LETTERS
It is of no particular relevance to know that the operative mortality in the VA study “compares favorably with the surgical experience of many large surgical centers in the U.S. during 1972 to 1974,” 2 at least as far as answering any of these specific questions in concerned, although such comparisons serve to distract attention from the real issues. The VA study is another worthy attempt to make a silk purse out of a sow’s ear, and (may I be forgiven the double metaphor) has turned out to be a pig in a poke. The data, appropriately arranged, can be applied only to an attempt to answer question 2 above. The more critical issue remains the one that is revealed by another failure of a carefully designed randomized controlled prospective study to answer, to general satisfaction, the question that it set out to answer. It is generally assumed that this approach is the one that is most likely to lead to the establishment of “the truth,” on the predication that “the truth” exists and that there is an answer to every question. Loop et al.,* for instance, throw a sop to Cerberus by stating “No clinician argues with the potential validity of this investigative method. Clinical trials have enormous value.” Chalmers has argued passionately in favor of the methodology, as a consequence of which he has been called “the high priest among the randomizer theologians”-expressing incidentally the cult nature of the affair. Feinstein4 has said, in relation to the collection of vital statistics, that “the most lamentable aspect of the fundamental problem, however, is the credulity and complacency with which egregiously defective statistics are accepted, used and disseminated as the basis of conclusions about so many major diseases. . . .” Despite the assertion of Loop et al., there are a few clinicians who argue with the validity of the method and consider that the repeated failure of such studies to convince lies not in bad design or bad performance but in the basic invalidity of a method that involves the pooling of disparate data and the concept of “controls.” Sir Peter Medawar, himself a distinguished scientist, has stated his opinion. In discussing the nature of medical activity in terms of the broad demarcation between the “natural sciences” and “what can only he described as the ‘unnatural sciences,” he writes as follows5: “It will at once be recognized as a distinguishing mark of the latter that its practitioners try most painstakingly to imitate what they believe-quite wrongly alas for them-to be the distinctive manners and observances of the natural sciences. Among these are (a) the belief that measurement and numeration are intrinsically praiseworthy (the worship, indeed, of what Ernst Gombrich calls ‘idola quantitatis’); (b) the whole discredited farrago of inductivism-especially the belief that facts are prior to ideas and that a sufficiently voluminous compilation of facts can be processed by a calculus of discovery in such a way as to yield general principles and naturalseeming laws’; (c) faith in the efficacy of statistical formulae, particularly when processed by a computer-the use of which is interpreted as a mark of scientific manhood.” The retitling by Loop et al. of Braunwald’s editorial “Coronary Artery Surgery at the Crossroads” to “Randomized Prospective Studies of Coronary Artery Disease at the Crossroads” might with profit be further modified to “Randomized Prospective Studies at the Crossroads.” It is about this that debate is needed, rather than about the attempt to answer questions that, as posed, are unanswerable. If the VA study leads to such a dialog, it will have at least performed that signal service. Hywel Davies MD, FACC Valais, Switzerland
References 1. LoopFD,Roudlllm~WC:Coconarybypasssur~wei(tredinmebalanat. Am J Cardiol42:154-156, 1976 2. Huf@wt HH, T&m 1, D&m KM, Murphy ML: Evaluation of the efficacy of cwomry by& svgery-I. Am J Card101 42:157-180. 1976 3. Ikawtwskl E: Evaluatkm of corotwv bvrmss swow-II. Am J Cardiol42:161-162, 1976 4. Fefmtefn AR: The intellechml morbidity of vital statistics. Med Counterpoint, November 1969, p 34-40 5. Medawar p: New Yak Review of Books, February 3. 1977
._.
MORE ON CORONARY
_.
