In 1959 I purchased from Old Hickory Bookshop in Brinklow, Maryland, a book entitled Sir William Osler, Bart., Brief Tributes to His Personality, Influence and Public Service Written by His Friends, Associates and Former Pupils, In Honor of His Seventieth Birthday and First Published in The Bulletin of The Johns Hopkins Hospital for July, 1919. This 167-page book, which also contains Osler's bibliography, has since been a steady companion of mine. My favorite chapter was written by his former Johns Hopkins' chief resident, William S. Thayer, who described the third heart sound, and is entitled “Osler, the Teacher.” In it, Thayer paraphrases comments of Osler apparently reiterated many times during rounds and other discussions. The comments are as appropriate 64 years later as when they were recorded by Thayer:

Several months ago at our weekly conference, we examined a Holter monitor that had been in place at the time of a patient's sudden death. I asked my colleagues at the conference, “Who is Holter?” and no one knew. I then asked my young associate, Dr. Marc Silver, to “bring us the scoop” on Holter. Marc initially went to the library to round up some of Holter's publications and learned that Holter lived in Helena, Montana, and a telephone dialogue with Holter began. We asked Holter to send us his curriculum vitae, copies of his most important publications, and any other bits and pieces of information that might be useful in writing an article on him and his contributions to medicine. Shortly after Holter, his wife (Joan), and his assistant (Karma Alfredson)had gathered these materials together, Holter died (on July 21, 1983) of prostatic cancer. We received the package of Holter information 2 weeks later.

In collaboration with his life-long friend and former teacher, Joseph A. Gengerelli, PhD, Holter first demonstrated the effectiveness of radiotelemetry in broadcasting and recording an electrocardiogram in a person while active. Subsequently, nearly 7000 articles have been published on Holter monitoring (which Holter always preferred to call Holter electrocardiography), and a medical journal (Biotelemetry and Patient Monitoring) was started solely for publications on this subject. Holter's invention of continuous electrocardiographic recording on magnetic tape with accelerated interpretation was to conventional electrocardiography what motion-picture photography was to still photog-raphy—not a bad accomplishment for a man who had neither an MD nor a PhD degree, funded his own research, had his own laboratory in a former train station in a town with a population of <30,000, and was unassociated with a medical center and indeed located far away from any medical research center.

The article that introduced the concept of recording an electrocardiogram “at a distance” appeared in the Rocky Mountain Medical Journal in September 1949, when Holter was 35 years old. Holter was proud that he did not receive personal financial gain from the monitoring equipment that today is a $200 million industry. “Its name is the only return I have in the system,” he remarked.

It is clear from reading the writings of Holter and from examining his varied activities that this man was a force to be reckoned with. His family was among the original settlers of Montana, and his grandfather and father were involved in a number of business enterprises, which “Jeff” Holter inherited and expanded. He was elected to numerous boards of directors of major companies in Montana and elsewhere. He was an artist, and among his creations were sculptures called “Geometry in Steel,” a 40-piece collection displayed at the Helena Poindexter Gallery of Contemporary Art. His involvement in the evaluation of nuclear weapons shortly after World War II made him an active spokesman about the dangers of nuclear weapons. Holter reiterated often that “if statesmen fail to prevent atomic war, the war after that will be fought with sticks and stones.” He foresaw in 1947, however, that atomic research could create major advances in medicine and biology, and he was one of the organizers and later president of the Society of Nuclear Medicine.

It is good that the word “Holter” as used in present-day cardiology stands for a man of such distinction.

About 20 million Americans are runners or joggers. The difference between the two is the speed of the pace, with the divider being about 8 minutes/mile. About 70% of US runners or joggers log in <10 miles/week and 4%, >40 miles/week. The champion marathoners usually run 100 to 120 miles/week. The winner of the 1983 New York marathon had a 4.9-minute/ mile pace for the 26.22 miles, and the 327th finisher had a 5.9-minute/mile pace. I started running 4 years ago and now average 13 miles/week. I usually enjoy the run and afterwards I always feel better—both mentally and physically. It's virtually the only exercise I do now. I like it because of its efficiency and its lack of dependence on another person (a tennis partner, for example) or on a particular place (golf course, for example) or time. One can run day or night, rain or shine, and anywhere. I've run in most major cities in the USA and some abroad, and when I think back on those trips, it's usually what I saw during the runs that I remember the most. I think and plan during a run. I rethink my priorities. Many ideas for research projects and “From the Editor” columns have come during runs.

But what is the real value of running? I believe that running is a recapturing of some of our individual independence lost to the automobile and other industrial inventions of the 20th century. Paul Dudley White said that coronary heart disease came with the automobile. Running is getting out of the car and moving with one's own horsepower.

There is no question that running is healthful. It decreases the resting heart rate, resting blood pressure, body fat, appetite, low-density lipoprotein cholesterol, and triglyceride levels. It increases mental health and tolerance to stress; resistance to infections; soundness of sleep; fibrinolytic (clot-dissolving) capability; high-density lipoprotein cholesterol; cardiac, pulmonary, bowel, and thyroid glandular function; and the strength of ligaments, tendons, skeletal muscles, and bones. Running, then, is a pretty good “medicine” without the use of drugs or scalpels or psychiatrists.

A great benefit of running is that it makes one health-responsible. Few runners smoke, and those who do smoke less than before. Runners are diet-conscious. On a recent plane trip I sat next to a woman who, I learned, ran about 20 miles/week. When noticing that she did not eat her pie with the meal, I inquired as to why not. She answered that “it was 4 miles” (400 calories = 4 miles). It takes nearly 32 minutes to run those 4 miles and <3 minutes to eat those 400 calories! The trade-off for the runner is simply not worth it. The more the body weight, the harder the running. Fish is digested more easily than is red meat, and good gastrointestinal function is important to a runner. Running provides a calmer disposition, and few regular runners need psychiatrists.

Individual responsibility for health has taken a giant step forward in the USA in the last 2 decades. The US population is healthier today than it was 20 years ago. The death rate from coronary heart disease is decreasing in the USA, and the USA is the only country in the Western world where this is so. Renewed interest in exercise almost surely has played a role in this improvement in health.

A major stimulant for the emphasis on self-responsibility for health came from Dr. George Sheehan, who often writes pieces on the importance of exercise. George Sheehan was born 65 years ago in Brooklyn, New York. He went to Manhattan College on a track scholarship, was a member of a championship cross-country team, and was runner-up to the US champion miler in 1940. He graduated from Long Island College of Medicine and in 1949 began the private practice of internal medicine and cardiology in Red Bank, New Jersey. At the same time, his family was enlarging and eventually numbered 12 children.

In 1963 he broke a bone in his hand and could not play tennis, and thus, at age 44, his second running career began. Since then he has missed training on the road only when ill or injured. He runs about 30 miles/week—10 on Tuesday, 10 on Thursday, and a race every Sunday. He calls himself a “mainline jogger” who gets withdrawal symptoms if he goes more than 48 hours without running. At age 50, he was the world record holder for milers aged ≥50 years, with a time of 4 minutes, 47 seconds. He has run dozens of marathons and at age 61 ran his fastest one (3 hours, 1 minute). That means he averaged 7 minutes for each of the 26.22 miles. In recent years, he has run the 6-mile race in 37 minutes. He has, of course, the runner's physique (weight in pounds = twice height in inches) and mystique… .

Running not only brought out the writer in Sheehan, but also brought out the philosopher. He started going to the public library rather than the medical library. Someone remarked that James F. Fixx writes on how to run and George Sheehan on why we run. Sheehan found his philosophy in his many philosophical friends; they include Emerson, Thoreau, Ortega, Santayana, William James, certain Greek philosophers, and Goethe, and he introduced them to many readers for the first time. Sheehan shows that athletes do not need to retire by age 40. He is an inspiration to me and I suspect to many others. He has demonstrated that a single cardiologist can improve the health of the entire country by setting an example of healthfulness rather than serving entirely as an advisor for healthfulness.

Considerable study has been made through the years of behavioral characteristics of nonhuman animals—how they communicate, court, mate, fight, care for their young, acquire food, care for their bodies, and so on. Similar studies of humans, of course, are being performed constantly. In contrast to studying general features of one species or another, the pages of this journal focus on how the heart behaves under natural and unnatural conditions, primarily in humans, but in 10% or so of its pages, in nonhuman animals. Our methods of studying the heart change with the changing of our “instruments of precision,” our pharmacopia and our ideas, but all the while the heart remains more or less unchanged. Despite the enormous amount of information gained about the heart in the last 75 years, in some respects we have not begun. Our knowledge of the causes of cardiac diseases remains poor. Our diagnostic and therapeutic abilities far exceed our knowledge of why the diseases occur in the first place.

