cardiac hypertrophy in old age

1
785 CARDIAC HYPERTROPHY IN OLD AGE SIR,-In hypertrophic cardiomyopathy (HCM) the most common morphological feature is a hypertrophied but not dilated left ventricle. The echocardiographic picture is well defmed.l,2 We report here a group of clinically normal elderly Chinese people of whom 34% met echocardiographic criteria for HCM. 38 consecutive adults (22 female, 16 male) aged 60-85 were studied by echocardiography and continuous wave doppler as part of a large study of normal echocardiographic/doppler values. The participants were the healthy relatives or friends of hospital staff, outpatients, or geriatric day hospital attenders with musculoskeletal problems, parkinsonism, or leg ulcers. Subjects were normotensive, with no history of cardiac disease, and normal clinical findings, ECG, and chest X-ray. We used an Aloka SSD-280S ultrasound unit, a UGR-34 doppler unit, and a 3 mHz transducer. The volunteers were studied in the left lateral position and M-mode recordings were made from the long axis parasternal window. We used the leading edge technique.3 Asymmetric septal hypertrophy was defined as an interventricular septal thickness of more than 12 mm at end diastole with a septum-to-posterior wall ratio of 1.3:1 :1 or more. Concentric left-ventricular hypertrophy was defmed when septal and posterior wall thicknesses were greater than 12 mm and the septum to posterior wall ratio was less than 1 3:1. Relation between interventricular septal thickness (IVS) and age. Interventricular septal thickness ranged from 8 to 18 mm (mean 12-3 [SD 2-7] mm) and posterior wall thickness ranged from 6 to 17 mm (10.4 [2’8] mm). 7 (18%) had asymmetrical septal hypertrophy, the ratio being 13-18 (mean 15), and 6 patients (16%) had concentric left-ventricular hypertrophy. None had ECG evidence of left-ventricular hypertrophy. There was no significant relation between septal thickness and blood pressure. Mean left-ventricular diastolic dimension was 39 (6) mm and mean ejection fraction was 64 (10)%. 2 participants had mild systolic anterior motion of the mitral valve leaflets. However, doppler studies showed no evidence of left-ventricular outflow tract obstruction. Septal thickness was significantly greater than that of the normal subjects aged less than 60 years (p < 0-001, figure). In this series ofcardiologically normal people over 60 years of age, 18% had asymmetrical hypertrophy typical of that seen in HCM while a further 16% had concentric left-ventricular hypertrophy. Other investigators have found a tendency for the interventricular septal thickness and ratio to increase with age. However, those studies were often limited to patients less than 70 years of age or have had very small numbers.4-6 It seems that the interventricular septal thickness continues to thicken with age and that one-third or more of the ageing population may be affected. The left-ventricular hypertrophy observed seems unlikely to represent HCM in view of the absence of clinical fmdings, negative family history, and the fact that HCM usually presents in early adulthood or middle age. Although this left-ventricular hypertrophy in elderly people may be unique to Chinese, the trend has been seen in caucasians, and in Chinese people below the age of 60 we find the left-ventricular wall thickness to be normal. Cardiac amyloidosis has been found in 10% of patients over 80 and in 50% of those over 90 at necropsy. However, symptoms and abnormal clinical findings would be expected if amyloidosis were the explanation. Until more is known about unexplained left-ventricular hypertrophy in the elderly a diagnosis of HCM based on echocardiography alone should be treated with caution. We propose to follow up these people to look for any clinical signs or symptoms of cardiac disease or excess mortality. Department of Medicine, Prince of Wales Hospital, Chinese University of Hong Kong MARGARET J. MILNE* JEAN WOO IAN G. CROZIER *Present address: Cardiology Department, Princess Margaret Hospital, Christchurch 2, New Zealand. 1. Rossen RM, Goodman DJ, Ingham RE, Popp RL. Echocardiographic criteria in the diagnosis of idiopathic hypertrophic subaortic stenosis. Circulation 1974; 50: 747-51. 2. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy (ASH): Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 1973; 47: 225-33. 3. Sahn DJ, Demaria A, Kisslo J, Weyman A. The Committee on M-mode Standardization of the American Society of Echocardiography. Recommendation regarding quantitation in M-mode echocardiography: Results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072-83. 4. Marcomichelakis J, Withers R, Newman GB, O’Brien K, Emanuel R. The relation of age to the thickness ofthe interventricular septum, the posterior left ventricular wall and their ratio. Int J Cardiol 1983; 4: 405-15. 5. Gerstenblith G, Frederiksen J, Yin FCP, Fortuin NJ, Lakatta EG, Weisfeldt. Echocardiographic assessment of a normal adult aging population. Circulation 1977; 56: 273-78. 6. Gardin JM, Henry WL, Savage DD, Epstein SE. Echocardiographic evaluation of an older population without clinically apparent heart disease. Am J Cardiol 1977; 39: 277. HISTOPATHOLOGISTS, MALIGNANCIES, AND UNDEFINED HIGH-POWER FIELDS SIR,-In 1981 Ellis and Whiteheadl recorded a 600% variation in the size of a "high-power field", depending on which microscope was used. The term "mitoses per high-power field" is thus unscientific unless the measurement is standardised. Despite this and other2 warnings, histopathologists still use this expression in an unstandardised way when counting mitotic figures and other histological features. A review of the five leading histopathology journals (Histopathology,F Pathol,F Clin Pathol, Hum Pathol, and Am J Clin Pathol) from the early part of 1988 confirms that "high-power field" is still being used as an absolute unit of measurement in published work. We found 27 references in which counts were expressed per microscopic field. Sometimes the area was stated (or the measurement was used only in a relative way within the study) but in a significant proportion the area was not defmed. The numbers were: area defined (6) or measurement used only relatively (11) and high-power field used as an absolute measurement without defining the area (10) (in 5 the magnification was not stated). The counting of a feature per area of section is, in reality, an attempt at enumeration per unit volume of tissue, and the thickness of the section should be taken into account for small particles such as mitotic figures or cells. A correlation formula has been derived3 but none of the papers we reviewed made this correction. Those using "high-power field" as an arbitrary unit for comparison of categories within a study and not as an absolute unit may feel immune from criticism. However, none of these 11 papers stated that the same microscope was used throughout. If the counting was shared between co-workers different microscopes may have been used to produce potential error quite apart from the well-recognised inter-observer variation. Most worrying is the use of "high-power field" as an absolute unit without definition and sometimes without even the magnification ( x 25, x 40, or x 45 may all be regarded as a "high power"). Does this really matter? The answer must be yes. It is unscientific to draw conclusions on the basis of measurements involving an undefined area that may vary up to 600%. Histopathologists use "mitotic figures per high-power field" as a diagnostic and prognostic arbiter in the assessment of soft-tissue sarcomas and malignant melanomas and lymphomas. An example of this practice is in smooth muscle tumours. These tumours may show nuclear

