Septal Perforator Compression (Narrowing) in Idiopathic Hypertrophic Subaortic Stenosis
AUGUSTO D . PICHARD, MD JOSE MELLER, MD, FACC LOUIS E . TEICHHOLZ, MD, FACC STEPHEN LIPNIK, MD RICHARD GORLIN, MD, FACC MICFJAEL V. HERMAN, MD, FACC
Thirteen patients with Idiopathic hypertrophic subaortic stenosis were compared with two groups of subjects: 10 patients with chest pain, normal coronary arteries and a normal left ventricle, and 10 patients with left ventricular hypertrophy . Five of the latter had aortic stenosis and five had idiopathic left ventricular hypertrophy. Coronary arteriography revealed that the septal branches of the left anterior descending artery closed or narrowed during systole in patients with Idiopathic hypertrophic subaortic stenosis and did not do so in the other patient groups . This narrowing is possibly related to an abnormal position of the septet arteries within the septum In idiopathic hypertrophic subaortic stenosis . Systolic compression of the septal perforator arteries is not a pathognomonic sign of idiopathic hypertrophic subaortic stenosis .
New York, New York Boston, Massachusetts
Several workers' -5 have described the clinical, hemodynamic, angiographic and pathologic manifestations of idiopathic hypertrophic subaortic stenosis . Other investigators6," have studied these patients with coronary arteriography and described the association of idiopathic bypertrophic subaortic stenosis with coronary artery disease . The availability of echocardiography has provided the clinician with an accurate and sensitive means of confirming the suspected diagnosis of idiopathic hypertrophic subaortic stenosis .a . lo As a consequence, hemodynarnic and angiographic studies are not currently performed on a routine basis in all patients with suspected idiopathic hypertrophic subaortic stenosis . We have studied 13 patients with idiopathic hypertrophic subaortic stenosis who had high quality coronary arteriograms that revealed narrowing of the septal perforator branches of the left anterior descending coronary artery during systole . To our knowledge, this phenomenon has not previously been described and represents an additional angiographic sign in this syndrome . Material and Methods
From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital and Mount Sinai School of Medicine of the City University of New York, New York, New York and the Peter Bent Brigham Hospital, Boston, Massachusetts . Manuscript received November 4, 1976 ; revised manuscript received March 31, 1977, accepted April 6, 1977 . Address for reprints : Augusto D . Pichard, MD, the Division of Cardiology, Department of Medicine, Mount Sinai Hospital and Mount Sinai School of Medicine of the City University of New York, New York, New York 10029 .
310
September
1977
The American Journal
The files of the cardiac laboratories of The Mount Sinai Hospital, New York and Peter Bent Brigham Hospital, Boston were reviewed in consecutive fashion fur the 24 months between January 1974 arid February 1976, and all cases with hemodynamic and angiographic features of idiopathic hypertrophic subaortic stenosis were analyzed. Thirteen patients were selected who had diagnostic high quality selective coronary arteriograms ; eight others were rejected because of nonselective or unsatisfactory coronary arteriograms. Two control groups were also studied : one a group of 10 consecutive patients with a chest pain syndrome, normal coronary arteries and a normal left ventricle and the other a group of 10 consecutive patients with angiographic evidence of left ventricular hypertrophy due to significant aortic stenosis or other cause .
of
CARDIOLOGY
Volume
40
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL.
All patients with idiopathic hypertrophic subaortic stenosis underwent right and left heart catheterization in the postabsorptive state under light sedation with orally administered diazepam . The left side of the heart was entered in retrograde fashion by means of a brachial arterial arteriotomy or femoral arterial percutaneous prmcture . The left ventricular outflow tract gradient was measured with simultaneous aortic and left ventricular pressure recording or pullback from the left atrium to the aorta .' l Left ventriculography was performed in the right and left anterior oblique projections . Selective coronary arteriography was perforated with the Sones 12 or Judkinst 3 s technique. The branches of the left anterior descending coronary artery that perfuse the septum are perforating arteries . They branch perpendicularly and extend for a variable distance into the septum. Their number and size are variable . Their diameter normally does not vary through the cardiac cycle (Fig . 1) as visualized with cineangiography . "Septal perforator narrowing" is defined as a reduction in
FIGURE 1 . Control patient . Septa) perforator branches in luminal diameter is observed in control groups .
of the
diameter of the septal arteries during systole . This reduction leads to nonvisualization of these vessels during systole on cineangiography (Fig . 2) . Each angiogram was reviewed by three of us . Septal narrowing was graded 1+ to 3+, 1+ indicating systolic disappearance of the lower third, 2+ disappearance of the lower two thirds and 3+ disappearance of the entire septal artery . Bridging or narrowing of other coronary vessels was also looked for . Results Idiopathic hypertrophic suhaortic stenosis : Table I summarizes the clinical findings of the 13 patients in this group . Eight patients were men and five were women. Their ages ranged from 47 to 66 years (average 53 years) . All patients had symptoms related to the basic condition . Eight had angina pectoris, seven had dyspnea
left anterior descending coronary artery during diastole (A) and systole (B).
