Abstract
Objective
This study aims to evaluate the clinical efficacy of extracorporeal cardiac shock wave therapy(CSWT) and enhanced external counterpulsation(EECP),both individually and in combination,in patients with coronary artery disease(CAD),and to explore effective non-invasive treatment strategies.
Methods
A total of 259 patients with CAD admitted between January 2023 and June 2024 were enrolled and randomly assigned to four groups:the Control group(n = 65) received conventional medication only; the EECP group(n = 65) received conventional medication plus EECP treatment(EECP; total duration 36 h); the CSWT group(n = 64) received conventional medication plus CSWT therapy(CSWT; total duration 4.5 h); and the Combination group(EECP + CSWT group,n = 65) received conventional medication combined with both CSWT(4.5 h) and EECP(36 h).Coronary stenosis severity, cardiac function indices, blood biochemistry and other indicators were evaluated at baseline and 12 months after treatment.
Results
Baseline characteristics showed no significant differences among the groups(P > 0.05). After 12 months of treatment, the Gensini score of the EECP + CSWT group decreased by 20 points, which was significantly lower than that of the EECP group (−5 points, P < 0.05), the CSWT group (−15 points, P < 0.05) and the control group (−0.5 points, P < 0.05). Secondly, compared with the control group, the CSWT group, EECP group and EECP + CSWT group showed more significant improvements in cardiac function and blood biochemical parameters (P < 0.05). The EECP + CSWT group exhibited the most pronounced therapeutic efficacy, followed by the EECP group and the CSWT group; all three intervention groups were significantly superior to the Control group (P < 0.05).
Conclusion
Both CSWT and EECP effectively improve the severity of coronary artery disease, cardiac function,and blood biochemical parameters in CAD patients.The combination of these two therapies demonstrates synergistic effects, yielding significantly superior outcomes compared to either monotherapy.
Keywords: Enhanced external counterpulsation, Extracorporeal cardiac shock wave therapy, Coronary artery disease, Cardiac rehabilitation
Highlights
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First systematic comparison of CSWT, EECP alone and combined in CAD treatment, filling research gaps.
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Clarifies CSWT-EECP complementarity, explaining potential synergistic mechanisms.
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Confirms long-term safety of non-invasive therapies, offering safe options for non-invasive-intolerant patients.
1. Introduction
With the improvement of living standards, coronary artery disease(CAD) has become the leading cardiovascular disease affecting the health of global residents [1]. Although more and more patients with CAD have received drug treatment, percutaneous coronary intervention(PCI), coronary artery bypass grafting surgery(CABG), there are still recurrent symptoms such as chest tightness, chest pain,and heart failure, which lead to an increase in the incidence and re-hospitalization rate, reduce the quality of life of patients,and increase the economic burden of families [2,3]. Meanwhile, PCI is not suitable for all patients with coronary heart disease. For example, patients may have diffuse lesions, high-risk anatomy, coexisting conditions such as bleeding tendency or renal insufficiency, or patients may prefer to avoid invasive treatment [4]. Therefore, non-invasive physical cardiac rehabilitation has become an indispensable part of modern cardiac disease treatment, which can reduce cardiovascular risks and the incidence of cardiovascular events,thereby prolonging life and improving the quality of life [5]. There are various physical therapy methods to improve myocardial perfusion, such as enhanced external counterpulsation therapy, cardiac shock wave therapy, cardiovascular ultrasound therapy, and so on.
Enhanced external counterpulsation(EECP) involves applying specialized pneumatic cuffs to the patient's calves, thighs, and buttocks. During ventricular diastole, these cuffs undergo sequential compression, elevating diastolic pressure [6]. This augmentation enhances myocardial blood supply and alleviates myocardial ischemia EECP therapy accelerates arterial blood flow velocity, improves vascular endothelial function, promotes endothelial repair, inhibits neointimal hyperplasia, and suppresses the progression of atherosclerotic lesions [[6], [7], [8], [9]].
