J Clin Pathol: first published as 10.1136/jcp.12.4.355 on 1 July 1959. Downloaded from J. clin. Path. (1959), 12, 355. FAMILIAL CARDIOMEGALY BY G. GARRETT,* W. J. HAY, AND A. G. RICKARDS From the Royal Lancaster Infirmary, Lancaster (RECEIVED FOR PUBLICATION SEPTEMBER 18, 1957) In 1949 William Evans gave the name of these criteria and include eight necropsy studies. familial cardiomegaly to what he believed to be a Only these cases are included in Table I and the "distinct syndrome having a definite clinical, subsequent discussion. cardiographic, and pathological pattern." The The purpose of this paper is to present a further essential features were the familial incidence example of a family with cardiomegaly, the three of cardiomegaly without obvious cause and a affected members of which died suddenly. Post- marked tendency to arrhythmia and heart block mortem studies were made in all three cases with associated palpitation, giddiness, and although in one details of the necropsy findings syncope. Death may be sudden or rapid due to are no longer available. the development of left ventricular failure. In the electrocardiogram the QRS complexes are often Case Histories exceptionally wide and the T waves inverted. Case 1.-G. D., a man aged 30 years at death, came Conspicuous myocardial fibrosis and hypertrophy home from work one evening in April, 1956, in his of the remaining muscle fibres are the striking usual good health, and while playing with his children copyright. pathological findings. Both the degree of in the garden suddenly collapsed and died. There conduction defect and the prognosis seem to was no history of rheumatic fever or other serious depend on the extent of myocardial fibrosis and illness in the past. Eight months before his death he cardiac sustained a slight injury to the right groin with enlargement. haematoma formation in the spermatic cord. His Evans referred to two previous accounts of wife thought that he was slow to pick up after that obscure cardiomegaly occurring in members of accident, but he eventually recovered, and his mother, http://jcp.bmj.com/ the same family published in the case records of who was with him on the day before he died, the Massachusetts General Hospital in 1942 and remarked that she thought he was in excellent health. by Addarii (1943) and Addarii, Martini, Mahaim, At no time was he heard to complain of dyspnoea, and Winston (1946). Subsequently cases have chest pain, faintness, or palpitation. been published by Davies (1952), Parsons (1952), Necropsy performed by one of us (A. G. R.) on the De Matteis and Ozzano (1954), Campbell and instructions of the coroner 21 hours after death revealed the following abnormalities. Turner-Warwick (1956), Gaunt and Lecutier was that of a well-built male with The body young on September 25, 2021 by guest. Protected (1956), and Paulley, Jones, Green, and Kane a previous appendicectomy scar; significant macro- (1956). Among these, however, are included cases scopic findings were confined to the thoracic cavity. of cardiomegaly with no supporting family The heart was markedly enlarged (weight 500 g.), the history and others where there is good reason hypertrophy mostly affecting the left ventricle, which to believe that the cardiac hypertrophy was in parts was nearly 2 cm. thick and appeared at first secondary to acquired valvular disease, congenital sight to be of the usual hypertensive type. On closer cardiac malformations, or toxoplasmosis. In our inspection it was seen that the outer part of the view the diagnosis of familial cardiomegaly myocardium consisted of pale fibrous tissue almost giving the impression of an outer shell surrounding should only be made when other causes of cardiac the inner layer (Fig. 1). Strands of fibrous tissue enlargement have been excluded and when there could be seen penetrating the deeper aspects of the is a clear supporting family history. Moreover, myocardium, but the predominantly peripheral in the present state of knowledge, it seems wise distribution was striking. The compact outer rim was only to include those cases where the diagnosis well demarcated from the rest of the myocardium has been established by necropsy study in at least except in the region of the interventricular septum one affected member of the family. The reports where its discrete pattern became replaced by diffuse of seven affected families (15 cases) comply with fibrotic mottling. The trabeculae carnae, papillary and chordae tendineae showed no evidence *Present address: Department of Clinical Pathology, Manchester muscles, Royal Infirmary. of fibrosis. The right ventricle and both auricles J Clin Pathol: first published as 10.1136/jcp.12.4.355 on 1 July 1959. Downloaded from 356 G. GARRETT, W. J. HAY, anid A. G. RICKARDS TABLE I MAIN CLINICAL FEATURES Age Length of Author's () History Necropsy No. Author