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American Heart Journal. 2003; 146(3)
Enhanced External Counter Pulsation for the Relief of
Angina in Patients with Diabetes:
Safety, Efficacy and 1-Year Clinical Outcomes
Georgiann Linnemeier, MD, Martin K. Rutter, MB, MRCP (UK), Gregory Barsness, MD, FACC, Elizabeth D.
Kennard, PhD, Richard W. Nesto, MD, FACC
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Abstract
Background: Patients with diabetes are at greater risk for coronary events, yet they are less
likely to benefit from revascularization than those without diabetes. Enhanced External Counter
Pulsation has recently emerged as a treatment option for select patients with chronic stable
angina.
Methods: We examined baseline characteristics, angina response, and cardiac outcomes of
patients with diabetes mellitus treated with Enhanced External Counter Pulsation (EECP) for
chronic stable angina. Data were collected from patients enrolled in the International EECP
Patient Registry (IEPR) before and after a course of EECP, and at 1 year after completion of
treatment.
Results: Of 1532 IEPR patients studied, 43% had diabetes mellitus at baseline. Patients with
diabetes were experiencing, on average, 11 episodes of angina per week. Most had been
revascularized with prior percutaneous coronary intervention or coronary artery bypass graft
surgery (86%) and most were considered unsuitable for either additional procedure (87%).
Treatment was completed as prescribed in 79% of patients (mean, 32 hours). Immediately after
EECP, 69% of patients with diabetes demonstrated a reduction in angina of ≥1 Canadian
Cardiovascular Society angina class. After 1 year, maintenance of angina reduction was
reported in 72% of patients with diabetes. Quality of life was significantly improved. Despite a
high-risk profile among the diabetic group in this study, 1-year mortality was similar to
coronary intervention registry populations.
Conclusion: This study suggests that in select patients with diabetes, EECP can be a safe,
effective, well-tolerated treatment option for the relief of angina.
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Introduction: Coronary artery disease starts earlier, is often more advanced at presentation
and progresses more rapidly in patients with diabetes (DM). Despite a substantial decline in
mortality from coronary artery disease in recent years, smaller declines in mortality in patients
with DM have been realized.[1] Most previous studies have shown that diabetes is
associated with higher rates of re-stenosis after angioplasty,[2-4] increased graft occlusion
after bypass surgery,[5] and increased short[6-9] and long-term[2,3,6,7,10-13] morbidity and
mortality after both forms of revascularization. The risk of complications after repeat
revascularization procedures is increased particularly in patients with diabetes.[14,15]
The search for improved therapeutic options for patients with chronic angina has yielded a wide
range of coronary revascularization techniques and procedures. In 1995 the Food and Drug
Administration cleared Enhanced External Counterpulsation (EECP) for the treatment of
angina. The results of MUST-EECP, a multicenter, randomized, masked, sham-controlled study,
confirmed that EECP was safe and effective in treating chronic angina.[16] Further research has
shown objectively that EECP improves myocardial perfusion[17-19] and that improvement in
angina and quality of life may be sustained for many years.[17,20,21]
This report describes a prospective observational study of patients with diabetes undergoing
EECP for treatment of angina who were enrolled in the International EECP Patient Registry
(IEPR).
Methods: The EECP device consists of 3 paired pneumatic cuffs applied to the lower
extremities. Cuffs are inflated sequentially (applying 250–300 mm Hg of external pressure)
during diastole, returning blood from the legs to the central circulation, producing aortic diastolic
augmentation, increasing both venous return and cardiac output. The cuffs are then deflated at
end-diastole, reducing peripheral resistance and providing left ventricular unloading. Daily 1- to
2-hour treatment sessions are typically administered for a total treatment course of 35 hours.
The International EECP Patient Registry (IEPR) began in January 1998, and currently >5000
patients with chronic angina have been enrolled from >80 centers in the United States and other
countries. The study group consisted of 1532 patients enrolled in the registry from 44 clinical
sites between January 1998 and September 2000 and thus had reached their 1-year follow-up
time point. Registry methodology has been described previously.[22] All treatment was carried out
using EECP equipment (Vasomedical, Westbury, NY).
Patients were defined as having diabetes if they reported a physician diagnosis of diabetes; the
validity of this method has been demonstrated previously.[23] Data on demographics, medical
history, coronary disease status and medication were collected on patients before EECP
treatment. No attempt was made to maintain current medication regimens throughout the study,
although patients referred for EECP were considered “optimally medically managed.” Angina
severity was assessed using the Canadian Cardiovascular Society classification system.[24]
Angina frequency and sublingual nitroglycerin use were recorded as the number of weekly
episodes or doses averaged over the prior 6-week period. Patients were asked to assess their
current quality of life, health, and satisfaction with quality of life on 5-point Likert scales (1 =
excellent, 2 = very good, 3 = good, 4 = fair, 5 = poor). During the visit for the final EECP session,
data were collected on angina status, medication, quality of life, and adverse clinical events.
Events occurring in the time interval between the first session and 5 days after the last EECP
session were defined as having occurred in the ‘post-EECP’ period. Events occurring after this
but within 1 year of the last EECP session were defined as having occurred in the 1-year followup period. Major adverse cardiac events were defined as death, myocardial infarction, coronary
artery bypass graft surgery, or percutaneous coronary intervention. Patients were interviewed by
telephone at 6 months and 12 months after the final EECP treatment session to record angina
status, quality of life, cardiac and other events.
2 or Fisher exact test was used
Results are presented as percentages or means (± SD). The
to compare categorical data, and the Wilcoxon rank-sum test was used for continuous variables.
A P value of <.05 was considered statistically significant for comparison of groups. Events
occurring up to 12 months (mean 333 days [± 104 days]) from the start of EECP therapy have
been analyzed. Calculations were performed using the SAS (Cary, NC) statistical package.
Results: Baseline Characteristics: Of 1532 patients analyzed, 43% reported a physician
diagnosis of diabetes. At baseline, patients in groups with and without diabetes were
experiencing, on average, 11 angina episodes per week and required 10 to 11 sublingual doses
of nitroglycerin per week. More than 86% of patients in both groups had previous
revascularization procedures (Table 1). Patients with diabetes were more likely to have a history
of heart failure, and a greater proportion of patients with diabetes were considered unsuitable for
repeat revascularization procedures. There was a statistically significant difference between
groups in terms of sex: the group with diabetes had more female patients. In addition, family
history of coronary artery disease (DM vs no diabetes [ND], 80% vs 74%, P < .01), hypertension
(81% vs 63%, P < .001) and noncardiac vascular disease (35% vs 22%, P < .001) were reported
more often in the group with diabetes. Mean (SD) left ventricular ejection fraction was similar in
both groups (46% [14%] vs 47% [14%], P = not significant [NS]), as were the proportions with
left ventricular ejection fraction <35% (19.8% vs 18.7%, P = NS). Angiotensin-converting
enzyme inhibitors (45% vs 33%, P < .001), nitrates (84% vs 78%, P < .01) and angiotensin II
receptor blockers (11% vs 8%, P < .05) were prescribed more often in patients with diabetes.
There were no significant differences in the proportions taking β-blockers (71%), calciumchannel blockers (47% vs 48%), lipid-lowering agents (71% vs 72%), or aspirin (77% vs 76%).
Outcome of Initial Treatment Course: As presented in Table 2, mean (SD) EECP
therapy duration (DM versus ND, 32.3 [10.7] vs 33.2 [9.9] hours, P = NS) and completion rates
(79% vs 82% respectively) were similar in both groups. Reasons for failure to complete a course
of treatment included disruption of treatment due to a medical event or voluntary discontinuation
of treatment by the patient. Skin breakdown (2.0% vs 0.7%, P < .01) and musculoskeletal
complaints (1.5% vs 1.2%, P = NS) were infrequent in both groups. In the post-EECP period,
myocardial infarction and heart failure occurred more often in the DM group than in the ND
group. Post-EECP, angina had decreased by at least 1 Canadian Cardiovascular Society class
in the majority of patients (DM versus ND, 69% vs 72%, P = NS).
Events and Status at 1 Year: One-year follow-up was completed in 86.0% of patients with
diabetes (n = 572) and 89.9% of patients without diabetes (n = 779).
