tients) or for family screening (3 patients) were studied. All patients were .... and examiners. ... Case. AgeJGender. Adverse clinical features. Mode of death. Japanese 1. 4 4 M .... Yokota Y, Seo T. Fukuzaki H: Cardiac function and prognosis.
Comparison of Clinical, Morphological, and Prognostic Features in Hypertrophic Cardiomyopathy between Japanese and Western Patients YOSHINONL. Dor, M.D.,* MASASHI AKIZAWA, M.D.,* YOSHIHIRO YONEZAWA, M.D.,* WILLIAM J. MCKENNA,M.D.
TAIsHIRO CHIKAMORI, M.D., TOSHIO OZAWA, M.D.,*
apartment of Cardiological Sciences, St. George’s Hospital Medical School, London, U.K.; *Section of Cardiology, Department of Geriatrics and Medicine, Kochi Medical School, Kochi, Japan
Summary: Apical hypertrophic cardiomyopathy appears to be more common in Japan than in the West. Explanations for this difference include variable methods and criteria for the diagnosis. To assess morphological, clinical, and prognostic differences, 45 consecutive Japanese and 45 age- and gender-matchedWestern patients with hypertrophic cardiomyopathy were evaluated in two referral institutionsby the same individuals. The diagnosis of hypertrophic cardiomyopathy was based on the echocardiographic demonstration of unexplained left ventricular hypertrophy. Patients were aged 8 to 64 years (mean 50); there were 66 males and 24 females. The pattern of left ventricular hypertrophy was similar in Japanese and Western patients: asymmetric septa1 64 vs. 76%, concentric 22 vs. 13%, and apical 13 vs. 11% (p=NS). The incidence of an echocardiographicor Doppler calculated left ventricular gradient of >30mmHg was similar (1 1 vs. 18%; p = NS). The maximal left ventricular wall thickness was greater in Western patients (23_+ 7 vs. 20+ 4 mm; p = 0.03), but was not different when adjusted for body surface area. Clinical features including incidence of family history and ventricular tachycardia during 24-h ambulatory electrocardiography were similar. During follow-up (4.9 k4.0 years for Western vs. 4.4 2.0 years for Japanese), diseaserelated mortality was worse in Western patients (p < 0.05; 10 versus 2 patients). This evaluation, using the same diagnostic methods and criteria, reveals a worse prognosis in
+
Western patients despite a similar clinical and morphological spectrum of hypertrophic carhornyopathy.
Key words: hypertrophic cardiomyopathy, Japanese patients, Western patients, echocardiography, prognosis
Introduction Left ventricular hypertrophy is the characteristic finding in hypertrophic cardiomyopathy (HCM) and is usually generalized and maximal in the ventricular septum.lS2 Apical HCM, hypertrophy localized predominantly to the left ventricular apex, appears to be very common in Japan with reported prevalence of up to 30%. whereas the incidence in the West is less and was found to be 2 and 14% in the two largest series.>* Explanations for this difference include patient selection and variable methods and criteria for the diagnosis. To assess morphological differences, age- and gender-matched Japanese and Western patients with HCM were evaluated in two tertiary referral centers by the same individuals. This approach also enabled us to compare clinical and prognostic features in different institutions with minimal selection bias.
Methods Study Patients
Address for reprints: William J. McKenna, M.D. Department of Cardiological Sciences St. George’s Hospital Medical School Cranmer Terrace LondonSW17ORE,U.K. Received: July 1. 1992 Accepted: July 22, 1992
Forty-five consecutive patients with HCM who were referred to Kochi Medical School between 1981 and 1989 for assessment of symptoms (39 patients), abnormal electrocardiogram (ECG) with giant negative T waves (3 patients) or for family screening (3 patients) were studied. All patients were Japanese and were aged 8 to 64 years (mean 50); There were 33 males and 12 females. Fortyfive age- and gender-matched Western patients with HCM were randomly selected .from our population at St.
