography, (Haematoxylin and eosin.) another possible source. thromboemboli were ventricular leucomalacia were found in a further five

Unsuspected pulmonary http://jcp.bmj.com/ observed in six cases. Cerebral infarcts and peri- children. Changes of pulmonary hypertension were rarely seen as an unexpected finding at necropsy, as it was frequently correctly diagnosed in life. Three cases of pulmonary hypertension of an unexpected severity were found. In only one of these were the changes within the irreversible grades of the Heath Edward's classification. For simplicity we chose to include

infective complications in group B, even though it was on September 30, 2021 by guest. Protected sometimes unclear whether these were a result of the heart disease or incidental. Six children had unsuspected which probably caused death in four cases. Changes of adult respiratory distress syndrome ('shock lung') (11 cases) and hepatic pathology (five cases of midzonal necrosis and five cases of severe hepatic fibrosis) were not included in group B. This was because these conditions were clinically manifest and were being investigated and treated, even though the underlying pathology was not always appreciated clinically. Fig 3 Radiographic demonstration ofextensive subendocardial calcificationfrom the same case shown GROUPS C AND D infig 2. The cases in group C (incidental pathology) are listed J Clin Pathol: first published as 10.1136/jcp.42.9.912 on 1 September 1989. Downloaded from

916 Russell, Berry Table 5 Group C: where necropsy showed clinically well recognised though rare association and diagnostic inportant extracardiac pathology pitfall.5 Aortopulmonary window was also erroneously diagnosed in a child with a complete 3 atrioventriculoseptal defect. Minor unsuspected Cerebral arteriovenous malfonnation I Pulmonary hypoplasia I cardiac lesions were found in 28%, illustrating the di George's syndrome I incomplete resolution of these forms of cardiac Hepatoblastoma I 1 imaging. These lesions would not have influenced the Pulmonary haemangiomata I management or outcome had they been detected. They Abnormal karyotype I may assume greater importance, however, as methods Lymphocytic thyroiditis 1 of treating the severe concomitant abnormalities in table 5. In only one case was the extracardiac improve. pathology the cause of death (cerebral arteriovenous Scrutiny of highly skilled, complex surgery on tiny malformation with associated infarction). The other hearts at necropsy is essential for the continued anomalies, however, sometimes helped in the attribu- improvement in surgical technique. Flaws in surgical tion of a "syndrome" to the case. In 15 cases no technique were uncommon in our series but when additional information was obtained by necropsy present they provided valuable lessons for the man- agement of future cases. (group D). Myocardial necrosis is increasingly recognised in children dying in the perinatal period. Less well Discussion recognised is the association of necrosis with cardiac malformation when the distribution of dead tissue The claim that necropsy has been rendered obsolete by may reflect the site of an obstructive cardiac lesion.6 the improved techniques of modem clinical diagnosis The necroses in our cases were presumed to be related is refuted by this study. Admittedly, in only one ofour to recent cardiac surgery in most cases. Techniques of cases did postmortem examination show clinical paediatric myocardial preservation during bypass

cardiac diagnosis to be completely wrong. The criteria operations are less well determined than for adult copyright. for assessing the value of necropsy, however, must be procedures. broader than merely the complete disagreement of It is difficult to be certain of the clinical importance clinical and necropsy diagnosis. In our series 38% of of the foreign body embolism in the lungs of these cases had undiagnosed additional cardiac anomalies cases. The ease oftheir histological demonstration, on or surgical flaws which may have contributed to death random lung sections, suggest that they were present in 13 cases. Porter and Keeling's study found a high in large numbers. Filter material, plastic tubing, and rate of significant discrepancy between necropsy and antifoaming agents are well documented sources of clinical diagnoses.3 Forty four percent of postmortem embolism following cardiac bypass procedures but http://jcp.bmj.com/ examinations on neonatal deaths in that series yielded these usually have systemic distribution.! Other clinically important information. In our series ofmore sources also have to be excluded as not all the cases highly investigated children 80% ofnecropsies yielded occurred following surgery. Although we have no additional information, although the precise clinical evidence that these emboli caused problems in the importance of some of the findings has yet to be children, the long term consequences may be evaluated. Intensive clinical investigation in life important in these patients who often already have circulation. increases the need for detailed post mortem examina- impaired pulmonary on September 30, 2021 by guest. Protected tion to ensure that the basis for the adopted treatment Both these complications of myocardial necrosis was sound. and foreign body embolism were shown by histo- A disproportionate number of the major clinico- logical examination. This highlights the essential role pathological discrepancies arose in children who had ofroutine histological sampling even in the absence of only had echocardiographic assessment (four out of macroscopic lesions. seven cases). This supports the observation of Clinically important incidental abnormalities were Goldman,4 who found that discrepancies at necropsy uncommon but when present sometimes led to a were much more common in cases where diagnosis unifying diagnosis for the case. No additional infor- was based solely on the result of a newer technique mation was obtained from 20% ofcases. As paediatric such as ultrasound, computed tomography scanning, pathologists we are aware of the value of negative or nuclear medicine than those based on other findings in counselling bereaved parents. Although investigations. In our study aortopulmonary window unsatisfactory in explaining the outcome of the case, caused particular diagnostic problems on echo- the negative findings may still be used to comfort cardiography as this region is hard to visualise. It was parents that all appropriate measures had been taken. missed twice in children with interrupted aortic arch, a Pathologists must share some of the blame for the J Clin Pathol: first published as 10.1136/jcp.42.9.912 on 1 September 1989. Downloaded from

