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The AJC in February 1960
AJC 25 YEARS AGO
The AJC in February 1960 WILLIAM F. FRIEDMAN, MD of a quantitative variability in the pulmonary vascular bed, related to the number, not just the size and wall structure, of arterial vessels within the pulmonary circulation. Accordingly, the 1960 view of pulmonary vascular obstructive disease occurring as a result only of anatomic changes in the pulmonary arterial vessels has been expanded to appreciate the role of the growth and development of the pulmonary circulation. It is now clear that modeling occurs continuously, from before birth, of the blood vessels in the lung proximal to and within terminal bronchioles (pre- and intraacinar vessels, respectively). The intraacinar vessels, especially, increase in size and number from late fetal life throughout childhood, with minimal muscularization of their walls. This process increases the cross-sectional area of the pulmonary arterial circulation, and allows the cardiac output to rise substantially without increasing pulmonary arterial pressure or resistance. If, however, the presence of a cardiac lesion such as a large VSD, does not permit these most peripheral arteries to grow and multiply normally, the resulting elevation of pulmonary vascular resistance may be related initially to failure of the intraacinar pulmonary circulation to fully develop, and then, secondarily, to the morphologic changes of obliterative vascular disease.This conceptual framework very likely underlies the pivotal findings of DuShane and Kirklin7 more than a decade after the 1960 symposium, showing that reversibility of increased pulmonary vascular resistance is expected if pulmonary hypertensive infants with VSD are operated upon when younger than 2 years of age; reversibility is conjectural if defects are closed later in life. Their study showed that 28% of patients whose operation was performed after 2 years of age developed pulmonary vascular disease. Parenthetically, an important side benefit of closure of large VSD in infancy gained recognition in 1976, when Graham et al8 documented better postoperative left ventricular performance and reversal of hypertrophy than when operation was performed later in chi1dhood.s Hemodynamic observations of over 100 patients with VSD were described in 2 articles.gJO Previously, the issue had been controversial of the relation between hemodynamics and the location of VSD. Imperial et al9 resolved the debate by showing that the functional disturbance caused by a VSD depended primarily on its size and the status of the pulmonary vascular bed, rather than on the location of the VSD. Four articles dealt with the clinical,ir phonocardiographic,12 electro-vectocardiographic13 and roentgen-
The February 1960 issue of The American Journal of Cardiology was devoted primarily to a symposium on ventricular septal defect (VSD). Operative repair of the anomaly under direct vision and extracorporeal bypass had just emerged as the cornerstone of the modern surgical approach,l but still carried a high fatality rate, especially in infancy. The focus of the lead article by Damman et al2 was the anatomy, physiology and natural history of simple defects of the ventricular septum.2 Defects were categorized as membranous or muscular, and were thought to be the result of a deficiency of septal substance. The current classification3 recognizing that the muscular septum has inlet, trabecular and outlet components (separable by axial angiography and 2-dimensional echocardiography) would have been of special value to the 1960 surgeon in relating defects to the semilunar valves, and also in avoiding conduction system in repair. Unrecognized in 1960 was the genesis of defects by a malalignment of septal components in different planes preventing their fusion. Thus, right ventricular outflow tract obstruction, which evolves, in as many as 10% of patients born with clinical findings of a large VSD, into the classic picture of tetralogy of Fallot, was attributed in 1960 to “the prolonged stress of high pulmonary blood flow and high pulmonary pressure, leading to hypertrophy of the outflow tract and eventual infundibular stenosis.” Later advances in embryology and morphology provided our present understanding of the phenomenon as an underlying malalignment problem that results from an anterior, superior and leftward deviation of the infundibular ventricular septum away from its usual location in the heart between the limbs of the trabecular septum.4 In this same regard, in 1960 the physiologic considerations underlying the evolution of pulmonary vascular obstruction focused only on the direct damage to pulmonary blood vesselsand inflammatory arteritis caused by high pulmonary pressures and flows. Twenty-five years later, we are still vexed with the variability among patients in the time of appearance and rate of progression of pulmonary vascular obstructive disease. To better understand the latter phenomenon, we incorporate the importance of pre- and postnatal modifiers of pathogenesis.5+sThus, recent work has clarified the developmental context, in which the role is emphasized From the Department of Pediatrics, Division of Pediatric Cardiology, University of California, Los Angeles, School of Medicine, Los Angeles, California 90024. 616