No
change
FIGURE 2 . Patient with idiopathic hypertrophic subaortic stenosi5. Septal perforator branches of the left anterior descending coronary artery during diastole (A) . During systole (B), there is narrowing and almost complete obliteration (arrows) .
September
1977
The American Journal
of
CARDIOLOGY
Volume 40
31 1
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL .
TABLE I Clinical Characteristics in 13 Patients With Idiopathic Hypertrophic Subaortic Stenosis Case no .
Age (yr) & Sex
Angina Pectoris
Dyspnea on Effort or CHF
Dizziness or Syncope
Electrocardiogram
Chest X-ray Film
Echocardiogram
1 2 3 4 5 6 7 8 9 10 11 12 13
66M 52F 51M 49F 51M 60M 49M 53F 52M 56M 47F 50F 58M
No Yes Yes Yes No Yes No Yes Yes Yes Yes No No
Yes No Yes No No No No Yes Yes Yes No Yes Yes
Yes No No No No No No No No No No No Yes
LAE, LVH LVH LVH Inferior MI LVH + strain LVH + strain LVH + strain LVH, septa) Q waves LVH + strain LVH + strain 0 waves in leads II, III, aVF LVH + strain LVH
CE 2+ CE 1+ Normal CE 1+ Normal CE 1+ CE 1+ Normal CE 2+ CE 1+ Normal Normal Normal
IHSS
IHSS IHSS IHSS IHSS IHSS
` Echocardiogram not obtained . CE = cardiac enlargement; CHF = congestive heart failure ; IHSS = idiopathic hypertrophic subaortic stenosis ; LAE = left atrial enlargement ; LVH = left ventricular hypertrophy ; MI = myocardial infarction .
or other manifestations of congestive heart failure and two had dizzy spells or syncope . The electrocardiogram was abnormal in all patients, revealing left ventricular hypertrophy in five, left ventricular hypertrophy with strain in six and abnormal Q waves alone in two . The chest roentgenogram showed a normal heart size in six patients and cardiac enlargement in seven . Echocardiograms, obtained in six patients, were diagnostic of idiopathic hypertrophic subaortic stenosis in all . The hernodynamic and angiographic findings of these patients are presented in Table II . Seven patients had an intraventricular pressure gradient at rest (13 to 90 mm Hg, average 62) . With provocation (Valsalva maneuver, isoproterenol infusion, postextrasystolic potentiation), an intraventricular gradient (30 to 180 mm Hg, average 109) could be induced in all patients .
One patient had an associated significant gradient at rest across the outflow tract of the right ventricle . One patient had severe two vessel coronary artery disease . Two patients had mild to moderate narrowing of the left anterior descending artery in its middle third during systole (milking effect) . 14 No narrowing or bridging of other coronary arteries was observed . Septal perforator narrowing was found in all 13 patients with idiopathic hypertrophic subaortic stenosis (Fig . 2) . It was marked (3+) in five patients, moderate (2+) in six and mild (1+) in two. Grade 3+ septal narrowing was always found in association with a pressure gradient at rest and severe outflow obstruction during provocation . Patients with no gradient at rest had 1+ or 2+ septal arterial narrowing . Mitral regurgitation of mild to moderate degree was present in nine patients .
TABLE II Hemodynamic and Angiographic Findings in 13 Patients With Idiopathic Hypertrophic Subaortic Stenosis Case no .
_ LV (Rest)
Aorta (Rest)
Pressures (mm Hq) IV Gradient Rest Maneuver
PA
RV
CO
1 2 3 4 5 6 7
200/24 178/36 188/6 170/18 130/12 140/10 180/16
130/60 118/64 135/70 170/95 130/70 140/80 180/78
76-90 60 50 0 0 0 0
130-160 124 60 96180 30 100 65
70/30 48/18 20/6 18/4 20/12 32/13 30/10
70/10 50/2 20/2 23/0 40/20 32/9 30/6
3 .09 3 .8 4 .6 4 .8 5 .3 4 .2 5 .2
8 9
180/4 160/25
115/65 160/80
65 0
80 120
32/15 36/18
32/6 36/14
4 .3 2 .7
10 11 12 13
179/9 188/25 208/30 134/13
121/80 152/77 111/68 135/76
58 13-37 97 0
140 125 161 133
26/14 30/15 40/21 23/5
26/7 35/12 42/8 23/2
5 .1 6 .5 7 .9 4 .8
Coronary Arteriography 30% RCA normal 30% mid LAD Normal Normal 100% LAD, 100% LCx a Mild narrowing mid LAD Normal Mod . narrowing mid LAD Normal Normal Normal Normal
Septa/ Perforator Narrowing During Systole 3+ 3+ 3+ 2+ 1+
MR
2+
no no 1+ 1-2+ no no 2+
3+ 2+
1+ 1+
3+ 2+ 2+ 2+
2+ 1+ 2+ 1+
1+
CO = cardiac output (liters/min) ; IV = intraventricular; LAD = left anterior descending coronary artery ; LCx. = posterolateral left circumflex artery ; LV = left ventricle; Mod. = moderate; MR = mitral regurgitation ; PA = pulmonary artery ; RCA = right coronary artery ; RV = right ventricle .
