Immediate Reperfusion

Our Revolution in Acute Myocardial Infarction

The story of reperfusion in acute myocardial infarction was one of the high points of my career. The thrill of a totally new procedure is like a field of flower buds unfolding: the contents of the buds are unknown but when they open, one has a beautiful new flower. Reperfusion therapy was the new flower in the garden. Myocardial infarction has been conquered, albeit partially, and has opened a new vista in cardiology. Mortality has fallen, infirmity and disability have decreased and life prolonged in patients who suffer from the number one killer in Western Society.

A myocardial infarct occurs when one of the arteries (Coronary Artery) that supplies blood to heart muscle is blocked suddenly. This deprives it of oxygen and the muscle cannot contract, becomes stunned and within two hours it dies. The blockage occurs because cholesterol accumulates in the vessel wall, narrows the lumen, the hillock ruptures, a clot forms and the artery is occluded. This causes disturbances in heart rhythm often with sudden death, or damage to the pump with severe shock and later heart failure. The patient can die, suffer permanent disability or recover.

The new chapter in medicine started in 1954 when Sol Sherry revolutionized the treatment of acute thromboembolic vascular disease by dissolving a causative thrombus (clot) or embolus using the natural, lytic drug, streptokinase. His group treated acute myocardial infarction, pulmonary embolism, thrombophlebitis and peripheral arterial occlusion. (1959). He was uncertain about the effect of lysis in myocardial infarction and stopped these studies. The drug was approved for lysis in other thrombotic states in 1977 by the FDA.

Acute myocardial infarction had been treated conventionally by watchful expectancy, usually with three weeks rest in bed. (armchair rest treatment). In 1965 I analyzed its mortality in a general hospital ward at Groote Schuur hospital in Cape Town where we found it to be 34%. Our first revolution was to introduce intensive coronary care with ECG monitoring of the ECG to control and treat arrhythmias and more personalized care and nursing. In my first coronary intensive care unit, one year later, the mortality dropped dramatically to 14%.

The pathologists had argued about the pathogenesis (precipitating cause) of myocardial infarction. Was it due to acute thrombotic occlusion of the coronary artery or to sudden coronary spasm which caused long-term ischaemia (decreased blood supply) and myocardial necrosis? Peter Rentrop from Göttingen summarized the status in 1977. Autopsy studies in the mid-1960s provided fresh evidence that coronary thrombi were common in acute myocardial infarction and that intimal fissuring of the arterial intima (inner layer) caused both plaque haemorrhage and intraluminal thrombosis. Bill Roberts, the premier pathologist from the NIH suggested the plaque fissures were artefacts and resulting from sectioning arteries at postmortem, and that coronary thrombosis resulted from a prolonged low output state associated with large infarcts. European investigators continue to explore the possibility of lysis of the thrombus in acute myocardial infarction, although they believed that the lysis time for a coronary thrombus exceeded the time limit of myocardial tolerance from anoxia. They hoped to improve collateral flow (from other coronary arteries) and microcirculation by lysis (dissolving) and opening of the capillaries and venules within and around the infarct zone. The discussion about the pathogenesis of acute myocardial infarction was limited by the inherent selection bias of autopsy studies and the paucity of in vivo and angiographic data.

The great breakthrough took place when Earl Wood, a surgeon in Spokane, Washington presented a cohort of patients in 1979 who had undergone coronary artery bypass surgery to bypass the obstruction) and compared them with a similar group who underwent regular medical therapy. Mortally reduction was dramatic and improved in the patients treated early (hours). Early surgical reperfusion had succeeded.

Rentrop continued his studies of reperfusion in acute myocardial infarction, first using a wire to perforate the thrombus and later controlled dissolution studies with Steptokinase. The results were very successful and the clot in the coronary artery was successfully lysed, coronary flow restored and myocardium salvaged. Rentrop then moved to New York and started further studies in the United States. Marc Verstraete from Louvain in Belgium organised working groups in Europe, at first using Steptokinase and used mortality as his endpoint. Initially, the results were indifferent, but gradually they improved. Genentech, a new biotech company cloned tissue plasminogen activator (tPA) which is identical to the natural lytic (dissolving protein) protein in the blood. It was a superior lytic drug and doubled the reperfusion rates and the clinical results improved further. This aroused excitement in Europe and several centres embarked on large controlled studies. Hugenholtz, Simoons and van der Werf were real protagonists as was Harvey White in New Zealand.

The new catch phrase in medicine in 1980 was evidence-based medicine. This introduced the second phase of research – randomized double blinded controlled studies - half of the patients were treated with the new drug and the other half received normal accepted treatment. Peter Sleight from Oxford was the British pioneer (GISSI Trial). Braunwald from Harvard was the other leader and together with Passamani from the NIH set up the first Thrombolysis In Myocardial Infarction (TIMI) study. All their patients with an acute myocardial infarct had an initial coronary arteriogram (to demonstrate the narrowings and blockages in the coronary arteries) and half were given Steptokinase and the other half tPA. In patients with occluded arteries the patency rate at 90 minutes was 62% with tPA and 31% with Steptokinase. The trailblazing continued: TIMI progressed, and there were large international and national trials in England, Germany, France, Holland and Italy. It now became clear that early treatment within four hours of pain onset, together with adjunctive anticoagulant and antithrombotic therapy, and mechanical reperfusion improved the prognosis.

I heard Rentrop speak for the first time perchance in Oslo in 1979, at a meeting on Timolol, a new beta-blocker drug for high blood pressure, but which was also very effective for glaucoma. He was tall and erect and spoke with a very impressive and forceful voice: he was very convincing so that I realised that he had pioneered a new treatment, a real breakthrough in the management of acute myocardial infarction. He had proved that it was possible to lyse the thrombus using a thrombolytic drug. De Wood and his group from Seattle had also just published their paper on the prevalence of total coronary occlusion during the early hours of transmural myocardial infarction in the New England Journal of Medicine: the results were very impressive. It was now clear that 90% of these patients had complete thrombotic occlusion of the culprit artery in the first hour after infarct onset and that there was spontaneous thrombolysis in the following hours.

The obstruction set up a time dependent process of myocardial necrosis in the anoxic zone and this was complete within 4 hours of occlusion. 

The pathologists, Reimer and Jennings tied off a coronary artery in experimental dogs. They produced convincing microscopic sections of the “wavefront theory” of muscle ischaemia, concussion and death, which started soon after the occlusion and which was complete after 4 hours.

Prof Gabby Isaac, the head of Haematology at Hadassah was using urokinase to lyse thrombi in the veins of the leg after deep vein thrombosis and thrombi in the pulmonary artery in patients with acute pulmonary embolism. He wanted to administer a direct bolus into the pulmonary artery and recruited our help. The results of direct infusion through a catheter were dramatic, the clot was lysed and disappeared, and the artery reopened. I felt that the time had come to extend its use and infuse the drug directly into the occluded coronary artery which was causing the acute myocardial infarction

We started intracoronary lysis using urokinase.  It was unbelievable to watch the lysis of the clot in the culprit coronary artery during the infusion, relief of the intense chest pain and the return of the ECG to normal.  Our first patient was a 73-year-old gentleman who had been admitted to the internal medicine ward with severe unstable angina pectoris. I catheterised him urgently on a Tuesday afternoon and demonstrated severe disease of all three coronary arteries. We felt that he was a good candidate for coronary artery bypass surgery. At 6 o’clock on Wednesday morning, he developed acute, severe chest pain with ST segment elevation of the anterior cardiac leads on the ECG and it was clear that he was developing a new myocardial infarction. The surgeons had already started their two operations in the operating rooms, and the patient’s family asked me if there was any way of unblocking the artery. I had urokinase in the catheterisation laboratory and we brought him down for a repeat coronary angiogram. The left anterior descending artery which previously had a 90% obstruction, was now completely occluded, and there was no flow down the artery. We infused the urokinase and it was amazing to see, how, after 15 minutes, contrast medium trickled into the occluded artery and after another 15 minutes there was rapid flow. The clot had been lysed, and flow restored. The ST segment elevation on the ECG, started to disappear and then suddenly he had ventricular fibrillation and a cardiac arrest. His blood pressure dropped to zero. Jacob, our technician, defibrillated him immediately while Basil Lewis started artificial ventilation. The resuscitation was successful, his blood pressure rose and I could see the heart beating on the x-ray screen. At the same time, Prof Eliakim, the head of internal medicine department, appeared at the door of the catheterisation laboratory and said ‘Gotsman, how can you snatch the patient from my ward without a formal discussion at the afternoon departmental conference!” He watched the resuscitation and was really quite upset. At that time I did not realise that the ventricular fibrillation was a reperfusion arrhythmia due to oxygenated blood entering the anoxic myocardium. The patient had a fairly small infarct, recovered uneventfully, later underwent a successful triple vessel coronary artery bypass graft and lived for another 15 years. The thrombolytic reperfusion was dramatic and proved that we could open the artery, restore blood flow and decrease the size of the infarct. The paradigm had shifted.

