Hypertrophic
Norman Richard
cardiomyopathy
in the aged
Krasnow, M.D. A. Stein, M.D.
Brooklyn, N. Y.
Hypertrophic cardiomyopathy is a not uncommon disease which has been well characterized since the early reports presenting a composite picture of the disease by Brachfeld and Gorlin,’ Braunwald and associates,’ and others.:‘-” The obstructive variant, also called idiopathic hypertrophic subaortic stenosis, is associated with characteristic clinical findings,’ including a systolic ejection murmur, unusually brisk carotid pulses, bifid apical impulses, increase in the intensity of the murmur with Valsalva maneuver, and often associated mitral insufficiency. Symptoms and signs include syncope, heart failure, arrhythmias, and angina. Left ventricular hypertrophy is often present on the electrocardiogram and chest x-ray. When any one or more of these abnormalities occurs in a young healthy adult, detailed investigation is likely to be carried out, and a diagnosis established. The echocardiogram has contributed enormously to the non-invasive diagnosis of this condition, especially in its non-obstructive variety (asymmetric septal hypertrophy). Previous studies have indicated that the disease predominates in the young or middle-aged population, although instances of hypertrophic cardiomyopathy in older patients have been noted in these studies.“-“’ In the past 28 months, 23 new cases of hypertrophic cardiomyopathy have been detected at the Cardiac Graphics Laboratory of the Downstate Medical Center. Twenty of the patients were over the age of 50 years and form the subject of this report. Fifteen of these patients From the Department of Medicine, Medical Center, Brooklyn, N. Y.
Cardiology
Received
for publication
Sept.
7, 1977.
Accepted
for publication
Nov.
7, 1977.
Reprint requests: Norman ology Division, Downstate lyn, N. Y. 11203.
326
September,
Krasnow, Medical
M.D., Center,
Division,
Downstate
Dept. of Medicine, 450 Clarkson Ave.,
1978, Vol. 96, No. 3
CardiBrook-
were over the age of 60 years. In the majority the correct diagnosis was not made clinically, either because it was not considered in these elderly patients, or because some of the usual characteristic features were masked or attributed to other conditions more common in this age group. Cardiac catheterization is often avoided in the elderly if a clear therapeutic decision is not apparent. The twofold purpose of this paper is (1) to emphasize the occurrence of hypertrophic cardiomyopathy in the older patient, in whom the diagnosis is more likely to be missed, and (2) to emphasize the apparent compatibility of this diseasewith long life which, in part, conflicts with current thinking on the natural history of the disease. Materials
and
methods
Clinical echocardiograms were performed on a Smith-Kline Echocardiograph Model 20A, using a Honeywell 1856 ultraviolet recorder and a 2.25 MHz, ‘/z inch diameter transducer. Phonocardiograms and carotid pulse recordings were performed on a Honeywell recorder, using two microphones sinultaneously, each recording in 50 to 120 Hz and 100 to 500 Hz bands, or on a Schwarzer six-channel direct writing polygraph. Echocardiograms from many of these elderly patients were difficult technically because of overlying lung tissue damping the high-frequency sound. Nevertheless, great care was taken to delineate as well as possible both right and left margins of the interventricular septum in order to define thickness carefully at the level of the mitral valve and posterior wall. Echoes from the septal leaflet of the tricuspid valve were carefully differentiated from the right (anterior) margin of the septum.
0002-8703/78/0396-0326$01.10/O
0 1978 The
C. V. Mosby
Co.
Hypertrophic
cardiom~~op~rth? in the aged
ECG WON0
CAROTID
SEPTUM
POST WALL
Fig. 1. Hypertrophic obstructive cardiomyopathy in a 61-year-old woman (H. M.) with a history of’ rheumatic fever in childhood, and a clinical diagnosis of mitral insufficiency. The right side of the septum in this portion of the rec,ording is obscured. There is a SAM, narrow transverse LV diameter, notched aortic valve and spike-and-dome carotid pulse.
Patient selection. Of about 2,000 subjects studied, twenty patients over the age of 50 had hypertrophic cardiomyopathy. Seventeen of these met the criteria for hypertrophic obstructive cardiomyopathy (e.g., Fig. 1). These required criteria included: (a) septal hypertrophy (greater than 1.2 cm. thickness), out of proportion to posterior wall thickness (septum/posterior wall thickness ratio 1.4 or greater), (b) systolic anterior motion (SAM) of the anterior mitral leaflet, present either at rest or after amyl nitrate inhalation. The SAM in all cases was discrete and abrupt. It did not appear to be related to underlying papillary muscle motion.” Additional criteria, not sufficient in themselves for diagnosis, were: (c) anterior displacement and slowing of the early diastolic closing motion of the anterior mitral leaflet in diastole, (d) decrease in transverse left ventricular diameter at the level of the mitral valve, (usually producing a characteristic “busy” appearance of the recording), and (e) notching of the aortic valves.“’ In each case there was no stenosis of the aortic valve. Characteristic pulse abnormalities (Fig. 1) were a rapid rate of carotid upstroke, with spike-and-
American Heart Journal
dome configuration.’ Prolonged ejection time index and decreased systolic time intervals were taken as indices of outflow tract obstruction,‘” but not differential for valvular vs. subvalvular location. The presence of pulse abnormalities was considered confirmatory but not diagnostic, and the absence of pulse abnormalities did not exclude the diagnosis. In three cases, the diagnosis of hypertrophic cardiomyopathy, without outflow tract. obstruction, was based on disproportionate septal hypertrophy (criterion a as above) in thr absence of other clinical or echocardiographic c>xplanations for a thickened septum. Results Patient profile (Tables I and II). The oldest patient in this series was 76. Fifteen of the 20 in the group were 60 years of age, or older. Fifteen were women. The most common presenting complaints (Table I) were syncope or dizziness in nine, signs of heart failure in five, and chest pain in four. In two cases the cardiac lesion was discovered and diagnosed incidenial to other unrelated events.
327
Krasnow
and
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I. Hypertrophic
Table
cardiomyopathy Duration
Patient
Age
Sex
Symptoms
D. A.
65
M
4 yr.
E. B.
68
F
10 + yr.
S. B.
65
F
A. B. N. B.
50 57
F. E. B. G. H. A. M. J.
C. G. J. L. M. M. M. P.
P. E. R. A. A. R. K.
P. S. W. Wl. Wn. F. M.
Abbreviations: insufficiency;
in the aged: Clinical characteristics
of presenting Complaint
Associated findings CHF
Pain
HBP
+
i-
HBP; dyspnea Syncopd
+
-
++
-
6 yr.
Syncope
++
+
+
ii
F F
3 days 7 yr
Dyspnea Syncope
+
+
++
73 58 75 67 62 63 76 75
F F F F F M M F
0 8 yr. 4 yr. 60 days 4 yr. 7 days
Syncope Dyspnea Pain Syncope Dyspnea Paid
+ +++
f
+
+
1 yr.
Syncope
2 yr.
Dizziness
64 73 68 61 58 57 65
M F F F F F F
1 yr. 5+yr. 9 yr. 0 6 yr. 0.5 yr. 41 yr.
Dizziness Pain Pain None None CVA Dyspnea
CHF HOCM
= congestive = hypertrophic
HBP = hypertension; AS = aortic stenosis;
heart
failure; obstructive
Arrhythmia
Positive family history
+
+ +
The correct diagnosis was suspected in only four cases, but was not made definitively by the referring or consulting physician (usually a cardiology Attending or Fellow). Valvular heart disease, either aortic stenosis or mitral insufficiency, or both, was considered in 11, hypertensive and/or atherosclerotic heart disease in nine; in one patient both valvular and atherosclerotic heart disease were the prime diagnostic considerations. The duration of symptoms prior to diagnosis averaged 5.5 years, excluding two patients who had no symptoms, and three who had symptoms for less than 1 week before admission. Seven patients were aware of a heart murmur for at least several years previously, but had not undergone diagnostic study. Palpable carotid pulse abnormalities were present in only five cases, all of whom had evidence of outflow tract obstruction on echocardiogram.
328
Murmur
+
+
+
+
+ f
+
+ + + +
+-
-
f
+ + -
+ +
+
+
+
+
+
Referring diagnoses HBP; CAD;? valve disease HBP; CAD;? valve disease MI, AS; ? HOCM MI, AS Angina; ? HOCM AS; ? HOCM CAD CAD AS, MI MI AS; CAD CAD; ? HOCM AS; ?MI ?HOCM HOCM AS, MI AS; CAD MI CAD CAD AS
CVA = cerebrovascular accident; CAD = coronary artery disease; cardiomyopathy. Symptoms graded on scale + to + + +.
