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Coexistent aortic valvular and functional hypertrophic subaortic stenosis
Clinical
Studies
Coexistent
Aortic Valvular
Hypertrophic Clinical, DAVID
Subaortic
Physiologic
and Functional. Stenosis
and Angiographic
Aspects*
P. PARKER, M.D., MARVIN A. KAPLAN, M.D. and JOHN E. CONNOLLY, Irvine,
M.D.
California
Four cases of coexistent aortic valvular stenosis and functional subaortic stenosis are presented. The first patient died of low cardiac output after replacement of the aortic valve, and concomitant subvalvular hypertrophy was discovered at autopsy. Patients presenting clinically with aortic valvular stenosis were subsequently challenged with isoproterenol at cardiac catheterization. Three had hemodynamic evidence of subaortic functional hypertrophy and aortic valvular stenosis. Postextrasystolic beats were also indicative of subaortic stenosis in these cases. All had angiographic evidence of subaortic functional hypertrophy and, in 1, confirmation was obtained at postmortem examination. These studies indicate: (1) patients with both conditions appear clinically to have valvular stenosis; (2) all patients with apparent aortic stenosis should be studied with isoproterenol at catheterization; (3) patients with both lesions should be treated with propranolol; and (4) if this treatment does not result in improvement, then the subvalvular narrowing should be carefully evaluated and relieved at the time of valvular operation.
10 per cent of patients with severe aortic valvular stenosis have functional hypertrophic subaortic stenosis.’ The coexistence of these lesions has been demonstrated at operation,24 after operationSs5m7 or at postmortem examination1,3 but has not been documented before these procedures. It is important to recognize both lesions when they occur together since surgical treatment for aortic valvular stenosis alone may leave the patient with significant functional subaortic narrowing and, thus, the expected postoperative improvement may not occur or the patient’s condition may deteriorate clinically or hemodynamically, or both.2,3,5 This study was undertaken following the postoperative death of a patient with severe
I
T HAS BEEN ESTIMATED that
calcific aortic valvular stenosis who was found at postmortem examination also to have marked subvalvular hypertrophy.8 It is not the purpose of this report to describe the differential diagnosis between aortic valvular and functional hypertrophic subaortic stenosis. Many excellent reviews have appeared on the latter.6,‘sg We wish to emphasize that (1) the two lesions probably coexist more commonly than is realized; (2) the diagnosis of functional hypertrophic subaortic stenosis is masked when aortic valvular stenosis is presen@; (3) certain clinical features should arouse a suspicion that both lesions are present; and (4) certain simple methods will improve the accuracy of diagnosis during cardiac catheterization and angio
* Fmn the Departments of Medicine and Surgery, the Long Beach Veterans Administration Hospital, Long Beach, Calif., and the University of California at Irvine, Irvine, Calif. Manuscript received August 8, 1968, accepte.d January 7, 1969. Address for reprints: Marvin A. Kaplan, M.D., Cardiology Section, Veterans Administration Hospital, 5901 E. 7 St.. Long Beach, Calif. 90801. VOLUME
24, SEPTEMBER1969
307
Parker
308
both lesions are described herein. Three of the 4 were diagnosed by catheterization. METHODS Phonocardiograms, apex cardiograms and external carotid arterial pulse tracings were made on a Sanborn-Hewlett Packard 350 Series multiple channel recorder or an Electronics for Medicine DR8 recorder. A Sanborn dynamic microphone or, in the case of the Electronics for Medicine recorder, a Cambridge dynamic microphone was used. The apex cardiograms and carotid arterial pulse tracings were made with use of a pulse wave crystal microphone (Sanborn No. 374). When the Electronics for Medicine recorder was used, the apex and carotid tracings were obtained with a Statham P58 strain gauge. The ejection time in the external carotid tracings was corrected by the method of Weissler et al.10 as follows: ETc = ET plus (0.0017 times heart rate) for male subjects; for female subjects 0.0016 was substituted. Normal values for men are 0.418 & 0.01 sec. and for women 0.413 -F- 0.01 sec. The upstroke time was measured from the beginning of the carotid arterial pulse rise to the highest peak. Correction for heart rate was made by dividing the measured value by the square root of the R-R interval. Normal values are 0.088 + 0.013 sec.5 Right and left heart catheterizations with pressure measurements and cardiac output determinations were performed on all patients. Pressures were measured with Statham P23Db strain gauges and an Electronics for Medicine DRS recorder. The cardiac output determinations were performed by the Fick method. Expired air was analyzed on the Scholander apparatus, and blood oxygen capacity was determined on the Van Slyke apparatus. Pulmonary arterial and aortic oxygen saturation determinations were made on the Beckman DU spectrophotometer. Simultaneous pressure measurements were recorded from the left ventricle and aorta or femoral artery before and during the intravenous administration of isoproterenol (2 mg. in 500 cc. of 5 per cent dextrose in water, at a rate of 4 pg./min.). In two instances the left ventricle was catheterized by the transseptal route using the technic of Brockenbrough and Braunwald.11 In the other 2 cases, the left ventricle was entered retrograde across the aortic valve from a brachial artery cutdown site. Each patient was studied with a left ventricular angiogram performed in the left and right anterior oblique positions and a supravalvular injection in the left anterior oblique position; 75 per cent Hypaque-M@ was used in volumes of 40 cc. Pressure injections were made at a pressure of 350 Ib./sq. in. using either a Tavaris or a Gidlund pressure injector. Three patients underwent selective coronary angiography by the Judkin’s technic.12
et al. RESLJLTS Table I details trocardiographic patients.
the historical, physical, elecand x-ray findings on all
HISTOKY
Two of the 4 patients had a history of rheumatic fever and 2 were not certain of such a history. All had dyspnea and chest pain. The chest pain was that of typical angina in 2 patients and of atypical angina in 1; it was thought to be nonanginal in the fourth. Syncope was noted by 2 patients and near syncope by a third. Dizziness was experienced by 3 of the 4 patients. Orthopnea was not present in any patient, but 1 had had paroxysmal nocturnal dyspnea; another had had peripheral edema. There was a positive family history of sudden death at a young age in 2 patients. SIGNS ON
PHYSICAL EXAMINATION
Two of the patients showed signs of left ventricular hypertrophy. This assumption was made when the apex was displaced laterally and downward and when it was more propulsive than the usual. A bisferiens peripheral pulse was noted in 2 of the 4 patients, and 3 showed a typical pulsus parvus et tardus. A double peaked apex which was prolonged was palpated in Patient 1. A systolic thrill was present at the aortic area in all 4 patients. An ejection click ‘and a fourth heart sound were heard in Patient 1 but not in the other patients. All patients had a loud (grade 4/6) systolic murmur of the ejection type heard at the aortic area which radiated well to the left sternal border and to the neck. Three of the patients had clear-cut early diastolic decrescendo blowing murmurs. ELECTROCARDIOGRAPHICFINDINGS Two patients had increased voltage in the precordial leads and ST-T changes consistent
with left ventricular hypertrophy. The other 2 patients had no criteria which made a diagnosis of left ventricular enlargement possible. Of these 2, 1 showed left atria1 enlargement; the other had a tall R wave in lead VI with an RS ratio greater than one. X-RAY FINDINGS Two of the 4 patients had x-ray findings consistent with either left ventricular enlargement or a prominent left ventricular border. Two THE AMERICANJOURNALOF
CARDIOLOGY
LAortic Valvular
and Hypertrophic Table
Patient
I.
