Influence of enhanced external counterpulsation on endothelial function: a meta-analysis of randomized controlled trials

Abstract

Objectives

Enhanced external counterpulsation (EECP) is an effective and noninvasive treatment for patients with refractory angina and chronic heart failure. However, previous studies evaluating the influence of EECP on endothelial function showed inconsistent results. This systematic review and meta-analysis was conducted to evaluate the effects of EECP on endothelial function measured by brachial artery flow-mediated dilation (FMD).

Design

PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials comparing the influence of EECP versus usual care on FMD in adult population. A random-effects model incorporating the potential influence of heterogeneity was used to pool the results.

Results

Nineteen studies with 1647 patients were included in the meta-analysis. Compared with usual care or conventional therapy, additional treatment with EECP for 3–7 weeks was associated with a significantly improved FMD (mean difference [MD]: 1.96%, 95% confidence interval [CI]: 1.57–2.36, p < 0.001, I² = 52%). Subgroup analysis showed consistent results in patients with coronary artery disease and in patients with other diseases (p for subgroup difference = 0.21). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p < 0.001). Results of subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% (MD: 2.69, 95% CI: 2.27–3.10, p < 0.001; I² = 15%) compared to those with baseline FMD < 5% (MD: 1.49, 95% CI: 1.13–1.85, p < 0.001; I² = 0%; p for subgroup difference < 0.001).

Conclusions

EECP may be effective in improving endothelial function measured by FMD.

Keywords:

• Endothelial function
• flow-mediated dilation
• enhanced external counterpulsation
• randomized controlled trials
• meta-analysis

Introduction

Endothelial dysfunction has been recognized as a hallmark of coronary artery disease (CAD) and chronic heart failure (CHF) [1–3]. Physiologically, endothelial dysfunction is associated with increased expression of adhesion molecules and inflammatory cytokines, which have been involved in the formation and rupture of atherosclerotic lesions [4]. Clinically, brachial artery flow-mediated dilation (FMD) has been well used as a non-invasive indicator of vascular endothelial function [5,6]. In response to ischemia-induced hyperemia, FMD reflects the availability of endothelium-derived vasodilators in the brachial artery, which mainly includes nitric oxide (NO) [7]. The existing body of evidence indicates that specialized laboratories adhering to standardized protocols can attain highly reliable measurements of FMD [8]. Additionally, FMD could be used to investigate the acute and long-term effects of physiological and pharmacological interventions on endothelial function in human subjects [8]. In addition, according to previous studies, endothelial function determined by FMD is also a predictive and prognostic factor for CVDs [9,10], suggesting that improving FMD may favorably affect the clinical outcomes of these patients.

Accumulating evidence suggests that enhanced external counterpulsation (EECP) is an effective noninvasive treatment strategy for patients with refractory angina and CHF [11,12]. The EECP therapy works via sequential inflation of three sets of cuffs around the lower extremities during diastole and deflation during systole, thereby leading to the pulsatile enhancement of the aortic diastolic blood flow and coronary perfusion, and increment of arterial wall shear stress [13]. In CAD patients with refractory angina, EECP therapy is shown to be effective in attenuating the symptoms of chest pain and improving the exercise tolerance [14]. In patients with CHF, EECP treatment is related to improved cardiac function and exercise capacity [15]. The underlying mechanisms of the benefits of EECP in these patients may involve the improvement of endothelial function [16]. However, previous clinical studies evaluating the influence of EECP treatment on brachial artery FMD showed inconsistent results [16]. Therefore, this systematic review and meta-analysis was performed to comprehensively evaluate the effect of EECP on FMD in adult patients.

Methods

This study was designed and performed according to the Cochrane Handbook guidelines [17] and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement [18,19]. The PRISMA Checklist of the current systematic review and meta-analysis is shown in Supplementary File 1.

Search strategy

A combination of strategies was used to search PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant studies with: (1) “enhanced external counterpulsation” OR “EECP” OR “external counterpulsation”; and (2) “endothelial” OR “endothelium” OR “flow-mediated dilation” OR “FMD” OR “flow mediated dilation,” limited studies in human. The detailed search protocol for PubMed is shown in Supplemental File 2. We also manually searched for reference lists of the reviews and original articles that were related to the topic. Database searches were conducted on 18 March 2023.

Study selection

Studies were included if they fulfilled the following criteria according to the PICOS principles.

P (patients): adult patients at risk for CVDs or with established diagnosis of CVDs. The definition of adult patients at risk for CVDs (such as those with conventional cardiovascular risk factors, such as hypertension, diabetes, dyslipidemia, metabolic syndrome, and chronic kidney disease) or with established diagnosis of CVDs (such as those with CAD, CHF, stroke, peripheral artery disease) were defined according to the criteria of the original studies.

I (intervention): EECP on the basis of usual care or conventional treatments.

C (control): usual care or conventional treatments only.

