Apical hypertrophic cardiomyopathy: Clinical follow-up and diagnostic correlates

ic cardiomyopathy is a i; that is characterized by e extent of the hypertro c cardiomyopathy localized to of first described in Japan in 1974 cul , the syndrome included “giant T (2). As originally descn wave negativity” (2 10mm T wave inversion) in the precordial electrocardiogra~bic (ECG) leads associated with an angiographic spade-shaped appearance of the !eft ventricle at end-diastole due to severe hype~rophy localized to the

thy has been described in non Altbougb apical hype~rophy is o ormality, little is known of its pathophysiology or natural history. The purpo study was to extend prior observations on the mo and pathophysio~ogic features of apical hyperteophy in North American patients, with emphasis on the clinical and ECG natural history.

From the Division of Cardiology, Toronto General Toronto, Toronto, Ontario, Canada and the *Cardiovascular Research Institute, Moffitt Hospital. University of California. San Francisco, San Francisco, California. Dr. Webb’s current address is Cardiology Division, St. Paul’s ospital, Vancouver. British Columbia, Canada. This study was supported in part by the Canadian Heart Foundation, Ottawa, Ontario, Canada. Manuscript received April 24. 1989; revised manuscript received August t 23, 1989. 2, 1 : E. Douglas Wigle. MD. Cardiology Division, Toronto General Hospital, Toronto, Ontario, Canada MSG 2C4.

. Twenty-six patieantswere ~~c~~dedin the criteria were based on two-dimensional stu ecbocardiograph~c demonstration of asymmetric bypertroapex, an phy confined predominantly to the left ve apical to apical thickness of 2 15mm and a ratio of posterobasal wall thickness ~1.5 : 1. Technically adequate apical echocardiographic views were required to confirm localized apical hypertrophy with other standard views used

81990 by the American College of Cardiology

0735-10971901163.50

84

WEBB ET AL. APICAL HYPER’IHOPHIC

JACC Vol. IS. No. I January 1990:83-90

CARDIOMYOPATHY

Figure1. Patient 21. Two-dimensional apical four chamber echocardiogram demonstratingapicalhypertrophy(arrows).LA = left atrium;LV = ieft ventricle;RA = tight atrium; RV = right ventricle.

to confirm the absence of significant hypertrophy in the basal

septum or free wall (Fig. 1). One patient with inadequate echocardiographic images but with typical angiographic findings of apical hypertrophy was included in the study. Patients were seen and studied at the Toronto Genera! Hospital Hypertrophic Cardiomyopathy Clinic. Eleckocardiographicanalysis. The most recently obtained standard 12 lead ECGs were reviewed. Left ventricular hypertrophy was assessed by precordia! voltage criteria (SV, + RV52 35 mm) (9) and by the method of Romhilt and Estes (10)(point score 25). T wave amplitude was noted in a!! leads. The QT interval was measured from lead V, and was corrected (QTc)for heart rate with the method of Bazett (11). In one patient who had an apical myocardia! infarction during follow-up, only ECG findings before infarction were included in the analysis. Twenty-four patients had ambulatory ECG monitoring performed for one or more 24 h periods. Recordings were independently reviewed for the presence of atria! and ventricular arrhythmias. Ecbcardiographicstudy. Complete M-mode and twodimensional echocardiographic studies were performed with the use of standard criteria (12).Septa! and posterobasa! wall thicknesses at the level of the mitral valve leaflet tips were measured from the two-dimensional left parasterna! image at end-diastole by electronic calipers. Left atria! size was measured from the same view at end-systole. Maxima!apical thickness at end-diastole was measured from twodmrensiona! echocardiographic apical four chamber views angulated to best define endocardium and papillary muscle structures. Twenty patients were further evaluated with