February 15, 1985
ographic14 findings in patients with VSD. Recognition existed of the wide spectrum of findings, within the dynamic framework of the natural history of VSD, ranging from congestive cardiac failure and death in early infancy to the possible development of pulmonary vascular obstruction, right ventricular outflow tract obstruction and infective endocarditis. Absent from these reports was an appreciation of the remarkably high incidence of spontaneous closurel5, and recognition that the natural history framework of VSD included the subset of patients with aortic regurgitation.16 Elsewhere in the issue, but not a part of the symposium, one of the first successful surgical corrections is described of VSD with aortic regurgitation.i7 The reports in 196011-14of the correlations between anatomy and physiology by clinical examination, vector-electrocardiography and x-ray are models of sophisticated clinical investigation to which little has been added in ensuing years, and whose findings remain at the foundation of the clinician’s approach to the patient. Of course, the basic approach to diagnosis and evaluation of the clinical course of patients with VSD changed dramatically in 1974, with the introduction of 2-dimensional echocardiography to image congenital cardiac malformations.l* It is now routine to detect, localize and quantify the size of VSD directly by 2-dimensional echocardiography and indirectly analyze the physiologic consequences of the pressure and volume load by 2dimensional echocardiography, Doppler ultrasound and, occasionally, with radionuclide angiography. Substantial interest existed in most of the symposium reports, and particularly in an article by Blount and Woodwark,ls in defining the manner in which proper selection of casesfor definitive correction would assist in improving chances for survival. Banding of the pulmonary trunk was urged to manage infants in the first 2 years of life, when a significant number of patients would die if treated medically. In these young patients, Blount and Woodwark estimated a 50%mortality from medical treatment alone, compared with an expected surgical mortality of at least 50% if corrective, rather than palliative, operation was undertaken. Thus, of special interest in the symposium were the reports of Kirklinse and Nogueira et al,2l of the operative approach and results of surgery in patients with this cardiac malformation. The Kirklin article is a model of excellence in underscoring the attention to detail required in intraoperative management and post-operative intensive care to enhance survival. These principles of
THE AMERICAN
JOURNAL
OF CARDIOLOGY
Volume 55
617
care, and the skills of Kirklin and other pioneers in congenital cardiac surgery, paved the way for the subsequent refinements that form the basis of recommending primary intracardiac repair of VSD, rather than surgical banding of the pulmonary trunk, as the procedure of choice to reduce pulmonary blood flow and alleviate heart failure in infants with a large left-to-right shunt and an unrestricted VSD.22 References 1. Kirklin JW, Donald DE, Harshberger HG, Hetzel PS, Patrick RT, Swan HJC, Wood EH. Studies in extracorporeal circulation. I. Applicability of gibbon type pump oxygenator to human intracardiac surgery, forty cases. Ann Surg 1956;144:2-12. 2. Dammann JF Jr, Thompson WM Jr, Sosa 0, Christlieb I. Anatomy, physioloav and natural historv of simole ventricular seotal defects. Am J Cardiol 1966;5:136-166. ’ ’ 3. Soto B, Becker AE, Moulaert AJ, Lie GT, Anderson RH. Classification of ventricular seotal defects. Br Heart J 1980:43:332-343. 4. Becker AE, Conner M, Anderson RH. Tetralogy of Fallot, a morphometric and geometric study. Am J Cardiol 1975;35:402-442. 5. Haworth SG, Sauer U, Buhlmeyer K, Reid L. Development of the pulmonary circulation of ventricular septal defect: a quantitative structural study. Am J Cardiol 1977;40:781-788. 6. Rabinovitch M, Haworth SG, Castaneda AR, Nadas AS, Reid LM. Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease. Circulation 1978;58:1107-1122. 7. DuShane JW, Kirklin JW. Late results of repair of ventricular septal defect on pulmonary vascular disease. In: Kirklin JW, ed. Advances in Cardiovascular Surgery. New York: Grune & Stratton, 1973:9. 