Extracorporeal cardiac shock wave therapy (CSWT), utilizes externally applied low-energy ultrasound waves targeted at localized myocardial tissue. Within myocardial cells, this generates mechanical shear stress and cavitation effects. These forces elicit biomechanical responses at the subcellular level, subsequently triggering a cascade of biochemical reactions. Studies have demonstrated that CSWT promotes vascular regeneration, increases myocardial perfusion, improves left ventricular remodeling,and reduces symptoms in patients with chronic myocardial ischemia [10,11].
Typically, both CSWT and EECP are used in patients with refractory angina. Studies have shown that CSWT, as a noninvasive therapy, is mainly used in patients with refractory coronary heart disease, that is, those who cannot benefit from further revascularization (such as PCI or CABG) or who have contraindications to revascularization [12]. While numerous studies have primarily investigated the molecular biological mechanisms and clinical efficacy of each therapy(CSWT or EECP) in CAD patients [[13], [14], [15], [16], [17], [18], [19], [20], [21]], a direct comparison of these two non-invasive modalities is lacking. Therefore, this study was designed to compare the long-term clinical outcomes of CSWT with EECP in a wider range of CAD patients, including those who are not candidates for or refuse PCI.The study was conducted in strict accordance with the ethical principles outlined in the Declaration of Helsinki.
2. Methods
2.1. Participants
A total of 259 patients with CAD admitted between January 2023 and June 2024 were enrolled and randomly assigned to four groups. This study has been approved by the medical ethics Review Committee of Caoxian People's Hospital (ethical approval number: 202316010577).
2.2. Inclusion criteria
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Aged 18–80 years with confirmed CAD;
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Presence of moderate to severe coronary artery stenosis confirmed by coronary angiography or coronary CT angiography(CCTA) (Defined as lumen stenosis of ≥50 % in coronary arteries);
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Chronic Stable Heart Failure: the NYHA classification of heart function was II-III;
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Hemodynamically Stable;
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Patients who did not undergo PCI because of unfavorable coronary anatomy, high surgical risk, patient refusal, or patients with moderate vessel stenosis who did not temporarily require intervention.
2.3. Exclusion criteria
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NYHA grade IV;
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Acute myocarditis, pericarditis, moderate or large pericardial effusion, infectious endocarditis, intracardiac thrombus;
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Severe aortic valve stenosis, aortic aneurysm, thoracic aortic dissection, thoracic aortic aneurysm;
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After heart transplantation, after heart metal valve replacement, pulmonary embolism;
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Deep vein thrombosis of the lower extremities, active thrombotic phlebitis;
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Hemorrhagic disease or significant bleeding tendency;
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Infection focus in the counterpulsating limb;
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Moderate to severe pulmonary hypertension(mean pulmonary artery pressure >50 mmHg);
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Uncontrolled hypertension(>180/110 mmHg).
2.4. Interventions
The control group received conventional drug therapy; Supplementing drug therapy, the EECP group underwent 36-h enhanced external counterpulsation(P-ECP/T1 device, Chongqing Push Kang) with 30–60 min daily sessions. Treatment pressure(0.025–0.040 MPa) was titrated to optimize diastolic augmentation peaks at minimal effective intensity. The CSWT group underwent extracorporeal shock wave therapy in addition to drug therapy, the ischemic region was identified by clinicians based on coronary angiography or coronary CTA findings. Subsequently, 1–2 target segments were selected for therapy. At each segment, treatment was administered across nine sites, with 200 pulses delivered per site at an energy level of 0.024–0.090 mJ/mm2. The complete therapeutic course comprised nine sessions. The combination therapy group received both CSWT therapy and EECP treatment in addition to pharmacological treatment.
