“If It Isn’t Fun.” – The Minnesota Code. Background and Correspondence
Though I did all the compiling of the Minnesota Code, with the crucial aid of Punsar, Rautaharju, and Blomquist in testing it, a major source of data was the material that Ernst Simonson had acquired on the normal and abnormal ECG. Our chief encouragers and collaborators in the early days were Fred Epstein of Michigan, Geoffrey Rose of London, and Ian Higgins of Cardiff. The original impetus was, of course, from Ancel Keys, when he commissioned me in the larger enterprise of developing field methods for the Seven Countries Study. He took an active role in sending my early drafts of the Code around the world to get the reaction of outstanding authorities with whom he was on a first-name basis. Some of the correspondence is reproduced here for its historical interest.
Fred Epstein was much involved from the outset and discussed our criteria with his Michigan colleagues Park Willis and Franklin Johnson, the latter having developed the chest V leads of the standard ECG, still used 50 years later.
Fred Epstein wrote to Ancel Keys in 1957:
“I had an impression from Dr. Doyle’s correspondence that [he considered] diagnostic criteria of the type you now propose are not practical or even desirable. I disagree with this point of view, in all friendliness, and have said so with no little emphasis in my letter to him. In general, I would like to say, and I think this is very important, that we need not quarrel as to what each of us means by definite or possible disease. All we have to do is to agree to list our findings, irrespective of their meaning, in a standardized way. For this purpose, I believe that the categories you propose are not open to any major criticism though one might even out some minor points.”
Thus, Fred gave me ammunition to return to my plan not to label the ECG classes with diagnostic terms; these had been added during the short period when the code was adapted and “adopted” by Keys and Simonson for their presentation at the Princeton Conference on epidemiological methods. Characteristic of those times, despite having done the work, I was considered too “junior” to be invited to represent myself or this effort at such an important international conference of experts. Never mind.
Correspondence was ongoing with our biggest skeptic, Joe Doyle of the Albany Study, and this letter to him from Fred Epstein contains the gist of what we were seeking:
July 15, 1957
I am surely in agreement with everything you say in your statement, and if I may say so, it was a pleasure to see it said so elegantly and well. However, can we go beyond this and be more specific without getting into controversy and rules and regulations to which others may not subscribe, and which may prove, like all uniformity, stifling and sterile? I think that the task is not quite as complicated in practice as it seems in theory. For one thing, one is at an advantage in longitudinal studies, inasmuch as one does not have to commit oneself entirely on the significance of a given finding at the time it is taken, it being one of the very purposes of these studies to determine the meaning of, in your words, “borderline abnormalities.” As long as we don’t call them normal or abnormal, I believe we are safe.
I believe failure to make some attempt at standardizing the criteria might cause major inconsistencies when comparing results of different studies. Clearly, when one places a cutting point high enough to exclude most of the false positives, one increases the number of false negatives. I think this is not too bad from our particular point of view, since the lesser evil is to miss some true positives, the greater evil to include too many false positives. Due to the insensitivity of the ECG, one misses many instances of more or less advanced disease anyway. My feeling is that ECGs should not be too precisely standardized, and reading between the lines, this seems to be your feeling, too. I gathered the impression in Boston that most people, whether they wanted it or not, resort largely to pattern reading. This certainly appears to apply to Framingham. I rather think that we should at least make an attempt to go a little bit further than this. Otherwise, our advice would merely consist in giving the green light to everybody to go his own merry way.
Frederick H. Epstein,
Research Associate and Lecturer in Epidemiology.”
Paul Dudley White
Keys initiated correspondence with many cardiologists internationally about early versions of the Minnesota Code. Here is a reply from Paul Dudley White, the Dean of world cardiologists:
264 Beacon Street, Boston.
February 11, 1958
Thanks very much for your letter of February 7. Yes, I suppose it is a good idea to have a uniform system of reporting electrocardiographic findings. I shall refer the list to Conger Williams for comment and then return it to you. I have edited an item or two myself, for example, about the physiological effect of exercise in producing ST depression and the possibility of horizontal heart position giving a fair amount of left axis deviation as shown in the limb leads. Also, I have said that one should exclude a normal, narrow split of the R in V2 in the diagnosis of right bundle branch block. One might also add an item on elevated ST segments and on bigger, wide T-waves don’t you think?
“Dear Dr. White: I am returning the [Minnesota] criteria for electrocardiographic interpretation. It seems to me that these criteria are very adequate for such studies as Dr. Keys has proposed. I presume that a few mistakes could be made in following these closely, but I do not see how one can improve upon this collection of criteria in attempting to do what Dr. Keys has in mind. I wish to thank you for allowing me to see these criteria. I am sorry about the delay in sending the papers back to you. Yours very truly, Conger Williams, MD”
It seems that Ancel sent out criteria that labeled definite and possible infarction when I never used such terms; presumably he used Ernst Simonson’s Princeton version. At any rate, there was much criticism about such diagnostic probabilities.
“Keys starts off with the assumption that only the observation can be completely objective and an interpretation may vary, but from there on he seems to apply his scheme in an opposite manner; the differentiation of definite from possible is not quite as clear as he makes it.”
Many months later, in September 1958, I got a letter from Paul Langner talking about the importance of notched QRS waves representing patchy infarction.