1
_ ..__
Clinical
Suhaortic
309
Stenosis
Data
Patient 2 --
Patient
3
Patient 4
HIJ/Oly Known rheumatic fever Dizziness Syncope Chest pain ‘Typical angina .\typical angina Nonanginal Exertional dyspnea Orthopnea Paroxysmal nocturnal dyspnra Edema Family history of heart disease or sudden death
+
13 yr. -
+
3 yr.
-
6 yr. + -
+ + -
13 yr. -
-
-
Brother died, age 39
Father died, age 47
+
5 mo.
+ Recent + + _ +* -
3
Recent Near syncope Recent + + + -
-
P/w&z1 Signs
Pulse (carotid) Bisferiens Slow rise Slow downstroke .\pex Double-peaked Prolonged Left ventricular hypertrophy Thrill .\uscultation .Murmurs Systolic Diastolic Ejection click Fourth heart sound
-
+ + -
+ + + +
T + -
-
: -
Left ventricular hypertrophy Left atria1 enlargement Tall R in Lead VI
+ _
_ +
+ -
.Y-rq Findings Left ventricular enlargement .\ortic dilatation .\ortic calcification
+
-
+ + +
Electrocardiogram
-
* \liith atria1 fibrillation.
showed definite poststenotic dilatation of the proximal aorta and 3 had dense (4+) calcification of the aortic valve.
E~~~~~LTRACINGS(TABLEIIANDFIG
1)
All 4 patients had a typical high frequency systolic murmur of the ejection type recorded best at the aortic area. Third and fourth heart sounds as well as an ejection click were noted in Patient 1, but the other patients did not have these findings. Carotid Tracings: The rise time was prolonged in the 3 patients in whom it was measured; the ejection time was prolonged in 2 of these 3 and at the upper limits of normal in Phonocardiograms:
VOLUME
24, SEPTEMBER
1969
the third. A bisferiens pulse was recorded in !l patient. A systolic shudder was noted in the external carotid tracing in 2 of the 3 patients whose tracings were technically satisfactory. Patient 1, although he had a palpable thrill, did not have a noticeable shudder on the carotid tracing, and it may be that this was because the tracing was recorded through a strain gauge which was not capable of picking up the higher frequencies. Apex Tracings: An abnormally large A wave (20 per cent or more of the succeeding E-O ratio) was found in 1 patient, and 1 showed a late systolic bulge in the apex tracing. Three demonstrated a prolonged E point in the apex tracing: 1 did not.
Parker et al. Table
II. Findings on Phonocardiograms, Indirect Carotid Tracings and Apex Cardiograms Patient
Phonocordiogram Murmurs
Systolic ejection
sa s4 Ejection click Carotid tracing Rise time(c) Ejection tilllC(C)
Bisfericns “Shudder” Apa .l wave Systolic bulge Prolonged
1
Patient
2
Patient
3
+ +
Systolic ejection -
Systolic ejection -
+
-
-
Patient
Systolic ejection -
AF
-
0.28 sec.
0.27 sec.
0.17 sec.
TITM
0.51 sec. -
0.46 sec.
0.42 sec.
TITM
- *
7
7
Present, not increased
-
AF
4
Table LU.
+ TITM
-
Present, increasedt
;
* = recorded through strain gauge. t = amplitude of a 20% of EO. AF = atria1 fibrillation; (c) = corrected;
TITM
=
technically
im-
possibleto measure. ANGIOGRAPHIC
FINDINGS
The angiographic findings are shown in Table III and Figures 2 to 6. All 4 patients showed a very small systolic volume of the ,-I I I I
Angiographic
Patient
E
left ventricular cavity. Three had left ventricular angiograms in both oblique views; 1 had a right anterior oblique view only. Of the former, 2 had tongue-like projections characteristic of subaortic stenosis and all 3 had an infundibular chamber. Narrowing of the outflow tract was seen in all three. One patient had concomitant mild mitral insufficiency.
Cavitv size “Ton&“-like projection Infund. chamber O.F.T. narrowing MI Coronary artery disease Right Left Papillary muscle hypertrophy AI
1
Patient
2
Findings Patient
3
Small
-
-
Minimal
Severe,
+ 2+
LAD
+ 2+
Patient
S”ldl
-
* *
+ -
* *
_
*
2+
*
+
*
2+
*
* Parameters could not be evaluated bccausc of lack ot sufficeint views. AI = aortic insufficiency; LAD = left anterior descending; MI mitral insufficiency; O.F.T. = outflow tract.
I 1 t III I I I I I t I I I I I I I I I I: I t I
. ..
:
AORTIC
AREA
4
50 CPS
APEX CARDIOGRAM
1. Case 2. External phonocardiograms and arterial tracing. A, phonocardiogram at aortic area and indirect carotid tracing. Note the typical systolic murmur of the ejection type and the diminished A, in the phonocardiogram. The carotid tracing shows a prolonged ejection time (0.46 set). B, phonocardiogram and apex cardiogram; the latter shows a prolonged E point. (Time lines = 0.04 sec.)
Figure
THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Figure
2.
Case 2. Left ventricular left anterior oblique view. A shows opaque material filling the body of the left ventricle (LVB) and the infundibular chamber (IC). A tongue-like projection (TLP) is also seen. B (several frames later) demonstrates sequential filling of the aorta (Ao) and mitral insufficiency. LA = left atrium: MV = mitral valve. C is a drawing of frame B. nngiograln,
C
Marked papillary muscle hypertrophy was evident in all the angiocardiograms, and 3 of the 4 patients demonstrated some aortic insufficiency. Calcium was present in three of the four aortic valves, and 1 subject (Patient 3) showed a thickened and rigid aortic valve which did not move well. Concomitant Coronary Disease (Table III): Selective coronary angiocardiography revealed severe disease of the anterior descending coronary in 1 patient and marked disease in all branches of the left coronary artery in another. PHYSIOLOGIC
DATA
Table IV details the cardiac catheterization findings. Patients 2 and 3 showed minor gradients across the pulmonic valve and Patient 3, in addition, showed a restrictive pattern (“square root sign”) in the right ventricle. The right ventricular diastolic pressure was normal in all patients. Systolic gradients were present across the aortic valve in all 4 patients. The cardiac index was reduced in 2 of the four. It was possible to demonstrate a subvalvular gradient before the use of isoproterenol within the body of the left ventricle in 2 patients (Fig. 7). Effect of Zsoproterenol: As can be seen from Table IV, the 3 patients who were studied with VOLUME
24,
SEPTEMBER
1969
Figure 3. Case 2. Supravalr~nlar injection. Aortic insufficiency is demonstrated. The infundibular chamber is present above the narrowed area formed by the anterior mitral leaflet (a) and the interventricular septum (b) bulging into the left ventricular outflow tract.
an infusion of isoproterenol (2 mg./500 cc. of 5 per cent glucose in water) showed the typical response diagnostic of functional hypertrophic subaortic stenosis; the left ventricular cavity systolic pressure rose while the peripheral arterial systolic pressure fell (Fig. 8). Patient 1, just before administration of isoproterenol, exhibited a systolic gradient of 59 mm. Hg. Isoproterenol increased the gradient to 79 mm. Hg, and the peripheral arterial pressure fell
312
Parker Table Patient
RA RV PA PPC LA LV Body Subvalve Aorta CI Isuprel LV FA LV FA
1
3; t20 28/3 28/12
Data*
Patient 2
Patient 3
Patient
4
8 36/2-11 32/10 14
151/8-15 119/8-15 119/54 2.2
262/10 D = 18
146/66 2.67
180/O; t207/12 152/O 107/59 2.2
126/14 67/43 143/14 64/35
172/4 115/60 224/O 76/34
151/13 119/52 185/3.3 102!45
: : i
182/6 (3-19) 146/66 199i? 136/?
