ISBN 978-93-5547-295-3 (Print)
ISBN 978-93-5547-296-0 (eBook)
DOI: 10.9734/bpi/mono/978-93-5547-295-3

Treatment of ischemic heart disease (IHD) has moved on gradually from the use of simple vasodilator nitrates to complex multiple medications and interventional procedures including coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). Current treatments for IHD are able to decrease the incidence of morbidity and mortality in many patients. The concept of increasing the aortic diastolic pressure increase coronary perfusion pressure and blood flow was first introduced in USA by Kantrowitz in 1953. He showed in an animal study that, if coronary arteries are perfused at elevated pressure during diastole the coronary blood flow can be increased by 20-40%. This concept of Counterpulsation leads to development of invasive Intra-aortic balloon pump (IABP) Counterpulsation and non-Invasive Enhanced External (EECP) Counterpulsation. Initial equipment for non-Invasive Counterpulsation was hydraulic driven with a single water filled bladder applied in the lower limb. In 1975 air driven pneumatic EECP system was developed. Several studies on MI and Cardiogenic shock were reported during the 1970’s.This book has been written with the basic concept of Enhanced External Counterpulsation (EECP) therapy. EECP therapy is approved by USA FDA for stable Angina, heart failure (HF), cardiogenic shock and acute myocardial infarction (MI). The treatment is widely used for the first two indications angina and heart failure and there are more than 150 papers published in peer reviewed medical journals support its uses in these selected group of patients. Enhanced external counterpulsation (EECP) has been shown to reduce angina and to improve objective measures of myocardial ischemia in patients with refractory angina. Prospective clinical studies and large treatment registries suggest that a course of EECP is associated with prolongation of the time to exercise-induced ST-segment depression and resolution of myocardial perfusion defects, as well as with enhanced exercise tolerance and quality of life. With a growing knowledge base supporting the safety and beneficial clinical effects associated with EECP, this therapy can be considered a valuable treatment option, particularly in patients who have exhausted traditional revascularization methods and yet remain symptomatic despite optimal medical care. However, although the concept of external counterpulsation was introduced almost four decades ago, and despite growing evidence supporting the clinical benefit and safety of this therapeutic modality, little is firmly established regarding the mechanisms responsible for the beneficial effects associated with this technique. Suggested mechanisms contributing to the clinical benefit of EECP include improvement in endothelial function, promotion of coronary collateralization, enhancement of ventricular function, and peripheral effects similar to those observed with regular physical exercise.Enhanced external counterpulsation (EECP) is a noninvasive outpatient therapy for the treatment of chronic angina. EECP treatment produces an acute hemodynamic effect that is similar to that produced by the invasive intra-aortic balloon pump. Three sets of cuffs on the upper thigh, lower thigh, and calves of each leg are inflated with compressed air during the diastolic phase of the cardiac cycle and are deflated in early systole. This rapid inflation and deflation raises diastolic aortic pressure, increases coronary perfusion pressure, and provides improved after load reduction and increased venous return with a subsequent increase in cardiac output. Enhanced external counterpulsation has been shown to provide long-term symptom relief in patients with ischemic heart disease in several case series, as well as in a randomized trial. Up to 80% of patients selected for treatment have a positive clinical response, and an associated objective improvement has been demonstrated by functional imaging in several case series. A treatment course consists of 35 1-hour sessions over a 7-week period and is generally well tolerated with a low risk of adverse events. Development and enhancement of collateral channels, as well as peripheral conditioning and neuro humoral effects, may play a role in providing symptomatic relief. Studies are ongoing to determine the mechanism of action and to further define subsets of patients who might benefit.

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##### Enhanced External Counterpulsation: Current Practices and Future Directions

Enhanced External Counterpulsation: Current Practices and Future Directions, 29 November 2021, Page 1
https://doi.org/10.9734/bpi/mono/978-93-5547-295-3/CH0

