THE NON-INVASIVE PROCEDURE THAT IS BECOMING PREFERRED OPTION FOR TREATING ANGINA.

The evolution of External Counter Pulsation techniques has been driven by the need to improve the technical performance of equipment, and by the need to explore and demonstrate success in clinical applications.

External Counter Pulsation has developed over the past 44 years. It has now become a practical way to increase blood flow to the ischemic myocardium and other organs throughout the body. While it may seem that the theoretical benefits of external Counter Pulsation are evident, this non-invasive method for treating coronary artery disease had been eclipsed by other technologies until the past few years. The first systems built and tested used water as the compression medium and produced mixed results, however when augmentation was positive, good results were observed.

1950's

In 1953, Kantrowitz and Kantrowitz proposed the concept that elevations of diastolic pressure in the arteries could improve blood flow in the heart and be beneficial to patients with coronary insufficiency.

Kantrowitz and Kantrowitz first described the principle of "phase shift" diastolic augmentation.
Soroff, et al related this principle to the oxygen consumption difference between flow work and pressure work by the heart. It was this understanding that eventually led to the concept of a mechanically induced Counter Pulsation to provide assistance to patients with low cardiac output syndromes.

Early research used direct counter pulsation techniques first developed by Harken and associates at Harvard in the late 1950's. Through femoral cutdown and external pulse actuation, this technique withdrew and then returned the blood to the arterial system. In a number of studies this direct technique was used to document increased coronary flow, decreased coronary AVO2 difference, and reduced left ventricular pressure work.

1960's

In 1963, Dennis and coworkers used a pressure sleeve on the hind legs of dogs that was inflated and deflated in synchrony with their electrocardiogram.

In 1968, Kantrowitz and associates demonstrated the principle of "phase shift", of increasing diastolic blood flow with the intra-aortic balloon pump in 27 patients.

In 1969, Ruiz and associates evaluated the use of external pulsatile pressure to the lower extremities in five normal subjects. The aortic diastolic pressure was increased by 50 mm Hg with a 20% increase in cardiac output. In two patients with cardiogenic shock, an increase in perfusion pressure was associated with clinical improvement.

During the early 60's, laboratory studies with animals demonstrated the potential efficacy of Counter Pulsation as a treatment following coronary occlusion. Jacobey and associates provided the first evidence that Counter Pulsation could quickly enhance the development of coronary collateral circulation. It also suggested the possible clinical application of Counter Pulsation to the treatment of patients with coronary insufficiency and angina.

During this same period at Harvard, Birtwell and Clauss produced Counter Pulsation by introducing a catheter with a balloon into the ascending aorta via the femoral artery. The Intra-aortic Balloon Pump was thus invented. This approach has found clinical application in support of circulation during and after cardiac surgery and in cardiogenic shock.

Also in the 1960's, several scientists were involved in the evolution of Counter Pulsation to a completely non-invasive technique using externally applied pressure generated by hydraulic systems. The system used various materials to encase the patient's lower extremities. It then compressed the vascular bed, displacing arterial and venous blood centrally. Though these devices were somewhat primitive, several studies demonstrated the potential of this approach to increase survival in patients with myocardial infarction and cardiogenic shock as well as relief of angina pectoris.

During the late 1960's, scientists at the National Institute of Health believed that results could be improved if the blood was moved from the lower limbs in a sequential manner. The development and testing of sequenced systems determined that they achieved greater cardiac output and increased the ratio of diastolic to systolic pressures.

In the early 1960's laboratory studies with animals demonstrated the potential efficacy of counter pulsation as a treatment following coronary occlusion. This finding provided the first evidence that counter pulsation could quickly enhance the development of coronary collateral circulation, suggesting the possible clinical application of counter pulsation to the treatment of patients with coronary insufficiency and angina. While promising, it was also evident that the requirement for femoral cutdown and hemolysis caused by this technique severely limited the clinical usefulness of this invasive approach.

Also at Harvard, during this same time period, Birtwell and Clauss, produced counter pulsation by introducing a catheter with a long slender balloon into the ascending aorta via the femoral artery (Intra-aortic Balloon Pump [IABP]). Saline was pumped in and out of this bassoon by means of the cournterpulsing actuator. There have been continuing developments in the design of the IABP and its inflation/deflation techniques, and, although surgical insertion is still required, this approach has found clinical application in support of circulation during and after coronary surgery and in cardiogenic shock. IABP offers advantages over direct counter pulsation in that its effects are created close to the aorta, and the hemolysis associated with direct counter pulsation is avoided.

In the mid 1960's, several scientists were involved in the evolution of counter pulsation to a non-invasive technique using externally applied pressure generated by hydraulic systems. These systems used various devices to encase the patient's lower limbs and compress the vascular bed displacing arterial and venous blood centrally.