Death and episodes of heart failure occurring in the 1-year period after EECP were reported
more frequently in the DM group. The incidences of unstable angina and repeat
revascularization were similar in both groups (Table 3).
Figure 1 shows the proportion of patients with diabetes and symptoms consistent with Canadian
Cardiovascular Society angina class III and IV at baseline and during follow-up. There was a
statistically significant reduction in angina class (P < .001) from pre- to post-EECP. The most
frequent angina class was reduced from III to II after EECP and improvement was maintained at
1 year after completion of treatment. Episodes of angina and on-demand sublingual nitroglycerin
use were also reduced during the follow-up period (Figure 2). In addition, patients reported
significant improvement in quality of life (QoL), with improvement persisting at 1 year (Figure 3).
The difference between pre- and post-EECP was statistically significant (health related QoL P <
.001, overall QoL P < .001, and satisfaction with QoL P < .001).
Figure 1.
Patients with diabetes with Canadian Cardiovascular Society angina Class III and IV.
(Enlarge
Image)
Figure 2.
Angina frequency and nitroglycerin use in patients with diabetes. NTG, Sublingual
nitroglycerin.
(Enlarge
Image)
Figure 3.
Patients with diabetes reporting good, very good or excellent quality of life. QoL,
Quality of life
(Enlarge
Image)
Discussion
Effect on Angina: This large, prospective, observational study suggests that EECP is safe
and effective in treating angina in patients with diabetes. This effect was maintained in most
patients at 1 year despite a high prevalence of severe symptomatic disease and prior
revascularization, and a high proportion of patients who were considered unsuitable for
additional standard revascularization procedures. Moreover, reduction in angina was achieved
despite more advanced and severe cardiovascular disease in those with DM.
Mechanisms of Action: It has recently been demonstrated that EECP unequivocally and
significantly increases directly measured coronary flow velocity and pressure accompanied by
left ventricular systolic unloading.[27] Objective evidence of improved myocardial perfusion has
been documented in patients after EECP,[17-19,28] and this may be due in part to improved
collateral circulation,[29,30] perhaps secondary to increased transmyocardial pressure gradients
occurring during therapy. Masuda et al have provided indirect evidence of improved collateral
circulation by showing that EECP therapy is associated with improved myocardial perfusion by
positron emission tomography, improved coronary flow reserve and improvement of time to ST
depression during exercise.[18] Improvement in endothelial function was suggested in an early
report showing that duration of EECP therapy correlates positively with levels of nitric oxide, and
negatively with the vasoconstrictor endothelin-I, and that these biochemical changes persist for 3
months.[31] Augmented blood flow and increased shear stresses in the coronary and peripheral
arterial beds could initiate these biochemical changes that could lead to vasodilation and
vascular remodeling.[32] Another recent study has shown improved myocardial perfusion and
improved left ventricular diastolic filling and decreased cardiac work after EECP.[28]
Cardiac Events: Comparison of patients with symptomatic coronary artery disease treated
with EECP to patients treated with elective PCI (National Heart, Lung, and Blood Institute
Dynamic Registry of Coronary Interventions) has recently been reported. [33] This comparison
showed that patients treated with EECP have a higher prevalence of risk factors; and, although
PCI was associated with substantially lower rates of 1-year anginal symptoms, 1-year survival
and major event rates were comparable in both cohorts. Comparison of patients with diabetes
with symptomatic coronary artery disease treated with EECP to patients enrolled in the Dynamic
Registry and the Bypass Angioplasty Revascularization Investigation (BARI) has been explored
(personal communication, Sheryl Kelsey). Initial evaluation reveals that, although patients with
diabetes differ in the 2 registries, there is no evidence that 1-year mortality is increased in
patients with diabetes treated with EECP (Table 4).
Clinical Implications: Many patients have angina despite aggressive medical therapy and
previous revascularization procedures. EECP can extend the range of treatment options for such
patients. Although intracoronary stenting[34] and aggressive antiplatelet therapy[35,36] have
improved immediate outcome and increased coronary patency rates after percutaneous
coronary intervention,[37] the presence of diabetes is usually associated with worse outcomes[24,10-13] even with the application of these advances. The same relationship exists for patients
undergoing coronary artery bypass surgery[6,7,9,13] and repeat revascularization procedures.[14,15]
The noninvasive nature of EECP therapy makes it an attractive alternative for patients with
diabetes, particularly for those who have had previous revascularization procedures. [38]
Limitations: It is possible that some patients have been misclassified with respect to diabetes
status and clinical events. However, this is the first study of its kind and clinical outcome is
reported in a large number of patients. Angina classification is self-reported and therefore it is
likely that there has been some placebo effect, though there is no reason to believe that this
would have been different in groups with and without DM.
Conclusions: This study suggests that in patients with diabetes, EECP is safe, well tolerated
and associated with improvement in angina, functional status and quality of life. Clinical benefit
was maintained in most patients at 1 year. EECP may be useful in select patients with diabetes
with severe cardiovascular disease who are considered unsuitable for further coronary
intervention.[25,26]
Angiology 2001 vol. 52 no. 10: 653-658
Acute Hemodynamic Effects and Angina Improvement with
Enhanced External Counter Pulsation
Tomasz Stys, MD; William E. Lawson, MD; John C. K. Hui, PhD; Gudrun Lang, RN; John
Liuzzo, MD; Peter F. Cohn
Abstract
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 neurohormonal changes, may have a significant role in mediating the observed EECP benefits.
BMC Cardiovascular Disorders 2008, 8:39 doi:10.1186/1471-2261-8-39
Enhanced external counter pulsation in treatment of refractory
angina pectoris: two year outcome and baseline factors
associated with treatment failure
André Erdling1*, Susanne Bondesson1, Thomas Pettersson1 and Lars Edvinsson2
* Corresponding author: André Erdling [email protected]
Author Affiliations
1 Department of Medicine, Centralsjukhuset, SE-291 85 Kristianstad, Sweden
2 Department of Emergency Medicine, Clinical Sciences Lund, Lund University, SE-221 85 Lund,
Sweden
For all author emails, please log on.
BMC Cardiovascular Disorders 2008, 8:39 doi:10.1186/1471-2261-8-39
-------------------------------------------------------------------------------------------------------------Abstract
Background: Enhanced External Counter Pulsation (EECP) is a non-invasive treatment option for
patients with refractory angina pectoris ineligible to further traditional treatment. The aim of this study was
to evaluate the effect of EECP on patients at a Scandinavian medical centre and to investigate if outcome
can be predicted by analysing baseline factors.
Methods: 86 consecutive patients (70 male, 16 female) were treated with EECP and followed for two
years post treatment. Canadian cardiovascular society (CCS) class was analysed, and medication and
adverse clinical events were researched prior to EECP, at the end of the treatment, and at six, 12 and 24
months thereafter. Patients responding to therapy by improving at least one CCS class were compared
with those who failed to respond. Any differences in background factors were recorded and analysed.
Results: 79% of the patients responded to therapy by improving at least one CCS class. In general,
the CCS class improved by one class after EECP treatment (3.05 before versus 2.14 after treatment). A
total of 61.5% of the initial responders showed sustained improvement at the 12 month follow-up while
29% presented sustained improvement after 24 months. Treatment was most effective among patients
suffering from CCS class III-IV angina pectoris, while patients suffering from CCS class II angina pectoris
improved transiently but failed to show sustained improvement after the 12 month follow-up. Diabetes
mellitus and calcium channel antagonists were more common among the non-responders (p < 0.05).
Conclusion: This study confirms the safety and efficiency of EECP as a treatment option for patients
suffering from refractory angina pectoris. The therapy is most beneficial in patients suffering from severe
angina (CCS III-IV) while sustained response to therapy could not be verified among patients suffering
from CCS class II angina pectoris.
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Background:
Stable angina pectoris is a common and sometimes disabling disorder characterized by chest
pain due to ischemia of the myocardium, generally caused by obstruction or spasm of the
coronary arteries. Atherosclerosis of coronary vessels is the main cause of angina pectoris while
coronary artery spasm is seen in a minor number of angina pectoris patients. Other causes such
as connective tissue disorders, valvular disease and arrhythmia are even less common.
Prevalence of angina pectoris increases with age in both males and females. It has been
estimated that 2–4% of the adult European population is affected by angina pectoris [1]. This
number is likely to increase further since life expectancy continues to improve worldwide.
