AORTIC VALVE DISEASE
ventricular performance is present, surgical therapy is recommended even for class II (New York Heart Association) patients. In asymptomatic patients in whom there is evidence of progressive left ventricular enlargement on physical examination, chest x-ray or echocardiogram, or in whom electrocardiograms show increasing signs of left ventricular hypertrophy, or in patients in whom echocardiographic indices of left ventricular performance indicate a progression from normal to abnormal left ventricular systolic performance, cardiac catheterization is done. If left ventricular systolic function as assessed at catheterization is normal, careful medical management is recommended. The presence of significant depression of \eft ventricular performance warrants considerat on for valve replacement. It is worth emphasizing that symptoms of congestive heart failure in patients with chronic aortic regurgitation are not as valuable in predicting survival following valve replacement as other measures of cardiac performance.47 A vexing problem encountered in patients with chronic aortic regurgitation is management of a patient who has significant aortic regurgitation and established, severe myocardial dysfunction. The natural history in this setting is poor, with progression of myocardial disease and limited longevity.5 '; However, valve replacement in such cases does not appear to result in the reversal of myocardial dysfunction20 and in preliminary studies the long-term results of surgical operation in this situation have not been encouraging.48 In summary, one must decide between medical management with almost certain worsening of myocardial function, and the risk of surgical operation with the possibility of arrest without reversal of the deterioration of myocardial function, and no current evidence that the natural history will be positively affected. If symptoms are refractory to optimum medical management, valve replacement can be undertaken with the above mentioned expectations kept in mind. At present, cardiac catheterization provides the most reliable means of assessing the function of the left ventricle in patients with aortic regurgitation; therefore, appropriate care and attention should be directed toward the assessment of left ventricular performance at the time of catheterization in these patients. Ideally, quantitative biplane ventriculography should be employed in patients with chronic aortic regurgitation. A recent study by Bolen and associates identified a
group of patients with aortic regurgitation and normal basal left ventricular ejection fraction who responded to afterload stress (angiotensin) with a decrease in ejection fraction and left ventricular stroke work index. The authors felt that this response might indicate a state of latent left ventricular dysfunction.49 Employment of a welldefined stress of this type might prove to be useful in the routine evaluation of left ventricular performance in aortic regurgitation. Supravalve aortic root angiography is employed to roughly quantitate the degree of aortic regurgitation (trivial to 4 + ) and to document the anatomy of the aortic root, which may be quite dilated in Marfan syndrome or cystic medial necrosis. Coronary angiograms are routinely obtained in patients over age 40. Associated mitral valve disease-rheumatic and mitral prolapse in particular -should be evaluated with appropriate pressure recordings and analysis of the left ventricular cineangiogram. Acute aortic regurgitation may overwhelm the usual compensatory mechanisms accompanying a volume overload, and left ventricular end-diastolic pressure may rise to produce severe pulmonary vascular congestion. If medical therapy, as outlined by Dr. Karliner, is not effective in relieving the congestive heart failure, cardiac catheterization followed by aortic valve replacement may be required, even in patients with active infective endocarditis. In patients with acute aortic regurgitation, therefore, the timing of cardiac catheterization and aortic valve replacement is dependent upon the severity of associated signs and symptoms of heart failure, in contrast to chronic aortic regurgitation.
Surgical Considerations in Aortic Valve Disease PAT 0. DAILY, MD*
As DR. JOHNSON has discussed, the timing of aortic valve surgical therapy in a given patient requires synthesis and consideration of all the available clinical, noninvasive, angiographic and hemodynamic information. Presented with a patient in whom the decision for valve replacement has been made, a surgeon is faced with two prob*Associate Professor of Surgery.
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lems which at present do not have ideal solutions: (1) selection of a prosthetic replacement for the diseased aortic valve and (2) deciding upon a surgical technique which will provide the best operative results and the least chance of causing myocardial damage. Let us first consider selection of a prosthetic aortic valve. Although many factors relate to selection of a valve substitute, the three primary considerations are hemodynamic performance, durability and the incidence of thromboembolism. Additional aspects such as availability and ease of insertion are important but are relatively equivalent for most of the currently used valve replacement devices. However, when aortic allografts were at the height of their popularity, procurement was a major obstacle in their use. It is, therefore, an evaluation of these three basic determinants that accounts for the selection of a particular valve replacement device for a specific patient.
Hemodynamic Considerations Substitute valves can be basically divided into those having a central flow orifice and those with a lateral flow orifice. These designations relate to the fact that in central flow valves the direction of blood passage through the valve is not changed from the normal situation. Porcine xenografts and allografts are examples of central flow valves. In lateral flow valves, after passage through the primary orifice, blood flow is directed laterally upon striking the poppet. The various ball and disc valves are examples of lateral flow. Valves with a tilting disc such as the Bjork-Shiley and LilleheiKaster valves may be described as semicentral flow valves. Valves of this type have been reported to have very favorable hemodynamic characteristics, particularly in the smaller sizes.50 From a hemodynamic standpoint alone, it appears that central flow type valves are more physiologically appropriate. However, a number of different prosthetic aortic valves appear to offer acceptable hemodynamic results.52
Durability Most prosthetic valves have satisfactory durability, but problems have been encountered. In Braunwald-Cutter aortic prostheses cloth wear has been noted, as well as poppet embolization.53 Cloth wear has also been a significant problem with the 2300 series Starr-Edwards valves. Allografts appear to have a poor record for durability; Karp and co-workers54 found that in 10 to 15 474
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percent of patients with aortic allografts reoperation was needed, despite a more enthusiastic early report.55 Similar results were reported by Wallace and associates, with the probability of reoperation for valve failure being 7 percent within three years and 22 percent at five .years in this series.56 The method of allograft preparation is important; long-term results favor the fresh frozen57 or fresh antibiotic preserved allografts.58 Early experience with formalin preserved porcine xenografts resulted in a 50 percent failure rate at 42 months.59 However, experience with gluteraldehyde fixed xenografts followed up to 46 months showed no valve failures.60'62 The question of long-term durability in excess of four to five years of gluteraldehyde fixed porcine xenografts remains unanswered.