Postmortem audit in a paediatric cardiology unit 917 Fig 5 Suggestedprotocol forpaediatric cardiac necropsy and a technique adapted to suit the clinical problems posed. Review notes/discuss with clinicians Appendix: a protocol for the cardiac necropsy in children Take blood for culture vitreous for urea and sodium The basis of the "cardiac necropsy" must be a skin for karyotype standard thorough paediatric postmortem examina- tion, of which several excellent accounts may be found.8 There is no single correct method for perform- Consider contrast radiology"0 ing the necropsy on the child with congenital heart disease. The optimal method takes into account the .4 clinical diagnoses and investigations done in life and is Document external anomalies tailored to the optimal demonstration of the scars/drains/pacing wires anticipated anomalies. The risk ofsuch an approach is that the pathologist becomes blinkered by natural attention to the cardiovascular system and neglecting CARDIAC EXTRACARDIAC the remaining examination. examine in-situ lung for culture The protocol outlined in fig 5 is time consuming and especially bilateral SVC, search foremboli as such is probably only appropriate to specialist pulmonary veins infarcts centres where most ofthese necropsies are performed. cardiac position anatomical anomalies Some of the methods are mutually exclusive-for suture lines/pacing wires situs example, histological examination of the conducting phrenic nerves (s) system prevents preparation of a specimen impreg- IVC continuity lung markings nated with wax.9 The most appropriate methods must azygous veins bronchi aortic arch/coronaries fix brain and cord be selected for the individual case. collaterals inflate lungs copyright. formalin perfusion or histology: all viscera inflation" dissection: lung lobes Standard planes traditional brain of section or windows liver or echo planes kidneys photograph adrenals draw anomalies thromboemboli Short axis histology: all chambers http://jcp.bmj.com/ conducting system wax impregnate specimen9

ISSUE REPORT PROMPTLY on September 30, 2021 by guest. Protected REVIEW AT REGULAR AUDIT MEETINGS Fig 5 A protocolfor cardiac necropsy. decline in necropsy rate in this country through their lack ofadvocacy and their unwillingness to modify age old practice to suit changing clinical needs. We must I1 monitor the value of our work constantly and publicise it to our clinical colleagues. As well as giving us insights into the mechanisms ofdeath the necropsy may highlight unsuspected problems whose importance is uncertain and which require further -/ Long axis study for their prevention. Effective audit of deaths in Fig 6 Standardplanes ofsectionfor comparison with specialist clinical centres requires a high necropsy rate echocardiograms. J Clin Pathol: first published as 10.1136/jcp.42.9.912 on 1 September 1989. Downloaded from

918 Russell, Berry

right pul.onary right pulmonary vein shown in life. Simple blocking of the conducting IC vein/ system is performed where gross lesions are sought. Svc

net Subtle abnormalities require serial sectioning of the left r~~~~~~~~~~~ightatrial pulmonary appemkge coronay vein entire system.'2 Even so, the method in children right- nuht AVcalve generates far fewer sections than in adults and can give appendage s valuable information.

valve large left ventricle Documentation of cardiac lesions is essential for subsequent clinicopathological discussion. We issue drawings ofcomplex anomalies with the initial report.