MI
= mitral
III). A spike-anddome configuration was recorded in 10 of 18 subjects, and the corrected ejection time index’* was increased by more than 2 standard deviations from the normal in nine of 17 subjects. The systolic time interval (ratio of pre-ejection period to ejection time, PEP/ET),” was less than 0.25 in six of 15 subjects. Echocardiogram (Table Ill). The average septal thickness was 2.2 cm., with a septum/posterior wall ratio of 2.2 in 17 cases. A systolic anterior motion (SAM) was recorded at rest, or with amyl nitrate inhalation in 17 cases, although in most casesit was qualitatively not severe. Six patients had increased right ventricular anterior wall thickness, ranging from 4 to 11 mm. An incidental finding was a small echo-free space posteriorly in eight patients. Cardiac catheterization was performed in seven cases (Table III). Care was taken to avoid catheter entrapment during pressure recordings and Carotid
pulse
tracings
(Table
September, 1978, Vol. 96, No. 3
Hypertrophic
II. Hypertrophic
Table
cardiomyopathy Physical
Patient D. A. E. B. S. B.
Quick pulse +
Ejection murmur
Pansystolic murmur
F. C.
2
E. G.
S,-S,
Blood pressure
+ + -
160/90 160/80 130/80
Congestive heart failure
Cardiomegaly
C’ordiac ctrtheteriLCifiOfl
Chest x-7-a-y
EGG
+
140/90
-
130/86
-
RBBB
Nl
Camitral annulus Ca car. artery Nl
+
+
+ +
LVH LVH LVH
+
LVH
LVH; dilated Ao
LVH Dilated
+
-
-
200/110
+
LVH
+
-
-
130/90
+
-
-
150/110
-
LVH; LAH RBBB
Nl
+ +
+
140/70 120/70
+
+
+
LVH LVH
EH EH
+
Ao
LV 1651:; C.I. 2.6; OTG 35; 3+ mitral insufficiency LV 165/ 16; C.I. 3.3; OTG 3:,;76 wit.h amyl nitrate
+
+
-
-
130/90
+
LVH
EH
M.
+
+
-
+
130/90
+
LVH; dilated Ao
+
+
+
+ -
170/90 120/80 130/80
+ + +
LVH; ASMI; PVC LVH LVH LVH
J. P. P. P. E. S.
+ +
+
R. W. A. Wl.
+
+ +
+ -
140/80 125/80
A. Wn.
+
-
-
zoo/90
+
R. F. K. M.
-
+ -
+
130/80 165/55
+
+
Abbreviations: LVH = left ventricular bundle branch block; Ao = aorta; EH M.?); OTG = left ventricular outflow
American
Heart
Journal
hypertrophy; = cardiomegaly; tract gradient
+
+ -
ASMI ST-T change Vent. Tachycardia LVH LVH; RBBB
LAH = left atria1 hypertrophy; ASMI LV = left ventricular systolic/end-diastolic (mm. Hg); nl s normal.
= anteroseptal pressures
LV 155:2”; (‘.I. 3.1; OTG ();(I with exercise; septal bulge in qstole LV 220/2l): C.I. 2.2; OTG 9(1: ?+ aortic insufficiency LV 13OIX: (f.1. 4.2: OTG 26:46 with isoprotcrenol
LV 16015: normal EDV; obliterated cavity at end-systole; moderate CAD
A. M.
M.
in the aged
findings
+
B. J.
G. L. H. M.
Lahoratov
findings
+
N. B.
thy
in the aged: Objective clinical data
+ -
+ +
A. B.
cardiomvopct
LVH LVH LVH; pleural effusion Nl LVH; dilated Ao Nl
Nl EH
LV 200/,12; C.I. 2.6; OTG 6; normal EDV; 2+ aortic insufficiency; calcified c’oronary artery myocardial infarction; (mm. Hg); C.I. = cardiac
RBBB = right index (L./min./
329
Krasnow
and
Stein
III. Hypertrophic
Table
cardiomyopathy
Phonocardiogram
Carotid pulse
Patient D. E. S. A. N. F. E. B. G. H. A. M. J. P. E. R. A. A. R. K.
A. B. B. B. B. C. G. J. L. M. M. M. P. P. S. W. Wl. Wn. F. M.
Corrected ejection time (sec.)
PEP ET
Systolic ejection murmur
.41 .43 .42 .44 .46 .39 .39
.32 .26 .19 .33 .21
-I-
.37
++ -
+ +
.48 .47
.I9 .34
++
+
.44 .34 .48 .49 .45 .46 .41
.28 .29 .28 .13 .14 .15 .27
++
Spike and dome
+ + + -
+ + + + -
.40
in the aged: Graphic data
+ + + ++
Pansystolic murmur
+ + + f ++
++
+
++ ++ ++ i-f + + +
++
“pullback” recording. An intraventricular gradient was found at rest in four cases,all of whom had evidence of obstruction on the resting echocardiogram. In one case there was marked obliteration of the left ventricular cavity at end-systole, without distortion of the chamber configuration. In one case the end-systole appearance of the left ventricular cavity, had a “bent banana” shape related to septal hypertrophy. Illustrative
cases
Case 1. (B. J., Fig. 2). A 75year-old female had severe classical angina pectoris and hypertension for several years without evidence of infarction. Physical examination was entirely normal, except for a blood pressure of 160/110 before treatment. ECG showed right bundle branch block, and heart size and shape were normal on chest x-ray. At cardiac catheterization, there was mild diffuse narrowing of the coronary arteries, with no obstruction greater than 50 per cent of the arterial diameter. Left ventriculography demonstrated a normal chamber in end-diastole, and a marked obliteration of the left ventricular cavity at end systole (Fig. 1). No outflow tract gradient
330
Echocardiogram S, Post. or Septum wall S, (cm.) (cm.) SIPW
+ + + + + + + + + + + +
2.0 2.4 1.8 2.0 2.1 2.3 1.6 1.8 2.4 3.3 1.9 3.3 2.4 2.0 2.1 2.2 2.4 1.9 2.1 2.0
0.9 1.3 .8 1.0 1.1
2.2 1.9 2.1 2.0 1.9
0.9 1.0
1.8 1.8
1.1 0.9 0.8 0.9 1.0
3.0 2.2 4.1 2.7 2.0
1.2 1.1 1.0 0.9 0.9
1.8 2.2 1.9 2.2 2.1
EDD (cm.)
ESD (cm.)
3.9 3.6 3.9 4.2 4.6 1.7 4.0 3.5 2.9 3.9 4.4 4.6 4.7 1.9 3.0 3.1 5.0 4.5 3.9
2.5 1.9 3.3 3.2 2.8 1.5 2.3 1.9 2.7 1.8 3.5 3.3 2.0
SAM
Septal motion
Amy1 nitrate effect
1+ 2+ 0 4+ 1+ 2+ 2+ 0 2+ 3+ 3+ 2+ 2+ 2+ 3+ 3+ 2+ 0 4+ 0
1+ 2+ 1+ 1+ 0 0 1+ 2+ 3+ 2+ 0 0 1+ 3+ 0 0 + 2+ 0 4+
N.D. + N.D. f + + N.D. + N.D. + N.D. 0 0 0 0 0 0 0 N.D.
