Wang et al.

Cardiovascular Ultrasound 2012, 10:35

http://www.cardiovascularultrasound.com/content/10/1/35

CARDIOVASCULAR
ULTRASOUND

RESEARCH

Open Access

A modified regimen of extracorporeal cardiac

shock wave therapy for treatment of coronary
artery disease
Yu Wang1, Tao Guo1,6*, Tie-kun Ma2, Hong-yan Cai1, Si-ming Tao3, Yun-zhu Peng1, Ping Yang4,
Ming-qing Chen5 and Yun Gu1

Abstract
Background: Cardiac shock wave therapy (CSWT) improves cardiac function in patients with severe coronary artery
disease (CAD). We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen.
Methods: The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group
(n = 14) received only medical therapy. In group A (n = 20), CSWT was performed 3 times within 3 months. In
group B (n = 21), patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within
1 month. Primary outcome measurement was 6-minute walk test (6MWT). Other measurements were also evaluated.
Results: The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were
improved in group A and B compared to control group.
Conclusions: A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a
protocol of 3 months duration.
Clinical trial registry: We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.
Keywords: Coronary artery disease, Angina pectoris, Myocardial ischemia, Cardiac shock wave therapy

Background
The most common treatments for coronary artery disease
(CAD) are medications combined with percutaneous coronary intervention (PCI) and coronary artery bypass graft
surgery (CABG). While PCI and CABG are not without
risks, overall results are satisfactory in patients who are
suitable candidates. However, the prognosis for patients
with refractory angina who are not candidates for PCI or
CABG is poor as maximal medical therapy is ineffective in
a large portion of these patients [1,2].
Shock wave (SW) therapy has been used successfully
to treat renal calculi (lithotripsy) and for a number of
orthopedic disorders [3,4]. Recently, experiments have
shown that SWs with energy output at approximately
* Correspondence: [email protected]
1
Department of Cardiology, 1st Hospital of Kunming Medical University,
Kunming, Yunnan, PRC
6
Department of Cardiology, Cardiovascular Center, 1st Hospital of Kunming
Medical University, No.259, Xichang Road, Kunming, Yunnan 650032, PRC
Full list of author information is available at the end of the article

10 % of what is used for lithotripsy can promote neovascularization of cardiac tissue [5,6]. Subsequent clinical
studies have shown that cardiac shock wave therapy
(CSWT) can significantly improve cardiac function in
patients with severe CAD and refractory angina who are
not candidates for PCI or CABG [7-15]. One study that
treated 24 patients with ischemic heart failure and a left
ventricular ejection fraction (LVEF) < 40 % with CSWT
demonstrated that the treatment significantly improved
the cardiac functions assayed [9].
Though the results of CSWT for treating ischemic
heart disease are encouraging, current protocol demands
a treatment duration of three months. A one month
protocol has not previously been developed, but a
shorter protocol would save time and cost, produce better compliance, and might be a more suitable protocol
than a three month protocol in China. Thus, the purpose of this prospective study was to evaluate the clinical
outcome of a 1 month treatment regime as compared to
the standard 3 month treatment regimen as well as to

2012 Wang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Wang et al. Cardiovascular Ultrasound 2012, 10:35

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compare this treatment regime with controls who

received medication only.

