CARDIOLOGY IN THE MILLENNIUM.

Prof. B. M. Hegde,
Vice Chancellor,
MAHE University,
Manipal-576 119. India.

“The man who never alters his opinion is like standing water,
and breeds reptiles of the mind.”…………………………..Blake.

Heart diseases became big news in the twentieth century. As with many other areas of modern medicine, hi-tech cardiology has been the main till-mover in the medical world, especially in the fee-for-service system. In fact, many of the interventional procedures, when audited, showed that they were carried out mainly “ because they could net billions of dollars in cash, prestige and status for the doctors, hospitals and the manufacturers of electronic equipment” wrote Prof. Krumholz of the Yale University recently.1

William Osler described coronary artery disease in 1892 as a relatively rare disease. In less than two decades it was reported that one in eight deaths in the western world were due to heart disease. Lately even lay people think that there is an epidemic of heart diseases especially coronary heart disease. But a serious study by Professor Stehabens showed no absolute increase in the incidence of coronary artery disease in the last one hundred years! The apparent increase was mainly due to the ageing population and also better labelling methods in recent times!2

Knowledge of cardiovascular diseases grew in this century rather fast. John Hunter studied the blood. The physiological basis of high blood pressure was enunciated by Bernard and Brown-Sequard regarding vasoconstriction and vasodilation. Reverend Stephen Hales recorded the arterial pressure in the year 1733, in his illustrious mare.

Michael Foster in the year 1859 showed that the snail’s heart showed rhythmic contractions and later Gaskell, using the frog’s heart, proved that the heart beat was myogenic in origin. This had been suggested by Haller earlier; but was not proved until Gaskell’s experiments.

Jean-Baptiste Senac first recorded symptoms of heart disease in a textbook Traite de la structure du coeur in 1749. Morgagni had published his morbid anatomy in 1768. In 1768 William Heberden coined the term angina pectoris to describe the typical choking pain. ( angere in Latin means choking):

“ They who are afflicted with it, are seized while they are walking, (more especially if it be uphill, and soon after eating) with painful and most disagreeable sensation in the breast, which seems as if it would extinguish life, if it were to continue or increase; but the moment they stand still, all this uneasiness vanishes.”
-------------------------------------------------------------------------------------------------------------------------William Heberden 1768.

One must remember here that the first authentic description of angina was given in the Shushruta Samhita in much more graphic way than described above. The curious thing is that Shushruta knew that the pain came from the heart, whereas Heberden was not aware of its origin. It was much later in 1905 that William Osler thought that it could have come from the heart!

Celeb Parry wrote Inquiry into the Symptoms and Causes of the Syncope Anginosa commonly called angina pectoris in 1799, where he talked about ossification and obstruction to the coronaries. It was Antonio Scarpa who described arteriosclerosis in 1812. Virchow pointed out the first evidence of clots in the pulmonary artery and introduced the concept of thrombosis.

Diagnostic methods were also refined in this century. Corvisart, Laennec, and Bayle listened to the heart and showed how damaged valves produced murmurs. These were proved by postmortem studies. Examination of the pulse was refined very much. Two Dublin physicians Robert Adams and William Stokes identified very slow pulse resulting in syncope, complete heart block, which condition is named after them. It was Julius Cohnheim, who first thought of ischaemia of the heart muscle; he showed the presence of heart aneurysm with coronary obstructions around 1839 and 1884. It was in the year 1880 Carl Weigert gave the classic description of a heart attack.

Newer measurements started with Karl Vierordt’s (1818-84) sphygmograph and Scipione Riva-Rocci’s (1863-1937) sphygmomanometer in 1896. In the year 1859 Etienne-Jules Marey (1830-1904) modified Ludwig’s kymograph to give us the permanent record of the pulse on a moving drum. James Mackenzie (1853-1925) was responsible for the polygraph.

I think the greatest credit for credible advances in cardiology should go to Mackenzie. In his Diseases of the Heart, Mackenzie rightly emphasized the importance of clinical features in the diagnosis; he was feeling sorry that the technology-oriented diagnosis missed many important aspects of the patient’s illness. He emphasized the dangers of “mechanistic- technology driven diagnosis.” This book is relevant even today, what with all the array of scanners and scopes and angiograms, the patient and his symptoms still form the basis of diagnosis in cardiology. Both during Mackenzie’s time and even today management of patients in cardiology remains only palliative! What are we palliating if we do not assess the patient’s symptoms on the bedside? Mackenzie’s advice, as also that of Paul Wood, who was the next great cardiologist that Britain had produced, are relevant to the present times.3

Recent studies in the field of heart muscle disease did show that it is the patient’s symptoms and family history that determine the fate of the patient and, not the sophisticated left ventricular function tests. This holds good for coronary artery disease as well. Diagnosis and the management strategies in this field also depend on the patients’ symptoms, more than all the technology put together. Still the medi-business insists on tests for everything under the sun, to the exclusion of talking with the patient. The latter is not a good business proposition, anyway!