An October 15, 1958 letter to Ancel and me from Ian Higgins, then working with Archie Cochrane in Cardiff, read, in part:
“I think we all agree that precise quantitative criteria for ECG interpretation that would be generally accepted in epidemiological comparisons are urgently needed. Your criteria form an admirable starting point. It might be possible to reduce the number of criteria by excluding any that are poorly reproducible. I hope you won’t consider these [detailed enclosed] criticisms as too outspoken. We are as anxious as you to decide on generally acceptable criteria and must congratulate you on the progress you are making in this direction.”
Ancel replied to Higgins letter with greater than usual warmth and diplomacy: “We are delighted at the prospect of developing close cooperation with you and your group and I am sure that this will be valuable to progress in the epidemiology of heart diseases as well as it being personally pleasant and interesting.”
Bob Grant, then author of a popular new book on vectorcardiography, and soon to become director of the National Heart Institute, was quoted by then director James Watt in a letter to Keys:
“Dr. Grant is quite impressed with these criteria and feels that they are the best that he has yet seen. He does have some specific suggestions to follow which he feels may make the criteria more accurate.”
Grant himself responded to our next draft in a letter to me, as follows:
“I read with interest the definitive criteria and note with some dismay they have become more complicated and curiously no longer up to date. They sound more like the New York Heart Criteria of the 40s than what the 50s can produce. Q/R ratios do the job incompletely and, frankly, miss many cases, and I thought they had long since been abandoned as they should be; far more rational patterns to identify terminal QRS abnormalities are now available. Either magnitude or directional differences can produce the same Q/R ratio on a given lead, but only the directional ones are abnormal. There are other evidences of “backsliding” that sadden me — such as the term posterior infarction, eliminating the QRS criteria for truly posterior infarction. But perhaps the retrogression is because there are now too many cooks who have taken part. Probably, I am making the brewings too hard; so I am not carrying my critique further.”
And that’s the last we heard from him.
A letter to Keys from Pierre Duchosal, distinguished professor of cardiology in Geneva, pioneer vectorcardiographer, and secretary general of the International Society of Cardiology, states:
“The system that you suggest for reporting ECG findings seems to be very adequate on the condition that the recorders reply to all questions. Teams of doctors from certain countries may be reluctant to do it properly. Anyway, I do not see any better system for obtaining the results which would fill your purposes.”
Howard Burchell, then Senior Consultant at the Mayo Clinic, replied on February 17, 1958:
“I appreciate your sending me the proposed system of reporting electrocardiographic findings, and I believe that the outline is a very excellent one. The actual incidence of [confounding] conditions is so small that I doubt they would seriously interfere with the statistical appraisal of the electrocardiographic abnormalities as indicating coronary disease in a population.”
Carl Chapman wrote to Ancel: “Let me say at the outset that I think it [the code] would work out very well and will certainly bring some order into the undoubted chaos that electrocardiographic reporting now displays. [My critique] will undoubtedly set Ernst [Simonson] off on some sort of a tirade. I hope, however, that he will sit down and educate me along these lines, knowing, as I am sure he does, that I never liked electrocardiography very much and I am bewildered and, at times, impatient with attaching a massive meaning to minor changes.”
In a July 29, 1958, letter to Joe Doyle, I wrote:
“We are particularly delighted in your response to these criteria as it seems to represent a considerable change in your feelings since the Boston [Brookline] meeting. As you see, we have incorporated your excellent suggestions concerning ST depression into the criteria. Please comment further if you feel inclined. Very cordially yours, HB.”
I have a collection of generally supportive letters from other cardiological leaders of the day, including Kossman, Kimura, Astrup, Karvonen, Aravanis, Aaron Schaeffer, Milnor, Bronte-Stewart, Briller, Chapman, Kannel, and A.J. Thomas. Ancel’s thoroughgoing effort to get the input of these experts surely facilitated eventual acceptance of the Minnesota Code, perhaps in that no one was in a position to lambaste it once they were on record as for it!
Drafts of April, 1959, indicate the Minnesota Code in an advanced pre-publication stage. I introduced it to correspondents a last time, pre-publication in “Circulation,” with this comment:
“This system is not offered for clinical application in the diagnosis and treatment of patients. It merely aims to provide objective and uniform classification of ECG characteristics with the minimum of debatable interpretation. Pathological significance for most of the items must await better follow-up studies than are available now.”
Compiling and honing of the Minnesota Code criteria over the early years, and studies of test-retest reliability, was a huge amount of work. But the published code met the immediate need in the field for cross-sectional comparison of prevalence of objective findings reasonably attributable to heart disease. It is not so surprising that the code and procedure became widely used at that time of great need. It is remarkable, however, that the Minnesota Code and its elaborations since the late ’50s are still in use after 40 years. Theoretically superior systems, such as the NOVACODE of co-author Rautaharju, are subject to similar problems of reproducibility. The “latest” computerized version of the code (Netherlands system of Jan Kors et al.) is 100 percent reproducible because it is 100 percent computerized, and it also agrees well with improved diagnostic systems such as NOVACODE. But the simple, discontinuous Minnesota Code criteria, with their many and obvious limitations, have somehow persisted. The classification and reporting schemes provided by the Minnesota ECG Coding center, now directed by Richard Crow and his assistant, Carmine O’Donnell, continue to serve numerous studies internationally that collect both taped and paper electrocardiograms.