Download EECP Clinical Guide 2008 (VASO)

Clinical Guide
Introduction
Enhanced External Counterpulsation (EECP) is a FDA cleared noninvasive medical
device for the treatment of patients suffering from coronary artery disease (CAD). It is a device
that improves cardiac output, increases circulation and pressure gradient across stenosis to
recruit collaterals. It also increases shear stress on the endothelium, improving endothelial
function, reduces circulating inflammatory markers and arterial stiffness, inhibits smooth
muscle cells proliferation and migration. It has been demonstrated to be safe and effective in
the treatment of angina pectoris as well as chronic heart failure. 1,2
EECP Therapy Operations
EECP system consists of three sets of inflatable pressure cuffs wrapped around the
calves, the lower and upper thighs, including the buttocks. The cuffs are rapidly and sequentially
inflated, starting from the calves and proceeding upward to the buttocks during the relaxation
(diastolic) phase of each heartbeat, creating a strong arterial retrograde flow towards the heart
and significantly increasing blood flow to the coronary arteries at a time when resistance to
coronary blood flow is at its lowest level. The inflation of the cuffs also simultaneously increases
the volume of venous blood returned to the right side of the heart, providing greater filling of the
ventricle for ejection. Just before the beginning of the next cardiac cycle when the heart begins to
contract, all three cuffs simultaneously deflate, leaving an empty vascular space in the lower
extremities to receive blood ejecting from the heart, thereby significantly reducing the workload
of the heart. The inflation/deflation activity is monitored constantly and coordinated by a
microprocessor that interprets electrocardiogram signals, monitors heart rhythm and rate
information, and actuates the inflation and deflation in synchronization with each cardiac cycle
(see Figure 1). The inflation/deflation cycle is repeated every heartbeat, increasing energy supply
to the heart, improving cardiac output, while at the same time reducing the workload of the heart.
Figure 1: The QRS complex of
the electrocardiogram is used to
Sequential inflation of
Simultaneous deflation of
provide a triggering signal for the
three sets of cuffs at the
all three sets of cuffs at the
calf inflation valve to open
end of systole
end of diastole
around the peak of T-wave, the
lower thigh valve will open 50 ms
later, to be followed by the upper
Upper
Upper
thigh valve another 50 ms later.
Thigh Cuffs
Thigh
Cuffs
The pressure in the cuffs will hold
Lower
Lower
as long as possible to allow
Thigh
Thigh
Cuffs
maximization of diastolic
Cuffs
augmentation. Then all threeCalf
Calf
deflation valves will open at the
Cuffs
Cuffs
same time around the peak of Pwave to let the emptied peripheral vasculature to receive the blood ejected by the heart, leading
to systolic unloading.
EECP Treatment System
The EECP therapy systems are Food and Drug Administration (FDA) cleared for
marketing in the treatment of stable and unstable angina, congestive heart failure, acute
myocardial infarction, and cardiogenic shock.
Figure 2: EECP Lumenair system. Patient
selection and contraindications as well as
precautions should be followed carefully to
avoid risk of adverse clinical events. Blood
pressure, respiration rate, oxygen saturation
and weight should be monitored during
EECP treatment to avoid exacerbation of
heart failure, especially in patients with
low ejection fraction. Physical assessment,
especially peripheral skin condition, should
be examined after every treatment session.
The treatment is administered to patients on an outpatient basis, usually in daily one-hour
sessions, five days per week over seven weeks for a total of 35 treatments. EECP is equally
effective if it is given twice daily, each with one-hour session separated by a minimum of 30minutes break for a total of three and a half week. The procedure is well tolerated and most
patients begin to experience relief of chest pain due to their coronary artery disease after 15 to 20
hours of therapy.
Patient Selection
EECP is primary used as a non-pharmacologic outpatient therapy for patients with
chronic stable angina pectoris as well as symptoms of heart failure.3-8, 11-18 Effective July 1,
1999, The Centers for Medicare and Medicaid (CMS) and other third-party insurance payers
reimburse for the treatment of angina symptoms in patients who have been diagnosed with
disabling angina (Class III or Class IV, Canadian Cardiovascular Society Classification or
equivalent classification) who are not readily amenable to surgical intervention, such as PTCA
or cardiac bypass.