Doppler echocardiography for the presence of left ventricular out!!ow tract obstruction and mitral re~rgitatio~. Nuclear magnetic resonance ients with the use of ages of the heart were obtained in a 0.15 T resistive imaging magnet (13). After initia! corona! spin-echo views were used to localize the major cardiac axes, multislice spin-echo imaging was performed along the true cardiac axis in the four chamber orientation, as we!! as along the true car c short axis. These images corresponded to standa two-dimensional echocardiographic apical four chamber and left parasterna! short-axis views. To obtain multislice images in the same relative portion of cardiac cycle, short TR (TR = time of repetition = interval) and short TE (TE = time to echo, 20 ms) techniques were used with a gate delay of 300 ms to acquire a!! image slices during diastole. dionuclidestudies. Equilibrium radionuclide ventricus were obtained in the anterior, left anterior oblique and left lateral views after in vivo labeling with technetium99m pertechnetate. Images were obtained at rest (16 patients) and during supine bicycle exercise (12 patients). Ejection fraction was calculated with use of a standa semiautomated edge detection algorithm after backgroun subtraction. Diastolic

function

studies were performed

separately

(32

frames/cardiac cycle) in 18 patients and 10 . ?*~!thysubjects. Variables assessed were the peak filling rate (stroke volumes/s), time to peak filling rate from end-systole (ms) and the relative contribution of atria! s)rsto!e to left ventricular end-diastolic volume (expressed as percent of left ventricular stroke volume). Stroke volume was used to adjust for the variations in end-diastolic volume among different subjects. The tirst derivative of the left ventricular time-activity curve was used to determine the end of the rapid filling phase and the onset of atria! systole. Values obtained were compared with those of IO healthy control subjects studied in our laboratory under identical conditions. Planar thallium perfusion studies were performed after maxima! treadmill exerckc to assess myocardia! perfusion in eight patients with undiagnosed chest pain. Postexercise and redistribution images were obtained in the anterior, left anterior oblique and lateral views. Images were reviewed by two unbiased observers and a consensus result was obtained regarding the presence of fixed or reversible perfusion defects. Cardiac catheterization. Eleven patients underwent selective coronary angiography and right and left heart catheterization for clinical purposes. This included evaluation for out!!ow tract obstruction at rest and usually with provocation (isoprotereno!, extrasystoles, amy! nitcite). Statistics. Results are expressed as mean values + SD unless o!herwise specified. Variables were compared by two-tailed unpaired Student’s t test analyses of probability.

JACC Vol. IS. No. January 1

I

Echo (mm)

Patient

Age

T Neg

(YF)

(mm)

--...

Cardiac Cat~~~~e~i~at~~~ LVEDP

Rest EF

amm Hgl

G’o)

35

33

65

41

20

7!

Arrhythmia

Apex

LA

15

AF AF

20

1

50

2

73

17 IO

3

47

12

15

46

4

45

7

20

39

5

61

17

1.5

6

55

15

7

56

8

65

9

75

IQ

33

CA

19

8

76

4.4

217

33

~

64

4.1

248

21

38

+

7

75

4.9

186

24

19

38

0

15

4

15

39

-

4.7 -

144 -

24 -

2

17

30

7

16

-

70 -

II

36

-

22

40

16

37

0 0 -

VT

II

60

3

12

71

4

13

74

11

14

59

25

18

35

15

74

6

17

41

0 -

16

71

20

20

40

-

17

41

17

21

31

18

37

5

15

37

0 -

19

18

2

24

38

-

20

35

4

19

39

-

21

45

15

23

53

22

36

16

20

44

23

52

16

48

AF

40

VTn

24

36

26

47

-

25

46

4

17

46

0

26

41

12

15

41

-

AF

AS = atria! systolic co~tr~~~t~on to left ventricular

-

-

-

68

3.3

174

31

25 -

76 -

4.3

162

24

4.1

2

18

-

65

132

21

58

4.5 -

22 -

-

-

-

-

-

4.6 -

116 -

4.5 4.9 4.1 5.3 4.4 4.8 4.1 4.7

204

15

169

17

136

32

I6

-

73 69 8

II -

60

77 75 62

c

WJ

tients (20 male, 6 female) e identified (Table I). None ean age at presentation was were of Japanese ancestry. 44.9 years (range 15 to 72) at fo~ow-up was 52.2 years. Mean follow-up duration was 7.3 2 6.2 years (range 1 to 22). Ten patients were asymptomatic and were referred with precordial T wave negativity alone. In the remaining 16 s included atypic patients, major sym tations (n = 8, es lo), angina (n = 6), (n = 5), presyncope (n = 4) acd fatigue: patients had more than one sym$om). A ily history of asymmetric se identified in two patients. Ten patients engaged in regular strenuous physical activity, whereas the remainder were sedentary. Eleven had a prior history of mild, treated systemic hypertension that was controlled on repeated clinic

