Refer to: Criley JM: The bottom line syndrome-Hypertrophic cardiomyopathy revisited (Editorial Comment). West J Med 130:350-353, Apr 1979
EDITORIAL COMMENT
The Bottom Line Syndrome Hypertrophic Cardiomyopathy Revisited J. MICHAEL CRILEY, MD, Torrance, California
PROLIFERATION of biomedical literature leads many of us into bad habits. Faced with the impossibility of keeping up, we tend to read the ab-
THE
stract rather than the full article, seeking the
"bottom line." On the other hand, review articles, such as that by Shabetai and co-workers in this issue of the journal, require that interested readers digest a meatier text. Many of us breathe a sigh of relief when we encounter such a comprehensive article, summarizing upwards of 100 well-chosen references (which we now do not have to read). However, we must be wary of the bottom line syndrome even when we read comprehensive review articles, because the authors cannot avoid bias in presenting what they sincerely believe to be the bottom line in a clear and understandable manner. The bottom line that will be carried away by the reader of Shabetai's article is that there is a "dynamic obstruction to outflow" of the left ventricle, and that it therefore must be a significant manifestation of hypertrophic cardiomyopathy (HCM). Having an admitted bias against this "obstructionistic" viewpoint, and realizing that few readers will bother reading the 96 references cited, I will take the editorialist's prerogative to present the other side, going over some of the same ground with differing emphasis. My bottom line is "an obstruction, if present, has little or nothing to do with the morbidity and mortality from HCM."
Discovery Brock's"2 discovery in the late 1950's of the condition now known as hypertrophic cardiomyDr. Criley is Professor of Medicine and Radiological Sciences, UCLA School of Medicine, and Chief, Division of Cardiology, Harbor General-UCLA Medical Center, Torrance, California. Dr. Criley's project was supported by American Heart Association (Greater Los Angeles Affiliate) Research Award No.
4271G8, 1978-1979, and NIH Grant No. HL-14714. Reprint requests to: J. Michael Criley, MD, Chief, Div. of Cardiology, Harbor General-UCLA Medical Center, 1000 Carson Street, Torrance, CA 90509.
350
APRIL 1979
*
130
*
4
opathy sparked two decades of investigation, prolific documentation and unresolved controversy. The premortem recognition of HCM required techniques which only came into existence in the past 25 years, hence its relatively late discovery, considering the apparent prevalence of the condition. Brock's pioneering discovery resulted from observations made at left heart catheterization and during intracardiac surgical procedures, techniques then in their infancy. As left heart catheterization and selective angiocardiography became widespread, a flood of observations and interpretations came forth. A more recent resurgence of interest followed the advent of conventional echocardiography, and it can be predicted that two-dimensional echocardiography will spark yet another era of discovery and controversy.
The Controversy It may be surprising to some that any significant controversy should remain after all of this modern technology has been brought to bear on this disease entity. The heart of the controversy is the role of obstruction in the pathophysiology of the disease. The focus of virtually every article written in the formative years of our knowledge of HCM as well as the current review article is on the primacy of obstruction. The sheer weight of these articles, in which HCM was referred to as functional obstruction of the left ventricle,1 2 pseudoaortic stenosis,3 functional aortic stenosis,4 muscular subaortic stenosis,5 idiopathic hypertrophic subaortic stenosis (IHSS) ," obstructive cardiomyopathy,7 diffuse subvalvular aortic stenosis8 and subaortic hypertrophic stenosis9 renders the task of challenging the pivotal role of obstruction difficult. It is hoped that a careful reading of this editorial (and the supporting references) will show that the case for obstruction remains cir-
HYPERTROPHIC CARDIOMYOPATHIES
cumstantial, and that continued challenge and open-minded investigation is justified. A Reexamination of the Original Case for Obstruction A reexamination should begin with Brock's" 2 and Teare's'0 articles, which introduced HCM to the medical literature. Brock, contrary to popular belief, failed to find any obstruction while thoroughly exploring the outflow tract of the beating heart with bougies and fully expanded dilators passed through the left ventricular apex: A 4 mm bougie was passed and encountered no obstruction and could be moved freely from side to side. The same findings were obtained with a 7 mm bougie. Finally an expanding dilator was passed and was opened gently in the valvar and subvalvar regions and encountered no sense of resistance; it could be moved up and down freely.2