Patients with severe, diffuse coronary atherosclerosis and persistent angina, or
significant silent ischemia burden, in whom coronary revascularization has been unsuccessful
or incomplete, and symptomatic patients at high risk of adverse events related to invasive
revascularization, such as elderly patients and those with diabetes, challenging coronary
anatomies, or debilitating heart failure, renal failure, or pulmonary disease, have also been
shown to derive benefit from EECP therapy.1, 2, 23 EECP therapy has also been shown to be
effective in relieving angina symptoms in patients with cardiac syndrome X.22 Benefits of
EECP have also been determined in the management of angina in the elderly, 24 angina
patients with left main disease,27 and in patients with mild refractory angina (CCS Class II).8
EECP therapy is equally effective in reducing angina symptoms in patients with or without
diabetes, 25 and in patients with all ranges of body mass index.26
EECP therapy has also been shown to improve exercise capacity in heart failure
patients with NYHA Class II/III, 12-14 and in exercise peak oxygen consumption in older
patients with heart failure.15 EECP therapy has also been demonstrated to be equally effective
in providing symptomatic benefits in angina patients with either systolic or diastolic heart
failure.16 For patients with left ventricular dysfunction, the beneficial effects of EECP therapy
has been shown to sustain up to 2-year at follow-up.17-18
Contraindications
According to the current FDA labeling, EECP® Therapy System should not be used for
the treatment of patients with:






Arrhythmias that interfere with machine triggering,
Bleeding diathesis,
Active thrombophlebitis,
Severe lower extremity vaso-occlusive disease,
Presence of a documented aortic aneurysm requiring surgical repair,
Pregnancy.
Precautions




Patients with blood pressure higher than 180/110 mmHg should be controlled prior to
treatment with enhanced external counterpulsation.
Patients with a heart rate more than 120 bpm should be controlled prior to treatment
with enhanced external counterpulsation.
Patients at high risk of complications from increased venous return should be
carefully chosen and monitored during treatment with enhanced external
counterpulsation. Decreasing cardiac afterload by optimizing diastolic augmentation
may help minimize increased cardiac filling pressures due to venous return.
Patients with clinically significant valvular disease should be carefully chosen and
monitored during treatment with enhanced external counterpulsation. Certain valve
conditions, such as significant aortic insufficiency, or severe mitral or aortic stenosis,
may prevent the patient from obtaining benefit from diastolic augmentation and
reduced cardiac afterload in the presence of increased venous return.
Special clinical issues









Elderly patients with age 80 years or older can be treated with EECP with angina
classification reduced by at least 1 class and quality of life improved in 76%. At 1 year,
81% reported maintenance of angina improvement.24
Diabetes: CAD patients with diabetes can safely and effectively be treated with comparable
results to non-diabetic CAD patients.25
Obesity: EECP treatment is equally safe and effective across patients with diverse range
of body mass index, including obese patients (BMI > 30 kg.m2) and morbidly obese (BMI
> 40 kg.m2). 26
Peripheral vascular disease: listed as precaution due to inadequate diastolic augmentation
can gain benefits from EECP treatment similar to all other CAD patients.1
Abdominal aortic aneurysm (AAA) with increased risk of rupture or retrograde
thromboembolic events has not been reported with EECP treatment. AAA larger than 4.0
cm should be referred to vascular surgeon for evaluation.1
Atrial fibrillation can be treated with EECP with rate control between 40-100 bpm
Pacemakers and defibrillators could undergo EECP safely and derive clinical benefits
with appropriate monitoring. Rate-adaptive pacemaker may lead to trigger a paced
tachycardia due to patient’s body motion and can be turned off during EECP.
Treatment protocol: the 35 hours daily treatment is associated with angina reduction and
improved exercise tolerance in at least 75% of patients. Extension of therapy by 10-12
hours is associated with further improvement.1
Repeat therapy: within 2 years after initial EECP treatment, 18% of patients undergo
another course of re-treatment due to recurrent angina, persistent angina with benefit
similar to patients who respond to their first course.34, 35
Evidence-Based Clinical Results
There are more then 150 papers published in peer reviewed medical journals
documenting EECP therapy is a noninvasive, safe, low-cost and highly effective treatment for
patients with coronary artery disease. For a list of all published paper, visit: www.Vasomedical.com.
Major results of a few selected papers are summarized below:
1. There are two randomized controlled
trials, one for patients with chronic
angina pectoris and one for patients with
chronic heart failure.