312
September 1977 The American Journal of CARDIOLOGY Volume 40
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL .
Normal control group : The first control group had 10 patients with a chest pain syndrome, normal coronary arteries, no outflow tract gradient and normal left ventricular function . None of these patients had septal perforator narrowing (Fig . 1) . The echocardiogram was normal in 7 of the 10 and showed mitral valve prolapse in 2 ; it was not obtained in 1 patient . Control group with left ventricular hypertrophy: A second control group had five consecutive patients with aortic stenosis and five consecutive patients with left ventricular hypertrophy of other cause . Among the patients with aortic stenosis, the outflow tract gradient ranged from 85 to 185 mm Hg (average 107) . Among the patients with idiopathic left ventricular hypertrophy, no outflow tract gradient was found (at rest or with provocation) . Angiographic left ventricular hypertrophy was significant in all 10 patients . None had obstructive coronary artery disease or septa] perforator narrowing . Bridging or narrowing of the left anterior descending or other coronary arteries was not observed in any of these 10 patients. Discussion The first publications 15,16 on coronary arteriography in patients with idiopathic hypertrophic subaortic stenosis demonstrated a normal coronary arterial tree although prominent Q waves in the electrocardiogram suggested myocardial infarction . Atherosclerotic obstruction of the coronary arteries was later described in association with idiopathic hypertrophic subaortic stenosis .6,7,17,18 Coronary arteriography is now recommended routinely for evaluating adult patients with the diagnosis of idiopathic hypertrophic subaortic stenosis who undergo cardiac catheterization . Our study demonstrates the presence of systolic narrowing (compression) of the septal perforator branches of the left anterior descending coronary artery during systole in patients with idiopathic hypertrophic subaortic stcnosis . To our knowledge, this finding has not previously been reported . Although varying in degree (1+ to R+) this was a consistent finding in this group of patients with idiopathic hypertrophic subaortic stenosis . The most severe degree of septal perforator narrowing (3+) was found in patients with an intraventricular gradient at rest or severe outflow tract obstruction on provocation with specific interventions such as the Valsalva maneuver or isoproterenol infusion . Septal perforator compression was not seen in the control groups of patients, that is, those with normal coronary arteries and normal left ventricle, those with severe aortic stenosis and those with idiopathic left ventricular hypertrophy. We recently observed one patient with hyperdynamic cardiomyopathy without outflow obstruction at rest or on provocation, who presented the phenomenon of septal perforator narrowing during systole . No elevation in right-sided pressures or other abnormalities were seen in this patient . The echocardiogram revealed a hyperdynamic left ventricle, normal thickness of the posterior left ven-
tricular wall and septum and decreased end-systolic volume. In view of this case, septa] perforator narrowing during systole, although unique, does not appear to be specific for idiopathic hypertrophic subaortic stenosis. Mechanism of septal perforator narrowing in idiopathic hypertrophic subaortic stenosis: The mechanism is not clear. Under normal circumstances, the septal perforator branches of the left anterior descending artery course close to the endocardium on the right side of the septum until their terminal arborization . 19 In this way, these vessels are not subjected to left ventricular pressures (except for the terminal ramifications that leave the parent vessel at a right angle) and have the flow pattern of epicardial vessels. Systolic narrowing of a coronary vessel occurs when it courses through the left ventricular myocardium (wall tension is greater than aortic pressure during systole 20 ) as demonstrated on coronary arteriography by the "bridging" or "milking" effeCt 14 of the left anterior descending artery. In consequence, the septal perforator narrowing observed in patients with idiopathic hypertrophic subaortic stenosis suggests that these vessels are subjected to intramyocardial tension during systole . Several theoretical possibilities would explain this phenomenon: 1. It is possible that the septal perforator branches course anomalously through the left ventricular side of the septum instead of lying in their normal position close to the right ventricular endocardium . This could be a coronary arterial malformation. Such a phenomenon could result in selective ischemia of the septum and might be related in some way to the pathogenesis of asymmetric septal hypertrophy and fibrosis because hypoxia is a well known stimulus for hypertrophy . 21,22 A similar phenomenon is seen in the hypertrophic fibrotic left ventricle of cases with anomalous origin of the left coronary artery from the pulmonary artery . 23 No pathologic studies are available to confirm this hypothesis . 2. The characteristic histologic findings in the septum of idiopathic hypertrophic subaortic stenosis are the presence of disorderly arranged muscle fibers, variable degrees of interstitial fibrosis and a bizarre type of cell hypertrophy.24.25 It is possible that this disorganized hypertrophy engulfs the septal perforator branches as a secondary phenomenon, subjecting these vessels to increased pressure during systole . Again, the subendocardial fibrosis of the septum may be due to the secondary new segmental ischemia . In summary, we have described the association of idiopathic hypertrophic subaortic stenosis with systolic narrowing of the septal perforator branches of the left anterior descending coronary artery as a consistent phenomenon . We have no definitive explanation for the physiopathologic mechanism involved but have analyzed some possibilities . This phenomenon, although unique, does not appear to be exclusive for idiopathic hypertrophic subaortic stenosis and can occur in any situation under similar physiologic conditions .
