(Circulation. 1995;92:2488-2495.)
© 1995 American Heart Association, Inc.
Articles |
Natural History of Hypertrophic Cardiomyopathy
A Population-Based Study, 1976 Through 1990
From the Division of Cardiovascular Diseases (C.R.C., G.S.R.) and the Department of Health Sciences Research (K.R.B., L.J.M.), Mayo Clinic and Mayo Foundation, Rochester, Minn, and the Division of Cardiology, Georgetown University Medical Center (B.J.G.), Washington, DC.
Correspondence and reprint requests to Guy S. Reeder, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Hypertrophic cardiomyopathy is a disease entity characterized by marked heterogeneity in morphology and natural history. Most of our knowledge of the natural history of this disorder derives from the study of hospital-based populations and is influenced by referral bias. Therefore, this population-based study was undertaken to examine the natural history of hypertrophic cardiomyopathy among unselected residents of Olmsted County, Minnesota.
Methods and Results Patients with hypertrophic cardiomyopathy, confirmed by echocardiography, were identified by use of the resources of the Rochester Epidemiology Project. Patients with the echocardiographic features of hypertrophic cardiomyopathy but with long-standing hypertension requiring drug therapy were categorized as having hypertensive hypertrophic cardiomyopathy. Baseline clinical details and follow-up events were obtained by retrospective chart review. Thirty-seven patients were diagnosed with hypertrophic cardiomyopathy and 24 with hypertensive hypertrophic cardiomyopathy. Eight additional patients were first diagnosed at autopsy. The mean age of the 37 patients with hypertrophic cardiomyopathy was 59±20 years (range, 1 week to 92 years); the mean ventricular septal thickness was 17.5±3 mm. Follow-up was obtained for a median of 7.7 years (range, 45 days to 17.2 years). The 1- and 5-year survival rates were 95% and 92%, respectively; these rates did not differ from those of an age- and sex-matched population (P=NS). The annual risk of cardiac death was 0.7%. The mean age of patients with hypertensive hypertrophic cardiomyopathy was 79±8 years (range, 62 to 91 years), and the mean ventricular septal thickness was 19±2.5 mm. Follow-up was obtained for a median of 2.8 years (range, 4 days to 16.7 years). The 1- and 5-year survival rates were 75% and 43%, respectively, which differed sharply from the expected rates of 94% and 70% (P=.0028). The annual risk of cardiac death was 5%. Atrial fibrillation and evidence for myocardial infarction on ECG, use of digoxin and diuretics, and a high New York Heart Association functional class at presentation were all associated with decreased survival by multivariate analysis for both groups combined. A history of myocardial infarction, atrial fibrillation, and mitral annular calcification at presentation were associated with cardiac death.
Conclusions Hypertrophic cardiomyopathy is a more benign disease than previously reported from tertiary referral centers. Patients assessed as having hypertensive hypertrophic cardiomyopathy represent a subset at higher risk for cardiac and noncardiac death, with an overall decreased survival rate.
Key Words: cardiomyopathy • prognosis • follow-up studies
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Hypertrophic cardiomyopathy is a disease entity characterized by marked heterogeneity in morphology and natural history. Patients range in age from infants1 to the elderly,2 and the clinical spectrum varies from the asymptomatic form to sudden death as an initial presentation. In addition, hypertensive hypertrophic cardiomyopathy has been recognized recently as a distinct subtype of hypertrophic cardiomyopathy.3 An additional difficulty relates to the fact that most of our knowledge of the natural history of this diverse disorder derives from the study of hospital-based populations4 5 6 7 8 and thus may be biased by selective patient referral.9 10 More recent studies of the clinical course of hypertrophic cardiomyopathy, for example, suggest a more benign course,11 12 13 14 which contrasts with the 2% to 6% annual mortality reported in prior clinical investigations.4 5 6 7 8 This study was undertaken to examine the natural history of hypertrophic cardiomyopathy among unselected residents of Olmsted County, Minnesota, initially diagnosed during 1976 through 1990 who had ready access to high-quality medical care and were followed meticulously. The clinical spectrum and outcome among these patients should not have been distorted by referral bias.
