REVIEW ARTICLE
Enhanced external counterpulsation: mechanisms of
action and clinical applications
Vasiliki KITSOU1, MD; Theodoros XANTHOS1, PhD; Robin ROBERTS2, George M. KARLIS1, MD; Lila
PADADIMITRIOU1, PhD
1Department of Experimental Surgery and Surgical Research, University of Athens, Greece; Medical
School; 2Consultant Cardiologist London, UK.
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Symptomatic coronary artery disease (CAD) and heart failure (HF), either of
ischaemic or nonischaemic aetiology, are common medical problems. Despite
optimal medical treatment and improved revascularisation techniques, a
significant number of patients are not successfully managed. Among the nonpharmacological, alternative, non-invasive treatments suggested for these
patients, enhanced external counterpulsation (EECP) is considered the most
effective one. EECP, administered in an outpatient setting, consists of three
pneumatic cuffs applied to each of the patient’s legs that are sequentially inflated
and deflated synchronised with the cardiac cycle. Numerous clinical trials have
shown that EECP is safe and effective in patients with ischaemic heart disease,
with or without left ventricular dysfunction, improving their quality of life. EECP
appears to be beneficial as an adjunctive therapy in patients with HF of any
aetiology. Cardiac syndrome X has been shown to be effectively treated with
EECP. Research in EECP expanded in its potential use for entities other than
heart disease. More trials are necessary, including sham-controlled trials, to
further establish EECP among medical society.
Keywords: Enhanced external counterpulsation – angina pectoris – heart failure.
-----------------------------------------------------------------------------------------------------------------------------Address for correspondence: Theodoros Xanthos, University of Athens, Medical School,
Department of Experimental Surgery and Surgical Research, 15B Agiou Thoma Street, 11527
Athens, Greece. E-mail: theodorosxanthos@yahoo.com
Received 9 November 2009; revision accepted for publication 14 January 2010.
Acta Cardiol 2010; 65(2): 239-247 doi: 10.2143/AC.65.2.2047060 239
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INTRODUCTION
Coronary artery disease (CAD) is a major medical problem with a prevalence of 213 cases for
every 100,000 persons over the age of 301. Heart failure (HF) affects 1-2% of the population
worldwide, and in the United States it is responsible for almost 1∞∞million hospital admissions
and 50,000 deaths annually2. Despite the increasing success of conventional medical treatment
and improvement of mechanical revascularization approaches, a significant number of patients
with CAD cannot be successfully managed, suffering from refractory angina pectoris (RAP)3,4.
Moreover, for the group of patients with underlying HF, substantial unmet needs remain. As a
result many patients are left to suffer their symptoms, restrict their activities and anticipate a
reduced life expectancy5. Current non-pharmacological options for the treatment of patients
with RAP, with or without underlying HF, have been suggested. Of these modalities enhanced
external counterpulsion (EECP) therapy represents the most effective non-invasive
echnique5,6. Furthermore, the role of EECP therapy has been recently investigated for the
treatment of HF7. The aim of this review is to present the clinical applications of EECP therapy
in RAP, HF and other clinical entities and to describe the group of patients who are eligible for
this kind of treatment.
DESCRIPTION AND MECHANISMS OF EECP
EECP is a non-invasive procedure administered in an outpatient setting. The device consists of
three pneumatic compression cuffs applied to each of the patient‘s legs - on the calves, lower
thighs, upper thighs including the buttocks5,8. A computer controlled pneumatic system acts to
inflate and deflate them based on the patient’s electrocardiogram(ECG).A finger plethysmogram
is used throughout treatment to monitor diastolic and systolic pressure waveforms7. A course
of EECP treatment typically involves 35 one-hour sessions, usually 5∞∞days a week over a 7week period, though treatments twice per day have been effective as well9. The haemodynamic
effects produced by EECP are similar to intra-aortic balloon pump (IABP)9. Sequential inflation
of the cuffs, at the onset of diastole, produces aortic counterpulsation and an increase in
diastolic pressure while rapid deflation of the cuffs, at the onset of systole, decreases systolic
pressure in both the aorta and the coronary arteries10. Unlike IABP, EECP also increases
venous return further, enhancing thus cardiac output10,11. Furthermore, as diastolic
inflation pressure is increased, the preload is increased, afterload is decreased, contractility is
increased and mechanical efficiency is neutral12. Since shear stress is a stimulus for the
release of endothelium-derived vasodilator nitric oxide as well as a modulator of the
vasoconstrictor endothelin-1 release, it has been postulated that EECP, by enhancing
vascular shear stress, may favourably affect endothelial function13. Vascular mechanical forces
have been suggested to initiate collateral development14. Masuda et al.15, using ammonia
positron emission tomography, suggested that the development of collateral vessels is one of
the mechanisms of EECP therapy. EECP was proven to exert peripheral effects similar to
physical exercise16. EECP therapy exerts a ‘training’ effect decreasing thus peripheral vascular
resistance and the heart rate response to exercise17. EECP effect is considered analogous to
the peripheral vascular conditioning effect seen with exercise, in which improved vasomotor
tone decreases the blood pressure response to exercise18. Finally, the fact that many patients
experience significant symptomatic improvement, even in the absence of optimal diastolic
augmentation during treatment, indicates that a placebo effect may contribute to the
symptomatic benefit observed with EECP10. Evidence indicates that the use of medical devices
may be associated with an enhanced placebo effect19.
