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Fifty Years of Cardiology in Europe: From the Past Into the Future

Authors: D G Julian, MDFaculty and Disclosures

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Introduction

To the cardiologist of today, the 1950s must seem like the Dark Ages. The x-ray was the only imaging technique, there was no coronary angiography, no coronary surgery, or cardiac transplantation, no coronary care units, and there were no beta-blockers, calcium antagonists, or ACE inhibitors. What on Earth did cardiologists do?

In fact, the 1950s were a watershed in the history of cardiology. Just after World War II, the predominant concerns of the cardiologist were congenital and rheumatic heart disease. Although the prevalence of coronary artery disease (CAD) was increasing at an alarming rate, first in North America and then in Europe, it was not of great interest to the cardiologist (except as a source of income in private practice). Rather, CAD was primarily the responsibility of the general practitioner and internist, and at that, there was little treatment available. All of this changed, beginning in the 1960s, with the development of new coronary care drugs and the introduction of coronary surgery and angioplasty.

Congenital Heart Disease

In the 1950s, there were large numbers of children and adults with congenital heart disease. Robert Gross of Boston, Massachusetts (USA), had led the way to the future by ligating a persistent ductus arteriosus in 1939; then Clarence Crafoord in Sweden pioneered surgery for coarctation in 1945. Also in 1945, Alfred Blalock and Helen Taussig in Baltimore, Maryland (USA), used the subclavian artery to create a pulmonary artery shunt as a treatment for the tetralogy of Fallot, but the correction of most forms of congenital heart disease had to await the development of open heart surgery in the 1950s.

Inevitably, the possibility of treating congenital heart disease with open heart surgery required cardiologists to become more expert in diagnosis. Fortunately, cardiac catheterization had become commonplace by this time, and this helped the leading cardiologists of the day, such as Paul Wood in London, to refine clinical skills so that with a combination of inspection, palpation, auscultation, electrocardiography, radiology, and catheterization, most congenital heart disease could be correctly diagnosed and assessed for surgery.

Valvular Heart Disease

In the industrialized world, the major reason for hospitalizing children up through the 1920s had been acute rheumatic fever. In the succeeding decades the incidence of this disease declined remarkably in Western Europe, probably largely due to improving social conditions, but the chronic sequelae of the disease were a major problem even into the 1950s.

Most valve disease was a consequence of rheumatism (although, as late as the 1950s, syphilis was the most common cause of pure aortic regurgitation). In the 1950s, the diagnosis of valve lesions was largely dependent on the stethoscope, supplemented by cardiac catheterization. Inge Edler and Helmuth Hertz produced the first echocardiograms in 1953, but it took many years before this technique was developed into the invaluable tool it is today.

Dwight Harken and Charles Bailey in the United States and Russell Brock in London had introduced mitral valvotomy in the late 1940s, and this operation became very common throughout Europe in the 1950s. The development of open heart surgery in 1953-1955 by Russell Gibbon and John Kirklin of the Mayo Clinic and Walton Lillehei of Minnesota (USA) paved the way for more radical repair of valve disease, and for valve replacement.

Coronary Artery Disease

From the 1930s, CAD escalated as the leading cause of death in the industrialized world, and this continued to increase in Western Europe until the late 1970s. Then the trend was reversed to the extent that over the last 2 decades of the 20 th century, its incidence has decreased by about 50% in several of these countries.

There are, however, striking differences in the prevalence of CAD between different parts of Europe. A remarkable phenomenon is the contrast between the southern countries of France, Italy, and Spain and the countries of Northern Europe.

Finland topped the league for deaths from ischemic heart disease and, in spite of a successful campaign to target the causes, the death rate from CAD remained high in Finland at the end of the 20 th century. Furthermore, CAD deaths are 4 times as common in Belfast, Northern Ireland, as in Toulouse (in the South of France), in spite of the fact that there is little difference in the conventional risk factors of cholesterol, hypertension, and smoking. This "French paradox" has been variously attributed to wine, dietary antioxidants, and genetic factors -- but it remains unexplained.

The last decade of the 20 th century also saw an alarming rise in CAD deaths in Eastern Europe, especially Russia.

The trigger that transformed the management of CAD was the development of closed-chest cardiac resuscitation, by William Kouwenhoven and colleagues in Baltimore, Maryland, in 1959. This led Desmond Julian of Edinburgh, Scotland, to propose the concept of what was to become known as the coronary care unit (CCU), in an article in The Lancet in 1961.The first 4 units were created in 1962 by Hughes Day (Kansas, USA), Lawrence Meltzer (Philadelphia, Pennsylvania, USA), Kenneth MacMillan (Toronto, Canada) and Desmond Julian (then of Sydney, Australia). Following these pioneering units, CCUs were rapidly developed in North America, but much more slowly in Europe. However, Pantridge of Belfast, recognizing the high proportion of acute heart attack patients who died before reaching hospital, pioneered the mobile CCU in 1966. At the same time, doctor-manned cardiac ambulances were developed in the Soviet Union.