resected These rapidly convey the essence ofthe long report in a duct s more digestible form (fig 7). All hearts are photo- lef atia croipalmacy staftofthpstorepu/reamnaivtc_vaartery graphed; complex lesions may require multiple views at different stages of dissection. We attend regular y left atrial d atteryartiloevcaaoleftetrceatsertyrdappendage2 U l bandf ublva review meetings in which cases are discussed by largetar cardiologists, surgeons, radiologists, anaesthetists and svc l vary valve the Ventri cul ore ria1d crac deliaieing e d pathologists. The aim is to formulate strategies for rtery right c danocarotid prevention of the problems shown at necropsy where datrd planesi(ig6)yeldsusfceftlcaon witid these problems are avoidable.

dimensionaleodryr left vertebral

rudimentary right ventricle We thank Mr JD Wisheart, consultant cardiac surgeon, for reviewing the manuscript, and our clinical colleagues in the departments of cardiology and M Msuper 9 and resectiproxing.a resected pDoble inlet left ventricle aorta coarctatiin cardiac surgery for their support. Mrs Jill Tyley Left sided rudimentary right ventricle mVntriculoarterial discordancew iiorersi lean Coarctatioatesectedn cliniconstriction provided invaluable secretarial assistance.

7 of at necropsy issued with Fig Swnmary diagram findings References copyright. the descriptive report. I McPhee SJ, Bottles K. Autopsy: Moribund art or vital science? Am J Med 1985;78:107-13. 2 Anonymous. Autopsy rate [Editorial]. Hum Pathol 1985;16:1179. Much useful information can be obtained before the 3 Porter HJ, Keeling JW. Value ofperinatal necropsy examination. start of the postmortem examination. Contrast J Clin Pathol 1987;40:180-4. radiology is a simple means of accurately documenting 4 Goldman L, Sayson R, Robbins S. Value of autopsy in three the vascular abnormahties before they are disrupted medical eras. N Engl J Med 1983;308:1000-5. 5 Fisher EA, Dubrow IW, Eckner FAD, Hastreiter AR. Aortico- by dissection and may detect minor anomalies that are pulmonary septal defect and interrupted aortic arch: a http://jcp.bmj.com/ easily missed."' Perfusion fixation of the heart" makes diagnostic challenge. Am J Cardiol 1974;16:406-26. dissection much easier and leaves an organ whose 6 Franciosi RA, Blanc WA. Myocardial infarcts in infants and

bears more resemblance to the in vivo heart children. I. A necropsy study in congenital heart disease. anatomy J Paediatr 1968;73:309-19. than the residue of the routine cardiac dissection 7 Orenstein JM, Sato N, Aaron B, Bucholz B, Bloom S. Micro- performed at most necropsies. Sectioning along stan- emboli observed in deaths following cardiopulmonary bypass dard planes (fig 6) yields useful correlation with two surgery. Hum Pathol 1982;13:1082-90. 8 Keeling JW. The perinatal necropsy. In: Keeling JW ed. Fetal and dimensional echocardiography. More than one plane

neonatalpathology. London: Springer Verlag, 1987:1-30. on September 30, 2021 by guest. Protected may be examined by reassembling the heart with 9 Russell GA, Berry PJ. Approaches to the demonstration of "4superglue" and resectioning. Photographs of each congenital heart disease. J Clin Pathol 1986;39:503-7. plane of section should be taken. Cutting windows 10 Russell GA, Berry PJ. Postmortem radiology in children with into the free walls of the chambers leaves a congenital heart disease. J Clin Pathol 1988;41:830-8. specimen 11 Thomas AC, Davies MJ. The demonstration ofcardiac pathology more suited to wax impregnation and subsequent using perfusion-fixation. Histopathology 1985;9:5-19. examination at clinicopathological meetings. This 12 Anderson RH, Yen Ho S, Smith A, Wilkinson JL. Study of the method may also be used effectively on postoperative cardiac conduction system in the paediatric age group. Diagn hearts where grafts, shunts, and sutures may confuse Histopathol 1981;4:3-15. interpretation -following other dissection techniques. Histological examination of the conducting system is Requests for reprints to: Dr G A Russell, Department of only indicated where surgery has been performed in its Paediatric Pathology, Bristol Maternity Hospital, Southwell proximity or where rhythm disturbances have been Street, Bristol, England.