An estimated 6.4 million patients in the United State (U. S.) suffer from symptomatic coronary artery disease, and about 400,000 new cases develop each year. Despite optimal medical therapy and invasive procedures, such as angioplasty and cardiac bypass surgery, there are an estimated 300,000to 900,000 patients in the U.S. who have refractory anginapectoris (RAP). About 25,000 to 75,000 new cases of RAP are diagnosed each year. The technique of Enhanced External Counter pulsation (EECP) therapy consists of electrocardiogram-gated rapid, sequential compression of the lower extremities taking place during diastole, followed by simultaneous de compression during systole. These actions produce hemodynamic effects similar to those of an intra-aortic balloon pump, but unlike an intra-aortic balloon pump, EECP therapy also increases venous return. The Mulita-center Study of Enhanced External Counter Pulsation (MUST-EECP) is the first multi-center, prospective, randomized controlled trial that studied the effect of EECP on stable angina patients. The Research on Enhanced external Counter pulsation therapy in coronary artery disease (RECC) study found that EECP on top of optimal medical therapy improves myocardial ischemia and prognosis in patients with stable angina. In addition, EECP has been shown to induce collateral formation in the coronaries. Although EECP is a relatively safe and well-developed treatment, a safety assessment to rule out contraindications and lower treatment-related risks is necessary for high-risk and elderly patients before administration. The technique of counter pulsation, studied for almost one-half century now, is considered a safe, highly beneficial, low-cost, noninvasive treatment for these angina patients, and now for heart failure patients’ as well. Recent evidence suggests that enhanced external counter pulsation (EECP) therapy may improve symptoms and decrease long-term morbidity via more than 1 mechanism, including improvement in endothelial function, promotion of collateralization, enhancement of ventricular function, improvement in oxygen consumption (VO2), regression of atherosclerosis, and peripheral training effects similar to exercise.

##### EECP Therapy Exigency and Historical Perspective

Enhanced External Counterpulsation: Current Practices and Future Directions, 29 November 2021, Page 2-6
https://doi.org/10.9734/bpi/mono/978-93-5547-295-3/CH1

Cardiovascular disease associated with death and disability remains as a serious medical problem. The cost of the cardiovascular disorders in 2010 approaching 450 billion American dollars per year and projected to reach to one trillion American dollar a year by 2030. Pharmacotherapy and revascularization therapy considered as an initial strategy in refractory angina pectoris treatment. Revascularization strategies includes percutaneous coronary intervention, coronary artery bypass grafting, enhanced external counter pulsation or intra-aortic balloon pump may also provide effective symptom control in certain patients. Enhanced external counter pulsation is one of the non-invasive therapies, designed for coronary artery disorder and for RAP patients who not respond to the procedures of revascularization and for pharmacotherapy. The anti-ischemic effects of EECP occur early and these effects are sustained to five years. Enhanced External Counter pulsation (EECP) therapy is approved by USA FDA for stable and unstable Angina, heart failure (HF), cardiogenic shock and acute myocardial infarction (MI).  Benefits associated with EECP include reduction of angina and nitrate use, increased exercise tolerance, favorable psychosocial effects and enhanced quality of life, as well as prolongation of the time to exercise-induced ST-segment depression and an accompanying resolution of myocardial perfusion defects.

##### Working Principles and Mechanism of Benefit of EECP

Enhanced External Counterpulsation: Current Practices and Future Directions, 29 November 2021, Page 7-19
https://doi.org/10.9734/bpi/mono/978-93-5547-295-3/CH2

Enhanced External Counter pulsation therapy involves of a bed connected to an air compressor which is connected to a computerized control. Also, there are 3 sets of cuffs covered the patient’s lower legs and patients’ buttocks. It is controlled by electrocardiography, which liberates a hemodynamic activity same of an intra-aortic balloon pump. The EECP-therapy is designed to raise the venous return, by this mechanism the EECP- therapy differs from intra-aortic balloon pump (IABP) therapy. EECP-Therapy produces high external pressure which reaches to 300 mmHg. The course of EECP-therapy composed of 35 treatments as one hour every day for seven weeks. The EECP-therapy raises venous return, increases cardiac preload, raises cardiac output and reduces the vascular resistance. The EECP-Therapy had a beneficial effect on endothelial-derived vasoactive agents and also had anti-inflammatory activities may decrease the future risk of cardiovascular disorders. Following EECP-therapy, plasma NOx level increased, nitric oxide has antioxidative properties could suppress oxidative stress. The simplest mechanism by which EECP might increase collateral perfusion is by opening preformed collateral channels, either directly via increasing diastolic blood pressure and flow or indirectly via release of vasodilatory mediators such as NO. Angiogenesis, the de novo formation of capillary blood vessels via sprouting of endothelial cells from existing blood vessels, may also be promoted by EECP therapy.