21

96

IO

228

25

160

17

170

9

l&l

19

fillisg; CAD = angiographic coronary artery disease; EF = ejection fraction; LA

parasternal diameter; LVEDP = ler’; veot~cM~~ end-diastolic pressure; PFR = peak tilling rate; SV = Stroke volumes; T Neg = depth lead V,; TPFR = time to peak filling rate: VT = veatrkular tachycardia (n = nonsustained); + = present; 0 = absent: - = study not performed.

ixences were rega level 4.05.

-

20

0

10 9

AF = atrial fibrillation;

203

ofT wave

in

(n = 25), a third heati sound (n = 17)and a grade I-2/6 apical systolic rn~rrn~r(n = 12). increasingly frequent patients developed epi worsening angina, one of whom had coronary disease and had a non-Q wave . Another patient, without a rdial infarction with aneurysm history of angina, ha formation. At age 17 this patient had “giant T wave negativity” (Fig. 2, top) and angiographic evidence of marked apical hype~r~phy with normal coronary arteries (Fig. 3A). ed with sustained ve At age 33 retrosternal pressure and enzy dia assoc evidence of myocardial i~fa~ctiQ~.The ECG (Fig. 2, bo revealed loss of giant T wave negativity amplitude and persistent ST segment ele with infection and a~e~~srn formation. a~giogram (Fig. 3 ) showed a new left ventricular apical aneurysm with residual midvent~c~~ar ~~~e~ro~~y. This occurred despite not-ma!coronary arteries ds demonstrated

AGE

JACC Vol. 15, No. B :83-W January I

WEBB ET AL. APICAL HYPERTROPHIC CARDIOMYOPATHY

86

I

II

Ill

aVL

i3VR

aVF

VI

VZ

V3

I

V4

Vs

Va

re 2. Patieot 18. Seventeen year electroiographic (ECC) follow-op in a patient with apical hypertrophy and normal coronary arteries. Top,. At age 17 years, s~~w~~g left ventricular hypertrophy and precordiai giant T wave negativity. Note that lea d V, are recorded at one-half standard. ECG at age 33 years after apical myocardial infarction and aneurysm formation. T wave negativity has disappeared and the ECG reflects left ventricular aneurysm formation.

2). In one of these

en earliest and most recent precordial leads had increase ECGs were compared. Over T wave amplitude in lead V4 prog - 11.2 f 8.0 mm. Although at pre had giant T wave negativity, thre at last follow-up. Mild increases in precordial QRS voltage were also noted (SV, + RV5 increased from 32.2 f 13.6 to 38.3 & 12.8 mm). Progression of KG changes over an %8 year period in a patient with normal coronary arteries is demonstrated in Figure 4. Paroxysmal atria1 fibrillation was recorde tory ECG monitoring in four patients, all o echocardiographic left atrial enlargement (le left atrial diameter >40 mm). One patient nonsustained ventricular tachycardia and another developed recurrent sustained (>30 s) ventricular tachycardia associate All patients had normal or hyperdynamic left ventricular’systolic function and none had systolic anterior motion of the mitral valve. Maximal apical thickness averaged 18.6 2 3.3 mm (range 15 to 26). Septal thickness was 11.2 & 2.3 mm (range 7 to 15) and posterobasal thickness was 9.4 * 2.2 mm. Of the 20 patients undergoing Doppler echocardiographic studies, 6 had mild mitral regurgitation and none had obstruction to left ventricular outflow.