Materials and methods

Patients

This study was approved by the Institutional Review

Board and Ethics Committee of 1st Hospital of Kumming Medical University, and all study subjects signed
informed consent for participation in the study and all
treatments performed. Subjects were patients who were
hospitalized at Department of Cardiology of our hospital
from December 2008 to December 2009. Patients were
eligible to be included in the study if they met any of the
following criteria: 1) Coronary angiography (CA) or
multi-slice CT coronary angiography (CTCA) suggestive
of moderate to severe coronary artery stenosis. 2)
Demonstrated cardiac infarction and > 50 % stenosis
after radioactive and sonographic examinations. 3) Chest
tightness, onset of shortness of breath, and poor exercise
tolerance after receiving formal drug treatment (with or
without stent or bypass graft). 4) Hospitalized more than
2 times within 1 year due to the aforementioned problems. 5) CCS angina grading higher than grade II, and
NYHA functional classification of I-III. 6) More than
1 month after acute myocardial infarction (AMI) and
more than 2 weeks after PCI surgery. A history of PCI
or CABG was not a contraindication for inclusion. All
patients included in the study were no option patients
and had coronary heart disease and an imaging examination that confirmed the presence of ischemic myocardium. The diagnosis and treatment in all the patients
was in accordance with the related domestic and European guidelines developed in 2007 [16].
Patients were excluded from the study if they met any
of the following criteria. 1) AMI or CABG within the
4 weeks prior to the study. 2) History of heart transplantation. 3) History of metal valve replacement surgery. 4) Intracardiac thrombus. 5) LVEF < 30 % and
unstable hemodynamics. 6) Arrhythmia with a rate
< 40 bpm or > 120 bpm. 7) Skin ulceration or infection
in the treatment area. 8) Severe obstructive lung disease.
Grouping

Initially, consecutive patients who met the inclusion criteria were randomly divided into the regimen A treatment group and the regimen B treatment group. After
three months, the additional group, a control group, was
added and subsequent patients were randomly added to
the regimen A and B groups and the control group.
Patients in the three groups were enrolled by a physician
who was familiar with patients conditions, and that
physician drew lots to divide the patients into the different groups. The experimental grouping was blinded to
both the physicians who were responsible for treatment

Page 2 of 10

and follow-up and to the patients themselves. The majority of patients with coronary heart disease in this
study had severe symptoms so that they had a strong desire to receive CSWT. Therefore, we pre-set a smaller
sample size for the control group and the sample size
for this group was limited to no more than 15 patients.
The control group did not receive CSWT. The treatment protocol of group A followed the recommended
protocol developed by Tohoku University of Japan with
respect to the shockwave output and the number of
shots delivered to each spot and the protocol developed
by the University of Essen, Germany [10,11]. In group A,
a sequence of 1 week treatment followed by three weeks
rest was repeated 3 times. During each treatment week,
CSWT was performed on days 1, 3 and 5, one session
each day. The total duration of treatment was 3 months,
thus patients received a total of 9 CSWT treatment sessions. In group B, a modified CSWT treatment schedule
was adopted. Patients underwent 3 CSWT sessions/
week, and the 9 treatment sessions were completed
within 1 month. During follow-up, if the patient exhibited no observable lessening of myocardial ischemia, 14
treatment courses were repeated.
Examinations before treatment

Dobutamine stress echocardiography (DSE). Patients

underwent DSE after vascular lesions were identified by
CA and/or CTCA. The use of -blockers, calcium
antagonists, and nitrates were stopped for at least
24 hours before testing. Continuous intravenous infusion
of dobutamine (510 g/kg/min) was administered, and
if regional wall motion abnormalities (RWMA) could
not be induced by low-dose dobutamine the dose was
increased to 2040 g/kg/min. The wall motion score
index (WMSI) was used to assess the state of motion.
Amplitude of regional myocardial motion was the
range of motion measured using M-type echocardiography (Figure 1A). This allows semiquantification of
myocardial motion which can be displayed as a standard
M mode image. Viable myocardial segments were
defined as the 2 adjacent abnormal segments with improvement in contraction during drug administration
(decrease 1 point) [17,18].
Tissue Doppler-based strain rate (SR) was used to
measure peak systolic (PS) SR under resting and load
conditions (Figure 1B) [19,20]. Strain rate measures the
rate of deformation of a tissue segment and is measured
in S1. PSSR represents the maximal rate of deformation
in systole. Strain is obtained by integrating strain rate
over time and represents deformation of a tissue segment over time. Strain is expressed as the percent
change from the original dimension. Systolic strain
represents the magnitude of deformation between end
diastole used as a reference point and end systole. One

Wang et al. Cardiovascular Ultrasound 2012, 10:35

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Figure 1 Imaging methods. (A) Amplitude of regional myocardial motion was the range of motion measured using M-type echocardiography.
(B) PSSR was the measurement of the peak systolic strain rate using tissue Doppler imaging.

