No abstract

Background-In vivo studies with intravascular ultrasound have shown that complex plaque anatomy and plaque rupture are more frequent in the presence of marked outward remodeling. A large lipid core and a high macrophage count are recognized histological markers for plaque vulnerability. The link between plaque vulnerability in terms of these markers and remodeling in coronary arteries has not been explored. Methods and Results-In 88 male subjects who died suddenly with coronary artery disease, 108 plaques were studied. The percent remodeling was calculated. Lesions with remodeling Ն0% were considered to have positive remodeling, and those in which remodeling was Ͻ0% were considered to have negative remodeling. Percent lipid core and macrophage count at the plaque were assessed.

Quantitative studies on the sinoatrial (SA) node and internodal tracts in IOO heartsfrom patients coming to necropsy with atrialfibrillation have been carried out. In patients with atrialfibrillation developing only in the last two weeks of life, pulmonary emboli and acute pericarditis were common precipitating factors. Atrial dilatation was common but the SA node and internodal tracts were within normal limits. In contrast patients with long-term atrial fibrillation showed combinations of nodal artery stenosis, muscle loss in the SA node or internodal tracts, and atrial dilatation. The pathological conditions found most commonly were chronic rheumatic valve disease, ischaemic heart disease, hypertension, and cor pulmonale. Atrialfibrillation in some aged patients was associated with loss of muscle fibres in the SA node without any clear pathological cause.The sinoatrial (SA) node is now universally accepted as the site of initiation of the impulse for cardiac contraction; it is also well established that specialized myogenic fibres are responsible for its inherent rhythm (HofEman and Cranefield, I960). The impulse passes to the atrioventricular node via internodaltracts within the atria (James, i96i, I963) and, while in man these tracts do not have specific histological features, there is ample physiological proof of their existence (Vassalle et al., I964).Great emphasis has always been placed on the pathophysiological basis of atrial fibrillation, both in man and animals. The morphological changes which may predispose to or accompany this arrhythmia have received considerably less attention. Clinical studies in man have shown conditions such as rheumatic valve disease to be strongly associated with atrial fibrillation (Stock, I970). Old age seems both to predispose to atrial fibrillation (Taran and Szilagyi, I958) and to mitigate against DC conversion (Waris, Kreus, and Salokannel, 197I).Though our knowledge of the pathology of atrial fibrillation is far from complete, valuable work has been carried out by Hudson (I965) who suggested that damage to the SA node was one factor. Other features described in this arrhythmia include damage to internodal pathways (James, i962), atrial dilatation (Laas, i962), and occlusion of the nodal artery Received 28 July 1971.(Lippestad and Marton, I967). It is uncertain, however, whether each of these lesions can cause arrhythmia acting singly, or in combination or, indeed, if they are invariably present in atrial fibrillation. It is also probable that in some transitory episodes of atrial fibrillation, as in digitalis therapy, purely physiological mechanisms are acting without structural damage. Materials and methodsHearts were taken from I00 patients with atrial fibrillation coming to necropsy at St. George's Hospital and The Central Middlesex Hospital, London. These patients represent a consecutive series over a one-year period. All the patients had an electrocardiogram recording atrial fibrillation during the last two weeks of life, and cases were only included when clin...

Genes on five loci on separate chromosomes are responsible for a familial disease in which all or part of the ventricular muscle undergoes thickening with a histological picture of irregular hypertrophy and disorganized arrangement of myocytes (disarray). The three genes identified so far encode for beta heavy chain myosin (chromosome 14), troponin T (chromosome 1) and alpha tropomyosin (chromosome 15). It is postulated that the phenotype within the heart is produced by abnormal myofibril formation and alignment leading to an abnormal cell shape and, thus, disarray. While all the myocytes carry the gene, the regional selectivity of the hypertrophy is unexplained. The phenotypic expression of the disease within affected members of one family, all of whom are heterozygous for the same gene abnormality, is very varied. Asymptomatic carriers are common, and new mutations do not account for most apparently isolated cases. The phenotypic expression of the disease was studied in 75 hearts. The increase in total heart weight ranged from near normal to over 800 g. Ventricular involvement was diffuse and symmetric in 42%. The commonest asymmetric form involved the anteroseptal region (31%) but sporadic cases involved only the posterior or lateral wall. A minority of cases (9.5%) did not show macroscopic wall thickening. Fibrosis is often associated with dysplastic changes in the media of small intramyocardial arteries and may lead to the ventricular wall simulating a dilated cardiomyopathy. A subaortic patch of endocardial thickening on the ventricular septum due to contact with the anterior cusp of the mitral valve was found in a third of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

In 4.1% of sudden unexpected deaths under 65 years, no cause was found. Until it becomes accepted practice to identify these cases by a name, such as Sudden Adult Death Syndrome (SADS), it will not be possible to study their aetiology systematically.