Although these early external counter pulsation devices were somewhat primitive, studies with them demonstrated the potential of this approach to increase survival in patients with myocardium infarction and cardiogenic shock, and in relief of angina pectoris.

As the evolution of non-invasive external counter pulsation devices progressed, hydraulic systems were replaced with pneumatics, and redesign of compression elements sought to improve results and patient comfort. Clinical applications of this modality, beyond cardiac or circulatory assistance in acute conditions, were also explored with varying degrees of success. In a 1986 review of the progress of external counter pulsation, Soroff and associates reported that mixed results of clinical trials with these systems were owing to technical difficulties with the equipment.

All of the external counter pulsation systems used in studies before the 1970's employed "non sequenced" pulsation - that is, compression of the vessels was performed simultaneously along the full length of the compression element.

During the late 1960', scientists at the National Institutes of Health suggested that results could be improved if blood was expressed from the extremities in a sequential manner. Development and testing of these "sequenced" systems determined that they achieved greater cardiac output and increased the ratio of diastolic to systolic pressures than did non-sequenced systems.

1970's

During the 1970's, Zheng and colleagues at Sun Yat Sen University in China, reported on their studies with a newly designed sequenced pulsation system that used four sets of compression bladders on the patient's legs, buttocks, and arms. In these trials, effects of the sequenced system were studied in patients with angina pectoris and acute myocardial infarction. In more than 90% of the 200 patients with angina pectoris, this device provided long-term symptomatic relief with minimal relapse.

These same investigators also compared the hemodynamic effects of sequenced and non-sequenced compression, and various configurations of compression devices in healthy volunteers and patients with coronary heart disease. Results confirmed that sequenced systems were far more effective in raising diastolic pressures.

Favourable results reported by Chinese investigators, led scientists at the Health Sciences Centre at the State University of New York at Stony Brook, to reassess the efficacy of this modality in the treatment of patients with chronic angina pectoris. Their studies, which included patients with sub acute pectoris refractory to other medical intervention and with evidence of myocardial ischemia, were performed using a newly developed and "enhanced,” counter pulsation system. Designated EECP - Enhanced External Counter pulsation, the system employs a three-cuff compression configuration and sophisticated computerized control of the inflation/deflation sequence. It has been studied for its ability to provide both short-term and sustained relief of symptoms of angina pectoris, and to provide sustained improvements in perfusion of ischemic areas of the myocardium.

In 1973, Cohen and associates investigated the effects of sequential (inflating the cuffs around the calves area, then thigh area, then buttocks in sequence) and non-sequential (uniform inflation) external Counter Pulsation in seven normal subjects. Diastolic augmentation was equivalent in both groups but cardiac output increased 17% with the sequential method. Cardiac output did not rise significantly with the uniform inflation method. The authors also compared sequential external Counter Pulsation to the Intra-aortic Balloon Pump (IABP) in experimental animals before and after inducing cardiac shock. Cardiac output was increased an average of 25% with external Counter Pulsation compared to 4% with IABP. The effects were due to an increase in venous return caused by the diastolic augmentation.

In 1974, Harry Soroff and coworkers reported the results of early models of External Counter Pulsation in 20 patients suffering from cardiac shock following a heart attack. Cardiac shock had a 15% survival rate, but 45% of Soroff’s patients survived; a significant increase in survival due to treatment with the ECP. Soroff originally used a device having a fibreglass leg unit with water-filled bladders that enclosed the patient’s lower extremities. It was hydraulically operated, triggered by the electrocardiogram signals, filling at diastole and emptying the bladders surrounding the legs at systole.

In 1976, John Watson and his associates compared external Counter Pulsation and intra-aortic balloon pumping in anaesthetized dogs. Both methods increased the amount of blood returning to the heart; but external Counter Pulsation also significantly increased collateral coronary blood flow to the ischemic heart tissue. External Counter Pulsation also had the advantage of being non-invasive.

In 1976, a joint program of 11 Chinese medical centres and factories developed the first sequential external Counter Pulsation device, followed by clinical investigations.

In 1977, Rene Langou and associates published a review paper, giving a historical perspective of ECP and explanation of the Tension Time Index (originally presented by Sarnoff in 1958) and how the ECP increases the rest period of the heart which maximizes oxygen extraction and oxygen delivery to the myocardium while reducing oxygen consumption (cardiac work load).

