Br J: first published as 10.1136/hrt.52.2.233 on 1 August 1984. Downloaded from

Br Heart J 1984; 52: 233-6

Primary cardiac in a young man presenting with pectoris

STEPHEN SALTISSI, PAUL J KERTES, DESMOND G JULIAN From the University Department ofCardiology, Freeman Hospital, Newcastle upon Tyne

suMMARY A 32 year old man presenting with typical angina pectoris was found to have primary cardiac amyloidosis. Myocardial infiltration was strongly suggested by , and a histological diagnosis was confirmed by renal biopsy. Nevertheless, technetium pyrophosphate myocardial scanning, recently proposed as a sensitive non-invasive test, showed negative results despite widespread cardiac involvement confirmed at necropsy after unexpected sudden death. Postmortem findings also showed subintimal material in a severely narrowed right coronary artery. This case highlights several unusual clinical features in a patient with advanced primary cardiac amyloidosis.

Primary cardiac amyloidosis is a rare disease, which tory. Exertional chest tightness radiating to both arms usually presents with in the middle and was first noted four months before admission and had later years of life. Presentation with angina pectoris gradually increased in severity. Preliminary investiga- has been reported rarely. Although the therapeutic tions had shown a with 6-7 g options are limited and the treatment generally urinary protein loss per 24 hours with otherwise nor- unsatisfactory, the antemortem diagnosis of primary mal renal function determined biochemically and by cardiac amyloidosis is important to exclude poten- intravenous pyelography. tially remediable conditions which it may mimic. On examination he was normotensive with a sinus http://heart.bmj.com/ Haemodynamic values obtained at cardiac catheterisa- of 100 beats/min. The jugular venous tion are diagnostically unreliable as they may not pressure was slightly raised with a prominent "a" clearly differentiate restriction from pericardial con- wave. The apical impulse was not easily felt, and on striction.' Thus the diagnostic value of several non- auscultation a third heart sound was audible with no invasive investigations has been studied, including murmurs. The lung fields were clear, and the liver, echocardiography2-4 and radionuclide myocardial spleen, and kidneys were all impalpable. imaging.5-8 In particular, the sensitivity and

specificity of technetium-99m pyrophosphate INVESTIGATIONS on September 24, 2021 by guest. Protected copyright. myocardial are reported to be high.8 The electrocardiogram showed sinus rhythm with an We report the case of a patient presenting with axis of +100°. There was a Q wave in leads VI and V2 angina, in whom primary cardiac amyloidosis was with clockwise rotation. Downsloping ST depression indicated by echocardiography but not by myocardial and inversion were prominent in the scanning. anterolateral leads. The complexes were reduced in amplitude in the limb leads only. The chest x ray film Case report showed prominence of the upper lobe vessels with small bilateral pleural effusions; these changes cleared A 32 year old white man presented with a four month rapidly after treatment with an oral diuretic. The car- history of progressively increasing chest pain on exer- diothoracic ratio was 0-5. An echocardiogram showed tion which was typical of angina pectoris. He was a a pronounced concentric increase in both left and non-smoker with no relevant medical or family his- right ventricular wall thickness (Figure), and the myocardium appeared to be granular with echo dense Requests for reprints to Professor D G Julian, University Depart- speckling. Left ventricular cavity size was normal, ment of , Freeman Hospital, Newcastle upon Tyne and a small was evident. The M NE7 7DN. mode echocardiograms of left ventricular wall motion 233 Br Heart J: first published as 10.1136/hrt.52.2.233 on 1 August 1984. Downloaded from

234 Saltissi, Kertes, Julian

'4"7,' -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~S'':RVAW 04".1 7A Figure Parastemal M mode echocardiogram showing pronounced thickening ofthe interventicular septun (IVS 15 mm, normal sll mm), left vericularposteior wall (LVPW 19 mn, normal ,1I mm), and right venricular anterior wall (RVAWM. A smaaU pericardial effusion is visible (PE). The kft ventricar end diastolic dimension of43 mm is within the normal range (up to 52 mn), but the end systolic dimension of29 mmyields a subnormalfractionl shortening of 25% (normal 2280%6).