190/4 115/56 209/4 100/43
W2/6;
Tl26/20
StudJ,
Effect ofPVC LV (before PVC) Aorta or FA (before PVC) LV (post PVC) Aorta or FA (post PVC)
Physiologic
4; t3 33/3 24jlO (14) 8 t14
6; j21
(control) (control) (with Isuprel) (with Isuprel)
IV.
et al.
5 36/5 36/12 13
(sq. rt.)
; 04/70 4.4
i
: : : :
* All values in mm. Hg except cardiac index (CI) (L./min. per M.2). t After Hypaque study. $ Not performed. CI = cardiac index; FA = femoral artery; LA = left atrium; LV = left ventricle; PA = pulmonary artery; PPC = peripheral pulmonary capillary wedge pressure; PVC = premature ventricular contractions; RA = right atrium; RV = right ventricle; sq: rt. = square root sign.
slightly. Patient 2 showed a systolic gradient of 57 before and 148 mm. Hg during the administration of isoproterenol. The femoral arterial systolic pressure fell 39 mm. Hg as the gradient across the aortic valve rose from 57 to 148 mm. Hg. Patient 3 showed a control systolic gradient of 32 mm. Hg between the left ventricle and femoral artery. Wisth isoproterenol this gradient rose to 8.3 mm. Hg while the systolic pressure in the femoral artery fell 17 mm. Hg. Two patients showed typical responses to induced premature ventricular contractions as we1113 (Table IV; Fig. 9 shows a typical example). SURGICAL
AND AUTOPSY
FINDINGS
Patient 4 died after operation and an autopsy was subsequently performed. The pertinent details of the operative and autopsy reports are presented below: “Following aortic Starr [-Edwards] valve replacement, the patient was weaned from the pump but it was evident that the left ventricle would not take over. It wlas also evident that the aortic valve was not opening and closing under the amount of pressure the left ventricle could exert.” After the patient was found not able to tolerate removal from total bypass, he was placed on left heart by Patient
4:
As mentioned,
pass. Later
in the day he was again placed on total bypass and a right ventriculotomy was performed. “An enormously hypertrophied interventricular septum was identified. A large amount of muscle the septum to was then resected. . . allowing protrude into the right ventricle.” The left ven tricular cavity was then explored and “it was found to be enormously hypertrophied throughout, involving the papillary muscles. . . In spite of all efforts, low cardiac output continued with subsequent demise.” At autopsy (Fig. 10) the heart weighed 620 p-m. The right ventricular wall was 0.5 cm. in thickness
and the left ventricular wall measured 2.0 cm. A Starr-Edwards aortic valve prosthesis with a mobile hall was in place. When the heart was opened the ventricular septum was noted to he markedly thickened. Th’e right ventricular cavity was very small because oC this thickening of the septum which compromised the right ventricular lumen. The papillary muscles of the left ventricle were markedly hypertrophied.
Pntient I: This patient died while straining at stool. The cardiac findings at autopsy showed that the heart weighed 750 gm. and appeared somewhat enlarged. The thickness of the right ventricular wall measured 4 mm. and that of the left measured 15 mm. Valvular measurements were normal except for the aortic valve which was stenotic THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Aortic
Valvular
and Hypertrophic
Subaortic
wa5 IO per cent narrowing nal-v artery by atherosclerotic
1‘11~ tional
cliffercrl
313
Stenosis
tial
ot the lrft changes.
diagnosis
IlyfxWrophic
szrbaortic
main
coro-
l~('lii1('('17
fil;vc-
.stmo.sis
and
on the basis of liistor\ and physical examination is difficult, as has been pointed out previously.G~i~l~ The arterial pulse is of great importance, showing a rapid rise and a bisferiens quality in. functional hypertrophic subaortic stenosis; the pulse of valvular stenosis is slow rising with an anaerotic notch and a slow fall.5~r~15~1(~ In a series of 126 cases of idiopathic hypertrophic sul,aortic stenosis, 9 per cent showed a prolonged upstroke time, and it was therefore concluded that this finding does not negate this cliagnosis.li As can be seen in the 4 cases presented, the coexistence of both lesions led to the physical findings of aortic valvular stenosis. The phonocardiograms, apex cardiograms and arterial pulse tracings also were characteristic aortic
ualuular
stenosis
Figure 4. Case 1. Left ventricular angiogram, left anterior oblique view. A demonstrates apposition of the anterior mitral leaflet and the bulging interventricular septum producing an infundibular chamber. B is a drawing delineating the structure more clearly. DAo = descending aorta.
and heavily calcified. The aortic annulus measured 10 cm. in circumference and the valvular orifice was 7 cm. in circumference. The valvular orifice was ellipsoid in shape and measured 3 by 1 cm. The valve appeared bicuspid. Several small whitish pockets were seen in the endocardium of the left ventricular cavity beneath the left anterior coronary leaflet (insufficiency pockets). Several small white scars were noted in the free left ventricular wall. The septal wall was markedly hypertrophied and a prominent ridge was present at its superior aspect. Between this ridge and the aortic valve was a depression (subvalvular chamber, Fig. 11). The anterior leaflet of the mitral valve abutted against the hypertrophied region. Both mitral leaflets
showed minimal thickening, and there was equivocal thickening of a few of the chordae tendineae. The left ventricular chamber was not dilated. There was moderate hypertrophy of the papillary muscles and columnae carneae of the left ventricle. The right coronary artery was widely patent: there VOLUME
24,
SEPTEMBER
1969
B injection, left anFigure 5. Case 1. Supravalvular terior oblique position. Aortic insufficiency is seen and demonstrates the same structures as shown in Figure 4.
314
Parker
et al.
Fi&qre 6. Case 1. Left uentriculogram. A, right anterior oblique view. Arrows indicate hypertrophy of both papillary muscles and minimal residual cavity size of the left ventricle in systole. B, left anterior oblique view. Arrow indicates the infundibular chamber. Also seen is the nearly obliterated left ventricular cavity in systole.
of aortic valvular stenosis, showing prolonged ejection and rise times in the carotid tracings of 3 cases, a carotid shudder in 2, and a prolonged E point on the apex cardiogram in three. None exhibited a bisferiens pulse in the carotid tracing; 1 showed a systolic bulge in the apex cardiogram, but the patient had no other features of functional hypertrophic subaortic stenosis (although perhaps the significance of this finding was overlooked). Subvalvular obstruction was thus masked by aortic valvular stenosis. Conventional x-ray examination further strengthened the diagnosis of the latter by showing calcification of the aortic
valve in 3 and dilatation of the aortic root in two. Electrocardiographic findings of left ventricular hypertrophy or left atria1 enlargement, or both, may be common to both conditions and do not lead to a suggestion that aortic valve stenosis and functional hypertrophic subaortic stenosis coexist. In general, it appears that the diagnosis of both lesions in the same patient on the basis of history, physical electrocardiograms, findings, phonocardiograms, apex cardiograms, carotid artery pulse tracings and routine radio,graphic procedures is not possible. Features Suggesting Coexisting HyperAORTA
Figure 7. Case 2. Pullthrough tracing from left ventricle to aorta showing an intermediate chamber between the free left ventricular cavity (LV) and the aorta. There is also a systolic gradient across the aortic valve. THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Aortic LVI'I
Valvular
and Hypertrophic
LV & "FA - CONTROL
Subaortic LV&FA
! !I/
Stenosis
WITH ISUPREL
FA
Figure 8. Case 2. Effect of isoproterenol. Control tracing of the left ventricular (Lv) and femoral arterial (FA) pressures (lefipank) and the response to is
Subaortic Stenosis: In the presence of typical physical, graphic and x-ray findings of aortic valvular stenosis, certain features may suggest that functional hypertrophic subaortic stenosis is also present. Of all the factors, a prolonged history of syncope or dizziness, or both, in the presence of outflow tract obstruction suggests that the symptoms should not be attributed to aortic valvular stenosis alone since this disease usually pursues a relatively short course once it becomes symptomatic. Furthermore, spontaneous decrease or cessation of the symptoms for variable periods of time in a patient with aortic valvular stenosis should raise the suspicion that functional hypertrophic subaortic stenosis also exists.7vl7 Although not noted in our patients, if digitalis or nitroglycerine worsens the symptoms in a patient with aortic valve stenosis, functional hypertrophic subaortic stenosis should be suspected as also being presen,t.T A tall R wave in lead VI of the electrocardiogram, as has been previously shown, may indicate septal hypertrophy in muscular subaortic stenosis.18 This finding in the presence of the clinical picture of aortic valvular stenosis should raise the possibility of accompanying functional hypertrophic
VOLlIME
24,
SEPTEMBER
1969
I,
,:
LV
Figure
PVC
9.