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Page 1: CARDIAC HYPERTROPHY IN OLD AGE

785

CARDIAC HYPERTROPHY IN OLD AGE

SIR,-In hypertrophic cardiomyopathy (HCM) the most

common morphological feature is a hypertrophied but not dilatedleft ventricle. The echocardiographic picture is well defmed.l,2 Wereport here a group of clinically normal elderly Chinese people ofwhom 34% met echocardiographic criteria for HCM.

38 consecutive adults (22 female, 16 male) aged 60-85 werestudied by echocardiography and continuous wave doppler as partof a large study of normal echocardiographic/doppler values. Theparticipants were the healthy relatives or friends of hospital staff,outpatients, or geriatric day hospital attenders with musculoskeletalproblems, parkinsonism, or leg ulcers. Subjects were normotensive,with no history of cardiac disease, and normal clinical findings,ECG, and chest X-ray. We used an Aloka SSD-280S ultrasoundunit, a UGR-34 doppler unit, and a 3 mHz transducer. Thevolunteers were studied in the left lateral position and M-moderecordings were made from the long axis parasternal window. Weused the leading edge technique.3 Asymmetric septal hypertrophywas defined as an interventricular septal thickness of more than12 mm at end diastole with a septum-to-posterior wall ratio of 1.3:1 :1or more. Concentric left-ventricular hypertrophy was defmed whenseptal and posterior wall thicknesses were greater than 12 mm andthe septum to posterior wall ratio was less than 1 3:1.

Relation between interventricular septal thickness (IVS) and age.

Interventricular septal thickness ranged from 8 to 18 mm (mean12-3 [SD 2-7] mm) and posterior wall thickness ranged from 6 to 17mm (10.4 [2’8] mm). 7 (18%) had asymmetrical septal hypertrophy,the ratio being 13-18 (mean 15), and 6 patients (16%) hadconcentric left-ventricular hypertrophy. None had ECG evidenceof left-ventricular hypertrophy. There was no significant relationbetween septal thickness and blood pressure. Mean left-ventriculardiastolic dimension was 39 (6) mm and mean ejection fraction was64 (10)%. 2 participants had mild systolic anterior motion of themitral valve leaflets. However, doppler studies showed no evidenceof left-ventricular outflow tract obstruction. Septal thickness wassignificantly greater than that of the normal subjects aged less than60 years (p < 0-001, figure).