The second patient was no less dramatic. He was a 42-year-old director of finance of the local sick fund and came to tell me that I was undertaking too many coronary angiograms and wasting part of his budget. He felt a sudden pain, put his hand on his chest and then the pain increased in intensity. I sat him down and gave him a coronary vasodilator. The electrocardiogram showed ST segment elevation in the inferior leads, a sign of an impending myocardial infarction. He had heard of our successful reperfusion and asked me to take him to the catheterisation laboratory immediately. He had a single, total occlusion of the right coronary artery and the obstructing thrombus created a picture that looked as if the artery had been amputated. We started an infusion of urokinase and within 15 minutes restoration of flow started. It continued for another 30 minutes, the pain subsided, the ST segment elevation disappeared and he asked for a cigarette. He recovered after a very small infarct (heart muscle death) and was discharged home after a few days. The patient continued to smoke,the  atherosclerosis in the coronary arteries continued to develop and later needed and underwent several balloon dilatations. He is alive and well, some 30 years later.

Teddy Weiss, my senior cardiologist at Mt Scopus Hospital had returned from a post graduate Fellowship at Cedars Sinai hospital in Los Angeles in 1984. Willie Ganz, the local proponent of thrombolysis suggested that we use our mobile ambulances that were manned by a physician as well as trained paramedics to   use intravenous Steptokinase for lysis and the best method of shortening the time delay from pain onset to lysis was to initiate and administer the treatment at home before transport to the hospital.  Teddy undertook the organization of the project. We were joined by Dr. David Applebaum who oversaw the Magen David Emergency Ambulance Service.  The ambulance was staffed by a trained physician and supplementary experienced ambulance staff and was equipped with ECG monitoring, an ECG recorder and an external defibrillator.  David was a sterling and active protagonist. He trained and mentored a motivated team who could arrive at the patient’s home with a median of 5 minutes from the moment of call. They made an immediate diagnosis, treated any arrhythmias and quickly transferred the patient to the receiving hospital. This service soon became available throughout Israel. Unfortunately, David was murdered in a Palestinian suicide bombing at Café Hillel in Jerusalem on September 9, 2003.

We turned this clinical service into a most exciting and unusual research project and showed that it was possible to start thrombolysis in a pre-hospital setting within one hour of pain onset. The mortality was so low that we needed a more sensitive index of myocardial salvage and infarct size. We had already studied left ventricular function in detail by left ventricular angiography and we used infarct size to show that the this was a function of time delay, and that death of the heart muscle was complete after 2 hours.  Once pain started, the clock started ticking and every minute of delay was crucial.

We were conquering acute myocardial infarction and preserving heart muscle and function. At the same time, there were similar studies in Rotterdam, Brussels, Paris and the rural areas around Aberdeen, in Scotland and Belfast in Northern Ireland.  We invited our coworkers to a series of meetings to compare procedures and notes and published a series of monographs.

I became known as “the cardiologist who ran around the city with his ECG and syringe” opening coronary arteries in acute myocardial infarction.

Basil Lewis and I had learned a great deal from Hal Dodge and Florence Sheehan in Seattle about understanding global and regional left ventricular function of the heart.  We had used the computer to analyze the left ventricular angiograms and had defined different patterns of contraction after the obstruction of the different coronary arteries. It was simple to study patients after thrombolysis to determine the extent of myocardial infarction.  We produced different models of measuring left ventricular dysfunction and developed 3-dimensional representations.  The extent of myocardial necrosis was related to the volume of muscle supplied by the affected artery, the site of the coronary obstruction, the extent of the collateral circulation and to the delay from pain onset to reperfusion. The research produced at least 20 major publications and was the pivotal research thrust of the department for the next 10 years.

Sima Welber joined us as a research fellow, and completed her MSc degree.  David Fine came from the Mayo Clinic and joined the research team but after 2 years returned to practice in Minneapolis. He had to return a large loan he had taken as a student.  Teddy Weiss was full of ideas and all the younger staff participated with great enthusiasm.

We had shown that prehospital thrombolysis was very effective.     Mortality had fallen to 2 ½%.

 

The most exciting of all the other studies was the Great study undertaken by general practitioners in the rural Grampian region of Scotland, near Aberdeen. The general practitioners were trained to make an initial diagnosis of impending myocardial infarction and provide immediate thrombolysis. Half of the patients were given APSAC (a streptokinase derivative) at home and the other half on admission to hospital. Prehospital initiation of thrombolytic therapy saved one hour (105 versus 240 minutes) and was associated with halving of the three-month mortality (from 15.5% to 8%). Besides the reduction in mortality there were fewer cardiac arrests, fewer Q-wave MI’s, and improved left ventricular function. GP training improved the speed of physician response, clinical assessment and diagnosis, relief of pain and anxiety, correction of autonomic disturbances, and, arrhythmias, and resuscitation. Telephonic transmission of the ECG via the general practitioner to the regional hospital was the most effective approach in rural areas, before the ambulance arrived. It is ideal where the local hospital is 1 to 2 hours away from the patient.

Other randomised controlled studies such as the EMIP study in France and the West Washington study in Seattle were less decisive because the time delays were much longer.

There was a spate of major international studies that showed the superiority of thrombolysis. We introduced new antithrombotic drugs but now we had to be careful of excessive bleeding. The major problem was a small, but significant group of patients who developed intra-cerebral haemorrhage.

I travelled abroad extensively discussing our results. The most interesting experience occurred after I had spoken at the Friday morning cardiology meeting in Seattle. The group had studied all the acute infarcts in Seattle. Doug Weaver and Ward Kennedy who lead the randomized controlled studies had excellent results with mortality reduction in the anterior infarcts but were less successful with inferior infarcts. These infarcts in the inferior wall were usually small, and their time delays too long to make a significant impact.

In Rotterdam the ambulance was also very active. In Belgium they were using general practitioners and in rural northern Ireland the ambulance was going out into the country. I was invited to develop thrombolytic programs in Spain and Portugal and when the Iron Curtain came down eastern Europe started to lead the field. The medical metamorphosis was complete. Poland and Hungary were the first countries to implement the treatment. The countries had cardiologists whose IQ’s were identical to Western Europe but they had been deprived of adequate financial budgets. The opening of the intellectual gates, the cross communication of information with the Western countries and their extreme enthusiasm took then out of the darker ages into a new intellectual sunshine and while it took a generation to eliminate the old communistic bureaucracy, the drug and medical device companies discovered a fertile field for research and supported new projects and the medical machine of progress escalated.

Eric Topol, a young dynamic cardiologist from Ann Arbor, started a series of major multicentered international mega trials (TAMI and GISSI trials). He showed that thrombolytic treatment with TPA was very effective. Eric was a most impressive physician. He would enter the lecture theatre with his little bag and give a most exciting presentation. I went to visit him in Ann Arbor, and found that he was doing 7 to 8 catheterisation studies a day in addition to his clinical load and research studies. He moved to Cleveland clinic as director of cardiology and then director of the clinic and eventually moved on to San Diego. Braunwald was the father of myocardial salvage and mortality reduction continued with his TIMI studies, andhe and his group continued to introduce new supplementary thrombolytic regimes to improve the reperfusion and prevent further reocclusion and showed that not only opening the artery and re-establishing flow but also re-establishing the micro circulation was very important. They used mortality as endpoints whereas we used infarct size.