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Methods |
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Data Source
Study subjects were identified through the resources of the Rochester Epidemiology Project, which provides a valuable database for large-scale population-based investigations of the natural histories of diseases. Such studies are possible because medical care is delivered by a limited number of providers and is virtually self-contained within the community.15 The Mayo Clinic and its two large affiliated hospitals (St Mary's and Rochester Methodist), together with the Olmsted Medical Group and its affiliated Olmsted Community Hospital, provide almost all the medical care delivered to Rochester residents, including cardiology services. Each provider uses a unit or dossier type of medical record system that is based on the patient's unique identification number. Identification and retrieval of all potential cases are possible because diagnoses and surgical procedures recorded in these records have been coded at Mayo since 1910. This index includes outpatient office or clinic consultations, emergency room visits, and nursing home care, as well as diagnoses recorded for hospital inpatients, on death certificates, and at autopsy examination. The Rochester Epidemiology Project supports a comparable index to the health care delivered by the other providers of medical services to community residents. It is estimated that in any 3-year period about 95% of the population of Olmsted County is seen for routine medical examination or for minor or major illness at the Mayo Clinic or its affiliates.16 This medical-record linkage system has been used in many studies of cardiovascular and other diseases.15 17 In addition, the databases of the echocardiography and cardiac catheterization laboratories at the Mayo Clinic were screened for Olmsted County residents. Echocardiography has become the cornerstone for the diagnosis of hypertrophic cardiomyopathy, and use of this procedure increased in Olmsted County during the time period of this study.18 These resources ensured complete ascertainment of clinically diagnosed cases of hypertrophic cardiomyopathy in the population and provided a reliable basis for follow-up.
With the described database, all Olmsted County residents with an initial diagnosis of hypertrophic cardiomyopathy, idiopathic hypertrophic subaortic stenosis, or asymmetrical septal hypertrophy in the 15-year period of 1976 through 1990 were identified. Review of a sample of 100 cases with the broader diagnosis of cardiomyopathy did not reveal any further cases. Exclusion criteria included any concomitant cardiac disorders that could produce left ventricular hypertrophy. Potential patients with hypertrophic cardiomyopathy with systemic hypertension were not excluded from the screening process. Patients were assigned to either hypertrophic cardiomyopathy (obstructive, nonobstructive, or apical) or hypertensive hypertrophic cardiomyopathy on the basis of clinical and echocardiographic findings, as outlined below. All potential cases confirmed by echocardiography that met residency requirements were included. Established residence in Olmsted County for at least 1 year before diagnosis was required; thus, those individuals who may have moved to the area for treatment of underlying diseases were excluded.
Hypertrophic Cardiomyopathy
Cohort
Echocardiographic diagnosis of hypertrophic
cardiomyopathy required the presence of
asymmetrical septal hypertrophy
(septal-to-free-wall ratio of 
1.3) and a nondilated left
ventricle with normal or hyperdynamic function or concentric
hypertrophy with features of outflow tract obstruction. In
patients with inadequate M-mode measurements at the initial
echocardiogram, the presence of septal hypertrophy was
confirmed on two-dimensional imaging. Supportive criteria included
systolic anterior motion of the mitral valve in those patients
with outflow tract obstruction and demonstration of a left
ventricular outflow tract gradient by Doppler
echocardiography. Localized basal septal
hypertrophy was not considered to represent
hypertrophic cardiomyopathy unless septal thickness
was 20 mm or accompanied by mitral systolic anterior motion
and/or evidence of left ventricular outflow obstruction.
Patients with a questionable history of hypertension or a short
duration of mild or borderline hypertension were included in the
hypertrophic cardiomyopathy cohort.
Hypertensive Hypertrophic
Cardiomyopathy
Patients meeting the echocardiographic
diagnostic criteria described above but with
long-standing histories of hypertension requiring drug therapy were
included in the hypertensive hypertrophic
cardiomyopathy cohort. Patients with uncontrolled
hypertension were excluded from the study. Hypertension was defined as
>140/90 mm Hg for patients younger than 65 years of age and >160/95
mm Hg for patients 65 years of age or older. The 8 patients with
ambiguous diagnoses and a predominantly concentric pattern of left
ventricular hypertrophy were assigned to the
hypertensive hypertrophic cardiomyopathy
cohort.