+
was present at rest, and in this case isoproterenol stimulation was not performed. Echocardiogram showed marked asymmetrical hypertrophy of the interventricular septum, a small left ventricular cavity, and increased thickness of the anterior right ventricular free wall were seen. No SAM was demonstrable at rest or after amyl nitrate, and the anterior mitral leaflet morphology was normal. The patient improved after more intensive treatment with propranolol. Comment. This patient had no clinical stigmata of hypertrophic cardiomyopathy, except for severe angina. The correct diagnosis was made at ventriculography and confirmed by subsequent echocardiography. Case 2. (F. C.). A 73-year-old female was admitted for trauma associated with her first episode of syncope. She was otherwise well, except for rheumatoid arthritis. Carotid pulses were somewhat brisk. The apex impulse was tapping, 2 cm. left of mid-clavicular line and a Grade III + systolic ejection murmur was heard in the third intercostal space, 3 cm. to the left of the sternum. Electrocardiogram showed mild left
September, 1978, Vol. 96, No, 3
Hypertrophir
ventricular hypertrophy, with small q waves in Leads 1 and aV,.. Echocardiogram showed a thick septum, SAM, small left ventricular cavity, abnormal anterior mitral leaflet in diastole, and a calcified mitral annulus. Fluoroscopy confirmed the calcification of the mitral annulus, and showed extensive calcification of the coronary arteries as well. Treatment with propranolol 160 mg./day reduced the intensity of the murmur and diminished the SAM on echocardiogram. Comment. In the absence of echocardiography, the murmur might well have been attributed exclusively to the calcified mitral annulus, or to valvular aortic stenosis. Case 3. (N. B.). A 57-year-old female complained of chest pain, syncope, and palpitation for seven years. Her mother was said to have had an enlarged heart for at least 30 years. Her first two syncopal episodes were associated with seizures, and pulmonary congestion was diagnosed clinically 2 years previously. Physical examination showed slightly distended neck veins without right ventricular heave. A right bundle branch block was present on electrocardiogram. X-ray of the chest was normal. Carotid pulse studies showed a spike-dome configuration; the PEP/ET was 0.21, and the ejection time index was increased. A regurgitant systolic murmur was recorded at apex and lower left sternal border. Echocardiogram showed a thickened septum (2.1 cm.) with a septum/posterior wall ratio of 1.9. A small SAM was present which was increased by amyl nitrate. The mitral EF slope was 45. At cardiac catheterization, a 25 mm. Hg subvalvular outflow tract gradient was found. The ventriculogram showed a markedly reduced end-systolic volume; the coronary arteries were normal. Comment. In this case, the symptoms were sufficiently vague and atypical that cardiac neurosis was suspected initially. Case 4. (R. W.). A 68-year-old female was told of a murmur many years previously. She had angina for 9 years and signs of congestive heart failure for 3 years. She was thought to be hypothyroid. She was admitted for acute chest pain, and found to have an apex impulse in fifth interspace near the anterior axillary line. There was a Grade III pansystolic murmur at apex, an S I gallop, and basilar &es. Electrocardiogram suggested an anterior subendocardial infarction without left ventricular hypertrophy. X-ray
American
Heart
Journal
curdionx.vop~
th?
in fhp
agrd
Fig. 2. Hypertrophic non-obstructivr cardiom> apathy in a 76-year-old woman with mild hypertension anrt severe angina pectoris. Angiogram shows marked reduction of end-systolic cavity, similar to the echocardiogram. which showed a septum 1.8 cm. thick.
showed the heart to be at normal size. Pulse and heart sound recording showed a spike-and-dome configuration, with prolonged ejection time, PEP/ET was 0.14, and a regurgitant murmur was seen. Echocardiography showed n thickened septum (2.2 cm.) and a septum/posterior wall ratio of 1.8 with prominent SAM, narrowing t,he outflow tract diamet.er in syst.ole to ;3 mm. Comment. In this patient, there w;\s electrocardiographic evidence of associated cot,onary heart disease. The murmur and heart failure would have been attributed to papillary muscle dysfunction and myocardial infarction exclusively, whereas the hypert,rophic ohstructirbn may have played a significant role. Case 5. (E. B. ). A 68-year-old female had a long history of heart disease and d?spnea, with
331
Krasnow
and
Stein
CONTROL
AMYL
NITRITE
AMYL NITRITE
Fig. 3. Hypertrophic cardiomyopathy The septum is thick, but obstruction murmur, carotid pulse abnormality,
332
in a 65-year-old man being followed for hypertension is not present at rest. With Valsalva maneuver and amyl and SAM appear.
and mild dyspnea. nitrate inhalation, a
September,
1978, Vol. 96, No. 3
cardiomegaly known for 6 years. She was being treated for mild hypertension when she was admitted for syncope associated with a respiratory infection. BP was 160/80. An S, gallop was present. A regurgitant murmur was present at the apex, and a systolic ejection type murmur was heard along the sternal border which radiated to the neck. ECG and x-ray indicated left ventricular hypertrophy. Carotid pulse showed a spikedome pattern, with normal ejection time index, and PEP/ET and 0.26. Phonocardiogram confirmed the ejection and regurgitant murmurs. The echocardiogram revealed a thickened septum (2.4 cm.) with septum/posterior wall ratio of 1.9, 2+ SAM with 4 mm. systolic outflow tract diameter, and the mitral leaflet was displaced anteriorly. The aortic valve was noted to be notched late in systole. Propranolol2 mg. administered intravenously during the study decreased the SAM within five minutes. Case 6. (D. A., Fig. 3). This 65year-old man was told of a “leaky valve” at age 17 but knew no more of heart disease till 5 years prior to study (age 60) when he noted dyspnea on walking rapidly. Cardiomegaly was noted and he was being treated for hypertension. His mother died in her thirties during the 1918 influenza epidemic; a son died suddenly during a soccer match, without known prior heart disease. Blood pressure was 160/90. There was an apical systolic ejection murmur increasing during Valsalva maneuver, and an S,, was present. The pulses were normal and the ECG showed LVH. Echocardiogram and phonocardiogram showed development of a murmur and SAM during amyl nitrate inhalation. There was moderate asymmetric septal hypertropb. Comment. This patient has apparently mild disease clinically. The findings could have been dismissed as compatible with hypertension. The son who died during exertion was presumably severely affected. Discussion
Hypertrophic cardiomyopathy is easily diagnosed in young or middle-aged patients when there are characteristic clinical findings’-’ consisting of dyspnea or signs of congestive heart failure, chest pain, syncope, or palpitations, in association with the findings of a brisk carotid upstroke and a systolic murmur heard best along the left sternal
American
Heart
Journal
border which is poorly transmitted to the neck. The picture is complete with an ECG meeting the criteria of left ventricular hypertrophy and a chest x-ray revealing a small ascending aorta and left ventricular predominance. Mitral insufficiency is frequently present, occasionally dominating the clinical picture. In the aged, our clinical study of hkpertrophic obstructive cardiomyopathy shows that. the diagnosis was frequently missed, similar to the experience of Hamby and Antablian” and Whiting and colleagues. :‘I The symptoms and signs are frequently misinterpreted as manifestations of more common diseases such as coronary artery diseaseor hypertensive heart disease. Mild hypertension, common in this age group, is frequently considered the basis of the cardiomegaly-. Syncope or dizziness, a common presenting sign in this series, as in that of Whiting and associates,‘” may be ascribed to cerebrovascular insufficiency or heart block. The brisk carotid pulse may be ascribed to rigidity of the arterial walls, or conversely, it may be sluggish due to associated intrinsic atherosclerotic and thromhotic: disease (one patient in this series had total obstruction of a carotid artery and underwent endarterectomy). The ascending aorta may be dilated, rather than small, leading one to ascribe the systolic murmur to aortic stenosis. The associated mitral insufficiency was often explained as papillary muscle dysfunction, or as in one patient in our series, to a calcified mitral annulus. Carotid pulse tracings and heart sound recordings offer important clues to the proper diagnosis, but the echocardiogram provides the most accurate, specific diagnostic support short of cardiac catheterization. The characterisbic echocardiographic features include a thickened septum, out of proportion to the thickness of the posterior left ventricular wall; an anterior mitral valve leaflet echo showing anterior posterior; an anterior systolic motion, often abutting the septum; and a slow early diast.oiic thing motion. Septal motion is often diminished but may be normal. The left ventricular valve cavny is small and the record appears “busy.” The aortic valve leaflets appear thin and open wide{!-. hut may show a notch of midsystolic closure. The extensive use of the echocardiogram in a large medical teaching service contributed to the increasing frequency of diagnosis, in a group of
333
Krasnow
and
Stein
