John C.K. Hui

Three-year sustained benefit from enhanced external counterpulsation in chronic angina pectoris.

Abstract Both the short-term and now long-term (over a 3-year period) clinical benefits of EECP appear to be maintained in almost all patients treated for chronic disabling angina. That most patients maintained their 3-year benefits suggests that long-term improvement in myocardial perfusion can occur. Future angiographic studies are planned to evaluate collateral function in these patients.

Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by Modifying Shear Stress–Responsive Gene Expression in Hypercholesterolemic Pigs

Background— Enhanced external counterpulsation (EECP) is a circulation assist device that may improve endothelial dysfunction by increasing shear stress. Chronic exposure of vascular endothelial cells and vascular smooth muscle cells to relatively high physiological shear stress has antiproliferative and vasoprotective effects. The present study hypothesizes that EECP inhibits intimal hyperplasia and atherogenesis by modifying shear stress–responsive gene expression. Methods and Results— Thirty-five male pigs were randomly assigned to 3 groups: high-cholesterol diet (n=11), high-cholesterol diet plus EECP (n=17), and usual diet (control; n=7). The coronary arteries and aortas were collected for histopathological study and immunohistochemical and Western blot analysis. The peak diastolic arterial wall shear stress during EECP increased significantly compared with before EECP (49.62±10.71 versus 23.92±7.28 dyne/cm2; P<0.001). Intimal hyperplasia was observed in the coronary arteries of the high-cholesterol diet group, whereas in animals receiving EECP, the intima-to-media area ratio was significantly decreased by 41.59% (21.27±10.00% versus 36.41±16.69%; P=0.008). Hypercholesterolemia attenuated the protein expression of endothelial NO synthase and enhanced the phosphorylation of extracellular signal-regulated kinases 1/2. EECP treatment alleviated these adverse changes. Conclusions— EECP reduces hypercholesterolemia-induced endothelial damage, arrests vascular smooth muscle cell proliferation and migration, decreases proliferating cell nuclear antigen proliferative index, suppresses extracellular matrix formation, and eventually inhibits intimal hyperplasia and the development of atherosclerosis by increasing the arterial wall shear stress, which in turn activates the endothelial NO synthase/NO pathway and probably suppresses extracellular signal-regulated kinases 1/2 overactivation.

Treatment Benefit in the Enhanced External Counterpulsation Consortium

The present study utilized a cohort of 2,289 consecutive patients enrolled in the Enhanced External Counterpulsation (EECP) Consortium to evaluate whether results of university studies showing EECP safety and effectiveness in treating angina can be generalized. EECP was found to be safe and well tolerated with a 4.0% rate of adverse experiences. Angina class improved in 74% of patients with limiting angina (Canadian Cardiovascular Society, CCS, functional class II–IV), with patients most impaired at baseline demonstrating the greatest improvement (39.5% of patients in CCS III and IV improved 2 or more classes). Efficacy was independent of provider setting or experience, women responded as well as men, and although younger patients demonstrated a greater likelihood of improvement, EECP was effective in patients ranging from 19 to 97 years. Extending the benefit of EECP treatment to a wider range of patients may be indicated based on these findings.

Can angiographic findings predict which coronary patients will benefit from enhanced external counterpulsation

Enhanced external counterpulsation is an effective treatment for chronic angina. Theoretical considerations predict greatest benefit in patients with at least 1 patent conduit in this group of 50 patients (all of whom improved clinically). Improvement in radionuclide stress perfusion imaging was seen in 80% of treated patients and was inversely related to extent of coronary disease.

Acute Hemodynamic Effects and Angina Improvement with Enhanced External Counterpulsation

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for coronary artery disease. The mechanism of action is felt to be hemodynamic. The complex hemody namic effects have been simply quantified by calculating a previously described effectiveness ratio (ER). The EECP Clinical Consortium, a clinical registry of 37 centers, prospectively enrolled 395 chronic stable angina patients (79 women, 316 men, mean age 66 years) to examine the relation of the ER to posttreatment improvement in Canadian Cardiovascular Society angina class (CCS). Women and the elderly underwent planned subgroup analysis. The ER was calcu lated during the first and last hours of a 35-hour course of EECP treatment. After EECP, CCS improved by at least 1 class in 88% of patients, 87% of men and 92% of women (p = NS), and in 89% of patients ≤ 66 years and 88% of patients > 66 years old (p = NS). The initial and final ER were similar in patients with and without improvement in CCS. Significant first-hour ER differences were seen between men and women (0.96 ±0.03 vs 0.76 ±0.04, p < 0.005), and between ages ≤ 66 and > 66 years old (1.04 ±0.04 vs 0.81 ±0.03, p < 0.0001). However, all subgroups responded equally well to EECP treatment. EECP is effective in improving CCS in chronic stable angina patients; it has comparable effects in men and women and across a broad range of ages. The hemodynamic effect of EECP (ER) does not predict improvement in CCS and may indicate that other factors, such as neuro- hormonal changes, may have a significant role in mediating the observed EECP benefits.