patients @reviously described), precordial giant T wave negativity disappearecjafier an apical myocardial infarction (Fig. 2). In the other six patients, T wave inversion in the

ies were performed in 12 patients to aid in localization of hypertrophy. Standard coronal views were generally inade-

at cardiac catheterization before and after the infarction. The remaining 21 patients remained in relatively stable condition during follow-up. No patient deveioped congestive heart

failure, had a thromboembolic event or died. Elec~ographk aualyds. At latest follow-up all patients were in sinus rhythm. The mean frontal QRS axis was 33”. Let? ventricular hypertrophy was diagnosed by precordial voltage criteria of Sokolow and Lyon (9) alone in 2 patients, by the point score system of Romhilt and Estes (10)

alone in 1 patient and by both criteria in 13 patients. In 10 patients neither criterion for hypertrophy was met. Mean QTc duration was 412 & 69 ms with prolongation @I40 ms) in seven patients, four of whom were taking a type la antiarrhythmic drug. All patients had precordial ST segment abnormalities and symmetric T waue inversion; 14 had the syndrome of “giant T wave negativity.” T negativity frequently varied in ampli-

tude on sequential EC&, even in patients without clinical or angiographicevidence of coronary disease. Maximal T wave negativity was seen in lead V4in 16patients and was seen in either lead VJ or V, in the remaining 10. Maximal T wave negativity ranged from 2 to 25 mm (mean 10.2 f 6.2). Similarly, maximal R wave amplitude was usually seen in lead V,, (n = 13)or in V5 (n = 9). in seven patients, ECGs taken more than 10 years apart were available

for comparison

(Table

Figure 3. ?atient IQ (same patient as in Fig. 2). Left ventriculograms (right anterior Gblique projection). A, At age 17 years, showing spadeshaped appearance of the left ventricle at enddiastole due to apical At age 33 years. Systolic image demonstrates a new apical aneurysm Cthe ofwhick is ~fldi~ated by residual midventricular hypertrophy.

JACC Vol. IS. No. 1 January 1 33

IC CA

Longatients Presentation

Follow-Uo

FQlbW-Up

Years . Patient

CAD

(No.)

(mm)

(mm)

(mm)

tmm~

5

t

13

15

t2

37

-17

6

0

18

45

+5

52

-20

8

10)

I4

19

-P

26

-2

IO*

0

13

4.5

-%O

21

-4

18

(0)

12

41

-2

32

-4

22

0

10

46

-6

56

-18

0

I.5

27

-3

27

-6

*Patient IO badl an apical myocardia~ in~arct~~~ S voltage and T wave riod with loss of precordia! 3). CAD = coronary aaerial disease [+ = a~~~o~rapbic abse& (0) = presumed absent in two patients witbout

dawns the ~Q~)~w-M~ ne~tivity t stenosis present: 0 = symptoms of angina

who did not undergo angiograpby!.

artery disease, whereas the ot analysis of left ventricular di

reports

(2,3)

ade-like ve~t~c~e,most

those of 10 healthy subjects (Table 1, SWR

4. Patient 5. Eighteen year electro~ardiog~phis follow-up in a patient with marked apical ~y~~~~~~y and normal coronary arteries showing progression of precordial T negativity and QRS amplitude. Rgre

have desc

Vk

&IF

VI

V2

V3

V,

V+j

Ve

WEBB ET AL. APICAL HYPERTROPHIC CARDIOMYOPATHY

88

3ACC Vol. 15, No. I :83-90 January I

Figure 5. Patient21 (same patient as

in Fig. 1).Nuclearmagneticresonance spin-echo images. A, Long-axis four chamber slice demonstrateslocalized left ventricularhypertrophyinvolving the apicalseptum,apicalfree wall and true apex (arrows).Note the spadeshaped left ventricularcavity. true cardiac short-axis basal slice shows normal left ventricular wall thickness. C, An apical slice demonstrates circumferentialhypertrophy. Abbreviationsas in Figure1.

non-Japanese reports (4-g) have described a somewhat different disease spectrum. Giant T wave negativity and a spade-like left ventricle at end-diastole was observed in 14of 26 patients in this study; thz remainder had lesser degrees of apical hypertrophy and precordial T wave negativity. Therefore, HO% of our patients appear similar to those described in Japan, suggesting that reported differences in the syndrome of apical hypertrophy are largelydue to definition and case selection.