were digitised and showed a reduced fractional cir- clear pericardial fluid, and the lungs were congested. cumferential fibre shortening of 25% (normal , 28%) The spleen was enlarged and of waxy consistency, as and subnormal maximum velocities of left ventricular were the kidneys. Histological examination showed systolic and diastolic dimension change of 9-2 cm/s extensive diffuse deposition of amyloid material in the and 9*7 cm/s respectively (normal > 10 cm/s). kidneys, spleen, and throughout the myocardium. A technetium-99m pyrophosphate myocardial scan Subintimal amyloid material was found in the obs- was negative, the myocardial uptake of the tracer (1+) tructing lesion in the right coronary artery. Bone mar- being of a lesser intensity than that of the rib cage. row examination was normal. The peripheral blood film was normal and the erythrocyte sedimentation rate 24 mm in the first Discussion hour. Serum electrolyte concentrations and liver func- http://heart.bmj.com/ tion tests were normal apart from moderate hypo- This report of a patient with primary cardiac albuminaemia. A repeat 24 hour urine collection amyloidosis confirmed at necropsy highlights several showed 14.8 g protein, and numerous red blood cell unusual features, which may be of importance with casts were present in the urinary sediment. Plasma respect to the clinical presentation and non-invasive concentrations of IgG, IgA, and IgM were all appreci- diagnosis of this condition. Primary cardiac ably reduced, and immunoelectrophoresis showed a amyloidosis is usually regarded as a disease oflater life band of free X chains. A renal biopsy was performed with a mean age at diagnosis of 61 years, over 98% of and showed early glomerular and vascular amyloid at > 40 10 This case patients presenting years of age.9 on September 24, 2021 by guest. Protected copyright. deposition. was negative. in a 32 year old patient, together with reports ofprim- In view of these findings a diagnosis of amyloidosis ary cardiac amyloidosis presenting in childhood,1' 12 with cardiac involvement was thought likely, and car- however, emphasises that the diagnosis is possible at diac catheterisation was not performed. After a rapid all ages. initial response to frusemide and nitrates the patient Congestive cardiac failure is the commonest mode was discharged from hospital with an early outpatient of presentation, occurring in 80% or more of patients review planned to consider treatment with colchicine. with primary cardiac amyloidosis.13 14 Typical anginal Unfortunately, he died suddenly at home two days chest pain has been reported but is rarely the present- later. ing symptom. In a recent study of 70 patients with systemic amyloidosis,10 angina occurred in four of 20 NECROPSY FINDINGS patients with primary amyloidosis and was the pres- Postmortem examination confirmed biventricular enting symptom in only one. The pathogenesis of the enlargement with the heart weighing 500 g. The wall angina is thought to be widespread amyloid infiltra- of the right coronary artery was appreciably thickened tion in the adventitia and media of small intramural halfway along its length with the lumen greatly coronary arteries.'013 Intimal deposits of sufficient reduced. Minor atheroma was seen in the left anterior degree appreciably to narrow such vessels are found descending artery. There was a moderate amount of less frequently, occurring in five of 15 patients with Br Heart J: first published as 10.1136/hrt.52.2.233 on 1 August 1984. Downloaded from