patients who otherwise would have remained misdiagnosed had cardiac catheterization been required. It is to be expected that the increasing utilization of the echocardiogram will be associated with fewer missed diagnoses of hypertrophic cardiomyopathy in the elderly. Hypertrophic cardiomyopathy is more common in older people than was previously thought. In earlier series of hypertrophic cardiomyopathy, aged patients were rare and most patients were young or middle-aged adults, or children. In the series of 119 patients followed by Hardarson and colleagues,’ only one was over 60 years of age, and Adelman and associates8 reported on 60 patients, the oldest of whom was 55. In the large early series of 126 patients analyzed by Frank and BraunwaldlJ only two were over 60. None of the 18 patients reported by Parker” was over 45. Recently, however, Whiting and colleagues1U reported 14 cases over the age of 60, and Hamby and Aintablian” found nine cases of hypertrophic cardiomyopathy in patients over 70. In our present series of 23 cases of hypertrophic cardiomyopathy of all ages seen in the past 3 years, 20 were over the age of 50 years. The recognition of hypertrophic cardiomyopathy in patients in the seventh and eighth decades of life, some of whom who are even then minimally symptomatic, extends our understanding of the natural history of the disease from that portrayed in previous studies. The patients in this series suggest that the lesion of hypertrophic cardiomyopathy is compatible with a long life, and that selected patients may remain asymptomatic to a late age. The explanation for this more benign prognosis in selected patients is not clear. Two possible explanations suggest themselves: one is that this group of patients had a relatively mild degree of obstruction, and thus survived to old age; the other, is that the obstructive process is not present in early years but develops and progresses in the course of aging. The possibility of our series representing a milder form of the obstructive lesion is suggested by the small resting gradients atcardiac catheterization and normal cardiac indices among the seven subjects who underwent cardiac catheterization. Also the echocardiogram did not suggest high grade obstruction’j-i.e., the outflow tract was not completely obliterated for long periods of systole in most patients. Previous studies do not,
334
however, suggest a milder obstructive lesion in the elderly. Whiting and associates”’ found more severe gradients at catheterization among his older patients, as compared to the younger group. Pomerance and Davies”’ found severe hypertrophy at necropsy in the older patients, with an average heart weight of 560 grams, even though in some cases of their series, the lesion was an incidental finding, and was not symptomatic or diagnosed during life. There is, however, difficulty in defining clinical severity of this disease, especially when sudden death may occur at any stage of disease, unheralded by any symptoms. There is disagreement among investigators as to the prognostic usefulness of clinical or hemodynamic parameters. Hanania and colleagues’: found that clinical prognosis related only to the age of onset of symptoms. One agreed-upon datum is the poorer prognosis of the familial form of the disease, compared to the sporadic form.‘. Ii Only four subjects in the present series had a history suggestive of familial disease, but this datum is not reliable since in a number of our cases the family history was not well known to the patient. The present study with its predominance (80 per cent) of female patients suggests also that males may have a severer form of the disease. In the series of Frank and Braunwald,‘,’ there was an equal sex incidence in younger patients, but in the older patients, females predominated. Hamby and Aintablian” also found seven females out of nine aged patients with hypertrophic cardiomyopathy. In the series of necropsy cases studied by Pomerance and Davies,“’ the sex incidence was equal, but females averaged 76 years of age compared to 66 for males. Whiting and coworkers”’ found 10 of 14 elderly patients to be females. One could thus infer that women have a better chance of living longer with the disease. The second possible explanation for the prolonged survival is that in this disease, albeit often a familial one, the obstructive process is not present in early years, but develops and progresses with age. This contention is supported by the work of Williams and colleagues,” who documented the development of the obstructive component over 4 years in a 15-year-old girl. Even the disordered myocardial architecture, previously thought to be a feature of the congenital myopathic character of the disease, may repre-
September,
1978, Vol. 96, No. 3
Hypertrophic
sent the result, not the cause, of prolonged obstruction’g and could possibly be progressive in character. The mechanism of progressive obstruction may become clearer now that longitudinal studies by echocardiography are possible. A corollary of the thesis of progressive development of the lesion is that the clinical course is slow. In several recent studies, a gradual progression of symptoms is described for many patients, regardless of the clinical classification of the patients when first studied. Hardarson and colleagues’ postulates a long phase of asymptomatic disease until about age 30, after which symptoms may supervene with progressive clinical deterioration. Sudden death can occur at any time in this course, however, even in asymptomatic subject,s responding well to medical or surgical therapy. In the 49 patients followed for an average of 7.5 years by Hanania and associates,” 66 per cent survived 20 years from the onset of the first symptoms. These data support the concept of Hardarson and co-workers’ on the prolonged course of the disease. To confound the description of the natural history and prognosis further, Hanania and colleagues” found that more casesimproved with time than deteriorated; treatment with propranolo1 did not account for this result. Adelman and co-workers’ and Powell and colleaguesz” also noted significant improvement in many patients of their respective series, attributing the change to medical therapy with beta-adrenergic blocking drugs but without a true control series for comparison. The present series thus extends the potential survival curve even further than that suggested by Hardarson, Hanania, and their associates.’ ‘:
American
Heart
Journal
;n the aged
causes, including valvular aortic st,enosis, arteriosclerotic or hypertensive heart disease, or cerebrovascular disease. Left ventricular hypertrophy was more consistently present on ECG than on x-ray. The not-infrequent occurrence of hypertrophic cardiomyopathy in older patients, predominantly females, indicates that the natural history of this disease includes a group who suffer few or no symptoms until late in life. Clinical management of younger patients with this diagnosis should be considered in light of this more favorable possible course. The excellent technical and Miss Shirley Staiano Yetta Israelite is gratefully
assistance of Mrs. Henrietta and secretarial assistance acknowledged
Stokes of Mrs.
REFERENCES
1. 2.
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9.
Summary
Although usually considered a disease of young or middle-aged adults, hypertrophic cardiomyopathy is not infrequently seen in older patients as well. Twenty of 23 cases of hypertrophie cardiomyopathy seen in the past 2% years at our institution have been in patients whose average age was 65 years, and who ranged up to 76 years. Sixteen of these had evidence of an obstructive component at cardiac catheterization or echocardiography. Symptoms and signs were similar to those described for the younger patients in the literature, but were often attributed to other
cnrdiomyopnth~
10.
11. 12. 13. 14.
15.
Brachfeld, N., and Gorlin, R.: Suhaortil, stenosis: -4 revised concept of the disease, Medicine 38:415, 1959. Braunwald, E., Morrow, A. G., Cornefl. W. P., Aygen, M. M.. and Hilbish, T. F.: Idiopathic hypertrophic subaortic stenosis: Clinical, hemodynamic: and angiographic manifestations, Am. J. Med. 29:924. 1960. Wigle. E. D., Heimbecker, R. O., and Gunton, and R. W.: Idiopathic ventricular septal hypertrophy causing muscular suhaortic stenosis. Circulation 26:325, 1962. Cohen, J., Effat, H., Goodwin, J. F., Oakley, C. M., and Steiner, R. E.: Hypertrophic obstructive cardiomyopathy, Br. Heart J. 26:16, 1964. Menges, H., Jr., Brandenburg, R. O., and Brown. A. L.. Jr.: The clinical hemodynamic and pathologic diagnosis of muscular suhvalvular aortic stenosis, Circulation 24: 1126. 1961. Goodwin, d. F.: Congestive and hvpertrophic cardiomyopathies, Lancet 1:731, 1970. Hardarson. T., Curiel, R., DeLaCalzada. C. S., and Goodwin, J. F.: Prognosis and mortality of hypertrophic obstructive cardiomyopathy, Lancet 2: 1462, 1973. Adelman, A. G., Wigle, E. D., Ranganathan, N., Webb. G. D., Kidd. S. S. S., Bigelow, W. G., and Silver, M. D.: The clinical course in muscular suhaortic stenosis, Ann. Intern. Med. 77:515. 1972. Parker. B. M.: The course in idiopathic hypertrophic muscular subaortic stenosis, Ann. lntern. Med. 70:903, 1969. Whiting, R. B.. Powell, W. d., Jr., Dinsmore, R. E., and Sanders, C. A.: Idiopathic hypertrophic subaortic stenosis in the elderly, N. Engl. J. Med. 285:196, 1971. Popp. R. L.: Echocardiographic assessment of cardiac disease, Circulation 54:538. 1976. Weissler, A. M.: Non-invasive cardiologv, New York. 1974, Grune & Stratton, Inc. Frank. S.. and Braunwald. E.: Idionathic, hvnertroahic ’ subaortic’stenosis, Circulation 37:7;9, 1968. a Hamby, R. I., and Aintablian, A.: Idiopathic hypertrophic suhaortic stenosis in the septuagenarian, (‘lin. Ites. 24:22OA, 1976. Henry, W. L., Clark, C. E., Glancy. I,., and Epstein, S. E.: Echocardiographic measurement of the left ventricular outflow gradient in idiopathic hypertrophic suhaortic stenosis, N. Engl. J. Med. 2883989, 1973
335
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16.
17.
18.
and
Stein
Pomerance, A., and Davies, M. J.: Pathological features of hypertrophic obstructive cardiomyopathy (HOCM) in the elderly, Br. Heart J. 37:305, 1975. Hanania, G., Marino, J. P., Magnier, S., Baragan, J., Guillemaut, P., Fernandez, F., and Gerbaux, A.: Evolution Spontanee des Myocardiopathies Obstructives, Arch. Mal. Coeur 69:1023, 1976. Williams, R. G., Ellison, C., and Nadas, A. S.: Development of left ventricular outflow obstruction in idiopathic hypertrophic subaortic stenosis, N. Engl. J. Med. 288:868, 1973.
Copyright
19.
20.
21.
Bulkley, B. H., Weisfeldt, M. L., and Hutchins. G. M.: Isometric cardiac contractiolr. A possible cause of the disorganized myocardial pattern of idiopathic hypertrophic subaortic stenosis, N. Engl. J. Med. 296:135, 1977. Powell, W. J., Jr., Whiting, R. B., Dinsmore, R. E., and Sanders, C. A.: Symptomatic prognosis in patients with idiopathic hypertrophic subaortic stenosis (IHSS), Am. J. Med. 5615, 1973. Glaser, J.: Mid-systolic AV Closure in IHSS, Circulation 61:1172, 1975.