Although he bracketed these manipulations with pressure withdrawal tracings to confirm the persistence of the gradient, he was repeatedly unable to find any obstruction in the four patients he operated upon, three of whom died. He stated "the functional nature of the obstruction is concealed in death. Indeed it is concealed in life unless we are able to document its presence by means of a pressure withdrawal record."2 Brock began his second article describing the skepticism with which his first article was received citing that there was ". . . doubt about the very occurrence of functional obstruction of the ventricle." He referred the reader to his earlier classical studies on right ventricular infundibular stenosis complicating pulmonic stenosis. He was cognizant of the important anatomical differences between the muscular right ventricular infundibulum and the noncontractile subaortic vestibule, but stated that "below this rigid vestibule the walls of the outflow tract are chiefly muscular and, when sufficiently hypertrophied, they can come together at an early stage of systole and constitute an obstruction to the continued emptying of the left ventricle." He offered as sole proof of this obstruction the pressure gradient on catheter withdrawal recordings, despite the fact that his meticulous exploration of the beating heart failed to find the elusive sphincter. Thus Brock's "bottom line" that the gradient proved the existence of an obstruction established a bias that could not fail to influence future investigators studying HCM. Teare's'0 original article entitled "Asymmetrical hypertrophy of the heart in young adults" (sub-
mitted for publication before Brock's first article) pointed out the inordinate septal hypertrophy with bizarre cellular disarray in nine patients, eight of whom had died suddenly, but he made no mention of outflow tract narrowing or obstruction. Later, while describing his pioneering studies on the "tumour-like" septum he said "A bizarre and disorderly arrangement of bundles of muscle fibres runs in divers directions . . . giving the impression of inefficiency in muscular contraction of the tumour as a whole... ." In the ensuing discussion of his paper Dr. John Goodwin questioned this "inefficient contraction." citing the tremendous pressure generation and high output of the left ventricle to the contrary. Dr. Teare replied ". . . one gets the impression, looking at these sections, that bundles of muscles are all pulling in different directions rather than together, but if you say that in fact they produce a powerful ejection, I naturally accept it."" In the next five years, Brock's observation that a pressure gradient could develop in the left ventricle was repeatedly confirmed in laboratories all over the world, and the unique characteristics of the phenomenon were explored. The gradient increased with inotropic stimulation or by decreasing preload or afterload, and the gradient could be decreased by increasing the preload or afterload. "Gradient" and "obstruction" were considered synonymous by all but a few authors. Selective angiocardiograms purporting to show the muscular sphincter as a conical or hourglass narrowing of the outflow tract were published,'2-'5 and the tip of the cone was considered to be the site of obstruction.'4"15 Surgical descriptions of the muscular sphincter followed: "Forceful contraction of the outflow tract on the beating finger is evident during systole" (Morrow).15 "Upon making a small apical ventriculotomy, palpation with the finger of the ventricular chamber showed a small apical chamber. During systole, the musculature of the outflow tract contracted over a long segment, squeezing the operator's finger to a degree which could only be duplicated with some effort within the fist of the other hand" (Julian)."" "That this obstruction is dynamic is immediately appreciated by the surgeon who passes his finger down through the obstruction in a beating heart. The compression around the finger is nothing short of painful" (Dobell). By the mid-1960's, the case for a muscular sphincter which progressively narrowed during systole and obstructed left ventricular outflow THE WESTERN JOURNAL OF MEDICINE
351
HYPERTROPHIC CARDIOMYOPATHIES
seemed firmly established,15 and the equation pressure gradient=obstruction seemed secure, in light of angiographic "cone" and the surgical proof of the muscular sphincter. The Challenge The equation was questioned'8 by Hernandez and co-workers in 1964. They stated the intraventricular pressure drop characteristic of these patients has led to the postulate that obstruction takes place in systole because of a constricting ring of hypertrophied muscle in the outflow tract of the left ventricle below the aortic valve. This pressure drop, however, is not in itself proof of a discrete obstruction in the infundibulum. An abnormally powerful and rapid contraction of the ventricle may possibly produce almost total ejection early in systole so that late in systole there remains a virtually empty ventricle contracting on the catheter tip trapped in small, isolated pockets of blood among the trabeculae . . . careful ventricular volume studies will be necessary to settle this question.'8
Gauer,' 120 working in animals with hypovolemia, had previously shown that regions of high intraventricular pressure can be generated when "the ventricle continues to contract after having expelled its pathologically small blood content." Cineangiographic studies in patients with HCM and pressure gradients showed the following: (1) The ventricle emptied more rapidly and completely than the normal. (2) When the gradient was increased after premature beats or isoproterenol infusion, more rapid and more complete emptying resulted. (3) The "conical" or "hourglass" narrowing of the left ventricle displayed by other authors was in fact a diastolic event. (4) There was no angiographically demonstrable systolic muscular narrowing of the outflow tract.2"22 The intraventricular pressure gradient was attributed to "cavity obliteration," the phenomenon described by Gauer in which the ventricle expels its blood rapidly and then continues to exert pressure isometrically in late systole in contractile regions of the ventricle (the body and the apex) while the noncontractile region (the aortic vestibule) maintains a lower systolic pressure equal to that in the aorta. The angiographic findings (high ejection fraction rapidly expelled) supported this concept since they frequently showed virtual obliteration of the cavity of the left ventriclel5'222 to within a few centimeters of the aortic valve which offered an explanation for the squeeze on the surgeon's finger'5-'7 as well. Although the term "cavity obliteration" has been used consistently by this author to describe the pressure phenomenon in which the virtually 352