September 1977
The American Journal of CARDIOLOGY Volume 40
313
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL .
References 1 . Epstein SE, Henry WL, Clark CH, et al : Asymmetric septal hypertrophy . Ann Intern Med 81 :650 -680, 1974 2. Adelman AG, Willie ED, Ranganatan N, et al : The clinical course in muscular subaortic stenosis . A restrospective and prospective study of 60 hemodynamically proved cases . Ann Intern Med 77 : 515-525,1972 3. Shah PM, Adelman AG, Wlgle ED, at al : The natural (and unnatural) history of hypertrophic obstructive cardiomyopathy . A multicenter study. Circ Res 34,35:Suppl II :II-179-II-195, 1974 4 . Braunwald E, Morrow AG, Comell WP, et al : Idiopathic hypertrophic subaortic stenosis : clinical, hemodynamic, and angiographic manifestations . Am J Med 29 :924-925, 1960 5. Frank S, Braunwald E : Idiopathic hypertrophic subaortic stenosis : clinical analysis of 126 patients with emphasis on natural history . Circulation 37 :759-788, 1968 6. Gulotta SJ, Hamby RI, Aronson AL, et al : Coexistent idiopathic hypertrophic subaortic stenosis and coronary arterial disease . Circulation 46 :890-896, 1972 7 . Oran E, Gupta S, Yeo B, et al : Idiopathic hypertrophic subaortic stenosis in patients with coronary artery disease . Importance, recognition and principles of management . Angiology 24 :538-547, 1973 8 . King JF, deMaria AN, Reis RL, et al : Echocardiographic assessment of idiopathic hypertrophic subaortic stenosis . Chest 64: 723-731,1973 9 . Tajik AJ, Giuliani ER : Echocardiographic observations in idiopathic hypertrophic subaortic stenosis . Mayo Clin Proc 49:89-97, 1974 10 . Rossen RM, Goodman DJ, Ingham RE, et al : Ventricular systolic septa) thickening and excursion in idiopathic hypertrophic subaortic stenosis . N Engl J Med 291 :1317-1319, 1974 11 . Wong B, Langon RA, Cohen LS, at al : Retrograde catheterization of the left atrium in idiopathic hypertrophic subaortic stenosis . Am J Cardiol 36 :62-66, 1975 12 . Sones FM, Shiner EK : Cine coronary arteriography . Mod Concepts Cardiovasc Dis 31 :735-738, 1962
314
September 1977
13. Judkins MP: Selective coronary arteriography . I . A percutaneous transfemoral technique . Radiology 89:815-824, 1967 14 . Noble J, Bourassa MG, Petitclare R, at al : Myocardial bridging and milking effect of the left anterior descending coronary artery : normal variant or obstruction? Am J Cardiol 37 :993-999, 1976 15 . Cohen RJ, Kaljot V, Czarnecki SW : Septal hypertrophy of hypertrophic subaortic stenosis simulating the electrocardiographic pattern of myocardial infarction . Vasc Dis 1 :269, 1964 16 . Klein MD, Mathur V, Levin HD, et al : Electromechanical correlations in hypertrophic subaortic stenosis . Circulation 38 :635-648, 1968 17 . Giuliani ER, Tajik AJ, Frye RL, et al: Idiopathic hypertrophic subaortic stenosis (IHSS) and associated coronary artery disease (abstr). Circulation 45,46 :Suppl II :II-156, 1972 18 . Marcus GB, Popp RL, Stinson EB: Coronary-artery disease with Idiopathic hypertrophle subaortic stenosis . Lancet 1 :901-903, 1974 19 . James TM, Burch GE : Blood supply of the human interventricular septum . Circulation 17:391-396, 1958 20 . Gorlin R: Physiology of the coronary circulation . In, The Heart, third edition (Hurst JW, Logue RR, ad) . New York, McGraw Hill, 1974, p 110 21 . Van Liere EJ, Krames BB, Northup DW : Differences in cardiac hypertrophy in exercise and hypoxia . Circ Res 16 :244-248, 1965 22 . Hollenberg M : Effect of oxygen on growth of cultured myocardial cells. Circ Res 28 :148-157, 1971 23 . Cohen M, Slew S : Aberrant left coronary artery . Report of a case and review of literature . Circulation 20 :918-927, 1959 24 . Ferrans VJ, Morrow AG, Roberts WC : Myocardial ultrastructure in indicpathic hypertrophic subaortic stenosis . A study of operatively excised left ventricular outflow tract muscle in 14 patients . Circulation 45 :769-792, 1972 25 . Ferrans VJ: Characteristic cellular abnormalities of ventricular septal myocardium in asymmetric septal hypertrophy. Ann Intern Med 81 :650-680, 1974
The American Journal of CARDIOLOGY Volume 40
AUGUSTO D . PICHARD, MD JOSE MELLER, MD, FACC LOUIS E . TEICHHOLZ, MD, FACC STEPHEN LIPNIK, MD RICHARD GORLIN, MD, FACC MICFJAEL V. HERMAN, MD, FACC
Thirteen patients with Idiopathic hypertrophic subaortic stenosis were compared with two groups of subjects: 10 patients with chest pain, normal coronary arteries and a normal left ventricle, and 10 patients with left ventricular hypertrophy . Five of the latter had aortic stenosis and five had idiopathic left ventricular hypertrophy. Coronary arteriography revealed that the septal branches of the left anterior descending artery closed or narrowed during systole in patients with Idiopathic hypertrophic subaortic stenosis and did not do so in the other patient groups . This narrowing is possibly related to an abnormal position of the septet arteries within the septum In idiopathic hypertrophic subaortic stenosis . Systolic compression of the septal perforator arteries is not a pathognomonic sign of idiopathic hypertrophic subaortic stenosis .