Despite not knowing precisely why most heart diseases occur, we do know how to prevent many of them. If our total serum cholesterol remains <150 mg/dL, our chances of developing atherosclerosis severe enough to obstruct or aneurysmally dilate an artery are extremely small. If we totally discard salt from the diet, our chances of developing systemic hypertension and all of its consequences, including stroke, are virtually nonexistent. If we live in sanitary, uncrowded, and nonpromiscuous environments, our chances of developing rheumatic and syphilitic heart disease are minimal. If alcohol intake is not abused, our chances of developing our most common primary myocardial disease—dilated cardiomyopathy—are relatively small. Thus, most of our present-day common cardiologic conditions are acquired, man-made, of our own doing. The congenital cardiac conditions—holes in cardiac septa, obstructions to flow into or out of a cardiac chamber, improperly connected arteries and veins, malformed valves (bicuspid), which are prone to degenerate (calcify) or to become infected, floppy mitral valves and hypertrophic cardiomyopathy—will remain despite our alterations in dietary and living habits. As we continue to learn more about, and do more for, heart disease, it is humbling to reflect that the heart is only one of the body's many organs and that our major subjects of study are only one of the many species on this earth.

No medical group appears to have more meetings than cardiologists. From October 1960 until December 1983, I participated in 577 medical meetings, all but a few of which were cardiologic meetings, and 450 (78%) were located in cities outside the Washington, DC, area. Medical meetings often are located at sites that are vacation attractions. These meetings often include the opportunity to increase medical knowledge and, at the same time, obtain “a vacation” at a price less costly than if unconnected with a medical meeting because of the tax deductibility. But can both a vacation and increased medical knowledge really be obtained simultaneously? I think the answer is more often “no” than “yes.”

All of us obviously need rest and relaxation. Because each is different, each is usually obtained by different means. Rest is always passive and includes activities such as sitting in an easy chair, lying on a beach, or rocking in a hammock or sleeping. Rest allows tired muscles time to recover so that they can work efficiently again. It permits the rejuvenation of the physical being.

Relaxation, in contrast, may be either active or passive and includes such diverse activities as playing tennis, collecting stamps, lying on a beach, talking with another person, walking, or picnicking. Relaxation rejuvenates the emotional being so that we can cope better with pressures, challenges, and responsibilities of work and daily living. Relaxation helps prevent or relieve a general pessimism, diminished ability to cope, loss of enthusiasm, anger or irritability, a sense of personal isolation, and a utilization of tremendous amounts of energy to get very little accomplished. Relaxation, then, depends on how we experience an activity, not on what our body is doing or where we are during the activity. True relaxation is any satisfying involvement in any activity in which the primary reward is the experience itself. Therefore, absent from the relaxation experience is a win-lose goal orientation, an ego enhancement, or creation of “products” for later evaluation and justification of the time spent. Active relaxation is actually play, which is active involvement in an activity that one enjoys for the experience itself rather than for a payoff. Passive relaxation involves withdrawing into “inner space” to shut out the distractions and concerns of the surroundings. Thus, rest relieves primarily physical fatigue, and relaxation, primarily emotional fatigue.

By knowing exactly what rest and relaxation are, it is clear that it can be difficult combining a true vacation with a medical meeting or vice versa. One might argue that the physician is not required to spend the entire day at the medical meeting. The problem with this position is the element of guilt (also Uncle Sam). For each of the last 11 years I have directed a 3-day course in cardiology in Williamsburg, Virginia. The medical program lasts from 8 am to about 5:30 pm each day. A number of enrollees have complained to me that there is no time off during the daylight hours to enjoy the lovely Williamsburg setting and that at least 1 or 2 of the afternoons should be free to browse and savor the atmosphere. My position has been that enrollees are free to “take off” from the meeting at any time and by having the meeting continuously through the day those enrollees desiring entirely medical refreshment have the opportunity of obtaining it in concentrated form. This view sets poorly with the enrollees who want both medical and emotional refreshment, because guilt from “skipping the meeting” prevents full enjoyment of the sightseeing or vacation portion of the trip. I have finally come to realize that the only way to prevent the “professional” guilt in many enrollees and allow the obtainment of at least some relaxation for the enrollees is to recess the meeting for some of the daylight hours.

To obtain rest and relaxation in conjunction with a medical meeting, I believe that thorough premeeting planning is essential. If the meeting is to run continuously and “guilt” is a problem with the attendee, that person must plan for 1 or 2 days off before or after the meeting for concentrated physical and emotional rebuilding. If the additional days are not possible, missing some portion of the meeting is necessary.

Attending a medical meeting in one's hometown prevents the problem of trying to attend a medical meeting and have a vacation simultaneously, but then the medical meeting often is interrupted by practice obligations. One could also argue that not all pure vacations provide full rest and relaxation, but certainly the odds of obtaining them are greater without interruption by a professional meeting.

In conclusion, I find it difficult to infuse leisure time with work and obtain either good rest or full relaxation. Although a medical meeting in a vacation spot produces a change and a break from the “dailyness” of medical practice and in itself may provide some rest and relaxation, the medical meeting itself generally prevents the obtainment of either full rest or full relaxation. The latter two, in my opinion, are better obtained by completely separating the medical meeting from the vacation and vice versa.

In the USA today (1980 life tables), life expectancy from birth for white females is 78.1 years; for black females, 72.3 years; for white males, 70.7 years; and for black males, 63.7 years. For persons who have reached age 25 years in the USA, an age reached by >95% of persons at the time of graduation from medical school, life expectancy is even greater. Thus, of persons reaching age 25 years, 54.5 additional years (to age 79.5) can be expected for white women and 49.5 additional years (to age 74.5) for black women, 47.8 additional years for white men (to age 72.8) and 41.7 additional years for black men (to age 66.7).

Although physicians, of course, are included in these 1980 statistics, these expected ages are not reached by most US graduates of US medical schools. In the Journal of the American Medical Association each week is a column entitled “Obituaries.” Included in it are the names of recently deceased physicians, their ages at death, the name of the medical school from which they graduated, frequently the American specialty board by which they were certified, and the date of their death. Their race is not included. For the 3 years 1981, 1982, and 1983, the age at death of the male and female physicians according to specialty was determined… .

The average age at death of both the male and female physicians was below the national average for persons who had reached age 25 years; the mean age at death of the female physicians was younger than that of their male counterparts; and the mean age at death varied among the various subspecialties. The 9705 male physicians lived a total of 689,184 years, an average of 71.0 years each; the 365 female physicians lived a total of 25,495 years, an average of 69.9 years each. Among the various subspecialties, those surviving the shortest periods on the average were neurosurgeons (58.9 years), anesthesiologists (58.9 years), family practitioners (62.4 years), and pathologists (63.9 years). The longest survivors on the average were those classified as both ophthalmologists and otolaryngologists (79.3 years), next those classified as otolaryngologists (76.7 years), and then those boarded in preventive medicine (74.4 years). The pediatricians survived on an average longer than did the internists (69.2 years vs 66.7 years). The specific numbers on survival for adult cardiologists, pediatric cardiologists, and cardiovascular surgeons are not available.

In December 1982 at a cardiology course, I gave a talk on “sudden cardiac death” and described its many causes. One that I did not mention was nuclear explosion. On the same program was Dr. Bernard Lown, who spoke on “physicians, nuclear weapons, and nuclear war.” The insignificance of my earlier talk on sudden cardiac death was dramatically exposed by Lown's description of the “litany of horrors resulting from blast, fire, and radiation” were a nuclear war to occur. Since the dropping of the “small” (only 13 kilotons) nuclear bombs on Hiroshima and Nagasaki just over 40 years ago, world arsenals of nuclear weapons have increased to 15,000 megatons, the equivalent of 1 million Hiroshimas, and now nuclear weapons are “the greatest threat to health that human kind has ever known.” As so eloquently described by Cassel and associates:

The International Physicians for the Prevention of Nuclear War (IPPNW), an organization started by cardiologists Bernard Lown and Eugene Chazov and which was awarded the Nobel Peace Prize in 1985, gathered in Budapest in June 1985 under the slogan, “Cooperation not confrontation is the imperative of a nuclear age.” Since its inception 5 years ago, this organization has grown to 145,000 members from 45 countries. It has established a broad-based, free-flowing dialogue between physicians of the 2 major power blocs—the USA and the USSR—and it now calls for a moratorium on all nuclear explosions. It has previously urged freezing, reducing, and eliminating nuclear weapons and a commitment to no first use as the best means of eradicating the greatest public health threat of all time.