834
Clin. Cardiol. Vol. 15, November 1992
George's Hospital for comparison.The diagnosis of HCM was based upon the echocardiographic demonstration of unexplained left ventricular None of the patients had systolic or diastolic blood pressure of >140 or >90 d g , respectively. Echocardiography
Echocardiograms were performed by one of the authors using a Toshiba SSH-65A, an Aloka SSD-710, or a General Electric Pass-C with 2.5 to 3.75 MHz transducers. A complete M-mode and two-dimensional (2-D) study was performed and recorded on video tape for subsequent analysis. Criteria for the echocardiographic assessment of severity and extent of left ventricular hypertrophy has been described previously.*From the 2-D echocardiogram, two short-axis scans were used for analysis, one in the upper left ventricle at the level of the mitral valve tips and the second toward the apex at a level below the papillary muscles. Wall thickness measurements were made at the quadrants at end-diastole after careful localization of epicardiurn and endocardium using normal and slow forward playback. In patients who fulfilled the diagnosticcriteria of at least one segment 2 15 mm, the pattern of hypertrophy was assessed as previously described.2In brief, a ratio of wall thickness 2 1.5 between the anterior andor posterior septum and the left ventricular posterior wall defined asymmetric septal hypertrophy, while the same ratio between at least two of four segmental wall thickness measurements in the lower versus the upper left ventricle defined apical hypertrophy, and neither of the above defined concentric hypertrophy.2 Systolic anterior motion of the mitral valve was defined as complete if there was septal contact of the mitral valve during systole, incomplete if there was anterior motion of the valve without septal contact during systole, and absent if there was no anterior motion. The presence of obstruction to the left ventricular outflow tract under basal conditions was assessed either by or from Mcontinuous wave Doppler echocardi~graphy~ mode echocardiographyon the basis of the magnitude and duration of systolic anterior motion of the mitral valve.Io Conventional measurements of left ventricular dimension and derived indices of function were also made according to standard criteria." Ambulatory Electrocardiography
All patients underwent 24-h (in Japanese) or 48-h (in Western) ambulatory ECG monitoring off cardioactive medications at the time of diagnosis. Nonsustained ventricular tachycardia was defined as 2 3 consecutive ventricular premature complexes at a mean rate of >120 beatdmin. Exercise Testing
Symptom-limited treadmill exercise testing according to a modified Bruce protocol was performed in 39 (87%)
Japanese and 24 (53%) Western patients. Systolic blo pressure was measured using a mercury sphygmoma, meter at rest, at 1 min intervals during exercise and 1 recovery period postexercise. Measurements were ma by digital palpation of the radial or brachial artery. Blo pressure response was defined as hypotensive if systo blood pressure fell > 20 mmHg from peak value during e ercise, as abnormal recovery if systolic blood pressure fl initially and subsequently rose > 10 m H g from the mi imum value during the recovery period, or as normal neither of above was observed.I2 FOUOW-Up
Follow-up period was defined as the time from the in tial evaluation at each institution until death or data 01 tained in January 1990. All Japanese patients were fo lowed by cardiologists at Kochi Medical School at montl ly intervals; Western patients were followed at 6- to 1; month intervals at St. George's Hospital Medical School Statistical Analysis
Results are expressed as mean f l standard deviation An unpaired t-test was used to compare the means of th, continuous variables and contingency tables were analym using a chi-squared test. Kaplan-Meier survival estimate. were used to compare Japanese and Western population: and significance was tested using the generalized Wilcox on test. The computations were performed using the SPSS. pC+ computer program.