FA
Case 2. Effect of premature zwztricular (PVC). Simultaneous left ventricular and femoral arterial tracings showing typical postextrasystolic increase in the gradient as a result of an increased ventricular systolic pressure and a decreased aortic systolic pressure.
contraction
Parker et al,
Figure 10. Case 4. Autopsy specimen demonstrating left ventricular thickening and hypertrophied papillary muscles. The prosthetic aortic valve has been removed. The arrow points to the subvalvular hypertrophy of the septum; a chamber is seen above this area.
trophic subaortic stenosis (Patient 3, Table I). The absence of x-ray findings of proximal aortic dilation7 or aortic valvular calcification,* or both, in a patient with the physical findings of aortic valvular stenosis should also point to coexistent functional hypettrophic subaortic stenosis. Further hinlts of the simultaneous presence of both lesions may be found at the time of cardiac catheterization. A patient with aortic valvular calcification and a significant gradient between the left ventricle and aorta would not be expected to show also a gradient be-
Figure 11. Case 1. Autopsy specimen. The calcified aortic valve is seen. Below this is a markedly hypertrophied area of the septum (arrows). Again, the left ventricular wall is thickened and there is papillary muscle hypertrophy.
tween the right ventricle and puhnonary artery. It is well known that many patients with idiopathic hypertrophic subaortic stenosis alone will show right-sided gradients of var)ing severity. 17,1V Therefore, any right-sidctl gradient should arouse the suspicion of septal hypertrophy and functional hypertrophic subaortic stenosis, as shown by Patients 2 and 3 in this study. Another suggestive finding during heart catheterization is a drop in peripheral blood pressure during the beat after a compensatory pause created by a premature beat’3 as was noted in 2 of our patients. The catheter should be drawn from the body of the left ventricle to the aorta very slowly while one is searching for a subvalvular chamber. On the basis of our experience we believe that even if a subvalvular chamber is not demonstrated, all patierrts with aortic valvular stenosis should have an isoproterenol study performed with simultaneous pressures being measured in the left ventricle and a systemic artery. This is important because: (1) the subvalvular hypertrophy may be situated too close to the valve to permit demonstration of a chamber,as14 and (2) the hypertrophy may not be functionally apparent at the time of routine study.T,*O Management: The patient with aortic valvular stenosis who is treated surgically may fail to make the expected improvement or a low cardiac output may develop postoperatively and he may die if an accompanying functional hypertrophic subaortic stenosis has been overlooked. Cases have been cited in which the gradient from the left ventricle to the aorta did not decrease significantly or actually increased after surgical treatment for the aortic valvular stenosis. This is due to an accompanying unrecognized functional hypertrophic subaortic stenosis.*Jv5 Theoretically a beta adrenergic blocking drug must be expected to produce a favorable effect on the course of muscular subaortic stenosis. We believe that treatment in individuals with both aortic valvular stenosis and functional hypertrophic subaortic stenosis should be conservative initially, employing the use of a beta adrenergic blocking agent such as propranolol. It would appear reasonable to assume that if the functional hypertrophic subaortic stenosis is relieved, symptoms would improve in some patients whose valvular stenosis is not yet severe enough to require operation. Should there be no signifi’can’t improvement with the use of a THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Aortic
Valvular
and Hypertrophic
beta adrenergic blocker, the surgeon should be alerted to the presence of both lesions and should he prepared to remove the subvalvular hypertrophy at the same time that the aortic valvr is replaced.*
VERSKA, J.
9. ;\DDENlXJM
Since acceptance of this manuscript, we have studied 6 additional patients whose clinical and hemodynamic profile is substantially the same as that of the 4 patients presented. The data of these patients and their implications provide the basis of an on-going study we are currently carrying out to determine the frequency and significance of the concomitance of aortic valvular stenosis and functional hypertrophic subaortic stenosis.
10.
11.
12.
13.
REFERENCES 1. HUNT, J. W., JR. and LOCUE, R. B. The Heart, Arteries and Veins, p. 579. New York, 1966. McGraw-Hill. 2. BROCK, R. Functional obstruction of the left ventricle (acquired aortic subvalvular stenosis). Guyi Hosp. Rep., 106221, 1957. 3. GORDON, 0. S. The surgical management of congenital supravalvular, valvular, and subvalvular aortic stenosis using deep hypothermia. J. ThoI-c&c & Cnrdiovns. Szrrg., 43:141, 1962. 4. ELLIS, F. H., JR., ONCLFY, P. A. and KIRKLIN, J. W. Results of surgical treatment for congenital aortic stenosis. Circulation, 25:29, 1962. 5. BENCHIMOL, A., LEGLER, J. F. and DIMOND, E. G. The carotid tracing and apexcardiogram in subaortic stenosis and idiopathic myocardial hypertrophy. Am. J. Cnrdiol., 11:427, 1963. 6. HANCOCK, E. W. Differentiation of valvar, subvalvar and supravalvar aortic stenosis. Guy’s Hosp. Rep., llO:l, 1961. 7. BRAUNWALD, E., LAMBREW, C. T., ROCKOFF, S. D., Ross, J. and MORROW, A. G. Idiopathic hypertrophic suhaortic stenosis: Description of the disease based upon an analysis of 64 patients. Cirrtrlntion, 30 (Suppl IV):~,1964. 8. CONNOLLY, J. E., KAPLAN, M. A., PARKER, D. P. and
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Subaortic
14. 15.
16. 17.
18.
19.
20.
Stenosis
317
The muscle-bound heart: Danger of aortic valve replacement in the presence of COILcomitant functional subvalvular muscular hypertrophy. In: Prosthetic Heart X’altes. \‘ol. 2, chap. 3, pp. 741-753. Springfield, Ill., 1969. Charles C I‘homas. PERLOFF, J. K. Clinical recognition of aortic stenosis. The physical signs and differential diagnosis of various forms of obstruction to left ventricular outflow. Progr. Cardiovas. LG., 10:323, 1968. WEISSLER, A. M., HARRIS, W. S. and SCHOENFELD, C. D. Systolic time intervals in heart failure in man. Circulation, 37:149, 1968. BROCKENBROUGH, E. C. and BRAUNWALD, E. A new technic for left ventricular angiography and transseptal left heart cathereriration.