Cardiologist E. Greg Diamond has suggested an exchange program of university students between the USA and the USSR as a means of preventing nuclear confrontation. Earlier, Diamond had stated that the 10,000 Chinese scholars in American universities today serve as virtual guarantors of peace with China. Diamond now advocates exchange of 250,000 university students between the USA and USSR to act as agents of security for both sides because “people are unlikely to bomb their children.” George Lundberg, the editor of the Journal of the American Medical Association, added 4 other prescriptions: “1) extensive international travel at all times because people are unlikely to bomb their friends; 2) further development of global economy because people are unlikely to bomb their own companies; 3) extensive scientific and cultural exchanges because people are unlikely to bomb their colleagues; and 4) widespread intermarriage across countries because people are unlikely to bomb their own families and progeny.”

About 2 years ago my physician son asked me, “What makes a good researcher?” The question has intrigued me. This piece attempts to answer the question by describing predictable characteristics observed in long-term, productive physician researchers whom I have known or studied during the past 30 years.

• Absolute commitment (determination) to do research. Research is priority number 1 for the successful physician researcher. Patient care, teaching, administration, travels for lectures, etc., are performed around the research work. Energies for nonresearch activities are carefully allocated so that enough energy is left for creating, collecting, and writing. I have found that the energies required for research surpass those required for teaching, speaking, editing, and patient service. The ability to refuse requests for one's time is vital. A commitment to research is incompatible with full development of nonmedical interests. Beach and mountain houses, country clubs, and heavy social schedules rarely are compatible with successful long-term productive research.
• Industriousness. To say that chronic hard work is mandatory for success in research is almost trite. A week consists of 168 hours, not 40. Most writing is done before 8 am, after 5 pm, or during weekends and holidays. Spending the long hours necessary for success requires love and enthusiasm for one's work. Research is both avocation and vocation.
• Talent. This characteristic includes an ability to generate ideas, to formulate good questions, and to design studies capable of converting ideas into facts and questions into answers. New ideas and good questions exhilarate researchers. Good instincts are useful in asking the most pertinent questions. Skepticism is common—“Convince me, show me the data.” The researcher possesses the ability to spot “holes” in accepted knowledge.
• An ability to effectively and efficiently generate data to answer questions. The effective researcher is well organized and task oriented. The words effective and efficient are crucial. Results are measured not in terms of the number of hours worked, but in terms of accomplishment. Long hours of labor do not substitute for well-planned and -conceived experiments. Data are collected, not in a vacuum, but with an eye always seeking proper relations, underlying principles, and proper conclusions. Answers are pursued in a planned logical fashion. Daily, weekly, monthly, and yearly objectives are delineated and achieved.
• Absolute honesty. This attribute includes accuracy in collecting and collating data and also acknowledgment of predecessors who previously contributed information on the subject under investigation. Dishonest researchers are short-term survivors. Unintentional errors, however, are far more common than intentional (dishonest) ones. Whether the error is intentional or unintentional does not negate an error's being an error. The long-term researcher interprets data as they are, not as he/she wishes them to be.
• Pursuit of the highest standards of excellence. Sloppy work, “the easy way” rather than “the right way,” prevents long-term survival. “Getting it right” before “getting it out” requires much effort. Because errors are commonly found in manuscripts, all collected data are cross-checked. Standards of excellence rise with experience.
• Resourcefulness. This characteristic is essential in finding answers to questions, in acquiring funds to support the research, and in finding appropriate patients for the various studies.
• Flexibility. Ability to change course quickly is essential. The rigid, commander-type personality is out of place in a research laboratory.
• Perseverance. Strength and patience are essential, for the researcher's life, like others, has its disappointments. Not all research endeavors are successful, manuscripts are rejected, research grants are not approved or funded, personnel bring disappointment, and unpredictable and/or uncontrollable factors prevent completion of projects. The successful researcher, however, anticipates obstacles and overcomes them.
• Confidence. The long-term researcher believes in his/her abilities, judgments, and instincts but nevertheless welcomes criticism at any time from anyone (including manuscript reviewers) for he/she wants the product to be the best it can be. Hypersensitivity is the price of keen perceptiveness, but it is a small price to pay.
• An ability to recognize and develop opportunities. Opportunities for research are not equally divided among individuals or among medical institutions. An opportunity once available is grasped and held. A move to another institution is made primarily for better opportunities in research, not for better titles, unless, of course, a change from a research career to another type of challenge is desired. The true researcher often converts nonresearch centers into research ones.
• Congeniality. Long-term investigators work well and “deal straight” with all associates, both those above and below on the hierarchical scale. They are neither selfish nor greedy. They have good negotiating skills, possess humility, and provide a pleasant and stimulating atmosphere in which to work.
• Competitiveness. Although not often discussed, the medical research community is competitive, and the successful physician researcher finds the competitive element fun, challenging, and stimulating, knowing that it enhances efficiency in completing projects. Researchers can be compared to ducks moving on a pond—on the surface things are calm, but the rapidly moving legs beneath the water's surface are invisible. Researchers do not withhold information from colleagues because of this characteristic.
• Good writing skills. Good writing requires good thinking, and clear writing indicates clear thinking. Ability to describe observations clearly and concisely on paper is essential for long-term success in medical research.

For nearly 25 years, my professional fate was determined by what I wrote and had published in medical journals. One of the hardest lessons for me to learn during that long period was that creating, “packaging,” and publishing of new ideas really never got easier. Although the focusing and writing got easier, standards continued to improve, and therefore, the amount of time and energy—both physical and mental—expended continued to be about the same for each major published investigation. This period of trying to go to work every day with a new idea was obviously challenging but enormously rewarding and fulfilling. To have a position that stretches one's potential to the fullest and to be paid for this work is certainly one of life's greatest blessings.

After this near-25-year production period, the editorship of a major cardiovascular journal was offered. Again, a mentally and physically “stretching” position, but, unlike writing, one that involves not creating new ideas but determining which ones of those created, and to some extent in what form, reach the cardiovascular community. Editing, however, is quite different from writing. Writing is relatively lonely and selfish. One's time must be enormously protected to create new ideas and publish them. Editing, in contrast, is relatively social and unselfish in that it requires much communication with authors, publishers, and readers. But after nearly 25 years in the other role, the change to editorship is surprisingly easy to make. Of the two, however, editing is much easier than writing, judging is much easier than creating; it is the creator who will provide the significant change, and deservedly so, not the judger of the creator's work.

For many years I submitted manuscripts to medical journals for publication immediately after the final draft had been typed. Before the final typing I would check the manuscript carefully for accuracy, clarity and precision of meaning, conciseness of expression, and for errors in grammar, punctuation, and spelling. Then, when the manuscript was returned from the journal's editor for revision after the 1-to 3-month review process, I was always surprised on reexamining the manuscript that I was almost always able to detect some minor inaccuracy, delete one or more paragraphs that now did not seem so pertinent, or more concisely describe a method, result, or idea. Why could these improvements not have been accomplished before the initial submission of the manuscript?

The answer, I believe, has to do with the “hot-eye”–“cold-eye” concept. Before initial submission of the manuscript, one draft was followed by another without essentially any cooling-off period between the various manuscript drafts. The manuscript in this circumstance may be thought of as being examined with a “hot eye.” Return of the manuscript to the author after the 1- to 3-month review process provides a needed cooling-off period for the authors so that now the manuscript can be reexamined with a “cold eye.” This first reexamination allows authors to identify previously unrecognized errors; unwarranted conclusions; flawed reasonings; exaggerated statements; redundancies; needless words, sentences, and paragraphs; and grammatical and spelling errors. I am convinced that this cooling-off period provides such an opportunity for manuscript improvement that even manuscripts in which both reviewers and editor have found few or no faults usually are returned to the authors for reexamination.

One reason almost any editor or reviewer can find defects in the work of almost any writer, however talented, is that they view the manuscript with a “cold eye” because they have not seen it before. The cooling-off period provided for authors by the review process allows the author to review his manuscript more like an editor or reviewer—with a “cold eye.” I suspect that all of our manuscripts would be improved if we shelved them for a week or so before our final check preceding the final typing for initial submission to a medical journal.