New York, New York Boston, Massachusetts
Several workers' -5 have described the clinical, hemodynamic, angiographic and pathologic manifestations of idiopathic hypertrophic subaortic stenosis . Other investigators6," have studied these patients with coronary arteriography and described the association of idiopathic bypertrophic subaortic stenosis with coronary artery disease . The availability of echocardiography has provided the clinician with an accurate and sensitive means of confirming the suspected diagnosis of idiopathic hypertrophic subaortic stenosis .a . lo As a consequence, hemodynarnic and angiographic studies are not currently performed on a routine basis in all patients with suspected idiopathic hypertrophic subaortic stenosis . We have studied 13 patients with idiopathic hypertrophic subaortic stenosis who had high quality coronary arteriograms that revealed narrowing of the septal perforator branches of the left anterior descending coronary artery during systole . To our knowledge, this phenomenon has not previously been described and represents an additional angiographic sign in this syndrome . Material and Methods
From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital and Mount Sinai School of Medicine of the City University of New York, New York, New York and the Peter Bent Brigham Hospital, Boston, Massachusetts . Manuscript received November 4, 1976 ; revised manuscript received March 31, 1977, accepted April 6, 1977 . Address for reprints : Augusto D . Pichard, MD, the Division of Cardiology, Department of Medicine, Mount Sinai Hospital and Mount Sinai School of Medicine of the City University of New York, New York, New York 10029 .
310
September
1977
The American Journal
The files of the cardiac laboratories of The Mount Sinai Hospital, New York and Peter Bent Brigham Hospital, Boston were reviewed in consecutive fashion fur the 24 months between January 1974 arid February 1976, and all cases with hemodynamic and angiographic features of idiopathic hypertrophic subaortic stenosis were analyzed. Thirteen patients were selected who had diagnostic high quality selective coronary arteriograms ; eight others were rejected because of nonselective or unsatisfactory coronary arteriograms. Two control groups were also studied : one a group of 10 consecutive patients with a chest pain syndrome, normal coronary arteries and a normal left ventricle and the other a group of 10 consecutive patients with angiographic evidence of left ventricular hypertrophy due to significant aortic stenosis or other cause .
of
CARDIOLOGY
Volume
40
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL.
All patients with idiopathic hypertrophic subaortic stenosis underwent right and left heart catheterization in the postabsorptive state under light sedation with orally administered diazepam . The left side of the heart was entered in retrograde fashion by means of a brachial arterial arteriotomy or femoral arterial percutaneous prmcture . The left ventricular outflow tract gradient was measured with simultaneous aortic and left ventricular pressure recording or pullback from the left atrium to the aorta .' l Left ventriculography was performed in the right and left anterior oblique projections . Selective coronary arteriography was perforated with the Sones 12 or Judkinst 3 s technique. The branches of the left anterior descending coronary artery that perfuse the septum are perforating arteries . They branch perpendicularly and extend for a variable distance into the septum. Their number and size are variable . Their diameter normally does not vary through the cardiac cycle (Fig . 1) as visualized with cineangiography . "Septal perforator narrowing" is defined as a reduction in
FIGURE 1 . Control patient . Septa) perforator branches in luminal diameter is observed in control groups .
of the
diameter of the septal arteries during systole . This reduction leads to nonvisualization of these vessels during systole on cineangiography (Fig . 2) . Each angiogram was reviewed by three of us . Septal narrowing was graded 1+ to 3+, 1+ indicating systolic disappearance of the lower third, 2+ disappearance of the lower two thirds and 3+ disappearance of the entire septal artery . Bridging or narrowing of other coronary vessels was also looked for . Results Idiopathic hypertrophic suhaortic stenosis : Table I summarizes the clinical findings of the 13 patients in this group . Eight patients were men and five were women. Their ages ranged from 47 to 66 years (average 53 years) . All patients had symptoms related to the basic condition . Eight had angina pectoris, seven had dyspnea
left anterior descending coronary artery during diastole (A) and systole (B).