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336
September,
1978, Vol. 96, No. 3
Norman Richard
cardiomyopathy
in the aged
Krasnow, M.D. A. Stein, M.D.
Brooklyn, N. Y.
Hypertrophic cardiomyopathy is a not uncommon disease which has been well characterized since the early reports presenting a composite picture of the disease by Brachfeld and Gorlin,’ Braunwald and associates,’ and others.:‘-” The obstructive variant, also called idiopathic hypertrophic subaortic stenosis, is associated with characteristic clinical findings,’ including a systolic ejection murmur, unusually brisk carotid pulses, bifid apical impulses, increase in the intensity of the murmur with Valsalva maneuver, and often associated mitral insufficiency. Symptoms and signs include syncope, heart failure, arrhythmias, and angina. Left ventricular hypertrophy is often present on the electrocardiogram and chest x-ray. When any one or more of these abnormalities occurs in a young healthy adult, detailed investigation is likely to be carried out, and a diagnosis established. The echocardiogram has contributed enormously to the non-invasive diagnosis of this condition, especially in its non-obstructive variety (asymmetric septal hypertrophy). Previous studies have indicated that the disease predominates in the young or middle-aged population, although instances of hypertrophic cardiomyopathy in older patients have been noted in these studies.“-“’ In the past 28 months, 23 new cases of hypertrophic cardiomyopathy have been detected at the Cardiac Graphics Laboratory of the Downstate Medical Center. Twenty of the patients were over the age of 50 years and form the subject of this report. Fifteen of these patients From the Department of Medicine, Medical Center, Brooklyn, N. Y.
Cardiology
Received
for publication
Sept.
7, 1977.
Accepted
for publication
Nov.
7, 1977.
Reprint requests: Norman ology Division, Downstate lyn, N. Y. 11203.
326
September,
Krasnow, Medical
M.D., Center,
Division,
Downstate
Dept. of Medicine, 450 Clarkson Ave.,
1978, Vol. 96, No. 3
CardiBrook-
were over the age of 60 years. In the majority the correct diagnosis was not made clinically, either because it was not considered in these elderly patients, or because some of the usual characteristic features were masked or attributed to other conditions more common in this age group. Cardiac catheterization is often avoided in the elderly if a clear therapeutic decision is not apparent. The twofold purpose of this paper is (1) to emphasize the occurrence of hypertrophic cardiomyopathy in the older patient, in whom the diagnosis is more likely to be missed, and (2) to emphasize the apparent compatibility of this diseasewith long life which, in part, conflicts with current thinking on the natural history of the disease. Materials
and
methods
Clinical echocardiograms were performed on a Smith-Kline Echocardiograph Model 20A, using a Honeywell 1856 ultraviolet recorder and a 2.25 MHz, ‘/z inch diameter transducer. Phonocardiograms and carotid pulse recordings were performed on a Honeywell recorder, using two microphones sinultaneously, each recording in 50 to 120 Hz and 100 to 500 Hz bands, or on a Schwarzer six-channel direct writing polygraph. Echocardiograms from many of these elderly patients were difficult technically because of overlying lung tissue damping the high-frequency sound. Nevertheless, great care was taken to delineate as well as possible both right and left margins of the interventricular septum in order to define thickness carefully at the level of the mitral valve and posterior wall. Echoes from the septal leaflet of the tricuspid valve were carefully differentiated from the right (anterior) margin of the septum.
0002-8703/78/0396-0326$01.10/O
0 1978 The
C. V. Mosby
Co.
Hypertrophic
cardiom~~op~rth? in the aged
ECG WON0
CAROTID
SEPTUM
POST WALL
Fig. 1. Hypertrophic obstructive cardiomyopathy in a 61-year-old woman (H. M.) with a history of’ rheumatic fever in childhood, and a clinical diagnosis of mitral insufficiency. The right side of the septum in this portion of the rec,ording is obscured. There is a SAM, narrow transverse LV diameter, notched aortic valve and spike-and-dome carotid pulse.
Patient selection. Of about 2,000 subjects studied, twenty patients over the age of 50 had hypertrophic cardiomyopathy. Seventeen of these met the criteria for hypertrophic obstructive cardiomyopathy (e.g., Fig. 1). These required criteria included: (a) septal hypertrophy (greater than 1.2 cm. thickness), out of proportion to posterior wall thickness (septum/posterior wall thickness ratio 1.4 or greater), (b) systolic anterior motion (SAM) of the anterior mitral leaflet, present either at rest or after amyl nitrate inhalation. The SAM in all cases was discrete and abrupt. It did not appear to be related to underlying papillary muscle motion.” Additional criteria, not sufficient in themselves for diagnosis, were: (c) anterior displacement and slowing of the early diastolic closing motion of the anterior mitral leaflet in diastole, (d) decrease in transverse left ventricular diameter at the level of the mitral valve, (usually producing a characteristic “busy” appearance of the recording), and (e) notching of the aortic valves.“’ In each case there was no stenosis of the aortic valve. Characteristic pulse abnormalities (Fig. 1) were a rapid rate of carotid upstroke, with spike-and-
American Heart Journal
dome configuration.’ Prolonged ejection time index and decreased systolic time intervals were taken as indices of outflow tract obstruction,‘” but not differential for valvular vs. subvalvular location. The presence of pulse abnormalities was considered confirmatory but not diagnostic, and the absence of pulse abnormalities did not exclude the diagnosis. In three cases, the diagnosis of hypertrophic cardiomyopathy, without outflow tract. obstruction, was based on disproportionate septal hypertrophy (criterion a as above) in thr absence of other clinical or echocardiographic c>xplanations for a thickened septum. Results Patient profile (Tables I and II). The oldest patient in this series was 76. Fifteen of the 20 in the group were 60 years of age, or older. Fifteen were women. The most common presenting complaints (Table I) were syncope or dizziness in nine, signs of heart failure in five, and chest pain in four. In two cases the cardiac lesion was discovered and diagnosed incidenial to other unrelated events.
327
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I. Hypertrophic
Table
cardiomyopathy Duration
Patient
Age
Sex
Symptoms
D. A.
65
M
4 yr.
E. B.
68
F
10 + yr.
S. B.
65
F
A. B. N. B.
50 57
F. E. B. G. H. A. M. J.
C. G. J. L. M. M. M. P.
P. E. R. A. A. R. K.
P. S. W. Wl. Wn. F. M.
Abbreviations: insufficiency;
in the aged: Clinical characteristics
of presenting Complaint
Associated findings CHF
Pain
HBP
+
i-
HBP; dyspnea Syncopd
+
-
++
-
6 yr.
Syncope
++
+
+
ii
F F
3 days 7 yr
Dyspnea Syncope
+
+
++
73 58 75 67 62 63 76 75
F F F F F M M F
0 8 yr. 4 yr. 60 days 4 yr. 7 days
Syncope Dyspnea Pain Syncope Dyspnea Paid
+ +++
f
+
+
1 yr.
Syncope
2 yr.
Dizziness
64 73 68 61 58 57 65
M F F F F F F
1 yr. 5+yr. 9 yr. 0 6 yr. 0.5 yr. 41 yr.
Dizziness Pain Pain None None CVA Dyspnea
CHF HOCM
= congestive = hypertrophic
HBP = hypertension; AS = aortic stenosis;
heart
failure; obstructive
Arrhythmia
Positive family history
+
+ +
The correct diagnosis was suspected in only four cases, but was not made definitively by the referring or consulting physician (usually a cardiology Attending or Fellow). Valvular heart disease, either aortic stenosis or mitral insufficiency, or both, was considered in 11, hypertensive and/or atherosclerotic heart disease in nine; in one patient both valvular and atherosclerotic heart disease were the prime diagnostic considerations. The duration of symptoms prior to diagnosis averaged 5.5 years, excluding two patients who had no symptoms, and three who had symptoms for less than 1 week before admission. Seven patients were aware of a heart murmur for at least several years previously, but had not undergone diagnostic study. Palpable carotid pulse abnormalities were present in only five cases, all of whom had evidence of outflow tract obstruction on echocardiogram.
328
Murmur
+
+
+
+
+ f
+
+ + + +
+-
-
f
+ + -
+ +
+
+
+
+
+
Referring diagnoses HBP; CAD;? valve disease HBP; CAD;? valve disease MI, AS; ? HOCM MI, AS Angina; ? HOCM AS; ? HOCM CAD CAD AS, MI MI AS; CAD CAD; ? HOCM AS; ?MI ?HOCM HOCM AS, MI AS; CAD MI CAD CAD AS
CVA = cerebrovascular accident; CAD = coronary artery disease; cardiomyopathy. Symptoms graded on scale + to + + +.