Willem Einthoven (1860-1927) was the first to record the electrical events inside the heart muscle cell, with the help of a galvanometer in 1903 in Leiden. The machine was a huge contrivance to begin with and has become a small tool now totally computerized! The whole credit for putting cardiology on the scientific pedestal should certainly go to that enigmatic British physician, Sir Thomas Lewis, “a great aficianado.” His tireless work with this huge contrivance, parked behind the lift shaft at the London Hospital, helped bring out his first book on the Electrocardiogram in 1926 which, even today, stands out as a classic. It was a Chicago physician, James Herrick (1861-1954) who clarified the ECG changes of a heart attack.

By this time high blood pressure made its mark as a killer disease, although even to this day it remains an enigma! Enormous progress has taken place in the drug treatment to lower blood pressure; but one is not sure if all this results in lasting good to the patient, except in those with severe hypertension and/or organ damage. Newer problems crop up daily!

War years in the 1940s saw a quantum jump in cardiology. One of the stars in the firmament at that time was Paul Wood, who during his relatively short life span of 52 years, did more than all his predecessors put together in placing cardiology, especially clinical cardiology, on a scientific pedestal. His treatise Diseases of the Heart and Circulation is a treat for all times. After his death this book saw only one more edition, helped by Paul Wood’s friends and colleagues and edited by Walter Somerville, the then editor of the British Heart Journal. Progress was in evidence on the other side of the Atlantic as well at that time with people like Paul Dudley White and Sam Levine, the two New England giants leading the way.

When Americans come on the scene one sees big money playing havoc in the field. This happened to cardiology in no small measure. Every single scientific discovery, of which there were quite a few daring ones, like the first catherterization of his own heart by a young German intern, Werner Forssmann in 1929, (Altman LK. Don’t touch the Heart. Book On Doctoring. 1991. Ed: Reynolds R AND Stone J Simon and Schuster, NewYork London) and the self-catheterization by Sir John McMichael in England, and other related technologies are now being used to collect “ billions of dollars in cash and prestige to doctors and hospitals.” Today cardiac care in the West has become very expensive. The contagion is making its way into the developing world as well.

Angiocardiography was followed by computerized tomography of the heart and fast CT. Ultrasound examination of the heart, magnetic resonance imaging as also positron emission tomography followed them.

With better diagnostic methods came better and more expensive medical treatments for hypertension, heart failure and also coronary artery disease. The single most important drug discovery, after the advent of digoxin by William Withering in the mid eighteenth century, was the introduction of diuretics for the treatment of heart failure. The latter also helped treat hypertension. Sir James Black was the first to introduce beta-blockers, which remain the mainstay of the management of hypertension and a host of other conditions, including heart failure!

Newer agents like angiotensin converting enzyme inhibitors, their receptor blockers, the alpha-blockers, calcium channel blockers and many other newer drugs have since been introduced. Another money-spinner seems to be the lipid lowering agent. The risk factor hypothesis has been taken to ridiculous levels and lipid-lowering drugs themselves must be a billion-dollar industry, despite the fact that most of them, if not all of them, result in higher total mortality at the end of the day.

Digoxin, which has been there for more than two hundred years is being still evaluated, and the latest study, DIG, gave surprising new data. Most other drugs in cardiology await such audit. Another class of drugs, introduced in the last two decades to control abnormal cardiac rhythms, has not acquitted well! 4

Diet and life style changes have come to fore lately in the treatment both of coronary heart disease and hypertension. Many other relaxation methods have also been introduced with varying degrees of success, their main drawback being compliance; not that compliance is not a problem with drug treatment.5

The other major group of drugs that came on the scene is the blood thinners and clot busters. Both came in with a bang and have remained there in some measure but they did not make a big dent in total mortality although they did reduce in-hospital mortality. Started in Kansas City in 1962, the special area for care of the heart attack patients, the Coronary Care Units, has now mushroomed even into remote villages. A recent audit did not show them in very good light. The conventional CCUs might not have been very useful!

Pace makers, implanted defibrillators, and cardioverters have all made life easier for the cardiac patient. Many of them have not been audited. The Swan-Ganz catheters, introduced to study the pressures, have possibly done some harm! Electrophysiological studies have given better insight into the cardiac rhythm abnormalities. Cardiopulmonary resuscitation methods have developed very well and even non-medical ambulance personnel have been trained in this life saving method. Mobile CCUs, mounted inside ambulances, have taken emergency care of heart attack patients to their doorsteps.

Starting with the discovery of the nucleic acid by the Swiss biochemist Friedrich Miescher in 1869, research has now led to the launching of the Human Genome Project. They predict that the genome would be ready by the year 2001. Newer genes are being reported daily. When the full human genome becomes a reality man would not be very happy, but could even be miserable.6 Genes may not make us realize all our dreams in reality. However, genetic engineering is being used in experimental set up now for treating vessel diseases with promising results.