Thromboembolism The primary argument for the use of allografts and xenografts is the very low incidence of thromboembolism without the necessity for anticoagulation. Aortic allografts seem virtually free of thromboembolism; several large series have reported no thromboembolic complications in the absence of atrial fibrillation.62'63 With porcine xenografts there is an acceptably low incidence of thromboembolism without the use of anticoagulants.59'60 Thromboembolism is significantly more frequent after aortic valve replacement with caged poppet or tilting disc prosthetic valve. The early Starr-Edwards Model 1000 prosthetic aortic valve was reported to have a thromboembolic incidence of 34 percent at three years.63 Extension of fabric over the valve seat reduced the embolic rate to 5 percent at three years in the Starr-Edwards 1260 aortic valve. However, complete fabric enclosure of the metallic surfaces did not further reduce the thromboembolic rate in the 2300 series valves and resulted in the same thromboembolic rate as the Model 1260 valve. A recent comparison showed that the incidence of emboli at one year was 14.0 percent for the Braunwald-Cutter valve, 9.1 percent for the Starr-Edwards composite seat 2320 valve and 7.4 percent for the Starr-Edwards 1200 and 1260 silastic valves.54 Anticoagulants were not used with the first two valves but were with the last. It therefore appears that complete covering of the entire valve cage has not achieved the goal of an acceptably low incidence of thromboembolism without anticoagulants. Accordingly, it is now recommended that anticoagulants be used with these valves.54'65
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From the preceding discussion, it is apparent that no one valve is clearly superior in all respects to the others. This situation was very clearly portrayed as a graph in a recent editorial by McGoon.66 With permission this graph has been updated and is presented in Figure 8. It is apparent that confusion exists; with the bare-strut ball valve, cloth covered ball valve, tilting-disc valve and xenograft enjoying nearly equal popularity. It is our preference to routinely use the Hancock porcine xenograft because of the very low incidence of thromboembolism without anticoagulants. While long-range durability of the xenograft is unknown, the current model has been associated with an extremely low incidence of failure over a 46 month period. In the case of smaller aortic roots, consideration is given to the Bjork-Shiley valve, with that valve being definitely preferred with aortic valve sizes of 21 mm and under.
Surgical Technique The primary controversy regarding aortic valve replacement relates to the method of myocardial protection during the period of aortic cross clamping. Although a number of variations exist, the basic methods of myocardial protection are coronary perfusion by cannulation of the individual coronary arteries and myocardial hypothermia. Each method can produce clinically acceptable results. For example, McGoon 67 using coronary perfusion reported a series of 100 consecutive aortic valve replacements without mortality, and DeBoer and Midell68 attributed continuous coronary perfusion as the single most important factor in achieving an operative mortality of 1.8 percent in 104 consecutive patients in whom aortic valve replacement was done. Myocardial surface cooling as described by Shumway and co-workers69 has been used with equal success in several series of patients. 70-72 Our own experience is that myocardial surface cooling, although yielding an opera-
tive mortality of 1 percent in 100 consecutive patients in whom aortic, mitral and multiple valve replacement was done does not produce constant myocardial cooling.73 Temperature gradients of as much as 20°C between the left ventricular epicardium and endocardium occur and persist. Furthermore, in a series of patients being evaluated after mitral valve replacement, a significant decrease in myocardial contractility was detected in several patients.74 With refinement of surgical methods, evaluation of the adequacy of surgical results and myocardial protection must primarily be concerned with chronic preservation of left ventricular function, rather than operative mortality.75 As emphasized in a randomized study reported by Sapsford and associates,76 it appears that either coronary perfusion or myocardial hypothermia can offer very acceptable clinical results. Unfortunately, there is evidence that neither method results in complete preservation of myocardial function. In a chronic experimental study, Brody and coworkers77 found that coronary perfusion and myocardial surface cooling resulted in late depression of left ventricular function and produced myocardial fibrosis. Accordingly, refinements of existing techniques and other methods are being sought in an endeavor to enhance preservation of myocardial function. Because of the inconsistency of myocardial surface cooling mentioned above, our laboratory is presently involved in a comparison of myocardial surface cooling and cold cardioplegia (infusion of a cold electrolyte solution of high potassium content into the cross clamped aortic root and coronary arteries) as described recently by Roe and associates.78 Results of Aortic Valve Replacement Although aortic valvuloplasty was extensively done in earlier years,79 80 because of suboptimal long-term results, it has largely been replaced by aortic valve replacement. Consequently, this discussion will relate to valve replacement. The essential aspects in considering the results of aortic valve replacement include operative mortality (30 days from operation), late mortality, symptomatic improvement and complications associated with valve replacement. Current operative mortality is between 5 and 15 percent in most reported series and is less than 5 percent in selected reports. It is increasingly apparent that this mortality is determined more by patient selection than use of a particular prosTHE WESTERN JOURNAL OF MEDICINE
475
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Figure 9.-Composite graph showing in the upper curve survival in 962 patients after aortic valve replacement as reported by Barnhorst et al." An operative mortality of 6.3 percent is not reflected in this curve. The lower curve shows survival of patients with aortic stenosis treated medically as described by Rapaport.8"
thetic valve. Hospital and late mortality rates with the Bjork-Shiley, Braunwald-Cutter, LilleheiKaster and Smeloff-Cutter valves have been shown to be similar,81 and comparable to mortality rates for the Starr-Edwards aortic prosthesis64 and the Smeloff-Cutter prosthesis.82 Late mortality seems to be more clearly associated with the preoperative status of the patient rather than the type of prosthesis. Heart size at the time of operation and the type of dominant aortic valvular lesions are more important in affecting late survival than the type of prosthetic valve.64 In considering the utility of aortic valve replacement it is useful to compare late mortality of aortic valve replacement with the natural history of aortic stenosis treated medically. A composite graph (Figure 9) has been constructed with operative mortality and late mortality reported by Barnhorst and co-workers64 compared with those in a group of patients with aortic stenosis treated medically, as recently described by Rapaport.83 The late mortality at nine years after aortic valve replacement was 27 percent compared with 78 percent in the group medically treated. (The surgical mortality excludes the low operative mortality.) Furthermore, in most patients in whom operations are done there is significant symptomatic improvement. Typical results were reported by Behrendt and Austen5l of 113 patients in whom aortic valve replacement was done; most were New York Heart Association class III. After operation, 72 percent became class I and 28 percent class II. In addition to thromboembolism and late valve failure, several other complications of aortic valve replacement require brief comment. Endocarditis involving the prosthetic valve is an extremely serious problem. This occurs in approximately 4 per476
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cent of patients84 and if it occurs early is associated with a 79 percent mortality, compared with a 35 percent mortality if occurring after 60 days. Periprosthetic leak, with currently used prosthetic valves and techniques, is infrequent in the absence of infection. Poppet embolization, a disastrous complication, has also been reported,53 but previous problems with poppet wear have been minimized in current prosthetic valves by appropriate selection of material. Cloth covering of the valve cage has also resulted in a significant degree of hemolysis as compared with the earlier StarrEdwards valves,85 and can occasionally be an important clinical problem.