MI
= mitral
III). A spike-anddome configuration was recorded in 10 of 18 subjects, and the corrected ejection time index’* was increased by more than 2 standard deviations from the normal in nine of 17 subjects. The systolic time interval (ratio of pre-ejection period to ejection time, PEP/ET),” was less than 0.25 in six of 15 subjects. Echocardiogram (Table Ill). The average septal thickness was 2.2 cm., with a septum/posterior wall ratio of 2.2 in 17 cases. A systolic anterior motion (SAM) was recorded at rest, or with amyl nitrate inhalation in 17 cases, although in most casesit was qualitatively not severe. Six patients had increased right ventricular anterior wall thickness, ranging from 4 to 11 mm. An incidental finding was a small echo-free space posteriorly in eight patients. Cardiac catheterization was performed in seven cases (Table III). Care was taken to avoid catheter entrapment during pressure recordings and Carotid
pulse
tracings
(Table
September, 1978, Vol. 96, No. 3
Hypertrophic
II. Hypertrophic
Table
cardiomyopathy Physical
Patient D. A. E. B. S. B.
Quick pulse +
Ejection murmur
Pansystolic murmur
F. C.
2
E. G.
S,-S,
Blood pressure
+ + -
160/90 160/80 130/80
Congestive heart failure
Cardiomegaly
C’ordiac ctrtheteriLCifiOfl
Chest x-7-a-y
EGG
+
140/90
-
130/86
-
RBBB
Nl
Camitral annulus Ca car. artery Nl
+
+
+ +
LVH LVH LVH
+
LVH
LVH; dilated Ao
LVH Dilated
+
-
-
200/110
+
LVH
+
-
-
130/90
+
-
-
150/110
-
LVH; LAH RBBB
Nl
+ +
+
140/70 120/70
+
+
+
LVH LVH
EH EH
+
Ao
LV 1651:; C.I. 2.6; OTG 35; 3+ mitral insufficiency LV 165/ 16; C.I. 3.3; OTG 3:,;76 wit.h amyl nitrate
+
+
-
-
130/90
+
LVH
EH
M.
+
+
-
+
130/90
+
LVH; dilated Ao
+
+
+
+ -
170/90 120/80 130/80
+ + +
LVH; ASMI; PVC LVH LVH LVH
J. P. P. P. E. S.
+ +
+
R. W. A. Wl.
+
+ +
+ -
140/80 125/80
A. Wn.
+
-
-
zoo/90
+
R. F. K. M.
-
+ -
+
130/80 165/55
+
+
Abbreviations: LVH = left ventricular bundle branch block; Ao = aorta; EH M.?); OTG = left ventricular outflow
American
Heart
Journal
hypertrophy; = cardiomegaly; tract gradient
+
+ -
ASMI ST-T change Vent. Tachycardia LVH LVH; RBBB
LAH = left atria1 hypertrophy; ASMI LV = left ventricular systolic/end-diastolic (mm. Hg); nl s normal.
= anteroseptal pressures
LV 155:2”; (‘.I. 3.1; OTG ();(I with exercise; septal bulge in qstole LV 220/2l): C.I. 2.2; OTG 9(1: ?+ aortic insufficiency LV 13OIX: (f.1. 4.2: OTG 26:46 with isoprotcrenol
LV 16015: normal EDV; obliterated cavity at end-systole; moderate CAD
A. M.
M.
in the aged
findings
+
B. J.
G. L. H. M.
Lahoratov
findings
+
N. B.
thy
in the aged: Objective clinical data
+ -
+ +
A. B.
cardiomvopct
LVH LVH LVH; pleural effusion Nl LVH; dilated Ao Nl
Nl EH
LV 200/,12; C.I. 2.6; OTG 6; normal EDV; 2+ aortic insufficiency; calcified c’oronary artery myocardial infarction; (mm. Hg); C.I. = cardiac
RBBB = right index (L./min./
329
Krasnow
and
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III. Hypertrophic
Table
cardiomyopathy
Phonocardiogram
Carotid pulse
Patient D. E. S. A. N. F. E. B. G. H. A. M. J. P. E. R. A. A. R. K.
A. B. B. B. B. C. G. J. L. M. M. M. P. P. S. W. Wl. Wn. F. M.
Corrected ejection time (sec.)
PEP ET
Systolic ejection murmur
.41 .43 .42 .44 .46 .39 .39
.32 .26 .19 .33 .21
-I-
.37
++ -
+ +
.48 .47
.I9 .34
++
+
.44 .34 .48 .49 .45 .46 .41
.28 .29 .28 .13 .14 .15 .27
++
Spike and dome
+ + + -
+ + + + -
.40
in the aged: Graphic data
+ + + ++
Pansystolic murmur
+ + + f ++
++
+
++ ++ ++ i-f + + +
++
“pullback” recording. An intraventricular gradient was found at rest in four cases,all of whom had evidence of obstruction on the resting echocardiogram. In one case there was marked obliteration of the left ventricular cavity at end-systole, without distortion of the chamber configuration. In one case the end-systole appearance of the left ventricular cavity, had a “bent banana” shape related to septal hypertrophy. Illustrative
cases
Case 1. (B. J., Fig. 2). A 75year-old female had severe classical angina pectoris and hypertension for several years without evidence of infarction. Physical examination was entirely normal, except for a blood pressure of 160/110 before treatment. ECG showed right bundle branch block, and heart size and shape were normal on chest x-ray. At cardiac catheterization, there was mild diffuse narrowing of the coronary arteries, with no obstruction greater than 50 per cent of the arterial diameter. Left ventriculography demonstrated a normal chamber in end-diastole, and a marked obliteration of the left ventricular cavity at end systole (Fig. 1). No outflow tract gradient
330
Echocardiogram S, Post. or Septum wall S, (cm.) (cm.) SIPW
+ + + + + + + + + + + +
2.0 2.4 1.8 2.0 2.1 2.3 1.6 1.8 2.4 3.3 1.9 3.3 2.4 2.0 2.1 2.2 2.4 1.9 2.1 2.0
0.9 1.3 .8 1.0 1.1
2.2 1.9 2.1 2.0 1.9
0.9 1.0
1.8 1.8
1.1 0.9 0.8 0.9 1.0
3.0 2.2 4.1 2.7 2.0
1.2 1.1 1.0 0.9 0.9
1.8 2.2 1.9 2.2 2.1
EDD (cm.)
ESD (cm.)
3.9 3.6 3.9 4.2 4.6 1.7 4.0 3.5 2.9 3.9 4.4 4.6 4.7 1.9 3.0 3.1 5.0 4.5 3.9
2.5 1.9 3.3 3.2 2.8 1.5 2.3 1.9 2.7 1.8 3.5 3.3 2.0
SAM
Septal motion
Amy1 nitrate effect
1+ 2+ 0 4+ 1+ 2+ 2+ 0 2+ 3+ 3+ 2+ 2+ 2+ 3+ 3+ 2+ 0 4+ 0
1+ 2+ 1+ 1+ 0 0 1+ 2+ 3+ 2+ 0 0 1+ 3+ 0 0 + 2+ 0 4+
N.D. + N.D. f + + N.D. + N.D. + N.D. 0 0 0 0 0 0 0 N.D.