Studies
Coexistent
Aortic Valvular
Hypertrophic Clinical, DAVID
Subaortic
Physiologic
and Functional. Stenosis
and Angiographic
Aspects*
P. PARKER, M.D., MARVIN A. KAPLAN, M.D. and JOHN E. CONNOLLY, Irvine,
M.D.
California
Four cases of coexistent aortic valvular stenosis and functional subaortic stenosis are presented. The first patient died of low cardiac output after replacement of the aortic valve, and concomitant subvalvular hypertrophy was discovered at autopsy. Patients presenting clinically with aortic valvular stenosis were subsequently challenged with isoproterenol at cardiac catheterization. Three had hemodynamic evidence of subaortic functional hypertrophy and aortic valvular stenosis. Postextrasystolic beats were also indicative of subaortic stenosis in these cases. All had angiographic evidence of subaortic functional hypertrophy and, in 1, confirmation was obtained at postmortem examination. These studies indicate: (1) patients with both conditions appear clinically to have valvular stenosis; (2) all patients with apparent aortic stenosis should be studied with isoproterenol at catheterization; (3) patients with both lesions should be treated with propranolol; and (4) if this treatment does not result in improvement, then the subvalvular narrowing should be carefully evaluated and relieved at the time of valvular operation.
10 per cent of patients with severe aortic valvular stenosis have functional hypertrophic subaortic stenosis.’ The coexistence of these lesions has been demonstrated at operation,24 after operationSs5m7 or at postmortem examination1,3 but has not been documented before these procedures. It is important to recognize both lesions when they occur together since surgical treatment for aortic valvular stenosis alone may leave the patient with significant functional subaortic narrowing and, thus, the expected postoperative improvement may not occur or the patient’s condition may deteriorate clinically or hemodynamically, or both.2,3,5 This study was undertaken following the postoperative death of a patient with severe
I
T HAS BEEN ESTIMATED that
calcific aortic valvular stenosis who was found at postmortem examination also to have marked subvalvular hypertrophy.8 It is not the purpose of this report to describe the differential diagnosis between aortic valvular and functional hypertrophic subaortic stenosis. Many excellent reviews have appeared on the latter.6,‘sg We wish to emphasize that (1) the two lesions probably coexist more commonly than is realized; (2) the diagnosis of functional hypertrophic subaortic stenosis is masked when aortic valvular stenosis is presen@; (3) certain clinical features should arouse a suspicion that both lesions are present; and (4) certain simple methods will improve the accuracy of diagnosis during cardiac catheterization and angio
* Fmn the Departments of Medicine and Surgery, the Long Beach Veterans Administration Hospital, Long Beach, Calif., and the University of California at Irvine, Irvine, Calif. Manuscript received August 8, 1968, accepte.d January 7, 1969. Address for reprints: Marvin A. Kaplan, M.D., Cardiology Section, Veterans Administration Hospital, 5901 E. 7 St.. Long Beach, Calif. 90801. VOLUME
24, SEPTEMBER1969
307
Parker
308
both lesions are described herein. Three of the 4 were diagnosed by catheterization. METHODS Phonocardiograms, apex cardiograms and external carotid arterial pulse tracings were made on a Sanborn-Hewlett Packard 350 Series multiple channel recorder or an Electronics for Medicine DR8 recorder. A Sanborn dynamic microphone or, in the case of the Electronics for Medicine recorder, a Cambridge dynamic microphone was used. The apex cardiograms and carotid arterial pulse tracings were made with use of a pulse wave crystal microphone (Sanborn No. 374). When the Electronics for Medicine recorder was used, the apex and carotid tracings were obtained with a Statham P58 strain gauge. The ejection time in the external carotid tracings was corrected by the method of Weissler et al.10 as follows: ETc = ET plus (0.0017 times heart rate) for male subjects; for female subjects 0.0016 was substituted. Normal values for men are 0.418 & 0.01 sec. and for women 0.413 -F- 0.01 sec. The upstroke time was measured from the beginning of the carotid arterial pulse rise to the highest peak. Correction for heart rate was made by dividing the measured value by the square root of the R-R interval. Normal values are 0.088 + 0.013 sec.5 Right and left heart catheterizations with pressure measurements and cardiac output determinations were performed on all patients. Pressures were measured with Statham P23Db strain gauges and an Electronics for Medicine DRS recorder. The cardiac output determinations were performed by the Fick method. Expired air was analyzed on the Scholander apparatus, and blood oxygen capacity was determined on the Van Slyke apparatus. Pulmonary arterial and aortic oxygen saturation determinations were made on the Beckman DU spectrophotometer. Simultaneous pressure measurements were recorded from the left ventricle and aorta or femoral artery before and during the intravenous administration of isoproterenol (2 mg. in 500 cc. of 5 per cent dextrose in water, at a rate of 4 pg./min.). In two instances the left ventricle was catheterized by the transseptal route using the technic of Brockenbrough and Braunwald.11 In the other 2 cases, the left ventricle was entered retrograde across the aortic valve from a brachial artery cutdown site. Each patient was studied with a left ventricular angiogram performed in the left and right anterior oblique positions and a supravalvular injection in the left anterior oblique position; 75 per cent Hypaque-M@ was used in volumes of 40 cc. Pressure injections were made at a pressure of 350 Ib./sq. in. using either a Tavaris or a Gidlund pressure injector. Three patients underwent selective coronary angiography by the Judkin’s technic.12
et al. RESLJLTS Table I details trocardiographic patients.
the historical, physical, elecand x-ray findings on all
HISTOKY
Two of the 4 patients had a history of rheumatic fever and 2 were not certain of such a history. All had dyspnea and chest pain. The chest pain was that of typical angina in 2 patients and of atypical angina in 1; it was thought to be nonanginal in the fourth. Syncope was noted by 2 patients and near syncope by a third. Dizziness was experienced by 3 of the 4 patients. Orthopnea was not present in any patient, but 1 had had paroxysmal nocturnal dyspnea; another had had peripheral edema. There was a positive family history of sudden death at a young age in 2 patients. SIGNS ON
PHYSICAL EXAMINATION
Two of the patients showed signs of left ventricular hypertrophy. This assumption was made when the apex was displaced laterally and downward and when it was more propulsive than the usual. A bisferiens peripheral pulse was noted in 2 of the 4 patients, and 3 showed a typical pulsus parvus et tardus. A double peaked apex which was prolonged was palpated in Patient 1. A systolic thrill was present at the aortic area in all 4 patients. An ejection click ‘and a fourth heart sound were heard in Patient 1 but not in the other patients. All patients had a loud (grade 4/6) systolic murmur of the ejection type heard at the aortic area which radiated well to the left sternal border and to the neck. Three of the patients had clear-cut early diastolic decrescendo blowing murmurs. ELECTROCARDIOGRAPHICFINDINGS Two patients had increased voltage in the precordial leads and ST-T changes consistent
with left ventricular hypertrophy. The other 2 patients had no criteria which made a diagnosis of left ventricular enlargement possible. Of these 2, 1 showed left atria1 enlargement; the other had a tall R wave in lead VI with an RS ratio greater than one. X-RAY FINDINGS Two of the 4 patients had x-ray findings consistent with either left ventricular enlargement or a prominent left ventricular border. Two THE AMERICANJOURNALOF
CARDIOLOGY
LAortic Valvular
and Hypertrophic Table
Patient
I.