BYPASS SURGERY-II
The recent trio of editorials testifies to the continuing argument over the exact place of coronary bypass surgery. The Cleveland Clinic group make what might be telling criticisms if they had not been ably answered by Hultgren and colleagues. In this context, observer variability and indeed the argument over the Veterans Administration’s coronary angiograms are somewhat mitigated by the fact that randomization should have distributed their quality levels equally in both the surgically and medically treated patients. Braunwakl’s editorial has also ably countered the comments of Loop and colleagues. The point here is, however, that this dispute (not to mention the volume of literature on this subject in the past few years) need not have taken place. Braunwald mentions the need for “randomized clinical trials.” This is the crux of the problem, but only a part of the general picture. The campaign for randomized trials of both coronary surgery la& and other cardiac surgery (aortic stenosis,lc Vineberg implantsld) began with a series of letters in 19701 when it became obvious that bypass was to become a growth industry. The first formal essay analyzing the problems and indicating the urgent need for controlled trials appeared in The American Heart Journal in February 19712 and was followed by Braunwald’s editorial in Hospital Practice.3 Despite these efforts and subsequent attempts to point out for surgery what is an accepted fact in medicine, the number of surgical procedures has progressively burgeoned with a torrent of puhlished reports. Why does this continue? It is clear that most surgeons and their more enthusiastic medical colleagues deeply believe in the efficacy of coronary bypass (ultimately justified, at least for symptomatic relief and for left main coronary occlusion). One cannot deal directly with such feelings in persons who are honestly convinced that what they are doing is best for their patients. The problem was, is (and will be unless changed) the malfeasance (no other word will do) of the natural referees of medicine-journal editors and reviewers and the evaluators of abstracts for national meetings. Had they applied standards comparable with those demanded of controlled trials of medical therapies from the outset, it is likely that we would have had better answers and much less argument by this time. I have only one cavil with Braunwald’s excellent analysis of the situation. He proposes that prospective randomized trials be performed “after pilot studies.” I hope he means pilot studies in animals. Chalmers4 has analyzed the “pernicious effect of pilot studies,” and all interested parties are encouraged to check this reference. He demonstrated that it is possible to randomize patients for any kind of therapy from the very outset. Random allocation in pilot studies would tend to make them conclusive, while permitting 50 percent of the possible candidates to avoid a promising, but untested treatment. At the same time, physicians who become excessively convinced on the basis of such appropriately designed pilot studies would not be able to escape by using the argu-
May 1979
The American Journal of CARDIOLOGY
Volume 43
1061
LETTERS
ment that they would find subsequent randomization to be unethical. David H. Spodick, MD, DSc, FACC Department of Medicine University of Massachusetts Medical School Division of Cardiology St. Vincent Hospital Worcester, Massachusetts References 1. Spodkk On: Letters. (a) American Heart Jownal79:579.1970. (b) Mod Med 26 January 1970. (c)N Eng J Msd 282:340, 1970. (d) Lance1 1:724. 1970 2. Spodfck DH: Revascufarlzation of the heart-numerators in search of denominators. Am Heart J 81:149-157, 1971 3. Sraumekf E: Direct cowtary revascularization. A plea not to let the genie escape from the bottle. Hasp Practics: 9-10, May 1971 4. Chalmns TC: Randomization of ttw first patient. f&d Clin North Am 59~1035-1038, 1975
MORE ON CORONARY
BYPASS SURGERY-III