Results Echocardiographic Findings (Table I)
The pattern of left ventricular hypertrophy including the incidence of apical hypertrophy was similar in Japanese and Western patients. The maximal left ventricular wall thickness was less and interventricular septum was thinner in Japanese than in Western patients but the differences were not statistically significant when the measurement was adjusted for body surface area. The incidence of an echocardiographic or Doppler calculated left ventricular gradient of >30mmHg and left ventricular cavity dimensions were similar in both patient populations. Clinical Findings (Table 11)
Western patients experienced syncope more frequently, but this did not achieve statistical significance. The incidence of other symptoms including chest pain and dyspnea, family history of HCM, established atrial fibrillation, and frequent ventricular premature complexes and ventricular tachycardia during ambulatory ECG monitoring was similar. The male-female ratio in Japanese patients
T. Chikamori ef al.: Hypertrophic cardiomyopathy in Japanese and Western patients TABLE I
835
Echocardiographic findings in Japanese and Western patients with HCM
/
-
LVED tVES LVOTobstruction pattern of LVH ASH
Concentric Apical Thickness of IVS Thickness of PW Maximal Lv W d thickness Maximal Lv Wall thickness/BSA
Japanese (n = 45)
Western (n = 45)
44f6(mm) 26f4 5 (11%)
42 f 7 (mm) 26f4 8 (18%)
29 (64) 10 (22) 6 (13) 18 f 5 (mm) 13f4 20f4 12 f 3 (mm/m*)
34 (76) 6 (13) 5 (11) 21 f 7 (mm) 12f6 23 f 7 12 f 4 (mm/m*)
p Value NS NS NS NS
0.05
NS 0.03 NS
septa1 hypertrophy; BSA = body surface area; HCM = hypertrophic cardiomyopathy; IVS = interventricular septum; Lv = left ventricular; LVED = left ventricular end-diastolicdimension; LVES = left ventricular end-systolic dimension; LVH = left ventricular hypertrophy;LVOT = left ventricular outflow tract; NS = not significant; PW = posterior wall.
Abhmviations: ASH = asymmetric
TABLE I1 Clinical features in Japanese and Western patients with HCM Japanese (n = 45)
Western (n = 45)
50f 13 33 12
5 0 f 13 33 12
NS
37 (82%) 4 (9%) 4 (9%)
31 (69%) 10 (22%) 4 (9%)
NS
20 (44%)
21 (47%) 3 (7%) 12 (27%) 9 (20%)
NS
23 (51%) 19 (42%) 3 (7%)
NS
13 (29%) 1(2%) 36 (80%) 5 (11%) 4 (9%) 1(2%)
30 (67%) I(2%) 14 (31%) 3 (7%)
0.06
None < 250 beatdday 2 250 beatdday
I 1 (24%) 29 (64%)
NS
Nonsustained VT
15 (33%)
10(22%) 28 (62%) 7 (16%) 12(27%)
Age (years) Male
Female Fami I y history None
HCM HCM + sudden death Clinical symptoms Angina None
Atypical 15 (33%) Exertional 7 (16%) Atypical + exertional 3 (7%) Dyspnea” I 31 (69%) 11 111 + IV
I, Value
Presyncope Syncope Atrial fibrillation Ambulatory ECG VPCS
5(11%)
Exercise Blood Pressure Response
All examinations were performed without serious complications. In the Japanese patients, the reasons for the termination of exercise testing were fatigue and breathlessness in 36, chest pain in 3; in the Western patients, fatigue and breathlessness in 18, chest pain in 5, and progressive hypotension in 1. Duration of exercise was similar in the two groups (8.1 f 2 . 2 vs. 10.2f5.4 min; p=NS). One Japanese and five Western patients demonstrated exercise hypotension, and one Japanese and six Western patients had abnormal recovery; the incidence of exercise hypotension was higher in Western patients (5124 vs. 1/39; ~ ~ 0 . 0 2 ) . Prognosis
Syncope None
with a family history of HCM was 5:3 while the ratio in those without family history was 28:9, respectively. The ratios in Western patients who were selected were similar (1 1:3 and 22:9, respectively).
NS
NS
Classified by New York Heart Association functional class. Abbreviations: ECG =electrocardiography;HCM =hypertrophic
cardiomyopathy; NS = not significant; VPC = ventricular premature complex; VT = ventricular tachycardia.
Follow-up period was 4.4f 1.9 years in Japanese patients and 4.91t4.1 years in Western patients (p=NS). During this period, disease-related mortality (p < 0.05) was greater in Western patients (Fig. 1). Of the Japanese patients, one died suddenly and one died following a cerebrovascular accident; of the Western patients, four died suddenly, five died of heart failure, and one died following a cerebrovascular accident. Clinical features of those who died are listed in Table 111. Twenty-nine Japanese patients received beta blockers, 16 had calcium antagonists and 2 had diuretics, while 8 Western patients received beta blockers and 5 had verapamil. Amiodarone was prescribed (mean dose 200 mg daily) in 13 Western patients. No Japanese patients received amiodarone since this drug was not available in Japan.