1
_ ..__
Clinical
Suhaortic
309
Stenosis
Data
Patient 2 --
Patient
3
Patient 4
HIJ/Oly Known rheumatic fever Dizziness Syncope Chest pain ‘Typical angina .\typical angina Nonanginal Exertional dyspnea Orthopnea Paroxysmal nocturnal dyspnra Edema Family history of heart disease or sudden death
+
13 yr. -
+
3 yr.
-
6 yr. + -
+ + -
13 yr. -
-
-
Brother died, age 39
Father died, age 47
+
5 mo.
+ Recent + + _ +* -
3
Recent Near syncope Recent + + + -
-
P/w&z1 Signs
Pulse (carotid) Bisferiens Slow rise Slow downstroke .\pex Double-peaked Prolonged Left ventricular hypertrophy Thrill .\uscultation .Murmurs Systolic Diastolic Ejection click Fourth heart sound
-
+ + -
+ + + +
T + -
-
: -
Left ventricular hypertrophy Left atria1 enlargement Tall R in Lead VI
+ _
_ +
+ -
.Y-rq Findings Left ventricular enlargement .\ortic dilatation .\ortic calcification
+
-
+ + +
Electrocardiogram
-
* \liith atria1 fibrillation.
showed definite poststenotic dilatation of the proximal aorta and 3 had dense (4+) calcification of the aortic valve.
E~~~~~LTRACINGS(TABLEIIANDFIG
1)
All 4 patients had a typical high frequency systolic murmur of the ejection type recorded best at the aortic area. Third and fourth heart sounds as well as an ejection click were noted in Patient 1, but the other patients did not have these findings. Carotid Tracings: The rise time was prolonged in the 3 patients in whom it was measured; the ejection time was prolonged in 2 of these 3 and at the upper limits of normal in Phonocardiograms:
VOLUME
24, SEPTEMBER
1969
the third. A bisferiens pulse was recorded in !l patient. A systolic shudder was noted in the external carotid tracing in 2 of the 3 patients whose tracings were technically satisfactory. Patient 1, although he had a palpable thrill, did not have a noticeable shudder on the carotid tracing, and it may be that this was because the tracing was recorded through a strain gauge which was not capable of picking up the higher frequencies. Apex Tracings: An abnormally large A wave (20 per cent or more of the succeeding E-O ratio) was found in 1 patient, and 1 showed a late systolic bulge in the apex tracing. Three demonstrated a prolonged E point in the apex tracing: 1 did not.
Parker et al. Table
II. Findings on Phonocardiograms, Indirect Carotid Tracings and Apex Cardiograms Patient
Phonocordiogram Murmurs
Systolic ejection
sa s4 Ejection click Carotid tracing Rise time(c) Ejection tilllC(C)
Bisfericns “Shudder” Apa .l wave Systolic bulge Prolonged
1
Patient
2
Patient
3
+ +
Systolic ejection -
Systolic ejection -
+
-
-
Patient
Systolic ejection -
AF
-
0.28 sec.
0.27 sec.
0.17 sec.
TITM
0.51 sec. -
0.46 sec.
0.42 sec.
TITM
- *
7
7
Present, not increased
-
AF
4
Table LU.
+ TITM
-
Present, increasedt
;
* = recorded through strain gauge. t = amplitude of a 20% of EO. AF = atria1 fibrillation; (c) = corrected;
TITM
=
technically
im-
possibleto measure. ANGIOGRAPHIC
FINDINGS
The angiographic findings are shown in Table III and Figures 2 to 6. All 4 patients showed a very small systolic volume of the ,-I I I I
Angiographic
Patient
E
left ventricular cavity. Three had left ventricular angiograms in both oblique views; 1 had a right anterior oblique view only. Of the former, 2 had tongue-like projections characteristic of subaortic stenosis and all 3 had an infundibular chamber. Narrowing of the outflow tract was seen in all three. One patient had concomitant mild mitral insufficiency.
Cavitv size “Ton&“-like projection Infund. chamber O.F.T. narrowing MI Coronary artery disease Right Left Papillary muscle hypertrophy AI
1
Patient
2
Findings Patient
3
Small
-
-
Minimal
Severe,
+ 2+
LAD
+ 2+
Patient
S”ldl
-
* *
+ -
* *
_
*
2+
*
+
*
2+
*
* Parameters could not be evaluated bccausc of lack ot sufficeint views. AI = aortic insufficiency; LAD = left anterior descending; MI mitral insufficiency; O.F.T. = outflow tract.
I 1 t III I I I I I t I I I I I I I I I I: I t I
. ..
:
AORTIC
AREA
4
50 CPS
APEX CARDIOGRAM
1. Case 2. External phonocardiograms and arterial tracing. A, phonocardiogram at aortic area and indirect carotid tracing. Note the typical systolic murmur of the ejection type and the diminished A, in the phonocardiogram. The carotid tracing shows a prolonged ejection time (0.46 set). B, phonocardiogram and apex cardiogram; the latter shows a prolonged E point. (Time lines = 0.04 sec.)
Figure
THE
AMERICAN
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OF
CARDIOLOGY
Figure
2.
Case 2. Left ventricular left anterior oblique view. A shows opaque material filling the body of the left ventricle (LVB) and the infundibular chamber (IC). A tongue-like projection (TLP) is also seen. B (several frames later) demonstrates sequential filling of the aorta (Ao) and mitral insufficiency. LA = left atrium: MV = mitral valve. C is a drawing of frame B. nngiograln,
C
Marked papillary muscle hypertrophy was evident in all the angiocardiograms, and 3 of the 4 patients demonstrated some aortic insufficiency. Calcium was present in three of the four aortic valves, and 1 subject (Patient 3) showed a thickened and rigid aortic valve which did not move well. Concomitant Coronary Disease (Table III): Selective coronary angiocardiography revealed severe disease of the anterior descending coronary in 1 patient and marked disease in all branches of the left coronary artery in another. PHYSIOLOGIC
DATA
Table IV details the cardiac catheterization findings. Patients 2 and 3 showed minor gradients across the pulmonic valve and Patient 3, in addition, showed a restrictive pattern (“square root sign”) in the right ventricle. The right ventricular diastolic pressure was normal in all patients. Systolic gradients were present across the aortic valve in all 4 patients. The cardiac index was reduced in 2 of the four. It was possible to demonstrate a subvalvular gradient before the use of isoproterenol within the body of the left ventricle in 2 patients (Fig. 7). Effect of Zsoproterenol: As can be seen from Table IV, the 3 patients who were studied with VOLUME
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1969
Figure 3. Case 2. Supravalr~nlar injection. Aortic insufficiency is demonstrated. The infundibular chamber is present above the narrowed area formed by the anterior mitral leaflet (a) and the interventricular septum (b) bulging into the left ventricular outflow tract.
an infusion of isoproterenol (2 mg./500 cc. of 5 per cent glucose in water) showed the typical response diagnostic of functional hypertrophic subaortic stenosis; the left ventricular cavity systolic pressure rose while the peripheral arterial systolic pressure fell (Fig. 8). Patient 1, just before administration of isoproterenol, exhibited a systolic gradient of 59 mm. Hg. Isoproterenol increased the gradient to 79 mm. Hg, and the peripheral arterial pressure fell
312
Parker Table Patient
RA RV PA PPC LA LV Body Subvalve Aorta CI Isuprel LV FA LV FA
1
3; t20 28/3 28/12
Data*
Patient 2
Patient 3
Patient
4
8 36/2-11 32/10 14
151/8-15 119/8-15 119/54 2.2
262/10 D = 18
146/66 2.67
180/O; t207/12 152/O 107/59 2.2
126/14 67/43 143/14 64/35
172/4 115/60 224/O 76/34
151/13 119/52 185/3.3 102!45
: : i
182/6 (3-19) 146/66 199i? 136/?