No
change
FIGURE 2 . Patient with idiopathic hypertrophic subaortic stenosi5. Septal perforator branches of the left anterior descending coronary artery during diastole (A) . During systole (B), there is narrowing and almost complete obliteration (arrows) .
September
1977
The American Journal
of
CARDIOLOGY
Volume 40
31 1
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL .
TABLE I Clinical Characteristics in 13 Patients With Idiopathic Hypertrophic Subaortic Stenosis Case no .
Age (yr) & Sex
Angina Pectoris
Dyspnea on Effort or CHF
Dizziness or Syncope
Electrocardiogram
Chest X-ray Film
Echocardiogram
1 2 3 4 5 6 7 8 9 10 11 12 13
66M 52F 51M 49F 51M 60M 49M 53F 52M 56M 47F 50F 58M
No Yes Yes Yes No Yes No Yes Yes Yes Yes No No
Yes No Yes No No No No Yes Yes Yes No Yes Yes
Yes No No No No No No No No No No No Yes
LAE, LVH LVH LVH Inferior MI LVH + strain LVH + strain LVH + strain LVH, septa) Q waves LVH + strain LVH + strain 0 waves in leads II, III, aVF LVH + strain LVH
CE 2+ CE 1+ Normal CE 1+ Normal CE 1+ CE 1+ Normal CE 2+ CE 1+ Normal Normal Normal
IHSS
IHSS IHSS IHSS IHSS IHSS
` Echocardiogram not obtained . CE = cardiac enlargement; CHF = congestive heart failure ; IHSS = idiopathic hypertrophic subaortic stenosis ; LAE = left atrial enlargement ; LVH = left ventricular hypertrophy ; MI = myocardial infarction .
or other manifestations of congestive heart failure and two had dizzy spells or syncope . The electrocardiogram was abnormal in all patients, revealing left ventricular hypertrophy in five, left ventricular hypertrophy with strain in six and abnormal Q waves alone in two . The chest roentgenogram showed a normal heart size in six patients and cardiac enlargement in seven . Echocardiograms, obtained in six patients, were diagnostic of idiopathic hypertrophic subaortic stenosis in all . The hernodynamic and angiographic findings of these patients are presented in Table II . Seven patients had an intraventricular pressure gradient at rest (13 to 90 mm Hg, average 62) . With provocation (Valsalva maneuver, isoproterenol infusion, postextrasystolic potentiation), an intraventricular gradient (30 to 180 mm Hg, average 109) could be induced in all patients .
One patient had an associated significant gradient at rest across the outflow tract of the right ventricle . One patient had severe two vessel coronary artery disease . Two patients had mild to moderate narrowing of the left anterior descending artery in its middle third during systole (milking effect) . 14 No narrowing or bridging of other coronary arteries was observed . Septal perforator narrowing was found in all 13 patients with idiopathic hypertrophic subaortic stenosis (Fig . 2) . It was marked (3+) in five patients, moderate (2+) in six and mild (1+) in two. Grade 3+ septal narrowing was always found in association with a pressure gradient at rest and severe outflow obstruction during provocation . Patients with no gradient at rest had 1+ or 2+ septal arterial narrowing . Mitral regurgitation of mild to moderate degree was present in nine patients .
TABLE II Hemodynamic and Angiographic Findings in 13 Patients With Idiopathic Hypertrophic Subaortic Stenosis Case no .
_ LV (Rest)
Aorta (Rest)
Pressures (mm Hq) IV Gradient Rest Maneuver
PA
RV
CO
1 2 3 4 5 6 7
200/24 178/36 188/6 170/18 130/12 140/10 180/16
130/60 118/64 135/70 170/95 130/70 140/80 180/78
76-90 60 50 0 0 0 0
130-160 124 60 96180 30 100 65
70/30 48/18 20/6 18/4 20/12 32/13 30/10
70/10 50/2 20/2 23/0 40/20 32/9 30/6
3 .09 3 .8 4 .6 4 .8 5 .3 4 .2 5 .2
8 9
180/4 160/25
115/65 160/80
65 0
80 120
32/15 36/18
32/6 36/14
4 .3 2 .7
10 11 12 13
179/9 188/25 208/30 134/13
121/80 152/77 111/68 135/76
58 13-37 97 0
140 125 161 133
26/14 30/15 40/21 23/5
26/7 35/12 42/8 23/2
5 .1 6 .5 7 .9 4 .8
Coronary Arteriography 30% RCA normal 30% mid LAD Normal Normal 100% LAD, 100% LCx a Mild narrowing mid LAD Normal Mod . narrowing mid LAD Normal Normal Normal Normal
Septa/ Perforator Narrowing During Systole 3+ 3+ 3+ 2+ 1+
MR
2+
no no 1+ 1-2+ no no 2+
3+ 2+
1+ 1+
3+ 2+ 2+ 2+
2+ 1+ 2+ 1+
1+
CO = cardiac output (liters/min) ; IV = intraventricular; LAD = left anterior descending coronary artery ; LCx. = posterolateral left circumflex artery ; LV = left ventricle; Mod. = moderate; MR = mitral regurgitation ; PA = pulmonary artery ; RCA = right coronary artery ; RV = right ventricle .