A manuscript submitted to the AJC generally receives 2 reviews. On the review form the recommendations available to the reviewer are “definitely accept,” “probably accept,” “definitely reject,” and “probably reject.” The most frequent recommendations from 2 reviewers of the same manuscript are “probably accept” from one and “probably reject” from the other. It is rare for both reviewers of the same manuscript to recommend “definitely accept” or “definitely reject.” For both to recommend “probably accept” or for both to recommend “probably reject” is common. On occasion, the same manuscript receives a “definitely accept” recommendation from 1 reviewer and “definitely reject” from the other reviewer. When this situation occurs, the reputation and experience of both reviewers are carefully weighed and the reasons for their respective recommendations are analyzed. Unfortunately, when this situation exists both reviewers may be major forces in their particular areas of expertise. Thus, when a manuscript reviewed by 2 leaders receives completely opposite recommendations, the reviewer recommending “definitely reject” may be upset if the manuscript is accepted, and the reviewer who recommended “definitely accept” may be upset if the manuscript is rejected. Obviously, the same manuscript cannot be both “terrible” and “excellent.” Does this particular example illustrate more about the reviewer than it does about the manuscript? How can 2 experts have such opposite reactions to the same subject matter? If 2 experts disagree so sharply, how meaningful are recommendations, similar or divergent, from reviewers who are not major forces or leaders in their area of expertise?

It is clear to me that no one—including editors—has a monopoly on correct decisions when it comes to degrees of quality of our manuscripts. With these conflicting recommendations from experts in mind, I was delighted to acquire the recently published book Rotten Reviews: A Literary Companion, edited by Bill Henderson (Pushcart Press, 93 pages, 1986). The book contains excerpts from 175 scathing notices about a number of famous books and poems published up to 1961. While researching for his book, Henderson was impressed by the balance, intelligence, and fairness of most reviews and emphasized that truly malicious reviews were rare. He found, however, striking examples of the inability of reviewers to appreciate quality or the lack thereof in the books they were evaluating. Often reviewers went into spasms of appreciation for books of slight value: “Martin Tupper (1810–1889) has won for himself the vacant throne waiting for him amidst the immortals, and has been adopted by the suffrage of mankind and the final decrees of publishers into the same rank with Wordsworth, Tennyson and Browning”(The Spectator—1866). Even bad reviews sometimes were appreciated. When the Concord, Massachusetts, public library banned Huckleberry Finn, Mark Twain exulted: “That will sell 25,000 books for sure!”

Rotten Reviews is filled with examples of how great writers can be wrong about other great writers, a reason for some humility in those of us passing judgments on works of others. It was Henry James who called Wuthering Heights (1847) by Emily Brontë “a crude and morbid story” and said of Charles Dickens' great novel, Our Mutual Friend, “We are convinced that it is one of the chief conditions of his genius not to see beneath the surface of things… . We are aware that this definition confines him to an inferior rank.” It was Emile Zola who said of Charles Baudelaire's Les Fleurs Du Mal (1857), “In a hundred years the histories of the French literature will only mention [this work] as a curio.” It was Gertrude Stein who called Ezra Pound “a village explainer, excellent if you were a village, but if you were not, not.” It was Ralph Waldo Emerson who said of Jane Austen: “I am at a loss to understand why people hold Miss Austen's novels at so high a rate, which seem to me vulgar in tone, sterile in artistic invention, imprisoned in the wretched conventions of English society, without genius, wit, or knowledge of the world. Never was life so pinched and narrow. The one problem in the mind of the writer … is marriageableness… . Suicide is more respectable.” And Edmund Wilson on W. H. Auden: “Mr. Auden himself has presented the curious case of a poet who writes an original poetic language in the most robust English tradition but who seems to have been arrested in the mentality of an adolescent schoolboy.”

And virtually every reviewer had a field day with Walt Whitman and Herman Melville. On Walt Whitman's Drum-Taps (1865), Henry James wrote: “Mr. Whitman's attitude seems monstrous. It is monstrous because it pretends to persuade the soul while it slights the intellect; because it pretends to gratify the feelings while it outrages the taste… . Our hearts are often touched through a compromise with the artistic sense, but never in direct violation of it.” Robert Louis Stevenson: “Whitman, like a shaggy dog, just unchained, scouring the beaches of the world and baying at the moon.” Peter Bayne: “Incapable of true poetical originality, Whitman had the cleverness to invent a literary trick, and the shrewdness to stick to it.” And Francis Fisher Browne: Whitman's “… lack of a sense of poetic fitness, his failure to understand the business of a poet, is clearly astounding.”

A few reviewers' comments on Herman Melville: “Redburn was a stupid failure, Mardi was hopelessly dull, White Jacket was worse than either; and, in fact was such a very bad book, that, until the appearance of Moby Dick we had set it down at the very ultimatum of weakness to which the author could attain. It seems, however, that we were mistaken. In bombast, in caricature, in rhetorical artifice—generally as clumsy as it is ineffectual—and in low attempts at humor, each of his volumes has been an advance upon its predecessors.” Another reviewer: “The captain's ravings and those of Mr. Melville are such as would justify a writ de lunatico against all parties.” And another “… a huge dose of hyperbolical slang, maudlin sentimentalism and tragic-comic bubble and squeak.” Still another: “This sea novel is a singular medley of naval observation, magazine article writing, satiric reflection upon the conventionalisms of civilized life and rhapsody run mad… .” Herman Melville, who was in his early 30s when he wrote Moby Dick, was so upset by the reviews of his 4 books that he went over 40 years before writing his fifth and final book in his last year of life. The manuscript was found 5 months after his death in 1891. Its title was Billy Budd.

Criticism, of course, serves a useful function, but not all criticisms are justified. Not all changes in manuscripts to pacify critics produce improvements in manuscripts. No one has a monopoly on justifiable criticisms or on correctness of the decision to accept or reject a manuscript. The power to pass judgment on the works of others is a power which should generate humility, not arrogance. “Writers” [investigators], notes Saul Bellow, “seldom wish other writers [investigators] well.” Thus, recommendations of reviewers have complex origins, and these must be taken into consideration when evaluating the quality of a manuscript.

The use of the word “blessing” when speaking of angina pectoris needs considerable explanation because the patient who has angina clearly does not consider himself/herself “blessed.” But when applied on a relative rather than on an absolute basis, there is justification for the use of this word. Over 95% of patients with atherosclerotic coronary artery disease (CAD) present clinically in 1 of 3 ways: acute myocardial infarction (AMI), cardiac arrest (sudden coronary death), or angina pectoris.

Although the amount of left ventricular myocardium lost is variable, AMI indicates permanent, irreplaceable loss of ventricular myocardium. The amount of myocardium lost is generally much less in the patients with so-called uncomplicated AMI compared with those in whom the acute event is complicated by cardiogenic shock or in whom chronic intractable congestive heart failure, with or without aneurysmal formation, is a late consequence. Irrespective of the size of the AMI, however, the patient whose initial manifestation of atherosclerotic CAD is AMI begins a symptomatic course with a partially but permanently damaged left ventricle, and therapy thereafter—either medical or surgical or both—is usually not as beneficial as in the patient with symptomatic CAD without permanent left ventricular damage.

The patient whose initial manifestation of atherosclerotic CAD is fatal cardiac arrest has no opportunity to receive long-term medical or surgical therapy irrespective of the presence or absence of underlying previous (clinically silent) myocardial damage. About 50% of successfully resuscitated survivors of cardiac arrest are left with no apparent permanent left ventricular damage.

Thus, relative to the initial clinical appearance of atherosclerotic CAD as manifested by AMI or fatal cardiac arrest, the patient whose initial clinical manifestation of CAD is angina pectoris (or nonfatal cardiac arrest) is “blessed.” Angina, of course, in about 90% of the patients, indicates the presence of severe narrowing of ≥1 major epicardial coronary artery and is the result of transient, not permanent, myocardial ischemia. The left ventricular myocardium at the time of the initial appearance of angina is usually normal, or if a scar (indicative of a previously silent AMI that healed) is present, it is usually small and infrequently results in left ventricular dysfunction. Thus, the patient with initial angina can undergo the definitive diagnostic study—selective coronary angiography—before the occurrence of permanent significant left ventricular damage. Of all patients with symptomatic CAD, those who deserve the most “aggressive” diagnostic and therapeutic approaches, unless contraindicated by extremely advanced age, presence of another more life-threatening condition, or simply no desire on the part of the patient, are the patients whose only manifestation of atherosclerotic CAD is unequivocal angina pectoris.

If I develop angina pectoris as the first manifestation of CAD, I want a coronary angiogram. Only 1 test during life can determine the presence or absence of significant coronary narrowing unequivocally, and that is injection of contrast material into the coronary arteries. Angiography demonstrates the presence of normal (a 10% occurrence) or abnormal (a 90% occurrence) coronary arteries and if abnormal, the degree of, and the distribution of, the narrowings. In my view, most patients with significant (>50% diameter reduction) narrowing of ≥1 vital coronary arteries should be treated definitively at this juncture (before significant left ventricular damage has occurred from subsequent AMI or subsequent cardiac arrest). The most definitive therapy, of course, is dilatation of or bypass of the coronary narrowings.