190/4 115/56 209/4 100/43
W2/6;
Tl26/20
StudJ,
Effect ofPVC LV (before PVC) Aorta or FA (before PVC) LV (post PVC) Aorta or FA (post PVC)
Physiologic
4; t3 33/3 24jlO (14) 8 t14
6; j21
(control) (control) (with Isuprel) (with Isuprel)
IV.
et al.
5 36/5 36/12 13
(sq. rt.)
; 04/70 4.4
i
: : : :
* All values in mm. Hg except cardiac index (CI) (L./min. per M.2). t After Hypaque study. $ Not performed. CI = cardiac index; FA = femoral artery; LA = left atrium; LV = left ventricle; PA = pulmonary artery; PPC = peripheral pulmonary capillary wedge pressure; PVC = premature ventricular contractions; RA = right atrium; RV = right ventricle; sq: rt. = square root sign.
slightly. Patient 2 showed a systolic gradient of 57 before and 148 mm. Hg during the administration of isoproterenol. The femoral arterial systolic pressure fell 39 mm. Hg as the gradient across the aortic valve rose from 57 to 148 mm. Hg. Patient 3 showed a control systolic gradient of 32 mm. Hg between the left ventricle and femoral artery. Wisth isoproterenol this gradient rose to 8.3 mm. Hg while the systolic pressure in the femoral artery fell 17 mm. Hg. Two patients showed typical responses to induced premature ventricular contractions as we1113 (Table IV; Fig. 9 shows a typical example). SURGICAL
AND AUTOPSY
FINDINGS
Patient 4 died after operation and an autopsy was subsequently performed. The pertinent details of the operative and autopsy reports are presented below: “Following aortic Starr [-Edwards] valve replacement, the patient was weaned from the pump but it was evident that the left ventricle would not take over. It wlas also evident that the aortic valve was not opening and closing under the amount of pressure the left ventricle could exert.” After the patient was found not able to tolerate removal from total bypass, he was placed on left heart by Patient
4:
As mentioned,
pass. Later
in the day he was again placed on total bypass and a right ventriculotomy was performed. “An enormously hypertrophied interventricular septum was identified. A large amount of muscle the septum to was then resected. . . allowing protrude into the right ventricle.” The left ven tricular cavity was then explored and “it was found to be enormously hypertrophied throughout, involving the papillary muscles. . . In spite of all efforts, low cardiac output continued with subsequent demise.” At autopsy (Fig. 10) the heart weighed 620 p-m. The right ventricular wall was 0.5 cm. in thickness
and the left ventricular wall measured 2.0 cm. A Starr-Edwards aortic valve prosthesis with a mobile hall was in place. When the heart was opened the ventricular septum was noted to he markedly thickened. Th’e right ventricular cavity was very small because oC this thickening of the septum which compromised the right ventricular lumen. The papillary muscles of the left ventricle were markedly hypertrophied.
Pntient I: This patient died while straining at stool. The cardiac findings at autopsy showed that the heart weighed 750 gm. and appeared somewhat enlarged. The thickness of the right ventricular wall measured 4 mm. and that of the left measured 15 mm. Valvular measurements were normal except for the aortic valve which was stenotic THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Aortic
Valvular
and Hypertrophic
Subaortic
wa5 IO per cent narrowing nal-v artery by atherosclerotic
1‘11~ tional
cliffercrl
313
Stenosis
tial
ot the lrft changes.
diagnosis
IlyfxWrophic
szrbaortic
main
coro-
l~('lii1('('17
fil;vc-
.stmo.sis
and
on the basis of liistor\ and physical examination is difficult, as has been pointed out previously.G~i~l~ The arterial pulse is of great importance, showing a rapid rise and a bisferiens quality in. functional hypertrophic subaortic stenosis; the pulse of valvular stenosis is slow rising with an anaerotic notch and a slow fall.5~r~15~1(~ In a series of 126 cases of idiopathic hypertrophic sul,aortic stenosis, 9 per cent showed a prolonged upstroke time, and it was therefore concluded that this finding does not negate this cliagnosis.li As can be seen in the 4 cases presented, the coexistence of both lesions led to the physical findings of aortic valvular stenosis. The phonocardiograms, apex cardiograms and arterial pulse tracings also were characteristic aortic
ualuular
stenosis
Figure 4. Case 1. Left ventricular angiogram, left anterior oblique view. A demonstrates apposition of the anterior mitral leaflet and the bulging interventricular septum producing an infundibular chamber. B is a drawing delineating the structure more clearly. DAo = descending aorta.
and heavily calcified. The aortic annulus measured 10 cm. in circumference and the valvular orifice was 7 cm. in circumference. The valvular orifice was ellipsoid in shape and measured 3 by 1 cm. The valve appeared bicuspid. Several small whitish pockets were seen in the endocardium of the left ventricular cavity beneath the left anterior coronary leaflet (insufficiency pockets). Several small white scars were noted in the free left ventricular wall. The septal wall was markedly hypertrophied and a prominent ridge was present at its superior aspect. Between this ridge and the aortic valve was a depression (subvalvular chamber, Fig. 11). The anterior leaflet of the mitral valve abutted against the hypertrophied region. Both mitral leaflets
showed minimal thickening, and there was equivocal thickening of a few of the chordae tendineae. The left ventricular chamber was not dilated. There was moderate hypertrophy of the papillary muscles and columnae carneae of the left ventricle. The right coronary artery was widely patent: there VOLUME
24,
SEPTEMBER
1969
B injection, left anFigure 5. Case 1. Supravalvular terior oblique position. Aortic insufficiency is seen and demonstrates the same structures as shown in Figure 4.
314
Parker
et al.
Fi&qre 6. Case 1. Left uentriculogram. A, right anterior oblique view. Arrows indicate hypertrophy of both papillary muscles and minimal residual cavity size of the left ventricle in systole. B, left anterior oblique view. Arrow indicates the infundibular chamber. Also seen is the nearly obliterated left ventricular cavity in systole.
of aortic valvular stenosis, showing prolonged ejection and rise times in the carotid tracings of 3 cases, a carotid shudder in 2, and a prolonged E point on the apex cardiogram in three. None exhibited a bisferiens pulse in the carotid tracing; 1 showed a systolic bulge in the apex cardiogram, but the patient had no other features of functional hypertrophic subaortic stenosis (although perhaps the significance of this finding was overlooked). Subvalvular obstruction was thus masked by aortic valvular stenosis. Conventional x-ray examination further strengthened the diagnosis of the latter by showing calcification of the aortic
valve in 3 and dilatation of the aortic root in two. Electrocardiographic findings of left ventricular hypertrophy or left atria1 enlargement, or both, may be common to both conditions and do not lead to a suggestion that aortic valve stenosis and functional hypertrophic subaortic stenosis coexist. In general, it appears that the diagnosis of both lesions in the same patient on the basis of history, physical electrocardiograms, findings, phonocardiograms, apex cardiograms, carotid artery pulse tracings and routine radio,graphic procedures is not possible. Features Suggesting Coexisting HyperAORTA
Figure 7. Case 2. Pullthrough tracing from left ventricle to aorta showing an intermediate chamber between the free left ventricular cavity (LV) and the aorta. There is also a systolic gradient across the aortic valve. THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Aortic LVI'I
Valvular
and Hypertrophic
LV & "FA - CONTROL
Subaortic LV&FA
! !I/
Stenosis
WITH ISUPREL
FA
Figure 8. Case 2. Effect of isoproterenol. Control tracing of the left ventricular (Lv) and femoral arterial (FA) pressures (lefipank) and the response to is
Subaortic Stenosis: In the presence of typical physical, graphic and x-ray findings of aortic valvular stenosis, certain features may suggest that functional hypertrophic subaortic stenosis is also present. Of all the factors, a prolonged history of syncope or dizziness, or both, in the presence of outflow tract obstruction suggests that the symptoms should not be attributed to aortic valvular stenosis alone since this disease usually pursues a relatively short course once it becomes symptomatic. Furthermore, spontaneous decrease or cessation of the symptoms for variable periods of time in a patient with aortic valvular stenosis should raise the suspicion that functional hypertrophic subaortic stenosis also exists.7vl7 Although not noted in our patients, if digitalis or nitroglycerine worsens the symptoms in a patient with aortic valve stenosis, functional hypertrophic subaortic stenosis should be suspected as also being presen,t.T A tall R wave in lead VI of the electrocardiogram, as has been previously shown, may indicate septal hypertrophy in muscular subaortic stenosis.18 This finding in the presence of the clinical picture of aortic valvular stenosis should raise the possibility of accompanying functional hypertrophic
VOLlIME
24,
SEPTEMBER
1969
I,
,:
LV
Figure
PVC
9.