 
During the 1970's a great deal of study was done on external Counter Pulsation. Among the distinguished physicians and scientists publishing on this subject were: Amsterdam and Associates, Messer and Associates, Banas and Associates, Mueller and Associates, Birtwell and Associates, Parmley and Associates, Harken and Associates Rosensweig and Associates, Jacobey and Associates, Soroff and Associates, Kennedy and Associates, Sugg and Associates, Langou and Associates, Watson and Associates, Loeb and Associates, Wemple and Associates, Leinback and Associates, Wright and Associates

Among those scientists was a group at the Cardiassist Corporation in the Chicago, Illinois area. The team developed a sequenced hydraulic device called CardiAssist. Many years of study and development went into this device. A large multi-centre study involving 258 patients in 25 institutions was undertaken in the late 1970's.

1980’s

In 1980, Ezra Amsterdam and coworkers published the clinical results of an early ECP device used for acute myocardial infarction in a prospective, randomised trail of 258 patients in 25 hospitals. Hospital mortality (6.5%; 7 of 108 patients died) was significantly reduced in those receiving 4 or more hours of ECP within the first 24 hours after admission. Mortality in the control group was 14.7 % (17 of 116 patients died). Patients receiving the external Counter Pulsation treatment showed a reduction in chest pain, decreased progression of cardiac failure, reduced ventricular fibrillation, a reduction in heart size and improved clinical cardiac functional status at discharge.

Results from the 25 institution, 258 patient, multi-centre study using the Cardiassist device(published in 1980), indicated those patients receiving therapy within the first 24 hours after admission had a mortality rate of 6.5% versus 14.7% in the control group.

Zheng and associates at Sun Yat Sen University in China, reported their studies with a newly designed sequenced pneumatic system, which produced excellent results. In trials, effects of the sequenced system were studied producing long-term symptomatic relief. These favourable results caused numerous U.S. scientists to rethink their approach to external Counter Pulsation.

Cardiomedics, Inc. was incorporated under the laws of the state of Nevada on August 25,1986. On August 29, 1986, the Company acquired the assets of CardiAssist Corporation. CardiAssist Corporation had been engaged in the development and testing of earlier versions of the Company's external Counter Pulsation system, which it had acquired from Medical Innovations, Inc., one of the original developers of external Counter Pulsation at Harvard/MIT.

Cardiomedics owns patent, manufacturing and marketing rights to CardiAssist, a non-invasive, external Counter Pulsation therapy for patients with coronary artery disease. Since its inception, the Company has been engaged in development and testing of its CardiAssist System.

In September of 1987, the Company was the first to receive 510(k) marketing clearance from the FDA for its external Counter Pulsation system.

1990's

In 1990, Yu-yun Xu and Zhen-sheng Zheng published a review article of research with ECP in China. At that time, the equipment was used extensively in over 1,800 research, clinic and hospital facilities. In the short term evaluation of 6,116 patients with Angina pectoris, 52.6% of the patients showed significant improvement in cardiac symptoms, 30.3% showed some improvement, 8% had no change and 2% deteriorated. Of the total number of patients, the procedure was effective in promoting improvement in 92% of the cases (5,630 out of 6,116). In another study of 5,067 angina cases, 20.5% showed significant improvement, 47.8% showed some improvement, 30.5% had no change, and 1.2% deteriorated. The total effective rate in this study was 68.3%. In the evaluation of long-term effects 5-7 years after therapy, 102 patients treated with ECP were compared with 111 patients treated with medication. There was significant improvement in clinical symptoms in 67.79% of those treated with ECP compared to 38.74% of those treated with medication. There was also significant improvement in electrocardiogram results for 62.47% of the patients treated with ECP compared to 28.35% of those treated with medication. Mortality rates for cardiovascular disease for the ECP groups were 8.82% compared to 13.51% for the medication group. Acute myocardial infarction rates for the ECP groups were 2.94% compared to 8.11% for the medication group. ECP significantly improved clinical symptoms and electrocardiogram results and significantly reduced the risk of death and heart attack in an 8 year follow up. In 24 patients with cerebral ischemic disease, 54% showed significant improvement with ECP compared to 29% treated with medication. The total effective rate was 95.8% for the ECP group compared to 75% in the medication group. The author cautions that ECP not be used during the acute phase of cerebral ischemia or for hypertensive patients (those with blood pressures exceeding 160/100 mm Hg). External Counter Pulsation was also effective in treating sudden deafness and eye diseases (thrombus of the retinal artery, traumatic optic atrophy and optic neuritis).

In 1992, William Lawson and associates studied 18 patients (aged 45-75) with chronic angina that persisted despite surgical and medical therapy. After 36 sessions (1 hr each) of External Counter Pulsation, all of the 18 patients improved in their chest pain symptoms with 16 reporting complete relief. The treatment was usually well tolerated with less improvement seen in those with blockages in three vessels or with diffuse coronary artery disease.