In summary, the initial appearance of angina pectoris is the time to do coronary angiography and if significant and appropriately located coronary narrowing is present, unless other factors preclude its performance, the time to dilate or to bypass the narrowing. This aggressive approach initially almost certainly will delay for a reasonable period in most patients the occurrence of sudden coronary death(the most frequent cause of death in patients with angina) and permanent myocardial damage from AMI.

When a sick person is taken to a hospital in an ambulance, the driver is required in most cities to transport this passenger to the nearest hospital irrespective of the diagnostic and therapeutic facilities present in that hospital. When and if I develop an acute myocardial infarction (AMI), I want to be transported by ambulance to the nearest hospital that has a cardiac catheterization laboratory and open cardiac surgical facilities, if such a hospital is available somewhere in the local community. If coronary flow is to be predictably reinstituted, appropriate therapy must be started within 6 hours after onset of the pain of AMI. If the passenger having an AMI is initially taken to a hospital where these facilities are unavailable, later transfer to a hospital equipped for invasive cardiologic procedures causes an additional delay that may prevent early reestablishment of coronary flow… .

I realize that it is impossible for all patients having an AMI in the USA to be treated in a hospital having a cardiac catheterization laboratory and open cardiac surgical facilities; use of either or both during AMI has not been proved at this time to increase long-term survival after AMI. No data are available comparing mortality rates of patients with AMI treated in hospitals that have catheterization laboratories and cardiac operative facilities with those that do not. Nevertheless, in my view, in large metropolitan areas, patients with AMI ideally should be brought to hospitals with invasive cardiologic and cardiac surgical facilities. Without these invasive facilities, patients with AMI simply do not have access to today's presently available maximal care… .

Thus, for me, when and if I have an AMI, please, ambulance driver, take me to the hospital that has a cardiac catheterization laboratory and a cardiac surgical unit even if that hospital is not the closest one.

In virtually every article or book I have read on the frequency of the various congenital anomalies of the heart and great vessels, ventricular septal defect has been listed as the most frequent anomaly. But ventricular septal defect is not nearly as frequent as mitral valve prolapse (MVP) or bicuspid aortic valve (BAV). MVP occurs clinically in at least 5% of persons >20 years of age and the congenitally BAV occurs in probably 1% of persons >20 years. Although fusion of 1 of 3 commissures may occur in a normally formed 3-cuspid aortic valve and this fusion yields an acquired BAV, the congenitally BAV is generally readily discernible from the acquired one and there is no disagreement on the congenital nature of this 2-cuspid aortic valve, which may or may not have a raphe in 1 of its 2 cusps. MVP, in contrast, has not generally been thought of as a congenital anomaly because a systolic click and/or a late systolic precordial murmur is rarely if ever present from birth. On occasion, however, necropsy in infants has revealed the presence of MVP even though signs of mitral valve dysfunction may not have been detected clinically.

I like to put both MVP and BAV in the category of “congenital anomalies present at birth but usually clinically silent until adulthood.” Although both conditions predispose to infective endocarditis, infection is not the major complication of either. The most common complication of MVP is mitral regurgitation, but usually it is mild and its usual mechanism is “overshooting” of 1 mitral leaflet during ventricular systole. Severe mitral regurgitation is an infrequent consequence, and when it occurs its mechanism is usually mitral anular dilatation and, less frequently, rupture of chordae tendineae, usually spontaneous, i.e., not secondary to infective endocarditis. We recently found MVP to be the most frequent cause of isolated (normal aortic valve function), pure (no element of mitral stenosis) mitral regurgitation severe enough to warrant mitral valve repair or replacement in patients >20 years.

Although some patients with BAV develop pure aortic regurgitation, some secondary to infective endocarditis and some not, the most common complication of BAV is not pure regurgitation but stenosis. Indeed, the BAV is the underlying aortic valve structure in about 50% of adults with aortic stenosis severe enough to warrant aortic valve replacement or severe enough to be fatal.

Thus, although the frequency of rheumatic heart disease is diminishing in the Western world, the frequency of MVP and BAV likely will not diminish because each of them represents congenitally defective or malformed tissue. Not only are MVP and BAV the most frequent congenital heart conditions, but after hypertensive and coronary heart diseases, MVP and BAV are the most common cardiac conditions observed in adults in the Western world. Thus, adult cardiologists do indeed see many patients with “congenital heart disease,” patients who usually do not manifest cardiac dysfunction during childhood, and therefore their “congenital heart disease” is usually not detected by pediatric cardiologists. The presence or absence of MVP and BAV should be determined in all our patients, and, if either is present, prophylactic antibiotics against infective endocarditis are warranted.

In adults with plasma total cholesterol (TC) levels <150 mg/dL, atherosclerotic plaques large enough to narrow arterial lumens rarely develop, and symptomatic or fatal organ ischemia rarely occurs. Most such adults live in underdeveloped countries or in the Eastern world or both. In contrast, in adults with plasma TC levels >150 mg/dL, atherosclerotic plaques large enough to narrow arterial lumens often develop, and symptomatic or fatal ischemia of 1 or more body organs is frequent; most of these adults live in developed or Western world countries.

In the USA, the average plasma TC level of persons 20 years of age is about 160 mg/dL, but thereafter the level progressively increases. The increase, however, is not as high today as it was a decade ago. The average plasma TC of adults >40 years in the USA is down to 210 mg/dL, from about 225 mg/dL a decade ago. The average plasma TC of persons in coronary care units with acute myocardial infarction is about 225 mg/dL. All these figures, however, are considered “normal” in most laboratories in the USA. In the Clinical Chemistry Laboratory of the Clinical Center (i.e., the hospital) of the National Institutes of Health, the “normal” range for serum TC is stated to be 163 to 263 mg/dL. The upper limit in some laboratories is 300 mg/dL. For laboratories, particularly those of prominent research institutions, to present values of this level as “normal” prevents attempts of physicians and of patients to make efforts to lower the plasma TC to levels where signs and symptoms of organ ischemia do not occur, and that level, for practical purposes, is <150 mg/dL. I consider any plasma TC level >150 mg/dL to be elevated.

If the upper limit of the normal plasma TC level is considered to be 250 or 300 mg/dL, hypercholesterolemia does not fall out as a greater risk factor for development of symptomatic or fatal cardiovascular atherosclerosis than does systemic hypertension or cigarette smoking. In areas of the world, however, where the frequency of systemic hypertension and cigarette smoking is high but the level of plasma TC is low, i.e., <150 mg/dL, the occurrence of symptomatic or fatal coronary heart disease is virtually nonexistent. About 15 years ago, I visited Kampala, Uganda, and examined many aortas, coronary arteries, and circles of Willis at necropsy. Other than a few small yellow dots or streaks that produced virtually no luminal narrowing, these arteries were free of atherosclerotic plaques. Yet, the frequency of systemic hypertension in this central African population was extremely high—indeed, hypertension was their most common cardiovascular condition—and a high percentage of the hearts were heavier than normal, presumably the result of the systemic hypertension. I was also impressed with the high frequency of cigarette smoking among the population. In Central Africa, many adults have plasma TC levels of about 100 mg/dL, a value less than half the average plasma TC level in adult Americans. In my view, evidence is lacking to implicate either systemic hypertension or cigarette smoking as an accelerator of atherosclerosis in the absence of hypercholesterolemia if the normal plasma TC level is defined as a level <150 mg/dL; if the TC level, however, is >150 mg/dL, as is the situation in 95% of adults over 40 years of age in the USA, both systemic hypertension and cigarette smoking are highly atherogenic.

In contrast to the levels in Central Africa, where symptomatic and fatal coronary heart disease is virtually nonexistent, only 5% of Americans >40 years have plasma TC levels <150 mg/dL. Thus, to perform studies on meaningful numbers of adults >40 years of age in the USA with plasma TC levels <150 mg/dL (ideal normal value) and compare findings to those with levels 160 to 260 mg/dL (usual values) is virtually impossible. In contrast to the 5% of middle-aged and older adult Americans with plasma TC levels <150 mg/dL, 5% of American adults >40 years have plasma TC levels >265 mg/dL, and about 1 in a million have plasma TC levels >600 mg/dL and normal plasma triglyceride levels.