APRIL 1979 * 130 * 4
obliterated portions of the left ventricle created a higher intracavitary pressure than that in the noncontractile subaortic region,2'-23 other authors later substituted the term "catheter entrapment."26'27 This change in terminology implied that the observed pressure phenomenon was artifactual and in some way caused by compression or distortion of the catheter. It was and still is our contention that these pressures are not artifacts, but represent true pressure conditions in the ventricle.23 The Rebuttal-Emergence of the Mitral Valve as the New Site of Obstruction These articles which challenged the holy triad of IHSS-HCM (the pressure gradient, the angiographic cone and the surgeon's sphincter) sparked considerable rebuttal, during which the sphincter or contraction ringl5-'7 was replaced by mitral valve-septal apposition as the site of obstruction.24 This subtle shift is not apparent to the "bottom line" reader, since the muscular sphincter was not formally renounced-the new obstruction quietly took its place. Echocardiography showed that the thickened septum, which was the prime mover in the old contraction ring was in fact almost inert, and that the active part of the new obstruction was apparently the systolic anterior movement (SAM) of the mitral valve.25 The same angiographic frames used to show the "old"28(Fig. 6) obstruction were merely republished with newly positioned arrows pointing to the "new" obstruction.24 The "bottom line" emerging from the rebuttal was that there is indeed an obstruction, and its presence can be "proved" hemodynamically by placing a transseptal catheter in the inflow tract,24 or just inside the mitral valve,26 a catheter position which is purported to rule out "catheter en-
trapment."26'27 Angiocardiographic demonstrations of a "lucent line" representing anterior leafletseptal apposition and echocardiographic systolic tnterior motion (SAM)24 seemingly provided the anatomical clinchers. It is of interest to note that the surgical approach to the "new" site of obstruction remained essentially the same as it had been when the obstruction was a contraction ring:. incision and resection of a strip of muscle from the hypertrophied septum. In 1964 Morrow stated "when obstruction to outflow existed, it resulted from the contraction of the abnormal muscle mass during systole," and described and illustrated (in Figures
HYPERTROPHIC CARDIOMYOPATHIES
117 and 118) the "contraction ring."'15 In 1975 he stated "the operative method presently utilized to relieve outflow tract obstruction in IHSS is similar in principle to the technique of left ventriculomyotomy and myectomy described in 1 964."29
Current Status of the Nonobstructive Concept Before accepting the "bottom line" espoused anew in the current review article, the reader is advised to ponder some of the following dilemmas, many of which are mentioned (but might be overlooked by a "bottom line" reader) in Shabetai's article: (1) HCM patients without pressure gradients (and therefore without obstruction) often have as much or more hypertrophy, may be as or more symptomatic and may have a significantly higher mortality than those who do.30 (2) The left ventricle in HCM empties more rapidly and more completely than the normal22-24'3' (see Figure 4 of the review article), a finding that challenges the accepted definition of obstruction. (3) Echocardiographic "SAM" iS seen in non-HCM ventricles without "obstruction," and may not always represent anterior mitral leaflet, but chordae or papillary muscles,32 which may oppose the septum without obstructing outflow. (4) Pressure gradients indistinguishable from those seen in HCM can be recorded in normal ventricles without any evidence of obstruction,19, 20,23,33 when the ventricle contracts excessively due to inotropic stimulation combined with reduced preload or afterload. (5) An angiographic "lucent line" representing "SAM" can be produced in experimental animals by creating a chronically hypertrophied ventricle which empties vigorously,34 and therefore may result from distortion of the mitral valve in an excessively contracted left ventricular cavity. The evidence that a significant obstruction exists (that is, one that impedes left ventricular emptying), and that it is responsible for the morbidity and mortality in HCM iS still not established 21 years after its discovery. And that is the bottom line. REFERENCES 1. Brock R: Functional obstruction of the left ventricle (acquired aortic subvalvar stenosis). Guy's Hosp Rep 106:221, 1957 2. Brock R: Functional obstruction of the left ventricle (acquired aortic subvalvar stenosis). Guy's Hosp Rep 108:126, 1959 3. Bercu BA, Diettert GA, Danforth WH, et al: Pseudoaortic stenosis produced by ventricular hypertrophy. Am J Med 25:814, 1958