Treatment of angina pectoris is traditionally aimed at reduction of symptoms as well as
prevention of future cardiac events such as myocardial infarction or death. Pharmacological
agents such as nitrates, aspirin, beta-adrenoreceptor antagonists and calcium channel blockers
are used [2] as well as surgical therapies aimed at restoring blood flow, e.g. coronary artery
bypass graft (CABG) or percutaneous coronary intervention (PCI) [3]. As many as 15% of the
patients either fail to respond fully to therapy as described above or are ineligible to further
intervention, thus said to suffer from refractory angina pectoris [4]. These patients suffer from
marked limitation of everyday physical activity due to their pain, which in some cases are more
or less constant. In the last few years, the lack of efficient therapy for refractory angina pectoris
in combination with increased survival rates after myocardial infarction and an ageing population
has caused increased need for new therapeutic methods. Intense research has yielded methods
such as laser revascularization, left stellate ganglion blockade, spinal cord stimulation (SCS) and
enhanced external counterpulsation (EECP)[3].
EECP is a non-invasive method used to treat patients with refractory angina pectoris, ineligible
to further pharmacological or surgical intervention. Pneumatic cuffs are applied to the lower
limbs and set to inflate sequentially during diastole and deflate before the onset of systole. This
causes an increased diastolic pressure resulting in augmented coronary blood flow [5] as well as
increased venous return [6] and improved cardiac output [7]. The systolic blood pressure is
lowered due to deflation before systole, thereby decreasing afterload and preventing heart
failure and pulmonary oedema [8].
The aim of the current study was to assess the two-year outcome of EECP treatment of
refractory angina pectoris and to determine whether the response to treatment can be predicted
by analysis of baseline factors.
Methods:
Patients: A total of 86 consecutive patients (70 male, 16 female) were treated with EECP and
followed for two years after completion of treatment.
Referral, treatment and follow-ups were conducted at the Central hospital in Kristianstad in
southern Sweden. All patients had angiographically verified significant stenosis in at least one
major coronary artery. Patients were considered at optimal pharmacological treatment and
unsuitable for further revascularization by the time of referral as evaluated by a board of
cardiologists and thoracic surgeons at the Lund University hospital. Anginal status, medical
history, glyceryl trinitrate (GTN) consumption and demographics were obtained at baseline with
follow-up immediately after treatment, at 6, 12 and 24 months after therapy. Pharmacological
treatment was adjusted whenever the need for adjustments arose.
Patients were divided into two groups depending on response to therapy. Those who improved
at least one Canadian cardiovascular society (CCS) class after treatment were considered
responders whereas those who failed to respond to therapy were considered non-responders at
the immediate follow-up. Baseline factors (Table 1) were compared between the two groups in
an attempt to find factors predisposing patients to treatment failure. Patients had a long history
of coronary artery disease (mean duration 11.5 years) and risk factors for arteriosclerosis were
common. Most patients had suffered from one or more acute myocardial infarctions, most of
which had been treated with either PCI or CABG.
Table 1. Baseline characteristics
Informed written consent was obtained from all patients included in the study. The study was
conducted in accordance with the declaration of Helsinki and ethical guidelines determined by
the ethics council at Lund University. Patients who were forced to leave the follow-up due to the
need of a new course of treatment were considered to have fallen back to the same CCS class
as at referral.
EECP:
The EECP device consists of three paired pneumatic cuffs applied to the calves, thighs and
buttocks (Vasomedical, Westbury, New York, USA). The cuffs are inflated sequentially, applying
250 – 300 mmHg of external pressure during diastole, causing the return of blood from the legs
to the central circulation and producing aortic diastolic augmentation thus increasing both
venous return and cardiac output. The cuffs are then rapidly deflated at the end of the diastole
(thereby) reducing peripheral resistance and cardiac afterload. Treatment was given as 35 onehour sessions administered five days a week for seven consecutive weeks.
Statistics and calculations:
All calculations and statistics were performed using GraphpadPrism 4.0. Descriptive data are
presented as mean and standard error of the mean (SEM) or median and range depending on
whether the material is normally distributed or not. Statistical significance was assumed when p
< 0.05. Student's t-test was used when comparing two groups and Fisher's exact test or the chi2-test was used when comparing baseline factors between responders and non-responders.
AVOVA with Dunn's post hoc test was used when comparing more than two groups. The risk for
mass significance was not taken into consideration when analysing the results.
Results:
Response to therapy: Response to therapy, defined as improvement by at least one CCS
class, was seen in 79% of the patients. Among the responders, 13% improved two CCS classes
or more. Failure to respond to therapy occurred in 21% of the patients. Two patients among the
non-responders had improved their CCS class at the 6 months follow-up in spite of failure to
respond immediately after therapy.
During follow-up, sustained response to therapy was seen for at least 12 months among 61.5%
of the responding patients, while 29% of the patients maintained a response to therapy for at
least 24 months (p < 0.001 and < 0.01 vs. pre-treatment, figure 1). Patients in CCS class III and
IV at referral maintained response to therapy for at least 24 months in 22.4% and 70% of the
cases, respectively. Patients in CCS class II at referral showed initial response to therapy, but
failed to maintain the reduction in anginal status for 24 months (figure 2).
Figure 1. Overall changes in CCS class before EECP, after EECP and during follow-up. The figure shows
marked reduction in the number of patients suffering from severe angina pectoris after treatment and
during the follow-up period.
Figure 2. Changes in CCS class over time. The figure shows CCS class distribution over time, subdivided
into groups depending on CCS class at referral. A = CCS II, B = CCS III and C = CCS IV at referral.
The CCS class improved by, in general, one class after EECP treatment (3.05 before versus
2.14 after treatment).
Weekly GTN usage was reduced in 64% of the patients (p < 0.001, Table 2) and none of the
patients had to increase their use of short acting nitrates after completing EECP therapy.
Table 2. GTN usage before and after treatment
Anginal status did not worsen in any of the patients after EECP treatment.
Adverse events:
Eight patients suffered from adverse events during the EECP therapy and had to terminate their
treatment prematurely, including 2 patients who died due to myocardial infarction (Table 3).
These patients were excluded from the follow-up investigations. A total of 13 patients had to
abort their participation in the follow-up (Table 4). Ten of them left due to recurring angina
pectoris in need of further EECP treatment. These patients are included in the study, but
calculations were adjusted as if they relapsed to pre-EECP CCS class at the time of abortion.
One patient left the follow-up program satisfied with his current anginal status and did not wish to
participate in further evaluation. Three patients died during the follow-up. The cause of death
remains unknown in the first case while the second patient died from cardiac faliure and the third
patient from end-stage amyloidosis.
Table 3. Adverse events during treatment
Table 4. Adverse events during follow-up
Analysis of background factors:
Diabetes mellitus, use of calcium channel blockers and use of oral antidiabetic agents were each
more common among non-responders than among those responding to therapy (p < 0.05, p <
0.05 and p < 0.01, respectively, Table 1). The other baseline factors studied did not affect the
outcome of EECP treatment (Table 1).
Smoking and previous myocardial infarction were more common among patients that were
forced to withdraw from the follow-up due to recurring angina pectoris (both p < 0.05).
Discussion:
The present study is a follow-up study performed on the results of EECP treatment of patients
with refractory angina pectoris at a major Scandinavian medical centre for EECP. A majority of
the patients were men suffering from long time extensive coronary artery disease refractory to
further medical or surgical therapy. This study confirms the safety and efficiency of EECP as a
method for reducing CCS class scores in patients with refractory angina pectoris. The reduction
in anginal symptoms lasted for up to two years. These results are in accordance with similar
studies of long term benefit performed at American medical centres [9-11]. Five patients died
during the study, three patients during the follow-up and two during the actual treatment. This is
well within what can be expected in this group of patients with end stage coronary artery
disease. The overall mortality among a similar set of patients receiving SCS has been shown to
be 7–8%, the majority due to cardiac death [12]. Studies where other modes of treatment for
refractory angina pectoris have been used report an annual in-treatment mortality of 5–17% [13]
The exact mechanism by which EECP exerts its effect on the cardiovascular system is not fully
known. The immediate benefits are similar to those provided by the intra-aortic balloon pump,
namely increased blood flow through coronary vessels during diastole and decreased afterload
during systole [5]. EECP has been shown to be more efficient than intra-aortic balloon pumping
in increasing venous return and enhancing cardiac output [6].