Closing Remarks DR. JOHNSON: The management of patients with aortic valve disease remains a challenging problem, and requires the closest interaction among patient, physician-cardiologist and cardiac surgeon. In this conference, we have stressed the clinical features of aortic valve disease, contrasting aortic stenosis-with its triad of congestive failure, ischemic chest pain and syncopal episodes-with aortic regurgitation in which the onset of symptomns and myocardial damage is much more insidious. The structural and functional abnormalities of the left ventricular myocardium caused by the pressure or volume overload, or both, accompanying aortic valve disease are important determinants of clinical symptoms and operative results, and their detection and prevention are therefore of paramount importance. Decisions regarding medical or surgical (or medical and surgical) management follow the accumulation of all pertinent historical, physical and laboratory data relative to the patient's disease process. This, added to the clinical information from noninvasive and catheterization studies, will allow a decision regarding the appropriate timing for valve replacement. We have emphasized the difficulty in identifying the optimum time for operative intervention in chronic aortic regurgitation, the requirement for careful medical management in this situation and the need for further investigation in this area. In our opinion, valve selection at present would favor the use of the glutaraldehyde preserved porcine heterograft in all but the small aortic root because of its relative freedom from the need for anticoagulation and the low thromboembolic rate.
AORTIC VALVE DISEASE
The long-term durability of this valve is currently unknown, however. When, for technical reasons, the use of the aortic heterograft is precluded, a variety of suitable prosthetic valves are available with the use of the tilting disc valves enjoying the most rapid rise in popularity. Protection of the myocardium during operation is a most important factor in determining the success or failure of a given operation. That satisfactory operative resuits mnay be obtained with either continuous coronary perfusion or myocardial hypothermia has been shown by many series. With careful attention to the proper timing of operation, technical competence in valve replacement and adequate protection of the myocardium, the operative mortality should be less than S percent and, it is hoped, any significant insult to left ventricular myocardial function will be prevented. With the gratifying progress in cardiovascular surgical techniques and results, it becomes all the more important for internists and cardiologists to identify and nmeticulously manage patients with aortic valve disease so that there can be optimal timing of surgical therapy to patients' clinical status and nmyocardial function. REFERENCES 1. Roberts WC: The structure of the aortic valve in clinically isoiated aortic stenosis. Circulation 42:91-97, 1970 2. Roberts WC, Perloff JK, Constantin T: Severe valvular aortic stenosis in patients over 65 years of age. Am J Cardiol 27:497-506, 1971 3. Roberts WC: The congenitally abnormal bicuspid aortic valve-A study of 85 autopsy cases. Am J Cardiol 26:72-83, 1970 4. Frank S, Johnson A, Ross J Jr: Natural history of valvular aortic stenosis. Br heart J 35:41-46, 1973 5. Goldschlager N, Pfeifer J, Cohn K, et al: The natural history of aortic regurgitation-A clinical and hemodynamic study. Am
Med 54:577-588, 1973 6. Spagnuolo M, Kloth H, Taranta A, et al: The natural history of aortic regurgitation-Criteria predictive of death, congestive heart failure, and angina in young patients. Circulation 44:368-380, 1971 7. Kennedy JW, Twiss RD, Blackmon MD, et al: Quantitative angiocardiography-Ill. Relationship of left ventricular pressure, volume, and mass in aortic valve disease. Circulation 38: 838-845, 1968 8. Hood WP Jr, Rackley CE, Rolett EL: Wall stress in the normal and hypertrophied human left ventricle. Am J Cardiol 22:550-558, 1968 9. Gould KL, Lipscomb K, Hamilton GW, et al: Relation of left ventricular shape, function and wall stress in man. Am J Cardiol 34:627-634, 1974 10. Spann JF, Buccino RA, Sonnenblick EH, et al: Contractile state of cardiac muscle obtained from cat with experimentally produced ventricular hypertrophy and heart failure. Circ Res 21: 341-354, 1967 11. Williams JF Jr, Potter RD: Normal contractile state of hypertrophied myocardium after pulmonary artery constriction in the cat. J Clin Invest 54:1266-1272, 1974 12. Sasayama S, Ross J Jr, Franklin D, et al: Adaptations of the left ventricle to chronic pressure overload. Circ Res 38:172178, 1976 13. Ross J Jr: Afterload mismatch and preload reserve: A conceptual framework for the analysis of ventricular function. Prog Cardiovasc Dis 18:255-264, 1976 14. Grossman W, McLaurin LP, Stefadouros MA: Left ventricular stiffness associated with chronic pressure and volume overloads in man. Circ Res 35:793-800, 1974 15. Sonnenblick EH, Ross J Jr, Covell JW, et al: Ultrastructure of the heart in systole and diastole: Changes in sarcomere length. Circ Res 21:423-431, 1967 16. Mahler F, Ross J Jr, O'Rourke RA, et al: Effects of changes in preload, afterload, and inotropic state on ejection and isoi
volumic phase measures of contractility in the conscious dog. Am J Cardiol 35:626-634, 1975 17. Ross J Jr, Sonnenblick EH, Taylor RR, et al: Diastolic geometry and sarcomere lengths in the chronically dilated canine left ventricle. Circ Res 28:49-61, 1971 18. Ross J Jr, McCullagh WH: Nature of enhanced performance of the dilated left ventricle in the dog during chronic volunme overloading. Circ Res 30:549-556, 1972 19. Taylor RR, Covell JW, Ross J Jr: Left ventricular function in experimental aorto-caval fistula with circulatory congestion and fluid retention. J Clin Invest 47:1333-1342, 1968 20. Gault JH, Covell JW, Braunwald E, et al: Left ventricular performance following correction of free aortic regurgitation. Circulation 42:773-780, 1970 21. Ross J Jr, Braunwald E: Aortic stenosis. Circulation 61(Suppl V):37-38, 1968 22. Buckberg G, Eber L, Nerman M, et al: lschemia in aortic stenosis: Hemodynamic prediction. Am J Cardiol 35:778-784, 1975 23. Basta LL, Raines RD, Najjar S, et al: Clinical, hemodynamic and angiographic correlation of angina pectoris in severe aortic valve oisease. Clin Res 21:810, 1973 24. Mark AL, Kioschos JM, Abboud FM, et al: Abnormal vascular responses to exercise in patients with aortic stenosis. J Clin Invest 52:1138-1146, 1973 25. Flamm MD, Braniff BA, Kimball R, et al: Mechanisms of effort syncope