4. Morrow AG, Braunwald E: Functional aortic stenosis-A malformation characterized by resistance to left ventricular outflow without anatomic obstruction. Circulation 20:181, 1959 5. Wigle ED, Heimbecker RO, Gunton RW: Idiopathic ventricular septal hypertrophy causing muscular subaortic stenosis. Circulation 26:325, 1962 6. Braunwald E, Morrow AG, Cornell WP, et al: Idiopathic hypertrophic subaortic stenosis. Am J Med 29:924, 1960 7. Goodwin JF, Hollman A, Cleland WP, et al: Obstructive cardiomyopathy simulating aortic stenosis. Br Heart J 22:403, 1960 8. Kirklin JW, Ellis FH Jr: Surgical relief of diffuse subvalvular aortic stenosis. Circulation 24:739, 1961 9. Kittle CF, Reed WA, Crockett JE: Infundibulectomy for subaortic hypertrophic stenosis. Circulation 29 (Suppl) :119-124, Apr 1964 10. Teare D: Asymmetrical hypertrophy of the heart in young adults. Br Heart J 20:1-8, 1958 11. Teare RD: The pathological recognition of obstructive cardiomyopathy, In Wolstenholme GEW, O'Connor M (Eds): Ciba Foundation Symposium Cardiomyopathies. Boston, Little Brown & Co., 1964 12. Morrow AG, Braunwald E: Functional aortic stenosis: A malformation characterized by resistance to left ventricular outflow without anatomic obstruction. Circulation 20:181, 1959 (Fig. 8) 13. Perloff JP: The Clinical Recognition of Congenital Heart Disease. Philadelphia, WB Saunders Co, 1970 (Fig. 6-3) 14. Sokolow M, Mcllroy MB: Clinical Cardiology. Los Altos, Lange Medical Publication, 1977 (Fig. 17-14) 15. Braunwald E, Lambrew CT, Morrow AG, et al: Idiopathic hypertrophic subaortic stenosis. Circulation 30 (Suppl 1V): IV-lIV-213, 1964 16. Julian OC, Dye WS, Javid H, et al: Apical left ventriculotomy in subaortic stenosis due to a fibromuscular hypertrophy. Circulation (Suppl 1):1-44, 1965 17. Dobell ARC, Scott HJ: Hypertrophic subaortic stenosis: Evolution of a surgical technique. J Thoracic Cardiovasc Surg 47:26, 1964 18. Hernandez RR, Greenfield JC Jr, McCall BW: Pressure flow studies in hypertrophic subaortic stenosis. J Clin Invest 43: 401, 1964 19. Gauer OH: Evidence in circulatory shock of an isometric phase of ventricular contraction following ejection (Abstr). Fed Proc 9:47, 1950 20. Gauer OH, Henry JP: Negative (-G2) acceleration in relation to arterial oxygen saturation, subendocardial hemorrhage and venous pressure in the forehead. Aerospace Med 35:533, 1964 21. Criley JM, Lewis KB, White RI Jr, et al: Pressure gradients without obstruction: A new concept of "hypertrophic subaortic stenosis." Circulation 32:881, 1965 22. Wilson WS, Criley JM, Ross RS: Dynamics of left ventricular emptying in hypertrophic subaortic stenosis. Am Heart J 74:4, 1967 23. White RI Jr, Criley JM, Lewis KB, et al: Experimental production of intracavity pressure differences-Possible significance in the interpretation of human hemodynamic studies. Am J Cardiol 19:806, 1967 24. Ross J Jr, Braunwald E, Gault JH, et al: The mechanism of the intraventricular pressure gradient in idiopathic hypertrophic subaortic stenosis. Circulation 34:558, 1966 25. Shah PM, Gramiak R, Kramer DH: Ultrasound localization of left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40:3-11, 1969 26. Wigle ED, Auger P, Marquis Y: Muscular subaortic stenosis. The initial left ventricular inflow tract pressure as evidence of outflow tract obstruction. Can Med Assoc J 95:793-797, 1966 27. Adelman AG, Wigle ED: Two types of intraventricular pressure difference in the same patient-Left ventricular catheter entrapment and right ventricular outflow tract obstruction. Circulation 38:649, 1968 28. Braunwald E, Morrow AG, Cornell, et al: Idiopathic hypertrophic subaortic stenosis: Clinical, hemodynamic and angiographic manifestations. Am J Med 29:924, 1960 29. Morrow AG, Reitz BA, Epstein SE, et al: Operative treatment in hypertrophic subaortic stenosis. Circulation 52:88-102, 1975 30. Frank S, Braunwald E: Idiopathic hypertrophic subaortic stenosis: Clinical analysis of 126 patients-Emphasis on the natural history. Circulation 37:759-788, 1968 31. Murgo JP, Alter B, Dorethy J, et al: Aortic flow dynamics in hypertrophic cardiomyopathy with and without left ventricular pressure gradients (Abstr). Circulation 56:11-37, 1977 32. Gehrke J: Reliability of systolic anterior motion (SAM) of the mitral valve and asymmetric septal hypertrophy (ASH) in hypertrophic cardiomyopathy (HCM). Am J Cardiol 39:271, 1977 33. Shabetai R: A new syndrome in hypovolemic shock. Am J Cardiol 24:404, 1969 34. Criley JM, Lennon PA, Abbasi AS, et al: Hypertrophic cardiomyopathy, In Levine HJ (Ed): Clinical Cardiovascular Physiology. New York, Grune & Stratton, 1976
THE WESTERN JOURNAL OF MEDICINE
353
EDITORIAL COMMENT
The Bottom Line Syndrome Hypertrophic Cardiomyopathy Revisited J. MICHAEL CRILEY, MD, Torrance, California
PROLIFERATION of biomedical literature leads many of us into bad habits. Faced with the impossibility of keeping up, we tend to read the ab-
THE
stract rather than the full article, seeking the
"bottom line." On the other hand, review articles, such as that by Shabetai and co-workers in this issue of the journal, require that interested readers digest a meatier text. Many of us breathe a sigh of relief when we encounter such a comprehensive article, summarizing upwards of 100 well-chosen references (which we now do not have to read). However, we must be wary of the bottom line syndrome even when we read comprehensive review articles, because the authors cannot avoid bias in presenting what they sincerely believe to be the bottom line in a clear and understandable manner. The bottom line that will be carried away by the reader of Shabetai's article is that there is a "dynamic obstruction to outflow" of the left ventricle, and that it therefore must be a significant manifestation of hypertrophic cardiomyopathy (HCM). Having an admitted bias against this "obstructionistic" viewpoint, and realizing that few readers will bother reading the 96 references cited, I will take the editorialist's prerogative to present the other side, going over some of the same ground with differing emphasis. My bottom line is "an obstruction, if present, has little or nothing to do with the morbidity and mortality from HCM."