The next innovation was to use immediate coronary angiography to define the coronary anatomy, followed by immediate balloon dilation in order to accelerate opening of the artery more rapidly and completely. This was pioneered by Cindy Grines and Bill O’Neill in the Beaumont Hospital in Royal Oak, Michigan. She was a tall, thin, athletic lady, always on the move and with a very intense work ethic. She would come to the hospital immediately at night and run a 24-hour, seven-day a week service and was prepared to catheterize patients with acute myocardial infarction at any time of the day or week. She started a series of PAMI studies to compare treatment with immediate balloon angioplasty to thrombolysis. She reduced the mortality from 10% percent to 2% and re-infarction within six months from 16 to 8%. There was a gradual acceptance of her new technology, and within five years virtually all the patients with acute infarction were being treated by percutaneous coronary interventions. Stents were introduced, followed by drug, eluting stents, and the long-term results were excellent. Once again, the paradigm had shifted.

We also entered the field of emergency 24 hour per day angioplasty and because of the new DRG, which reimbursed the hospitals for the extra work and cost, larger  than the previous payments for angioplasty, the hospital found it profitable to undertake these procedures and we now have two on duty residents and two senior cardiologists on-call. Our mortality also plummeted and within two years the system had been introduced throughout Israel. The patient calls the ambulance, who radios to the on-call hospital, contacting the cath lab immediately and we try to have a door to balloon time of under one hour.

Percutaneous Coronary Intervention (PCI) in acute myocardial infarction is quite different from PCI in chronic coronary artery disease. Acute myocardial infarction is an active process in which a coronary artery has been occluded, part of the myocardium has been destroyed and many of the patients come to the catheterisation laboratory, cold and shocked, with a low cardiac output and poor tissue perfusion. The patient needs immediate acute intensive care, to raise the BP, improve the cardiac output and often to use mechanical support such as an intra-aortic balloon pump, or inserting a temporary pacemaker. In many patients the artery must be opened quickly but the artery is filled with fresh thrombus. The balloon dilatations can cause distal embolisation as the clot breaks off and fills the distal capillary bed with clot. The operator’s need greater experience and more manual dexterity and a sharp eye – brain – finger interaction and the ability to take immediate lifesaving procedures. We tried aspiration of the clot through the catheter but it did not improve outcomes.

A typical example is a 40-year-old man who has blocked his left anterior descending artery and may have disease in his other coronary arteries. He comes into the cath lab with a low blood pressure of 50/30, cold, pale and sweating. He needs immediate intravenous fluids and often needs immediate insertion of an intra-aortic balloon to support the circulation. The catheter lab staff are working under extreme pressure and it is essential to open the artery without delay. This may happen at 2 o’clock in the morning where everybody has been summoned from their beds and the entire catheter lab team is shifted into top gear. If the patient  develops ventricular fibrillation, he needs resuscitation, defibrillation and intensive drug therapy.

The Cardiac Department at Tel Hashomer Hospital under the guidance of Shimon Behar and The Israel Cardiac Society started a national registry (ACSIS) and the country-wide mortality has dropped progressively to 4% .

Non–transmural infarction was also upgraded and early interventional procedures undertaken. The workload in our department changed completely and since there were very few patients who developed restenosis, the workload changed and most of the patients are admitted directly from the emergency room.

The department now runs a 24/7 cath lab service. The mortality has dropped dramatically and in more than 70% of the patients we salvage most of the myocardium at risk.

There remain many unresolved issues: training the population to call the emergency services earlier when chest pain starts, reducing the time delay from pain onset to reperfusion, better methods of preventing myocardial damage, management of large or second infarcts with cardiogenic shock, use of new auxiliary pumps to assist the heart in shocked patients, and management of patients with prolonged cardiac arrest and severe anoxic brain damage. Nonetheless we have excellent new methods for centralized, cloud based monitoring services, to manage high risk ambulatory patients and anticipate the heart attack, internet communication between the ambulance and the receiving hospital cardiac service and more immediate response using neighborhood motorcycle response systems.

I can look back on this complete revolution, from a 34% mortality with a 3-week rest in bed program, to 3-4% by immediate emergency restoration of normal coronary flow in less than 2 hours of occlusion by a well-trained  ambulance service and an efficient coronary catheterisation team of trained interventional cardiologists, technicians and nurses.

I am proud of our energy, push, research and enthusiasm and the continued vitality of my dynamic successor, Prof Chaim Lotan and his hyperactive crew.

 The sun never sets on cardiology: the lights on the cardiology floor never dim at night.

Immediate Reperfusion

Our Revolution in Acute Myocardial Infarction

The story of reperfusion in acute myocardial infarction was one of the high points of my career. The thrill of a totally new procedure is like a field of flower buds unfolding: the contents of the buds are unknown but when they open, one has a beautiful new flower. Reperfusion therapy was the new flower in the garden. Myocardial infarction has been conquered, albeit partially, and has opened a new vista in cardiology. Mortality has fallen, infirmity and disability have decreased and life prolonged in patients who suffer from the number one killer in Western Society.

A myocardial infarct occurs when one of the arteries (Coronary Artery) that supplies blood to heart muscle is blocked suddenly. This deprives it of oxygen and the muscle cannot contract, becomes stunned and within two hours it dies. The blockage occurs because cholesterol accumulates in the vessel wall, narrows the lumen, the hillock ruptures, a clot forms and the artery is occluded. This causes disturbances in heart rhythm often with sudden death, or damage to the pump with severe shock and later heart failure. The patient can die, suffer permanent disability or recover.

The new chapter in medicine started in 1954 when Sol Sherry revolutionized the treatment of acute thromboembolic vascular disease by dissolving a causative thrombus (clot) or embolus using the natural, lytic drug, streptokinase. His group treated acute myocardial infarction, pulmonary embolism, thrombophlebitis and peripheral arterial occlusion. (1959). He was uncertain about the effect of lysis in myocardial infarction and stopped these studies. The drug was approved for lysis in other thrombotic states in 1977 by the FDA.

Acute myocardial infarction had been treated conventionally by watchful expectancy, usually with three weeks rest in bed. (armchair rest treatment). In 1965 I analyzed its mortality in a general hospital ward at Groote Schuur hospital in Cape Town where we found it to be 34%. Our first revolution was to introduce intensive coronary care with ECG monitoring of the ECG to control and treat arrhythmias and more personalized care and nursing. In my first coronary intensive care unit, one year later, the mortality dropped dramatically to 14%.

The pathologists had argued about the pathogenesis (precipitating cause) of myocardial infarction. Was it due to acute thrombotic occlusion of the coronary artery or to sudden coronary spasm which caused long-term ischaemia (decreased blood supply) and myocardial necrosis? Peter Rentrop from Göttingen summarized the status in 1977. Autopsy studies in the mid-1960s provided fresh evidence that coronary thrombi were common in acute myocardial infarction and that intimal fissuring of the arterial intima (inner layer) caused both plaque haemorrhage and intraluminal thrombosis. Bill Roberts, the premier pathologist from the NIH suggested the plaque fissures were artefacts and resulting from sectioning arteries at postmortem, and that coronary thrombosis resulted from a prolonged low output state associated with large infarcts. European investigators continue to explore the possibility of lysis of the thrombus in acute myocardial infarction, although they believed that the lysis time for a coronary thrombus exceeded the time limit of myocardial tolerance from anoxia. They hoped to improve collateral flow (from other coronary arteries) and microcirculation by lysis (dissolving) and opening of the capillaries and venules within and around the infarct zone. The discussion about the pathogenesis of acute myocardial infarction was limited by the inherent selection bias of autopsy studies and the paucity of in vivo and angiographic data.

The great breakthrough took place when Earl Wood, a surgeon in Spokane, Washington presented a cohort of patients in 1979 who had undergone coronary artery bypass surgery to bypass the obstruction) and compared them with a similar group who underwent regular medical therapy. Mortally reduction was dramatic and improved in the patients treated early (hours). Early surgical reperfusion had succeeded.

Rentrop continued his studies of reperfusion in acute myocardial infarction, first using a wire to perforate the thrombus and later controlled dissolution studies with Steptokinase. The results were very successful and the clot in the coronary artery was successfully lysed, coronary flow restored and myocardium salvaged. Rentrop then moved to New York and started further studies in the United States. Marc Verstraete from Louvain in Belgium organised working groups in Europe, at first using Steptokinase and used mortality as his endpoint. Initially, the results were indifferent, but gradually they improved. Genentech, a new biotech company cloned tissue plasminogen activator (tPA) which is identical to the natural lytic (dissolving protein) protein in the blood. It was a superior lytic drug and doubled the reperfusion rates and the clinical results improved further. This aroused excitement in Europe and several centres embarked on large controlled studies. Hugenholtz, Simoons and van der Werf were real protagonists as was Harvey White in New Zealand.