placement or other factors. We did not observe a direct correlation between the magnitude of precordial T wave measu ents of inversion and echocardiographic or N is our mass. apical wall thickness or left ventric impression that precordial T wave negativity bears some relation not only to the amount of hypertrophy but also to the degree with which the hyF?rtrophy is limited to the true

Reiationof apical wall (tbickmssand degreeof precordialT wave negativity. This relation is controversial (4.7). Al-

history of mild controlled hypertension and of strenuous physical activity raises the possibility that elevated left ventricular wall stress and work hypertrophy may be significant etiologic factors in the development of localized apical hypetirophy in some patients. Apical hypertrophy in Japanese patients is sometimes associated with systemic hypertension (2,3). Similarly, Louie and Maron (8) reportedmild hypertension,believed to be insufficient to explain significanthypertrophy,in 5 of 23 North American patients.

though marked apical bypertrophy is usutilly associated with deep precordial T waves, this findingis nut specific and inay also be present with only mild apical hypertrophy. We found a definite increase in precordial T wave negativity in the six patients followed up for more than a decade; however, there also exists a clear day-to-day variability of T wave negativity. This variability is unlikely to reflect true changes in apical thickness and may be related to lead

Figure6. Left ventricular radionuclidetime-activity curves. A, Norma1control subject.Ventricularsystolic emptyingis rapid.Immediatelyafterend-systole (ES), counts increaserapidly, representingearly ventricular filling:counts plateauduringdiastasis.In late diastole, atrialsystolic contraction(AS) makes a furthersmall contributionto diastolicfilling.B, Apicalhypertrophy.

Systolicemptyingis normal.The peakfillingrate (PFR) is decreasedznd the time to peak fillingrate(TPFR)is prolonged.Atrialsystole(AS)contributesa largerthan normalpercentageof ventricularend-diastolicvolume. EM: = end-diastoliccounts.

TPFR!

&A 0

,ES -4s x 10 msec

---a

JAW Vol. 95, No. I

$anuary I

:a-w

I

2 as a mam~festaFicm ventricle: ec~Qca~diQ~ap~jc

et al. Giant negarive T apicalRypertrophy and ralFPasono-ca9didi,mo

Heart J P976:17:611-29. 3.

~s~~~~~ T. Nishiyama S, et al. Hypcmophic nonrdiomyopathywith giant negative “f-waves(apica!byperFropby):ve~t~~c~~~g~a~~~c and ecboca~diog~apbic features io 30pa;iCKjts. Am 5 Cardiol ~~~9;~:~~-~2.

4. Maroa BJ. Bonow RO, SasbagiriTN, Roberts WC. Epstein SE. HyperFrophiccardiomyopathywith ventricular septal hypettrophylocalizedto the aP&aF%egionOfthe FefiQenwkk (apiCa!hyptx-mphk Car&~ thy). Am 9 Cardiol 1982;49:1838-48. 5.

6.

ilmant PY. Lablanche yopatby: clinicd and

Thieuleux FA. ApicalFlyperFabok studies. Eur Heati J

eroan TL. Apicalhypert.rophic cardiomyopathyin American patients. Am HearFJ 1984;108:15OL-6.

7. Keres G. Belhassen B, Sherez9, et al. Apical hypertrophiccardiomyopathy: evaluation by noninvasive and invasive techniques in 23 patieels. CircuFaFion1985;7!:&-%I. 8. Louie EK. Marou BJ. Apical hypcrtrophiccardiomyopathy:clinical aad tw~di~ems~oma~ echocardiogtaphicassessment. Ann Intern Med 1983; 104:663-m. 9. Sokolow M, Lym TP, The ventricular complex in left ventricular Aypertrophyas obtained by onipolarprecordialand limb leads. ArmHeart 3 1949;37:163-t%. 10. RomhikDW, Testes EM. Experimental J M&58:752-8.

be responsible for complaints of dyspnea with exertion. Similarly, hi& filling pressures and increased atrial systolic contribution to ~e~t~~~~~ar fillingmay favor Leftatria1dilation and atrial fibrillation. Treatment of diastolic dysf~~~tio~has and, despite reports of benefit from calcium g agents (Z--27), we have not observed a consistent beneficial response to these agents in our patients with apical ~y~e~ro~~y. s. The tiyndnme of kwdize

and laboralory

reports.

