What is IEPR? The International EECP Patient Registry is a study which enrolls patients who are undergoing EECP for treatment of angina pectoris. IEPR Phase 1 was initiated in January 1998 and completed three-year follow-up in September 2004. Phase 2 was initiated in January 2002 and reached the target enrollment of 2500 patients in September 2004. Data points captured at the beginning of treatment include patient demographic characteristics, medical history and pre-treatment quality of life (Duke Activity Status Index - DASI). Phase 2 added heart failure specific data (including the Kansas City Cardiomyopathy Questionnaire). After treatment completion data are collected on improvement in anginal symptoms, quality of life, and on any adverse events occurring during the treatment period. Patients are contacted for follow-up at six and 12 months and then annually (up to three years post-treatment in Phase1, up to 2 years in Phase 2).   What is EECP? Enhanced External Counterpulsation is a non-surgical, non-invasive, outpatient therapy that has been shown to reduce the symptoms of angina pectoris, possibly by increasing coronary blood flow in ischemic areas of the heart. While the exact mechanism of action of EECP remains to be specifically defined, the beneficial effects of EECP in patients with coronary artery disease appear to be sustained between treatments and may persist long after completion of a course of therapy. Registry data document duration of benefit to three years post treatment. The Vasomedical EECP therapy system is intended for the treatment of patients suffering with stable and unstable angina, congestive heart failure, acute myocardial infarction, and cardiogenic shock.   Background Since the early studies with counterpulsation at the Massachusetts General Hospital in the 1950's, it has been repeatedly demonstrated that this technique can reduce left ventricular workload and myocardial oxygen consumption. As the technology improved it became apparent that internal and external counterpulsation were capable of improving survival in patients with cardiogenic shock following myocardial infarction. The clinical benefits of external counterpulsation were less consistently observed in early studies because the external counterpulsation systems lacked the computer-controlled operating system that made sequential cuff inflation possible. In the 1980's, Dr. Zhen Sheng Zheng and colleagues at Sun-Yat Sen University in China reported on their extensive experience in treating angina using a newly developed sequential external counterpulsation treatment system. Dr. Zheng et.al. found, in direct comparative trials, that the sequential system was superior to the precursor non-sequential treatment system in augmenting diastolic perfusion. Not only did a course of treatment reduce the frequency and severity of anginal symptoms during activities of daily living and exercise, the improvements were sustained for years after completion of therapy in some patients. The experience in China prompted a group of investigators at the Health Sciences Center of SUNY at Stony Brook, New York to develop a new "Enhanced External Counterpulsation" (EECP) treatment system and to initiate a pilot study to reproduce the Chinese results. The study group consisted of 18 patients with chronic, stable angina, despite optimum medical management and surgical intervention, as well as evidence, assessed by thallium-201 perfusion imaging, of ischemia during an exercise stress test. Patients were treated with EECP for one hour a day for 35 days over seven weeks. During the course of treatment, all 18 patients experienced substantial subjective improvements in symptoms and 16 were completely free of angina during normal daily activities. Looking at objective measures of benefit, a comparison of maximal stress test results before and after treatment showed that EECP produced a significant increase in exercise tolerance. Results of thallium scans before and after treatment demonstrated a complete resolution of perfusion defects in 12 patients and a decrease in the size of the ischemic defect in another two. Thus 14 of 18 patients experienced a reduction in ischemia as assessed by radionuclide imaging. A subgroup analysis of exercise stress tests for these patients revealed that EECP not only produced significant improvements in exercise duration, but also increases in double product (blood pressure x heart rate), a measure of cardiac work. The conclusion - treatment with EECP was capable of producing a sustained improvement in myocardial oxygen supply and a decrease in oxygen consumption i.e. a decrease in cardiac workload. A subsequent study in 50 patients confirmed these results; all patients reported subjective reductions in symptoms, and 80% showed improvements in perfusion by radionuclide imaging. The results of the Stony Brook studies, supported by the experience in China, provided the first indications that an extended course of EECP therapy may stimulate development of persisting collateral vascular channels in chronic stable angina patients.   