+
was present at rest, and in this case isoproterenol stimulation was not performed. Echocardiogram showed marked asymmetrical hypertrophy of the interventricular septum, a small left ventricular cavity, and increased thickness of the anterior right ventricular free wall were seen. No SAM was demonstrable at rest or after amyl nitrate, and the anterior mitral leaflet morphology was normal. The patient improved after more intensive treatment with propranolol. Comment. This patient had no clinical stigmata of hypertrophic cardiomyopathy, except for severe angina. The correct diagnosis was made at ventriculography and confirmed by subsequent echocardiography. Case 2. (F. C.). A 73-year-old female was admitted for trauma associated with her first episode of syncope. She was otherwise well, except for rheumatoid arthritis. Carotid pulses were somewhat brisk. The apex impulse was tapping, 2 cm. left of mid-clavicular line and a Grade III + systolic ejection murmur was heard in the third intercostal space, 3 cm. to the left of the sternum. Electrocardiogram showed mild left
September, 1978, Vol. 96, No, 3
Hypertrophir
ventricular hypertrophy, with small q waves in Leads 1 and aV,.. Echocardiogram showed a thick septum, SAM, small left ventricular cavity, abnormal anterior mitral leaflet in diastole, and a calcified mitral annulus. Fluoroscopy confirmed the calcification of the mitral annulus, and showed extensive calcification of the coronary arteries as well. Treatment with propranolol 160 mg./day reduced the intensity of the murmur and diminished the SAM on echocardiogram. Comment. In the absence of echocardiography, the murmur might well have been attributed exclusively to the calcified mitral annulus, or to valvular aortic stenosis. Case 3. (N. B.). A 57-year-old female complained of chest pain, syncope, and palpitation for seven years. Her mother was said to have had an enlarged heart for at least 30 years. Her first two syncopal episodes were associated with seizures, and pulmonary congestion was diagnosed clinically 2 years previously. Physical examination showed slightly distended neck veins without right ventricular heave. A right bundle branch block was present on electrocardiogram. X-ray of the chest was normal. Carotid pulse studies showed a spike-dome configuration; the PEP/ET was 0.21, and the ejection time index was increased. A regurgitant systolic murmur was recorded at apex and lower left sternal border. Echocardiogram showed a thickened septum (2.1 cm.) with a septum/posterior wall ratio of 1.9. A small SAM was present which was increased by amyl nitrate. The mitral EF slope was 45. At cardiac catheterization, a 25 mm. Hg subvalvular outflow tract gradient was found. The ventriculogram showed a markedly reduced end-systolic volume; the coronary arteries were normal. Comment. In this case, the symptoms were sufficiently vague and atypical that cardiac neurosis was suspected initially. Case 4. (R. W.). A 68-year-old female was told of a murmur many years previously. She had angina for 9 years and signs of congestive heart failure for 3 years. She was thought to be hypothyroid. She was admitted for acute chest pain, and found to have an apex impulse in fifth interspace near the anterior axillary line. There was a Grade III pansystolic murmur at apex, an S I gallop, and basilar &es. Electrocardiogram suggested an anterior subendocardial infarction without left ventricular hypertrophy. X-ray
American
Heart
Journal
curdionx.vop~
th?
in fhp
agrd
Fig. 2. Hypertrophic non-obstructivr cardiom> apathy in a 76-year-old woman with mild hypertension anrt severe angina pectoris. Angiogram shows marked reduction of end-systolic cavity, similar to the echocardiogram. which showed a septum 1.8 cm. thick.
showed the heart to be at normal size. Pulse and heart sound recording showed a spike-and-dome configuration, with prolonged ejection time, PEP/ET was 0.14, and a regurgitant murmur was seen. Echocardiography showed n thickened septum (2.2 cm.) and a septum/posterior wall ratio of 1.8 with prominent SAM, narrowing t,he outflow tract diamet.er in syst.ole to ;3 mm. Comment. In this patient, there w;\s electrocardiographic evidence of associated cot,onary heart disease. The murmur and heart failure would have been attributed to papillary muscle dysfunction and myocardial infarction exclusively, whereas the hypert,rophic ohstructirbn may have played a significant role. Case 5. (E. B. ). A 68-year-old female had a long history of heart disease and d?spnea, with
331
Krasnow
and
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CONTROL
AMYL
NITRITE
AMYL NITRITE
Fig. 3. Hypertrophic cardiomyopathy The septum is thick, but obstruction murmur, carotid pulse abnormality,
332
in a 65-year-old man being followed for hypertension is not present at rest. With Valsalva maneuver and amyl and SAM appear.
and mild dyspnea. nitrate inhalation, a
September,
1978, Vol. 96, No. 3
cardiomegaly known for 6 years. She was being treated for mild hypertension when she was admitted for syncope associated with a respiratory infection. BP was 160/80. An S, gallop was present. A regurgitant murmur was present at the apex, and a systolic ejection type murmur was heard along the sternal border which radiated to the neck. ECG and x-ray indicated left ventricular hypertrophy. Carotid pulse showed a spikedome pattern, with normal ejection time index, and PEP/ET and 0.26. Phonocardiogram confirmed the ejection and regurgitant murmurs. The echocardiogram revealed a thickened septum (2.4 cm.) with septum/posterior wall ratio of 1.9, 2+ SAM with 4 mm. systolic outflow tract diameter, and the mitral leaflet was displaced anteriorly. The aortic valve was noted to be notched late in systole. Propranolol2 mg. administered intravenously during the study decreased the SAM within five minutes. Case 6. (D. A., Fig. 3). This 65year-old man was told of a “leaky valve” at age 17 but knew no more of heart disease till 5 years prior to study (age 60) when he noted dyspnea on walking rapidly. Cardiomegaly was noted and he was being treated for hypertension. His mother died in her thirties during the 1918 influenza epidemic; a son died suddenly during a soccer match, without known prior heart disease. Blood pressure was 160/90. There was an apical systolic ejection murmur increasing during Valsalva maneuver, and an S,, was present. The pulses were normal and the ECG showed LVH. Echocardiogram and phonocardiogram showed development of a murmur and SAM during amyl nitrate inhalation. There was moderate asymmetric septal hypertropb. Comment. This patient has apparently mild disease clinically. The findings could have been dismissed as compatible with hypertension. The son who died during exertion was presumably severely affected. Discussion
Hypertrophic cardiomyopathy is easily diagnosed in young or middle-aged patients when there are characteristic clinical findings’-’ consisting of dyspnea or signs of congestive heart failure, chest pain, syncope, or palpitations, in association with the findings of a brisk carotid upstroke and a systolic murmur heard best along the left sternal
American
Heart
Journal
border which is poorly transmitted to the neck. The picture is complete with an ECG meeting the criteria of left ventricular hypertrophy and a chest x-ray revealing a small ascending aorta and left ventricular predominance. Mitral insufficiency is frequently present, occasionally dominating the clinical picture. In the aged, our clinical study of hkpertrophic obstructive cardiomyopathy shows that. the diagnosis was frequently missed, similar to the experience of Hamby and Antablian” and Whiting and colleagues. :‘I The symptoms and signs are frequently misinterpreted as manifestations of more common diseases such as coronary artery diseaseor hypertensive heart disease. Mild hypertension, common in this age group, is frequently considered the basis of the cardiomegaly-. Syncope or dizziness, a common presenting sign in this series, as in that of Whiting and associates,‘” may be ascribed to cerebrovascular insufficiency or heart block. The brisk carotid pulse may be ascribed to rigidity of the arterial walls, or conversely, it may be sluggish due to associated intrinsic atherosclerotic and thromhotic: disease (one patient in this series had total obstruction of a carotid artery and underwent endarterectomy). The ascending aorta may be dilated, rather than small, leading one to ascribe the systolic murmur to aortic stenosis. The associated mitral insufficiency was often explained as papillary muscle dysfunction, or as in one patient in our series, to a calcified mitral annulus. Carotid pulse tracings and heart sound recordings offer important clues to the proper diagnosis, but the echocardiogram provides the most accurate, specific diagnostic support short of cardiac catheterization. The characterisbic echocardiographic features include a thickened septum, out of proportion to the thickness of the posterior left ventricular wall; an anterior mitral valve leaflet echo showing anterior posterior; an anterior systolic motion, often abutting the septum; and a slow early diast.oiic thing motion. Septal motion is often diminished but may be normal. The left ventricular valve cavny is small and the record appears “busy.” The aortic valve leaflets appear thin and open wide{!-. hut may show a notch of midsystolic closure. The extensive use of the echocardiogram in a large medical teaching service contributed to the increasing frequency of diagnosis, in a group of
333
Krasnow
and