of authors of this paper carried out the PSSR measurement for all the patients during the entire follow-up
period. However, that author did not know the treatment of each patient. Before this study, that author conducted a preliminary study on the feasibility and
repeatability of PSSR measurement of all 16 segments of
the left ventricle and the results showed no statistically
significant difference (P > 0.05). Before CSWT treatment, radionuclide imaging and stress echocardiography
were used to locate the ischemic segments in each patient. These segments might be the middle or the apical
segment of interventricular septum, or the lateral basal
segment. The PSSR was measured in the specific ischemic segments.
Resting and dobutamine stress myocardial perfusion
imaging (MPI)

In order to assess myocardial perfusion more accurately,

identify the target for CSWT, and evaluate the therapeutic effects during follow-up, MPI was performed after
vascular lesions were identified. The use of -blockers,
calcium antagonists, and nitrates were stopped at least
24 hours before testing. A two-day method was adopted
for dobutamine load and resting technetium (TC-99 m)
methoxy isobutyl isonitrile (99mTc-MIBI) MPI. The patient was asked to consume a high-fat meal after injection of contrast medium on the first day. Intravenous
continuous infusion of dobutamine (2040 g/kg/min)
was performed 40 min after the contrast medium in the
biliary tract was excreted and it was required that the
target heart rate (220 - age) was reached. Resting scan
was performed 40 min after injection of contrast
medium on the second day. Target myocardium was
located and quantified according to the 17-segment

Myocardial Scoring and the 4-grade scoring system

recommended by American Society of Nuclear Cardiology [21-23]. An increase of 1-point or more in MPI
compared to baseline under both basic and loaded conditions was considered as the criterion for local myocardial blood flow improvement.
Six-minute walk test (6MWT)

A 20-meter quiet and spacious corridor was designated,

and the patients were asked to walk in the corridor at
the maximum speed. If the patient experienced fatigue,
dizziness, angina, or shortness of breath within 6 min,
the test was stopped.
CSWT treatment and control group

CSWT was performed with the MODULITH SLC SW

therapy device (Storz Medical, Switzerland). In brief,
after performing a 12-lead ECG, an ultrasound probe
was used to locate the target myocardium based on the
results of preoperative testing. A water bag was lowered
until it touched the chest wall. Shock waves were applied
to the ischemic areas, and were triggered by the R-wave
of the ECG when the instrument was activated. The
shock wave energy was increased up 0.09 mJ/mm2 if the
patient did not experience discomfort such as chest pain.
Point-to-point combination treatment (8 extra shock
wave treatments around the ischemic area) with 200
pulses delivered to each point was given. Thus, there
were 1800 shock waves administered for each infarcted
segment.
The control group did not undergo CSWT. During the
12-month follow-up, periodic telephone inquiries, outpatient follow-up, and hospitalization were used to

Wang et al. Cardiovascular Ultrasound 2012, 10:35

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adjust the drugs and treat emergencies in addition to the

regular 3-month, 6-month, and 12-month follow-ups.
In both A and B groups, if acute heart failure, unregulated blood pressure, and frequent chest tightness occurred, the treatment was supplemented by timely drug
reinforcement and interventional treatment.
Follow-up

Patients were followed-up at 3, 6, and 12 months after

completion of treatment. Physicians who performed the
follow-up examinations were not aware as to which
treatment the patients received or if they were in the
control group. Follow-up examinations included clinical
assessment using the CCS grading of angina, NYHA
functional classification, Seattle Angina Questionnaire
(SAQ) [24], 6MWT, and recording the nitroglycerin dosage (times/week). Morphological assessment included
measurements of the left ventricular end-diastolic diameter (LVDd) (two-dimensional long axis view of the left
ventricle), left ventricular end-diastolic volume (EDV)
(Simpson method), left ventricular end-systolic volume
(ESV) (Simpson method), LVEF (Simpson method), regional wall motion under resting and load conditions
(M-type measurement), PSSR under resting and load
conditions (quantitative analysis using tissue velocity imaging), MPI score under resting and load conditions
(semi-quantitative analysis using bulls-eye map).
Statistical analysis