In parallel with the development of the CCU in the 1960s, the decade also saw the introduction of drugs for the treatment of CAD. James Black of the British company ICI was pre-eminent in the development of the beta-adrenergic receptor blockers ("beta-blockers"), and the German pharmacologist Albert Fleckenstein played a similar role in the evolution of the first calcium antagonists.

However, even with these developments, in-hospital mortality from acute myocardial infarction (MI) was approximately 25% to 30% in 1960; the subsequent dramatic fall in this risk of death has been due to a number of factors.

First, CCUs were responsible for a substantial reduction in mortality because their organization of facilities and personnel brought about the ability to prevent and treat serious arrhythmias.

Subsequently, the discovery and introduction of fibrinolysis was probably the most important single development for reducing death from acute MI. Although practiced widely in Germany and the Soviet Union in the 1970s, it was not until the Italian GISSI trial and the Oxford-based ISIS-2 trial were published in the 1980s that application of fibrinolysis was accepted as standard of care for acute MI in the United States and the rest of Europe.

In fact, these mega-trials, together with the earlier ISIS-1, transformed the investigation of new treatments of cardiac disease by showing the necessity of recruiting very large numbers of patients in order for the results of clinical trials to have a certain fairly rigorous level of statistical validity. ISIS-2 also demonstrated the effectiveness of aspirin in acute MI, and the subsequent GISSI-3 and ISIS-4 trials established the place of angiotensin converting enzyme (ACE) inhibitors in this condition.

Although the Canadian Arthur M. Vineberg had pioneered the operation that bears his name, coronary surgery only became established after the pioneering work of the Argentinian Rený Favoloro at the Cleveland Clinic. This had followed the introduction of coronary angiography in the same clinic by Mason Sones. Coronary surgery developed slowly in Europe, but was given an impetus by the favorable findings of the European Coronary Surgery Study, which was led by the Lithuanian/Swedish cardiologist Edvard Varnauskas and involved many different countries on the continent.

Andreas Grýntzig, a German working in Zurich, Switzerland, deserves the credit for developing coronary angioplasty in 1977. This technique has revolutionized the management of both angina pectoris and MI.

In the 1950s, there was little interest in developing the methodology or large-scale programs for the prevention of CAD. Although there was accumulating evidence to implicate cholesterol, there was much skepticism about the effectiveness and safety of lowering lipid levels. Unfortunately, this skepticism was enhanced after the WHO clofibrate trial (carried out in Edinburgh, Prague, and Budapest) showed an increased mortality in those receiving the lipid-lowering drug.

In fact, the subject of whether lipid-lowering therapy was efficacious was not put to rest until the Scandinavian Simvastatin Survival Study (4S) was published in 1994, showing that lipid lowering with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) was highly beneficial and safe in patients who had suffered an event (secondary prevention). This was followed closely thereafter by results with pravastatin in lower-risk patients (primary prevention) in the West Of SCOtland Prevention Study (WOSCOPS).

Hypertension

In the 1950s, there was much dispute about the importance of hypertension as a cause of cardiac disease and heart failure. The only real treatment for malignant hypertension was extreme salt restriction, until drugs such as hexamethonium were introduced later in the decade. Diuretics were later recognized as effective antihypertensive treatment in the 1960s, but it was not until a long time after the introduction of beta-blockers that Brian Prichard of London convinced the skeptics of their effectiveness, and these are now recommended as first-line treatment by the Sixth Joint National Committee (JNC-VI) guidelines in the United States and the WHO-ISH guidelines in Europe.

Heart Failure

There was little effective treatment for heart failure in the 1950s. Rest, salt restriction, and injectable mercurial diuretics were all that were available until the introduction of thiazide diuretics and spironolactone in the late 1950s.

The ACE inhibitors were developed in the 1980s, initially as antihypertensive agents. It soon became clear that these agents were highly effective for cardiac failure when the Scandinavian CONSENSUS trial showed that the high mortality of advanced heart failure was substantially reduced by enalapril.

Finally, in the last half decade of the 20 th century, beta-blockers -- an old treatment modality -- were demonstrated in another series of large, well-controlled, randomized clinical trials (CIBIS II, MERIT-HF, and COPERNICUS) to have a therapeutic effect in heart failure in spite of previous serious concerns about their safety.

The Future of Cardiology

No doubt cardiology in the next 50 years will be transformed in ways we cannot imagine today. Genetic research is bound to bring about fundamental changes in the prevention and treatment of heart disease, but we are a long way from seeing the disappearance of the disease. A curious paradox is that in spite of the advances of previous years, coronary disease and, especially, heart failure are becoming more prevalent rather than less. In the economically advanced countries, this is due not only to the aging of the population but also to fact that secondary prevention is more successful than primary. However, in the rest of the world the increase can be traced to the fact that societies -- as they develop economically -- are adopting the deleterious lifestyle and dietary habits of the developed countries, to the extent that within 20 years, cardiovascular disease is projected to surpass infectious disease as the number one cause of death throughout the world.

So it appears certain that the cardiologist will continue to have large numbers of patients to treat. No doubt the best approach on the societal level will be to create and pursue coronary prevention programs, but then the more pressing question becomes: Will prevention be in the hands of the nutritionists, geneticists, and lipidologists -- or will it be under the control (and mishandling) of the accountants and politicians?

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