in aortic stenosis. Circulation 36(Suppl 11): 109-110, 1967 26. Ellison RC, Wagner HR, Weidman WH, et al: Congenital valvular aortic stenosis: clinical detection of small pressure gradient. Am J Cardiol 37:757-761, 1970 27. Caulfied WH, Deleon AC Jr, Perloff JK, et al: The clinical significance of the fourth heart sound in aortic stenosis. Am J Cardiol 38:179-182, 1971 28. Kavalier MA, Stewart J, Tavel ME: The apical A wave versus the fourth heart sound in assessing the severity of aortic stenosis. Circulation 51:324-327, 1975 29. Cobbs BW Jr: Clinical recognition and medical management of rheumatic heart disease and other acquired valvular disease, In Hurst JW (Ed): rhe Heart. New York City, McGrawHill Book Co., 1974, p 929 30. Fortuin NJ, Craige E: On the mechanisms of the AustinFlint murmur. Circulation 45:558-570, 1972 31. Parker E, Craige E, Hood WPJ Jr: The Austin Flint murmur and the A wave of the apex cardiogram in aortic regurgitation. Circulation 43:349-359, 1971 32. Spring DA, Fulti JD, Young WP, et al: Premature closure of the mitral and tricuspid valves. Circulation 45:663671, 1972 33. Bonner A, Sacks H, Tavel M: Assessing the severity of aortic stenosis by phonocardiography and external carotid pulse recordings. Circulation 48:247-252, 1973 34. Parisi AF, Salzman SH, Sclechter E: Systolic time intervals in severe aortic valve disease. Circulation 44:539-547, 1971 35. Cooper RH, O'Rourke RA, Karliner JS, et al: Comparison of ultrasound and cineangiographic measurements of the mean rate of circu%mferential fiber shortening in man. Circulation 46: 9 14-923, 1972 36. Winsberg I, Gabor GE, Hernberg, JG, et al: Fluttering of the mitral valve in aortic insufficiency. Circulation 41:225229, 1970 37. Botvinick E, Schiller NB, Wickramasekeran R, et al: Echocardiographic demonstration of early mitral valve closure in severe aortic insufficiency. Circulation 51:836-847, 1975 38. Corya BC, Feigenbaum H, Rasmussen S, et al: Anterior left ventricular wall echoes in coronary artery disease. Am J Cardiol 34:652-657, 1974 39. Johnson AD, Alpert JS, Francis GS, Viewig WV, et al: Left ventricular function in severe aortic insufficiency. Circulation 54:975-979, 1976 40. Bergeron J, Abelmann WH, Vasquez M, et al: Aortic stenosis-Clinical manifestations and course of the disease. Arch Intern Med 90:911-924, 1954 41. Judge TP, Kennedy JW, Bennett LJ, et al: Quantitative hemodynamic effects of heart rate in aortic regurgitation. Circulation 44:355-367, 1971 42. Levinson E, Frank MJ, Schwartz CJ: The effect of rest and physical effort on the left ventricular burden in mitral and aortic regurgitation. Am Heart J 80:791-801, 1970 43. Johnson AD, Lonky S, Carleton RA: Combined hypertrophic subaortic stenosis and calcific aortic stenosis. Am J Cardiol 35:706-709, 1975 44. Harris CN, Kaplan MA, Parker DP, et al: Aortic stenosis, angina, and coronary artery disease interrelations. Br Heart J 37:656-661, 1975 45. Berndt TB, Hancock EW, Shumway NE, et al: Aortic valve replacement with and without coronary artery bypass surgery. Circulation 50:967-971, 1974 46. Linhart JW, de la Torre A, Ramsey HW, et al: The significance of coronary artery disease in aortic valve replacement. J Thorac Cardiovasc Surg 55:811-819, 1968 47. Hirshfeld JW, Epstein SE, Roberts AJ, et al: Indices predicting long-term survival after valve replacement in patients
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AORTIC VALVE DISEASE with aortic regurgitation and patients with aortic stenosis. Circulation 50:1190-1199, 1974 48. Bailey MT, Feild BJ, Baxley WA: Left ventricular function prior to surgery for aortic valve incompetence: Prognostic implications. Circulation 49/50(Suppl III) :41, 1974 49. Bolen JL, Holloway EL, Zener JC, et al: Evaluation of left ventricular function in patients with aortic regurgitation using afterload stress. Circulation 53:132-138, 1976 50. Bjork VO, Henze A, Holmgren A, et al: Evaluation of the 21 mm Bjork-Shiley tilting disc valve in patients with narrow aortic roots. Scand J Thorac Cardiovasc Surg 7:203-213, 1973 51. Behrendt DM, Austen WG: Current status of prosthetics for heart valve replacement. Prog in Cardiovasc Dis 15:369-401, 1973 52. Bonchek LI, Starr A: Ball valve prostheses: Current appraisal of late results. Am J Cardiol 35:843-854, 1975 53. Pluth JR, Danielson GK: Poppet embolization in clothcovered silastic poppet valves. Mayo Clin Proc 49:811-814, 1974 54. Karp RB, Kirklin JW, Kuchoukos NT, et al: Comparison of three devices to repair the aortic valve. Circulation 49/50 (Suppl II):163, 1974 55. Karp RB, Kirklin JW: Replacement of diseased aortic valves with homografts. Ann Surg 169:921-926, 1969 56. Wallace RB, Londe SP, Titus JL: Aortic valve replacement with preserved aortic valve homografts. J Thorac Cardiovasc Surg 67:44-52, 1974 57. Moore CH, Martilli V, Al-Janabi N, et al: Analysis of homograft valve failure in 311 patients followed up to 10 years. Ann Thorac Surg 20:274-281, 1975 58. Wallace RB: Tissue valves. Am J Cardiol 35:866-871, 1975 59. Zuhdi N, Hawley W, Voehl V, et al: Porcine aortic valves as replacements for human heart valves. Ann Thor Surg 17:479-491, 1974 60. Pipkin RD, Buch WS, Fogarty TJ: Evaluation of aortic valve replacement with a porcine xenograft without long-term anticoagulation. J Thorac Cardiovasc Surg 71:179-186, 1976 61. Cohn LH, Lamberti JJ, Castaneda AR, et al: Cardiac valve replacement with stabilized gluteraldehyde porcine aortic valve: Indications, operative results, and follow-up. Chest 68: 162-165, 1975 62. Pacifico AD, Karp RB, Kirklin JW: Homografts for replacement of the aortic valve. Circulation 45(Suppl I) :36, 1972 63. Stinson EB, Angell WW, Iben AB, et al: Aortic valve replacement with the fresh valve homograft. Am J Surg 116:204209, 1968 64. Barnhorst DA, Oxman HA, Connolly DC, et al: Isolated replacement of the aortic valve with the Starr-Edwards prosthesis. J Thorac Cardiovasc Surg 70:113-118, 1975 65. Starr A: Comparison of long-term results after ball valve replacement, In: 11th World Congress of the International Cardiovascular Society, Symposium on Long Term Results of Cardiac Valve Replacement, Minerva Medica, 1973 pp 359-369 66. McGoon DC: On evaluating valves. Mayo Clin Proc 49: 233-235, 1974