EECP AND ISCHAEMIC HEART DISEASE (IHD)
The role of EECP in the treatment of IHD has been known since the early 1970s, however, it did
not receive significant attention. The first pivotal turn of events came in 1999 when the
Multicenter Study-EECP trial (MUST-EECP) was published1. MUST-EECP is the first
prospective, randomized, blinded, placebo controlled trial that assessed safety and efficacy of
EECP after treating outpatients with angina, documented CAD and positive exercise treadmill
test. The trial concluded that EECP reduces angina and extends time to exercise-induced
ischaemia20. Despite the impressive results controversy and doubt remained, mostly in regard
with the role placebo played in the study. A sub-study of MUST-EECP trial21 concluded that
improvements on patients’ health and quality of life were present 12∞∞months after treatment
with EECP. EECP was suggested as a safe treatment option for selected symptomatic
percutaneous coronary intervention (PCI) candidates with obstructive CAD22. It was further
suggested that EECP, as a noninvasive treatment, could be used as a first-line treatment with
invasive revascularization reserved for EECP failures, or high-risk patients23. Based on its
acute haemodynamic effects, comparable to those of IABP, EECP was proposed as a potential
treatment for coronary syndromes in an acute setting, as an inpatient therapy for patients with
IABP contraindications24. Currently, EECP has been considered to be a more effective
alternative treatment for patients with RAP who are not proper candidates for established,
available non-pharmacologic options such as spinal cord stimulation25. In addition, an antiinflammatory effect of EECP in patients with angina pectoris has been suggested when a
decrease in circulating pro-inflammatory biomarker levels was demonstrated after 35 1-hour
sessions26. However, in current studies, despite that endothelial improvement has been
observed during the course of EECP treatment, long-term benefits of EECP could not be
attributed to improved endothelial function27. Over the years, there have been many interesting
studies of EECP therapy in ischaemic heart disease summarized in table 128-41 and table 24250,13.
EECP AND HEART FAILURE
An interesting turn in EECP research was the prescription of the technique to patients with RAP
combined with left ventricular (LV) dysfunction. The primary concern of initial researchers was
that the increased venous return, resulting from EECP treatment, would precipitate pulmonary
oedema in these patients and might exacerbate heart failure. Nevertheless, earlier small reports
demonstrated that patients with depressed ventricular function responded to treatment
with EECP considerably improving angina function and quality of life both immediately after
treatment and in a 6-month follow-up51. Furthermore, benefits and safety of EECP were
demonstrated to be similar in angina patients with a history of heart failure and severe systolic
dysfunction with those with angina and heart failure with diastolic dysfunction25,52.
More recently, Soran e t al.53 concluded that EECP offers an effective, durable therapeutic
approach for refractory angina combined with high-risk LV dysfunction. 240 V. Kitsou et al.
Clinical applications of EECP 241
Currently, systolic blood pressure improvements have been documented during and after EECP
treatment, as well as after a 6-week follow-up54. However, EECP did not improve any
measurements of LV systolic or diastolic function, performed by two-dimensional and Doppler
echocardiography55. Unlike the efficacy and safety of EECP treatment in RAP evidence
regarding the efficacy of the procedure in patients with HF is just beginning to emerge56.
In an earlier study57, in patients with class II or III heart failure and ejection fraction less than
35%, EECP treatment was associated with a significant improvement in LV function, as
measured by an increase in ejection fraction, and a significant decrease in heart rate. It was
further demonstrated by later studies that EECP can be safe and well tolerated in patients with
relatively stable heart failure and no fluid overload. Also, according to a pilot study, in these
patients EECP can improve exercise capacity, quality of life and functional status, both in the
short term and for a period of 6∞∞months 58. Nevertheless, the results of this pilot study should
be interpreted with caution given the small sample size. Nevertheless, these promising results
revealed the need for a randomized control study to ascertain the efficacy of EECP as an
adjunctive therapy in the management of patients with chronic stable heart failure. The
Prospective Evaluation of EECP in Heart Failure (PEECH) trial concluded that EECP improved
exercise tolerance, quality of life and New York Heart Association (NYHA) functional
classification without an accompanying increase in peak oxygen consumption in patients with
HF59,60. Futhermore, a subgroup analysis of the PEECH trial61 confirmed the beneficial
effects of EECP in elderly patients, older than 65, with chronic, stable mild-to-moderate heart
failure. EECP can benefit patients with HF who already receive optimal medical therapy without
achieving the desired effects. Yet, only when the haemodynamic effects of EECP during
diastole and during systole are synchronised properly will the increase in venous return be
compensated and not result in pulmonary congestion or even pulmonary oedema. However,
while the safety of EECP in patients without significant fluid overload has been demonstrated,
further studies are needed to guide the use of the technique in patients with more severe
overload or acute decompensated heart failure62. EECP appears to be relatively safe in heart
failure patients but the treatment‘s efficacy is more nebulous and more research is
necessary63.