Data were summarized as mean SD for continuous

data with a normal distribution, median with interquartile range (IQR: Q1, Q3) for data not normally distributed, and as number (%) for categorical data. Differences
among groups were compared using one-way ANOVA
with a post-hoc Bonferroni adjustment for continuous
data or Kruskal-Wallis test for continuous data that were
not normally distributed; Pearson chi-square test or
Fisher's exact test was used for categorical data.
ANCOVA was applied for comparing the effect between
groups and within groups. Non-parametric methods,
Kruskal-Wallis and MannWhitney U tests, were used
for comparing differences among groups, and pair-wise
comparison and Wilcoxon sign-rank test were used for
comparing the differences within groups as data were
not normally distributed. McNemars test was also applied for identifying the rate of subjects with improvement MPI within groups. The 6MWT was designated as
the primary endpoint, and the b value of the 6MWT as
estimated by the difference between baseline and the
12 month time point was 91.39 % for the control vs.
group A, 70.15 % for the control vs. group B, and
12.17 % for group A vs. group B. All statistical assessments were two-tailed and a value of P < 0.05 was considered statistically significant. Statistical analyses were

Page 4 of 10

performed using SPSS 15.0 statistics software (SPSS Inc.,

Chicago, IL, USA).

Results
A total of 55 patients who met the inclusion criteria
were enrolled. Patient characteristics are summarized in
Table 1. The 55 patients were randomly divided into one
control group (n = 14) and two treatment groups: treatment group A (n = 20) and group B (n = 21). The mean
age in the control group, group A, and group B was 67.9
7.8 years, 62.7 12.0 years, and 64.1 9.8 years, respectively with no significant difference. The only significant difference between the groups was disease history
(P = 0.006). In the control group, all patients completed
follow-up until 12 months. One patient experienced a
recurrent AMI at the 3-month follow-up and underwent
emergency PCI. In group A, 20 patients completed the
6-month follow-up and 19 completed the 12-month follow-up. One patient died from malignant arrhythmias
which induced sudden cardiac arrest after the 6-month
follow-up and 1 patient underwent PCI after the 6month follow-up due to aggravated angina. In group B,
21 patients completed the 6-month follow-up and 10
patients completed the 12-month follow-up. One patient
underwent PCI after the 6-month follow-up due to
aggravated angina. Thus, 39 patients (19 in group A and
10 in group B) completed CSWT treatment and
12 months follow-up without heart failure, syncope, palpitations, breathing difficulty, bleeding, embolism, or
shock.
There were no significant differences in myocardial
enzymes or indicators of liver and kidney function between groups A and B before CSWT, or after the third
and ninth treatment (P > 0.05). Premature ventricular
contractions (PVCs) occurred in 4 cases in group A and
2 cases in group B during CSWT, but these did not
affect blood pressure, heart rate, or oxygen saturation.
The PVCs did not occur again during the following
weeks of treatment. Three patients in group A experienced chest pain during the treatment of the ventricular
septum and the apical segment, and it was relieved after
the shock wave energy was reduced to 0.075-0.06 mJ/
mm2. Those patients were then treated with the same
lower energy, and chest pain did not occur again.
Table 2 shows the comparison of CCS grade, SAQ
score, 6MWT, nitroglycerin dosage, and NYHA classification of the groups 0, 3, 6, and 12 months after treatment. Within-group comparisons (compared with
month 0) revealed the mean CCS was significantly
decreased in both groups A and B from month 3 to
month 12. In the control group, mean CCS was only significantly decreased at month 6 as compared with
month 0. The mean SAQ score at month 6 and month
12 in group A and at months 3, 6, and 12 in group B

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Table 1 Subject characteristics

Age, years

Control group (n = 14)

Group A (n = 20)

Group B (n = 21)

67.9 7.8

62.7 12.0

64.1 9.8

0.337

Sex, male (%)

12 (85.7)

18 (90)

17 (81)

0.882

BMI, kg/m2

24.0 3.2

24.5 2.8

23.4 2.7

0.513

Disease history, years

3 (2, 5)

4 (2.0 , 7.8)

2 (1 , 2)

0.006*

Smokers

6 (42.9)

7 (35.0)