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67. McGoon DC, Pestana C, Moffitt EA: Decreased risk of aortic valve replacement. Arch Surg 91:779-786, 1965 68. DeBoer A, Midell Al: Isolated aortic valve replacement. Ann Thorac Surg 17:360-367, 1974 69. Shumway NE, Lower RR: Topical cardiac hypothermia for extended periods of anoxic arrest. Surg Forum 10:563-566, 1959 70. Pupello DF, Blank RH, Connar RG, et al: Fifty-two consecutive aortic valve replacements employing local deep hypothermia. Ann Thor Surg 19:487-493, 1975 71. Griepp RB, Stinson EB, Shumway NE: Profound local hypothermia for myocardial protection during open heart surgery. J Thorac Cardiovasc Surg 66:731-741, 1973 72. Cohn LH, Fujiwara Y, Kirk E, et al: Effects of local cardiac hypothermia on the magnitude and distribution of coronary blood flow and on myocardial function and metabolism. Ann Thorac Surg 19:10-16, 1975 73. Chapin DC, Daily PO, Blair GL, et al: Inadequacy of myocardial surface cooling during cardioplegia. (In preparation) 74. Chapin DC, Peterson KL, Daily PO, et al: Depressed left ventricular function following mitral valve replacement. (In preparation) 75. Daily PO: In discussion of Roe: Myocardial protection with cold ischemic potassium cardioplegia. Presented at the 2nd Annual Meeting, The Samson Thoracic Surgical Society, Jun 1976 76. Sapsford RN, Blackstone EH, Kirklin JW, et al: Coronary perfusion versus cold ischemic arrest during aortic valve surgery: A randomized study. Circulation 49:1190-1199, 1974 77. Brody WR, Reitz BA, Andrews MJ, et al: Long-term morphologic and hemodynamic evaluation of the left ventricle after cardiopulmonary bypass. J Thorac Cardiovasc Surg 70: 1073-1087, 1975 78. Roe BB, Hutchinson JC, Fishman NH, et al: Myocardial protection with cold ischemic potassium cardioplegia. Presented at 2nd Annual Meeting, The Samson Thoracic Surgical Society, Jun 1976 79. Rees JR, Holswade GR, Lillehei CW, et al: Aortic valvuloplasty for stenosis in adults: Late results. J Thorac Cardiovasc Surg 67:390-394, 1974 80. Enright LP, Hancock EW, Shumway NE: Aortic debridement: Long term follow-up. Surgery 69:404-409, 1971 81. Brawley RK, Donahoo JS, Gott VL: Current status of the Beall, Bjork-Shiley, Braunwald-Cutter, Lillehei-Kaster and Smeloff-Cutter cardiac valve prostheses. Am J Cardiol 35:855-865, 1975 82. Lee SJK, Barr C, Callaghan JC, et al: Long-term survival after aortic valve replacement using Smeloff-Cutter prosthesis. Circulation 52:1132-1137, 1975 83. Rapaport E: Natural history of aortic and mitral valve disease. Am J Cardiol 35:221-227, 1975 84. Kloster FE: Diagnosis and management of complications of prosthetic heart valves. Am J Cardiol 35:872-885, 1975 85. Santinga JT, Kirsh MM, Batsakis JT: Hemolysis in different series of the Starr-Edwards aortic valve prostheses. Chest 63:905-908, 1973
ventricular performance is present, surgical therapy is recommended even for class II (New York Heart Association) patients. In asymptomatic patients in whom there is evidence of progressive left ventricular enlargement on physical examination, chest x-ray or echocardiogram, or in whom electrocardiograms show increasing signs of left ventricular hypertrophy, or in patients in whom echocardiographic indices of left ventricular performance indicate a progression from normal to abnormal left ventricular systolic performance, cardiac catheterization is done. If left ventricular systolic function as assessed at catheterization is normal, careful medical management is recommended. The presence of significant depression of \eft ventricular performance warrants considerat on for valve replacement. It is worth emphasizing that symptoms of congestive heart failure in patients with chronic aortic regurgitation are not as valuable in predicting survival following valve replacement as other measures of cardiac performance.47 A vexing problem encountered in patients with chronic aortic regurgitation is management of a patient who has significant aortic regurgitation and established, severe myocardial dysfunction. The natural history in this setting is poor, with progression of myocardial disease and limited longevity.5 '; However, valve replacement in such cases does not appear to result in the reversal of myocardial dysfunction20 and in preliminary studies the long-term results of surgical operation in this situation have not been encouraging.48 In summary, one must decide between medical management with almost certain worsening of myocardial function, and the risk of surgical operation with the possibility of arrest without reversal of the deterioration of myocardial function, and no current evidence that the natural history will be positively affected. If symptoms are refractory to optimum medical management, valve replacement can be undertaken with the above mentioned expectations kept in mind. At present, cardiac catheterization provides the most reliable means of assessing the function of the left ventricle in patients with aortic regurgitation; therefore, appropriate care and attention should be directed toward the assessment of left ventricular performance at the time of catheterization in these patients. Ideally, quantitative biplane ventriculography should be employed in patients with chronic aortic regurgitation. A recent study by Bolen and associates identified a
group of patients with aortic regurgitation and normal basal left ventricular ejection fraction who responded to afterload stress (angiotensin) with a decrease in ejection fraction and left ventricular stroke work index. The authors felt that this response might indicate a state of latent left ventricular dysfunction.49 Employment of a welldefined stress of this type might prove to be useful in the routine evaluation of left ventricular performance in aortic regurgitation. Supravalve aortic root angiography is employed to roughly quantitate the degree of aortic regurgitation (trivial to 4 + ) and to document the anatomy of the aortic root, which may be quite dilated in Marfan syndrome or cystic medial necrosis. Coronary angiograms are routinely obtained in patients over age 40. Associated mitral valve disease-rheumatic and mitral prolapse in particular -should be evaluated with appropriate pressure recordings and analysis of the left ventricular cineangiogram. Acute aortic regurgitation may overwhelm the usual compensatory mechanisms accompanying a volume overload, and left ventricular end-diastolic pressure may rise to produce severe pulmonary vascular congestion. If medical therapy, as outlined by Dr. Karliner, is not effective in relieving the congestive heart failure, cardiac catheterization followed by aortic valve replacement may be required, even in patients with active infective endocarditis. In patients with acute aortic regurgitation, therefore, the timing of cardiac catheterization and aortic valve replacement is dependent upon the severity of associated signs and symptoms of heart failure, in contrast to chronic aortic regurgitation.