Data Collection
Clinical details and follow-up were obtained
by review of
each subject's complete (inpatient and outpatient) medical records
and by mail or telephone contact when necessary. In addition to
demographic data and vital status at last follow-up, information
was collected on presenting history, medications used, physical
examination findings, and results of ECGs, chest radiographs, and
echocardiograms. The results of cardiac
catheterization, 24-hour Holter monitoring, and
functional testing were recorded when available. Primary clinical
end points included sudden cardiac death (within 1 hour of
presentation), nonsudden cardiac death, and death from
noncardiac causes. The occurrence of presyncope, syncope,
tachyarrhythmias, myocardial infarction,
cerebrovascular accidents and transient ischemic attacks,
infective endocarditis, systemic embolization, and cardiac
hospitalization was also recorded during the follow-up period.
Specific therapy aimed at hypertrophic
cardiomyopathy through the study period and New
York Heart Association (NYHA) classification of functional status at
last follow-up were also recorded.
Data Analysis
Demographic and clinical data were summarized
by mean±SD or
percentages. Comparisons between the hypertrophic
cardiomyopathy and hypertensive hypertrophic
cardiomyopathy groups were performed with the
two-sample t test or Pearson's 
2
test of proportions. Survival was estimated by the
Kaplan-Meier19 product-limit method, and
comparisons to survival rates of the US white population were made with
the one-sample log-rank test.
Associations of variables with survival and cardiac death were estimated and tested with simple and multiple Cox proportional-hazards models. After a multiple regression model (not including the group variable) was selected for the overall cohort, a risk score based on this model was calculated for each individual. The two groups were compared with respect to this risk score, and a Cox model was fitted by use of the risk score, group, and interaction. This analysis was intended to detect an effect of the subdiagnostic group on risk independent of these other baseline factors and to detect whether the risk score had a similar impact in both groups. Finally, a separate set of analyses of survival was done in which survival time was replaced by a pseudotime variable based on the actuarial life tables for each given age and sex. This pseudotime variable, the negative logarithm of the age- and sex-specific survival probability for the observed follow-up time, was chosen to make the survival time distribution independent of age and sex.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Thirty-seven Olmsted County residents were initially diagnosed during life with hypertrophic cardiomyopathy and 24 with hypertensive hypertrophic cardiomyopathy during 1976 through 1990. Eight additional patients were first identified at autopsy (6 with hypertrophic cardiomyopathy and 2 with hypertensive hypertrophic cardiomyopathy). Table 1
gives
further details on the patients diagnosed at autopsy. For the purposes
of this study, subsequent discussion relates to the 61 patients
diagnosed during life.
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Hypertrophic Cardiomyopathy
Patient Characteristics
The mean age of these 37 patients (16 men, 21 women) was 59±20
years (range, 1 week to 92 years). At presentation, 16
patients (43%) had a history of chest pain, 6 patients (16%) had
symptoms of dyspnea, and 4 patients (11%) had a history of syncope.
Although 17 patients (46%) had a history of hypertension, mean
systolic and diastolic pressures at the time of
diagnosis were 142±24 and 83±13 mm Hg, respectively. Four
patients
(11%) had a history of myocardial infarction; 10 patients (27%) had
additional medical conditions, including chronic obstructive airways
disease, diabetes, malignancy, Parkinson's disease, and respiratory
distress syndrome in a premature neonate. At the time of
presentation, 3 patients (8%) were taking
ß-adrenergic blocking drugs, 2 patients (5%) were taking calcium
channel antagonists, and 11 patients (30%) were using
diuretics. Table 2 gives further detail on
baseline characteristics.
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Echocardiographic Data
Two-dimensional echocardiography was
performed in all 37 patients, and Doppler studies were obtained in
20 patients (54%). Adequate M-mode measurements of the
ventricular septum were available in 27 patients (73%) at
the time of the diagnostic study. The mean
ventricular septal diastolic thickness was
17.5±3 mm (normal, 
12 mm). Systolic anterior motion of the
mitral valve was present in 21 patients (57%), and mitral annular
calcification was observed in 5 patients (14%). The most common
pattern of left ventricular hypertrophy was
asymmetrical septal hypertrophy (46%). Eight patients
(22%) had concentric hypertrophy with septal prominence, 6
patients (16%) had concentric hypertrophy, 3 patients
(8%) had basal septal hypertrophy, and 3 patients (8%)
had apical hypertrophy. Of the 20 patients undergoing
Doppler echocardiography, 15 (75%) had a left
ventricular outflow gradient (mean maximal instantaneous
gradient, 39±32 mm Hg). Table 3 gives more
echocardiographic data.