The new catch phrase in medicine in 1980 was evidence-based medicine. This introduced the second phase of research – randomized double blinded controlled studies - half of the patients were treated with the new drug and the other half received normal accepted treatment. Peter Sleight from Oxford was the British pioneer (GISSI Trial). Braunwald from Harvard was the other leader and together with Passamani from the NIH set up the first Thrombolysis In Myocardial Infarction (TIMI) study. All their patients with an acute myocardial infarct had an initial coronary arteriogram (to demonstrate the narrowings and blockages in the coronary arteries) and half were given Steptokinase and the other half tPA. In patients with occluded arteries the patency rate at 90 minutes was 62% with tPA and 31% with Steptokinase. The trailblazing continued: TIMI progressed, and there were large international and national trials in England, Germany, France, Holland and Italy. It now became clear that early treatment within four hours of pain onset, together with adjunctive anticoagulant and antithrombotic therapy, and mechanical reperfusion improved the prognosis.

I heard Rentrop speak for the first time perchance in Oslo in 1979, at a meeting on Timolol, a new beta-blocker drug for high blood pressure, but which was also very effective for glaucoma. He was tall and erect and spoke with a very impressive and forceful voice: he was very convincing so that I realised that he had pioneered a new treatment, a real breakthrough in the management of acute myocardial infarction. He had proved that it was possible to lyse the thrombus using a thrombolytic drug. De Wood and his group from Seattle had also just published their paper on the prevalence of total coronary occlusion during the early hours of transmural myocardial infarction in the New England Journal of Medicine: the results were very impressive. It was now clear that 90% of these patients had complete thrombotic occlusion of the culprit artery in the first hour after infarct onset and that there was spontaneous thrombolysis in the following hours.

The obstruction set up a time dependent process of myocardial necrosis in the anoxic zone and this was complete within 4 hours of occlusion. 

The pathologists, Reimer and Jennings tied off a coronary artery in experimental dogs. They produced convincing microscopic sections of the “wavefront theory” of muscle ischaemia, concussion and death, which started soon after the occlusion and which was complete after 4 hours.

Prof Gabby Isaac, the head of Haematology at Hadassah was using urokinase to lyse thrombi in the veins of the leg after deep vein thrombosis and thrombi in the pulmonary artery in patients with acute pulmonary embolism. He wanted to administer a direct bolus into the pulmonary artery and recruited our help. The results of direct infusion through a catheter were dramatic, the clot was lysed and disappeared, and the artery reopened. I felt that the time had come to extend its use and infuse the drug directly into the occluded coronary artery which was causing the acute myocardial infarction

We started intracoronary lysis using urokinase.  It was unbelievable to watch the lysis of the clot in the culprit coronary artery during the infusion, relief of the intense chest pain and the return of the ECG to normal.  Our first patient was a 73-year-old gentleman who had been admitted to the internal medicine ward with severe unstable angina pectoris. I catheterised him urgently on a Tuesday afternoon and demonstrated severe disease of all three coronary arteries. We felt that he was a good candidate for coronary artery bypass surgery. At 6 o’clock on Wednesday morning, he developed acute, severe chest pain with ST segment elevation of the anterior cardiac leads on the ECG and it was clear that he was developing a new myocardial infarction. The surgeons had already started their two operations in the operating rooms, and the patient’s family asked me if there was any way of unblocking the artery. I had urokinase in the catheterisation laboratory and we brought him down for a repeat coronary angiogram. The left anterior descending artery which previously had a 90% obstruction, was now completely occluded, and there was no flow down the artery. We infused the urokinase and it was amazing to see, how, after 15 minutes, contrast medium trickled into the occluded artery and after another 15 minutes there was rapid flow. The clot had been lysed, and flow restored. The ST segment elevation on the ECG, started to disappear and then suddenly he had ventricular fibrillation and a cardiac arrest. His blood pressure dropped to zero. Jacob, our technician, defibrillated him immediately while Basil Lewis started artificial ventilation. The resuscitation was successful, his blood pressure rose and I could see the heart beating on the x-ray screen. At the same time, Prof Eliakim, the head of internal medicine department, appeared at the door of the catheterisation laboratory and said ‘Gotsman, how can you snatch the patient from my ward without a formal discussion at the afternoon departmental conference!” He watched the resuscitation and was really quite upset. At that time I did not realise that the ventricular fibrillation was a reperfusion arrhythmia due to oxygenated blood entering the anoxic myocardium. The patient had a fairly small infarct, recovered uneventfully, later underwent a successful triple vessel coronary artery bypass graft and lived for another 15 years. The thrombolytic reperfusion was dramatic and proved that we could open the artery, restore blood flow and decrease the size of the infarct. The paradigm had shifted.

The second patient was no less dramatic. He was a 42-year-old director of finance of the local sick fund and came to tell me that I was undertaking too many coronary angiograms and wasting part of his budget. He felt a sudden pain, put his hand on his chest and then the pain increased in intensity. I sat him down and gave him a coronary vasodilator. The electrocardiogram showed ST segment elevation in the inferior leads, a sign of an impending myocardial infarction. He had heard of our successful reperfusion and asked me to take him to the catheterisation laboratory immediately. He had a single, total occlusion of the right coronary artery and the obstructing thrombus created a picture that looked as if the artery had been amputated. We started an infusion of urokinase and within 15 minutes restoration of flow started. It continued for another 30 minutes, the pain subsided, the ST segment elevation disappeared and he asked for a cigarette. He recovered after a very small infarct (heart muscle death) and was discharged home after a few days. The patient continued to smoke,the  atherosclerosis in the coronary arteries continued to develop and later needed and underwent several balloon dilatations. He is alive and well, some 30 years later.

Teddy Weiss, my senior cardiologist at Mt Scopus Hospital had returned from a post graduate Fellowship at Cedars Sinai hospital in Los Angeles in 1984. Willie Ganz, the local proponent of thrombolysis suggested that we use our mobile ambulances that were manned by a physician as well as trained paramedics to   use intravenous Steptokinase for lysis and the best method of shortening the time delay from pain onset to lysis was to initiate and administer the treatment at home before transport to the hospital.  Teddy undertook the organization of the project. We were joined by Dr. David Applebaum who oversaw the Magen David Emergency Ambulance Service.  The ambulance was staffed by a trained physician and supplementary experienced ambulance staff and was equipped with ECG monitoring, an ECG recorder and an external defibrillator.  David was a sterling and active protagonist. He trained and mentored a motivated team who could arrive at the patient’s home with a median of 5 minutes from the moment of call. They made an immediate diagnosis, treated any arrhythmia and quickly transferred the patient to the receiving hospital. This service soon became available throughout Israel. Unfortunately, David was murdered in a Palestinian suicide bombing at Café Hillel in Jerusalem on September 9, 2003.

We turned this clinical service into a most exciting and unusual research project and showed that it was possible to start thrombolysis in a pre-hospital setting within one hour of pain onset. The mortality was so low that we needed a more sensitive index of myocardial salvage and infarct size. We had already studied left ventricular function in detail by left ventricular angiography and we used infarct size to show that the this was a function of time delay, and that death of the heart muscle was complete after 2 hours.  Once pain started, the clock started ticking and every minute of delay was crucial.

We were conquering acute myocardial infarction and preserving heart muscle and function. At the same time, there were similar studies in Rotterdam, Brussels, Paris and the rural areas around Aberdeen, in Scotland and Belfast in Northern Ireland.  We invited our coworkers to a series of meetings to compare procedures and notes and published a series of monographs.

I became known as “the cardiologist who ran around the city with his ECG and syringe” opening coronary arteries in acute myocardial infarction.

Basil Lewis and I had learned a great deal from Hal Dodge and Florence Sheehan in Seattle about understanding global and regional left ventricular function of the heart.  We had used the computer to analyze the left ventricular angiograms and had defined different patterns of contraction after the obstruction of the different coronary arteries. It was simple to study patients after thrombolysis to determine the extent of myocardial infarction.  We produced different models of measuring left ventricular dysfunction and developed 3-dimensional representations.  The extent of myocardial necrosis was related to the volume of muscle supplied by the affected artery, the site of the coronary obstruction, the extent of the collateral circulation and to the delay from pain onset to reperfusion. The research produced at least 20 major publications and was the pivotal research thrust of the department for the next 10 years.