##### Indications of EECP and Clinical Studies

Enhanced External Counterpulsation: Current Practices and Future Directions, 29 November 2021, Page 20-38
https://doi.org/10.9734/bpi/mono/978-93-5547-295-3/CH3

An abundance of clinical studies has consistently confirmed the efficacy and safety of EECP for the treatment of angina. The Mulita-center Study of Enhanced External Counter Pulsation (MUST-EECP) is the first multi-center, prospective, randomized controlled trial that studied the effect of EECP on stable angina patients. The Research on Enhanced external Counter pulsation therapy in coronary artery disease (RECC) study found that EECP on top of optimal medical therapy improves myocardial ischemia and prognosis in patients with stable angina. In addition, EECP has been shown to induce collateral formation in the coronaries, thus it is expected to be useful for rest enos is prevention in post-PCI patients [4].  Current evidence suggests that EECP on top of standard medical therapy improves quality of life and rehospitalization rates among patients with NYHA grade II to III stable heart failure. The EECP improved exercise tolerance, cardiac function and quality of life, but not maximal oxygen intake at six months of follow-up, subgroup analysis further showed that among patients >65 years of age, maximal oxygen intake was increased after EECP treatment, indicating a greater extent of benefit for the elderly patients [26]. Evidence from clinical trials indicates that EECP improves psychological and psychiatric symptoms, along with social function and work capacity. MUST-EECP showed that EECP improves daily activity, work, body pain, confidence, stamina, social activities, and anxiety and depression among patients with angina [3]. Incidence of neurodegenerative diseases is increasing. EECP therapy, a safe, non-invasive treatment technique was attempted in these diseases [1].

##### Safety and Future Directions of ECP Therapy

Enhanced External Counterpulsation: Current Practices and Future Directions, 29 November 2021, Page 39-46
https://doi.org/10.9734/bpi/mono/978-93-5547-295-3/CH4

In 1998, the International EECP Patient Registry (IEPR) was organized to document patient characteristics, safety, and efficacy during the treatment period, as well aslong term outcomes. All centers with EECP facilities were invited to join this voluntary registry. The registry population comprises all patients starting EECP for treatment of angina pectoris in participating centers. It is crucial to monitor treatment efficacy during EECP sessions. Parameters are adjusted accordingly to ensure optimal benefit. Different conditions require different data points to be monitored. Indices for immediate hemodynamic effects are inflation/deflation time, inflation pressure, ECG, blood pressure, D/S ratio and DP/SP ratio, and in some cases, stroke volume, cardiac output, myocardial contractility, cardiac preload, peripheral vascular resistance. The American Heart Association recommends it as a Class IIb (Level of Evidence: B) intervention for treatment of RAP, among other nonpharmacological approaches such as Neurostimulation (Class IIb, Level of Evidence: B) and Transmyocardial laser revascularization (Class IIa, Level of Evidence: A). The European Society of Cardiology views EECP therapy as an interesting modality available for treatment of RAP with more clinical trials needed to define its role in treating RAP.  Enhanced external counter pulsation therapy is a valuable outpatient procedure providing acute and long-term relief of anginal symptoms and improved quality of life among a group of patients with symptomatic ischemic heart disease with or without congestive HF. Enhanced external counter pulsation therapy is generally well tolerated. Due to the vigorous compression applied to the lower extremities, certain factors may theoretically pre dispose patients to complications, including a bleeding diathesis, severe valvular disease, uncompensated heart failure with significant peripheral edema or pulmonary hypertension, or a high likelihood of venous thrombotic disease.

##### EECP Therapy Clinical Studies

Between 25,000 and 75,000 new cases of angina refractory to maximal medical therapy and standard coronary revascularization procedures are diagnosed each year. In addition, heart failure also places an enormous burden on the U.S. health care system, with an estimated economic impact ranging from $20 billion to more than$50billion per year. The technique of counter pulsation, studied for almost one-half century now, is considered a safe, highly beneficial, low-cost, noninvasive treatment for these angina patients, and now for heart failure patients’ as well. Recent evidence suggests that enhanced external counter pulsation (EECP) therapy may improve symptoms and decrease long-term morbidity via more than 1 mechanism, including improvement in endothelial function, promotion of collateralization, enhancement of ventricular function, improvement in oxygen consumption (VO2), regression of atherosclerosis, and peripheral training effects similar to exercise. Numerous clinical trials in the last 2 decades have shown EECP therapy to be safe and effective for patients with refractory angina with a clinical response rate averaging 70% to 80%, which is sustained up to 5 years. It is not only safe in patients with coexisting heart failure, but also is shown to improve quality of life and exercise capacity and to improve left ventricular function long-term. Interestingly, EECP therapy has been studied for various potential uses other than heart disease, such as restless leg syndrome, sudden deafness, hepatorenal syndrome, erectile dysfunction, and so on.