PATIENT SELECTION AND LIMITATIONS
EECP is a Food and Drug Administration approved class IIb-recommended treatment for
refractory angina63. Indications for EECP therapy include stable and unstable angina, class IIIII stable congestive heart failure, acute myocardial infarction, and Cardiogenic shock62. As
more is learned about EECP, patients once excluded from early clinical trials are now able to
take advantage of EECP. Nevertheless, EECP is not suitable for some patients64,65,66 (table
3). Furthermore, another impediment to the widespread use of EECP is that many cardiologists
are not fully informed about the concept of EECP as well as about the technique itself.
Physicians and patients are eager to see quick results and fast improvement of their health
status, whereas with EECP therapy a considerable amount of time is needed in order to
observe results9.
Contraindications
Arrhythmias that interfere with machine triggering (atrial fibrillation)
Decompensated heart failure
Severe uncontrolled hypertension (> 180/110∞∞mmHg)
Cardiac catheterization or arterial puncture within 2∞∞weeks
Severe pulmonary hypertension
Severe aortic insufficiency
Severe peripheral arterial disease with rest claudication ornon-healing ulcers
Venous diseases (thrombophlebitis, deep venous thrombosis)
Bleeding diathesis or warfarin therapy
Pregnancy
Aortic aneurysm or dissection
Side effects
Skin abrasion
Haematoma of the legs
Severe pain of the legs
FURTHER CLINICAL APPLICATIONS
There has been much concern over other potential clinical applications of EECP. Kronhaus et
al.67 treated with EECP 30∞∞patients with refractory angina due to cardiac syndrome X. There
was a significant reduction in angina class and in inducible ischaemia. The effect Clinical
applications of EECP 243 following treatment was durable, with a low incidence of recurrent
angina.
Investigating the hypothesis that symptom improvement from EECP is related to improved heart
rate variability (HRV).
To assess the efficacy of EECP in relieving angina and improving objective measures of
myocardial ischaemia. There was no significant change in the time- or frequency-domain HRV
measures after EECP.
In diabetic individuals, there was an increase in low frequency HRV, which has been associated
with reduced mortality. The results of this study suggested that EECP is a safe, well tolerated,
and significantly effective treatment for angina pectoris.
Improvement of endothelial dysfunction was suggested as the underlying mechanism of action;
however, the efficacy of EECP in syndrome X remains unknown68.
Further studies investigate the benefits of EECP on entities other than cardiac disease. EECP
improved skin oxygenation and decreased carbon dioxide load. These effects were attributed to
microcirculation improvements caused by the increase of concentration and the decrease of
velocity of moving blood cells observed during counterpulsation69. Also, Werner et al. used
EECP in an effort to improve renal dysfunction of liver cirrhosis. They observed that EECP
improved diuresis, but did not influence the vasoconstrictive dysregulation of the kidneys in liver
cirrhosis70. Furthermore, it was suggested that EECP could be a clinically useful and safe
procedure in patients with acute central retinal artery occlusion or branch retinal artery
occlusion71. Rajaram et al. found some patients who underwent EECP for angina or congestive
heart failure who also coincidently had severe restless leg syndrome (RLS). They concluded
that EECP improved RLS symptoms significantly; still, a larger number of patients should be
investigated to draw further conclusions72. The effect of EECP was assessed on ischaemic
heart disease associated erectile dysfunction. Although preliminary results indicated an
improvement, large scale trials and long-term data are needed73,74. An interesting study by
Werner et al. Demonstrated that cerebral autoregulation ensures the constancy of cerebral
blood flow even though EECP creates marked systemic changes. The decrease of blood
pressure (BP) after EECP with maintained cerebral flow velocity (CBFV) indicates an improved
BP/CBFV relation75.
Experimental studies have demonstrated that EECP results in endothelium-dependent
vasorelaxation in the carotid arteries of hypercholesterolaemic pigs76. Furthermore,
it was suggested that EECP does not compromise cerebral autoregulation and, therefore, does
not seem to bear cerebrovascular risks77. These data suggest that EECP might be useful in the
treatment of stroke patients, as it improves neurological functional outcome78, increased power
in paretic extremities and decreased spasticity79. However, randomized-controlled trials with a
large sample size are needed to further define the efficacy and safety of EECP in acute stroke
management.
CONCLUSION
Safety and immediate benefits of the technique as well as the achievement of sustained
symptomatic benefits and quality of life have been confirmed in most patients for up to three
years80. However, patients with more severe angina and without history of HF are more likely to
gain immediate symptomatic benefit whereas patients with more severe angina, diabetes,
and a history of HF are more likely to suffer from unfavourable long-term outcome and major
adverse cardiovascular events81,82. Furthermore, residual high-grade angina after EECP can
occur, though uncommon, in patients with more severe angina at baseline48. More trials are
necessary, including sham-controlled trials, to further establish among medical society the
mechanisms, the benefits as well as the short and long-term outcome of the procedure in a
variety of pathologies.
Conflict of interest: none declared.
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