Sprecher and associates have described certain clinical and morphologic cardiovascular findings in a group of patients with extremely elevated plasma TC levels. Of the 16 patients, all but 2 before therapy had plasma TC levels >400 mg/dL and normal and near-normal plasma triglyceride levels; most had TC levels >600 mg/dL and the average was 729 mg/dL. Additionally, 90% of the TC was composed of low-density lipoprotein, the water-soluble, extremely atherogenic component of the TC, and little high-density lipoprotein was present. The consequence of this devastating hypercholesterolemia was what might be called “malignant atherosclerosis.” Without therapy to lower the plasma TC level dramatically, coronary heart disease is usually fatal by the teenage years in these unfortunate persons with homozygous familial (both mother and father had type II hyperlipoproteinemia) hypercholesterolemia.

Although the public may lump all diseases of the heart under the term “heart disease,” obviously there are many varieties of cardiac disease, and most allow long-term survival. The average age of death among men with coronary disease, for example, is 60 years, or 15 years below average life expectancy. Among patients with congenital heart disease, survival may be quite limited. The congenital malformation associated with the shortest life span, and indeed, of all cardiac diseases the one allowing shortest survival, is aortic valve atresia. This condition also is the most common cause of death from cardiovascular disease in the first week of life, and it is extremely rare for any infant with this malformation to live >1 month. Most, of course, never leave the hospital after birth.

The anomaly consists of total absence of the aortic valve and, with rare exception, the left ventricle is extremely small and often only slit-like. The mitral valve may or may not be atretic. Blood flows from the pulmonary veins into the left atrium and then across to the right side of the heart, usually through a valvular-incompetent patent foramen ovale. From the right atrium, blood flows into the right ventricle and out into the pulmonary trunk and into the systemic circuit through a patent ductus arteriosus. Thus, all blood exiting from the heart exits via the pulmonary trunk. In this circumstance the only purpose of the ascending aorta, which is severely hypoplastic, is to supply the coronary arteries. Because flow to the lungs is excessive, these infants usually die from pulmonary edema.

Aortic valve atresia may be difficult to diagnose clinically. It should be suspected in any newborn, however, having cardiorespiratory difficulties. As with any condition involving the aortic valve, 75% of those affected are males. A precordial murmur may be absent. Although usually present and occasionally severe, cyanosis also may be absent, and the arterial oxygen saturation may be almost normal. Echocardiography is helpful in diagnosis. Operative therapy, thus far, has been unsuccessful. Cardiac transplantation is probably the only potentially useful procedure.

In summary, of all cardiac conditions, aortic valve atresia is the worst, i.e., it allows the shortest survival.

The year was 1960. Forty-three-year-old John Fitzgerald Kennedy was elected president of the USA; 16-year-old Bobby Fischer successfully defended his US chess championship; To Kill a Mockingbird by Harper Lee and The Rise and Fall of the Third Reich by William Shirer were published; birth control pills were made available to the public; Polaris missiles were successfully fired from a submerged atomic submarine; the International System of Units (SI), based on the metric system, was adopted as the worldwide standard at a General Conference on Weights and Measures; Theodore Maiman, physicist, developed the first LASER (Light Amplification by Stimulated Emission of Radiation); and successful, i.e., prolonged survival, cardiac valve replacement occurred. When the annals of cardiology are written, 1960 will be remembered as the time that cardiac valve replacement became a predictably successful reality. Since 1960, over 1 million dysfunctioning native cardiac valves have been replaced with a mechanical prosthesis or a bioprosthesis (tissue valve)… .

Dwight Harken was the first to use a mechanical prosthesis successfully in the natural anatomic cardiac valve position. Charles Hufnagel in October 1952 had used a caged-ball prosthesis in the descending thoracic aorta for severe aortic regurgitation, but the insertion in this position of course only partially decreased the amount of regurgitant flow during ventricular diastole. It was obvious that the prosthesis had to be inserted proximal to the coronary arterial ostia to completely relieve the regurgitant flow and to have any effect in patients with aortic valve stenosis. The Lucite ball used initially by Hufnagel was eventually changed by him to a hollow nylon core covered by silicone rubber so that it would be less noisy and also so that it would be isobaric with blood. Hufnagel gave Harken several of his hollow nylon-silicone rubber-covered poppets, and Harken used them in his stainless steel double-caged prosthesis. Later, he used solid silicone rubber poppets. The outer cage prevented the poppet from touching the wall of the aorta in its excursion.

Harken's first aortic valve replacement using the caged-ball prosthesis with an Ivalon aorta-widening gusset extending cephalad from the prosthetic attachment ring was unsuccessful. His second patient, a 32-year-old woman who had had a previous transaortic valvuloplasty, underwent successful aortic valve replacement on March 10, 1960. Harken was nearly 50 years old at the time. The patient later developed significant peribasilar prosthetic regurgitation, and the prosthesis was replaced in 1963. This patient is still alive in 1985. Harken had 2 survivors among his first 7 patients having aortic valve replacement with his caged-ball prosthesis. The second successful operation was performed on June 7, 1960. This patient developed prosthetic endocarditis 23 years later, the prosthesis was replaced, and this patient is still alive in 1985. Thus, the initial prosthesis was in place for 23 years, the longest any prosthetic valve had been in place, and the poppet at reoperation “looked good.” Neither of Harken's first 2 successful human aortic valve replacement patients ever received anticoagulants and neither apparently has had embolic complications.

The first successful mitral valve replacement was performed by Albert Starr in September 1960. Although successful aortic valve replacement had never been accomplished in nonhuman animals before Harken's success in patients, Starr had successfully used a caged-ball prosthesis in dogs for mitral valve replacement before his attempt in humans. Indeed, he had canine survivors of mitral valve replacement with caged-ball prostheses for many months before he attempted, at the encouragement of his cardiologist colleague, Herbert Griswald, mitral valve replacement in a human patient. His first mitral valve replacement with a fully engineered caged-ball prosthesis was in a 33-year-old woman who had an air embolus at operation, and she died 10 hours later. The second patient in whom 34-year-old Albert Starr performed mitral valve replacement was a 52-year-old truck dispatcher, who also received a caged-ball prosthesis, and he lived for 15 years thereafter. After Starr presented his results of mitral valve replacement in March 1961 before the American Surgical Association, Michael E. DeBakey commented as follows: “I must say that this paper persuades me to reevaluate my attitude toward ball valves. I have been somewhat prejudiced against them because of my very early experience with their use in changing the directional flow in blood pumps. Our most recent experience with the use of such ball valves, as in the Hufnagel valve in aortic insufficiency, also tended to make me somewhat prejudiced… . Nonetheless, it seems to me that this is very impressive work on the part of Drs. Starr and Edwards… .”

Shortly after that surgical meeting, Starr visited Boston and observed Harken insert his double caged-ball prosthesis into the aortic valve position in a patient. At the time Starr became convinced that his fully engineered, single-unit, caged-ball prosthesis, which he had used in the mitral position, also could be adapted to the aortic valve position. Thus, he and his engineering associate, Lowell M. Edwards, also developed a factory-complete, caged-ball prosthesis for use in the aortic valve position, and Starr later successfully used it for aortic valve replacement.

During the past 25 years Starr has continued to use the caged-ball prosthesis (Starr-Edwards) as his first choice among mechanical prosthetic valves. Harken, in contrast, later considered the caged-ball type to be far less desirable than some tilting disc prostheses.

Although other varieties of caged-ball prostheses (Magovern, Smeloff-Cutter, Braunwald-Cutter, and DeBakey) followed the Harken and Starr-Edwards models, all but the Starr-Edwards type were discontinued. The Starr-Edwards caged-ball prosthesis underwent several changes before returning to an early model. The early processing procedures for the silicone rubber poppets proved to be poor, and as a consequence many of the Silastic poppets inserted before 1967 swelled by adsorbing lipids and some impacted in the cage; or they shrank or cracked and some dislodged from the cage. Although there have been some surface abrasion injuries, some to an extent that has allowed expulsion of the poppet from the cage, degeneration (variance) of the silicone rubber poppet of the fatty infiltration type has not been reported since the processing of the silicone was finally standardized in 1966. The use of cloth on the metallic struts as a means to decrease prosthetic thrombus in the Starr-Edwards model proved not to be an improvement. The hollow, metallic poppet, introduced almost simultaneously with the cloth covering of the metallic struts, caused disruption of the cloth on both base and stents, and this poppet and the cloth covering on the stents and the metallic studs on the metallic base have all been discontinued. Thus, a full circle has occurred with the caged ball. The only one presently manufactured in the USA is the model introduced in late 1965, and it consists of a silicone rubber poppet and non–cloth-covered stents and base (M 6120 in the mitral valve position and A 1260 in the aortic valve position).