1.1 The Multicenter Study of Enhanced
External Counterpulsation (MUSTECP): Effect of EECP on ExerciseInduced Myocardial Ischemia and
Anginal Episodes 3
A multicenter (7 university hospitals),
prospective, randomized, blinded,
control trial in 139 angina patients
Changes in Time to Exercise-induced
ST-segment Depression
60
se
c
p=0.01
50
40
30
20
10
37 sec
0
-10
-4 sec
Sham
n=56
EECP
n=56
with documented coronary artery disease and positive exercise treadmill test were treated
with either active counterpulsation (applied cuff pressure up to 350 mm Hg), and inactive
counterpulsation (<75 mm Hg). 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=0.01), as well as a significant reduction in the
number of angina episodes (p<0.05).
1.2a Prospective Evaluation of EECP in Heart Failure (PEECH): 13,14
187 subjects with mild-to-moderate
symptoms of heart failure were
% Subjects Who Met Threshold
randomized to either EECP®
40.0
treatment with protocol-defined
p=0.016
pharmacologic therapy (PT) or PT
35.0
alone. 35% in the EECP® therapy
Contro
EECP
l
30.0
group and 25% in control group
increased their exercise time by at
p=NS
25.0
least 60 sec (p=0.016) at 6 months.
However, there was no between
20.0
group difference in the percentage of
15.0
subjects with at least 1.25 ml/kg/min
increase in peak volume of oxygen
10.0
25.3%
35.4%
22.8%
24.1%
uptake. New York Heart Association
N=93
N=94
N=93
N=94
(NYHA) functional class improved
5.0
in the active treatment group at 10.0
Exercise Duration
Peak VO2
week (p<0.01), 3 months (p<0.02),
Increase  60 sec
Increase  1.25 ml/kg/min
and 6 months (p<0.01). The
from baseline
from baseline
Minnesota Living with Heart Failure
% responders at 6-month follow-up
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.
1.2b A Subgroup Analysis of the PEECH
Trial: EECP Improves Exercise
Duration and Peak Oxygen
Consumption in Older Patients
With Heart Failure 15
This paper reports the results of a prespecified subgroup analysis of 85
elderly patients (65 years or older)
enrolled in the PEECH trial. At 6months 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
% Subjects Who Met Threshold
40
p=0.008
EECP
35
35.1%
Control
p=0.017
30
29.7%
25
25.0
%
20
15
10
11.4%
5
13/37
0
11/44
Exercise Duration
Increase  60 sec
from baseline
11/37
5/44
Peak VO 2
Increase  1.25 ml/kg/min
from baseline
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.
2. Two International EECP Patient Registries (IEPR I with 5,000 patients and IEPR II with
2,500 patients) have been completed in July 2001 and Oct 2004 respectively by the
Epidemiology Data Center of the University of Pittsburgh to determine the patterns of use,
safety and efficacy of EECP for a period of 2- 3 years post treatment. Data collected were
patients’ demographics, medical history, CAD status, quality of life, CCS Classification,
medication, angina frequency and adverse clinical events before EECP, post EECP, and
during follow-up periods. 28-36
At Baseline, patients treated with EECP therapy have an average age of 67 years old,
with significant risk factors (43% diabetes, 84% hyperlipidemia and 75% hypertension) and
suffered from severe CAD (87% with prior PCI/CABG, 69% with prior MI, 31% heart
failure), 86% of patients were Canadian Cardiovasular Society (CCS) angina class III and IV
patients. 29 Post-EECP therapy, 81% of the patients
60
Baseline
30
60
improved with reduction of at least one CCS class. The
N=4,56
benefits were sustained at 1-year (75%), 30 2-year (73%), 50
5
32
33
and 3-year (74%) follow-up (see figures for the
40
Distribution of the percent of patients according to their
CCS angina class). The percent of patients in CCS class
26
30
III and IV reduced from 86% at baseline to 25% at 120
year, 24% at 2-year and 21% at 3-year follow-up, with
11
27%, 30% and 35% of patients had no angina during the
10
3
1
1, 2 and 3-year follow-up period.
1
0
60
60
1- year follow-up
50
50
40
20
30
27
19
19
10
40
30
20
6
28
18
18
25
19
20
6
10
Canadian Cardiovascular Society angina class
35
30
16
10
0
0
3-year Follow-up
50
40
30
30
60
2-year Follow-up
5
0
No Angina
I
II
III
IV
Mechanisms of Action
There are many pathophysically pathways by which EECP therapy achieves its longterm beneficial effects. There is evidence of improved endothelial function via the hemodynamic
effects of increased shear stress on the arterial wall, reducing arterial stiffness and providing
protective effects against inflammation, thereby inhabits intima hyperplasia. There is also
evidence to suggest that EECP therapy triggers a neurohomonal response that induces the
production of growth and vasodilatation factors, which together with the hemodynamic effects of
increasing pressure gradient across the occlusive site during EECP therapy, promotes
recruitment of new arteries, while dilates and normalizes the function of existing blood vessels.