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Angiographic Data
Ten
patients (27%) underwent cardiac
catheterization; a left ventricular outflow
tract gradient was observed at rest in 3 patients. Moderate
coronary artery disease was present in 1 patient.
Ambulatory ECG
Twenty patients (54%) had 24-hour
ambulatory ECGs; sinus rhythm
was present in 18 patients, and a wandering atrial pacemaker was
documented in the remaining 2 patients. Paroxysmal
supraventricular tachycardia was noted in
13 patients; complex ventricular ectopy
(ventricular premature complexes, >700 per hour, in pairs
or in bigeminy) was documented in 6 patients.
Treadmill
Exercise Test
Fourteen patients (38%) underwent treadmill exercise
testing; an
ischemic exercise ECG was documented in 1 patient.
Follow-up Data
Patients were followed for a median
of 7.6 years (mean, 8.0 years;
range, 23 days to 17.2 years). At least 5 years of follow-up was
obtained for 17 patients. The mean NYHA functional class at
presentation was 1.3. Among patients who initially
presented with class I symptoms, 43% progressed to class II,
III, or IV symptoms during the course of the follow-up period (Fig
1). The mean functional class at last clinical
follow-up was 1.75 for the 36 patients in whom this information was
available. Five patients (14%) had at least one syncopal episode, 4
patients (11%) had documented myocardial infarctions, 2 patients (5%)
suffered cerebrovascular accidents, and 15 patients (41%) had one or
more cardiac hospitalizations during the follow-up period (Table
4). The most common reason for cardiac hospitalization
was management of chest pain. No patient underwent myectomy for the
surgical relief of obstruction. There were 8 deaths (2 cardiac and 6
noncardiac). One of the cardiac deaths was assessed as sudden death
although it was not witnessed and the exact circumstances of death were
not clear. Another 2 patients suffered sudden cardiac arrest but were
successfully resuscitated and had automatic implantable cardiac
defibrillators inserted. Medical therapy during follow-up included
ß-blockers, calcium channel antagonists, or both in
33 patients (89%). Two patients had permanent cardiac pacemakers
implanted for complete heart block and sick sinus syndrome during the
follow-up period.
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Hypertensive Hypertrophic
Cardiomyopathy
Patient Characteristics
This group
consisted of 24 patients (3 men, 21 women) with a mean
age of 77±8 years (range, 62 to 91 years). At
presentation, 11 patients (46%) had a history of chest
pain, 13 patients (54%) had symptoms of dyspnea, and 3 patients (13%)
had a history of syncope. All had a history of hypertension, and the
mean systolic and diastolic pressures were 157±27
and 83±13 mm Hg, respectively, at the time of diagnosis. Seven
patients (29%) had a history of myocardial infarction; 11 patients
(46%) had additional medical conditions, including chronic obstructive
airways disease, diabetes, renal impairment, malignancy, liver
cirrhosis, and alcohol abuse. At the time of presentation,
3 patients (13%) were taking ß-adrenergic blocking drugs, 4
patients (17%) were taking calcium channel antagonists,
and 19 patients (79%) were using diuretics. Table 2
gives
additional details on baseline characteristics.
Echocardiographic Data
Two-dimensional
echocardiography was
performed in all patients, and Doppler studies were obtained in 18
patients (75%). Adequate M-mode measurements of the
ventricular septum were available in 12 patients (48%) at
the time of the diagnostic study. The mean
ventricular septal diastolic thickness was
19±3 mm (normal, 12 mm). Systolic anterior motion of the
mitral valve was present in 9 patients (38%), and mitral annular
calcification was observed in 6 patients (25%). The most common
pattern of left ventricular hypertrophy was
concentric hypertrophy (50%). Eleven patients (46%) had
concentric hypertrophy with septal prominence, and 1
patient (4%) had asymmetrical septal hypertrophy. Of the
18 patients undergoing Doppler
echocardiography, 13 (72%) had a left
ventricular outflow gradient (mean maximal instantaneous
gradient, 15±17 mm Hg). Table 3 gives further
echocardiographic data.
Angiographic Data
Three
patients (13%) underwent cardiac
catheterization; no left ventricular
outflow tract gradient was observed at rest in any patient. Severe
coronary artery disease was present in 1 patient.