Other prosthetic cardiac valves followed the caged ball. The first was a nontilting caged disc (1965), which was utilized by most surgeons only in the atrioventricular valve positions. This prosthesis proved to be highly thrombogenic and obstructive, and its use has virtually disappeared. The next development was the tilting disc, and the Björk-Shiley prosthesis proved to be highly effective. And, in the late 1970s, another tilting disc appeared, this one with a bileaflet configuration, the St. Jude Medical Prosthesis; it is the least obstructive and the least damaging to blood elements of any of the prosthetic valves.

Tissue values, of course, also have been used as replacements for dysfunctioning native aortic valves. Aortic valve homografts were first used for aortic valve replacement in the early 1960s. The initial results were gratifying: the valve lesions were usually ameliorated, and anticoagulant therapy was not required. The problem proved to be accelerated wear with development of aortic regurgitation. Other tissue valves followed, namely fascia lata, dura mater, parietal pericardium (human and bovine), and porcine aortic valve. The fascia lata and dura mater valves rapidly proved to be poor valve substitutes because they became stiff and relatively immobile. The porcine xenograft and bovine parietal pericardial valves preserved in glutaraldehyde and attached to a semiflexible stent proved to be effective. (The porcine bioprosthesis failed quickly when preserved in formalin.)

I have examined at necropsy well over 1000 hearts containing 1 or more prosthetic or bioprosthetic cardiac valves. From my vantage point, some views on cardiac valve replacement have been acquired, and some of them are discussed in the remainder of this piece.

• Perform cardiac valve replacement only when absolutely necessary. When I was a student in Emory medical school, the chief of surgery, J. D. Martin, often stated: “Never remove someone's stomach unless it is absolutely necessary.” Certainly the same can be said of a cardiac valve. Except possibly in patients with severe, usually pure, aortic regurgitation, cardiac valve replacement should be reserved for patients with clear-cut evidence of significant cardiac dysfunction (functional class III or IV, New York Heart Association classification). Cardiac valvular operations that preserve the native valve, in my view, should be performed more often. Mitral valvuloplasty (commissurotomy) now is too often displaced in favor of mitral valve replacement, and mitral and tricuspid valve reparative operations for pure regurgitation probably are too often displaced by valve replacement. Tricuspid valve replacement for pure tricuspid regurgitation secondary to mitral valve disease usually can be avoided. The tricuspid valve position simply is not ideal for either a mechanical prosthesis or a bioprosthesis.
• If anticoagulants are going to be administered chronically postoperatively (because of “chronic atrial fibrillation or a huge left atrial cavity”), a mechanical prosthesis, not a bioprosthesis, should be used for valve replacement. The only advantage of a bioprosthesis is that use of this type of substitute cardiac valve does not require the use of anticoagulants. If anticoagulants are going to be used chronically postoperatively, use of a bioprosthesis cannot be justified.
• In patients having double- or triple-valve replacement, either mechanical prostheses or bioprostheses, not both, should be used in all native valve positions. Utilizing a mechanical prosthesis in one valve position and a bioprosthesis in another is illogical because anticoagulants will be required because of the mechanical prosthesis. All bioprostheses will wear out if the patients survive long enough, and presently available mechanical valves are far more resistant to wear. Thus, because anticoagulants will have to be given if one of the native valves is replaced by a prosthesis, all valves replaced should be replaced by a mechanical prosthesis, or bioprostheses should be used for all native valves replaced.
• Bioprostheses should never be used in patients ≤20 years of age and, if possible, not in patients <30 years of age. Because not all patients can take anticoagulants, bioprosthetic (tissue) cardiac valves must be available, but except in older persons or in women wanting pregnancy or in vigorous outdoor persons in whom chronic anticoagulation might have excessively dangerous consequences, bioprostheses should be second-line rather than first-line cardiac valve substitutes. Persons having third or fourth valve replacements need mechanical prostheses, not bioprostheses, because each operation is more dangerous than the preceding one, and bioprostheses wear out.
• It is better to err on the side of using smaller-sized prostheses rather than larger-sized prostheses. After deciding which type of prosthesis or bioprosthesis to utilize in a particular patient, the next most important decision is which size of prosthesis or bioprosthesis to use. Although the sizing is generally not done until cardiotomy or aortotomy has been performed, the size of a substitute valve chosen should take into consideration the lean weight of the patient and the type of hemodynamic valvular lesion present and, in my view, be roughly decided on before the patient and the surgeon enter the operating room. Volume lesions, of course, if chronic, dilate the ventricular cavity and usually the ascending aorta, and consequently larger-sized prostheses can usually be used. In contrast, pressure lesions and mitral stenosis or aortic stenosis, or both, may not be associated with left ventricular dilatation and, consequently, a smaller-sized prosthesis or bioprosthesis will be required for the mitral position. Although the aortic root is usually dilated in chronic, isolated aortic stenosis and/or isolated regurgitation, when combined with chronic mitral valve stenosis or regurgitation, the aortic root is usually not dilated irrespective of whether the aortic valve is stenotic or purely regurgitant. Thus, in patients with combined mitral and aortic valve stenosis, or combined mitral and aortic regurgitation or mixed lesions, a smaller-sized prosthesis or bioprosthesis usually is preferred in the aortic valve position.
• Refrain from doing mitral valve replacement in the presence of massive mitral anular calcium.
• Use interrupted sutures only for insertion of either prosthetic or bioprosthetic cardiac valves. A single break of a continuous suture, despite 4 or 8 interrupted sutures, can produce massive regurgitation.
• Operative preciseness is far more important during insertion of tilting disc prostheses than during insertion of caged-ball prostheses. A single suture may cause irreversible interference to closure of an occluder of a disc valve but may have no effect with a caged-ball prosthesis. Careful orientation is far more important with tilting-disc prostheses than with caged-ball ones. The margin of error, in other words, is less with tilting-disc prostheses compared with caged-ball prostheses or bioprostheses.
• Predictably successful cardiac valve replacement can be achieved most often by surgeons who frequently perform cardiac valve replacement. Although over 50% of prosthetic and bio-prosthetic cardiac valves are supplied to surgeons who order relatively few substitute valves, predictably successful cardiac valve replacement cannot be obtained by an operator who only occasionally performs cardiac valve replacement. Predictable success requires a good prosthesis or bioprosthesis; a properly sized prosthesis or bioprosthesis; an absence of significant, associated, unpalliated valvular or coronary heart disease or both; a good surgeon; and good postoperative care.

Today, 5 March 1985, I visited an impressive local hospital for a cardiovascular conference. I was 5 minutes late; about 60 persons were waiting (5 × 60 = 5 hours of human time wasted). A table in the front of the conference room contained 3 hearts. I started with A86-28, a thick-walled, nondilated, nonscarred left ventricle with a transmural acute myocardial infarct in the posterolateral wall. On the epicardial surface was a 1-cm-long left ventricular rupture site. The 61-year-old woman had been well, except for systemic hypertension, until 7 days earlier when the substernal chest pain began, and within 4 hours streptokinase had been injected intravenously. The next day the serum creatinine kinase level was nearly 1400 with 10% MB fraction. The next 6 days were uneventful: no shock, no congestive heart failure, no arrhythmias. On day 7 she was found in bed dead; 450 mL of blood was present in the pericardial sac. The subepicardial fat was so extensive that the heart floated in water. All 3 major epicardial coronary arteries were narrowed >75% in cross-sectional area by plaque. She had been well for all 61 years, and chest pain occurred and disappeared quickly 7 days before death. Weight was too much: 149 pounds on the 62inch frame. Cardiac rupture occurs in about 10% of patients with fatal acute myocardial infarction. Rupture of the free wall, ventricular septum, or papillary muscle appears to be increasing as fewer arrhythmias are fatal in the coronary care units. Why are ruptured hearts so heavily covered with adipose tissue? Does a skinny person ever rupture the left ventricular wall during acute myocardial infarction? I thought no.

The next case was A86-29. An 8-cm-diameter aneurysm of the abdominal aorta was present, and it had ruptured. This 73-year-old man also had had systemic hypertension. Computed tomography had shown the abdominal aortic aneurysm also to be 8 cm in diameter, and its lumen was about 30% filled with thrombus. The abdominal aortic aneurysm was to be resected after the carcinoma of the lung had been treated by radiation and chemotherapy. But the aneurysm ruptured at home. Necropsy also disclosed severe coronary narrowing by atherosclerotic plaques. Most persons with abdominal aortic aneurysm die from coronary artery disease, not from complications of the aortic aneurysm. This man was different.