The recruitment of new arteries, known as “collateral blood vessels”, bypass blocked or
narrowed vessels and increase blood flow to ischemic areas of the heart muscle that are receiving
an inadequate supply of blood.
EECP® Mechanisms of Action
Acute Hemodynamic Effects
 Systolic Unloading
 Diastolic Augmentation
 Increase Cardiac Output
Improve Neurohormonal Factors
 BNP  and ANP 
 Angiotensin II 
Reduce Proinflammatory Cytokines and
Adhesion Molecules
 Tumor necrosis factor -  
 Monocyte chemoattractant protein – 1 
Collaterals Development
 Blood flow to ischemic region 
 Vascular growth factors 
 Capillary density 
Improve Endothelial Function
 Vasodilation 
 Intimal Hyperplasia 
 Release of Endothelial Progenitor Cell 
Reduce Arterial Stiffness
 Blood pressure 
 Vascular resistance 
 Cardiac efficiency 
Improve blood flow to ischemic regions
Clinical Benefits
Hemodynamic Effects
during EECP treatment has
been documented in the
descending aorta with
increased stroke volume and
presence of retrograde flow, 37
as well as significant increase
of blood flow in the coronary
arteries using intracoronary
Doppler. 38 The increase in
flow velocity increases shear
stress on the endothelium and
improves endothelial
functions with significant
increase of plasma nitric oxide
level 43 and improvement in
flow-mediated
vasodilatation.44
In addition, significant
decrease (29%) of
inflammatory cytokines
Descending Aorta
180
Nitric Oxide
160
†
140
†
Intracoronary flow
†
12
10
†
‡
*
120
Brachial Artery Flow-mediated dilatation
100
p = NS
p<0.01
Control
Baseline
EEC
P after
2-month
8
6
80
4
60
2
40
0
20
0 Baseline 1hr 12hr 24hr 36hr 1-mo 3-mo
*p=0.014;†p<0.0001;‡p=0.002 vs baseline
Plasma Tumor Necrosis Factor - 
20
10
0
-10
-20
-30
-40
p<0.0
5
EECP
N=12
-29%
Sham
N=9
+5%
N=20
20
18
16
14
12
10
8
6
4
2
0
Endothelial Progenitor Cells
p = 0.430
p=0.049
Sham
(N=10)
Baseline
EECP
(N=15)
Post-EECP
tumor necrosis factor- in patients with angina, and increase of circulating plasma endothelial
progenitor cell after EECP therapy have been reported.41, 40
The long-term benefits of EECP therapy from improvement in endothelial functions lead to
inhibition of vascular smooth muscle cells
Scanning Electron
migration and proliferation,
100Micrographs
µm
attenuation of oxidative stress and
Scale
inflammation and inhibits intimal
hyperplasia as demonstrated by the
experimental work on
hypercholesterolemic pigs in which
the coronary arteries and aortas of 35
male pigs randomly assigned to
control, high-cholesterol diet (HCD)
and HCD+EECP. The EECP group
enjoyed a reduction of intima-to50µm
media area ratio by 42% compared
with HCD group. EECP treated group
also increased the protein expression
of endothelial nitric oxide synthase
and suppressed the phosphorylation
50µm
of extracellular signal-regulated
46
kinases ½.