Ambulatory ECG
Eight patients (33%) had 24-hour
ambulatory ECGs recorded;
sinus rhythm was present in 6 patients, atrial fibrillation and a
nodal rhythm were present in the remaining 2 patients. Paroxysmal
supraventricular tachycardia was noted in 5
patients; complex ventricular ectopy (as defined above) was
documented in 2 patients. One patient had a run of nonsustained
ventricular tachycardia.
Treadmill Exercise Test
Five patients (21%) underwent treadmill exercise testing; an
ischemic exercise ECG was documented in 2 patients.
Follow-up Data
Patients were followed for a median
of 2.8 years (mean, 4.6 years;
range, 4 days to 16.7 years). At least 5 years of follow-up was
obtained for 8 patients. The mean NYHA functional class at
presentation was 1.95. Among patients who initially
presented with class I symptoms, 73% progressed to class II,
III, or IV symptoms during the course of follow-up (Fig 2). The
mean functional class at the last clinical
follow-up was 2.2. Five patients (21%) had at least one syncopal
episode, 3 patients (13%) had documented myocardial infarctions, 4
patients (17%) suffered cerebrovascular accidents, and 1 patient (4%)
had a transient ischemic attack. Nine (42%) had one or more
cardiac hospitalizations during the follow-up period (Table 4).
The
most common reason for cardiac hospitalization was management of chest
pain. There were 15 deaths (6 cardiac and 9 noncardiac). One of the
cardiac deaths was assessed as sudden death even though it was not
witnessed and the exact circumstances of death were not clear. Medical
therapy during follow-up included ß-blockers, calcium channel
antagonists, or both in 19 patients (79%).
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Survival Analysis
Survival rates of patients with
hypertrophic
cardiomyopathy at 1 and 5 years were 95% and 92%,
respectively, compared with an expected 97% and 87%. The difference
between observed and expected survival rates was not significant at the
5-year follow-up (P=.4; Fig 3). By
contrast, survival rates for the hypertensive hypertrophic
cardiomyopathy cohort were only 75% and 43% at 1
and 5 years, respectively, which differed sharply from the expected 1-
and 5-year survival rates of 94% and 70% (P=.0028; Fig
4). Of the deaths occurring in the hypertensive
hypertrophic cardiomyopathy cohort, 60% were
assessed as noncardiac. When the survival rates between the two groups
were compared without age adjustment, the difference was highly
significant (P=.0002), but the hypertensive hypertrophic
cardiomyopathy patients were much older (mean age,
77 years) than the hypertrophic cardiomyopathy
patients (mean age, 59 years). When survival was reanalyzed
with a pseudotime variable corresponding to the actuarial
probability of death, the difference between groups remained
significant (P=.02) despite this correction for age and
sex.
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A survival analysis within the hypertrophic
cardiomyopathy subgroup between patients with a
history of hypertension (1- and 5-year survival rates, 100% and 94%,
respectively) and those without hypertension (90% and 90%,
respectively) did not reveal any difference (P=.86; Fig
5).
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Clinical, ECG, and echocardiographic variables were
examined for an association with decreased survival during the
follow-up period for both groups combined because numbers were
insufficient to allow multivariate analysis for
each group separately. The 1-week-old neonate was not included in
the multivariate analysis. Atrial fibrillation
and evidence for myocardial infarction on ECG, use of digoxin and
diuretics, and a high NYHA functional class at
presentation were all associated with decreased survival by
multivariate analysis for both groups combined
(Table 5). By use of a risk score, these variables
were significantly associated with decreased survival within each
group, with a higher risk score noted in the hypertensive
cardiomyopathy group. However, despite correction
for the above parameters in multivariate
analysis, the diagnosis of hypertensive hypertrophic
cardiomyopathy itself remained a significant
prognostic indicator for survival.
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Cardiac Death
The risk of cardiac death was 0.7%/y and 5%/y
among the
hypertrophic cardiomyopathy and hypertensive
hypertrophic cardiomyopathy patients, respectively.
The risk of sudden cardiac death was not assessed separately because
the clinical circumstances surrounding the possible sudden deaths were
unclear. Atrial fibrillation on presentation ECG, a history
of myocardial infarction, and mitral annular calcification on the
initial echocardiogram were associated with an increased incidence of
cardiac death by multivariate analysis for both
groups combined (Table 6).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Our study is the first population-based assessment of the natural history of hypertrophic cardiomyopathy. The annual risk of cardiac death was 0.7% for hypertrophic cardiomyopathy, and there was no significant difference in overall survival compared with an age- and sex-matched population. This is in striking contrast to the poor prognosis among patients with hypertensive hypertrophic cardiomyopathy, whose survival rates were greatly reduced compared with that expected for people of like age and sex.