Long term effects of EECP treatment are thought to be mediated through shear stress on the
vascular endothelium, which in turn triggers angiogenesis and improves vascular endothelial
function [14] due to modulated release of vasoactive substances such as endothelin [15], nitric
oxide [15] and vascular endothelial growth factor [16]. Improvement in oxygen uptake after
treatment with EECP implies alterations in cellular metabolism as well as hemodynamic
improvement [16,17]. EECP has been shown to extend time until exercise-induced ischemia
occurs [18]. This may be caused by lowered oxygen demand due to lowered left ventricular
afterload and optimization of aortic augmenting index [19]. Relief in myocardial ischemia as well
as improved quality of life has been shown in a number of studies [20,21]
Improvement in quality of life may at least in part be due to a placebo effect as described by
Springer et al [15], but since the current patients suffer from end stage coronary artery disease,
are incapacitated and without conventional treatment options, any additional treatment that
relieves their pain without adverse effect on their condition is worth taking into consideration.
Available, data suggest that EECP improves coronary and systemic perfusion by enhancing
function of the vascular endothelium, by favouring angiogenesis and reducing oxygen
consumption.
The results from the present study indicate that the outcome of EECP treatment depends on
CCS class at referral ("the worse the better"), and negatively on the presence of diabetes
mellitus and calcium channel blockers. CCS class II at referral and diabetes [22,23], have
previously been described as predisposing to treatment failure. Further studies have to be
conducted in order to determine the exact mechanism by which they impair the therapeutic
effect of EECP. A possible explanation can however be hypothesized when it comes to calcium
channel blockers. Calcium channel blockers act as vasodilators reducing total peripheral
resistance. A patient under the influence of calcium channel blockers might fail to mount further
vasodilatation, thereby reducing or obliterating the peripheral effect of EECP treatment since
dilated blood vessels suffer from less shear stress than occluded ones. Thus, the treatment may
be more effective in patients with severe vascular narrowing.
The duration of sustained improvement might be impaired by smoking as seen among those
patients who had to cancel their follow-up due to recurring angina pectoris. The explanation
could be local effect on the vascular endothelium since tobacco smoking is known to cause
endothelial dysfunction [24,25], thereby negating the beneficial effects of shear stress and
release of vasoactive factors in the long run.
The present study confirms previous results that EECP is a safe and efficient method to alleviate
the symptoms in severe refractory angina. The effects on long time mortality are however yet to
be determined. Further studies on background factors associated with reduced response to
EECP are needed to confirm the findings presented in this study.
Limitation of the study:
This follow-up report does not include a control group, making the placebo effect a possible
confounding factor. The obvious effect of EECP could therefore, at least in part, be the result of
increased attention to the patients during treatment and follow-up. Evidence from this and
previous studies suggest that EECP treatment is effective in limiting symptoms of severe angina
pectoris. No such conclusions can be made of the effect on mortality. Small differences in
background factors can be difficult to detect in a material of this size. The possibility of mass
significance in the analysis of background factors associated with treatment failure cannot be
ruled out since multiple statistical analyses has been performed on the same material. This has
to be taken into consideration while evaluating the results of this study. In the results section,
some data (average CCS class) is presented as mean when it is ordinal rather than continuous.
This is a common approach in biomedical literature, but should be pointed out.
Conclusion:
This study confirms the safety and efficiency of EECP as a treatment option for patients suffering
from severe angina pectoris refractory to further pharmacological or surgical intervention.
Therapy is most beneficial for those in CCS class III and IV who demonstrated a sustained
improvement at the two year follow-up. No such long term response to therapy could be verified
among patients with CCS class II angina pectoris at referral. Diabetes mellitus and calcium
channel blockers were each significantly more common among patients who failed to respond to
EECP. Tobacco use and previous myocardial infarction were associated with early relapse in
angina in spite of an initial response.
Competing interests: The authors declare that they have no competing interests.
Authors' contributions: TP was responsible for the treatment of the patients and was
involved in initiating and designing the study. SB collected most of the data. AE was involved in
analyzing the data and writing the manuscript. LE supervised the writing of the final manuscript.
All authors have read and approved the final manuscript.
Acknowledgements: This study has received support by the Swedish Medical Research
Council (grant 5958), and the Swedish Heart Lung Foundation.
References:
1. Fox K et al: Guidelines on the management of stable angina pectoris: executive
summary: the Task Force on the Management of Stable Angina Pectoris of the
European Society of Cardiology. Eur Heart J 2006, 27:1341-1381.
2. Thadani U: Current medical management of chronic stable angina. J Cardiovasc
Pharmacol Ther 2004, 9 Suppl 1:S11-S29.
3. Kim MC, Kini A, Sharma SK: Refractory angina pectoris: mechanism and
therapeutic options. J Am Coll Cardiol 2002, 39:923-34.
4. Mannheimer C et al: The problem of chronic refractory angina; report from the ESC
Joint Study Group on the Treatment of Refractory Angina. Eur Heart J 2002,
23:355-370.
5. Michaels AD et al: Left ventricular systolic unloading and augmention of
intracoronary pressure and doppler flow during enhanced external
counterpulsation.Circulation 2002, 106:1237-1242.
6. Taguchi I et al: Comparison of hemodynamic effects of enhanced external
counterpulsation and intra-aortic balloon pumping in patients with acute myocardial
infarction. Am J Cardiol 2000, 86(10):1139-1141.
7. Barsness GW: Enhanced external counterpulsation in unrevascularizable patients.
Curr Interv Cardiol Rep 2001, 3:37-43.
8. Suresh K et al: Maximizing the hemodynamic benefit of enhanced external
counterpulsation. Clin Cardiol 1998, 21:649-653.
9. Arora RR et al: The multicenter study of enhanced external counterpulsation
(MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and
anginal episodes. J Am Coll Cardiol 1999, 33:1833-1840.
10. Michaels AD et al: Two-year outcomes after enhanced external counterpulsation
for stable angina pectoris (from the International EECP Patient Registry [IEPR]).
Am J Cardiol 2004, 93:461-464.
11. Lawson WE et al: Long term prognosis of patients with angina treated with
enhanced external counterpulsation: five-year follow-up study. Clin Cardiol 2000,
23:254-258.
12. TenVaarwerk IAM et al: Clinical outcome of patients treated with spinal cord
stimulation for therapeutically refractory angina pectoris. Heart 1999, 82:82-88.
13. Loh PH et al: The immediate and long-term outcome of enhanced external
counterpulsation in treatment of chronic stable refractory angina. J Intern Med
2006, 259:276-284.
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in patients with symptomatic coronary artery disease. J Am Coll Cardiol 2003,
41:1761-1768.
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endothelin-1 levels. Am J Cardiol 2006, 98:28-30.
16. Kersten JR et al: Multifactorial basis for coronary collateralization: a complex
adaptive response to ischemia. Cardiovasc Res 1999, 43:44-57.
17. Arora RR, Lopez S, Saric M: Enhanced external counterpulsation improves systolic
function by echocardiography in patients with coronary artery disease. Heart Lung
2005, 34:122-125.
18. Ochoa AB et al: Effect of enhanced external counterpulsation on resting oxygen
uptake in patients having previous coronary revascularization and in healthy
volunteers. Am J Cardiol 2006, 98:613-615.
19. Nichols WW et al: Enhanced external counterpulsation treatment improves arterial
wall properties and wave reflection characteristics in patients with refractory
angina. J Am Coll Cardiol 2006, 48:1208-1214.
20. Arora RR et al: Effects of enhanced external conterpulsation on Health-Related
Quality of Life continue 12 months after treatment: a substudy of the Multicenter
Study of Enhanced External Counterpulsation. J Investig Med 2002, 50:25-35.
21. Springer S et al: Psychosocial effects of enhanced external counterpulsation in the
angina patient: a second study. Psychosomatics 2001, 42:124-132.
22. Lawson WE et al: Analysis of baseline factors associated with reduction in chest
pain in patients with angina pectoris treated by enhanced external
counterpulsation. Am J Cardiol 2003, 92:439-443.