Case Age Sex Family from No. at Relationship Symptoms Arrhythmias Heart Block Onset of IFindings Death Symptoms 2 Case records----A_ , I1l i (21)X4|l, M Brother with...:,t- con- Dyspnoea, Complete A-V 6 months Yes of M.G. gestive failure. fatigue, block Hosp. Sister with car- congestive (1942) diomegaly A-V failure UIU6CK anaI conl- gestive failure 2 Addarrii et al. I (?) M Brother of Case 3 Dyspnoea, Auricular Complete A-V 9 ,. (t943) syncope fibrillation block, brancli bundle block 3 Addarii et al. I (21) M Brother of Case 2. Dyspnoea, Auricular fibril- Complete A-V 15 years ,, ((1946) Mother died fatigue, lation, parox- block, branch C.C.F. and syn- syncope, ysmal tachy- bundle block cope congestive cardia failure 4 Evans (1949) I (18) M Son of Case 6. Giddiness. Paroxysmal Branch bundle 2 tooiths Brother of Case paroxysmal tachycardia, block 5 tachycardia extrasystoles 5 2 20 M Son of Case 6. Giddiness Auricular fibril- 6 ,, Brother of Case lation, parox- 4 ysmal auricu- lar tachycardia 6 3 43 F Mother of4 and 5. Syncope Auricular fibril- 12 years Three of her sib- lation, extra- lings believed systoles affected - 7 8 (16) M Son of Case 8 Sinus brady- 412 *s Yes cardia 8 App. 42 F Mother of Case 7 Paroxysmal, Paroxysmal Prolonged P-R 2 months tachycardia tachycardia interval, with occa- branch bundle sional block copyright. syncope 9 Gaunt and I (51) M Brother of Case I I Dyspnoea, Auricular Comple:e A-V 20 Yes Lecutier syncope fibrillation block (1956) 10 2 23 F' Daughter of Case Arthralgia, 3 ,, 1t1 slight 1,* . dyspnoea 11 3 (531) F Mother of Case 10. Syncope, Complete A-V 4 years - Sister of Case 9 dyspnoea block, branclh bundle block 12 Campbell and (23) M Son of Case 13 Syncope, Paroxysmal Prolonged P-R, 3 years Yes http://jcp.bmj.com/ Turner- palpitation, tachycardia, branch bundle Warwick dyspnoea, ventricular block (1956) severe chest extrasystoles pain 13 ,. ..1 2 (29) F Mother of Case 12l Dyspnoea, Branch bundle I year Eight of her 12 congestive block siblings died of failure, heart disease syncope under 40 years 14 3 (36) M Son of Case 15 Syncope Sinus and nodal Varying degrees 6 months Yes bradycardia, of A-V block, nodal or ven- branch bundle on September 25, 2021 by guest. Protected tricular extra- block systoles 15 4 66 F Mother of Case 14. Faintness, Paroxysmal Branch bundle 40 years Her sister, fatigue, auricular block mother, three dyspnoea flutter, aunts, and grand- sinus mother died of bradycardia heart disease appeared unaffected, and the pericardium and myocardium distributed peripherally and correspond- endocardium were also macroscopically normal. The ing to the area seen with the naked eye. The fibrous aorta merely showed slight atheroma of its first part, strands tended to separate the muscle fibres into and there was no evidence of coarctation. The lungs bundles (Fig. 2) and many of these isolated lobules of were engorged and the trachea and bronchi contained muscle showed degenerative changes similar to those a large amount of mucus; all the other organs, seen in early cell death following ischaemia (Fig. 3); including the brain and spinal cord, appeared normal slight infiltration with lymphocytes was seen in to the naked eye. occasional areas of fibrosis (Fig. 4). The right Microscopic examination of the left ventricle ventricle showed a similar pattern of interstitial showed marked hypertrophy of individual muscle fibrosis, although of lesser extent, and its distribution fibres associated with gross fibrosis of the was more irregular and was not confined to the J Clin Pathol: first published as 10.1136/jcp.12.4.355 on 1 July 1959. Downloaded from FAMILIAL CARDIOMEGALY 357 4, *4:::: FIG. copyright. http://jcp.bmj.com/ cv, FIG. 3 on September 25, 2021 by guest. Protected 12"IN~~~~~~*.* FIG. I.-Cross section of left ventricular wall showing peripheral ~~~~~~~~~~~~~~~~ w fibrotic mottling in Case 1. tFG. FIG. 2.-Trabeculated fibrosis of the left ventricle in Case 1. Haema- toxylin and eosin, x 60. FIG. 3.-Degenerative change in muscle fibres surrounded by fibrous tissue in Case 1. Haematoxylin and eosin, x 150. J Clin Pathol: first published as 10.1136/jcp.12.4.355 on 1 July 1959. Downloaded from 358 G. GARRETT, W. J. HAY, and A. G. RICKARDS papillary tips," but unfortunately the myo- cardium was not examined histologically. The coronary arteries were recorded as being normal. Various organs were examined for a wide variety of chemical poisons with negative results, death being eventually attributed to " acute pulmonary oedema precipitated by streptococcal pneumonia." From the description of the lungs and heart 41 it seems clear that in fact death was due to ... .. left ventricular failure. Case 3.-P. D., the sister of Cases 1 and 2, also died suddenly at the age of 18 years .......... * on December 26, 1939, exactly seven years before the death of her sister.