Sima Welber joined us as a research fellow, and completed her MSc degree.  David Fine came from the Mayo Clinic and joined the research team but after 2 years returned to practice in Minneapolis. He had to return a large loan he had taken as a student.  Teddy Weiss was full of ideas and all the younger staff participated with great enthusiasm.

We had shown that prehospital thrombolysis was very effective.     Mortality had fallen to 2 ½%.

 

The most exciting of all the other studies was the Great study undertaken by general practitioners in the rural Grampian region of Scotland, near Aberdeen. The general practitioners were trained to make an initial diagnosis of impending myocardial infarction and provide immediate thrombolysis. Half of the patients were given APSAC (a streptokinase derivative) at home and the other half on admission to hospital. Prehospital initiation of thrombolytic therapy saved one hour (105 versus 240 minutes) and was associated with halving of the three-month mortality (from 15.5% to 8%). Besides the reduction in mortality there were fewer cardiac arrests, fewer Q-wave MI’s, and improved left ventricular function. GP training improved the speed of physician response, clinical assessment and diagnosis, relief of pain and anxiety, correction of autonomic disturbances, and, arrhythmias, and resuscitation. Telephonic transmission of the ECG via the general practitioner to the regional hospital was the most effective approach in rural areas, before the ambulance arrived. It is ideal where the local hospital is 1 to 2 hours away from the patient.

Other randomised controlled studies such as the EMIP study in France and the West Washington study in Seattle were less decisive because the time delays were much longer.

There was a spate of major international studies that showed the superiority of thrombolysis. We introduced new antithrombotic drugs but now we had to be careful of excessive bleeding. The major problem was a small, but significant group of patients who developed intra-cerebral haemorrhage.

I travelled abroad extensively discussing our results. The most interesting experience occurred after I had spoken at the Friday morning cardiology meeting in Seattle. The group had studied all the acute infarcts in Seattle. Doug Weaver and Ward Kennedy who lead the randomized controlled studies had excellent results with mortality reduction in the anterior infarcts but were less successful with inferior infarcts. These infarcts in the inferior wall were usually small, and their time delays too long to make a significant impact.

In Rotterdam the ambulance was also very active. In Belgium they were using general practitioners and in rural northern Ireland the ambulance was going out into the country. I was invited to develop thrombolytic programs in Spain and Portugal and when the Iron Curtain came down eastern Europe started to lead the field. The medical metamorphosis was complete. Poland and Hungary were the first countries to implement the treatment. The countries had cardiologists whose IQ’s were identical to Western Europe but they had been deprived of adequate financial budgets. The opening of the intellectual gates, the cross communication of information with the Western countries and their extreme enthusiasm took then out of the darker ages into a new intellectual sunshine and while it took a generation to eliminate the old communistic bureaucracy, the drug and medical device companies discovered a fertile field for research and supported new projects and the medical machine of progress escalated.

Eric Topol, a young dynamic cardiologist from Ann Arbor, started a series of major multicentered international mega trials (TAMI and GISSI trials). He showed that thrombolytic treatment with TPA was very effective. Eric was a most impressive physician. He would enter the lecture theatre with his little bag and give a most exciting presentation. I went to visit him in Ann Arbor, and found that he was doing 7 to 8 catheterisation studies a day in addition to his clinical load and research studies. He moved to Cleveland clinic as director of cardiology and then director of the clinic and eventually moved on to San Diego. Braunwald was the father of myocardial salvage and mortality reduction continued with his TIMI studies, andhe and his group continued to introduce new supplementary thrombolytic regimes to improve the reperfusion and prevent further reocclusion and showed that not only opening the artery and re-establishing flow but also re-establishing the micro circulation was very important. They used mortality as endpoints whereas we used infarct size.

The next innovation was to use immediate coronary angiography to define the coronary anatomy, followed by immediate balloon dilation in order to accelerate opening of the artery more rapidly and completely. This was pioneered by Cindy Grines and Bill O’Neill in the Beaumont Hospital in Royal Oak, Michigan. She was a tall, thin, athletic lady, always on the move and with a very intense work ethic. She would come to the hospital immediately at night and run a 24-hour, seven-day a week service and was prepared to catheterize patients with acute myocardial infarction at any time of the day or week. She started a series of PAMI studies to compare treatment with immediate balloon angioplasty to thrombolysis. She reduced the mortality from 10% percent to 2% and re-infarction within six months from 16 to 8%. There was a gradual acceptance of her new technology, and within five years virtually all the patients with acute infarction were being treated by percutaneous coronary interventions. Stents were introduced, followed by drug, eluting stents, and the long-term results were excellent. Once again, the paradigm had shifted.

We also entered the field of emergency 24 hour per day angioplasty and because of the new DRG, which reimbursed the hospitals for the extra work and cost, larger  than the previous payments for angioplasty, the hospital found it profitable to undertake these procedures and we now have two on duty residents and two senior cardiologists on-call. Our mortality also plummeted and within two years the system had been introduced throughout Israel. The patient calls the ambulance, who radios to the on-call hospital, contacting the cath lab immediately and we try to have a door to balloon time of under one hour.

Percutaneous Coronary Intervention (PCI) in acute myocardial infarction is quite different from PCI in chronic coronary artery disease. Acute myocardial infarction is an active process in which a coronary artery has been occluded, part of the myocardium has been destroyed and many of the patients come to the catheterisation laboratory, cold and shocked, with a low cardiac output and poor tissue perfusion. The patient needs immediate acute intensive care, to raise the BP, improve the cardiac output and often to use mechanical support such as an intra-aortic balloon pump, or inserting a temporary pacemaker. In many patients the artery must be opened quickly but the artery is filled with fresh thrombus. The balloon dilatations can cause distal embolisation as the clot breaks off and fills the distal capillary bed with clot. The operator’s need greater experience and more manual dexterity and a sharp eye – brain – finger interaction and the ability to take immediate lifesaving procedures. We tried aspiration of the clot through the catheter but it did not improve outcomes.

A typical example is a 40-year-old man who has blocked his left anterior descending artery and may have disease in his other coronary arteries. He comes into the cath lab with a low blood pressure of 50/30, cold, pale and sweating. He needs immediate intravenous fluids and often needs immediate insertion of an intra-aortic balloon to support the circulation. The catheter lab staff are working under extreme pressure and it is essential to open the artery without delay. This may happen at 2 o’clock in the morning where everybody has been summoned from their beds and the entire catheter lab team is shifted into top gear. If the patient  develops ventricular fibrillation, he needs resuscitation, defibrillation and intensive drug therapy.

The Cardiac Department at Tel Hashomer Hospital under the guidance of Shimon Behar and The Israel Cardiac Society started a national registry (ACSIS) and the country-wide mortality has dropped progressively to 4% .

Non–transmural infarction was also upgraded and early interventional procedures undertaken. The workload in our department changed completely and since there were very few patients who developed restenosis, the workload changed and most of the patients are admitted directly from the emergency room.

The department now runs a 24/7 cath lab service. The mortality has dropped dramatically and in more than 70% of the patients we salvage most of the myocardium at risk.

There remain many unresolved issues: training the population to call the emergency services earlier when chest pain starts, reducing the time delay from pain onset to reperfusion, better methods of preventing myocardial damage, management of large or second infarcts with cardiogenic shock, use of new auxiliary pumps to assist the heart in shocked patients, and management of patients with prolonged cardiac arrest and severe anoxic brain damage. Nonetheless we have excellent new methods for centralized, cloud based monitoring services, to manage high risk ambulatory patients and anticipate the heart attack, internet communication between the ambulance and the receiving hospital cardiac service and more immediate response using neighborhood motorcycle response systems.

I can look back on this complete revolution, from a 34% mortality with a 3-week rest in bed program, to 3-4% by immediate emergency restoration of normal coronary flow in less than 2 hours of occlusion by a well-trained  ambulance service and an efficient coronary catheterisation team of trained interventional cardiologists, technicians and nurses.

I am proud of our energy, push, research and enthusiasm and the continued vitality of my dynamic successor, Prof Chaim Lotan and his hyperactive crew.