Clin. Cardiol. Vol. 15, November 1992
836
l ao
o
o
1
I
201 45
45
39
33
24
20
14
4 (J)
Discussion Left ventricular hypertrophy confined to or predominantly localized to the apex is more common in Japanese series (20-30%) than in Western reports (2-14%).w To overcome the differences in diagnostic interpretation, this study used the same diagnostic echocardiographic criteria and examiners. Our results revealed that the severity and distribution of left ventricular hypertrophy were similar in both groups. Absolute maximal left ventricular wall thickness was less in Japanese patients, but was not different when body surface area in each group was taken into ac-
count, while the incidence of apical, asymmetric S q and concentric hypertrophy was similar. Thus, the res in this study indicate a similar morphological specmn HCM in Japanese and Western patients. Clinical/prognostic features including nonsustained v tricular tachycardia during ambulatory ECG monitor are important to predict the outcome of patients V, HCM.'>l5 This study showed that these features were a similar in Japanese and Western patients. The prognosis Japanese patients was, however, better than in West( patients with disease-related annual mortality of 1% a annual mortality due to sudden death of 0.5%. Spinto et suggested that the severity of the disease and its progno might differ in each institution and patients referred to t large specialized centers might have more severe disease The differences originating from referral bias in our two i stitutions could not be excluded entirely. However, the ft that direct comparison with careful matching showed I significant differences in morphology or established pro nostic features (malignant family history, syncope, fun tional limitation, ventricular tachycardia) suggested th this bias was probably small. The fact that clinical and established prognostic feahm were similar, but prognosis was worse in Western patient suggests that these prognostic features do not apply to Jal anese patients in the same way as to Western patients. A tematively, other risk factors may have been involved. Rt cently we observed a blood pressure fall during exercise i a third of a consecutive series of patients with HCM with a inappropriate fall in systemic vascular resistance despit normally rising cardiac output.l 2 In this study, 5 of 24 Wesl ern patients but only 1 of 39 Japanese patients had exercis hypotension. The prognostic significance of exercise hypo tension has not been established, but may be a factor in ex plaining the worse prognosis in Western patients. The literature suggests that male predominance is mort common in Japanese than in Western patients with HCM
TABLE I11 Adverse clinical features in patients who died
Case Japanese 1 Japanese 2 Western 1 Western 2 Western 3 Western 4 Western 5 Western 6 Western 7 Western 8 Western 9 Western 10
AgeJGender 44M
8F 13 M 36 M 49 M 51 M 52 M 54 M 62 M 62 M 24 F
60F
Adverse clinical features Presyncope, VT Family history of HCM + SD NYHA III, Syncope 0
Mode of death CVA SD
CHF SD SD
Syncope, VT Syncope Family history of HCM Family history of HCM Family history of HCM + SD, syncope
CHF CHF CHF
0
CVA
Family history of HCM, syncope VT
CHF
SD SD
Abbreviurions: CHF = congestive heart failure; CVA = cerebrovascular accident; F = female; HCM = hypertrophic cardiomyopathy; M = male; NYHA = New York Heart Association; SD = sudden death; VT = ventricular tachycardia; 0 = absent.
T. Chikamori er al.:Hypertrophic cardiomyopathy in Japanese and Western patients memale-female ratio was approximately 3: 1 in the stud-
ies including 658 Japanese patients (male: 499 vs. female: ,591from five different institution^.^.^,'^-'^ The results of his study are consistent with the literature. The male predominance in Japanese patients may reflect a different ratio of familial HCM to sporadic disease andor a different location of a responsible gene for familial HCM, and thus may provide a clue to the better prognosis in Japanese patients with HCM. In this study, the incidence of familial HCM based mainly upon patient interview was similar. Though detailed family studies including electrocardiography, echocardiography, and gene mapping were beyond the scope of this study, our results demonstrated better prognosis in Japanese than in Western patients with HCM. Further prospective study in relation to racial difference is warranted .
References I , Maron BJ, Gottdiener JS, Epstein SE: Patterns and significance
2.
3.
4.
5.