The natural history of hypertrophic cardiomyopathy has been described from several large studies. Most patients deteriorated clinically over various time spans, and a 2% to 6% annual mortality was reported.4 5 6 7 8 Patients from these studies were characterized by severe symptoms or a malignant family history and were predominantly referrals to tertiary care centers.4 5 8 Indeed, almost 50% of studies published on hypertrophic cardiomyopathy in the major cardiology journals originated from two centers.11 Accordingly, these patients reflect the more severe spectrum of the disease, leading to early referral. More recent reports on the natural history of hypertrophic cardiomyopathy as it occurs in the community also reflect a more benign course. Shapiro and Zezulka14 studied 39 patients over a 5-year period at a community hospital. Mortality among these patients was no different from normal. A report of a small outpatient population of 25 patients followed for a mean of 4.4 years demonstrated a similarly benign course.11 The largest series was a clinic population of 113 patients followed for a mean of 7 years12 ; in this series, the annual cardiac mortality was only 1%. Despite the more benign course, this study still represented a population of referrals from surrounding areas and was therefore still subject to referral bias. Others have described the course of hypertrophic cardiomyopathy in the elderly population2 and middle-aged asymptomatic patients.13 All concluded that the natural history of hypertrophic cardiomyopathy may be more benign than implied by earlier reports. Our results confirm their findings but identify a subgroup of patients at higher risk in a well-defined population in which very few patients went undiagnosed.
Multivariate analysis revealed NYHA functional class, use of digoxin and diuretics at presentation, and myocardial infarction and atrial fibrillation on baseline ECG to be associated with a poor prognosis. Not surprisingly, the decreased survival in the overall population was predicted by the severity of symptoms. The association with atrial fibrillation could be the consequence of severe disease or causal on the basis of the well-documented detrimental effects of atrial fibrillation in patients with diastolic dysfunction. The use of digoxin and diuretics is known to be detrimental in some instances of hypertrophic cardiomyopathy.3 Finally, the association of pathological Q waves on presentation ECG with prognosis is less certain but may pertain to the electrophysiological myocardial abnormalities known to occur in hypertrophic cardiomyopathy.20 Prior studies reported left ventricular hypertrophy,21 functional class and young age at presentation,8 a strong family history of sudden death,8 syncope,8 and ventricular tachycardia on ambulatory ECG22 to be associated with a worse prognosis. Our study confirms the association of functional class on presentation with outcome. No patient with hypertrophic cardiomyopathy was demonstrated to have ventricular tachycardia on ambulatory ECG; however, others questioned the significance of ventricular tachycardia during 24-hour ambulatory monitoring.23 Because only 46% of our patients had ambulatory monitoring performed, this result should be interpreted with caution. The prognostic significance of a family history of sudden death was not addressed because no reliable data on family history were available in this retrospective study. Although we did not find an association between prognosis and the other previously described parameters, the numbers in this study were small relative to the large referral center studies.
Although we believe that very few cases of hypertrophic cardiomyopathy in Olmsted County residents were missed, an important area of underdiagnosis was asymptomatic people who never seek medical care for any reason. These are usually young men, as emphasized by the finding of two young men who, with no known medical problems, presented at autopsy as having hypertrophic cardiomyopathy with sudden death. Thus, the younger patients included in this study could represent a more stable subgroup previously selected by sudden death and medical care. In our study, only 5 young patients (14%, <40 years of age) had hypertrophic cardiomyopathy, and no cardiac deaths were reported. In addition, the diagnosis of hypertrophic cardiomyopathy required the presence of ventricular hypertrophy on echocardiography; thus, patients in the early stages of the disease with no ventricular hypertrophy, as described by Maron et al,24 or genetically affected patients without echocardiographic changes25 would not be included. Despite this, we believe that this patient cohort accurately reflects the clinical spectrum of hypertrophic cardiomyopathy as identified by echocardiography in contemporary clinical practice.