In 1995, Lawson published a three-year follow-up of his 18 patients. Ten patients consented to being tested again. Of these, 8 continued to demonstrate improved myocardial perfusion (circulation). Two others returned to their pre-treatment baseline even though they showed clinical improvement in their symptoms. Lawson concluded that long-term improvement in myocardial perfusion and exercise tolerance can occur several years after ECP therapy, probably due to its promotion of collateral circulation.

In 1996, Lawson and his coworkers published an article on the effects of ECP on exercise hemodynamics and myocardial perfusion during a stress test in 27 patients with chronic stable angina. 81% (22 out of 27) of the patients improved their exercise tolerance after the ECP treatment and 78% (21 out of 27) improved on their radionuclide stress perfusion images. Because maximal heart rate did not significantly increase despite increased exercise duration, the authors suggest that the increase in exercise tolerance is due to improved myocardial perfusion and altered exercise hemodynamics. ECP therapy therefore appears to exert a "training" effect, decreasing peripheral vascular resistance and cardiac workload in coronary disease patients.

In 1997, Applebaum and associates, using a two-cuff protocol (leg and thigh), measured carotid artery flow in 35 patients (mean age 60) and renal artery flow in 18 patients (mean age 55). An increase in carotid and renal artery flow during diastole was observed in all patients. The mean carotid flow increased by 22%, from 27.7 ccm to 33.1 cm. The mean renal artery flow increased by 19%, from 21 cm to 25 cm. The pressure used was 150-180 mm Hg and all patients tolerated the procedure well without side effects. The authors conclude that ECP significantly increases carotid and renal blood flow and recommend the therapy to support those with decreased cerebral and/or renal circulation.

Also in 1997, Fricchione studied the psychological aspects of external Counter Pulsation and found that the treatment significantly improved depression scores. Patients often report feeling depressed following invasive procedures. Since depression is associated with poor outcome in those with cardiac disease, external Counter Pulsation offers clinical advantages beyond its circulatory benefits.

In the November, 1997 issue of the Cardiovascular Reviews and Reports, Dr. Strobeck and Dr. Tartaglia presented case studies of the effects of ECP on coronary artery disease. Stress scintigram images of pre- and post-treatment showed significant improvement in myocardial perfusion and a reduction in ischemia.

In 1999, Arora and his coworkers reported on the results on a multicentre randomized, placebo controlled multicentre trial to evaluate external Counter Pulsation in 139 patients with angina, documented myocardial ischemia and coronary artery disease. The program consisted of 35 hours of treatment, with one-hour sessions over a 4-7 week period. The authors concluded that the treatment was safe and effective in reducing angina symptoms in patients with coronary artery disease. The treatment was generally well tolerated and free of limiting side effects in most patients. Side effects that were reported included anxiety, dizziness, GI disturbances, arrhythmias, chest pain, edema, and skin abrasions.

Also in 1999,Werner and associates investigated the changes in flow volume in the carotid, vertebral, hepatic, renal and internal iliac arteries after a one-hour session with ECP in 16 healthy volunteers. The greatest increase in the carotid artery flow volume was 26%, seen in the three cuff method at a pressure of 300 mm Hg. The two cuff procedure at 200 mm Hg produced a 19% increase in blood flow to the carotid arteries. The three cuff method at 300 mm Hg increased blood flow 42% to the left main coronary stem compared to 18% in the two cuff method at 200 mm Hg. Werner concluded that the increase in blood flow to the coronary arteries leads to a significant increase in blood flow to the brain, liver, kidneys and myocardium. He also reported a 75-80% reduction in the vasocontrictive hormones endothelium and renin in both healthy volunteers and patients with coronary artery disease.
Ozlem Soran and associates published a paper suggesting that the increase in shear stress by the ECP may result in the release of various growth factors which stimulate angiogenesis (growth of new blood vessels) in the coronary beds. Patients who responded favorably to chronic therapy with ECP showed a significant increase in circulating vascular endothelial growth factor (VEGF) which promotes endothelial cell migration and collateral blood vessel growth.

The Zheng device from China was used extensively at State University at Stony Brook, New York. Extensive studies were performed and published by Lawson and Associates beginning in 1992.
A New York based company began importing the Chinese device in 1995 following the FDA's clearance to market 510(k) based on substantial equivalence to the CardiAssistª device.

Despite an extensive amount of clinical study over the past 45 years, Cardiomedics intends to conduct a minimum of 3 Multi-Centre studies to enhance external Counter Pulsation's acceptance by the medical profession, to obtain reimbursement for its use and for possible future regulatory purposes.

In China, External Counter Pulsation has been widely used since 1983 for heart disease as well as cerebrovascular disease. In the United States, the predominant research with ECP has been for ischemic heart disease

Other Articles >
THE BETTER ECP  |  HAEMODYNAMIC EFFECTS OF ECP  |  CHEMICAL EFFECTS OF ECP |  MECHANISM OF ECP