One point I would like to raise concerns the absolute acceptance of a left main coronary lesion as an indication for surgery. The only study that has explored this in a controlled manner is the Veterans Administration study. Criticism on this point has recently been published by Graham.’ An argument can be made that not all of the patients treated medically were receiving propranolol, none were receiving sulfinpyrazone (later shown to reduce the incidence of sudden death)* and all were taken care of in a clinic setting as provided by VA institutions. One could suggest that caring for patients in a private practice setting might favorably influence prognosis. In addition, subsets of patients with left main coronary artery disease have been described.3*4 Such patients should be further categorized as to whether the left main artery is narrowed by 50 to 70 percent, 70 to 90 percent or 90 percent or greater, the status of the right coronary artery and of the left ventricle, as well as other clinical and noninvasive indicators. It would appear that medical management has advanced significantly since the VA study and that further randomized trials of selected patients with left main coronary artery disease might very well be warranted. George B. Prozan, MD Burlingame, California
renal disease (creatinine clearance less than 30 ml/min) were generally excluded from surgery or experienced an increased mortality rate. All of these patient groups are now operated upon with a 1 percent, 30 day operative mortality rate.’ This practice pattern and these results in two settings (Penn State’s Milton S. Hershey Medical Center in Hershey, Pennsylvania, and the University of Texas Medical Branch in Galveston, Texas), best described as “cottage industries”compared with the Cleveland Clinic, contrast sharply with the exclusion of all but low risk candidates from the Veterans Administration Cooperative Study. To believe that in 1978, only lower risk patients are being operated upon, as the VA study group obviously does, further illustrates their separation from the main stream of cardiological and surgical experience. We also fail to see how Braunwald’s ability to find two reports of operative mortality as poor as those reported in the VA study answers Loop’s complaint that a clinical trial should be designated to study the operation, not the surgeon. It doesn’t take a prospective study to determine that any act of skill can be performed poorly. The fact that a few VA hospitals (for example, that of Hines) contributed a majority of the patients and that their results are well within the national average, is also “bypassed.” Equally important is the knowledge that many VA hospitals did coronary bypass surgery only occasionally with mortality and complication rates far above the national average. In short, the means in the VA study are less interesting than the ranges, which the apologists never mention. Finally, the sensational headlines generated by the original report and editorials in The New England Journal of Medicine2p3 and the subsequent interviews that portrayed cardiologists and cardiothoracic surgeons practically at battle over indications for bypass surgery can hardly be passed off as the “sober analysis” characterized by Braunwald.2 G. Frank 0. Tyers, MD, FRCS(C) Edward H. Williams, MD Division of Cardiovascular and Thoracic Surgery Department of Surgery The University of Texas Medical Branch Galveston, Texas References 1. Tyen GFO, Williams DR. Babb JD, et al: The changing status of e@ction fraction as a predictor of early mortality following surgery for acquired heart disease. Chest 71: 371-375.1977 2. Eraunwald E: Coronary artery surgery at the crossroads. N Engl J Med 297:661-663. 1977 3. Murphy ML, Hultgen HN, Detre K, et al: Treatment of chronic stable angina. A prsliminaw report of swvival data of the randomized Veterans Administration Cooperative Study. N Engl J Med 297:621-627. 1977
Reterences
2. The Anturane &infarction Trial Research c;roU~: Sulfinwrazone in the prevention of cardiac death after myocardial infarction. N En& J Med %269-295. 1676 3. Canfey MJ. Ek RL Kbsb J. I.M KL Met&u. JF.RoutI RA:Ttwwouwstic we&urn ._ of leftwmain St&&is. Circubtlon 57:947-952. 1478 4. CampOeU L, Corbua F, Crochet D. P~Stclerc R: Left main coronary artery stenosis. The influence of aortCUX_ bypaSS Sugery on suvival. Circulation 57: 111 l-l 115. 1978
RETROGRADE CROSSING OF AORTIC BJORK-SHILEY PROSTHESIS
.