Am

II. Ahnve S. Correction of the QT interval for heart rate: reviewof different formulas and the use of Bazelt’s foormulain myocardialinfarction. Am Heart J 1985;1Q9:568-74. 12. FeigenbaumH. Echocardiography.4th ed. Philadelphia:Lea & Febiger, 1986~624. 13. Higgins CB, Byrd BF, Stark D. et al. agnetic resonance imagingim hypertrophiccardiomryopathy.Am J Cardiol 1985:55:1121-6. 14. Wigle ED. Marquis Y, Auger P. Muscularsubaortic stenosis: initial left ventricular inflow tract pressure in the assessment of intravemtricular pressuredifferencesin man. Circulation 1%7;35:I Ml-7. 15. Maron BJ, Epstein SE, Roberts WC, HypertrophiccardiomyopaFhyand transmuualmyocardialFrUction withoutsigoiikamtatherosclerosisof the extramuralcoronary arterizs. kn J Cardi 16. Cannon RG, Rosieg DRJWOII SJ, et a!. trophic cardiomyopathy contribution of inadequate vimdilator resewe and elevated left ventricular pressurt? Circulation 1985;71:234-43.

ischemia in the absence of large vessel coronary artery disease as well as for diastotk dysfunction. Atrial arrhythtias may occur and appear related to atrial dilation, and

RCJ,CamnonSO, Leon MB,EpsFeinSE. Hypertrophic ;7. Earor, BJ, Boao_i* cardiomyopathy:interrelations of chmicaimanifesbtions. pathophysiology and therapy (Part 1). N Engl J Med 1987;3163780-9.

90

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18. MaronBJ, BonowRO, Cannon RO, Leon MB,Epstein SE. Hypertrophic cardiomyopathy:interrelations of clinical manifestations, pathophysiol08y and therapy (Part II). N Engl I Med 19B7;316%l4-52. 19. Opherk D, Mall G. Zebe H, et al. Reduction of coronary reserve: a mechanismfor aqina pectoris in patients with arterial hypertension and normal coronary arteries. Circulation 1984;69: l-7. 20. MarcusML, HarrisonDC, Chilian WM.et al. Alterationsin the coronary circulationin hypertrophiedventricles. Circulation1987;75(suppl&I-1825. 21. MarcusML, DotyDB, Hiitzka LF, Wright CB, EasthamCL. Decreased coronary reserve: a mechanismfor angina pectorisin patients with aortic stenosis and normal coronary arteries. N End J Med 1982;307: 1362-6. 22. Maron BJ, Wolfson IK, Epstein SE, Roberts WC. Intramural (“small vessel”) coronary artery disease in hypertrophiccardiomyopathy.J Am Coil Cardiol 1986;8:545-7.

JACC Vd. 15, No. )i January I :83-90

23. Wigle ED, Wilansky S. Diastolicdysfunction in hypertrophiccardiomyopathy. Heart Failure 1987;3:82-93. 24. Lorell BH, Grossman W. Cardiac hypertrophy: the consequences for diastole. J Am Coil Cardiol 1987;9:1189-93. 25. Fouad FM. Left ventricular diastolic function in hypertensive patients. Circulation 19?3$7;75(SupplI):1-48-55. 26. Bonow RO, Frederick TM, Bacharach SL, et al. Atrial qstole and left ventricular filling in hypertrophic cardiomyopathy: effect of verapamil. Am J Cardiol 1983;51:1386-91. 27. Iwase M, Sotobata 1. Takagi S, Miyaguchi K. Xiao Jing H. Yokota M. Effectsof diltiazemon IeR ventricular diastolic behavior in patients with hypertrophic cardiomyopathy:evaluation with exercise pulsed Doppler echocardiography.J Am Coil Cardiol 1987;9:lQ99-105.