9 (42.9)

0.884

Underwent stenting

11 (78.6)

14 (70)

9 (42.9)

0.080

Essential hypertension

10 (71.4)

13 (65.0)

16 (76.2)

0.708

Diabetes mellitus

4 (28.6)

7 (35.0)

4 (19.0)

0.553

Comorbid conditions

Hyperlipidemia

6 (42.9)

4 (20.0)

4 (19.0)

0.259

COPD

1 (7.1)

0 (0)

0 (0)

NA

Chronic renal failure

0 (0)

1 (5.0)

2 (9.5)

NA

Atrial fibrillation

0 (0)

1 (5.0)

0 (0)

NA

Ulcerative colitis

0 (0)

0 (0)

1 (4.8)

Condition

NA
0.383

Stable angina pectoris

2 (14.3)

0 (0)

0 (0)

Old myocardial infarction

8 (57.1)

13 (65.0)

14 (66.7)

Unstable angina pectoris

4 (28.6)

7 (35.0)

7 (33.3)

Anti-platelet agents

9 (64.3)

11 (55.0)

14 (66.7)

0.774

Aspirin

12 (85.7)

17 (85.0)

19 (90.5)

0.883

Medical therapy

Angiotensin-converting enzyme inhibitors

7 (50.0)

7 (35.0)

8 (38.1)

0.732

Angiotensin receptor blocker

1 (7.1)

4 (20.0)

4 (19.0)

0.659

-blockers

13 (92.9)

18 (90.0)

18 (85.7)

0.872

Calcium channel blockers

4 (28.6)

6 (30.0)

11 (52.4)

0.281

Statin

13 (92.9)

18 (90.0)

17 (81.0)

0.675

Nitrates

4 (28.6)

8 (40.0)

9 (42.9)

0.727

Diuretics

2 (14.3)

3 (15.0)

3 (14.3)

1.000

Oral hypoglycemic agents

3 (21.4)

2 (10.0)

3 (14.3)

0.648

Insulin

2 (14.3)

2 (10.0)

1 (4.8)

0.623

Patients who experienced re-infarction

1 (7.1)

0 (0)

0 (0)

NA

Once

4 (28.6)

2 (10)

2 (9.5)

Twice

1 (7.1)

1 (5)

1 (4.8)

Thrice

1 (7.1)

1 (5)

0 (0)

Mortality

0 (0)

1 (5.0)

0 (0)

NA

Ventricular septum

11 (78.6)

11 (55.0)

12 (57.1)

0.365

Anterior wall

2 (14.3)

4 (20)

4 (19)

1.000

Inferior wall

5 (35.7)

11 (55.0)

14 (66.7)

0.194

Re-hospitalization

0.461

Location of ischemic target area

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Page 6 of 10

Table 1 Subject characteristics (Continued)

Posterior wall

1 (7.1)

3 (15.0)

3 (14.3)

0.771

Lateral wall

2 (14.2)

3 (15.0)

0 (0)

0.161

Number of shock wave treatment (9 times/per treatment course)

NA

2 (1, 2.8)

2 (1, 2.5)

0.904

Duration of treatment interval, month

NA

5 (4, 6.5)

4 (4, 5.5)

0.231

COPD: chronic obstructive pulmonary disease.

Data are presented as mean standard deviation, number (%), or median (IRQ) as described in the statistical analysis methods.
*
P < 0.05, indicated significant difference was identified among control group, group A, and group B.
NA, not assessed.

was significantly increased as compared with month 0.

The mean 6MWT result at month 3, 6, and 12 in group
A and at months 3 and 6 in group B was significantly
increased as compared with month 0. We also performed a treadmill walk test for some, but not all, of the
patients (Additional file 1: Table S1.) This test showed a
significant increase in exercise tolerance in both CSWT

groups, but not in the control group. The median

NYHA classification score at month 3, 6, and 12 was significantly decreased as compared to month 0 in both
group A and B (all, P < 0.05, Table 2).
Figure 2 shows a comparison of the amplitude of regional myocardial motion and PSSR between- and
within-groups. The baseline PSSR at month 12, PSSR