MORE ON CORONARY BYPASS SURGERY-IV We take issue with the statement by Hultgren et al. that “improved patient selection” is an important factor in the decrease in operative mortality for coronary bypass surgery seen during the last 8 years. Before 1974, patients with a systolic ejection fraction of less than 0.30, recent myocardial infarction, unstable angina, poorly visualized vessels beyond obstructions and chronic
1082
May 1979
The American Journal of CARDlDLOOY
Karsh et al.’ report on the safety and efficacy of retrograde left ventricular catheterization in patients with aortic valve prostheses, and record their experience with 27 patients with either a Starr-Edwards or a Bjork-Shiley prosthesis. No mention is made of how many patients had each prosthesis. Their Figure 3 shows a catheter crossing a Starr-Edwards valve prosthesis, showing little disturbance of the poppet while the catheter is across the valve; however, this frame was taken during systole and would therefore not be expected to show interference with the diastolic closing mechanism of the valve. We strongly advise caution regarding the retrograde crossing of aortic Bjork-Shiley prostheses. Unlike the Starr-
Volume 43
It is of no particular relevance to know that the operative mortality in the VA study “compares favorably with the surgical experience of many large surgical centers in the U.S. during 1972 to 1974,” 2 at least as far as answering any of these specific questions in concerned, although such comparisons serve to distract attention from the real issues. The VA study is another worthy attempt to make a silk purse out of a sow’s ear, and (may I be forgiven the double metaphor) has turned out to be a pig in a poke. The data, appropriately arranged, can be applied only to an attempt to answer question 2 above. The more critical issue remains the one that is revealed by another failure of a carefully designed randomized controlled prospective study to answer, to general satisfaction, the question that it set out to answer. It is generally assumed that this approach is the one that is most likely to lead to the establishment of “the truth,” on the predication that “the truth” exists and that there is an answer to every question. Loop et al.,* for instance, throw a sop to Cerberus by stating “No clinician argues with the potential validity of this investigative method. Clinical trials have enormous value.” Chalmers has argued passionately in favor of the methodology, as a consequence of which he has been called “the high priest among the randomizer theologians”-expressing incidentally the cult nature of the affair. Feinstein4 has said, in relation to the collection of vital statistics, that “the most lamentable aspect of the fundamental problem, however, is the credulity and complacency with which egregiously defective statistics are accepted, used and disseminated as the basis of conclusions about so many major diseases. . . .” Despite the assertion of Loop et al., there are a few clinicians who argue with the validity of the method and consider that the repeated failure of such studies to convince lies not in bad design or bad performance but in the basic invalidity of a method that involves the pooling of disparate data and the concept of “controls.” Sir Peter Medawar, himself a distinguished scientist, has stated his opinion. In discussing the nature of medical activity in terms of the broad demarcation between the “natural sciences” and “what can only he described as the ‘unnatural sciences,” he writes as follows5: “It will at once be recognized as a distinguishing mark of the latter that its practitioners try most painstakingly to imitate what they believe-quite wrongly alas for them-to be the distinctive manners and observances of the natural sciences. Among these are (a) the belief that measurement and numeration are intrinsically praiseworthy (the worship, indeed, of what Ernst Gombrich calls ‘idola quantitatis’); (b) the whole discredited farrago of inductivism-especially the belief that facts are prior to ideas and that a sufficiently voluminous compilation of facts can be processed by a calculus of discovery in such a way as to yield general principles and naturalseeming laws’; (c) faith in the efficacy of statistical formulae, particularly when processed by a computer-the use of which is interpreted as a mark of scientific manhood.” The retitling by Loop et al. of Braunwald’s editorial “Coronary Artery Surgery at the Crossroads” to “Randomized Prospective Studies of Coronary Artery Disease at the Crossroads” might with profit be further modified to “Randomized Prospective Studies at the Crossroads.” It is about this that debate is needed, rather than about the attempt to answer questions that, as posed, are unanswerable. If the VA study leads to such a dialog, it will have at least performed that signal service. Hywel Davies MD, FACC Valais, Switzerland
References 1. LoopFD,Roudlllm~WC:Coconarybypasssur~wei(tredinmebalanat. Am J Cardiol42:154-156, 1976 2. Huf@wt HH, T&m 1, D&m KM, Murphy ML: Evaluation of the efficacy of cwomry by& svgery-I. Am J Card101 42:157-180. 1976 3. Ikawtwskl E: Evaluatkm of corotwv bvrmss swow-II. Am J Cardiol42:161-162, 1976 4. Fefmtefn AR: The intellechml morbidity of vital statistics. Med Counterpoint, November 1969, p 34-40 5. Medawar p: New Yak Review of Books, February 3. 1977
._.
MORE ON CORONARY
_.