 The sun never sets on cardiology: the lights on the cardiology floor never dim at night.

TEACHING

I had three goals for the department: clinical service, research and teaching. Apart from two years in Rhodesia, my entire life had been spent in teaching hospitals. Teaching and education was a pivotal and fundamental building block of my presence in the teaching hospital.

In 1973, I found myself running the introductory course in cardiology to the 4^th year students and undertook the brunt of the teaching, first in English and then in broken Hebrew.

I had brought English and South African clinical bedside medicine to a country which was based on European and American tradition and instrumentation with an emphasis on special tests, with little associated physical examination. I introduced the basics of physical examination to my residents in the out-patients and to the departments of internal medicine. The impact was great and soon Prof. Eliakim and all his staff would join me on the grand rounds. I applied myself to the students using the basic system of careful history taking, meticulous physical examination, precise analysis of the ECG, x-ray interpretation and only then analysis of the laboratory tests, echocardiography, and finally cardiac catheterization and angiography.  All of these were integrated into the final clinical diagnosis for correct prognosis, treatment and management. This logical approach upset my clinical and surgical counterparts and it took some years for them to slip seamlessly into this clinical pattern.

I had to undertake most of the teaching myself and although the teaching staff expanded gradually, I continued to provide the major portion of the teaching thrust.  We soon had elective students in the final year, and since they came in small groups of 6 students, this meant that every day we had students for 6 – 8 hours for 8 months of the year.

This was a heavy burden, since I became very active in the cath lab, operating room, and wards.

We had inadequate teaching space, as the students were squashed into our small seminar room and at one stage, I was given a small laboratory the pharmacology building to give seminars. It was very inconvenient, but it gave me good, physical exercise. In later years, Penchas would joke and say that Gotsman had brought the 3^rd heart sound and the cardiac catheter to Jerusalem.

We produced teaching pamphlets for the students using the power points presentations, but I had the feeling that they liked to have all their information pre-digested like porridge for breakfast.

We attracted many foreign students who came to Jerusalem for elective periods, and I took them under my wing. They were great fun. They were enthusiastic, very intelligent, and were well-educated, and I created a very special personal relationship with them. I took them into my private clinic, and between the patients and a white teaching board and colored pens, we were able to create a very personal teaching relationship. When I met them in later years, it was clear that this period had made a great impression on them.

The modern approach frowns on formal lectures to large classes, but I still believe that a well-prepared and organized lecture, given slowly without any time constraints, provides the student with a framework for understanding and digesting the material. Seminars of six to eight students provide intimate and personal eyeball contact with the students but this requires repetition of the material and is time consuming. I enjoyed these seminars, for which I not only produced outlines and power point presentations, but also used the white board and colored pens. I was a little disappointed by the students, who would simply listen passively and try to understand the material, but they rarely asked questions or took down notes. Ward rounds and bedside teaching was always very exciting. It provided intimate interaction with the patients, resulting in a close patient-student-teacher interaction. It was easy to determine the pace of the teaching and to appreciate how well the students understood the subject. I used the Socratic method of question and answer. Once again, a group of six students was too large, and I often divided large groups into two small sub groups. Often, I crowded too much material into a discussion on a single patient.

I had my own techniques of careful history taking, based on years of clinical practice: Unhurried, detailed, and comprehensive. Physical examination followed a precise pathway so as not to omit significant details, electro-cardiography gave a careful insight into the electrical and anatomical aberrations of the heart, detailed analysis of the echocardiogram, careful interpretation of the silhouette of the heart, and nature of the lung fields on x-ray, and then interpretation of the special tests. Differential diagnosis today is a lost art, but then it was an accurate diagnosis, often of multi-organ disease, knowledge of the prognosis and trajectory of the patient, and finally, an understanding of the physiological and pharmacological basis of treatment.  If the patient needed an intervention, the procedure would be discussed together with its advantages and disadvantages.

I had a perfect control of both English and Hebrew. My single disadvantage was impatience with the students, who often would not concentrate on the discussion, and the nurses, whose activities sometimes interfered with the flow of teaching.

As we received more space and moved the department to the eighth floor, I built a large teaching room using the most modern teaching methods with computers, overhead projectors, and we had discussions of recent research and simple seminars to introduce new material into our clinical practice.

Many years later I would meet my former students who are now heads of the army medicine, directors of hospitals, and leaders in different departments. They would always joke about the precise teaching methods and how much they had enjoyed studying cardiology as undergraduate students.

Teaching was my greatest investment in medicine in Israel and I had the opportunity to influence at least 50% of the students who passed through the Hebrew University.

Space and Expansion – Growth in the Hospital 

A university department of cardiology has to be well-balanced. Its primary function is patient care, but it is also responsible for teaching students and post-graduates. It should also encourage research to introduce all the latest technologies and innovations. The fundamental principles of organization are no different than that of a large business, which must be built on sound economic principles. Its final goal is patient health.

To proceed, it needs patients, persuading them that the department is excellent and better than others in the country, so that there is a continuous supply and input into the department.

Adequate space is essential to build a factory or a supermarket, and similarly, a medical department needs sufficient space – wards to hospitalise the patients, large outpatient clinics to care for the clients, offices to house the doctors, secretaries, nurses, technicians and research staff, and storage space for equipment and records.

Inadequate staffing prevents optimal production and patient care and creates inefficient work, backlogs, and waiting lists. In the hospital, insufficient or uncoordinated staff hampers an efficient patient flow. Outpatient clinics have to be optimal for services provided; insufficient nurses or technicians create long waiting lists; and the patients find other clinics or hospitals. Inadequate or insufficient equipment can create bottlenecks.

Funding  fees from the sick funds and private patients and charitable donations has to be maximised with income covering the costs, and leaving a small profit; while capital has to be carefully allocated to provide the most modern and efficient machinery or equipment.

I soon realised that my major function was to navigate the department through this maze of precise coordination.

Space is always a problem. When I arrived in 1973, all the available space in the hospital had been allocated, including the new oncology block and later the mother and child pavilion.

The echocardiography service, which started from scratch, occupied one room in the basement, and as we acquired more machines, we needed more space we were allocated space in the gastroenterology department on the fourth floor, and we converted it into the echocardiography department with two examination rooms and an animal research surgical laboratory. The area was far from the catheterization laboratory in the basement and the patient ward on the eighth floor. The rooms were not renovated; they were physically far from my center of work; and so, the area was not part of my daily route.

The next improvement was a new ward of six beds on the third floor. This had been part of the physiotherapy department, which had moved most of its activity to Mt. Scopus. The rooms were renovated with clean, white paint, spacious windows opening into the atrium of the hospital building and with completely new fittings. We now had more monitored beds to hospitalize our growing in-patient service in a shiny, modern ward. I felt rejuvenated, and we recruited new staff of young nurses. For the first time we had a really modern department.

Two years later, the administration decided that the bone marrow transplantation service was earning more than cardiology, and we were moved to the fourth floor, but shared less-renovated space with the emergency room short-term hospitalization ward. This was a hybrid of two different services, overseen by the same nursing staff. It was airy and spacious, but the patients were always mixed up.

Phase three of the expansion started 15 years later and we acquired the dermatology department inpatient wards, which transferred from the eighth to the fifth floor.  This consisted of half a wing of the hospital but it was ideal to move my office from the basement to the 8^th floor.  Fortunately, Prof. Penchas, the hospital director, was behind the move, and we had a good donor from New York.  The ward space had to be renovated completely and we built a new office for myself with a secretarial suite and a large room for Yonathan Hasin, two new large catheter suites, a control room, radiological facilities, a six bedded recovery room, kitchen and a small waiting space for the patients and their families.

There was more office space, and I moved my own office to the eighth floor. We had also continued with the extra beds on the third floor and then another ward on the fourth floor.

The catheterization suite and the radiological facilities were superb.  General Electric gave us a very good deal.  I ordered a L-Y gantry and with a biplane configuration and they added the equipment for the second room—a single plane at half price.  These new rooms gave us sterling service as we did 10 to 12 cases a day of which half were follow up angioplasties.  The machines were reliable with very little down time. 

The recovery room was a G-d send.  We now had extra beds to house the catheterized patients overnight and this solved our extreme bed shortage. 