312
September 1977 The American Journal of CARDIOLOGY Volume 40
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL .
Normal control group : The first control group had 10 patients with a chest pain syndrome, normal coronary arteries, no outflow tract gradient and normal left ventricular function . None of these patients had septal perforator narrowing (Fig . 1) . The echocardiogram was normal in 7 of the 10 and showed mitral valve prolapse in 2 ; it was not obtained in 1 patient . Control group with left ventricular hypertrophy: A second control group had five consecutive patients with aortic stenosis and five consecutive patients with left ventricular hypertrophy of other cause . Among the patients with aortic stenosis, the outflow tract gradient ranged from 85 to 185 mm Hg (average 107) . Among the patients with idiopathic left ventricular hypertrophy, no outflow tract gradient was found (at rest or with provocation) . Angiographic left ventricular hypertrophy was significant in all 10 patients . None had obstructive coronary artery disease or septa] perforator narrowing . Bridging or narrowing of the left anterior descending or other coronary arteries was not observed in any of these 10 patients. Discussion The first publications 15,16 on coronary arteriography in patients with idiopathic hypertrophic subaortic stenosis demonstrated a normal coronary arterial tree although prominent Q waves in the electrocardiogram suggested myocardial infarction . Atherosclerotic obstruction of the coronary arteries was later described in association with idiopathic hypertrophic subaortic stenosis .6,7,17,18 Coronary arteriography is now recommended routinely for evaluating adult patients with the diagnosis of idiopathic hypertrophic subaortic stenosis who undergo cardiac catheterization . Our study demonstrates the presence of systolic narrowing (compression) of the septal perforator branches of the left anterior descending coronary artery during systole in patients with idiopathic hypertrophic subaortic stcnosis . To our knowledge, this finding has not previously been reported . Although varying in degree (1+ to R+) this was a consistent finding in this group of patients with idiopathic hypertrophic subaortic stenosis . The most severe degree of septal perforator narrowing (3+) was found in patients with an intraventricular gradient at rest or severe outflow tract obstruction on provocation with specific interventions such as the Valsalva maneuver or isoproterenol infusion . Septal perforator compression was not seen in the control groups of patients, that is, those with normal coronary arteries and normal left ventricle, those with severe aortic stenosis and those with idiopathic left ventricular hypertrophy. We recently observed one patient with hyperdynamic cardiomyopathy without outflow obstruction at rest or on provocation, who presented the phenomenon of septal perforator narrowing during systole . No elevation in right-sided pressures or other abnormalities were seen in this patient . The echocardiogram revealed a hyperdynamic left ventricle, normal thickness of the posterior left ven-
tricular wall and septum and decreased end-systolic volume. In view of this case, septa] perforator narrowing during systole, although unique, does not appear to be specific for idiopathic hypertrophic subaortic stenosis. Mechanism of septal perforator narrowing in idiopathic hypertrophic subaortic stenosis: The mechanism is not clear. Under normal circumstances, the septal perforator branches of the left anterior descending artery course close to the endocardium on the right side of the septum until their terminal arborization . 19 In this way, these vessels are not subjected to left ventricular pressures (except for the terminal ramifications that leave the parent vessel at a right angle) and have the flow pattern of epicardial vessels. Systolic narrowing of a coronary vessel occurs when it courses through the left ventricular myocardium (wall tension is greater than aortic pressure during systole 20 ) as demonstrated on coronary arteriography by the "bridging" or "milking" effeCt 14 of the left anterior descending artery. In consequence, the septal perforator narrowing observed in patients with idiopathic hypertrophic subaortic stenosis suggests that these vessels are subjected to intramyocardial tension during systole . Several theoretical possibilities would explain this phenomenon: 1. It is possible that the septal perforator branches course anomalously through the left ventricular side of the septum instead of lying in their normal position close to the right ventricular endocardium . This could be a coronary arterial malformation. Such a phenomenon could result in selective ischemia of the septum and might be related in some way to the pathogenesis of asymmetric septal hypertrophy and fibrosis because hypoxia is a well known stimulus for hypertrophy . 21,22 A similar phenomenon is seen in the hypertrophic fibrotic left ventricle of cases with anomalous origin of the left coronary artery from the pulmonary artery . 23 No pathologic studies are available to confirm this hypothesis . 2. The characteristic histologic findings in the septum of idiopathic hypertrophic subaortic stenosis are the presence of disorderly arranged muscle fibers, variable degrees of interstitial fibrosis and a bizarre type of cell hypertrophy.24.25 It is possible that this disorganized hypertrophy engulfs the septal perforator branches as a secondary phenomenon, subjecting these vessels to increased pressure during systole . Again, the subendocardial fibrosis of the septum may be due to the secondary new segmental ischemia . In summary, we have described the association of idiopathic hypertrophic subaortic stenosis with systolic narrowing of the septal perforator branches of the left anterior descending coronary artery as a consistent phenomenon . We have no definitive explanation for the physiopathologic mechanism involved but have analyzed some possibilities . This phenomenon, although unique, does not appear to be exclusive for idiopathic hypertrophic subaortic stenosis and can occur in any situation under similar physiologic conditions .