Surgical Considerations in Aortic Valve Disease PAT 0. DAILY, MD*
As DR. JOHNSON has discussed, the timing of aortic valve surgical therapy in a given patient requires synthesis and consideration of all the available clinical, noninvasive, angiographic and hemodynamic information. Presented with a patient in whom the decision for valve replacement has been made, a surgeon is faced with two prob*Associate Professor of Surgery.
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lems which at present do not have ideal solutions: (1) selection of a prosthetic replacement for the diseased aortic valve and (2) deciding upon a surgical technique which will provide the best operative results and the least chance of causing myocardial damage. Let us first consider selection of a prosthetic aortic valve. Although many factors relate to selection of a valve substitute, the three primary considerations are hemodynamic performance, durability and the incidence of thromboembolism. Additional aspects such as availability and ease of insertion are important but are relatively equivalent for most of the currently used valve replacement devices. However, when aortic allografts were at the height of their popularity, procurement was a major obstacle in their use. It is, therefore, an evaluation of these three basic determinants that accounts for the selection of a particular valve replacement device for a specific patient.
Hemodynamic Considerations Substitute valves can be basically divided into those having a central flow orifice and those with a lateral flow orifice. These designations relate to the fact that in central flow valves the direction of blood passage through the valve is not changed from the normal situation. Porcine xenografts and allografts are examples of central flow valves. In lateral flow valves, after passage through the primary orifice, blood flow is directed laterally upon striking the poppet. The various ball and disc valves are examples of lateral flow. Valves with a tilting disc such as the Bjork-Shiley and LilleheiKaster valves may be described as semicentral flow valves. Valves of this type have been reported to have very favorable hemodynamic characteristics, particularly in the smaller sizes.50 From a hemodynamic standpoint alone, it appears that central flow type valves are more physiologically appropriate. However, a number of different prosthetic aortic valves appear to offer acceptable hemodynamic results.52
Durability Most prosthetic valves have satisfactory durability, but problems have been encountered. In Braunwald-Cutter aortic prostheses cloth wear has been noted, as well as poppet embolization.53 Cloth wear has also been a significant problem with the 2300 series Starr-Edwards valves. Allografts appear to have a poor record for durability; Karp and co-workers54 found that in 10 to 15 474
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percent of patients with aortic allografts reoperation was needed, despite a more enthusiastic early report.55 Similar results were reported by Wallace and associates, with the probability of reoperation for valve failure being 7 percent within three years and 22 percent at five .years in this series.56 The method of allograft preparation is important; long-term results favor the fresh frozen57 or fresh antibiotic preserved allografts.58 Early experience with formalin preserved porcine xenografts resulted in a 50 percent failure rate at 42 months.59 However, experience with gluteraldehyde fixed xenografts followed up to 46 months showed no valve failures.60'62 The question of long-term durability in excess of four to five years of gluteraldehyde fixed porcine xenografts remains unanswered.
Thromboembolism The primary argument for the use of allografts and xenografts is the very low incidence of thromboembolism without the necessity for anticoagulation. Aortic allografts seem virtually free of thromboembolism; several large series have reported no thromboembolic complications in the absence of atrial fibrillation.62'63 With porcine xenografts there is an acceptably low incidence of thromboembolism without the use of anticoagulants.59'60 Thromboembolism is significantly more frequent after aortic valve replacement with caged poppet or tilting disc prosthetic valve. The early Starr-Edwards Model 1000 prosthetic aortic valve was reported to have a thromboembolic incidence of 34 percent at three years.63 Extension of fabric over the valve seat reduced the embolic rate to 5 percent at three years in the Starr-Edwards 1260 aortic valve. However, complete fabric enclosure of the metallic surfaces did not further reduce the thromboembolic rate in the 2300 series valves and resulted in the same thromboembolic rate as the Model 1260 valve. A recent comparison showed that the incidence of emboli at one year was 14.0 percent for the Braunwald-Cutter valve, 9.1 percent for the Starr-Edwards composite seat 2320 valve and 7.4 percent for the Starr-Edwards 1200 and 1260 silastic valves.54 Anticoagulants were not used with the first two valves but were with the last. It therefore appears that complete covering of the entire valve cage has not achieved the goal of an acceptably low incidence of thromboembolism without anticoagulants. Accordingly, it is now recommended that anticoagulants be used with these valves.54'65
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From the preceding discussion, it is apparent that no one valve is clearly superior in all respects to the others. This situation was very clearly portrayed as a graph in a recent editorial by McGoon.66 With permission this graph has been updated and is presented in Figure 8. It is apparent that confusion exists; with the bare-strut ball valve, cloth covered ball valve, tilting-disc valve and xenograft enjoying nearly equal popularity. It is our preference to routinely use the Hancock porcine xenograft because of the very low incidence of thromboembolism without anticoagulants. While long-range durability of the xenograft is unknown, the current model has been associated with an extremely low incidence of failure over a 46 month period. In the case of smaller aortic roots, consideration is given to the Bjork-Shiley valve, with that valve being definitely preferred with aortic valve sizes of 21 mm and under.