The dermatology outpatient department occupied the transverse wing on the eighth floor and two years later moved to renovated space on the fifth floor.  This was our opportunity to provide more office space for the doctors and a new echocardiographic department, bringing it up from the basement.  There was a small conflict between myself and Prof., Stern, the hospital director.  He wanted to convert it into an outpatient clinic while I saw it as an outlet for my overcrowded doctors who had no personal office space.  The administration decided to use it as alternative space while they were renovating the ENT department so the building was delayed for two years.  It made me very sad as the corridor was half empty in the mornings when they held their public clinics and only filled in the afternoon when the seniors had their private practice.

I sat with the architects and with minimal structural changes we built a corridor of physician's offices, a conference room and a well organized echocardiographic suite and stress testing laboratory.  A new wind of change blew through the department and for the first time the physicians had their own comfortable personal offices. 

The echocardiographic suite was comfortable and the corridor waiting room was full with patients.

This overall expansion program took 25 years. I felt that it was 20 years too long. We always had too many patients, too many procedures, too few doctors and in adequate space. Yet this was the reason that I had come to Israel and despite the lack of coordination by the hospital directorate we developed the busiest and best  cardiovascular department in the country. The patients flowed from every direction: Nahariya and the Kibbutzim in the north, Haifa and its suburbs, Nazareth, Afula, Rehovot, Ashkelon and Beer Sheva. Less than half the patients came from Jerusalem. After I retired the situation reversed and now 90% of patients come from the Jerusalem conurbation.

It is not only the space that counted, but the vision, drive, passion, enthusiasm, team spirit and hard work that created success.

     

The Cardiac Revolution at Hadassah

The Cardiac Revolution at Hadassah

The Inheritance

Cardiology at Hadassah Hospital in 1973 was a very small operation, which functioned as a mere “service” to the more established departments. Cardiac patients were hospitalized in the Internal Medicine wards and treated by the Internists. Cardiology provided specialized services for consultations, ECG, arrhythmia monitoring, cardiac catheterization, pacemaker implantations and an outpatient clinic. The only beds that Cardiology had at its disposal were the four beds in a Intensive Cardiac Care Unit (ICCU), meant for the more severe cases and acute infarctions.

The cardiac diagnostic service was located on the second basement floor of the hospital along a corridor connecting the hospital and the medical school. The unit was located on one side of the corridor and the hematology department on the opposite side.

Since the corridor was the main thoroughfare from the medical school to the hospital and immediately adjacent to the main dining room, this created a continuous flow of human traffic in each direction and a very friendly, busy, market-like public environment. I soon became friendly with the hospital staff as they passed to and fro, but it was far too busy, and this disturbed our patients who used the corridor as their waiting room.

The unit was small. It had a conference room with a miniscule bookcase and library, a resident and secretarial offices. My office was three by three meters, opened into the main corridor and had no windows. The catheterization lab was also small (three by six meters) with very simple equipment, including a Philips patient table and a ceiling-suspended C-arm, which rotated in three planes. The X-ray generator was an old Westinghouse unit held together by a criss-cross of insulating tape to cover the exposed wires. There was a modern Arriflex 36-millimeter camera and a closed circuit television system. The Elema recording system worked with an ink-jet recorder. The lab could barely contain the equipment, the operators and the technician, and there were no nurses to attend to the patients.

We had three technicians, including Yaakov Fischer and Shmuel Raz. The cath lab investigated three patients a week. The techs worked in the experimental labs for the rest of the week.

There were two experimental labs: one directed by Prof. Braun which investigated isolated perfused rat hearts (the Langendorf preparation). They examined the effect of scorpion venom, which was toxic to the heart, and the ameliorating effect of beta blockers. The second lab was a dog lab dealing with electrophysiology.

The small ICCU was located on the eighth floor; it had four beds surrounded by curtains and a small monitoring station. The director of this unit, Prof. Rogel (Rosenberg), had a tastefully decorated, airy, adjacent office with a view of the hospital courtyard.

Full Throttle

My first priority was to improve my rudimentary Hebrew, so I attended a full-time Ulpan. After a month, I left the Ulpan and started activities at Hadassah.  

Time was short. It became apparent that the medical hiatus at Hadassah, without a new chief in charge had created a vacuum, which was being filled by the other senior staff. The department needed a new, fresh, active and dynamic chairman. I needed to start work and rev up the department.

The department had two senior associate professors, both born in Hungary. They had survived the Holocaust, and after the war had trained in Hadassah. Prof. Shlomo Rogel was the elder and ran the ICCU. Prof. Shlomo Stern was in charge of the cath lab and had an interest in 24-hour ECG monitoring and silent ischaemia. Danny Tzivoni was the senior registrar with Prof. Stern while Danny David worked with Rogel in the ICCU on the eighth floor.

I started working in the outpatient clinic. The environment was exciting. Instead of the Anglo-Saxon and Afrikaans patients, I was now working with and treating native Israelis, who were mostly from the Mediterranean littoral and who had a different outlook on life. I had never met people from Morocco, Libya, Egypt, Syria, Iraq, and Iran. They were more gentle but more vociferous and loaded me with presents of food and fruit. The clinic rooms were interconnected so that I could go from consulting room to consulting room without emerging into the patients’ corridor. The residents would see the patients, take their history, and then, I would supervise systematic history-taking and the detailed physical examination. We would discuss the diagnosis and plan a management program. There was a subtle difference in approach, as the Israeli graduates hade less training in physical examination. The number of patients in the clinic grew exponentially, as each patient brought his father, uncle and cousin. They were unaccustomed to a very friendly doctor, who placed the patient rather than the disease at the center of activity.

Soon, I had acquired sufficient patients to start catheterization. There were also sufficient patients in Internal Medicine with severe cardiovascular disease, who needed investigation, and it became possible to increase the number of studies. This disturbed the gentle pace of the technicians, but we soon expanded the program from three patients a week to three or four patients a day. Fortunately, this did not create a budget crisis, as we reused all the equipment; the catheters were cleaned carefully and sterilized in Cidex (gluteraldehyde). We also used Kifa tubing, which was heat malleable and we could fashion different shaped catheters. Later, we allowed ourselves the luxury of using disposable catheters.

I introduced daily meetings in order to analyze and discuss the catheterization studies and the patients in the ICCU. This was a new kind of clinical routine and inter-physician relationship, but soon, it became part of our daily activity and was the forerunner of what is now called “The Heart Team”.

I met with the hospital administration to plan a master program. Prof. Kalman Mann, the hospital director, and Dr Jack Karpas, his deputy, were very helpful. Mann was a father figure, who disliked arguments and confrontations, while Karpas, a fellow South African, who had been a general practitioner in Parow, near Cape Town was determined that my passage should be smooth and that I should succeed. We spent hours discussing the potential improvements. Hadassah had an important US Financial Aid Plan, which consisted of a large annual grant to buy American equipment that was shipped free of charge in American ships that had available cargo space. After two months, the new equipment began to arrive. First, the electric typewriter - the first one at Hadassah - an IBM Selectric with a golf-ball head. Then, the indicator dye dilution recorder to measure cardiac output, intracardiac shunts and valve incompetence. Then, the photographic recorder (NEP) for the catheter lab to make high fidelity pressure and phonocardiographic recordings. Next came the Elema X-ray cut film changer, so we could record angiograms of the patients with congenital heart disease at high resolution using full size X-ray films. This was a great improvement as we had to take the patents up 4 floors to the X-ray department with the catheters in place to use their roll film changer. The metamorphosis had started. There was a series of step-wise intellectual and technological advances. Once, one starts running, the race continues. The technicians changed their habits, as we streamlined the procedures and updated the laboratory to the standards of 1974.

It was clear that we did not have enough space, and Prof. Mann decided that we would inherit the basement area occupied by the Haematology Department. They had been allocated space in the new oncology block, but we had to wait until this was completed and opened. This took a year to materialize, but this addition provided space for a new catheterization theatre and anteroom, conference room, rooms for echocardiography, a new office for myself, and a rehabilitation suite. At last, I had a window overlooking the Jerusalem Hills and a separate examining room. Unfortunately, the Kupat Cholim would not subsidize the rehabilitation program, but we converted the suite into a spacious computer room with a large PDP-15 computer and hired Danny Sapoznikov from biomedical engineering to handle the programming.