Mechanisms of Action:   The Hypotheses The mechanisms accounting for the salutary benefits of EECP therapy remain largely undefined. Emerging data now point to three possible hypotheses to explain its efficacy - enhanced diastolic flow, changes in the neurohumoral milieu, and changes in ventricular function independent of changes in cardiac load. In the first hypothesis, EECP's effects are mediated through enhanced diastolic flow and a subsequent increase in shear stress. Shear stress, in turn, activates the release of angiogenic growth factors with the resultant development of new collateral blood vessels. The second hypothesis attributes the benefits of EECP to improved vascular reactivity, similar to the benefits seen after exercise. Improved endothelial function and vascular reactivity may be mediated by changes in the neurohumoral milieu - endothelin, a potent vasoconstrictor, nitric oxide (NO) a potent vasodilator, and natriuretic peptides, specifically atrial natriuretic peptide (ANP) and beta natriuretic peptide (BNP), which promote diuresis. BNP is also one of the most sensitive predictors of both systolic and diastolic left ventricular function. The third hypothesis postulates that EECP effects changes in ventricular function independent of changes in the coronary vasculature. The large IEPR database includes patients with both coronary disease and left ventricular dysfunction (LVD), providing the first opportunity to assess outcomes in patients with clinical heart failure. Concerns that increased venous return to the right ventricle during EECP would worsen heart failure symptoms precluded enrollment of patients with LVD in early trials. The IEPR data showed that subjects with angina and a history of heart failure experienced benefits similar to patients with normal left ventricular function - improvement in angina classification and improved quality of life - suggesting that EECP could be safely administered to patients with LVD. To better define the role of EECP therapy in patients with heart failure a pilot study was done. The results suggested that EECP might engender beneficial changes in the myocardium of heart failure patients, providing impetus for the multi-center, blinded, randomized PEECH trial (Prospective Evaluation of EECP in Congestive Heart Failure).   Conclusion During EECP therapy an increase in transmyocardial pressure gradients may open latent conduits. Combining this effect with increased endothelial shear forces and the release of growth factors may in turn induce capillary sprouting and endothelial migration. Increases in shear force may also increase NO levels and decrease endothelin levels, with peripheral benefits and the restoration of flow reserve. The 35-hour treatment course may serve to normalize neurohumoral signals, improving arterial compliance and arteriolar reactivity. Oxygen demand is reduced as oxygen is utilized more efficiently for a given workload.   An Overview of EECP Therapy EECP therapy is a noninvasive treatment for patients with chronic stable angina, and heart failure. EECP treatments are typically provided on an out patient basis in 35 one-hour sessions over a seven-week period. Additional hours may be safely and effectively added to this standard regimen if physician evaluation of the patient's response to treatment determines additional hours will result in better symptom relief. To receive EECP therapy the patient lies on a treatment table. Compressive cuffs (similar to large blood pressure cuffs) are securely wrapped around the patient's calves, thighs, and buttocks. These cuffs inflate in a distal to proximal sequence in early diastole, and deflate simultaneously in late diastole just prior to the onset of systole. The sequential cuff inflations create a retrograde arterial pressure wave that augments diastolic pressure increasing coronary perfusion pressure and venous return to the right heart (increased preload). Simultaneous cuff deflation decreases systemic vascular resistance, afterload, and cardiac workload and increases cardiac output. The inflation-deflation sequence is computer controlled and timed to events in the patient's cardiac cycle. Inflation-deflation time points are specifically adjusted to optimize therapeutic benefit. For the treatment the patient wears tight-fitting pants and pantyhose to minimize the possibility of skin irritation. The squeezing sensation of EECP is not painful; patients often read, listen to music, watch television or sleep during the treatment hour. Eligibility for EECP therapy is determined by the patient's physician.