Surgical Technique The primary controversy regarding aortic valve replacement relates to the method of myocardial protection during the period of aortic cross clamping. Although a number of variations exist, the basic methods of myocardial protection are coronary perfusion by cannulation of the individual coronary arteries and myocardial hypothermia. Each method can produce clinically acceptable results. For example, McGoon 67 using coronary perfusion reported a series of 100 consecutive aortic valve replacements without mortality, and DeBoer and Midell68 attributed continuous coronary perfusion as the single most important factor in achieving an operative mortality of 1.8 percent in 104 consecutive patients in whom aortic valve replacement was done. Myocardial surface cooling as described by Shumway and co-workers69 has been used with equal success in several series of patients. 70-72 Our own experience is that myocardial surface cooling, although yielding an opera-
tive mortality of 1 percent in 100 consecutive patients in whom aortic, mitral and multiple valve replacement was done does not produce constant myocardial cooling.73 Temperature gradients of as much as 20°C between the left ventricular epicardium and endocardium occur and persist. Furthermore, in a series of patients being evaluated after mitral valve replacement, a significant decrease in myocardial contractility was detected in several patients.74 With refinement of surgical methods, evaluation of the adequacy of surgical results and myocardial protection must primarily be concerned with chronic preservation of left ventricular function, rather than operative mortality.75 As emphasized in a randomized study reported by Sapsford and associates,76 it appears that either coronary perfusion or myocardial hypothermia can offer very acceptable clinical results. Unfortunately, there is evidence that neither method results in complete preservation of myocardial function. In a chronic experimental study, Brody and coworkers77 found that coronary perfusion and myocardial surface cooling resulted in late depression of left ventricular function and produced myocardial fibrosis. Accordingly, refinements of existing techniques and other methods are being sought in an endeavor to enhance preservation of myocardial function. Because of the inconsistency of myocardial surface cooling mentioned above, our laboratory is presently involved in a comparison of myocardial surface cooling and cold cardioplegia (infusion of a cold electrolyte solution of high potassium content into the cross clamped aortic root and coronary arteries) as described recently by Roe and associates.78 Results of Aortic Valve Replacement Although aortic valvuloplasty was extensively done in earlier years,79 80 because of suboptimal long-term results, it has largely been replaced by aortic valve replacement. Consequently, this discussion will relate to valve replacement. The essential aspects in considering the results of aortic valve replacement include operative mortality (30 days from operation), late mortality, symptomatic improvement and complications associated with valve replacement. Current operative mortality is between 5 and 15 percent in most reported series and is less than 5 percent in selected reports. It is increasingly apparent that this mortality is determined more by patient selection than use of a particular prosTHE WESTERN JOURNAL OF MEDICINE
475
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Figure 9.-Composite graph showing in the upper curve survival in 962 patients after aortic valve replacement as reported by Barnhorst et al." An operative mortality of 6.3 percent is not reflected in this curve. The lower curve shows survival of patients with aortic stenosis treated medically as described by Rapaport.8"
thetic valve. Hospital and late mortality rates with the Bjork-Shiley, Braunwald-Cutter, LilleheiKaster and Smeloff-Cutter valves have been shown to be similar,81 and comparable to mortality rates for the Starr-Edwards aortic prosthesis64 and the Smeloff-Cutter prosthesis.82 Late mortality seems to be more clearly associated with the preoperative status of the patient rather than the type of prosthesis. Heart size at the time of operation and the type of dominant aortic valvular lesions are more important in affecting late survival than the type of prosthetic valve.64 In considering the utility of aortic valve replacement it is useful to compare late mortality of aortic valve replacement with the natural history of aortic stenosis treated medically. A composite graph (Figure 9) has been constructed with operative mortality and late mortality reported by Barnhorst and co-workers64 compared with those in a group of patients with aortic stenosis treated medically, as recently described by Rapaport.83 The late mortality at nine years after aortic valve replacement was 27 percent compared with 78 percent in the group medically treated. (The surgical mortality excludes the low operative mortality.) Furthermore, in most patients in whom operations are done there is significant symptomatic improvement. Typical results were reported by Behrendt and Austen5l of 113 patients in whom aortic valve replacement was done; most were New York Heart Association class III. After operation, 72 percent became class I and 28 percent class II. In addition to thromboembolism and late valve failure, several other complications of aortic valve replacement require brief comment. Endocarditis involving the prosthetic valve is an extremely serious problem. This occurs in approximately 4 per476
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cent of patients84 and if it occurs early is associated with a 79 percent mortality, compared with a 35 percent mortality if occurring after 60 days. Periprosthetic leak, with currently used prosthetic valves and techniques, is infrequent in the absence of infection. Poppet embolization, a disastrous complication, has also been reported,53 but previous problems with poppet wear have been minimized in current prosthetic valves by appropriate selection of material. Cloth covering of the valve cage has also resulted in a significant degree of hemolysis as compared with the earlier StarrEdwards valves,85 and can occasionally be an important clinical problem.
Closing Remarks DR. JOHNSON: The management of patients with aortic valve disease remains a challenging problem, and requires the closest interaction among patient, physician-cardiologist and cardiac surgeon. In this conference, we have stressed the clinical features of aortic valve disease, contrasting aortic stenosis-with its triad of congestive failure, ischemic chest pain and syncopal episodes-with aortic regurgitation in which the onset of symptomns and myocardial damage is much more insidious. The structural and functional abnormalities of the left ventricular myocardium caused by the pressure or volume overload, or both, accompanying aortic valve disease are important determinants of clinical symptoms and operative results, and their detection and prevention are therefore of paramount importance. Decisions regarding medical or surgical (or medical and surgical) management follow the accumulation of all pertinent historical, physical and laboratory data relative to the patient's disease process. This, added to the clinical information from noninvasive and catheterization studies, will allow a decision regarding the appropriate timing for valve replacement. We have emphasized the difficulty in identifying the optimum time for operative intervention in chronic aortic regurgitation, the requirement for careful medical management in this situation and the need for further investigation in this area. In our opinion, valve selection at present would favor the use of the glutaraldehyde preserved porcine heterograft in all but the small aortic root because of its relative freedom from the need for anticoagulation and the low thromboembolic rate.