23. Lawson WE et al: Predictors of benefit in angina patients one year after completing
enhanced external counterpulsation: initial responders to treatment versus
nonresponders. Cardiology 2005, 103:201-206.
24. Mazzone A et al: Cigarette smoking and hypertension influence nitric oxide release
and plasma levels of adhesion molecules. Clin Chem Lab Med 2001, 39:822-826.
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J Am Coll Cardiol, 2007; 50:1523-1531
© 2007 by the American College of Cardiology Foundation
STATE-OF-THE-ART PAPER
Enhanced External Counterpulsation and Future Directions
Step Beyond Medical Management for Patients With Angina
and Heart Failure
Aarush Manchanda, MD* and Ozlem Soran, MD, MPH, FACC, FESC ,1,*
Department of Internal Medicine, The George Washington University, Washington, DC
Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
*
Manuscript received April 2, 2007; revised manuscript received May 25, 2007, accepted July 17, 2007.
Reprint requests and correspondence: Dr. Ozlem Soran, University of Pittsburgh Cardiovascular Institute, 200
Lothrop Street, UPMC, Presbyterian Hospital, F-748, Pittsburgh, Pennsylvania 15213. (Email: [email protected]
*
Abbreviations and Acronyms
CAD = coronary artery disease;
cGMP = cyclic guanosine Monophosphate
EECP = Enhanced External Counter
Pulsation
EF = Ejection Fraction
HF = Heart Failure
LVD = Left Ventricular Dysfunction
NYHA = New York Heart Association
RAP = Refractory Angina Pectoris
Abstract
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 $50 billion per year. The technique of
counterpulsation, studied for almost one-half century now, is considered a safe, highly beneficial,
low-cost, non-invasive treatment for these angina patients, and now for heart failure patients as
well. Recent evidence suggests that enhanced external counterpulsation (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 (VO 2), 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. This review
summarizes the current evidence for its use in stable angina and heart failure and its future
directions.
An estimated 6.4 million patients in the U.S. suffer from symptomatic coronary artery disease
(CAD), and about 400,000 new cases develop each year (1). Despite optimal medical therapy
and invasive procedures, such as angioplasty and cardiac bypass surgery, there are an
estimated 300,000 to 900,000 patients in the U.S. who have refractory angina pectoris (RAP).
About 25,000 to 75,000 new cases of RAP are diagnosed each year (1).
Daily tasks such as climbing a flight of stairs, walking a dog, or mowing the lawn become
impossible without experiencing chest pain for these difficult-to-treat patients. In addition, despite
advances in medical therapy for the treatment of heart failure (HF) over the past decade,
substantial unmet needs remain, particularly in patients with moderate to severe HF. Heart
failure is the number 1 diagnosis in Medicare patients and approximately 5 million Americans
experience HF, with 550,000 new cases per year reported (1). It has been estimated that in
2005, the total direct and indirect cost of HF in the U.S. will be equal to $27.9 billion, and
approximately $2.9 billion annually is spent on drugs for the treatment of HF (1). Only a few
consensus therapies exist to treat HF beyond medical management, and many patients now are
left to suffer their symptoms and restrict their activities chronically, and anticipate a reduced life
expectancy.
Current nonpharmacological options available for these patients with RAP with or without
underlying HF include neurostimulation (transcutaneous electrical nerve stimulation and spinal
cord stimulation), enhanced external counterpulsation (EECP) therapy, laser revascularization
techniques, gene therapy, and newer interventional procedures such as percutaneous in situ
coronary venous arterialization or percutaneous in situ coronary artery bypass (2). Of these
modalities, EECP therapy represents the only truly noninvasive technique for which both a
reduction of angina symptoms, improvement in objective measures of myocardial ischemia, and
improvement in left ventricular function (both systolic and diastolic) have been shown (3–5). This
review summarizes the current evidence for the use of EECP therapy in stable angina and HF
and its future directions.
Historical Perspective
Almost one-half century ago, researchers at Harvard University conducted experiments with
counterpulsation showing that this technique markedly reduces the workload, and thus oxygen
consumption, of the left ventricle. In 1953, Kantrowitz and Kantrowitz (6) described diastolic
augmentation as a means of improving coronary blood flow. Birtwell et al. (7) did pioneering
work toward the development of this technique and were first to apply this concept by developing
the initial arterial counterpulsator in the U.S. Zheng et al. (8) were the first to report the benefits
of external counterpulsation in the 1980s by using the first pneumatic counterpulsation device.
Lawson et al. (9–13) at the State University of New York, Stony Brook, undertook a number of
open-label studies with the enhanced system, EECP, between 1989 and 1998 using both
objective and subjective end points. These studies, although open and nonrandomized, showed
statistical improvement in exercise tolerance by patients as evidenced by thallium-stress testing
and partial or complete resolution of coronary perfusion defects as evidenced by radionuclide
imaging studies. In 1999, Arora et al. (14) reported results of the first double-blind randomized
placebo-controlled multicenter trial (MUST-EECP [Multicenter Study of Enhanced External
Counterpulsation]) (14). Since then, EECP therapy has emerged as an effective, noninvasive,
and durable therapeutic option for patients not only with angina but also with HF.
Technique
The technique of EECP therapy consists of electrocardiogram-gated rapid, sequential
compression of the lower extremities taking place during diastole, followed by simultaneous
decompression during systole. These actions produce hemodynamic effects similar to those of
an intraaortic balloon pump, but unlike an intra-aortic balloon pump, EECP therapy also
increases venous return (Fig. 1).
Figure 1 Technique of EECP
Three pairs of pneumatic cuffs are applied to the calves,
lower thighs, and upper thighs. The cuffs are inflated
sequentially during diastole, distal to proximal. The
compression of the lower-extremity vascular bed increases
diastolic pressure and flow and increases venous return. The
View larger version (14K): pressure is then released at the onset of systole. Inflation and
[in this window]
deflation are timed according to the R-wave on the patient’s
[in a new window]
cardiac monitor. The pressures applied and the inflation–
deflation timing can be altered by using the pressure
[Download PPT slide]
waveforms and electrocardiogram on the enhanced external
counterpulsation (EECP) therapy monitor.
Cuffs resembling oversized blood pressure cuffs—on the calves, the lower thighs, and the upper
thighs, including the buttocks, inflate rapidly and sequentially—via computer-interpreted
electrocardiogram signals—starting from the calves and proceeding upward to the buttocks (Fig.
1) during the resting phase of each heartbeat (diastole). This has the effect of creating a strong
retrograde counterpulse in the arterial system, forcing freshly oxygenated blood toward the heart
and coronary arteries, while simultaneously increasing the volume of venous blood return to the
heart under increased pressure.
Just before the next heartbeat, before the systole, all 3 cuffs simultaneously deflate, significantly
reducing the workload of the heart. This is achieved because the vascular beds in the lower
extremities are relatively empty when the cuffs are deflated, significantly lowering the resistance
to blood ejected by the heart, reducing the amount of work the heart must do to pump
oxygenated blood to the rest of the body. The inflation-deflation activity is monitored with the
help of a finger plethysmogram and coordinated by a microprocessor that interprets
electrocardiogram signals from the patient’s heart and actuates the inflation and deflation cycles.
The end result of this sequential squeezing of the legs is to create a pressure wave that
significantly increases peak diastolic pressure, benefiting circulation to the heart muscle and
other organs, while also reducing systolic pressure and systemic vascular resistance to the
general benefit of the vascular system. A typical treatment course consists of 35 outpatient
treatments administered as 1 h per day over 7 weeks.
Mechanism of Action of EECP
Recent advances in the understanding of coronary arterial physiology and response to EECP
therapy have provided some insight into possible modes of effect and an explanation for the
benefits seen with EECP therapy (Fig. 2.) However, most of the experience is from small animal
or human uncontrolled studies, and the mechanism of the sustained antianginal benefit with
EECP remains unclear.