Table 2 Comparison of CCS, SAQ, 6MWT, nitroglycerin dosage, and NYHA classification
Control group (14)

Group A (n = 20)

Group B (n = 21)

363.86 150.92

344.25 106.44

329.43 134.71

6MWT, meters
0 month
3 month

322.07 150.07

422.20 77.30

385.43 78.62

6 month

325.93 157.32

434.25 99.70}

405.33 104.36}

0.073
a

0.296

348.43 132.06

477.95 105.34

452.00 117.47

0.020*

0 month

2 (2.0, 3.0)

2 (1, 2)

3 (2, 3)b

0.045*

3 month

2 (2.0, 2.3)

1 (1, 1)a}

2 (1, 2)}

<0.001*

a}

0.016*

12 month

a}

0.617

CCS grading of angina

6 month

2 (1.0, 2.3)

1 (1, 1)

2 (1, 2)

12 month

2 (1.0, 3.0)

1 (1, 1)a}

1 (1, 2)a}

<0.001*

2 (1, 3)

1.5 (1, 3)

2 (1, 2.5)

0.822

NYHA classification
0 month

3 month

1 (1, 3)

1 (1, 2)

1 (1, 1)

0.138

6 month

1 (1, 2.3)

1 (1, 1)}

1 (1, 1)}

0.081

1 (1, 2.3)

1 (1, 1)

1 (1, 1)

0.018*

0 month

63.21 11.89

64.90 11.72

67.71 13.05

0.549

3 month

63.86 13.27

69.50 10.28

76.38 13.20a}

0.015*

a}

12 month

a}

SAQ score

a}

6 month

60.14 12.82

75.00 10.45

76.14 12.28

<0.001*

12 month

59.21 15.66

79.63 9.87a}

82.70 10.16a}

<0.001*

0 month

1 (0, 4)

1 (0, 2)

2 (0, 3)

0.589

3 month

1 (0, 4)

0 (0, 1)

0 (0, 2)

0.151

6 month

0 (0, 2)

0 (0, 1)

0 (0, 1)

0.597

Nitroglycerin (times/week)

12 month

1 (0, 3)

0 (0, 0)

0 (0, 0)

Data were presented as mean standard deviation, number (%), or median (IRQ) as described in the statistical analysis methods.
#
One patient in group A and 11 patients in group B had missing data of nitroglycerin dosage at month 12.
*P < 0.05, indicates significant difference among control group, group A, and group B.
a,b
P < 0.0167 (0.05/3), indicates significant difference was identified when compared with acontrol group and bgroup A.
}
P < 0.05, indicates significant difference was identified when compared with month 0 of the corresponding group.

0.023*

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Page 7 of 10

Figure 2 Comparison of amplitude of regional myocardial motion at baseline (A-1) and after dobutamine loading (A-2), and PSSR
score at baseline (B-1) and after dobutamine loading (B-2). Data were presented as mean standard deviation as described in the statistical
analysis methods. Twelve patients in group B had a missing record PSSR at baseline in 12 months. *P < 0.05, indicated significant difference was
identified among control group, group A, and group B. }P < 0.05, indicated there was significant difference as comparing with time = 0 months
for a given baseline or after load conditions in the corresponding group.

after the load at month 6 and 12, and baseline MPI at

month 0 were significantly different between the three
groups. Within-group comparisons showed that for both
group A and B, the amplitude of regional myocardial
motion at month 3, 6, and 12 were all significantly
higher than month 0 in both the baseline and the loaded
conditions. For PSSR, the between-group comparisons
showed significant differences at month 6 and 12 in both
the baseline and loaded conditions.
Results of MPI scores that measured the improvement
of individual myocardial segments are shown in Figure 3.
Successful treatment was defined as an increase of 1
point or more compared to month 0 in both baseline
and loaded conditions. Although there is an increase in
percentage of myocardia successfully treated in group A,
the difference is not significant between group A and B.

Discussion
In the current study, following 12 months of observation, the CSWT treatments using two different regimens
both provided satisfactory results that improved myocardial function comparing to pretreatment (month 0) and
to the control group. These results suggest a more frequent treatment regimen (one month) can also provide
equivalent therapeutic efficacy compared to the regimen
of less frequent CSWT treatment (three months).