8. Graham TP Jr, Cordell GD, Bender AH Jr. Ventricular function following surgery. In: Rowe RD, Kidd BSL, eds. The Child with Congenital Heart Disease After Surgery. Mt. Kisco, NY: Futura, 1976:277-294. 9. Imperial ES, Nogueira C, Kay EB, Zimmerman HA. Isolated ventricular septal defects: en anatomic hemodynamic correlation. Am J Cardiol 1960;5:176-184. 10. Garcia 0, Marcadl H, Caner0 AH, Castellanos A, Barera F. Some ohvsiologic and hemodynamic observations in ventricular septal defect.‘Am J Cardiol 1960:5:167-175. 11. Veasy LG. Clinical findings in ventricular septal defects. Am J Cardiol 1960;5:185-190. 12. Bleifer S, Donoso E, Grishman A. The ausculatory and phonocardiographic sians of ventricular seotal defects. Am J Cardiol 1960:5:191-198. 13. D&k S. The electrocardiogram and vectorcardiogram in ventricular septal defect. Am J Cardiol 1960:5:199-207. 14. Young D, Rubenstein B, Schwedel JB. The roentgenographic spectrum in interventricular septal defect. Am J Cardiol 1960;5:208-222. 15. Dickson DF, Arnold R, Wilkinson JL. Ventricular septal defect in children born in Liverpool, 1960-1969. Evaluation of natural course and surgical implications in a non-selected population. Br Heart J 1981;46:47-54. 16. Nadas AS, Thilenious OG, LaFarge CG, Hauck AJ. Ventricular septal defect with aortrc regurgitation: medical and pathologic aspects. Circulation 1964;29:862-873. 17. Garamella JJ, Cruz AB Jr, Heupel WH, Dahl JC, Jensen NK, Birhman R. Ventricular septal defect with aortic insufficiency: successful surgical corection of both defects by the trans-aortic approach. Am J Cardiol 1960; 5266-272. 10. Sahn DJ, Terry R, O’Rourke R, Leopold C, Friedman WF. Multiple crystal cross-sectional echocardiography in the diagnosis of cyanotic congenital heart disease. Circulation 1974;50:230-238. 19. Blount SG Jr, Woodwark GN. Considerations involved in the selection for surgery of patients with ventricular septal defects. Am J Cardiol 1960;5: 3X-3.1.1 - - - - - -. 20. Kirklin JW. Surgical treatment of ventricular septal defect. Am J Cardiol 1960:5:234-238. 21. Nogueira C, Zimmerman HA. Kay EB. Results for suraerv of ventricular sectal defects. Am J Cardiol i96d;5:239-241. - . 22. Rizzoli G, Blackslone EH, Kirklin JW, Pacific0 AD, Bargeron LN Jr. Incremental risk factors and hospital mortality rate after repair of ventricular septal defect. J Thorac Cardiovasc Surg 1980;80:494-505.
The AJC in February 1960 WILLIAM F. FRIEDMAN, MD of a quantitative variability in the pulmonary vascular bed, related to the number, not just the size and wall structure, of arterial vessels within the pulmonary circulation. Accordingly, the 1960 view of pulmonary vascular obstructive disease occurring as a result only of anatomic changes in the pulmonary arterial vessels has been expanded to appreciate the role of the growth and development of the pulmonary circulation. It is now clear that modeling occurs continuously, from before birth, of the blood vessels in the lung proximal to and within terminal bronchioles (pre- and intraacinar vessels, respectively). The intraacinar vessels, especially, increase in size and number from late fetal life throughout childhood, with minimal muscularization of their walls. This process increases the cross-sectional area of the pulmonary arterial circulation, and allows the cardiac output to rise substantially without increasing pulmonary arterial pressure or resistance. If, however, the presence of a cardiac lesion such as a large VSD, does not permit these most peripheral arteries to grow and multiply normally, the resulting elevation of pulmonary vascular resistance may be related initially to failure of the intraacinar pulmonary circulation to fully develop, and then, secondarily, to the morphologic changes of obliterative vascular disease.This conceptual framework very likely underlies the pivotal findings of DuShane and Kirklin7 more than a decade after the 1960 symposium, showing that reversibility of increased pulmonary vascular resistance is expected if pulmonary hypertensive infants with VSD are operated upon when younger than 2 years of age; reversibility is conjectural if defects are closed later in life. Their study showed that 28% of patients whose operation was performed after 2 years of age developed pulmonary vascular disease. Parenthetically, an important side benefit of closure of large VSD in infancy gained recognition in 1976, when Graham et al8 documented better postoperative left ventricular performance and reversal of hypertrophy than when operation was performed later in chi1dhood.s Hemodynamic observations of over 100 patients with VSD were described in 2 articles.gJO Previously, the issue had been controversial of the relation between hemodynamics and the location of VSD. Imperial et al9 resolved the debate by showing that the functional disturbance caused by a VSD depended primarily on its size and the status of the pulmonary vascular bed, rather than on the location of the VSD. Four articles dealt with the clinical,ir phonocardiographic,12 electro-vectocardiographic13 and roentgen-