Development of new functional collateral vessels by increasing nitric oxide and decreasing
endothelin-1 levels to the ischemic myocardium was postulated as the mechanism of action for
EECP therapy by many early studies conducted. Masuda et al. (15) reported that the
development of functional collateral vessels is one of the mechanisms of EECP therapy using
ammonia positron emission tomography. Endothelial shear stress from increased diastolic
augmentation after EECP therapy was shown to augment endothelium-derived relaxing
factor/nitric oxide production (16) and to cause down-regulation of endothelin-1 levels, thereby
recruiting more collateral vessels (17). Akhtar et al. (18) recently showed that EECP therapy has
a sustained, dose-related effect in stimulating endothelial cell production of the vasodilator nitric
oxide and in decreasing production of endothelin-1. However, an increase in myocardial
perfusion on nuclear stress tests was inconsistent with improvement in symptoms (Table 1),
making it unlikely as a sole mechanism of benefit.
In recent studies by Tao et al. (19,20), EECP therapy demonstrated stabilization of coronary
endothelium, an effect very similar to that of athletic training. These recent studies confirm the
earlier results by Bonetti et al. (21); they had seen improvement in the peripheral endothelial
function (RH-PAT) in their patients after 35 h of EECP treatment. Zhang et al. (22) also showed
retardation of the atherosclerosis process by the metabolic effects of external counterpulsation
therapy on the NF-kappa signaling pathways. Recently Levenson et al. (23) postulated that an
increase in cyclic guanosine monophosphate (cGMP) acutely after EECP therapy might in part
be responsible for the improved peripheral arterial function. Cyclic guanosine monophosphate
regulates vascular smooth muscle tone, which may improve arterial function. Fifty-five subjects
were randomized into 2 groups to receive either sham (control) or active EECP therapy during 1
h. Plasma and platelet cGMP were measured immediately before and after EECP therapy by
radioimmunoassay. One hour of EECP therapy increased cGMP plasma concentration by 52%
and platelet content by 19%. This theory of endothelial stabilization has attracted the most
attention in the recent past as one of the primary mechanisms of action, with more clinical trials
needed to further understand it completely.
Arora et al. (24) showed a trend toward increased vascular endothelial growth factor levels after
EECP therapy in human subjects, thereby confirming the findings of Chen et al. (25) in the
canine model. Vascular endothelial growth factor, along with other growth factors such as
fibroblast growth factor, is the most widely studied in gene therapy for RAP. It is considered
important in promoting angiogenesis or neorevascularization of the ischemic myocardium.
However, failure to show consistent improvement in myocardial perfusion as discussed above
makes neorevascularization unlikely, an argument similar to the one against collateralization.
Ochoa et al. (26) recently reported the acute effects of EECP therapy on oxygen uptake: VO 2 at
rest in adults with symptomatic CAD compared with healthy volunteers using sham control
group. They measured VO 2 continuously in 20 adults during a single treatment session of EECP
therapy, including 10 subjects with previous coronary revascularization who were referred for
EECP therapy for refractory angina and 10 healthy, sedentary volunteers. Both groups showed a
small, sustained increase in VO 2 during EECP treatment. Because VO 2 is an independent
predictor of increased exercise capacity, it led them to conclude that increase in VO 2 may also in
part be one of the mechanisms by which EECP therapy increases exercise tolerance in stable
angina patients (26).
In summary, further studies are needed to elucidate both the mechanism of action and the
overall effects of EECP therapy, or a combination of the above mechanisms may explain the
sustained benefit from EECP therapy in the clinical trials (27).
EECP and Angina
Several nonrandomized and randomized trials have shown a consistently positive clinical
response among patients of RAP treated with EECP therapy (Table 1) (8–14,28–39). Benefits
associated with EECP therapy 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 (Table 1). Patients with severely disabling angina at baseline and
those without a history of smoking are more likely to improve their angina class after EECP
therapy (40).
Most of the studies on EECP therapy cannot be double-blind and lack good control groups
because of technical limitations, which have frequently raised questions of operator bias in the
past. But the MUST-EECP study, a randomized, double-blind, sham-controlled trial, also showed
the clinical benefit of EECP therapy in patients with chronic stable angina and positive exercise
stress tests (14). In this study, 139 patients (mean age 63 years, range 35 years to 81 years)
with angina pectoris (typical Canadian Cardiovascular Society classes I, II, and III angina) and
documented coronary ischemia were equally randomized to hemodynamically inactive
counterpulsation with EECP versus active counterpulsation. Patients in the active EECP therapy
group showed a statistically significant increase in time to exercise-induced ST-segment
depression when compared with sham and baseline, and reported a statistically significant
decrease in the frequency of angina episodes when compared with sham and baseline. Exercise
duration increased significantly in both groups; however, the increase was greater in the active
EECP group. Moreover, a MUST-EECP substudy showed a significant improvement in qualityof-life parameters in patients assigned to active treatment, which was sustained during a 12month follow-up period (41).
Results from the International EECP Patient Registry (31,33,35) and the EECP Clinical
Consortium (28) have shown that the symptomatic benefit observed in controlled studies also
translates to the heterogeneous patient population seen in clinical practice. Moreover, follow-up
data indicate that the clinical benefit may be maintained for up to 5 years in patients with a
favorable initial clinical response (27,35). One of the ongoing debates with most of the published
trials discussed earlier (Table 1) is that the increased exercise tolerance reported after EECP
therapy may, at least in part, be attributed to a training effect.
EECP in Angina With Left Ventricular Dysfunction
When providing EECP therapy to the HF population, the primary concern of the initial
researchers was that the increased venous return resulting from EECP therapy could precipitate
pulmonary edema in angina patients with severe left ventricular dysfunction (LVD). Soran et al.
(42,43) evaluated the safety and efficacy of EECP therapy in patients with angina and severe
LVD (ejection fraction [EF] <35%). The outcomes of EECP treatment were followed up in 363
patients enrolled in the International EECP Patient Registry, an international multicenter study of
EECP therapy for the treatment of patients with chronic angina. The EECP therapy was
observed to be a safe and effective treatment of angina in patients with severe LVD who were
not considered good candidates for revascularization by coronary artery bypass graft or
percutaneous coronary intervention (43). After completion of treatment, there was a significant
reduction in severity of angina: 72% improved from severe angina to no angina or mild angina.
Fifty-two percent of patients discontinued nitroglycerin use. Quality of life showed a significant
increase. At 2-year follow-up, this angina reduction was maintained in 55%, 83% survived, and
event-free (death/myocardial infarction/percutaneous coronary intervention/coronary artery
bypass graft) survival rate was 70%. Forty-three percent had no cardiac hospitalization; 81% had
no congestive HF event (43).
Lawson et al. (44) also evaluated RAP patients with preserved left ventricular function (EF
>35%) and with severe left ventricular dysfunction (EF 35%) who were treated with a 35-h
course of EECP therapy. Bioimpedance measurements of cardiovascular function were obtained
before the first and again after the 35th hour of EECP therapy. Twenty-five patients were
enrolled, 20 with preserved left ventricular function and 5 with severe left ventricular dysfunction.
Angina class improved similarly in both groups. The severe left ventricular dysfunction group, in
contrast to the preserved left ventricular function group, increased cardiac power, stroke volume,
and cardiac index and decreased systemic vascular resistance with treatment. This study
suggests that EECP could benefit patients experiencing CAD with severe left ventricular
dysfunction directly by improving cardiac power and indirectly by decreasing systemic vascular
resistance (44).
EECP Therapy in HF
Most of the data to date on the efficacy and safety of EECP therapy in HF are from small studies
(45,46). In a pilot study of clinically stable patients diagnosed with mild to moderate HF (New
York Heart Association [NYHA] functional class II or III) and a left ventricular EF <35%, Soran et
al. (45) found EECP treatment to be safe with no unexpected adverse events during the
application of EECP treatment. Soran et al. (45) also conducted a multicenter feasibility study in
which stable HF (New York Heart Association functional class II to III, ischemic and nonischemic
etiology) patients with left ventricular EF <35% were treated with 35 1-h sessions of EECP
therapy over a 7-week period and followed up over a 6-month period. The mean EF for the
ischemic and nonischemic groups was 25.6 ± 7.1% and 18.7 ± 7.4%, respectively. Mild to
moderate valvular heart disease was the most common etiology for the group with nonischemic
etiology. Study results showed that EECP therapy was safe and well-tolerated in this group of
patients (46). In addition, EECP therapy was associated with significant improvements in
exercise capacity as measured by peak oxygen uptake and exercise duration and in quality of
life at 1 week and 6 months after EECP treatment. Although safety was the primary end point of
this feasibility study, the efficacy results suggest that EECP therapy can increase peak oxygen
uptake, improve exercise capacity and functional status, as well as improve the patient’s quality
of life, for both the short term and long term (6 months) after the completion of EECP therapy.