Discovery Brock's"2 discovery in the late 1950's of the condition now known as hypertrophic cardiomyDr. Criley is Professor of Medicine and Radiological Sciences, UCLA School of Medicine, and Chief, Division of Cardiology, Harbor General-UCLA Medical Center, Torrance, California. Dr. Criley's project was supported by American Heart Association (Greater Los Angeles Affiliate) Research Award No.
4271G8, 1978-1979, and NIH Grant No. HL-14714. Reprint requests to: J. Michael Criley, MD, Chief, Div. of Cardiology, Harbor General-UCLA Medical Center, 1000 Carson Street, Torrance, CA 90509.
350
APRIL 1979
*
130
*
4
opathy sparked two decades of investigation, prolific documentation and unresolved controversy. The premortem recognition of HCM required techniques which only came into existence in the past 25 years, hence its relatively late discovery, considering the apparent prevalence of the condition. Brock's pioneering discovery resulted from observations made at left heart catheterization and during intracardiac surgical procedures, techniques then in their infancy. As left heart catheterization and selective angiocardiography became widespread, a flood of observations and interpretations came forth. A more recent resurgence of interest followed the advent of conventional echocardiography, and it can be predicted that two-dimensional echocardiography will spark yet another era of discovery and controversy.
The Controversy It may be surprising to some that any significant controversy should remain after all of this modern technology has been brought to bear on this disease entity. The heart of the controversy is the role of obstruction in the pathophysiology of the disease. The focus of virtually every article written in the formative years of our knowledge of HCM as well as the current review article is on the primacy of obstruction. The sheer weight of these articles, in which HCM was referred to as functional obstruction of the left ventricle,1 2 pseudoaortic stenosis,3 functional aortic stenosis,4 muscular subaortic stenosis,5 idiopathic hypertrophic subaortic stenosis (IHSS) ," obstructive cardiomyopathy,7 diffuse subvalvular aortic stenosis8 and subaortic hypertrophic stenosis9 renders the task of challenging the pivotal role of obstruction difficult. It is hoped that a careful reading of this editorial (and the supporting references) will show that the case for obstruction remains cir-
HYPERTROPHIC CARDIOMYOPATHIES
cumstantial, and that continued challenge and open-minded investigation is justified. A Reexamination of the Original Case for Obstruction A reexamination should begin with Brock's" 2 and Teare's'0 articles, which introduced HCM to the medical literature. Brock, contrary to popular belief, failed to find any obstruction while thoroughly exploring the outflow tract of the beating heart with bougies and fully expanded dilators passed through the left ventricular apex: A 4 mm bougie was passed and encountered no obstruction and could be moved freely from side to side. The same findings were obtained with a 7 mm bougie. Finally an expanding dilator was passed and was opened gently in the valvar and subvalvar regions and encountered no sense of resistance; it could be moved up and down freely.2
Although he bracketed these manipulations with pressure withdrawal tracings to confirm the persistence of the gradient, he was repeatedly unable to find any obstruction in the four patients he operated upon, three of whom died. He stated "the functional nature of the obstruction is concealed in death. Indeed it is concealed in life unless we are able to document its presence by means of a pressure withdrawal record."2 Brock began his second article describing the skepticism with which his first article was received citing that there was ". . . doubt about the very occurrence of functional obstruction of the ventricle." He referred the reader to his earlier classical studies on right ventricular infundibular stenosis complicating pulmonic stenosis. He was cognizant of the important anatomical differences between the muscular right ventricular infundibulum and the noncontractile subaortic vestibule, but stated that "below this rigid vestibule the walls of the outflow tract are chiefly muscular and, when sufficiently hypertrophied, they can come together at an early stage of systole and constitute an obstruction to the continued emptying of the left ventricle." He offered as sole proof of this obstruction the pressure gradient on catheter withdrawal recordings, despite the fact that his meticulous exploration of the beating heart failed to find the elusive sphincter. Thus Brock's "bottom line" that the gradient proved the existence of an obstruction established a bias that could not fail to influence future investigators studying HCM. Teare's'0 original article entitled "Asymmetrical hypertrophy of the heart in young adults" (sub-