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patients who otherwise would have remained misdiagnosed had cardiac catheterization been required. It is to be expected that the increasing utilization of the echocardiogram will be associated with fewer missed diagnoses of hypertrophic cardiomyopathy in the elderly. Hypertrophic cardiomyopathy is more common in older people than was previously thought. In earlier series of hypertrophic cardiomyopathy, aged patients were rare and most patients were young or middle-aged adults, or children. In the series of 119 patients followed by Hardarson and colleagues,’ only one was over 60 years of age, and Adelman and associates8 reported on 60 patients, the oldest of whom was 55. In the large early series of 126 patients analyzed by Frank and BraunwaldlJ only two were over 60. None of the 18 patients reported by Parker” was over 45. Recently, however, Whiting and colleagues1U reported 14 cases over the age of 60, and Hamby and Aintablian” found nine cases of hypertrophic cardiomyopathy in patients over 70. In our present series of 23 cases of hypertrophic cardiomyopathy of all ages seen in the past 3 years, 20 were over the age of 50 years. The recognition of hypertrophic cardiomyopathy in patients in the seventh and eighth decades of life, some of whom who are even then minimally symptomatic, extends our understanding of the natural history of the disease from that portrayed in previous studies. The patients in this series suggest that the lesion of hypertrophic cardiomyopathy is compatible with a long life, and that selected patients may remain asymptomatic to a late age. The explanation for this more benign prognosis in selected patients is not clear. Two possible explanations suggest themselves: one is that this group of patients had a relatively mild degree of obstruction, and thus survived to old age; the other, is that the obstructive process is not present in early years but develops and progresses in the course of aging. The possibility of our series representing a milder form of the obstructive lesion is suggested by the small resting gradients atcardiac catheterization and normal cardiac indices among the seven subjects who underwent cardiac catheterization. Also the echocardiogram did not suggest high grade obstruction’j-i.e., the outflow tract was not completely obliterated for long periods of systole in most patients. Previous studies do not,
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however, suggest a milder obstructive lesion in the elderly. Whiting and associates”’ found more severe gradients at catheterization among his older patients, as compared to the younger group. Pomerance and Davies”’ found severe hypertrophy at necropsy in the older patients, with an average heart weight of 560 grams, even though in some cases of their series, the lesion was an incidental finding, and was not symptomatic or diagnosed during life. There is, however, difficulty in defining clinical severity of this disease, especially when sudden death may occur at any stage of disease, unheralded by any symptoms. There is disagreement among investigators as to the prognostic usefulness of clinical or hemodynamic parameters. Hanania and colleagues’: found that clinical prognosis related only to the age of onset of symptoms. One agreed-upon datum is the poorer prognosis of the familial form of the disease, compared to the sporadic form.‘. Ii Only four subjects in the present series had a history suggestive of familial disease, but this datum is not reliable since in a number of our cases the family history was not well known to the patient. The present study with its predominance (80 per cent) of female patients suggests also that males may have a severer form of the disease. In the series of Frank and Braunwald,‘,’ there was an equal sex incidence in younger patients, but in the older patients, females predominated. Hamby and Aintablian” also found seven females out of nine aged patients with hypertrophic cardiomyopathy. In the series of necropsy cases studied by Pomerance and Davies,“’ the sex incidence was equal, but females averaged 76 years of age compared to 66 for males. Whiting and coworkers”’ found 10 of 14 elderly patients to be females. One could thus infer that women have a better chance of living longer with the disease. The second possible explanation for the prolonged survival is that in this disease, albeit often a familial one, the obstructive process is not present in early years, but develops and progresses with age. This contention is supported by the work of Williams and colleagues,” who documented the development of the obstructive component over 4 years in a 15-year-old girl. Even the disordered myocardial architecture, previously thought to be a feature of the congenital myopathic character of the disease, may repre-
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1978, Vol. 96, No. 3
Hypertrophic
sent the result, not the cause, of prolonged obstruction’g and could possibly be progressive in character. The mechanism of progressive obstruction may become clearer now that longitudinal studies by echocardiography are possible. A corollary of the thesis of progressive development of the lesion is that the clinical course is slow. In several recent studies, a gradual progression of symptoms is described for many patients, regardless of the clinical classification of the patients when first studied. Hardarson and colleagues’ postulates a long phase of asymptomatic disease until about age 30, after which symptoms may supervene with progressive clinical deterioration. Sudden death can occur at any time in this course, however, even in asymptomatic subject,s responding well to medical or surgical therapy. In the 49 patients followed for an average of 7.5 years by Hanania and associates,” 66 per cent survived 20 years from the onset of the first symptoms. These data support the concept of Hardarson and co-workers’ on the prolonged course of the disease. To confound the description of the natural history and prognosis further, Hanania and colleagues” found that more casesimproved with time than deteriorated; treatment with propranolo1 did not account for this result. Adelman and co-workers’ and Powell and colleaguesz” also noted significant improvement in many patients of their respective series, attributing the change to medical therapy with beta-adrenergic blocking drugs but without a true control series for comparison. The present series thus extends the potential survival curve even further than that suggested by Hardarson, Hanania, and their associates.’ ‘:
American
Heart
Journal
;n the aged
causes, including valvular aortic st,enosis, arteriosclerotic or hypertensive heart disease, or cerebrovascular disease. Left ventricular hypertrophy was more consistently present on ECG than on x-ray. The not-infrequent occurrence of hypertrophic cardiomyopathy in older patients, predominantly females, indicates that the natural history of this disease includes a group who suffer few or no symptoms until late in life. Clinical management of younger patients with this diagnosis should be considered in light of this more favorable possible course. The excellent technical and Miss Shirley Staiano Yetta Israelite is gratefully
assistance of Mrs. Henrietta and secretarial assistance acknowledged
Stokes of Mrs.
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Summary
Although usually considered a disease of young or middle-aged adults, hypertrophic cardiomyopathy is not infrequently seen in older patients as well. Twenty of 23 cases of hypertrophie cardiomyopathy seen in the past 2% years at our institution have been in patients whose average age was 65 years, and who ranged up to 76 years. Sixteen of these had evidence of an obstructive component at cardiac catheterization or echocardiography. Symptoms and signs were similar to those described for the younger patients in the literature, but were often attributed to other
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Brachfeld, N., and Gorlin, R.: Suhaortil, stenosis: -4 revised concept of the disease, Medicine 38:415, 1959. Braunwald, E., Morrow, A. G., Cornefl. W. P., Aygen, M. M.. and Hilbish, T. F.: Idiopathic hypertrophic subaortic stenosis: Clinical, hemodynamic: and angiographic manifestations, Am. J. Med. 29:924. 1960. Wigle. E. D., Heimbecker, R. O., and Gunton, and R. W.: Idiopathic ventricular septal hypertrophy causing muscular suhaortic stenosis. Circulation 26:325, 1962. Cohen, J., Effat, H., Goodwin, J. F., Oakley, C. M., and Steiner, R. E.: Hypertrophic obstructive cardiomyopathy, Br. Heart J. 26:16, 1964. Menges, H., Jr., Brandenburg, R. O., and Brown. A. L.. Jr.: The clinical hemodynamic and pathologic diagnosis of muscular suhvalvular aortic stenosis, Circulation 24: 1126. 1961. Goodwin, d. F.: Congestive and hvpertrophic cardiomyopathies, Lancet 1:731, 1970. Hardarson. T., Curiel, R., DeLaCalzada. C. S., and Goodwin, J. F.: Prognosis and mortality of hypertrophic obstructive cardiomyopathy, Lancet 2: 1462, 1973. Adelman, A. G., Wigle, E. D., Ranganathan, N., Webb. G. D., Kidd. S. S. S., Bigelow, W. G., and Silver, M. D.: The clinical course in muscular suhaortic stenosis, Ann. Intern. Med. 77:515. 1972. Parker. B. M.: The course in idiopathic hypertrophic muscular subaortic stenosis, Ann. lntern. Med. 70:903, 1969. Whiting, R. B.. Powell, W. d., Jr., Dinsmore, R. E., and Sanders, C. A.: Idiopathic hypertrophic subaortic stenosis in the elderly, N. Engl. J. Med. 285:196, 1971. Popp. R. L.: Echocardiographic assessment of cardiac disease, Circulation 54:538. 1976. Weissler, A. M.: Non-invasive cardiologv, New York. 1974, Grune & Stratton, Inc. Frank. S.. and Braunwald. E.: Idionathic, hvnertroahic ’ subaortic’stenosis, Circulation 37:7;9, 1968. a Hamby, R. I., and Aintablian, A.: Idiopathic hypertrophic suhaortic stenosis in the septuagenarian, (‘lin. Ites. 24:22OA, 1976. Henry, W. L., Clark, C. E., Glancy. I,., and Epstein, S. E.: Echocardiographic measurement of the left ventricular outflow gradient in idiopathic hypertrophic suhaortic stenosis, N. Engl. J. Med. 2883989, 1973
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Pomerance, A., and Davies, M. J.: Pathological features of hypertrophic obstructive cardiomyopathy (HOCM) in the elderly, Br. Heart J. 37:305, 1975. Hanania, G., Marino, J. P., Magnier, S., Baragan, J., Guillemaut, P., Fernandez, F., and Gerbaux, A.: Evolution Spontanee des Myocardiopathies Obstructives, Arch. Mal. Coeur 69:1023, 1976. Williams, R. G., Ellison, C., and Nadas, A. S.: Development of left ventricular outflow obstruction in idiopathic hypertrophic subaortic stenosis, N. Engl. J. Med. 288:868, 1973.
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Bulkley, B. H., Weisfeldt, M. L., and Hutchins. G. M.: Isometric cardiac contractiolr. A possible cause of the disorganized myocardial pattern of idiopathic hypertrophic subaortic stenosis, N. Engl. J. Med. 296:135, 1977. Powell, W. J., Jr., Whiting, R. B., Dinsmore, R. E., and Sanders, C. A.: Symptomatic prognosis in patients with idiopathic hypertrophic subaortic stenosis (IHSS), Am. J. Med. 5615, 1973. Glaser, J.: Mid-systolic AV Closure in IHSS, Circulation 61:1172, 1975.
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