September 1977
The American Journal of CARDIOLOGY Volume 40
313
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS-PICHARD ET AL .
References 1 . Epstein SE, Henry WL, Clark CH, et al : Asymmetric septal hypertrophy . Ann Intern Med 81 :650 -680, 1974 2. Adelman AG, Willie ED, Ranganatan N, et al : The clinical course in muscular subaortic stenosis . A restrospective and prospective study of 60 hemodynamically proved cases . Ann Intern Med 77 : 515-525,1972 3. Shah PM, Adelman AG, Wlgle ED, at al : The natural (and unnatural) history of hypertrophic obstructive cardiomyopathy . A multicenter study. Circ Res 34,35:Suppl II :II-179-II-195, 1974 4 . Braunwald E, Morrow AG, Comell WP, et al : Idiopathic hypertrophic subaortic stenosis : clinical, hemodynamic, and angiographic manifestations . Am J Med 29 :924-925, 1960 5. Frank S, Braunwald E : Idiopathic hypertrophic subaortic stenosis : clinical analysis of 126 patients with emphasis on natural history . Circulation 37 :759-788, 1968 6. Gulotta SJ, Hamby RI, Aronson AL, et al : Coexistent idiopathic hypertrophic subaortic stenosis and coronary arterial disease . Circulation 46 :890-896, 1972 7 . Oran E, Gupta S, Yeo B, et al : Idiopathic hypertrophic subaortic stenosis in patients with coronary artery disease . Importance, recognition and principles of management . Angiology 24 :538-547, 1973 8 . King JF, deMaria AN, Reis RL, et al : Echocardiographic assessment of idiopathic hypertrophic subaortic stenosis . Chest 64: 723-731,1973 9 . Tajik AJ, Giuliani ER : Echocardiographic observations in idiopathic hypertrophic subaortic stenosis . Mayo Clin Proc 49:89-97, 1974 10 . Rossen RM, Goodman DJ, Ingham RE, et al : Ventricular systolic septa) thickening and excursion in idiopathic hypertrophic subaortic stenosis . N Engl J Med 291 :1317-1319, 1974 11 . Wong B, Langon RA, Cohen LS, at al : Retrograde catheterization of the left atrium in idiopathic hypertrophic subaortic stenosis . Am J Cardiol 36 :62-66, 1975 12 . Sones FM, Shiner EK : Cine coronary arteriography . Mod Concepts Cardiovasc Dis 31 :735-738, 1962
314
September 1977
13. Judkins MP: Selective coronary arteriography . I . A percutaneous transfemoral technique . Radiology 89:815-824, 1967 14 . Noble J, Bourassa MG, Petitclare R, at al : Myocardial bridging and milking effect of the left anterior descending coronary artery : normal variant or obstruction? Am J Cardiol 37 :993-999, 1976 15 . Cohen RJ, Kaljot V, Czarnecki SW : Septal hypertrophy of hypertrophic subaortic stenosis simulating the electrocardiographic pattern of myocardial infarction . Vasc Dis 1 :269, 1964 16 . Klein MD, Mathur V, Levin HD, et al : Electromechanical correlations in hypertrophic subaortic stenosis . Circulation 38 :635-648, 1968 17 . Giuliani ER, Tajik AJ, Frye RL, et al: Idiopathic hypertrophic subaortic stenosis (IHSS) and associated coronary artery disease (abstr). Circulation 45,46 :Suppl II :II-156, 1972 18 . Marcus GB, Popp RL, Stinson EB: Coronary-artery disease with Idiopathic hypertrophle subaortic stenosis . Lancet 1 :901-903, 1974 19 . James TM, Burch GE : Blood supply of the human interventricular septum . Circulation 17:391-396, 1958 20 . Gorlin R: Physiology of the coronary circulation . In, The Heart, third edition (Hurst JW, Logue RR, ad) . New York, McGraw Hill, 1974, p 110 21 . Van Liere EJ, Krames BB, Northup DW : Differences in cardiac hypertrophy in exercise and hypoxia . Circ Res 16 :244-248, 1965 22 . Hollenberg M : Effect of oxygen on growth of cultured myocardial cells. Circ Res 28 :148-157, 1971 23 . Cohen M, Slew S : Aberrant left coronary artery . Report of a case and review of literature . Circulation 20 :918-927, 1959 24 . Ferrans VJ, Morrow AG, Roberts WC : Myocardial ultrastructure in indicpathic hypertrophic subaortic stenosis . A study of operatively excised left ventricular outflow tract muscle in 14 patients . Circulation 45 :769-792, 1972 25 . Ferrans VJ: Characteristic cellular abnormalities of ventricular septal myocardium in asymmetric septal hypertrophy. Ann Intern Med 81 :650-680, 1974
The American Journal of CARDIOLOGY Volume 40