AORTIC VALVE DISEASE
The long-term durability of this valve is currently unknown, however. When, for technical reasons, the use of the aortic heterograft is precluded, a variety of suitable prosthetic valves are available with the use of the tilting disc valves enjoying the most rapid rise in popularity. Protection of the myocardium during operation is a most important factor in determining the success or failure of a given operation. That satisfactory operative resuits mnay be obtained with either continuous coronary perfusion or myocardial hypothermia has been shown by many series. With careful attention to the proper timing of operation, technical competence in valve replacement and adequate protection of the myocardium, the operative mortality should be less than S percent and, it is hoped, any significant insult to left ventricular myocardial function will be prevented. With the gratifying progress in cardiovascular surgical techniques and results, it becomes all the more important for internists and cardiologists to identify and nmeticulously manage patients with aortic valve disease so that there can be optimal timing of surgical therapy to patients' clinical status and nmyocardial function. REFERENCES 1. Roberts WC: The structure of the aortic valve in clinically isoiated aortic stenosis. Circulation 42:91-97, 1970 2. Roberts WC, Perloff JK, Constantin T: Severe valvular aortic stenosis in patients over 65 years of age. Am J Cardiol 27:497-506, 1971 3. Roberts WC: The congenitally abnormal bicuspid aortic valve-A study of 85 autopsy cases. Am J Cardiol 26:72-83, 1970 4. Frank S, Johnson A, Ross J Jr: Natural history of valvular aortic stenosis. Br heart J 35:41-46, 1973 5. Goldschlager N, Pfeifer J, Cohn K, et al: The natural history of aortic regurgitation-A clinical and hemodynamic study. Am
Med 54:577-588, 1973 6. Spagnuolo M, Kloth H, Taranta A, et al: The natural history of aortic regurgitation-Criteria predictive of death, congestive heart failure, and angina in young patients. Circulation 44:368-380, 1971 7. Kennedy JW, Twiss RD, Blackmon MD, et al: Quantitative angiocardiography-Ill. Relationship of left ventricular pressure, volume, and mass in aortic valve disease. Circulation 38: 838-845, 1968 8. Hood WP Jr, Rackley CE, Rolett EL: Wall stress in the normal and hypertrophied human left ventricle. Am J Cardiol 22:550-558, 1968 9. Gould KL, Lipscomb K, Hamilton GW, et al: Relation of left ventricular shape, function and wall stress in man. Am J Cardiol 34:627-634, 1974 10. Spann JF, Buccino RA, Sonnenblick EH, et al: Contractile state of cardiac muscle obtained from cat with experimentally produced ventricular hypertrophy and heart failure. Circ Res 21: 341-354, 1967 11. Williams JF Jr, Potter RD: Normal contractile state of hypertrophied myocardium after pulmonary artery constriction in the cat. J Clin Invest 54:1266-1272, 1974 12. Sasayama S, Ross J Jr, Franklin D, et al: Adaptations of the left ventricle to chronic pressure overload. Circ Res 38:172178, 1976 13. Ross J Jr: Afterload mismatch and preload reserve: A conceptual framework for the analysis of ventricular function. Prog Cardiovasc Dis 18:255-264, 1976 14. Grossman W, McLaurin LP, Stefadouros MA: Left ventricular stiffness associated with chronic pressure and volume overloads in man. Circ Res 35:793-800, 1974 15. Sonnenblick EH, Ross J Jr, Covell JW, et al: Ultrastructure of the heart in systole and diastole: Changes in sarcomere length. Circ Res 21:423-431, 1967 16. Mahler F, Ross J Jr, O'Rourke RA, et al: Effects of changes in preload, afterload, and inotropic state on ejection and isoi
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AORTIC VALVE DISEASE with aortic regurgitation and patients with aortic stenosis. Circulation 50:1190-1199, 1974 48. Bailey MT, Feild BJ, Baxley WA: Left ventricular function prior to surgery for aortic valve incompetence: Prognostic implications. Circulation 49/50(Suppl III) :41, 1974 49. Bolen JL, Holloway EL, Zener JC, et al: Evaluation of left ventricular function in patients with aortic regurgitation using afterload stress. Circulation 53:132-138, 1976 50. Bjork VO, Henze A, Holmgren A, et al: Evaluation of the 21 mm Bjork-Shiley tilting disc valve in patients with narrow aortic roots. Scand J Thorac Cardiovasc Surg 7:203-213, 1973 51. Behrendt DM, Austen WG: Current status of prosthetics for heart valve replacement. Prog in Cardiovasc Dis 15:369-401, 1973 52. Bonchek LI, Starr A: Ball valve prostheses: Current appraisal of late results. Am J Cardiol 35:843-854, 1975 53. Pluth JR, Danielson GK: Poppet embolization in clothcovered silastic poppet valves. Mayo Clin Proc 49:811-814, 1974 54. Karp RB, Kirklin JW, Kuchoukos NT, et al: Comparison of three devices to repair the aortic valve. Circulation 49/50 (Suppl II):163, 1974 55. Karp RB, Kirklin JW: Replacement of diseased aortic valves with homografts. Ann Surg 169:921-926, 1969 56. Wallace RB, Londe SP, Titus JL: Aortic valve replacement with preserved aortic valve homografts. J Thorac Cardiovasc Surg 67:44-52, 1974 57. Moore CH, Martilli V, Al-Janabi N, et al: Analysis of homograft valve failure in 311 patients followed up to 10 years. Ann Thorac Surg 20:274-281, 1975 58. Wallace RB: Tissue valves. Am J Cardiol 35:866-871, 1975 59. Zuhdi N, Hawley W, Voehl V, et al: Porcine aortic valves as replacements for human heart valves. Ann Thor Surg 17:479-491, 1974 60. Pipkin RD, Buch WS, Fogarty TJ: Evaluation of aortic valve replacement with a porcine xenograft without long-term anticoagulation. J Thorac Cardiovasc Surg 71:179-186, 1976 61. Cohn LH, Lamberti JJ, Castaneda AR, et al: Cardiac valve replacement with stabilized gluteraldehyde porcine aortic valve: Indications, operative results, and follow-up. Chest 68: 162-165, 1975 62. Pacifico AD, Karp RB, Kirklin JW: Homografts for replacement of the aortic valve. Circulation 45(Suppl I) :36, 1972 63. Stinson EB, Angell WW, Iben AB, et al: Aortic valve replacement with the fresh valve homograft. Am J Surg 116:204209, 1968 64. Barnhorst DA, Oxman HA, Connolly DC, et al: Isolated replacement of the aortic valve with the Starr-Edwards prosthesis. J Thorac Cardiovasc Surg 70:113-118, 1975 65. Starr A: Comparison of long-term results after ball valve replacement, In: 11th World Congress of the International Cardiovascular Society, Symposium on Long Term Results of Cardiac Valve Replacement, Minerva Medica, 1973 pp 359-369 66. McGoon DC: On evaluating valves. Mayo Clin Proc 49: 233-235, 1974
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