mitted for publication before Brock's first article) pointed out the inordinate septal hypertrophy with bizarre cellular disarray in nine patients, eight of whom had died suddenly, but he made no mention of outflow tract narrowing or obstruction. Later, while describing his pioneering studies on the "tumour-like" septum he said "A bizarre and disorderly arrangement of bundles of muscle fibres runs in divers directions . . . giving the impression of inefficiency in muscular contraction of the tumour as a whole... ." In the ensuing discussion of his paper Dr. John Goodwin questioned this "inefficient contraction." citing the tremendous pressure generation and high output of the left ventricle to the contrary. Dr. Teare replied ". . . one gets the impression, looking at these sections, that bundles of muscles are all pulling in different directions rather than together, but if you say that in fact they produce a powerful ejection, I naturally accept it."" In the next five years, Brock's observation that a pressure gradient could develop in the left ventricle was repeatedly confirmed in laboratories all over the world, and the unique characteristics of the phenomenon were explored. The gradient increased with inotropic stimulation or by decreasing preload or afterload, and the gradient could be decreased by increasing the preload or afterload. "Gradient" and "obstruction" were considered synonymous by all but a few authors. Selective angiocardiograms purporting to show the muscular sphincter as a conical or hourglass narrowing of the outflow tract were published,'2-'5 and the tip of the cone was considered to be the site of obstruction.'4"15 Surgical descriptions of the muscular sphincter followed: "Forceful contraction of the outflow tract on the beating finger is evident during systole" (Morrow).15 "Upon making a small apical ventriculotomy, palpation with the finger of the ventricular chamber showed a small apical chamber. During systole, the musculature of the outflow tract contracted over a long segment, squeezing the operator's finger to a degree which could only be duplicated with some effort within the fist of the other hand" (Julian)."" "That this obstruction is dynamic is immediately appreciated by the surgeon who passes his finger down through the obstruction in a beating heart. The compression around the finger is nothing short of painful" (Dobell). By the mid-1960's, the case for a muscular sphincter which progressively narrowed during systole and obstructed left ventricular outflow THE WESTERN JOURNAL OF MEDICINE
351
HYPERTROPHIC CARDIOMYOPATHIES
seemed firmly established,15 and the equation pressure gradient=obstruction seemed secure, in light of angiographic "cone" and the surgical proof of the muscular sphincter. The Challenge The equation was questioned'8 by Hernandez and co-workers in 1964. They stated the intraventricular pressure drop characteristic of these patients has led to the postulate that obstruction takes place in systole because of a constricting ring of hypertrophied muscle in the outflow tract of the left ventricle below the aortic valve. This pressure drop, however, is not in itself proof of a discrete obstruction in the infundibulum. An abnormally powerful and rapid contraction of the ventricle may possibly produce almost total ejection early in systole so that late in systole there remains a virtually empty ventricle contracting on the catheter tip trapped in small, isolated pockets of blood among the trabeculae . . . careful ventricular volume studies will be necessary to settle this question.'8
Gauer,' 120 working in animals with hypovolemia, had previously shown that regions of high intraventricular pressure can be generated when "the ventricle continues to contract after having expelled its pathologically small blood content." Cineangiographic studies in patients with HCM and pressure gradients showed the following: (1) The ventricle emptied more rapidly and completely than the normal. (2) When the gradient was increased after premature beats or isoproterenol infusion, more rapid and more complete emptying resulted. (3) The "conical" or "hourglass" narrowing of the left ventricle displayed by other authors was in fact a diastolic event. (4) There was no angiographically demonstrable systolic muscular narrowing of the outflow tract.2"22 The intraventricular pressure gradient was attributed to "cavity obliteration," the phenomenon described by Gauer in which the ventricle expels its blood rapidly and then continues to exert pressure isometrically in late systole in contractile regions of the ventricle (the body and the apex) while the noncontractile region (the aortic vestibule) maintains a lower systolic pressure equal to that in the aorta. The angiographic findings (high ejection fraction rapidly expelled) supported this concept since they frequently showed virtual obliteration of the cavity of the left ventriclel5'222 to within a few centimeters of the aortic valve which offered an explanation for the squeeze on the surgeon's finger'5-'7 as well. Although the term "cavity obliteration" has been used consistently by this author to describe the pressure phenomenon in which the virtually 352