In the year 1896 Sir Stephen Paget wrote: “ surgery of the heart has probably reached the limits set by Nature to all surgery; no new method, and no new discovery, can overcome the natural difficulties that attend a wound of the heart.” Twentieth century proved him wrong. Operations on the heart are a common thing now, even in smaller places. Even complicated congenital defects are being repaired with ease now, thanks to advances in anesthesia and the heart lung machine. A great surgeon from Lyons, Alexis Carrel (1873-1948), perfected the technique of vascular surgery and showed how to anastamose vessels. He also showed that the animals grafted with their own organs thrived while those grafted from other animals did not!

The ghost of rejection that raised its ugly head then has not completely died down and is bugging transplant surgeons even today. There are a host of immuno-suppressive drugs. They are both expensive and have side effects in the long run. Boston surgeon Dwight Harken and Sir Russel Brock of London were the pioneers in many areas of heart surgery. Another great names are that of Michael DeBakey of Texas and Norman Shumway of Stanford. Unlike what is reported, it was DeBakey who accidentally used the saphenous vein to bypass blocked coronary ostia in 1964. He did not report that till 1967 to see if it works. By then Rene Favaloro of Cleveland Clinic had reported one case done by him 1967. Now thousands of them are being done all over the world. A recent audit showed that 84% of those so bypassed, in their asymptomatic stage, did not get any survival benefit.7 Transplant surgery of the heart is also being done more frequently, but rejection remains the surgeon’s nightmare even now. The development of the heart-lung machine in 1950 by John Gibbons (1903-1973) was a mile stone in heart surgery. Use of low temperature techniques made cardiac surgery progress faster.

The Future:

“Take care of the present and the future will take care of itself.”

Predicting the future is impossible, but some guesses could be made, however. We have been using the linear mathematics in medicine and have now realized that this kind of linear relationships do not hold good in a dynamic system like the human body. Human body, like any other dynamic system in the Universe, follows the non-linear mathematics and the science of CHAOS and fractals. This is dawning on us now and the whole of human physiology; cardiac physiology included, has to change and would do so in the next millennium.

One example would suffice for want of space. We teach students that blood pressure is a product of cardiac output and peripheral resistance. This rule follows the Ohm's law. The latter states that only in straight tubes flow pressure is a product of flow volume and flow resistance. Where is the straight tube in the human body? The blood vessels bend and fold and are a closed system. Hence a lot of changes in the so-called risk factor hypothesis also will have to come about.

This is the reason why we have come to grief in predicting the future of a patient based on the data of the body (phenotype). To predict the future of an organism (man) we have to have the full knowledge of the initial state of the organism; the latter includes its genotype as also the consciousness! Pooling Project data showed that those who had a heart attack had one or less than one risk factor, whereas only 10% of those with more than five risk factors did get a heart attack as time evolved.8 Very well controlled hypertensives had higher death rates than their normotensive cousins did on a long-term basis. Total cholesterol distribution remains the same in those who have had vascular diseases as compared to those that did not have them.9

Another mistake that we have been making is to believe in changing the initial state of the phenotype to get benefit in the long run. In the Helsinki study there were more deaths in a cohort of healthy people who had regular check ups and interventions carried out on them, compared to those who went about their work as usual without any interventions, in the absence of symptoms. All these point to the futility of using linear relations in predicting the unpredictable future.10 The next millennium would certainly refine this technique.

Technology will certainly progress further as big money is involved in hi-tech medicine. Newer left ventricular assist devices, artificial hearts; endoscopic vascular surgery, angioscopy, keyhole surgery of the heart and xeno-transplantation etc. would be the future. Interventional cardiology would be in the forefront of management of heart diseases along with genetic engineering. Newer drugs would be introduced. There are many newer molecules of beta-blockers, calcium channel blockers, ACE inhibitors, clot busters, and blood thinning agents in the pipeline.

I have a hunch that clinical cardiology will come back to get its due place in the management of heart diseases in a big way. Preventive cardiology, starting with primordial prevention of even foetal causes of heart diseases, would be pursued more vigorously in the next millennium. Poverty eradication, more sensible diet based on fruits and vegetables, avoidance of alcohol and tobacco and the liberal use of relaxation techniques would be intensified.

Recent reports about the vital role played by the human mind in the causation of serious heart diseases would change the scenario drastically.11 The role of the mind in the causation of diseases should make today’s arrogant cardiac technician a better clinician. Medicine would still be doing what Hippocrates wrote years ago: “ cure rarely, comfort mostly, but console always.” Most of our hi-tech methods would only be palliative even in the next millennium!

That said, I am reminded of the danger of talking of the future. Write I must as the editor has ordered. I am reminded of the lines of the poem The Road Not Taken by Robert Frost (1874-1963).

I shall be telling this with a sigh,------
Somewhere ages and ages hence:-----
Two roads diverged in a wood, and I-
I took the one less travelled by,--------
And that has made all the difference.
-----------------------Robert Frost.

The greatest discovery of this century has been the discovery of man’s ignorance.