Control
High Cholesterol diet (HCD)
HCD + EECP ®
In patients suffering from angina
pectoris, 34 1-hour EECP® treatments
30
Arterial Stiffness
in 20 patients caused a significant
25
p=0.001
decline in the augmentation index and Augm
27  1 0 %
entatio
n
20
an increase in reflected wave travel
Index
time, demonstrating a reduction of
19  10 %
(%)
15
arterial stiffness, resulting in a
10
decrease in left ventricular afterload,
myocardial oxygen demand and
5
angina episodes and improved
0
Canadian Cardiovascular Society
Post-EECP
Pre-EECP
functional class. 42
In summary, the acute hemodynamic effects during EECP® Therapy of systolic unloading
and diastolic augmentation not only provide a chance for myocardial muscle to rest and
accumulate energy reserve, the higher pressure gradient across stenosis generated during
diastolic when resistance to coronary flow is at its minimum would help to enhance collateral
generation, while the increased cardiac output and promotion of retrograded flow induce higher
shear stress on the endothelium, improve endothelial functions and increase release of
neurohomonal and vascular growth factors that induce vasodilatation, inhibit intima
hyperplasia and develop collateral circulation to achieve long-term clinical benefits. There are
several review papers on EECP® therapy expanding these concepts. 47,48
Cost Effectiveness
1. Reimbursement for refractory angina
There are approximately 6.8 million people in the United States suffering from angina,
with 400,000 new cases diagnosed annually, and 80-100,000 patients suffered from refractory
angina. Effective July 1, 1999, the Centers for Medicare and Medicaid Services (CMS) and
many other third-party insurance payers provide coverage for patients who have been
diagnosed with disabling angina (Class III or Class IV, Canadian Cardiovascular Society
Classification or equivalent classification) who, in the opinion of a cardiologist or
cardiothoracic surgeon, are not readily amenable to surgical intervention, such as PTCA or
cardiac bypass because:
(1) Their condition is inoperable, or at high risk of operative complications or post-operative
failure,
(2) Their coronary anatomy is not readily amenable to such procedures; or
(3) They have co-morbid states, which create excessive risk.
Ø
2. Heart Failure patients with ischemic
ER Visits
Hospitalizations
etiology
1.4
In addition, there are 5 million
p<0.001
p<0.001
patients in the United States and
1.2
approximately 22 million worldwide
suffering from heart failure. It is the leading
1.0
cause of hospitalization in patients over age
65, and is one of the largest burdens on the
0.8
U.S. healthcare system, costing in excess of
®
$20 billion annually. EECP therapy offers
an opportunity to redefine the standard of
0.6
care in how this group of patients is treated
86% 
83% 
and has been demonstrated to reduce both
0.4
emergency room (ER) visits and
hospitalizations in heart failure patients with
0.2
left ventricular dysfunction by 86% and
83% respectively, from 1.4 to 0.2 ER visits
0
and 2.4 to 0.4 hospitalizations per patient
6-months 6-months
6-months 6-months
PrePostPrePostper year. 36
EECP
EECP
EECP
EECP
Reference
Clinical Practice
1. Primer: Practical Approach to the Selection of Patients for and Application of EECP
Michaels AD, McCullough PA, Soran OZ, Lawson WE, Barsness GW, Henry TD,
Linnemeier G, Ochoa A, Kelsey SF, Kennard ED. Nature Clinical Practice Cardiovascular
Medicine. 2006 Nov;3(11):623-632.
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JCK. The Journal of Critical Illness. 2000 Nov;15(11):629-636.
Angina Pectoris
3. 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
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Quality of Life
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Co-Morbidities
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KD, Lawson WE. International Journal of Cardiology. 2008 Jun 30. [Epub ahead of
print].
23. Residual High-Grade Angina After Enhanced External Counterpulsation Therapy.
McCullough PA, Henry TD, Kennard ED, Kelsey SF, Michaels AD; IEPR Investigators.
Cardiovascular Revascularization Medicine: Including Molecular Interventions. 2007 JulSep;8(3):161-165.
24. Enhanced External Counterpulsation in the Management of Angina in the Elderly
Linnemeier G, Michaels AD, Soran O, Kennard ED; International EECP Registry (IEPR)
Investigators. American Journal of Geriatric Cardiology. 2003 Mar-Apr;12(2):90-96.
25. Enhanced External Counterpulsation for the Relief of Angina in Patients with Diabetes:
Safety, Efficacy and 1-Year Clinical Outcomes. Linnemeier G, Rutter MK, Barsness G,
Kennard ED, Nesto RW; IEPR Investigators. American Heart Journal. 2003
Sep;146(3):453-458.
26. Impact of Body Mass Index on Outcomes of Enhanced External Counterpulsation Therapy.
McCullough PA, Silver MA, Kennard ED, Kelsey SF, Michaels AD; IEPR Investigators.
American Heart Journal. 2006 Jan;151(1):139 e9-e13.
27. Effectiveness of Enhanced External Counterpulsation in Patients with Left Main Disease
and Angina. Lawson WE, Hui JCK, Barsness GW, Kennard ED, Kelsey SF for the IEPR
Investigators. Clinical Cardiology. 2004 Aug;27(8):459-463.
International EECP Patient Registry/ Consortium
28. Treatment Benefit in the Enhanced External Counterpulsation Consortium. Lawson WE,
Hui JCK, Lang G. Cardiology. 2000;94(1):31-35.