APRIL 1979 * 130 * 4
obliterated portions of the left ventricle created a higher intracavitary pressure than that in the noncontractile subaortic region,2'-23 other authors later substituted the term "catheter entrapment."26'27 This change in terminology implied that the observed pressure phenomenon was artifactual and in some way caused by compression or distortion of the catheter. It was and still is our contention that these pressures are not artifacts, but represent true pressure conditions in the ventricle.23 The Rebuttal-Emergence of the Mitral Valve as the New Site of Obstruction These articles which challenged the holy triad of IHSS-HCM (the pressure gradient, the angiographic cone and the surgeon's sphincter) sparked considerable rebuttal, during which the sphincter or contraction ringl5-'7 was replaced by mitral valve-septal apposition as the site of obstruction.24 This subtle shift is not apparent to the "bottom line" reader, since the muscular sphincter was not formally renounced-the new obstruction quietly took its place. Echocardiography showed that the thickened septum, which was the prime mover in the old contraction ring was in fact almost inert, and that the active part of the new obstruction was apparently the systolic anterior movement (SAM) of the mitral valve.25 The same angiographic frames used to show the "old"28(Fig. 6) obstruction were merely republished with newly positioned arrows pointing to the "new" obstruction.24 The "bottom line" emerging from the rebuttal was that there is indeed an obstruction, and its presence can be "proved" hemodynamically by placing a transseptal catheter in the inflow tract,24 or just inside the mitral valve,26 a catheter position which is purported to rule out "catheter en-
trapment."26'27 Angiocardiographic demonstrations of a "lucent line" representing anterior leafletseptal apposition and echocardiographic systolic tnterior motion (SAM)24 seemingly provided the anatomical clinchers. It is of interest to note that the surgical approach to the "new" site of obstruction remained essentially the same as it had been when the obstruction was a contraction ring:. incision and resection of a strip of muscle from the hypertrophied septum. In 1964 Morrow stated "when obstruction to outflow existed, it resulted from the contraction of the abnormal muscle mass during systole," and described and illustrated (in Figures
HYPERTROPHIC CARDIOMYOPATHIES
117 and 118) the "contraction ring."'15 In 1975 he stated "the operative method presently utilized to relieve outflow tract obstruction in IHSS is similar in principle to the technique of left ventriculomyotomy and myectomy described in 1 964."29
Current Status of the Nonobstructive Concept Before accepting the "bottom line" espoused anew in the current review article, the reader is advised to ponder some of the following dilemmas, many of which are mentioned (but might be overlooked by a "bottom line" reader) in Shabetai's article: (1) HCM patients without pressure gradients (and therefore without obstruction) often have as much or more hypertrophy, may be as or more symptomatic and may have a significantly higher mortality than those who do.30 (2) The left ventricle in HCM empties more rapidly and more completely than the normal22-24'3' (see Figure 4 of the review article), a finding that challenges the accepted definition of obstruction. (3) Echocardiographic "SAM" iS seen in non-HCM ventricles without "obstruction," and may not always represent anterior mitral leaflet, but chordae or papillary muscles,32 which may oppose the septum without obstructing outflow. (4) Pressure gradients indistinguishable from those seen in HCM can be recorded in normal ventricles without any evidence of obstruction,19, 20,23,33 when the ventricle contracts excessively due to inotropic stimulation combined with reduced preload or afterload. (5) An angiographic "lucent line" representing "SAM" can be produced in experimental animals by creating a chronically hypertrophied ventricle which empties vigorously,34 and therefore may result from distortion of the mitral valve in an excessively contracted left ventricular cavity. The evidence that a significant obstruction exists (that is, one that impedes left ventricular emptying), and that it is responsible for the morbidity and mortality in HCM iS still not established 21 years after its discovery. And that is the bottom line. REFERENCES 1. Brock R: Functional obstruction of the left ventricle (acquired aortic subvalvar stenosis). Guy's Hosp Rep 106:221, 1957 2. Brock R: Functional obstruction of the left ventricle (acquired aortic subvalvar stenosis). Guy's Hosp Rep 108:126, 1959 3. Bercu BA, Diettert GA, Danforth WH, et al: Pseudoaortic stenosis produced by ventricular hypertrophy. Am J Med 25:814, 1958