It took two weeks to knock down the existing walls, but another year to finish the building with many unnecessary halts, while the builders went elsewhere to complete other building operations in parallel. My patience was stretched to the limit as the days, weeks, and months rolled by, and I sat watching the incomplete building project. Ultimately, it was finished, and we moved into our new cardiology department, which was already far too small for our needs.

I breathed a sigh of relief. We were up and running at full speed.

The Yom Kippur War

The Yom Kippur War was an abrupt introduction to the fiery dynamism of sudden change, which was so typical of Israeli life. Since Israel had taken control of the Sinai Peninsula in 1967, the Egyptians had been preparing to regain control of the Suez Canal and restore their pride. They rebuilt their armies on the Southern side of the Suez Canal. They also placed Russian heat-seeking SAM3 missiles to prevent the Israeli planes from penetrating Egyptian air space beyond the Canal Zone. Israeli army intelligence underestimated the Egyptian rearmament and despite the mounting signs of Egyptian activity, delayed mobilization of the army. The sudden attack on Yom Kippur of the Egyptians in the South and the Syrians in the North took the senior political echelon by surprise, and both fronts were unprepared for the sudden violent onslaught, particularly on Yom Kippur when most of the nation was in the synagogues. Mobilization of the Israeli Army was slow, and the Egyptians crossed the canal and started to penetrate into Sinai, while the Syrians rolled tank divisions across the Golan Heights. Mobilization of the army reserves took 72 hours. The opposing armies progressed unchecked, and their forces moved forward. Finally, after 72 hours, the Israeli forces started to dominate the battle, but the cost in casualties was very heavy.

The Yom Kippur War interrupted the renovation of the department. The entire staff, except myself and Rogel, were taken off to the army, and I was drafted to help Prof. Zaltz, Head of Surgery, to run an extended emergency room. The entire entrance foyer of the hospital was filled with beds. No one expected the ferociousness of the battle on the Southern Front. The Egyptians overran the Bar-Lev Line along the Suez Canal and decimated the Israeli Forces. There were hundreds of casualties, and after 12 hours, Soroka Hospital in Beer Sheva, the main hospital in the South, was inundated and the overflow poured into Hadassah. We had a major crisis, and the surgeons and anesthetists were swept off their feet in the operating rooms. I was left dealing with the acute emergencies as they arrived, including diagnoses along with emergency fluid and blood replacement for the patients in shock. The pragmatic instruction, which I received in surgery at medical school and my experience in Gatooma stood me in good stead.

All the cardiologists except Rogel were drafted. The staff disappeared overnight, so I offered temporary appointments to Andre Hirschorn (Keren) and David Halon. Both were studying at Ulpan Etzion, and soon, they came to work in the hospital. They were bright and eager beavers, absorbed the cardiology, and mastered Hebrew. Andre had just arrived from Targu-Mures in Rumania and David from Birmingham in England.

As the Egyptian onslaught abated and the Israeli troops reversed the tide of war, the Emergency Room became quieter, and I was able to return to cardiology and investigate the patients who had been deferred. Danny Tzivoni had been injured in the forearm and needed a period of convalescence, but the new medical team waded into the fray.

The two professors of Internal Medicine - Profs. Eliakim and Stein, who were in control of the hospitalization beds were interested in learning a more modern clinical approach to cardiology, so I spent an afternoon each week rounding in Internal Medicine A and B with the chiefs and the residents. I introduced the English tradition of bedside clinical cardiology and physical examination, which had dominated London since Paul Wood had taken charge of the National Heart Hospital. I became known as the cardiologist who had introduced the fourth heart sound and percutaneous coronary angiography.  

Expansion and Consolidation

The Cardiology Department at Hadassah continued to develop, grow, and expand. The outpatient clinic grew from 20 to 80 patients a week. I had my own program in working with the residents: they would receive the patients, and I then saw and examined all the patients personally with them, and, in this way, taught them good clinical medicine.

The department was very active. I put in long 12-hour clinical days, interspersed with regular ward rounds and staff meetings. I also made rounds in both internal medicine departments and liaised closely with the surgeons in pre- and post-operative care, carefully reading all the current literature and introducing new technologies. The clinical research, reviewing the different patient groups, progressed, and we spent most of our free evenings at my home with the residents poring over the results of the research and analyzing the information. The excitement was contagious.

We expanded and changed the secretarial staff, so they were able to handle the large clinical and research load.

We built the new catheterization suite. The space was limited but consisted of a very large room with an anteroom for preparing the patients. Unfortunately, the patients, who were awaiting a procedure, were parked in the corridor, as were the patients who had finished the angiography. This was very uncomfortable for the staff and the patients, since the corridor was the main passageway between the medical school and the hospital with very heavy foot traffic.  

We were limited to equipment made in the United States, as it was funded by a United States Congressional Grant, and we elected to purchase a General Electric unit, which had a rotating table, although I would have preferred a Phillips trapezoidal gantry, which would have provided additional caudal and cranial views.

There was no storage space, and all our equipment was stored in cupboards in the public corridor.

The number of patients who needed catheterization grew exponentially, and within a month or two, we studied four patients a day, and this continued to increase. The floodgates had opened, and patients poured in from all parts of Israel as our reputation expanded.

The technicians were unaccustomed to this workload, but gradually Ya’akov and Michael, our new technicians, adapted to the hard work schedule. They had to be the porters, technicians, and nurses, and we always worked with insufficient staff.

Our days became longer. Ya’akov, Michael, Bianca, and Leah, the new technicians, were prepared to work hard, and we rarely closed the cath lab before 7:00PM.

Ya’akov Fisher came from Slovakia, where he weathered the Holocaust and survived with difficulty. In the work camps, he volunteered to do any work that was available and made himself indispensable. He came to Hadassah as the cleaner, helped prepare the animals in the experimental lab, learned how to clean the cath lab and use the equipment, became an expert in photography, and was the most loyal of the workers in the department.

Michael and Leah came from Georgia, and for them, after-hour work was part of the daily routine.

Bianca came from Rumania and had great empathy with the patients.

Later, Rebecca Shein joined.

The work in the cath lab was very difficult and complicated. The technicians had to move the patient onto the catheter table, help with the cleaning of the skin, help drape each patient in a sterile fashion, prepare the pressure measurement and angiographic equipment, monitor the patients, help with resuscitation, record all the pressures, develop the angiographic films, and then, take down the blood-covered drapes, which were cleaned and then sent to the laundry. The catheters were cleaned meticulously and then re-sterilized. The cleaning process took as long as the actual catheterization, and the next patient was waiting impatiently in the corridor for his/her turn.

It was difficult to recruit Israeli medical staff, who were unwilling to work such long and demanding hours.

When I came to Jerusalem in 1973, I had been promised the beds of the pulmonary in-patient service on the eighth floor of the hospital. Unfortunately, when the administration closed the pulmonology in-patient service, they re-allocated the beds, which had been promised to me, to the new staff, who were recruited to open the new Department of Internal Medicine at Mount Scopus Hospital. The renovation of the old hospital was two years behind schedule, and the newly recruited medical staff were very impatient, as the hospital had no beds available for patients. Ultimately, the Mt. Scopus Hadassah Hospital was completed, and the internal medicine physicians moved out of the Ein Kerem facility. The area was renovated, albeit slowly at Israeli pace, and we expanded the ICCU to six beds with a pace-making suite and another eight beds for cardiology. We always had a chronic bed shortage, but the nurses were good, and the turnover of the patients was very quick and efficient.

We received a new generation of 3-channel ECG machines and provided a much more effective service.

We acquired our first echocardiographic recorder, and Basil Lewis, who had arrived from South Africa, took over the service. At first, we had a simple M-Mode machine, and with a few energetic young students, we produced our first studies on mitral stenosis and started studies on the heart in Thallasaemia. We had a group of very bright students running in and out of the echo room. Richard Popp from Stanford brought a 2-D echo machine for demonstration. It was so impressive that Prof. Mann found the funds for it immediately, so it never returned home. This was the great revolution in cardiology and provided non-invasive real time imaging of all the structures of the heart excluding the coronary arteries.

The service flourished, but it took 35 years to persuade the administration to realize that a second shift would triple the income of the unit.

When we introduced coronary angioplasty in 1979, we continued with the same staff, having doubled the workload.

The administration calculated my physician-staff needs on the basis of the department of health’s staffing structure, which had been drawn up in 1973, before expansion into coronary angioplasty had even been introduced.