2.5. Calculation of sample size
Power Analysis and Sample Size (PASS) professional software was used to select the "ANOVA: Fixed effects, omnibus, one-way" model for sample size calculation. According to the significance level of 0.05, the test Power (power = 1-β) was 80 %. Because there were multiple group comparisons (four groups) involved, a stricter alpha value of 0.0125 was used in the calculation of the initial sample size to be a conservative estimate and to ensure the final power of the test. We hypothesized that the combination treatment group (CSWT + EECP) would have the most significant effect in reducing the Gensini score compared with the control group. Referring to similar studies, we anticipated that the mean difference in the Gensini score change (ΔGensini) between the combination group and the control group would be approximately 15 points, predicted that the standard deviation (SD) of ΔGensini would be approximately 20 points across groups, and required a sample size of 259 to allow for a 15 % dropout rate.
2.6. Randomization
Block randomization of a multiple of four12 was used with the use of a computer-generated random-number sequence to maintain sample-size homeostasis between groups. The randomization sequence was generated by an independent statistician and stored under seal, and the clinical investigators assigned the treatment after enrollment on a sequential basis to avoid assignment bias.
2.7. Blinding
Blinding was not supported because of the treatment approach. Both CSWT and EECP are active physical therapies that involve specific equipment and procedures. The patient can sense the therapeutic intervention, and the operator must directly perform the treatment.
Although blinding to patients and operators was not possible, assessor blinding was used to reduce measurement bias. The primary end point, the Gensini score, was scored in a blinded manner by independent cardiovascular imaging experts who were not involved in patient treatment allocation or clinical management to ensure objectivity of end-point assessment. Statistical analyses were performed by blinded statisticians who processed the data without reference to group information to further minimize analysis bias.
2.8. Monitoring indicators
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Primary endpoint: Gensini score. Coronary artery stenosis was assessed by coronary CTA, and stenosis was quantified by the Gensini scoring system, including stenosis location, degree, and extent, with higher scores indicating greater coronary stenosis, to quantify the effect of treatment on stenosis progression or stabilization [22].
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Secondary endpoints:
Cardiac Function Parameter. Left ventricular ejection fraction(LVEF) was measured using Doppler echocardiography;
Blood Biochemical Parameters. Lipid profile(Total cholesterol(TC), Triglycerides (TG), Low-density lipoprotein cholesterol(LDL-C), High-density lipoprotein cholesterol(HDL-C), Lipoprotein(a)[Lp(a)]), Renal function markers(Creatinine (Cr), Urea, Uric acid (UA)).
All outcome measures were assessed at baseline prior to therapeutic initiation and at the 12-month follow-up visit after treatment completion.
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Safety indicators: incidence of major adverse cardiovascular events (MACE). MACE included recurrent angina pectoris, recurrent myocardial infarction, heart failure with new or worsening symptoms after treatment, cerebral infarction, cerebral hemorrhage, and gastrointestinal bleeding.
2.9. Statistical analysis
Categorical data are expressed as frequencies(percentages)[n(%)], with intergroup comparisons performed using χ2 or Fisher's exact tests. Continuous variables were initially assessed for normality(Shapiro-Wilk or Kolmogorov-Smirnov test) and homogeneity of variance (Levene's test). For variables violating normality and/or homoscedasticity assumptions, data are presented as median(interquartile range)[M(Q1,Q3)] and analyzed with the Kruskal-Wallis test for between-group comparisons. If the Kruskal-Wallis test showed statistically significant differences (P < 0.05), post hoc pairwise comparisons were performed using the Mann-Whitney U test with Bonferroni correction.Intragroup analyses employed the Wilcoxon signed-rank test. All analyses were conducted in SPSS 29.0 with statistical significance defined at α = 0.05.
3. Results
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As shown in Table 1,no significant differences were observed among the four groups in terms of age, sex composition, comorbidities(hypertension, diabetes and stroke), or baseline medication usage rates (P > 0.05). This meets the baseline comparability requirements for randomized controlled trials and provides a reliable foundation for subsequent efficacy comparisons (see Table 2).