BYPASS SURGERY-II
The recent trio of editorials testifies to the continuing argument over the exact place of coronary bypass surgery. The Cleveland Clinic group make what might be telling criticisms if they had not been ably answered by Hultgren and colleagues. In this context, observer variability and indeed the argument over the Veterans Administration’s coronary angiograms are somewhat mitigated by the fact that randomization should have distributed their quality levels equally in both the surgically and medically treated patients. Braunwakl’s editorial has also ably countered the comments of Loop and colleagues. The point here is, however, that this dispute (not to mention the volume of literature on this subject in the past few years) need not have taken place. Braunwald mentions the need for “randomized clinical trials.” This is the crux of the problem, but only a part of the general picture. The campaign for randomized trials of both coronary surgery la& and other cardiac surgery (aortic stenosis,lc Vineberg implantsld) began with a series of letters in 19701 when it became obvious that bypass was to become a growth industry. The first formal essay analyzing the problems and indicating the urgent need for controlled trials appeared in The American Heart Journal in February 19712 and was followed by Braunwald’s editorial in Hospital Practice.3 Despite these efforts and subsequent attempts to point out for surgery what is an accepted fact in medicine, the number of surgical procedures has progressively burgeoned with a torrent of puhlished reports. Why does this continue? It is clear that most surgeons and their more enthusiastic medical colleagues deeply believe in the efficacy of coronary bypass (ultimately justified, at least for symptomatic relief and for left main coronary occlusion). One cannot deal directly with such feelings in persons who are honestly convinced that what they are doing is best for their patients. The problem was, is (and will be unless changed) the malfeasance (no other word will do) of the natural referees of medicine-journal editors and reviewers and the evaluators of abstracts for national meetings. Had they applied standards comparable with those demanded of controlled trials of medical therapies from the outset, it is likely that we would have had better answers and much less argument by this time. I have only one cavil with Braunwald’s excellent analysis of the situation. He proposes that prospective randomized trials be performed “after pilot studies.” I hope he means pilot studies in animals. Chalmers4 has analyzed the “pernicious effect of pilot studies,” and all interested parties are encouraged to check this reference. He demonstrated that it is possible to randomize patients for any kind of therapy from the very outset. Random allocation in pilot studies would tend to make them conclusive, while permitting 50 percent of the possible candidates to avoid a promising, but untested treatment. At the same time, physicians who become excessively convinced on the basis of such appropriately designed pilot studies would not be able to escape by using the argu-
May 1979
The American Journal of CARDIOLOGY
Volume 43
1061
LETTERS
ment that they would find subsequent randomization to be unethical. David H. Spodick, MD, DSc, FACC Department of Medicine University of Massachusetts Medical School Division of Cardiology St. Vincent Hospital Worcester, Massachusetts References 1. Spodkk On: Letters. (a) American Heart Jownal79:579.1970. (b) Mod Med 26 January 1970. (c)N Eng J Msd 282:340, 1970. (d) Lance1 1:724. 1970 2. Spodfck DH: Revascufarlzation of the heart-numerators in search of denominators. Am Heart J 81:149-157, 1971 3. Sraumekf E: Direct cowtary revascularization. A plea not to let the genie escape from the bottle. Hasp Practics: 9-10, May 1971 4. Chalmns TC: Randomization of ttw first patient. f&d Clin North Am 59~1035-1038, 1975
MORE ON CORONARY
BYPASS SURGERY-III
One point I would like to raise concerns the absolute acceptance of a left main coronary lesion as an indication for surgery. The only study that has explored this in a controlled manner is the Veterans Administration study. Criticism on this point has recently been published by Graham.’ An argument can be made that not all of the patients treated medically were receiving propranolol, none were receiving sulfinpyrazone (later shown to reduce the incidence of sudden death)* and all were taken care of in a clinic setting as provided by VA institutions. One could suggest that caring for patients in a private practice setting might favorably influence prognosis. In addition, subsets of patients with left main coronary artery disease have been described.3*4 Such patients should be further categorized as to whether the left main artery is narrowed by 50 to 70 percent, 70 to 90 percent or 90 percent or greater, the status of the right coronary artery and of the left ventricle, as well as other clinical and noninvasive indicators. It would appear that medical management has advanced significantly since the VA study and that further randomized trials of selected patients with left main coronary artery disease might very well be warranted. George B. Prozan, MD Burlingame, California