The February 1960 issue of The American Journal of Cardiology was devoted primarily to a symposium on ventricular septal defect (VSD). Operative repair of the anomaly under direct vision and extracorporeal bypass had just emerged as the cornerstone of the modern surgical approach,l but still carried a high fatality rate, especially in infancy. The focus of the lead article by Damman et al2 was the anatomy, physiology and natural history of simple defects of the ventricular septum.2 Defects were categorized as membranous or muscular, and were thought to be the result of a deficiency of septal substance. The current classification3 recognizing that the muscular septum has inlet, trabecular and outlet components (separable by axial angiography and 2-dimensional echocardiography) would have been of special value to the 1960 surgeon in relating defects to the semilunar valves, and also in avoiding conduction system in repair. Unrecognized in 1960 was the genesis of defects by a malalignment of septal components in different planes preventing their fusion. Thus, right ventricular outflow tract obstruction, which evolves, in as many as 10% of patients born with clinical findings of a large VSD, into the classic picture of tetralogy of Fallot, was attributed in 1960 to “the prolonged stress of high pulmonary blood flow and high pulmonary pressure, leading to hypertrophy of the outflow tract and eventual infundibular stenosis.” Later advances in embryology and morphology provided our present understanding of the phenomenon as an underlying malalignment problem that results from an anterior, superior and leftward deviation of the infundibular ventricular septum away from its usual location in the heart between the limbs of the trabecular septum.4 In this same regard, in 1960 the physiologic considerations underlying the evolution of pulmonary vascular obstruction focused only on the direct damage to pulmonary blood vesselsand inflammatory arteritis caused by high pulmonary pressures and flows. Twenty-five years later, we are still vexed with the variability among patients in the time of appearance and rate of progression of pulmonary vascular obstructive disease. To better understand the latter phenomenon, we incorporate the importance of pre- and postnatal modifiers of pathogenesis.5+sThus, recent work has clarified the developmental context, in which the role is emphasized From the Department of Pediatrics, Division of Pediatric Cardiology, University of California, Los Angeles, School of Medicine, Los Angeles, California 90024. 616
February 15, 1985
ographic14 findings in patients with VSD. Recognition existed of the wide spectrum of findings, within the dynamic framework of the natural history of VSD, ranging from congestive cardiac failure and death in early infancy to the possible development of pulmonary vascular obstruction, right ventricular outflow tract obstruction and infective endocarditis. Absent from these reports was an appreciation of the remarkably high incidence of spontaneous closurel5, and recognition that the natural history framework of VSD included the subset of patients with aortic regurgitation.16 Elsewhere in the issue, but not a part of the symposium, one of the first successful surgical corrections is described of VSD with aortic regurgitation.i7 The reports in 196011-14of the correlations between anatomy and physiology by clinical examination, vector-electrocardiography and x-ray are models of sophisticated clinical investigation to which little has been added in ensuing years, and whose findings remain at the foundation of the clinician’s approach to the patient. Of course, the basic approach to diagnosis and evaluation of the clinical course of patients with VSD changed dramatically in 1974, with the introduction of 2-dimensional echocardiography to image congenital cardiac malformations.l* It is now routine to detect, localize and quantify the size of VSD directly by 2-dimensional echocardiography and indirectly analyze the physiologic consequences of the pressure and volume load by 2dimensional echocardiography, Doppler ultrasound and, occasionally, with radionuclide angiography. Substantial interest existed in most of the symposium reports, and particularly in an article by Blount and Woodwark,ls in defining the manner in which proper selection of casesfor definitive correction would assist in improving chances for survival. Banding of the pulmonary trunk