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No significant differences were observed among the four groups in baseline Gensini score, LVEF, creatinine, urea, or uric acid levels (P > 0.05). At 12-month follow-up, all groups showed significant improvement in the above indicators compared to the baseline, except for uric acid in the control group. Significant between-group differences emerged in both post-treatment values and change-from-baseline magnitudes. The EECP + CSWT group demonstrated significantly greater improvement than monotherapy groups (EECP/CSWT groups) (P < 0.05), while monotherapy groups outperformed the control group.
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Baseline lipid profiles showed no significant differences across the four groups (see Table 3). At the 12-month follow-up, significant improvements occurred in all lipid parameters across groups except for LDL-C and lipoprotein(a) in the control group. Between-group analyses revealed significant differences in both post-treatment levels and change magnitudes, and the EECP + CSWT group demonstrated significantly greater improvement than monotherapy groups (EECP/CSWT groups) (P < 0.05), while monotherapy groups showed superior efficacy to the control group(P < 0.05).
Table 1.
Comparison of baseline characteristics by group.
| Control group(n = 65) | EECP(n = 65) | CSWT(n = 64) | EECP + CSWT(n = 65) | χ2/F | P-value | |
|---|---|---|---|---|---|---|
| Age(years) | 69(61.5,72) | 67(59.5,72) | 65(59.25,71.75) | 68(56,74.5) | 0.202 | 0.929 |
| Gender(male:female)n(%) | 42:23(64.6:35.4) | 43:22(66.2:33.8) | 44:20(68.8:31.3) | 40:25(61.5:38.5) | 0.776 | 0.858 |
| Hypertension n(%) | 43(66.2) | 44(67.7) | 42(65.6) | 42(64.6) | 0.143 | 0.991 |
| Diabetes n(%) | 24(36.9) | 21(32.3) | 20(31.3) | 26(40.0) | 1.418 | 0.72 |
| Stroke n(%) | 18(27.7) | 15(23.1) | 13(20.3) | 8(12.3) | 4.925 | 0.177 |
| aspirin n(%) | 54(83.1) | 59(90.8) | 59(92.2) | 60(92.3) | 4.026 | 0.270 |
| Clopidogrel n(%) | 43(66.2) | 43(66.2) | 46(73.0) | 52(80) | 4.179 | 0.246 |
| Ticagrelor n(%) | 7(10.8) | 14(21.5) | 12(18.8) | 9(13.8) | 3.346 | 0.34 |
| Statins n(%) | 63(96.9) | 65(100) | 64(100) | 65(100) | 3.528 | 0.247 |
| Nitrates n(%) | 36(55.4) | 45(69.2) | 44(68.8) | 50(76.9) | 7.12 | 0.69 |
Table 2.
Comparison of gensini score, cardiac function, and renal function parameters between and within groups.
| Indicator | Group | Before treatment | After treatment | Change(△) | Intragroup P-value |
|---|---|---|---|---|---|
| Gensini | Control group | 25(12.25,40.50) | 30(20,47) | −0.5(-5,0) | 0.019 |
| EECP | 31(20,69) | 29.5(15,50) | −5(-15,0)∗ | <0.001 | |
| CSWT | 35(25,50) | 20(15,30) | −15(-20,-6) ∗ | <0.001 | |
| EECP + CSWT | 40(27,60) | 20(14,30) | −20(-34.75,-10) ∗@& | <0.001 | |
| P value | 0.297 | <0.001 | <0.001 | ||