Primary cardiac amyloidosis in a young man presenting with angina pectoris 235 cardiac amyloidosis in one study.13 In another nec- to or greater than that of the ribs (3+ or 4+) was ropsy study15 similar lesions producing focal suben- found in nine of 11 patients with abnormal echocar- docardial ischaemic injury were found in only five of diograms but in only two of nine with normal 108 patients with cardiac amyloidosis. In none of the echocardiograms, the extent of uptake correlating patients in these studies could the angina be attri- with wall thickness. Consequently, myocardial imag- buted to disease of the larger epicardial coronary ing has been advocated- as a sensitive (89%) and arteries. In a recent report of 54 patients with cardiac specific (100%) diagnostic test for primary cardiac amyloidosis studied at necropsy,'4 only four experi- amyloidosis, which is of particular value in moder- enced typical angina at some time in their illness and ately advanced cases with echocardiographic abnor- in only two were the epicardial coronary arteries obs- malities.8 In contrast, in our patient with advanced tructed, by atherosclerotic plaque in both cases. The myocardial disease and widespread typical echocar- present report emphasises the fact 'that cardiac diographic features technetium pyrophosphate imag- amyloidosis may present with typical angina of effort, ing was negative. This finding highlights the limita- which may be due to lesions containing amyloid in tions of this technique in diagnosing primary cardiac major coronary arteries as well as to diffuse myocar- amyloidosis in individual patients. dial infiltration. Primary cardiac amyloidosis may, therefore, pres- The definitive diagnosis of primary amyloidosis ent with typical angina pectoris, even in young men. rests with tissue biopsy. Although renal and liver Non-invasive test results may point to the diagnosis biopsy confirm the diagnosis in 90% and 95% of cases when positive but do not exclude the presence of even respectively,'6 these procedures are not without risk. advanced disease when negative. Histological exami- Rectal biopsy is safer but less sensitive, being diagnos- nation of appropriate tissue biopsy specimens remains tic in only 60-80% of cases.9 16 Endomyocardial the definitive diagnostic test. biopsy has also occasionally proved useful in patients with signs of cardiovascular involvement, but it also PJK is supported by the Australian National Heart carries an appreciable risk and requires appropriate Foundation. facilities and expertise. Recent interest has, therefore, focused on the non-invasive diagnosis of cardiac amyloidosis, in particular by echocardiography24 or technetium-99m pyrophosphate myocardial imag- References ing.5-8 Typically, echocardiography shows increased left and right ventricular wall thickness and reduced 1 Swanton RH, Brooksby IAB, Davies MJ, Coltart DJ, Jenkins BS, Webb-Peploe MM. Systolic and diastolic http://heart.bmj.com/ systolic left ventricular wall thickening in over 75% of ventricular function in cardiac amyloidosis. Studies in six patients.4 Global reduction of left ventricular func- cases diagnosed with . Am J Car- tion, left , and pericardial effusions diol 1977; 39: 658-64. are found in most patients. Left ventricular diastolic 2 St John Sutton MG, Reichek N, Kastor JA, Giuliani ER. function has been found to be more prominently Computerised M-mode echocardiographic analysis ofleft impaired in patients with cardiac amyloidosis than in ventricular dysfunction in cardiac amyloid. Circukuin control subjects with or hypertrophic 1982; 66: 790-9. .2 Although considerable overlap 3 Bhandari AK, Nanda NC. Myocardial texture character- existed between these groups, the results highLight the ization by two-dimensional echocardiography. Am J on September 24, 2021 by guest. Protected copyright. Cardiol 1983; 51: 817-25. importance of restricted diastolic filling due to 4 Siqueira-Filho AG, Cunha CLP, Tajik AJ, Seward JB, myocardial amyloid deposition. Some workers have Schattenberg TJ, Giuliani ER. M-mode and two- claimed that the granular sparkling appearance found dimensional echocardiographic features in cardiac in thickened ventricular muscle on cross sectional amyloidosis. Circukaion 1981; 63: 188-96. echocardiography in patients presenting with unex- 5 Wizenberg TA, Muz J, Sohn YH, Samlowski W, Weis- plained cardiac failure is virtually diagnostic of car- sler AM. Value of positive myocardial technetium-99m- diac amyloidosis,4 although others regard this appear- pyrophosphate scintgraphy in the noninvasive diagnosis ance as non-specific, occurring in other forms of of cardiac amyloidosis. Am HeartJ7 1982; 103: 468-73. Moffatt R, Davidson Bernan infiltrative cardiomyopathy, hypertrophic car- 6 Schiff S, Bateman T, R, D. Diagnostic considerations in cardiomyopathy: unique diomyopathy, and even chronic renal failure.3 scintigraphic pattern of diffuse biventricular With technetium-99m pyrophosphate imaging dif- technetium-99m-pyrophosphate uptake in amyloid heart fuse and intense accumulation of myocardial tracer disease. Am Heart J 1982; 103: 562-3. has been reported in primary cardiac amyloidosis5-8 7 Sobol SM, Brown JM, Bunker SR, Patel J, Lull RJ. with increased specificity when uptake is biventricu- Noninvasive diagnosis of cardiac amyloidosis by lar.6 In a study of 20 patients with cardiac amyloidosis technetium-99m-pyrophosphate myocardial scintigra- confirmed by biopsy,8 tracer uptake of intensity equal phy. Am Heart J 1982; 103: 563-6. Br Heart J: first published as 10.1136/hrt.52.2.233 on 1 August 1984. Downloaded from

236 Saltissi, Kertes, Julian 8 Falk RH, Lee VW, Rubinow A, Hood WB Jr, Cohen crasia, and amyloidosis in a 12-year old child. AmJ Dis AS. Sensitivity of technetium-99m-pyrophosphate Child 1977; 131: 682-6. scintigraphy in diagnosing cardiac amyloidosis. Am J 13 Buja LM, Khoi NB, Roberts WC. Clinically significant Cardiol 1983; 51: 826-30. cardiac amyloidosis. Clinicopathologic findings in 15 9 Kyle RA. Amyloidosis. Clin Haematol 1982; 11: 151-80. patients. Am J Cardiol 1970; 26: 394-405. 10 Wright JR, Calkins E. Clinical-pathologic differentiation 14 Roberts WC, Waller BF. Cardiac amyloidosis causing of common amyloid syndromes. (Baltimore) cardiac dysfunction: analysis of 54 necropsy patients. Am 1981; 60: 429-48. J Cardiol 1983; 52: 137-46. 11 Hake H, Goll U, Thoenes W. Primary perireticulin 15 Smith RRL, Hutchins GM. Ischemic heart disease sec- amyloidosis in a 14-year old girl. EurJ Pediatr 1976; 124: ondary to amyloidosis of intramyocardial arteries. Am J 43-9. Cardiol 1979; 44: 413-7. 12 Pick AI, Versano I, Schreibman S, Ben-Bassat M, 16 Kyle RA, Bayrd ED. Amyloidosis: review of 236 cases. Shoenfeld Y. Agmmaglobulinemia, dys- Medicine (Baltimore) 1975; 54: 271-99. http://heart.bmj.com/ on September 24, 2021 by guest. Protected copyright.