The mean age of patients in our hypertrophic cardiomyopathy cohort was 59 years. This age is significantly greater than the mean ages of 39 and 43 years reported by the two large referral centers11 but reflects instead the age distribution of unselected patients from the general population. The diagnosis of hypertrophic cardiomyopathy in the elderly is not a new finding. As early as 1971, Whiting et al26 reported that 32% of patients catheterized at the Massachusetts General Hospital were <60 years of age. In a community-based study, Petrin and Tavel27 found that 85% of patients were >50 years of age and 82% of these were women. In the present study, 41% and 88% of patients in the hypertrophic cardiomyopathy and hypertensive hypertrophic cardiomyopathy cohorts, respectively, were 65 years of age or older. Increasing age is associated with an increase in left ventricular mass and septal thickness.28 In the very old, the septum may be not only hypertrophied but also sigmoid, which may simulate the appearance of hypertrophic cardiomyopathy.29 Lever and colleagues30 highlighted the echocardiographic differences between young and old patients with hypertrophic cardiomyopathy and suggested that hypertrophic cardiomyopathy in the elderly may be a disease distinctly different from that which exists in the young. Thus, it is likely that the cardiac changes seen in various age groups of patients with hypertrophic cardiomyopathy reflect the spectrum of a heterogeneous disease.
We included all patients with mild or moderate hypertension. Hypertension is present in one third of the general population,31 and significant overlap with a rare condition such as hypertrophic cardiomyopathy should be expected, especially in the elderly population.2 3 26 Only a minority of patients with chronic mild or moderate hypertension develop detectable left ventricular hypertrophy.32 Furthermore, it has been shown that, except for increased posterior wall thickness, hypertensive patients with hypertrophic cardiomyopathy do not differ echocardiographically from an age- and sex-matched normotensive group of patients with the same disease.32 Patients with mild hypertension included in the hypertrophic cardiomyopathy cohort may well represent an inappropriate hypertrophy to an appropriate stimulus and possibly a milder subgroup. However, survival analysis between these patients and those without hypertension in the hypertrophic cardiomyopathy cohort did not reveal any difference.
The worse prognosis of the hypertensive hypertrophic cardiomyopathy cohort than the hypertrophic cardiomyopathy patients is not fully understood. The clinical entity of hypertensive hypertrophic cardiomyopathy may reflect an even more inappropriate response to hypertension. Furthermore, these patients were more symptomatic at presentation; patients with concomitant fatal disease were not excluded from the study and often had hypertensive hypertrophic cardiomyopathy diagnosed while in a hospital setting for other medical problems. Therefore, they may represent a sicker spectrum of hypertrophic cardiomyopathy patients with hypertension. Being older patients with hypertension, they would have been far more likely to have significant coronary artery disease, which might account for the increased incidence of cardiac death observed and the increased percentage with a history of myocardial infarction. This would concur with the finding of Lazzeroni et al33 that coronary artery disease was more prevalent in older than younger patients and played an important role in the natural history and prognosis of hypertrophic cardiomyopathy. Finally, could hypertensive hypertrophic cardiomyopathy simply be severe hypertension with the same hypertrophic and hemodynamic features of hypertrophic cardiomyopathy, even though the two diseases are unrelated? Considerable overlap between the two can exist, and left ventricular hypertrophy secondary to severe hypertension can mimic hypertrophic cardiomyopathy in as many as one third of patients in one study.34 We were careful to exclude patients with a record of severe or uncontrolled hypertension but acknowledge that this was a subjective assessment with a potential for error. Ultimately, the only way we could tell whether hypertensive hypertrophic cardiomyopathy is a forme fruste of hypertrophic cardiomyopathy or a different disease entity is genetic analysis,35 which is beyond the scope of this study and current clinical practice.
The present study demonstrates that hypertrophic cardiomyopathy is generally a more benign disease than previously reported from tertiary referral centers. NYHA functional class, use of digoxin and diuretics at presentation, and atrial fibrillation and myocardial infarction on baseline ECG were associated with a decreased survival rate. Predictors of cardiac death included a history of myocardial infarction, atrial fibrillation, and mitral annular calcification. Although we cannot adequately explain the discrepancy in survival, it appears that patients assessed as having hypertensive hypertrophic cardiomyopathy represent a subset of patients at higher risk for cardiac and noncardiac death with an overall decreased survival rate.
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Acknowledgments |
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This work was supported in part by research grant AR-30582 from the NIH, US Public Health Service.
Received January 18, 1995; revision received April 4, 1995; accepted April 7, 1995.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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