| EF(%) | Control group | 60(51.5,62) | 60(52.5,62) | 1(0,2) | 0.036 |
| EECP | 60(56,62) | 62(60,62) | 2(0,4) ∗ | <0.001 | |
| CSWT | 60(55,62) | 60.5(60,62) | 2(0,5) ∗ | <0.001 | |
| EECP + CSWT | 59(55,60) | 62(60,63) | 3(1,7) ∗@& | <0.001 | |
| P value | 0.469 | <0.001 | <0.001 | ||
| Cr, (μmol/L) | Control group | 79(59.5,99) | 71(60,83) | −6(-17.50,-2) | <0.001 |
| EECP | 77(60,95.5) | 60(54.5,70.5) | −12(-24.65,-2.80) ∗ | <0.001 | |
| CSWT | 78(65.25,96) | 66(60,74.98) | −12.85(-26.5,-2.7) ∗ | <0.001 | |
| EECP + CSWT | 79(68,99) | 60(52,73) | −20(-32,-9.3) ∗@& | <0.001 | |
| P value | 0.510 | <0.001 | <0.001 | ||
| Urea, (mmol/L) | Control group | 6.24(5.19,8.97) | 5.95(4.88,7.01) | −0.51(-1.22,-0.06) | <0.001 |
| EECP | 6.08(4.95,7.70) | 5.0(4.45,5.93) | −0.87(-1.80,-0.26) ∗ | <0.001 | |
| CSWT | 6.36(5.16,8.12) | 5.3(4.73,5.84) | −1.06(-2.45,-0.25) ∗ | <0.001 | |
| EECP + CSWT | 5.94(5.02,7.31) | 4.5(4.0,5.21) | −1.58(-2.3,-0.78) ∗@& | <0.001 | |
| P value | 0.819 | <0.001 | <0.001 | ||
| UA, (μmol/L) | Control group | 334(285,407.5) | 321(281.4371) | −30(-72,35.1) | 0.063 |
| EECP | 334(282.35,411.5) | 264(220,353.5) | −45(-118,-12)∗ | <0.001 | |
| CSWT | 352(278.10,434.50) | 276(235.5334.5) | −45(-117.75,-2.5)∗ | <0.001 | |
| EECP + CSWT | 327(265,405.5) | 219(203,280) | −77(-142,-36)∗@& | <0.001 | |
| P value | 0.560 | <0.001 | <0.001 |
∗p < 0.05vs control group @p < 0.05vsEECP & p < 0.05vsCSWT.
Table 3.
Comparison of serum lipid profiles between and within groups.
| Indicator | Group | Before treatment | After treatment | Change(△) | Intragroup P-value |
|---|---|---|---|---|---|
| TC,(mmol/L) | Control group | 4.45(3.60,5.18) | 4.46(3.39,5.21) | 0.05(-1.41,0.9) | 0.130 |
| EECP | 4.6(3.70,6.14) | 4.24(3.5,4.69) | −0.99(-2.36,0.81) ∗ | <0.001 | |
| CSWT | 4.32(3.62,5.60) | 3.48(3.16,4.17) | −0.69(-1.61,-0.085) ∗ | <0.001 | |
| EECP + CSWT | 4.63(4.11,5.95) | 3.58(2.94,3.93) | −1.11(-1.96,-0.64) ∗@& | <0.001 | |
| P value | 0.245 | <0.001 | <0.001 | ||
| TG,(mmol/L) | Control group | 1.20(0.89,1.67) | 1.21(0.82,1.7) | −0.06(-0.38,0.19) | 0.132 |
| EECP | 1.20(0.95,1.66) | 0.94(0.70,1.25) | −0.22(-0.70,0.01) ∗ | <0.001 | |
| CSWT | 1.32(0.97,1.91) | 1.02(0.84,1.48) | −0.27(-0.61,0.06) ∗ | <0.001 | |
| EECP + CSWT | 1.45(0.98,1.96) | 0.83(0.59,1.11) | −0.59(-1.05,-0.29) ∗@& | <0.001 | |
| P value | 0.341 | <0.001 | <0.001 | ||
| HDL-C,(mmol/L) | Control group | 1.13(0.99,1.42) | 1.23(1.07,1.42) | 0.02(-0.19,0.23) | 0.472 |
| EECP | 1.14(0.97,1.40) | 1.29(1.11,1.47) | 0.19(-0.13,0.33) ∗ | 0.001 | |
| CSWT | 1.22(1.04,1.43) | 1.37(1.17,1.51) | 0.17(-0.10,0.32) ∗ | <0.001 | |
| EECP + CSWT | 1.12(0.94,1.31) | 1.59(1.32,1.73) | 0.46(0.16,0.63) ∗@& | <0.001 | |
| P value | 0.349 | <0.001 | <0.001 | ||
| LDL-C,(mmol/L) | Control group | 2.71(2.45,3.07) | 2.01(1.64,2.58) | −0.75(-1.21,-0.22) | <0.001 |