was urged to manage infants in the first 2 years of life, when a significant number of patients would die if treated medically. In these young patients, Blount and Woodwark estimated a 50%mortality from medical treatment alone, compared with an expected surgical mortality of at least 50% if corrective, rather than palliative, operation was undertaken. Thus, of special interest in the symposium were the reports of Kirklinse and Nogueira et al,2l of the operative approach and results of surgery in patients with this cardiac malformation. The Kirklin article is a model of excellence in underscoring the attention to detail required in intraoperative management and post-operative intensive care to enhance survival. These principles of
THE AMERICAN
JOURNAL
OF CARDIOLOGY
Volume 55
617
care, and the skills of Kirklin and other pioneers in congenital cardiac surgery, paved the way for the subsequent refinements that form the basis of recommending primary intracardiac repair of VSD, rather than surgical banding of the pulmonary trunk, as the procedure of choice to reduce pulmonary blood flow and alleviate heart failure in infants with a large left-to-right shunt and an unrestricted VSD.22 References 1. Kirklin JW, Donald DE, Harshberger HG, Hetzel PS, Patrick RT, Swan HJC, Wood EH. Studies in extracorporeal circulation. I. Applicability of gibbon type pump oxygenator to human intracardiac surgery, forty cases. Ann Surg 1956;144:2-12. 2. Dammann JF Jr, Thompson WM Jr, Sosa 0, Christlieb I. Anatomy, physioloav and natural historv of simole ventricular seotal defects. Am J Cardiol 1966;5:136-166. ’ ’ 3. Soto B, Becker AE, Moulaert AJ, Lie GT, Anderson RH. Classification of ventricular seotal defects. Br Heart J 1980:43:332-343. 4. Becker AE, Conner M, Anderson RH. Tetralogy of Fallot, a morphometric and geometric study. Am J Cardiol 1975;35:402-442. 5. Haworth SG, Sauer U, Buhlmeyer K, Reid L. Development of the pulmonary circulation of ventricular septal defect: a quantitative structural study. Am J Cardiol 1977;40:781-788. 6. Rabinovitch M, Haworth SG, Castaneda AR, Nadas AS, Reid LM. Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease. Circulation 1978;58:1107-1122. 7. DuShane JW, Kirklin JW. Late results of repair of ventricular septal defect on pulmonary vascular disease. In: Kirklin JW, ed. Advances in Cardiovascular Surgery. New York: Grune & Stratton, 1973:9. 8. Graham TP Jr, Cordell GD, Bender AH Jr. Ventricular function following surgery. In: Rowe RD, Kidd BSL, eds. The Child with Congenital Heart Disease After Surgery. Mt. Kisco, NY: Futura, 1976:277-294. 9. Imperial ES, Nogueira C, Kay EB, Zimmerman HA. Isolated ventricular septal defects: en anatomic hemodynamic correlation. Am J Cardiol 1960;5:176-184. 10. Garcia 0, Marcadl H, Caner0 AH, Castellanos A, Barera F. Some ohvsiologic and hemodynamic observations in ventricular septal defect.‘Am J Cardiol 1960:5:167-175. 11. Veasy LG. Clinical findings in ventricular septal defects. Am J Cardiol 1960;5:185-190. 12. Bleifer S, Donoso E, Grishman A. The ausculatory and phonocardiographic sians of ventricular seotal defects. Am J Cardiol 1960:5:191-198. 13. D&k S. The electrocardiogram and vectorcardiogram in ventricular septal defect. Am J Cardiol 1960:5:199-207. 14. Young D, Rubenstein B, Schwedel JB. The roentgenographic spectrum in interventricular septal defect. Am J Cardiol 1960;5:208-222. 15. Dickson DF, Arnold R, Wilkinson JL. Ventricular septal defect in children born in Liverpool, 1960-1969. Evaluation of natural course and surgical implications in a non-selected population. Br Heart J 1981;46:47-54. 16. Nadas AS, Thilenious OG, LaFarge CG, Hauck AJ. Ventricular septal defect with aortrc regurgitation: medical and pathologic aspects. Circulation 1964;29:862-873. 17. Garamella JJ, Cruz AB Jr, Heupel WH, Dahl JC, Jensen NK, Birhman R. Ventricular septal defect with aortic insufficiency: successful surgical corection of both defects by the trans-aortic approach. Am J Cardiol 1960; 5266-272. 10. Sahn DJ, Terry R, O’Rourke R, Leopold C, Friedman WF. Multiple crystal cross-sectional echocardiography in the diagnosis of cyanotic congenital heart disease. Circulation 1974;50:230-238. 19. Blount SG Jr, Woodwark GN. Considerations involved in the selection for surgery of patients with ventricular septal defects. Am J Cardiol 1960;5: 3X-3.1.1 - - - - - -. 20. Kirklin JW. Surgical treatment of ventricular septal defect. Am J Cardiol 1960:5:234-238. 21. Nogueira C, Zimmerman HA. Kay EB. Results for suraerv of ventricular sectal defects. Am J Cardiol i96d;5:239-241. - . 22. Rizzoli G, Blackslone EH, Kirklin JW, Pacific0 AD, Bargeron LN Jr. Incremental risk factors and hospital mortality rate after repair of ventricular septal defect. J Thorac Cardiovasc Surg 1980;80:494-505.