4. Morrow AG, Braunwald E: Functional aortic stenosis-A malformation characterized by resistance to left ventricular outflow without anatomic obstruction. Circulation 20:181, 1959 5. Wigle ED, Heimbecker RO, Gunton RW: Idiopathic ventricular septal hypertrophy causing muscular subaortic stenosis. Circulation 26:325, 1962 6. Braunwald E, Morrow AG, Cornell WP, et al: Idiopathic hypertrophic subaortic stenosis. Am J Med 29:924, 1960 7. Goodwin JF, Hollman A, Cleland WP, et al: Obstructive cardiomyopathy simulating aortic stenosis. Br Heart J 22:403, 1960 8. Kirklin JW, Ellis FH Jr: Surgical relief of diffuse subvalvular aortic stenosis. Circulation 24:739, 1961 9. Kittle CF, Reed WA, Crockett JE: Infundibulectomy for subaortic hypertrophic stenosis. Circulation 29 (Suppl) :119-124, Apr 1964 10. Teare D: Asymmetrical hypertrophy of the heart in young adults. Br Heart J 20:1-8, 1958 11. Teare RD: The pathological recognition of obstructive cardiomyopathy, In Wolstenholme GEW, O'Connor M (Eds): Ciba Foundation Symposium Cardiomyopathies. Boston, Little Brown & Co., 1964 12. Morrow AG, Braunwald E: Functional aortic stenosis: A malformation characterized by resistance to left ventricular outflow without anatomic obstruction. Circulation 20:181, 1959 (Fig. 8) 13. Perloff JP: The Clinical Recognition of Congenital Heart Disease. Philadelphia, WB Saunders Co, 1970 (Fig. 6-3) 14. Sokolow M, Mcllroy MB: Clinical Cardiology. Los Altos, Lange Medical Publication, 1977 (Fig. 17-14) 15. Braunwald E, Lambrew CT, Morrow AG, et al: Idiopathic hypertrophic subaortic stenosis. Circulation 30 (Suppl 1V): IV-lIV-213, 1964 16. Julian OC, Dye WS, Javid H, et al: Apical left ventriculotomy in subaortic stenosis due to a fibromuscular hypertrophy. Circulation (Suppl 1):1-44, 1965 17. Dobell ARC, Scott HJ: Hypertrophic subaortic stenosis: Evolution of a surgical technique. J Thoracic Cardiovasc Surg 47:26, 1964 18. Hernandez RR, Greenfield JC Jr, McCall BW: Pressure flow studies in hypertrophic subaortic stenosis. J Clin Invest 43: 401, 1964 19. Gauer OH: Evidence in circulatory shock of an isometric phase of ventricular contraction following ejection (Abstr). Fed Proc 9:47, 1950 20. Gauer OH, Henry JP: Negative (-G2) acceleration in relation to arterial oxygen saturation, subendocardial hemorrhage and venous pressure in the forehead. Aerospace Med 35:533, 1964 21. Criley JM, Lewis KB, White RI Jr, et al: Pressure gradients without obstruction: A new concept of "hypertrophic subaortic stenosis." Circulation 32:881, 1965 22. Wilson WS, Criley JM, Ross RS: Dynamics of left ventricular emptying in hypertrophic subaortic stenosis. Am Heart J 74:4, 1967 23. White RI Jr, Criley JM, Lewis KB, et al: Experimental production of intracavity pressure differences-Possible significance in the interpretation of human hemodynamic studies. Am J Cardiol 19:806, 1967 24. Ross J Jr, Braunwald E, Gault JH, et al: The mechanism of the intraventricular pressure gradient in idiopathic hypertrophic subaortic stenosis. Circulation 34:558, 1966 25. Shah PM, Gramiak R, Kramer DH: Ultrasound localization of left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40:3-11, 1969 26. Wigle ED, Auger P, Marquis Y: Muscular subaortic stenosis. The initial left ventricular inflow tract pressure as evidence of outflow tract obstruction. Can Med Assoc J 95:793-797, 1966 27. Adelman AG, Wigle ED: Two types of intraventricular pressure difference in the same patient-Left ventricular catheter entrapment and right ventricular outflow tract obstruction. Circulation 38:649, 1968 28. Braunwald E, Morrow AG, Cornell, et al: Idiopathic hypertrophic subaortic stenosis: Clinical, hemodynamic and angiographic manifestations. Am J Med 29:924, 1960 29. Morrow AG, Reitz BA, Epstein SE, et al: Operative treatment in hypertrophic subaortic stenosis. Circulation 52:88-102, 1975 30. Frank S, Braunwald E: Idiopathic hypertrophic subaortic stenosis: Clinical analysis of 126 patients-Emphasis on the natural history. Circulation 37:759-788, 1968 31. Murgo JP, Alter B, Dorethy J, et al: Aortic flow dynamics in hypertrophic cardiomyopathy with and without left ventricular pressure gradients (Abstr). Circulation 56:11-37, 1977 32. Gehrke J: Reliability of systolic anterior motion (SAM) of the mitral valve and asymmetric septal hypertrophy (ASH) in hypertrophic cardiomyopathy (HCM). Am J Cardiol 39:271, 1977 33. Shabetai R: A new syndrome in hypovolemic shock. Am J Cardiol 24:404, 1969 34. Criley JM, Lennon PA, Abbasi AS, et al: Hypertrophic cardiomyopathy, In Levine HJ (Ed): Clinical Cardiovascular Physiology. New York, Grune & Stratton, 1976
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