| EECP | 2.86(2.03,4.01) | 1.82(1.41,2.30) | −0.98(-1.90,-0.33) ∗ | <0.001 | |
| CSWT | 2.93(2.50,3.91) | 1.84(1.42,2.25) | −1.0(-1.93,-0.25) ∗ | <0.001 | |
| EECP + CSWT | 3.03(2.41,3.99) | 1.78(1.35,2.12) | −1.29(-1.96,-0.75) ∗@& | <0.001 | |
| P value | 0.184 | 0.025 | <0.001 | ||
| Lp(a),mg/L | Control group | 179(90,347.5) | 150(69.5315) | −14(-57.5,12) | 0.004 |
| EECP | 169(86.5322.5) | 134(81,259) | −51(-96.50,0.50) ∗ | <0.001 | |
| CSWT | 244.5(117.25,388) | 153(88.75,324) | −50.50(-101.75,-10.25) ∗ | <0.001 | |
| EECP + CSWT | 201.8(75,445) | 120(64.50,169.50) | −90.00(-220.50,-10.00) ∗@& | <0.001 | |
| P value | 0.567 | 0.035 | <0.001 |
∗p < 0.05 vs control group @p < 0.05 vs EECP & p < 0.05vs CSWT.
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There were statistically significant differences among the groups in the major adverse cardiovascular events(χ2 = 24.248,P < 0.001). In terms of the total incidence of adverse events, the control group had the highest rate (see Table 4), which was 38.5 %(25/65); the EECP group was 21.5 %(14/65); the CSWT group was 12.5 %(8/63); and the EECP + CSWT group had the lowest rate, at 6.2 % (4/65).
Table 4.
Comparison of major adverse cardiovascular events (MACE) incidence among groups.
| Group | Recurrent angina pectoris | Recurrent myocardial infarction | Heart failure | Cerebral infarction | Cerebral hemorrhage | Gastrointestinal bleeding | Total incidence |
|---|---|---|---|---|---|---|---|
| Control group | 12(18.5 %) | 1(1.5 %) | 9(13.8 %) | 2(3.1 %) | 0(0 %) | 1(1.5 %) | 25(38.5 %) |
| EECP | 13(20 %) | 0(0 %) | 1(1.5 %) | 0(0 %) | 0(0 %) | 0(0 %) | 14(21.5 %) |
| CSWT | 4(6.3 %) | 0(0 %) | 0(0 %) | 2(3.1 %) | 1(1.6 %) | 1(1.6 %) | 8(12.5 %) |
| EECP + CSWT | 3(4.6 %) | 1(1.5 %) | 0(%) | 0(0 %) | 0(0 %) | 0(0 %) | 4(6.2 %) |
| χ2 | 24.248 | ||||||
| P | <0.001 |
Refers to HF with new or worsening symptoms only after treatment.
4. Discussion
This study systematically evaluated the interventional effects of different therapeutic approaches by monitoring multiple indicators in control, EECP, CSWT, and combination (EECP + CSWT) groups at baseline and 12 months post-treatment. The results demonstrated that after 12 months of intervention, all indicators in all groups were significantly improved, except for LDL-C, Lp(a),and UA in the control group. Moreover, the inter-group analysis indicated that there were significant differences in the levels after treatment and the amount of changes. The improvement range of the EECP + CSWT group was significantly greater than that of the single treatment groups (EECP/CSWT group), and the efficacy of the single treatment groups was better than that of the control group. This provides an important reference for the selection of clinical treatment schemes.