FA
Case 2. Effect of premature zwztricular (PVC). Simultaneous left ventricular and femoral arterial tracings showing typical postextrasystolic increase in the gradient as a result of an increased ventricular systolic pressure and a decreased aortic systolic pressure.
contraction
Parker et al,
Figure 10. Case 4. Autopsy specimen demonstrating left ventricular thickening and hypertrophied papillary muscles. The prosthetic aortic valve has been removed. The arrow points to the subvalvular hypertrophy of the septum; a chamber is seen above this area.
trophic subaortic stenosis (Patient 3, Table I). The absence of x-ray findings of proximal aortic dilation7 or aortic valvular calcification,* or both, in a patient with the physical findings of aortic valvular stenosis should also point to coexistent functional hypettrophic subaortic stenosis. Further hinlts of the simultaneous presence of both lesions may be found at the time of cardiac catheterization. A patient with aortic valvular calcification and a significant gradient between the left ventricle and aorta would not be expected to show also a gradient be-
Figure 11. Case 1. Autopsy specimen. The calcified aortic valve is seen. Below this is a markedly hypertrophied area of the septum (arrows). Again, the left ventricular wall is thickened and there is papillary muscle hypertrophy.
tween the right ventricle and puhnonary artery. It is well known that many patients with idiopathic hypertrophic subaortic stenosis alone will show right-sided gradients of var)ing severity. 17,1V Therefore, any right-sidctl gradient should arouse the suspicion of septal hypertrophy and functional hypertrophic subaortic stenosis, as shown by Patients 2 and 3 in this study. Another suggestive finding during heart catheterization is a drop in peripheral blood pressure during the beat after a compensatory pause created by a premature beat’3 as was noted in 2 of our patients. The catheter should be drawn from the body of the left ventricle to the aorta very slowly while one is searching for a subvalvular chamber. On the basis of our experience we believe that even if a subvalvular chamber is not demonstrated, all patierrts with aortic valvular stenosis should have an isoproterenol study performed with simultaneous pressures being measured in the left ventricle and a systemic artery. This is important because: (1) the subvalvular hypertrophy may be situated too close to the valve to permit demonstration of a chamber,as14 and (2) the hypertrophy may not be functionally apparent at the time of routine study.T,*O Management: The patient with aortic valvular stenosis who is treated surgically may fail to make the expected improvement or a low cardiac output may develop postoperatively and he may die if an accompanying functional hypertrophic subaortic stenosis has been overlooked. Cases have been cited in which the gradient from the left ventricle to the aorta did not decrease significantly or actually increased after surgical treatment for the aortic valvular stenosis. This is due to an accompanying unrecognized functional hypertrophic subaortic stenosis.*Jv5 Theoretically a beta adrenergic blocking drug must be expected to produce a favorable effect on the course of muscular subaortic stenosis. We believe that treatment in individuals with both aortic valvular stenosis and functional hypertrophic subaortic stenosis should be conservative initially, employing the use of a beta adrenergic blocking agent such as propranolol. It would appear reasonable to assume that if the functional hypertrophic subaortic stenosis is relieved, symptoms would improve in some patients whose valvular stenosis is not yet severe enough to require operation. Should there be no signifi’can’t improvement with the use of a THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Aortic
Valvular
and Hypertrophic
beta adrenergic blocker, the surgeon should be alerted to the presence of both lesions and should he prepared to remove the subvalvular hypertrophy at the same time that the aortic valvr is replaced.*
VERSKA, J.
9. ;\DDENlXJM
Since acceptance of this manuscript, we have studied 6 additional patients whose clinical and hemodynamic profile is substantially the same as that of the 4 patients presented. The data of these patients and their implications provide the basis of an on-going study we are currently carrying out to determine the frequency and significance of the concomitance of aortic valvular stenosis and functional hypertrophic subaortic stenosis.
10.
11.
12.
13.
REFERENCES 1. HUNT, J. W., JR. and LOCUE, R. B. The Heart, Arteries and Veins, p. 579. New York, 1966. McGraw-Hill. 2. BROCK, R. Functional obstruction of the left ventricle (acquired aortic subvalvular stenosis). Guyi Hosp. Rep., 106221, 1957. 3. GORDON, 0. S. The surgical management of congenital supravalvular, valvular, and subvalvular aortic stenosis using deep hypothermia. J. ThoI-c&c & Cnrdiovns. Szrrg., 43:141, 1962. 4. ELLIS, F. H., JR., ONCLFY, P. A. and KIRKLIN, J. W. Results of surgical treatment for congenital aortic stenosis. Circulation, 25:29, 1962. 5. BENCHIMOL, A., LEGLER, J. F. and DIMOND, E. G. The carotid tracing and apexcardiogram in subaortic stenosis and idiopathic myocardial hypertrophy. Am. J. Cnrdiol., 11:427, 1963. 6. HANCOCK, E. W. Differentiation of valvar, subvalvar and supravalvar aortic stenosis. Guy’s Hosp. Rep., llO:l, 1961. 7. BRAUNWALD, E., LAMBREW, C. T., ROCKOFF, S. D., Ross, J. and MORROW, A. G. Idiopathic hypertrophic suhaortic stenosis: Description of the disease based upon an analysis of 64 patients. Cirrtrlntion, 30 (Suppl IV):~,1964. 8. CONNOLLY, J. E., KAPLAN, M. A., PARKER, D. P. and
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Subaortic
14. 15.
16. 17.
18.
19.
20.
Stenosis
317
The muscle-bound heart: Danger of aortic valve replacement in the presence of COILcomitant functional subvalvular muscular hypertrophy. In: Prosthetic Heart X’altes. \‘ol. 2, chap. 3, pp. 741-753. Springfield, Ill., 1969. Charles C I‘homas. PERLOFF, J. K. Clinical recognition of aortic stenosis. The physical signs and differential diagnosis of various forms of obstruction to left ventricular outflow. Progr. Cardiovas. LG., 10:323, 1968. WEISSLER, A. M., HARRIS, W. S. and SCHOENFELD, C. D. Systolic time intervals in heart failure in man. Circulation, 37:149, 1968. BROCKENBROUGH, E. C. and BRAUNWALD, E. A new technic for left ventricular angiography and transseptal left heart cathereriration.