In this series ofcardiologically normal people over 60 years of age,18% had asymmetrical hypertrophy typical of that seen in HCMwhile a further 16% had concentric left-ventricular hypertrophy.Other investigators have found a tendency for the interventricularseptal thickness and ratio to increase with age. However, thosestudies were often limited to patients less than 70 years of age orhave had very small numbers.4-6 It seems that the interventricularseptal thickness continues to thicken with age and that one-third ormore of the ageing population may be affected.The left-ventricular hypertrophy observed seems unlikely to

represent HCM in view of the absence of clinical fmdings, negativefamily history, and the fact that HCM usually presents in earlyadulthood or middle age. Although this left-ventricular

hypertrophy in elderly people may be unique to Chinese, the trendhas been seen in caucasians, and in Chinese people below the age of60 we find the left-ventricular wall thickness to be normal. Cardiacamyloidosis has been found in 10% of patients over 80 and in 50%of those over 90 at necropsy. However, symptoms and abnormal

clinical findings would be expected if amyloidosis were theexplanation.

Until more is known about unexplained left-ventricular

hypertrophy in the elderly a diagnosis of HCM based on

echocardiography alone should be treated with caution. We proposeto follow up these people to look for any clinical signs or symptomsof cardiac disease or excess mortality.

Department of Medicine,Prince of Wales Hospital,Chinese University of Hong Kong

MARGARET J. MILNE*JEAN WOOIAN G. CROZIER

*Present address: Cardiology Department, Princess Margaret Hospital, Christchurch 2,New Zealand.

1. Rossen RM, Goodman DJ, Ingham RE, Popp RL. Echocardiographic criteria in thediagnosis of idiopathic hypertrophic subaortic stenosis. Circulation 1974; 50:747-51.

2. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy (ASH):Echocardiographic identification of the pathognomonic anatomic abnormality ofIHSS. Circulation 1973; 47: 225-33.

3. Sahn DJ, Demaria A, Kisslo J, Weyman A. The Committee on M-modeStandardization of the American Society of Echocardiography. Recommendationregarding quantitation in M-mode echocardiography: Results of a survey ofechocardiographic measurements. Circulation 1978; 58: 1072-83.

4. Marcomichelakis J, Withers R, Newman GB, O’Brien K, Emanuel R. The relation ofage to the thickness ofthe interventricular septum, the posterior left ventricular walland their ratio. Int J Cardiol 1983; 4: 405-15.

5. Gerstenblith G, Frederiksen J, Yin FCP, Fortuin NJ, Lakatta EG, Weisfeldt.Echocardiographic assessment of a normal adult aging population. Circulation1977; 56: 273-78.

6. Gardin JM, Henry WL, Savage DD, Epstein SE. Echocardiographic evaluation of anolder population without clinically apparent heart disease. Am J Cardiol 1977; 39:277.

HISTOPATHOLOGISTS, MALIGNANCIES, ANDUNDEFINED HIGH-POWER FIELDS

SIR,-In 1981 Ellis and Whiteheadl recorded a 600% variationin the size of a "high-power field", depending on which microscopewas used. The term "mitoses per high-power field" is thusunscientific unless the measurement is standardised. Despite thisand other2 warnings, histopathologists still use this expression in anunstandardised way when counting mitotic figures and otherhistological features. A review of the five leading histopathologyjournals (Histopathology,F Pathol,F Clin Pathol, Hum Pathol, andAm J Clin Pathol) from the early part of 1988 confirms that"high-power field" is still being used as an absolute unit ofmeasurement in published work.We found 27 references in which counts were expressed per

microscopic field. Sometimes the area was stated (or themeasurement was used only in a relative way within the study) butin a significant proportion the area was not defmed. The numberswere: area defined (6) or measurement used only relatively (11) andhigh-power field used as an absolute measurement without definingthe area (10) (in 5 the magnification was not stated).The counting of a feature per area of section is, in reality, an

attempt at enumeration per unit volume of tissue, and the thicknessof the section should be taken into account for small particles such asmitotic figures or cells. A correlation formula has been derived3 butnone of the papers we reviewed made this correction. Those using"high-power field" as an arbitrary unit for comparison of categorieswithin a study and not as an absolute unit may feel immune fromcriticism. However, none of these 11 papers stated that the samemicroscope was used throughout. If the counting was sharedbetween co-workers different microscopes may have been used toproduce potential error quite apart from the well-recognisedinter-observer variation. Most worrying is the use of "high-powerfield" as an absolute unit without definition and sometimes withouteven the magnification ( x 25, x 40, or x 45 may all be regarded as a"high power").Does this really matter? The answer must be yes. It is unscientific

to draw conclusions on the basis of measurements involving anundefined area that may vary up to 600%. Histopathologists use"mitotic figures per high-power field" as a diagnostic andprognostic arbiter in the assessment of soft-tissue sarcomas andmalignant melanomas and lymphomas. An example of this practiceis in smooth muscle tumours. These tumours may show nuclear