renal disease (creatinine clearance less than 30 ml/min) were generally excluded from surgery or experienced an increased mortality rate. All of these patient groups are now operated upon with a 1 percent, 30 day operative mortality rate.’ This practice pattern and these results in two settings (Penn State’s Milton S. Hershey Medical Center in Hershey, Pennsylvania, and the University of Texas Medical Branch in Galveston, Texas), best described as “cottage industries”compared with the Cleveland Clinic, contrast sharply with the exclusion of all but low risk candidates from the Veterans Administration Cooperative Study. To believe that in 1978, only lower risk patients are being operated upon, as the VA study group obviously does, further illustrates their separation from the main stream of cardiological and surgical experience. We also fail to see how Braunwald’s ability to find two reports of operative mortality as poor as those reported in the VA study answers Loop’s complaint that a clinical trial should be designated to study the operation, not the surgeon. It doesn’t take a prospective study to determine that any act of skill can be performed poorly. The fact that a few VA hospitals (for example, that of Hines) contributed a majority of the patients and that their results are well within the national average, is also “bypassed.” Equally important is the knowledge that many VA hospitals did coronary bypass surgery only occasionally with mortality and complication rates far above the national average. In short, the means in the VA study are less interesting than the ranges, which the apologists never mention. Finally, the sensational headlines generated by the original report and editorials in The New England Journal of Medicine2p3 and the subsequent interviews that portrayed cardiologists and cardiothoracic surgeons practically at battle over indications for bypass surgery can hardly be passed off as the “sober analysis” characterized by Braunwald.2 G. Frank 0. Tyers, MD, FRCS(C) Edward H. Williams, MD Division of Cardiovascular and Thoracic Surgery Department of Surgery The University of Texas Medical Branch Galveston, Texas References 1. Tyen GFO, Williams DR. Babb JD, et al: The changing status of e@ction fraction as a predictor of early mortality following surgery for acquired heart disease. Chest 71: 371-375.1977 2. Eraunwald E: Coronary artery surgery at the crossroads. N Engl J Med 297:661-663. 1977 3. Murphy ML, Hultgen HN, Detre K, et al: Treatment of chronic stable angina. A prsliminaw report of swvival data of the randomized Veterans Administration Cooperative Study. N Engl J Med 297:621-627. 1977
Reterences
2. The Anturane &infarction Trial Research c;roU~: Sulfinwrazone in the prevention of cardiac death after myocardial infarction. N En& J Med %269-295. 1676 3. Canfey MJ. Ek RL Kbsb J. I.M KL Met&u. JF.RoutI RA:Ttwwouwstic we&urn ._ of leftwmain St&&is. Circubtlon 57:947-952. 1478 4. CampOeU L, Corbua F, Crochet D. P~Stclerc R: Left main coronary artery stenosis. The influence of aortCUX_ bypaSS Sugery on suvival. Circulation 57: 111 l-l 115. 1978
RETROGRADE CROSSING OF AORTIC BJORK-SHILEY PROSTHESIS
.
MORE ON CORONARY BYPASS SURGERY-IV We take issue with the statement by Hultgren et al. that “improved patient selection” is an important factor in the decrease in operative mortality for coronary bypass surgery seen during the last 8 years. Before 1974, patients with a systolic ejection fraction of less than 0.30, recent myocardial infarction, unstable angina, poorly visualized vessels beyond obstructions and chronic
1082
May 1979
The American Journal of CARDlDLOOY
Karsh et al.’ report on the safety and efficacy of retrograde left ventricular catheterization in patients with aortic valve prostheses, and record their experience with 27 patients with either a Starr-Edwards or a Bjork-Shiley prosthesis. No mention is made of how many patients had each prosthesis. Their Figure 3 shows a catheter crossing a Starr-Edwards valve prosthesis, showing little disturbance of the poppet while the catheter is across the valve; however, this frame was taken during systole and would therefore not be expected to show interference with the diastolic closing mechanism of the valve. We strongly advise caution regarding the retrograde crossing of aortic Bjork-Shiley prostheses. Unlike the Starr-
Volume 43