PSSR, the technique used in this study, has higher

temporal and spatial resolution than M type imaging
[25,26]. Voights study showed that the peak systolic
strain rate (PSSR) in the long-axis view decreased with
the deterioration of the wall motion and that its sensitivity for determining myocardial ischemia was 86 % and
its specificity 90 % in the dobutamine stress test [25]
However, compared with the latest 2D-strain testing,
PSSR is affected by the angle and can only measure the
radial strain in the apical four-chamber and apical twochamber view. It cannot measure the strain in the shortaxis view. The present study selected PSSR to assess the
local cardiac function because it was the earliest and
most mature method available at the beginning of the
study. Our research team members have used it for
many years, therefore systematic errors can be reduced.
Another reason for using PSSR is that we use GE VV7
instrument in our lab, and it has complete TDI and
strain rate imaging software. The 2D-strain requires the
SIMENS Sequia 512 instrument, and that instrument
was not introduced until the late stage of this study.
Therefore, in order to keep the consistency of results,
we did not change the measurement indices.
Two prior studies were conducted by our research
team. In the first, CCS grading of angina and dosage of
nitrate esters were significantly reduced in 9 patients

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Figure 3 Number of ischemic segments with increased baseline

and post-dobutamine loading MPI scores. Results were presented
as bar chart as for the percentage of (A) increased from baseline
value at 3 month and 6 month for each group, (B) increased from
baseline dobutamine loading value at 3 month and 6 month for
each group, and (C) increased from baseline value and baseline
dobutamine loading value at 3 month and 6 month for each group.
*P < 0.05, indicates significant difference among groups through
Fishers exact test. aP < 0.0167 (0.05/3) indicates significant difference
between group A and B through Chi-square test. } P < 0.05 indicates
significant difference within groups (0 to 6 months vs. 0 to
3 months) through McNemars test.

Page 8 of 10

after 3 CSWT treatments and regional myocardial systolic function was improved significantly 1 month after
treatment [12]. In the second, 25 patients had 9 CSWT
treatments and two imaging methods were used, PSSR
and MPI. In this study, the CCS grading of angina and
dosage of nitrate esters, 6MWT, NYHA functional classification, and SAQ score were significantly improved
and the PSSR after load and resting MPI were also significantly improved at the one month follow-up [13].
Other reports have also been encouraging. Fukumoto
et al. [11] treated 9 patients with end-stage CAD who
were not candidates for CABG or PCI, and at 12 months
of follow-up reported that CSWT had significantly
reduced nitroglycerine use (from 5.4 2.5 to 0.3 0.3
times/week), improved CCS functional class score (from
2.7 0.2 to 1.8 0.2), and improved myocardial perfusion as assessed by dipyridamole stress thallium scintigraphy (severity score, 25.2 7.2 % improvement; extent
score, 23.3 9.0 % improvement). Khattab et al.[10]
treated 10 patients with refractory AP who were CCS
class III or IV despite maximal medical therapy with
CSWT and reported that the mean CCS class decreased
from 3.3 0.5 at baseline to 1.0 13 at follow-up and
the mean summed stress score decreased from 8.3 2.2
at baseline to 3.0 3.1 at follow-up.
A shock wave propagates though water as a spike <
1 s in duration with an amplitude up to 100 MPa, that
is followed by a lower amplitude tensile portion lasting
several microseconds [7]. Early studies with animal models of angina pectoris and AMI indicated that CSWT at
approximately 10 % of the energy used for lithotripsy
could improve left ventricular wall motion, LVEF, LV
end-diastolic volume, and regional blood flow and number of capillaries in the border zone (MI) [7]. However,
the molecular mechanism by which shock waves promote neovascularization and improvement of cardiac
function has not been determined.
Shock waves have been reported to activate Ras,
stimulate NO synthesis, produce anti-inflammatory
effects by affecting the expression of chemokines and
matrix metalloproteases, and upregulate VEFG and the
VEGF receptor (Flt-1) [5,27-31]. How these effects lead
to cardiac changes and improvement of cardiac function
are not clear; however, it is possible that shock waves increase the incorporation of circulating endothelial progenitor cells (EPCs) by up-regulating the expression of
stromal-derived factor 1 (SDF-1), which is necessary for
the recruitment and incorporation of EPCs, in ischemic
myocardium [7,32].
In our study, the one month treatment had the same
efficacy as the 3 month treatment at the 12 month follow-up. These results are exciting, but the mechanism
by which a shorter term, more frequent treatment produces the same effect as a longer term, less frequent