Although study subjects benefited from EECP therapy to a similar degree regardless of ischemic
or nonischemic etiology of their HF, because of a small number of patients in the nonischemic
group, further studies need to be conducted to evaluate the effectiveness of EECP in patients
with a nonischemic etiology (46).
Based on these results, a larger, controlled study of EECP therapy in patients with stable HF
(NYHA functional classes II and III) and LVD was undertaken called the PEECH (Prospective
Evaluation of EECP in Heart Failure) trial (47), results of which were recently published. It was a
controlled, randomized, single-blind, parallel-group, multicenter study of 187 patients with
symptomatic but stable HF (NYHA functional classes II and III, ischemic and nonischemic
etiology) and a left ventricular EF 35% was designed to assess the efficacy of EECP therapy in
patients with stable HF. Medical therapy is optimized in all patients based on the
recommendations of the Heart Failure Society of America (usual care), and then randomized
between 2 treatment groups, usual care or EECP therapy (35 h over 7 weeks). The EECP
therapy improved exercise tolerance, quality of life, and NYHA functional class without an
accompanying increase in peak VO 2. Investigators also assessed whether differences existed in
response to EECP therapy in patients with HF secondary to either ischemic or nonischemic
dilated cardiomyopathy. Albeit in a relatively small sample size, subgroup analysis based on
etiology of disease showed benefit in patients with ischemic cardiomyopathy, whereas this
difference was not seen in the small number of patients with nonischemic disease. Because
patients were not blinded to therapy, these benefits of EECP therapy may be attributable to a
placebo effect. However, the usefulness of EECP therapy by physicians must be individualized
based on their assessment of the totality of EECP therapy data. Further studies may help
elucidate both the mechanism of action and the overall effects of EECP therapy.
Limitations of the Technique
It is important to point out that EECP therapy is not for everyone. This noninvasive outpatient
procedure can be somewhat uncomfortable for patients because of the high-pressure sequential
compression of the cuffs. It is not recommended for certain types of valvular heart disease
(especially aortic insufficiency), or for those with recent cardiac catheterization, an irregular heart
rhythm, severe hypertension, significant blockages in the leg arteries, or a history of deep
venous thrombosis (Table 2). For anyone else, however, the procedure seems to be quite safe.
Future Directions and Conclusions
Throughout the world, EECP therapy has been studied for various potential uses other than
heart disease (48–53) (Table 3). Its role in improving endothelial function might be beneficial in
the treatment of patients with Cardiac Syndrome X, which is marked by severe chest pain
caused by myocardial dysfunction, often without detectable atherosclerosis. Mayo Clinic
investigators have reported successful treatment of Cardiac Syndrome X with severely
symptomatic coronary endothelial dysfunction in the absence of obstructive CAD with standard
35-h course of EECP therapy (54). However, it is important to realize that EECP therapy is an
option for patients with angina refractory to medical treatment who are not candidates for
interventional or surgical revascularization. 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) (55). 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 (56). Enhanced external
counterpulsation 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.
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improving athletic performance Paper presented at: Experimental Biology 2004 2004April 17–21,
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Enhanced external counterpulsation as a new treatment modality for patients with erectile dysfunction
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Circulation. 2002 Sep 3;106(10):1237-1242.
EECP Therapy Clinical Studies
The publications listed below will provide you a great start to learning about the benefits, mechanisms of
action, and long-term outcomes of ECP therapy.
Key Mechanisms of Action:
Hemodynamic Effects of EECP
Therapy
Left Ventricular Systolic Unloading and Augmentation
of Intracoronary Pressure and Doppler Flow During
Enhanced External Counterpulsation.
Michaels AD, Accad M, Ports TA, Grossman W.
Circulation. 2002 Sep 3;106(10):1237-1242.
Summary: 10 patients underwent left heart
catheterization significantly increasing their coronary diastolic pressure (93%), decreasing systolic
pressure (15%) and their peak coronary flow velocity increased by 109% as measured by intracoronary
Doppler ultrasound during EECP therapy when compared with baseline.
J Am Coll Cardiol 2003 May 21;41(10):1761-1768
Endothelial Cell Function
Enhanced External Counterpulsation Improves Endothelial
Function in Patients with Symptomatic Coronary Artery
Disease.
Bonetti PO, Barsness GW, Keelan PC, Schnell TI, Pumper GM, Kuvin JT, Schnall RP, Holmes DR,
Higano ST, Lerman A.
Journal of the American College of Cardiology. 2003 May 21;41(10):1761-1768.
Summary: 17 (74%) of the 23 patients with refractory angina improved at least 1 symptomatic Canadian
Cardiovascular Society class with a significant increase in their endothelial function as measured by
reactive hyperemia-peripheral arterial tonometry (RH-PAT) index which occurred after 1 hour of EECP
treatment and remained high at 1-month follow-up.
J Am Coll Cardiol. 2006 Sep 19; 48(6):1209-1215.
Arterial Stiffness
Enhanced External Counter
Pulsation Treatment Improves
Arterial Wall Properties and
Wave Reflection Characteristics
in Patients With Refractory
Angina.
Nichols WW, Estrada JC, Braith RW, Owens K,
Conti CR.
Journal of the American College of Cardiology. 2006 Sep
19;48(6):1209-1215. Epub 2006 Aug 25.
Summary: 34, 1-hour EECP treatments in 20 stable angina
patients caused a significant decline in the augmentation
index and an increase in reflected wave travel time,
demonstrating a reduction of arterial stiffness, resulting in a decrease in left ventricular afterload,
myocardial oxygen demand and angina episodes and improved Canadian Cardiovascular Society
functional class.
Am J Cardio. 2008 Feb 1; 101(3): 300-302.
Inflammatory Markers
Effect of Enhanced External Counterpulsation on
Inflammatory Cytokines and Adhesion Molecules in
Patients with Angina Pectoris and Angiographic Coronary
Artery Disease.
Casey DP, Conti CR, Nichols WW, Choi CY, Khuddus MA, Braith RW.
American Journal of Cardiology. 2008 Feb 1;101(3):300-302. Epub 2007 Dec 11.
Summary: 21 patients were randomly assigned to EECP or sham treatment, plasma tumor necrosis factor
was reduced by 29% and monocyte chemoattractant protein-1 by 19% after active treatment compared
with no significant changes in the sham group. Circulating level of proinflammatory cytokines are
predictors of future coronary events.
Cardiology. 2008; 110(3): 160-6.
Endothelial Progenitor Cell Release
The Effect of External Counter Pulsation Therapy on
Circulating Endothelial Progenitor Cells in Patients with
Angina Pectoris.
Barsheshet A, Hod H, Shechter M, Sharabani-Yosef O, Rosenthal E, Barbash IM, Matetzky S, Tal R,
Bentancur AG, Sela BA, Nagler A, Leor J..
Cardiology. 2008;110(3):160-6. Epub 2007 Dec 4.
Summary: Circulating endothelial progenitor cells (EPCs) positive for CD34 measured by flow
cytometry and kinase insert domain receptor (KDR) measured by the number of colony-forming units in
25 patients with angina pectoris randomized to 35 daily 1-hour EECP treatment sessions (n=15) and
control (n=10) were significantly increased in the EECP treated group and not in the control group.
Patients in the EECP therapy group also improved their anginal score from 3.0 pre-EECP therapy to 2.0
post EECP therapy (p<0.001). The improvement of angina post EECP treatment is associated with an
increased number of colony-forming capacities of circulating EPCs.
J Am Coll Cardio. 1999 Jun;33(7):1833-1840
Randomized Clinical Trials and Patient Registry Data in the Treatment of Angina Pectoris and Heart
Failure
The Multicenter Study of Enhanced External
Counterpulsation (MUST-EECP): Effect of EECP on
Exercise-Induced Myocardial Ischemia and Anginal
Episodes.
Arora RR, Chou TM, Jain D, Fleishman B, Crawford L, McKiernan T, Nesto R.
The Journal of the American College of Cardiology. 1999 Jun;33(7):1833-1840.