The next heart (A86-30) had blood within the wall of the swollen ascending aorta, around the pulmonary trunk, and around both left and right main pulmonary arteries. These findings meant dissection of the aorta. The patient, a 73-year-old woman, had been well all her life except for systemic hypertension until 2 days earlier when back pain, followed by abdominal pain, suddenly appeared. A radiograph showed the ascending aorta to be bigger than normal. Suddenly it was over. The outer partition of the false channel of the ascending aorta ruptured, first into the aortic adventitia, which shares a common adventitia with the pulmonary trunk. Blood entering the aortic adventitia rapidly spread to the adventitia of the pulmonary trunk and then into the adventitia of both right and left main pulmonary arteries. The adventitial hemorrhage into the wall of the left main pulmonary artery caused severe cross-sectional area narrowing of the lumen of this artery, i.e., peripheral pulmonic stenosis. The aortic dissection stopped shortly after origin of the innominate artery because severe atherosclerosis of the aortic arch had caused atrophy and fibrosis of the underlying aortic media. The left ventricular wall was thickened but free of scars and its cavity was of normal size. (The dilated left ventricle is not capable of generating a hypertensive pressure, which is essential for aortic dissection to occur.)

Thus, 3 ruptures: one of the left ventricular free wall, one of an abdominal aortic fusiform aneurysm, and one of the outer wall of the false channel of a dissected ascending aorta. All 3 patients had had systemic hypertension with hypertrophied hearts. Left ventricular rupture during acute myocardial infarction, abdominal aortic aneurysm, and aortic dissection rarely occur in the absence of earlier systemic hypertension. Of course, atherosclerosis was crucial in causing the coronary narrowing in case 1, in allowing the abdominal aortic aneurysmal formation in case 2, and in preventing progression of the dissection further than the ascending aorta in case 3, but it too is preventable by getting the plasma or serum total cholesterol level below 150 mg/dL. The best treatment for cardiac rupture and abdominal aortic aneurysm begins with proper eating in early life, and the proper treatment of aortic dissection begins with prevention of systemic hypertension at any time in life.

I hope the 5-minute wait will be forgiven and the benefit of blood pressure–lowering and lipid-lowering preventive therapies will be long remembered.

An article from this pen 30 years ago provided some evidence that systemic hypertension was a greater risk factor for development of other cardiovascular diseases than previously indicated (American Journal of Medicine, October 1975). That evidence was primarily increased cardiac mass (>350 g in adult women; >400 g in adult men) in a very high percentage of patients with nontraumatic sudden death; angina pectoris; acute myocardial infarction and certain of its complications (rupture, left ventricular aneurysm, mitral regurgitation); fusiform, saccular, and dissecting aneurysm of the aorta; cerebrovascular accidents; renal failure; and many cases of aortic valve stenosis and mitral anular calcium. These earlier observations have been reinforced subsequently.

It is estimated in the USA that there are about 65 million adults with systemic hypertension, 15 million who have survived ≥1 coronary events, 17 million with diabetes mellitus, 5 million with heart failure, 5 million with strokes, and 8 million with atrial fibrillation. Thus, more adults in the USA have elevated (>140/90 mm Hg) systemic blood pressure (BP) than all the patients with coronary heart disease, diabetes mellitus, heart failure, strokes, and atrial fibrillation combined. And yet, other than hyperlipidemia (low-density lipoprotein cholesterol >100 mg/dL), elevated systemic arterial BP is our most common cardiovascular condition, proper treatment of which prevents or certainly sharply decreases strokes, aortic dissections, both systolic and diastolic heart failure, and chronic renal failure.

In the late 1970s, of every 100 US adults with high BP, only 50 knew that they had it, only 30 of the 50 received ≥1 antihypertensive drugs, and only 15 of the 30 being treated had their BP “controlled” (<140/90 mm Hg). Today, awareness, treatment, and control are not much better: of every 100 with elevated BP, 70 are aware that they have it, 50 are receiving therapy, and 30 are controlled—a 50% increase in the “control” group in the last 30 years, but still 70% are receiving inadequate antihypertensive therapy or none at all.

Complications of elevated BP begin to rise when the BP passes 115/75 mm Hg. For every 20 mm Hg increase in the peak systolic pressure or 10 mm Hg increase in the end-diastolic pressure, the complication rate (stroke, heart failure, renal failure, aortic dissection) doubles. Thus, at 135/85 mm Hg, the risk is 2 times that at 115/75 mm Hg, and yet that level is considered “normal.” At 155/95 mm Hg the risk increases 4 times, and at 175/105 mm Hg the risk is 8 times that at the 115/75 mm Hg level. And it is much less expensive to treat high BP than to treat a stroke, heart or renal failure, or aortic dissection.

In the Western world, the systolic BP tends to rise with age such that by age 60, 50% of Americans have a systolic pressure >140 mm Hg and by age 100, 90% have an elevated systolic pressure. In other words, one's age minus 10% generally indicates the percentage of older individuals in the USA with systolic hypertension. The diastolic BP works in the opposite way. Most persons <50 years of age with hypertension have the diastolic form, i.e., diastolic BP >90 mm Hg. From age 50 to 60 years, the diastolic BP tends to level off, and after age 60 it tends to gradually decline. Because in older individuals the systolic BP tends to increase progressively with age and the diastolic BP tends to decrease progressively with age, the pulse pressure, the difference between the peak systolic and the end diastolic systemic BP, tends to rise progressively with age.

Although many studies have shown the systolic BP to be more predictive of untoward events (stroke, heart failure, renal failure, aortic dissection) than the diastolic BP, most studies examining the effects of “controlling” BP by 1 or more antihypertensive agents have focused on the diastolic rather than the systolic BP. (The Food and Drug Administration until the last decade or so also insisted on using the diastolic BP as the marker of a drug's effectiveness despite the finding in the Framingham study >30 years ago showing the systolic pressure to be more predictive of untoward events than the diastolic BP.) Indeed, after the systolic BP, the pulse pressure is more predictive of untoward events and the diastolic BP, the least predictive.

Although a blood pressure of 140/90 mm Hg has been used as the cutoff between normal and elevated BP, the BP level, just like the low-density-lipoprotein cholesterol level, is a continuum: the higher the level, the greater the risk. The systemic BP at birth is about 90/60 mm Hg, a level often characterized in adults in the USA as “shock,” but in societies where no salt is eaten, or at least the salt level is so low that it cannot be measured, the BP does not rise with age and remains at about 90/60 mm Hg throughout life. Thus, a systolic BP of 140 mm Hg is 36% higher than what our systolic BP probably should be. Fittingly, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) defined “normal” BP as that <120/<80 mm Hg.

Many things we do in living our lives affect our BP. Weighing too much, smoking cigarettes, eating high-fat and high-sodium calories, drinking alcohol and caffeine, experiencing stress, and taking nonsteroidal antiinflammatory drugs all raise our BP. In contrast, bed rest, sleep, weight loss, relaxation, exercise, vegetarian-fruit (fiber) diet, garlic, omega-3 polyunsaturated fatty acids, potassium, magnesium, vitamin C, marital harmony, and owning a pet all lower our BP.

Although systolic hypertension is more common than diastolic hypertension, the latter is far more easily controlled by antihypertensive drugs than is the systolic pressure. Isolated systolic hypertension(>160/<90 mm Hg)(stage 2 hypertension) is particularly resistant to control and, with few exceptions, requires ≥2 antihypertensive drugs.

The JNC 7 report published May 21, 2003—a splendid document—lists 66 individual oral antihypertensive agents and 27 combination oral antihypertensive agents containing 2 drugs in 1 pill. Of the 27 combinations, 24 contain a diuretic as 1 of the 2 drugs and the other 3 include a calcium antagonist with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. The latter 3 combinations can lower the systolic BP about 30 mm Hg and the diastolic BP about 15 mm Hg. Few patients with hypertension can have the elevated BP “controlled” (<140/90 mm Hg) with a single antihypertensive drug; most require ≥2 drugs. The type(s) of drug(s) chosen are not nearly as important as administering ≥1 drug and convincing patients that the best antistroke, anti–heart failure insurance is taking the antihypertensive drug(s) every day. And 70% of the hypertensive patients in the USA are not being “controlled.” We all can do better.

The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure listed 66 antihypertensive drugs with 27 combinations (24 with a diuretic) for treating patients with systemic hypertension (JAMA, May 21, 2003). The first effective drugs for lowering an elevated blood pressure came in the 1950s—thiazide diuretics, rauwolfia alkaloids, ganglion blockers, and sympathetic antagonists. So how were patients with elevated blood pressures managed before that time? My father, Stewart R. Roberts (1878–1941), authored an article on hypertension in 1936 and devoted 1 page to its management. Under the subheading “Treatment of Essential Hypertension,” he wrote the following: