EECP as a Noninvasive Treatment of Endothelial Dysfunction
Cross section of an artery showing a monolayer of endothelial cells lining the inner wall of the artery. The
arterial wall is composed of smooth muscle cells and collagen.
By John CK Hui, Ph.D.
Introduction
Over the past 30 years, endothelium has emerged as the key regulator in the initiation and progression of
1-4
cardiovascular disease. The endothelium is the monolayer of endothelial cells lining in the direction of
blood flow along the lumen of all blood vessels. The endothelial cells function as a protective barrier and
facilitate bi-directional transport of macromolecules and blood gases between all tissues and circulating
blood. Endothelial cells also control vasomotor function, regulating vasodilatation and vasoconstriction by
5,6
the release of nitric oxide (NO) and endothelin-1 (ET-1). These neurohomonal factors play a vital role in
hypertension, reduction of oxidative stress and arterial stiffness. Vascular endothelium is also responsible
for the regulation of angiogenic vascular remodeling, metabolic, anti-inflammatory, and anti-thrombogenic
processes.
Endothelial cells also play a critical role in the process of atherosclerosis, leading to coronary, renal and
peripheral artery disease. Endothelial dysfunction initiates expression of endothelial adhesion molecule-1
and monocyte chemoattractant protein-1 which incorporate circulating macrophage monocytes and Tcells into the subendothelial space, changing them into macrophage foam cell, while at the same time
promoting smooth muscle cell proliferation and migration, and increased platelet activity and coagulation,
leading to thrombosis, atherogenesis and neointimalization.
Enhanced External Counterpulsation (EECP)
®
An EECP therapy 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. 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. The QRS complex of the electrocardiogram is used
to provide a triggering signal for the calf inflation valve to open around the peak of T-wave, the lower thigh
valve will open 50 ms later, to be followed by the upper thigh valve another 50 ms later. The pressure in
the cuffs will hold as long as possible to allow maximization of diastolic augmentation. Then all threedeflation valves will open at the same time around the peak of P-wave to let the emptied peripheral
vasculature to receive the blood ejected by the heart, leading to systolic unloading.
®
There are many pathophysically pathways by which EECP therapy achieves its long-term clinical
7
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 inhibiting intimal hyperplasia and atherosclerosis. There is also evidence
suggesting that EECP therapy triggers a neurohomonal response by improvement of endothelial function
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 the
recruitment of new arteries, while exisiting blood vessels dilate and normalize in function. The recruitment
of new arteries, known as “collateral blood vessels”, bypasses blocked or narrowed vessels and increase
blood flow to ischemic areas of the organs that are receiving an inadequate supply of blood. A summary
of the proposed mechanisms of action of EECP therapy is shown in the following diagram:
®
EECP Therapy: Mechanisms of Action
Acute Hemodynamic Effects
Increase shear Stress Systolic Unloading
Diastolic Augmentation Increase Cardiac Output
Improve Endothelial Function
Vasodilation: NO↑ ET-1↓ Vascular resistance ↓
Arterial Stiffness ↓
Intimal Hyperplasia ↓
Circulating Endothelial Progenitor Cell ↑
Angiogenesis: microvascular density↑
Proinflammatory Cytokines and Adhesion Molecules:
TNF-α↓, MCAP– 1 ↓
Reduce hypertension
Improve Blood Flow
Reduce atherosclerosis
Clinical Benefits: Sequential inflation of three sets of cuffs at the end of systole Lower ThighCuffsUpper Thigh
CuffsCalfSimultaneous deflation of all three sets of cuffs at the end of diastole Lower ThighUpper ThighCuffsCalf
Published clinical data showing effectiveness of EECP therapy in improving endothelial dysfunction
Historically, an external counterpulsation (ECP) device is a cardiac assist device that reduces the
workload of the heart and increases energy supply to the myocardium. The objectives of ECP devices are
the maximal reduction of systolic blood pressure so that the heart does not have to generate high
pressure to eject the volume of arterial blood for the metabolic need of the body, and maximal
augmentation of diastolic pressure to increase coronary perfusion pressure to increase coronary blood
flow when resistance to coronary flow is at its lowest level. The optimal ECP operation is to achieve the
maximization of the ratio of the area under the diastolic pressure to the area under the systolic pressure.
1. Acute hemodynamic effects of EECP (Enhanced External Counterpulsation): Increase cardiac
output and coronary blood flow
The physiological and clinical goal of EECP is the improvement of cardiac function and increase of
cardiac output, as demonstrated by the increase of velocity of blood flow in the descending aorta using
8,9
Doppler echocardiography. Systolic time velocity integral as a measure of stroke volume (SV) increased
up to 60-70% over control with the heart rate (HR) remaining stable, demonstrating a significant increase
in cardiac output. EECP also created a significant diastolic retrograde blood flow, generating a bidirectional pulsatile fin the descending aorta, increashear stress on the endothelium.
EECP also resulted in a dramatic increase in intracoronary pressure and intracoronary flow velocity
10
measured by using a coronary catheter sensor-tipped guidewire. Coronary diastolic pressure increased
93% from 71 10 at baseline to 137 ± 21 mm Hg durinEECP, p<0.0001; with a decrease icoronary systolic
pressure of 15%from 116 ± 22 to 99 ± 26 mm Hg, p=0.002. The intracoronary average peak velocity
increased 109% from 11 ± 5 at baseline to 23 ± 5 cm/sec during EECP, p=0.001. The signific
inDescending Aorta ControlDuring EECP Stroke volume Diastolic retrograde flow Doppler echocardiography of the descending aorta
2. Effects of EECP pulsatile blood flow: increase endothelial shear stress Endothelial shear stress
flowing blood on the endothelial surface of the arterial wall and is expressed in un 2222
tress is proportional to the product of the blood viscosity (μ) and the spatial gradient of blood velocity at
the wall. Low endothelial shear stress modulates endothelial gene expression through complex
mechanoreception and mechanotransduction processes, inducing an atherogenic endothelial phenotype
11
and formation of an early atherosclerotic plaque. Therefore the significant increase of pulsatile,
oscillatory flow in the aorta durEECP treatment provides a form of “massage” on the endothelium and
improves its function. Effect of EECP on endothelial shear stress has been reported in an animal
moZhang in 112
ultrasound system during EECP in thebrachial artery was significantlcompared with the pre-EECP
measurement (24.62±4.74 versus 59.48±13.60 cm/sec, p<0.001). Theinternal diameter (id) of the right
brachial artery was not significantly changes durinEECP (1.65±0.42 versus 1.68±p<0.05). The blood
viscosity (μ) wa3.8±0.4 mPa (0.038±0.004 poise). Thpeak diastolic endothelial shear stress (τ) d τ
2
(dynes/cm ) = (4 μ V) / (id) Peak diastolic endothelial shear stress during EECP increased more then 23. Blood vessels vasodilate in response to an increase of flow through rather to the endothelial shear
stress. Conversely, low shear stress leads to const remodel vasodilation occurs in the earliest stages of
atherosclerosis, and this endothelial dysfunction is now considered to be the link between such risk
factors as dyslipidemia, hypertension, diabetes mellitus, cigarette smoking, hyperhomocysteinemia, and
aging to cardiovascular disease.
13,14
The endothelial response to shear stress activates a varietysignaling
pathways, including endotheoxide synthase (eNOs), an enzyme rethe synthesis of nitric oxide (NO), the
key endothelium-derived relaxing factor that plays a† p< 0.05 versus CHOL group 150200eNOs (% of control) †eNOs
ring EECP was calculated using the formula: 10.71 dynes/cm2; p<0.001). tone and reactivity. EECP has
been shown to increase the expression of eNOs by Zhang and co-workers in a hypercholesterolemic pigs
12
model using Western blotting technique. Expression of eNOs was significantly decreased in the group of
pigs (N=28) fed with high-cholesterol diet for 15 weeks compared with the 7 pigs with normal diet served
as control (p=0.009). 1 hour daily of EECP for 34±2 hours was initiated in 17 pigs after 8 weeks of
atherogenic diet and eNOs expression of the EECP treated group was 3.16 times that of thecholesterol
group (p=0.023).
4. EECP therapy increases the release of nitric oxide and reduces. In response to endothelial shear
stress, Nitric Oxide (NO) is synthesized in th In addition, NO also inhibits platelet and white cell activation
and maintains the vascular smooth muscle cells in a nonproliferative state. More importantly, NO interacts
with products of oxidative stress such as superoxide and hydrogen peroxide. Oxidative stressproduced
from any cardiovascular risk factors is one of the leading causes of endothdysfunction. EECP
16
published later in 2006. This study examined whether the flow mediated increase in endothelial shear
stress would activate plasma levels of the potent vasoactive agents ET-1 and NO. Thirteen coronary
disease patreceived 1-hour daily EECPtreatment for a total of 36 hourand their ET-1 and NO were
measured serially at baseline (Control), after the 1st, 12th, 24and 36th hours of EECP, and at 1 and 3
months post-EECP. During the course of treatment, plasma NO progressively increased and plasma ET-1
progressively decreased. After 36 hours of EECP, there was a 62 ± 17% increase in plasma NO
compared with baseline (43.6 ± 4.27.1 ± 2.6 μmol/L; p<0.0001),a 36 ± 8% decrease in plasm1 level (76.7
± 9.5 versus 119.8.5 pg/L; p<0.0001). At 3 months after completion of EECP, NO remained 13 ± 11%
above baseline (p=0.002), and ET-1 remained 11 ± 10% below baseline (p=0.0068). These results
demonstrate that EECP therapy has a dose related, sustained effect in stimulating endothelial cell
production of the vasodilator, NO, and in deceasing production of the vasocontrictor, ET-1, supporting the
hypothesis that EECP improves endothelial function. In another study, Masuda
and colleagues
demonstrated that EECP significant increased plasma NO levels compared with baseline in 1patients with
chronic stable anginthe day after the start of EECP, and 1 week, 1 month after completion of35 hours of
17
daily 1-hour EECP treatment (p<0.02). The treadmill exercise time, time to 1 mm ST-segment
depression, perfusion in ischemic regions of the myocardat rest and during dipyridamole stress measured
11
by N-ammonia positron emission tomography inthese patients also improved signifendothelial function
via increase oto the observed clinical benefits of EECP treatment.
There are s
with endothe
18,19
follow-up compared with patients with preserved endothelial function.
More importantlythe observation
that an intervention improves endothelial function in a group of patients suffering from cardiovascular
20
disease suggests that the intervention will also reduce cardiovascular risk. Currently the most promising
noninvasive endothelial function testinthe endothelial-dependent, flow-mediated dilation of the brachial
artery using high-resultrasound. In 2003
that improvement in per
21
EECP treatment in patients with symptomatic coronary artery disease (CAD). Reactive hyperemiaperipheral arterial tonometry (RH-PAT), a noninvasive method to assess peripheral endothelial function
by using a device manufactured by Itamar Medical in measuring reactive hyperemic response in the finger
(Endo PAT 2000, FDA 510k032was performed in 23 patients with refractory angina undergoing a 1-hour
daily EECP total course of 35-hour treatment. In each patient RH-PAT measurements were performed
th
before and after the first, at midcourse (17 hour), and after the last EECP course. In addition, RH-PAT
response was assessed one month after completion of EECP therapy. RH-PAT index, a measured of
reactive hyperemia, was calculated as the ratio of the dpulse volume during reactive hyperemia divided by
that at rest. EECP was associated withsignificant immediate increase in average RH-PAT index after
each treatment period (p<0.05). In addition, average RH-PAT index at one-month follow-up was
significantly higher than that before EECP therapy (p<0.05), demonstrating EECP therapy provided long
Nitric Oxide measured by the Griess method in 11 CAD patients. Control: before EECP therapy. Next day: 1 day following completion of 35hour course of therapy. 1 week: 1 week after completion of therapy , and 1 month: 1 month after completion. # p<0.02 vs control, and p<0.01
vs next day.
improvement of endothedysfunction in patieCAD. No major adverse cardiovascular evennoted during the
study perio In addition to RH-measurement of endothelial function, Canadian
Cardiovascular
function (CCS) class and Duke Activity Status Index (DASI) score were uassess the clinical benefEECP
therapy. EECP therled to an improvement by oCCS class in 12 (52%) patients and by two CCS class in 5
(22%) patients, whereas 6 (26%) patients showed no change in CCclass.
in this study, 74% experience an improvement in their functional status. Similarly, 17 (74%) patients
reported improvement in their functional status, as measured by the DASI score. Moreover, average RHPAT before initiation of EECP therapy and one month after completion of therapy significantly increased
only in patients showing improvement functional CCS class or DASI score. Patients failed to show
improvement in their endotheliafunction also failed to improve their cardiac function class and status,
demonstrating a direct relationship between endothelial dysfunction and cardiovascular disease,
supporting the role of EECP as an effective therapeutic strategy for patients with endothelial dysfunction.
1.0 0.5 01st h17th h35th h1-month follow-up *N=18Pre-Post-*p<0.05; †p<0.05 vs pre EECP index on 1st, 17th and 35th hr J Am Col Cardiol
2003:41101761-8*PAT Index 2.0Despite significant cardiac risk profiles and advanced CAD among patients
included
Results of the Mayo Clinic were supported by another paper in 2003 by Shechter and co-workers using
the endothelial-dependent, flow-mediated dilation (FMD) of the brachial artery with high-resolution
22
ultrasound technique to assess endothelial vasomotor function. This is a prospective age-matched
controlled study. The endothelial function in 20 consecutive CAD patients (15 males), mean age 68 ± 11
years, with refractory angina pectoris CCS class III and IV, unsuitable for coronary revascularization was
assessed by FMD before and after their ECP treatment. These measurements were compared with 20
matched control CAD patients (17 males). There were no significant group differences in baseline
characteristics between the ECP and Control group, with 75% in CCS class IV. There were no significant
changes in concomitant medication use and no serious adverse effects throughout the study. After
completion of 35 hours of daily 1 hour ECP treatment, FMD improved significantly from baseline 3.1 ±
2.2% to 8.2 ± 2.1%; p=0.01), whereas there were no changes in the Control group within the 2-month
period. ECP also improved angina symptoms by a reduction in mean number of sublingual nitrate tablets
consumption per day (from 4.2 ± 2.7 to 0.4 ± 0.5; p<0.001), compared with no change in the Control
group (4.5 ±2.3 to 4.4 ± 2.6; p=0.87). The mean CCS class also improved significantly in the ECP group
(3.5 ± 0.5 to 1.9 ± 0.3; p<0.0001), with no change in the Control group (3.3 ± 0.6 to 3.5 ± 0.5; p=0.89).
This study demonstrates that ECP intervention compared with controls results in significant improvement
in endothelial dysfunction and cardiac function status.
In 2004, Bonetti and co-workers reported a very interesting case of a 29 year-old woman with chest pain
23
despite medications with various calcium antagonists, β-blocker and antidepressant. Coronary
angiography revealed structurally normal vessels. Administration of adenosine into the left coronary
system showed an intact endothelium-independent microvasculature response; with a normal coronary
flow reserve of 2.5. However, intracoronary infusion of grades doses of endothelium-dependent
-6
-4
vasodilator acetylcholine (10 to 10 mol/L) into the left anterior descending (LAD) artery was associated
with a progressive decrease in coronary flow, ultimately resulted in complete LAD occlusion, compatible
with the presence of severe endothelial dysfunction of both the coronary microvasculature and the
coronary macrovasculature. Despite the addition of an angiotensin-converting enzyme (ACE) inhibitor and
L-arginine supplementation to the patient’s existing treatment regimen, the patient symptoms worsened
during the subsequent months and severely impaired her functional capacity. Patient status changed from
CCS Class III to CCS class IV. Patient was treated with 35-hour of daily 1-hour course of EECP. After
completion of EECP, the patient was free of angina and was able to perform her daily activities without
the dyspnea or fatigability experienced before EECP. At the last follow-up visit 3 months after completion
of EECP therapy, the patient was symptom free with a medication regimen of calcium channel blockade,
ACE inhibitor and L-arginine supplementation. Endothelial dysfunction is considered to be major key early
event in atherosclerosis. This case is interesting because the patient had no traditional cardiovascular risk
factors and no manifestations of advanced atherosclerotic disease and Baseline 2-month after EnrollmentJ Am Coll
Cardiol 2003;42:2090-5
yet suffered from severe coronary endothelial dysfunction. The sustained clinical improvement after a
standard course of EECP in a patient with severely symptomatic coronary endothelial dysfunction
supports the concept that EECP can be used as a treatment of endothelial dysfunction.
6. Effects of EECP treatment on arterial stiffness, a manifestation of endothelial dysfunction
Arterial stiffness is a strong independent predictor of cardiovascular outcomes above and beyond
traditional cardiovascular risk factors in both healthy subjects and patients with high risk of coronary artery
24,25
disease.
Muscular arterial stiffness is related to smooth muscle tone and NO bioavailability. Under
basal conditions, NO is continually released from healthy endothelial cells and serves to inhibit adhesion
of platelets and leukocytes to the vessel wall. After diffusion to the media, NO activates the enzyme
guanyl cyclase, which increases formation of cyclic guanosine monophosphate (cGMP) to relax smooth
muscle cells and maintain vascular patency and distensibility. When the endothelium becomes
dysfunctional, bioavailability of NO is limited, impairing smooth muscle cell relaxation, leading to arterial
stiffness.
The effect of EECP treatment on artery stiffness has been examined by Nichols and co-workers using
applanation tonometry to measure radial artery pressure waveforms for the generation of the central
26
aortic pressure waveforms using a mathematical transfer function. The constructed aortic pressure
waveform can be considered to have two components, the forward flow from cardiac ejection (from Pd to
Pi) and reflected wave from peripheral (Ps-Pi). As arterial stiffness incretransmission velocity of both
forward and reflected waves increase, causing the reflected wave to arrive earlier in late systole,
increasing systolic blood pressure, left ventricular (LV) workload and therefore tension time index. The
augmentation of aortic pressure can be expressed as augmented pressure [AP=(Ps-Pi)] or Augmentation
Index and the myocardial energy wasted in overcoming this additional systolic pressure can be cal
Nichols and colleagues measured the radial artery pressure waveforms of 20 patients with stable
refractory angina before and after 34 1-hour EECP sessions. The heart rate and ejection duration did not
change with EECP treatment. Brachial systolic and pulse pressure reduced significantly from 132 ± 18 to
121 ± 18 mm Hg (p<0.001) and 61 ± 15 to 54 ± 16 mm Hg (p<0.001) respectively. Aortic systolic pressure
reduced from 120 ± 18 to 108 ± 18 mm Hg (p<0.001), and aortic pulse pressure from 48 ± 14 to 41 ± 16
mm Hg Pressure Waveforms Pressure without reflectionPsPiPdPulse Pressure = (Ps – Pd) Augmentation Index = AIx =(Ps – Pi) / (Ps –
Pd) Time for pressure wave to travel from aortic root and back = Δt p Wasted LV pressure energy = 2.09 X Δtp * (Ps – Pi)
LVWorkload=TensionTimeIndex=areaundersystolicwave (p<0.001). Mean blood pressure also decreased
significantly
from 92 ± 13 to 84 ± 9.5 mm Hg (p<0.001). Associated with the fall in arterial blood pressure was an
improvement in wave reflection characteristics. Compared with baseline, reflected wave augmented
pressure AP decreased from 13 ± 7.1 to 8.7 ± 6.8 mm Hg (p<0.001) after EECP treatment, and Alx
referenced at a heart rate of 75 beats/min reduced from 18 ± 9.6 % to 12 ± 8.4 % (p<0.01), indicating a
significant reduction of arterial stiffness. The reduced arterial stiffness caused a decrease in transmission
velocity and increase travel time Δtp/2 of the reflected wave from the lower body to the heart (p<0.001),
and a decrease in reflected wave systolic duration Δtr from 182 ± 33 to 168 ± 41 ms (p<0.01).
The improvement in arterial wall properties and wave reflection characteristics indicated a significant
reduction in LV workload. These afterload changes were associated with improvement in indexes of
myocardial oxygen demand. The reduction in wave reflection pressure with EECP treatment and the
associated decrease in wave reflection duration caused a decline in LV wasted energy. Also, compared
with baseline, the tension-time index (representing myocardial oxygen demand) also reduced significantly
(p<0.001).
EECP treatment reduces arterial stiffness was also supported by the findings of Levenson and co-workers
in a prospective, randomized, controlled study using high-resolution ultrasound Echo-Doppler evaluation
of the diameters of the carotid artery in 30 patients (28 males and 2 females) with stable coronary artery
27
disease. The patients were randomly assigned to either an active EECP group (n=15) with 300 mm Hg
applied pressure or a sham group (n=15) with less then 75 mm Hg of applied external counterpulsation
pressure during EECP treatment. All subjects underwent 35 hours of either sham or active
st
th
th
counterpulsation. Echo-Doppler studies were performed after the 1 hour, the 17 hour and the 35 hour
of EECP therapy. A longitudinal scan of both right and left common carotid arteries allowed visualization
of the lumen-intima and media-adventitia interfaces of the proximal and distal wall, the maximum diameter
(dmax) and minimum diameter (dmin) were then determined for each cardiac cycle, average over 3-4
successive cycles. Average brachial blood pressures were measured during carotid examination and the
mathematically transformed to central systolic pressure (Ps) and central diastolic pressure (Pd).
Measurement of arterial stiffness can be estimated by the nondimensional pressure-independent β
stiffness index:
β stiffness index = Ln(Ps/Pd)/DD
where DD = (Dmax-Dmin)/Dmin is the arterial distension. Carotid artery blood flow was measured and carotid
vascular resistance (CVR) can be calculated as CVR=Mean blood pressure /volume blood flow (ml/min).
Platelet cGMP content was measured at baseline and after 17 and 35 hour of EECP therapy. There were
no significant between-group differences in baseline clinical characteristics or in baseline carotid
hemodynamics values. There were no major complications occurred during EECP treatment. The
absolute change from baseline before EECP in the β stiffness index was significantly reduced at 1 hour
(p<0.01), 17 hour (p<0.001) and 35 hour (p<0.01) after EECP treatment in the active EECP group, and
this decrease was statistically different when compared with controls at 1 and 35 hour (p<0.05,
respectively). Also, in contrast to controls, mean carotid blood flow in patients receiving active EECP
increased significantly at 1 hour (p<0.05) and again more strongly at 35 hour (p<0.001), with a trend
present at 17 hour (p=0.07). The difference between groups was significant at 17 hour (p<0.05) and 35
hour (p<0.01). Carotid vascular resistance was concomitantly reduced in active EECP treated group at 17
hour (p<0.05) and 35 hour (p<0.01), showing a significant difference between groups in carotid vascular
resistance at 17 hour (p<0.01) and 35 hour (p<0.001). Adjustment for multiple covariates (age, sex,
systolic and diastolic blood pressure, body mass index, smoke, glucose and low-density lipoprotein
cholesterol) did not change the observed differences in arterial stiffness or vascular resistance between
the study groups. Platelet cGMP contents increased at 1, 17 and 35 hour by 0.019 ± 0.02, 0.058 ± 0.05
8
and 0.052 ± 0.05 pmol/10 platelets in controls and by 0.097 ± 0.02, 0.059 ± 0.08 and 0.087 ± 0.09
pmol/108 platelets in the active EECP treated groups respectively. Platelet cGMP in the active group
negatively correlated with β stiffness index (n=59, r=-0.32, p<0.05), but not in patients in the control
group. Results of this study suggest that active EECP therapy relaxes the smooth muscle tone of the
carotid artery and consequently decreases their arterial stiffness via the signaling product of NO
pathways, supporting the hypothesis that EECP therapy improves endothelial dysfunction.
th
Recently, Braith and co-workers reported in the 2009 American College of Cardiology 58 Annual
Scientific Session the results of a prospective, randomized, controlled study on the effects of EECP in the
28
peripheral endothelial functions of 30 symptomatic patients with CAD (20 active and 10 sham).
Control (Sham) EECP
Active EECP
Variables
Baseline
BFMD (%)
4.2 ± 0.7
Post
Sham
4.3 ± 0.6
p
Baseline
NS
3.7 ± 0.2
PostEECP
5.8 ± 0.4
p
<0.05
FFMD (%)
2.8 ± 0.4
2.8 ± 0.3
NS
2.6 ± 0.2
3.5 ± 0.3
<0.05
FBF (ml/min/100ml)
19.0 ± 1.6
18.9 ±1.5
NS
19.3 ± 1.3
23.5 ± 1.4
<0.05
CBF (ml/min/100ml)
17.1 ± 1.6
16.9 ± 1.5
NS
15.2 ± 1.4
18.8 ± 1.0
<0.05
23 ± 2
22 ± 4
NS
24.2 ± 3
16.8 ± 4
<0.05
135 ± 4
131 ± 4
NS
134 ± 3
144 ± 2
<0.05
49 ± 8
48 ± 7
NS
54 ± 9
33 ± 6
<0.05
CF-PWV (m/sec)
11.5 ± 0.7
11.6 ± 0.5
NS
12.1 ± 0.5
10.2 ± 0.4
<0.05
Plasma Nox (μmol/L)
24.8 ± 5.2
25.3 ± 6.4
NS
21.5 ± 2.5
32.8 ± 3.4
<0.05
ADMA (μmol/L)
0.75±0.07
0.74±0.09
NS
0.66 ± 0.04
0.44 ±0.03
<0.05
ED (sec)
550 ± 71
566 ± 68
NS
582 ± 40
771 ± 56
<0.05
Time to angina (sec)
366 ± 43
374 ± 31
NS
392 ± 45
602 ± 44
<0.05
VO
16.0 ± 1.5
17.0 ± 1.3
NS
17.2 ± 1.0
21.2 ± 1.3
<0.05
Ala (%)
ΔT (ms)
p
LV
-2
we
(msec-mm Hg )
2peak
(ml/kg/min)