Gensini score is an important indicator for evaluating the severity of coronary artery disease [23], and the degree of its improvement directly reflects the therapeutic effect on coronary atherosclerosis. From a pathophysiological perspective, coronary atherosclerosis is a complex process involving multiple links such as lipid deposition, inflammatory response, plaque formation, and vascular stenosis. CSWT and EECP are effective mainly by improving perfusion and microcirculation. Their effects on stenosis may be reflected in delaying progression or promoting plaque stability, thereby indirectly reversing stenosis. EECP therapy reduces the risk of platelet aggregation and thrombosis by increasing coronary perfusion pressure and blood flow velocity [24]. At the same time, it promotes the establishment of collateral circulation, thereby improving coronary blood perfusion and reducing the degree of vascular stenosis. CSWT may stimulate vascular endothelial cells through mechanical stress, releasing active substances such as vascular endothelial growth factor, and promoting angiogenesis and plaque stabilization [25]. In the case of EECP + CSWT therapy, the mechanisms of action of the two treatment methods are synergistic. The hemodynamic environment improved by EECP therapy may provide more favorable conditions for the vascular repair induced by CSWT therapy, and the angiogenesis promoted by CSWT can further enhance the blood perfusion effect of EECP.
Although the patients in our study had a baseline LVEF in the normal range (mean, 60 %), changes in LVEF, a standard measure of cardiac function, may reflect subtle effects of treatment on myocardial function. Studies have shown that subclinical left ventricular dysfunction may be present even in CHD patients with normal LVEF, and these abnormalities are associated with metabolic control or microvascular lesions [26], which emphasizes the importance of monitoring LVEF in the assessment of CHD. At the same time, LVEF, as a part of multi-parameter evaluation, helps to fully understand the comprehensive effect of treatment regimens on cardiac function. EECP therapy enhances myocardial contractility by reducing cardiac afterload and myocardial oxygen consumption, while augmenting coronary blood flow to enhance myocardial metabolism [6,27], and these effects may be manifested through subtle changes in LVEF. CSWT can improve LVEF in patients with CAD, especially in patients with end-stage or severe disease. Studies on patients with end-stage diffuse CAD (EnD-CAD) have shown that CSWT can significantly improve LVEF [16]. In addition, a study on patients with severe CAD after CABG (sample size 30) also observed improvement in myocardial perfusion after CSWT, which may indirectly promote LVEF improvement [28]. EECP treatment has a positive effect on left ventricular function in patients with CAD and may indirectly improve LVEF. For example, EECP can provide long-term relief of ischemic chest pain and improve left ventricular function, and significant changes in hemodynamic parameters have been observed especially in patients with CAD [29]. At the same time, one study showed that EECP significantly improved myocardial perfusion (mean difference change was significant), which may have contributed to the overall improvement in left ventricular function [29,30]. In addition, EECP treatment is associated with the improvement of left ventricular function in patients with low systolic blood pressure, which can optimize LV functional parameters [31]. In the present study, we observed that CSWT can increase EF, which is consistent with the conclusions of previous meta-analyses [32,33]. This further supports the effectiveness of CSWT in improving cardiac function. When both treatments are used in combination, ejection fraction can be significantly increased, which may be associated with reduced cardiac burden, improved myocardial metabolism, cardiomyocyte repair, and improved myocardial structure. Studies have shown that the mechanism of CSWT mainly involves promoting myocardial angiogenesis and blood flow improvement. A prospective study showed that CSWT can significantly increase myocardial perfusion in patients with CAD, which may be achieved by increasing collateral circulation or coronary microvascular function, thereby alleviating myocardial ischemia and improving left ventricular function [28,34,35]. In AMI models, CSWT has been shown to reduce myocardial fibrosis and promote cardiac function recovery [36,37]. The transient effects of CSWT include vasodilation, which may indirectly increase LVEF by improving the balance between myocardial oxygen supply and demand [35,38]. The effect of EECP is mainly based on its hemodynamic and vascular function regulation. EECP indirectly improves LVEF by mechanically compressing the lower limbs, increasing diastolic aortic pressure and coronary blood flow, increasing cardiac output (such as increased cardiac output), optimizing left ventricular afterload and preload [29,30,39,40]. EECP can improve vascular endothelial function and reduce endothelial dysfunction, which may optimize coronary microcirculation (including microvascular disease) by regulating flow shear stress, and indirectly improve myocardial perfusion and left ventricular function [[41], [42], [43]]. The mechanism of CSWT and EECP is still partially unknown, especially the mechanism of combination therapy, which needs more high-quality randomized trials to verify in the future.