Summary: A multicenter (7 university hospitals), prospective, randomized, blinded, control trial of 139
angina patients with documented coronary artery disease and positive exercise treadmill tests were treated
with either active counterpulsation (applied cuff pressure up to 350 mmHg), and inactive counterpulsation
(<75 mmHg). Exercise duration increased in both groups, with time to ≥ 1-mm ST-segment depression
increased significantly from baseline in the active group compared with the inactive group (p=0.11), as
well as a significant reduction in the number of angina episodes (p<0.05). Nitroglycerin usage decreased
in the active group but did not change in the inactive group; the between-group difference was not
significant (p>0.7).
J Am Coll of Cardio. 2006; 48(6): 1199-1206.
Enhanced External
Counterpulsation Improves
Exercise Tolerance in Patients
With Chronic Heart Failure.
Feldman AM, Silver MA, Francis GS, Abbottsmith CW,
Fleishman BL, Soran O, de Lame PA, Varricchione T for
the PEECH Investigators.
Journal of the American College of Cardiology. 2006 Sep
19;48(6):1199-1206. Epub 2006 Aug 25.
Summary: 187 subjects with mild-to-moderate symptoms
of heart failure were randomized to either EECP treatment
with protocol-defined pharmacologic therapy (PT) or PT
alone. 35% in the EECP therapy group and 25% in control
group increased their exercise time by at least 60 sec
(p=0.016) at 6 months. However, there was no between
group difference in the percentage of subjects with at least
1.25 ml/kg/min increase in peak volume of oxygen uptake.
New York Heart Association (NYHA) functional class
improved in the active treatment group at 1-week (p<0.01), 3 months (p<0.02), and 6 months (p<0.01 post
treatment). The Minnesota Living with Heart Failure score also improved significantly in the treated
group at 1 week (p<0.002) and 3 months (p=0.01) after treatment, versus no significant changes in the
control group.
Congestive Heart Failure. 2006 Nov-Dec;12(6):307-311
Enhanced External Counterpulsation Improves Exercise
Duration and Peak Oxygen Consumption in Older Patients
With Heart Failure:
A Subgroup Analysis of the PEECH Trial.
Abbottsmith CW, Chung ES, Varricchione T, de Lame PA, Silver MA, Francis GS, Feldman AM;
Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) Investigators.
Congestive Heart Failure. 2006 Nov-Dec;12(6):307-311.
Summary: This paper reports the results of a pre-specified subgroup analysis of 85 elderly patients (65
years or older) enrolled in the PEECH trial. At 6-months post treatment, the percentage of subjects with
>60-second increase in exercise duration was significantly higher in EECP patients compared with the
control group (p=0.08). Moreover, in contrast to the overall PEECH study (see above), the older patient
group demonstrated a significantly higher percentage of responders with >1.25 ml/kg/min increase in
peak volume of oxygen consumption (p=0.017). In addition, the mean changes in exercise duration and
peak oxygen consumption from baseline were significantly increased compared with the control group at
1 week, 3 months and 6 months following completion of treatment.
Am J Cardiol. 2002; 89(7): 822-824.
Perfusion to Ischemic Region
Effects of Enhanced External Counterpulsation on Stress
Radionuclide Coronary Perfusion and Exercise Capacity in
Chronic Stable Angina Pectoris.
Stys TP, Lawson WE, Hui JCK, Fleishman B, Manzo K, Strobeck JE, Tartaglia J, Ramasamy S, Suwita
R, Zheng ZS, Liang H, Werner D.
The American Journal of Cardiology. 2002 Apr 1;89(7):822-824.
7-centers, 175 patients divided into two groups
Group 1
(4-centers, 97 pts)
Group 2
(3-centers, 78 pts)
Same Level Exercise Pre & Post
EECP
Maximal Exercise Pre & Post
EECP
Stress Nuclide Perfusion
• 83% had significant improvement
• 17% no change
• 0% worse RN
Double product no change
Stress Nuclide Perfusion
• 54% improved RN perfusion
• 42% no change
• 8% worse
Double product no change
Clinical Cardiology. 2008 Apr 10; 31(4): 159-164
Enhanced External Counterpulsation in the Treatment of
Chronic Refractory Angina: A Long-term Follow-up
Outcome from the International Enhanced External
Counterpulsation Patient Registry
Loh PH, Cleland JG, Louis AA, Kennard ED, Cook JF, Caplin JL, Barsness GW, Lawson WE, Soran OZ,
Michaels AD.
Clinical Cardiology. 2008 Apr 10;31(4):159-164
Circulation. 2007 Jul 31;116(5):526-534.
Experimental Studies
Enhanced External Counterpulsation Inhibits
Intimal Hyperplasia by Modifying Shear
Stress Responsive Gene Expression in
Hypercholesterolemic Pigs.
Zhang Y, He X, Chen X, Ma H, Liu D, Luo J, Du Z, Jin Y, Xiong Y, He J, Fang
D, Wang K, Lawson WE, Hui JC, Zheng Z, Wu G.
Circulation. 2007 Jul 31;116(5):526-534. Epub 2007 Jul 9.
Summary: The coronary arteries and aortas of 35 male pigs randomly assigned
to control, high-cholesterol diet and high-cholesterol diet +EECP (EECP started at week 9 to 15) were
analyzed after 15 weeks. There was significant increase in peak diastolic arterial wall shear stress during
EECP with reduction of intima-to-media area ratio by 42% compared with high-cholesterol group. EECP
treated group also increased the protein expression of endothelial nitric oxide synthase suppressed the
phosphorylation of extracellular signal-regulated kinases ½.
Congestive Heart Failure. 2007 Jan-Feb; 13(1): 36-40.
Cost-Effectiveness
Impact of External Counterpulsation Treatment on
Emergency Department Visits and Hospitalizations in
Refractory Angina Patients with Left Ventricular
Dysfunction.
Enhanced External Counterpulsation in the Treatment of
Chronic Refractory Angina: A Long-term Follow-up
Outcome from the International Enhanced External
Counterpulsation Patient Registry
Soran O, Kennard ED, Bart BA, Kelsey SF.
Congestive Heart Failure. 2007 Jan-Feb;13(1):36-40..
Review Paper
Enhanced External Counterpulsation and Future Directions: Step Beyond Medical Management
for Patients with Angina and Heart Failure.
Manchanda A, Soran O.
Journal of the American College of Cardiology. 2007 Oct 16;50(16):1523-1531. Epub 2007 Oct 1.
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.
Clin Cardiol. 2001 Jun;24(6):435-42.
The International EECP Patient Registry (IEPR): design,
methods, baseline characteristics and acute results.
Barsness G, Feldman AM, Holmes DR Jr, Holubkov R, Kelsey SF, Kennard ED;
International EECP Patient Registry Investigators
Mayo Clinic Foundation, Rochester, Minnesota, USA.
BACKGROUND: In 1998, the International EECP Patient Registry (IEPR) was organized to
document patient characteristics, safety, and efficacy during the treatment period, and long-term
outcomes. All centers with EECP facilities were invited to join the voluntary Registry. The
Registry population comprises all patients starting EECP therapy for treatment of angina pectoris
in participating centers.
HYPOTHESIS: The study was undertaken to determine whether EECP is a safe and effective
treatment for patients with angina pectoris regardless of their suitability for revascularization by
more conventional techniques.
METHODS: After 18 months of operation, 43 clinical centers representing over half of clinical
sites using the EECP system contributed cases. The data reported here were collected before
the first EECP treatment and upon completion of final treatment. EECP can be used for patients
ineligible for either coronary artery bypass graft (CABG) or percutaneous coronary intervention
(PCI), as well as for those who prefer noninvasive treatment to avoid or delay revascularization.
In this report, patients considered to be candidates for revascularization are compared with
those not considered suitable.
RESULTS: Of the 978 patients analyzed, 70% had Canadian Cardiovascular Society
Classification class III or IV angina before starting treatment, and 62% used nitroglycerin. Most
(81%) had been previously revascularized, and 69% were considered unsuited for either PCI or
CABG at the time of starting EECP. A full treatment course (usually 35 h) was completed in
86%, of whom 81% reported improvement of at least one angina class immediately after the last
treatment.
CONCLUSION: In a broad patient population, EECP has been shown to be a safe and effective
treatment.
PMID: 11403504 [PubMed - indexed for MEDLINE]