6.
of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy. A wide angle, two dimensional echocardiographic study of 125 patients.AmJCardiol48.418428 (1981) Shapiro LM, McKenna WJ: Distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: A two-dimensional echocardiographic study. J Am Coll Cardiol 2, 437-444 (1983) Yamaguchi H, Ishimura T, Nishiyama S, Nagasaki F, Nakanishi S, Takatsu F, Nishijo T, Umeda T, Machii K: Hypertrophic nonobstructive cardiomyopathy with giant negative T waves (apical hypertrophy): Ventriculographic and echocardiographic features in 30 patients. Am J Curdiol44,401-412 (1979) Mori H, Ogawa S , Noma S , Fujii I, Hayashi J, Yamazaki H, Nakazawa H, Handa S, Nakamura Y: Pattern of myocardial hypertrophy as a possible determinant of abnormal Q waves in hypertrophic cardiomyopathy. Jpn Circ J 47.51 3-521 (1983) Koga Y, Itaya K, Toshima H: Prognosis in hypertrophic cardiomyopathy. Am Hean J 108,351-359 (1984) Sakamoto T, Amano K, Hada Y, Tei C, Takenaka K, Hasegawa 1. Takahashi T Asymmetric apical hypertrophy: Ten years experience. Postgrud Med J 62,567-570 (1986)
837
7. Louie EK, Maron BJ: Apical hypertrophic cardiomyopathy: Clinical and two-dimensional echocardiographic assessment. Ann Intern Med 106.663470(1987) 8. Braunwald E, Lambrew CT,Rockoff SD, Ross J Jr, Morrow AC: Idiopathic hypertrophic subaortic stenosis. 1. A description of the disease based upon an analysis of 64 patients. Circulation 3qsuppl IV), 3-1 19 (1964) 9. Yock PG, Hatle L, Popp RL: Patterns and timing of Dopplerdetected intracavitary and aortic flow in hypertrophic cardiomyopathy. J A m Coll Cardiol8, 1047-1058 (1986) 10. Pollick C, Rakowski H, Wigle ED: Muscular subaortic stenosis: The quantitative relationship between systolic anterior motion and the pressure gradient. Circulation 69,4349 (1984) 11. Feigenbaum H: Echocardiographic measurements and normal values. In Echocardiography (Ed: Feigenbaum H). Lea and Febiger, Philadelphia (1986) 621-639 12. Frenneaux MP, Counihan PJ, Caforio ALP, Chikamori T, McKenna WJ: Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy. Circulation 82, 19952002 ( 1990) 13. McKenna WJ, Deanfield J, Famqui A, England D. Oakley CM, Goodwin JF: Prognosis in hypertrophic cardiomyopathy: Role of age and clinical, electrocardiographic and hemodynamic features. Am J Cardiol47,532-538 (1981) 14. McKenna WJ, England D, Doi YL, Deanfield JE, Oakley CM, Goodwin JF: Arrhythmia in hypertrophic cardiomyopathy. 1. Influence on prognosis. Br Hean J46, 168-172 (1981) 15. Maron BJ, Savage DD, Wolfson JK, Epstein SE: Prognostic significance of 24-hour ambulatory electrocardiographic monitoring in patients with hypertrophic cardiomyopathy: A prospective study. Am J Cardiol48,252-257 (1981) 16. Spirito P, Chiarella F, Carratino L. Berisso MZ, Bellotti P, Vecchio C: Clinical course and prognosis of hypertrophic cardiomyopathy in an outpatient population. N Engl J Med 320, 749-755 ( 1989) 17. Yokota Y, Seo T. Fukuzaki H: Cardiac function and prognosis in hypertrophic cardiomyopathy. J Cardiology 17(suppl XVI), 79-88 (1987) (in Japanese) 18. Uchida M, Fujiwara T, Wada T, Nakajima S, Sato H, Nakata Y, Yamaguchi H, Kawai S , Okada R, Kano T: Effect of hypertension on asymmetrical septa1 hypertrophy: An echocardiographic study. J Cardiology 18, 1043-1050 (1988) (in Japanese) 19. Suwa M, Hirota Y, Nakayama Y,Yoneda Y,Kusukawa J, Nakayama A, Kawamura K: Prevalence and clinical significance of development of conduction disturbances in patients with hypertrophic cardiomyopathy. J Cardiology 19. 147-153 (1989) (in Japanese)