Dyslipidemia is a key risk factor for the occurrence and development of atherosclerosis [44]. Changes in blood lipid indicators, especially the improvement of indicators such as LDL-C, are of great significance for preventing and delaying the progression of cardiovascular diseases [45]. Elevated LDL-C makes it more likely to deposit in the vascular wall, forming atherosclerotic plaques. One study explored the effect of CSWT combined with exercise rehabilitation in patients with CHD after PCI and found a significant increase in HDL-C levels after treatment, while other lipid parameters such as total cholesterol (TC) and LDL-C also tended to improve [25]. This suggests that CSWT may affect lipid metabolism through indirect mechanisms, such as enhanced exercise tolerance and antiinflammatory effects, but this is primarily an effect of the combination with rehabilitation training rather than CSWT alone. Regarding indicators of renal function (e.g., creatinine, urea, uric acid), there is a lack of direct evidence in the existing literature to support that CSWT or EECP can change these parameters. Studies have shown that CSWT enhances endothelial progenitor cell proliferation by promoting VEGF and IL-8 secretion, but it has not been implicated in renal function [26]. Therefore, based on the exploration of possible pleiotropic mechanisms of CSWT and EECP, including potential effects on metabolic and inflammatory states, the present study observed changes in blood biochemical parameters after EECP and CSWT treatment. In this study, the LDL-C levels decreased in both the EECP group and the CSWT group after 12 months,and the degree of decrease in the EECP + CSWT group was superior to that in the single-treatment groups(EECP + CSWT group vs.EECP/CSWT group: 1.29 mmol/L vs.-0.98/-1.0 mmol/L,P < 0.001). The advantage of the combined treatment group in improving blood lipid indicators may be due to the synergistic regulatory effect of EECP and shock wave therapy through different metabolic pathways. Their combined effect leads to a more significant reduction in atherogenic lipid components.
However, this study also has some limitations. First, the sample size may be relatively small, which could have a certain impact on the reliability of the research results.Second, the follow-up period of the study is 12 months, and further extension of the follow-up period is needed for the evaluation of long-term efficacy. This study did not use serial coronary angiography to directly assess plaque morphology, and the anatomical impact of CSWT and EECP on stenosis needs to be inferred indirectly by combining functional indicators (such as perfusion improvement) and long-term clinical endpoints, which can be further verified by using transluminal imaging (such as OCT or IVUS) in future studies. In addition, this study did not conduct in-depth molecular biological exploration of the therapeutic mechanism.In the future, in-depth research can be carried out on the mechanism of action of the combined therapy from aspects such as cellular signaling pathways.
5. Conclusion
Both CSWT and EECP therapy effectively improve the severity of coronary artery disease, cardiac function, and blood biochemical parameters in CAD patients. The combination of these two therapies demonstrates synergistic effects, yielding significantly superior outcomes compared to either monotherapy.
CRediT authorship contribution statement
Ting Zhao: Formal analysis, Conceptualization. Suping Lan: Formal analysis, Data curation, Conceptualization. Yun Zhang: Investigation. Yupin Dong: Resources. Lunyan Lu: Supervision. Xu Chen: Resources. Song Li: Resources, Project administration, Methodology. Yuncheng Li: Validation, Resources. Shen Wang: Writing – original draft. Yue Wang: Writing – review & editing. Xiaofan Wu: Visualization, Supervision, Resources. Xinjian Li: Project administration, Methodology.
Author agreement
All of authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Declaration of competing interest
The named authors have no conflict of interest, financial or otherwise.
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