29. The International EECP Patient Registry (IEPR): Design, Methods, Baseline characteristics
and Acute Results. Barsness G, Feldman AM, Holmes Jr. DR, Holubkov R, Kelsey SF,
Kennard ED. Clinical Cardiology. 2001 Jun;24(6):435-442.Clinical Cardiology. 2007
May;30(5):223-228.
30. Predictors of Benefit in Angina Patients One Year After Completing Enhanced External
Counterpulsation: Initial Responders to Treatment Versus Nonresponders. Lawson WE,
Hui JCK, Kennard ED, Barsness G, Kelsey SF. Cardiology. 2005 Apr 13;103(4):201-206.
31. External Counterpulsation as Treatment for Chronic Angina in Patients with Left
Ventricular Dysfunction: A Report from the International EECP Patient Registry (IEPR).
Soran O, Kennard ED, Kelsey SF, Holubkov R, Strobeck J, Feldman AM. Congestive
Heart Failure. 2002 Nov-Dec;8(6):297-302.
32. Two-Year Outcomes After Enhanced External Counterpulsation for Stable Angina Pectoris
(from the International Patient Registry [IEPR]). Michaels AD, Linnemeier G, Soran O,
Kelsey SF, Kennard ED. American Journal of Cardiology. 2004 Feb 15;93(4):461-464.
33. 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
34. Frequency and Efficacy of Repeat Enhanced External Counterpulsation for Stable Angina
Pectoris (from the International EECP Patient Registry). Michaels AD, Barsness GW,
Soran O, Kelsey SF, Kennard ED, Hui JCK, and Lawson WE for the International EECP
Patient Registry Investigators. American Journal of Cardiology. 2005 Feb;95(3):394-397.
35. Effectiveness of Repeat Enhanced External Counterpulsation for Refractory Angina in
Patients Failing to Complete an Initial Course of Therapy. Lawson WE, Barsness G,
Michaels AD, Soran O, Kennard ED, Kelsey SF, Hui J CK. Cardiology. 2006 Nov
1;108(3):170-175 [Epub ahead of print]
36. Impact of External Counterpulsation Treatment on Emergency Department Visits and
Hospitalizations in Refractory Angina Patients with Left Ventricular Dysfunction. Soran O,
Kennard ED, Bart BA, Kelsey SF. Congestive Heart Failure. 2007 Jan-Feb;13(1):36-40
Hemodynamics
37. Acute Hemodynamic Effects and Angina Improvement with Enhanced External
Counterpulsation. Stys T, Lawson WE, Hui JCK, Lang G, Liuzzo J, Cohn PF. Angiology.
2001 Oct;52(10):653-658.
38. 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.
39. Effects of Enhanced External Counterpulsation on Hemodynamics and its MechanismRelation to Neurohormonal Factors. Taguchi I, Ogawa K, Kanaya T, Matsuda R, Kuga H,
Nakatsugawa M. Circulation Journal. 2004 Nov;68(11):1030-1034.
Mechamisms of Action
40. The Effects 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):160-166. Epub 2007 Dec 4.
41. 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.
42. Enhanced External Counterpulsation 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.
43. Effect of External Counterpulsation on Plasma Nitric Oxide and Endothelin-1 Levels.
Akhtar M, Wu GF, Du ZM, Zheng ZS, Michaels AD. American Journal Cardiology. 2006
Jul 1;98(1):28-30. Epub 2006 May 3.
44. Successful Treatment of Symptomatic Coronary Endothelial Dysfunction with Enhanced External
Counterpulsation.Bonetti PO, Gadasalli SN, Lerman A, Barsness GW. Mayo Clinic Proceedings.
2004 May;79(5):690-692.
Experimental
45. Angiogenic Effects of Long-term Enhanced External Counterpulsation in a Dog Model of
Myocardial Infarction. Wu G, Du Z, Hu C, Zheng Z, Zhan C, Ma H, Fang D, Ahmed KT,
Laham RJ, Hui JCK, Lawson WE. American Journal of Physiology – Heart and Circulatory
Physiology. 2006 Jan;290(1):H248-54. Epub 2005 Aug 19.
46. 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.
Review Papers
47. 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.
48. Enhanced External Counterpulsation for Ischemic Heart Disease: What’s Behind the
Curtain? Bonetti PO, Holmes DR Jr, Lerman A, Barsness GW. Journal of the American
College of Cardiology. 2003 Jun 4;41(11):1918-1925.