Wang et al. Cardiovascular Ultrasound 2012, 10:35

http://www.cardiovascularultrasound.com/content/10/1/35

treatment is still unclear. We speculate that the mechanism might be related to the cellular and molecular
mechanisms of blood vessel formation [33-35]. In other
words, when repeated shock wave stimulations are given
within 1 month, the resulting succession of shear force
effects will produce a waterfall phenomenon, and a large
number of neovascular networks will form in a short
period of time, ultimately promoting the establishment
of collateral circulation in the ischemic area.
Limitations of the study are that we only used our second objective test of working capacity on a partial sample of the patient population. Also, because the patients
in group B were admitted to the study later than the
patients in group A, only 11 of the 21 patients in group
B had been followed up at the time the paper was
written.

Conclusions
In summary, our results showed that CSWT can improve clinical symptoms and morphological and functional indices in patients with complex CAD. A CSWT
treatment regimen of one month duration provided
similar therapeutic efficacy compared to a regimen with
three months duration. CSWT is proven effective and
useful for patients excluded from CABG and PCI therapies and patients whose medication treatments are no
longer effective.
Additional file
Additional file 1: Table S1. Comparison of treadmill exercise test
for control, 3 month and 1 month CSWT patients.

Abbreviations
6MWT: 6-minute walk test; CAD: Coronary artery disease; CSWT: Cardiac
shock wave therapy; CCS: Canadian cardiology society; NYHA: New York
heart association; SAQ: Seattle angina questionnaire; PSSR: Regional wall
motion, peak systolic strain rate; MPI: Myocardial perfusion imaging.
Competing interests
The authors declare no conflict of interest.
Authors contributions
We declare that all the listed authors have participated actively in the study
and all meet the requirements of the authorship. Dr. Tao Guo , Ming-Qing
Chen, Yun Gu designed the study and wrote the protocol, Dr. Yu Wang,
Hong-Yan Cai, Si-Ming Tao, Yun-Zhu Peng, Ping Yang performed research/
study, Dr. Tie-Kun Ma, Hong-Yan Cai contributed important reagents, Dr. Yu
Wang, Tao Guo managed the literature searches and analyses, Dr. Yu Wang,
Si-Ming Tao undertook the statistical analysis, Dr. Yu Wang wrote the first
draft of the manuscript. All authors read and approved the final manuscript.
Funding source
None to declare.
Acknowledgements
We thank Dr Ernest H.Marlinghaus, Storze Medical AG, Switzerland, for his
valuable help and comments.

Page 9 of 10

Author details
1
Department of Cardiology, 1st Hospital of Kunming Medical University,
Kunming, Yunnan, PRC. 2Department of Nuclear Medicine, 1st Hospital of
Kunming Medical University, Kunming, Yunnan, PRC. 3Department of
Cardiology, 2nd Peoples Hospital of Yunnan Province, Kunming, Yunnan,
PRC. 4Department of Cardiology, 1st Peoples Hospital of Kunming, Yunnan,
PRC. 5President of 1st Hospital of Kunming Medical University, Kunming,
Yunnan, PRC. 6Department of Cardiology, Cardiovascular Center, 1st Hospital
of Kunming Medical University, No.259, Xichang Road, Kunming, Yunnan
650032, PRC.
Received: 9 April 2012 Accepted: 9 August 2012
Published: 17 August 2012
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doi:10.1186/1476-7120-10-35
Cite this article as: Wang et al.: A modified regimen of extracorporeal
cardiac shock wave therapy for treatment of coronary artery disease.
Cardiovascular Ultrasound 2012 10:35.

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