Objective: To describe the characteristics of sudden arrhythmic death syndrome (SADS) and compare its incidence with official national mortality statistics for unascertained deaths. Design and setting: Sudden unexplained deaths were prospectively surveyed through 117 coroners' jurisdictions in England. Consecutive cases meeting the following criteria were included: white Caucasian, aged 4-64 years, no history of cardiac disease, last seen alive within 12 h of death, normal coroner's autopsy, cardiac pathologist's confirmation of a normal heart and negative toxicology. Main outcome measures: The estimated mortality from SADS was calculated and the official mortality statistics for unascertained causes of deaths in 4-64-year-olds was identified for the same time period. Results: 115 coroner's cases were reported and 56 (49%) SADS victims were identified: mean age 32 years, range 7-64 years and 35 (63%) male. 7 of 39 cases (18%) had a family history of other premature sudden deaths (,45). The estimated mortality from SADS was 0.16/100 000 per annum (95% CI 0.12 to 0.21), compared with an official mortality of 0.10/100 000 per annum for International Classification of Diseases 798.1 (sudden death, cause unknown-instantaneous death) or 1.34/100 000 per annum for unascertained causes of death. Conclusions: Deaths from SADS occur predominantly in young males. When compared with official mortality, the incidence of SADS may be up to eight times higher than estimated: more than 500 potential SADS cases per annum in England. Families with SADS carry genetic cardiac disease, placing them at risk of further sudden deaths. SADS should therefore be a certifiable cause of death prompting specialised cardiological evaluation of families.

SUMMARY The mitral annulus is the point at which the atrial and ventricular walls meet the base of the mitral valve cusps. The suggestion that a variant of this arrangement termed "disjunction" was associated with prolapse of the leaflets prompted examination of the mitral atrioventricular junctions in seven normal hearts and six with prolapse owing to floppy mitral valves. A complete cord-like ring of connective tissue that encircled the atrioventricular junction and into which the three components were inserted at the same point was found in only one heart. The remaining hearts all showed a mixture of segments in which either the three components were inserted into a cord or simply met. Disjunction, defined as a separation of the atrial wall-mitral valve junction from the other component, the left ventricular wall, can occur both with and without a cord-like annulus. There was no significant difference in the number of segments around the left atrioventricular junction which showed disjunction in hearts with normal or prolapsing leaflets.The feature termed disjunction is an anatomical variation of the normal morphological characteristics of the left atrioventricular junction. atrial wall-mitral valve junction and the left ventricular attachment.9 They argued that this anomalous feature, through a process of hypermobility of the tension apparatus, could lead to floppiness of the leaflets. This group, however, studied only limited histological sections from a large number of hearts to demonstrate the significant association between so-called "disjunction" and floppy and prolapsed leaflets.It seemed to us that it was important to test their hypothesis by examining in detail the entire atrioventricular junction in a smaller number of hearts. This report describes our findings. Patients and methodsWe examined 13 hearts obtained an necropsy. The mitral valve was normal in seven (from 3 men and 4 women) and floppy in six (from 4 men and 2 women). The specimens of normal hearts came from a group aged 66-80 years (mean 71-9) and those with floppy valves came from a group aged 56-89 years (mean 69-5).

Quantitative analysis of the amount of muscle,fat, and collagen in the human sinoatrial node and internodal tracts has been carried out. Subjects under 50 were compared with those over 75 years of age at death. In old age there is a significant fall in the amount of muscle present in the sinoatrial node and internodal tracts.It has long been accepted that the sinoatrial node is the normal pacemaker of the heart. More recently it has been established that specialized atrial myogenic conduction paths carry the impulse to the atrioventricular node (James, I963; Merideth and Titus, I968); it is now universally accepted that the automaticity of the sinoatrial node is a function of cardiac muscle fibres. Elderly subjects seem particularly prone to develop atrial arrhythmias (Taran and Szilagyi, I958), and ageing changes in the sinoatrial node and internodal tracts may be a factor accounting for this phenomenon. However, the very existence of such ageing changes is debated; Lev did note (i194) and has illustrated (I968) fibrosis in the sinoatrial nodes of elderly subjects but these findings were not confirmed by Rossi (I969). The present study is designed to resolve this point on a quantitative basis. Materials and methodsThe hearts of 50 subjects under 50 years of age were compared with 50 hearts from subjects over 75 years of age at death; the minimum age was 37 years and the maximum 89 years. Hearts were taken only from subjects with no principal causes of death were malignancy including many cerebral tumours, trauma, drug overdose, and bronchopneumonia.The entire sinoatrial ring was excised, opened posteriorly, and pinned flat for fixation. Subsequently the entire ring was divided into blocks, one or more of which contained the sinoatrial node, for examination by subserial section (Hudson, I965; Davies, I971). Serial blocks were taken of the three main internodal tracts, anterior, middle, and posterior, down to immediately above the atrioventricular node. In practice, therefore, the entire sinoatrial ring, interatrial septum, and posterior wall of the right atrium was blocked.Cavity size of the right and left atria was determined by filling them with molten paraffin wax. The weights of the solid casts of the atria were subsequently used to calculate volumes. In order to eliminate variation due to fixation shrinkage every heart was fixed for between 5 and 7 days in 4 per cent formaldehyde in saline.Histological slides were stained routinely by haematoxylin and eosin, elastic van Gieson, and a modification of the picro-Mallory stain.Identification of the sinoatrial node by naked eye is easily made in the slides stained by the picro-Mallory technique because of its collagen content, and its outline was marked on the cover glass in Indian ink. Subsequently the ratio of collagen (blue staining) to muscle (red staining) was calculated within this circle using a Zeiss i integrating eyepiece (Dunnill, I962). In all, 8 to I2 slides evenly distributed through the node were so assessed. The figures were used to calculate th...