Predictors of Benefit in Angina Patients One Year after Completing Enhanced External Counterpulsation: Initial Responders to Treatment versus Nonresponders

Enhanced external counterpulsation (EECP) has been shown to reduce Canadian Cardiovascular Society angina class. This study examines the factors that affect the reduction at 1 year, especially in patients who do not demonstrate an initial response. The data of 2,007 consecutive patients enrolled in the International EECP Patient Registry were analyzed. After 36.6 ± 4.9 h of EECP, angina was reduced by at least one class in 82.7%. At 1 year, 35.4% of initial nonresponders and 70.6% of responders remained improved by at least one angina class and free of major adverse cardiovascular events. Multivariate predictors of 1-year benefit are initial response to treatment (odds ratio 4.5, 95% CI 3.5–5.8), baseline angina class compared with class IV (odds ratios: class I 2.1, CI 0.93–4.81; class II 0.62, CI 0.43–0.87; class III 0.80, CI 0.62–1.01) and no history of congestive heart failure (odds ratio 1.41, CI 1.14–1.74).

Enhanced External Counterpulsation Attenuates Atherosclerosis Progression Through Modulation of Proinflammatory Signal Pathway

Objective—Shear stress may be the most crucial local factor affecting atherogenesis. The present study investigated the effect of exposure to increased shear stress promoted by enhanced external counterpulsation (EECP) on the progression of atherosclerosis and the underlying inflammation-related molecular mechanisms in a porcine model of hypercholesterolemia. Methods and Results—Hypercholesterolemic pigs were subjected to a 7-week EECP intervention while being fed a high-cholesterol diet. EECP resulted in a 34.38% increase of mean wall shear stress and a significantly lower pulsatility index in the brachial artery. The animals receiving EECP showed a marked reduction in atherosclerotic lesion size in the coronary artery and abdominal aorta compared with the hypercholesterolemic control group, associated with a decrease in macrophage accumulation. The expression of a set of genes involved in inflammation (including C-reactive protein [CRP], complement 3a, vascular cell adhesion molecule-1 [VCAM-1], and inducible nitric oxide synthase), mitogen-activated protein kinase (MAPK)-p38 phosphorylation, and nuclear factor-&kgr;B (NF-&kgr;B) activation, was attenuated. Conclusion—These findings suggested that long-term EECP exerts a retarding effect on atherosclerosis by downregulating proinflammatory gene expression. The underlying mechanisms are related to chronic exposure to increased pulsatile shear stress promoted by EECP; this exposure suppresses the overactivation of the MAPK-P38/NF-&kgr;B/VCAM-1 signaling pathway induced by hypercholesterolemia.

Psychosocial effects of enhanced external counterpulsation in the angina patient.

Enhanced external counterpulsation (EECP) is a noninvasive pantaloon device designed to increase coronary artery flow in the treatment of angina. This pilot study, conducted in 1992-1993, which used psychosocial testing pre- and posttreatment, yielded data suggesting that EECP is well tolerated psychosocially and produces improvement in the anginal syndrome. More comprehensive research is under way to test these preliminary conclusions.

Analysis of baseline factors associated with reduction in chest pain in patients with angina pectoris treated by enhanced external counterpulsation

Data from the International Enhanced External Counterpulsation (EECP) Patient Registry were analyzed to determine which patient characteristics influence improvement in angina class with EECP treatment. Patients with severely disabling angina at baseline, men, and those without a history of smoking are more likely to improve their angina class after EECP, whereas those with diabetes mellitus, prior bypass surgery, and heart failure were less likely to benefit.

Effectiveness of Repeat Enhanced External Counterpulsation for Refractory Angina in Patients Failing to Complete an Initial Course of Therapy

Aims: This study examined the causes and results of retreatment of patients who failed to complete an initial 35-hour Enhanced External Counterpulsation (EECP) course. Methods and Results:Data of 2,311 successive angina patients from the International EECP Patient Registry were analyzed, 86.5% completed their EECP course (Complete cohort). Of the 13.5% patients failing to complete the initial course (Incomplete cohort), 28.3% had repeat EECP within 1 year vs. 10.1% of the Complete group. The predictors of failure to complete the initial course of EECP were: female gender, heart failure, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and use of nitroglycerin. For the Complete group, 83.4% had a reduction of at least one Canadian Cardiovascular Society (CCS) class after their initial EECP course, vs. 21.7% in the Incomplete group (p < 0.001). After repeat treatment, 66.2% of the Incomplete group achieved at least one CCS class reduction vs. 69.4% of the Complete group (p = NS) undergoing retreatment. The independent predictors for those who return to successfully complete their second course were patients who stopped their first course because of clinical events, and candidacy for coronary artery bypass grafting at the time of initial treatment. Conclusion: The results of retreatment of those who failed to complete their initial EECP course were comparable to those who completed their initial treatment, with similar reductions of CCS angina class.