O (outcome): difference of the changes of brachial artery FMD between patients allocated to the intervention and control groups after the treatment.

S (study design): parallel-group randomized controlled trials (RCTs), published as full-length articles in peer-reviewed journals.

Non-RCTs, studies that did not include an intervention group of EECP, those comparing the effects of different protocols of EECP, single-arm studies without controls, or studies not evaluating the outcome of FMD were excluded. Studies with a single session EECP were also excluded because we did not aim to observe the acute influence of EECP on FMD. For studies with overlapping patients, the study with the largest sample size was included.

Data extraction and quality assessment

Literature search, data extraction, and study quality evaluations were performed by two independent authors. The agreement between the two authors was determined by using Cohen’s Kappa value. If a disagreement occurred, the corresponding author was consulted to resolve this inconsistency. Information regarding publication details (first author, publication year, and study country), study design (blind or open-label), patient characteristics (diagnosis, demographic information, smoking status, mean FMD at baseline), intervention (protocols, durations, and accumulating hours of EECP treatment), control, and methods for measuring FMD was extracted. We evaluated the quality of RCTs using the Cochrane Risk of Bias Tool [17] in accordance with the following criteria: (1) random generation of sequences; (2) concealing allocations; (3) blinding of participants and staff; (4) blinding of outcome assessors; (5) presenting incomplete outcome data; (6) reporting selective results; and (7) other potential biases. In addition, two reviewers evaluated the certainty of evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system, which includes risk of bias, inconsistency, indirectness, imprecision and publication bias [20]. The certainty of evidence was classified as very low, low, moderate or high. Disagreements were resolved by discussion with the corresponding author.

Statistical analysis

The influence of EECP on brachial artery FMD compared to control was summarized as mean difference (MD) and corresponding 95% confidence intervals (CIs). The Cochrane Q test was performed [21]. Heterogeneity was also estimated by calculating I², and I² >50% suggested significant heterogeneity [22]. A random-effects model was used in the pooled analyses to account for potential heterogeneity and provide a more general conclusion [17]. We conducted a sensitivity analysis to assess whether each study contributed to the pooled meta-analysis results irrespective of whether it was included or excluded [17]. A predefined subgroup analysis was also conducted according to the diagnosis of the patients. In case of significant heterogeneity, a univariate meta-regression analysis was performed to identify if difference of study characteristics may significantly affect the results, such as number of the patients, mean age, proportion of men, mean FMD at baseline, EECP treatment duration, and accumulated hours of EECP treatment. If significant modifier was identified, a subgroup analysis was further performed accordingly with the median of the variable as the cutoff value. Funnel plots and Egger’s regression asymmetry test were conducted to determine publication bias [23]. Statistical significance was defined as p < 0.05. Stata software (version 12.0; Stata Corporation) and RevMan (version 5.1; Cochrane, Oxford, UK) were used for statistical analysis.

Results

Search results

Figure 1 shows the diagram of database search and study inclusion. Briefly, 44 articles from 479 initially obtained studies were reviewed for full texts, and 19 RCTs [24–42] were included for the meta-analysis.

Figure 1. Flowchart of literature search.

Study characteristics and data quality

An overview of the included studies is presented in Table 1. Overall, 19 RCTs [24–42] with 1647 adult patients were included in the meta-analysis. Most of the studies included patients with CAD [25–27,29,31–34,36,38–42], while for the other studies, patients with metabolic syndrome [24], hypertension [37], impaired glucose tolerance [28], stroke [30], and coronary slow flow phenomenon [35] were included. The mean baseline FMD of the patients was 3.02–7.45% among the included studies. The protocols of the EECP treatment varied among the included studies, with accumulated hours ranging between 20 and 52.5. The treatment durations were 3–7 weeks. As for the control groups, sham EECP with an inflating pressure of 70 mmHg was used in two studies [25,26], while for the other studies, usual care or conventional treatments were used. The agreement between reviewers in data extraction reached a kappa value of 0.85. According to Table 2, quality of each included RCTs was assessed according to the Cochrane Risk of Bias Tool. The agreement between reviewers in study quality evaluation reached a kappa value of 0.80. Most of the included studies were open-label [24,27–42], while two of them were double-blind [25,26]. The details of random sequence generation were reported in 11 studies [26,28,30,34–36,38–42], while the details of the allocation concealment were not reported in any of the included RCTs.

Table 1. Characteristics of the included RCTs.

Study	Country	Design	Patient diagnosis	No of patients	Mean age (years)	Men (%)	Smoking (%)	Mean FMD at baseline (%)	EECP protocol	Control	Treatment duration (weeks)	Accumulating duration of EECP (h)	FMD measurement
Wang 2006	China	R, OL	MetS	50	53.8	46	28	5.94	60 min, 6 days/week	Usual care	6	36	Forearm inflating to 240 mmHg for 5 min
Braith 2010	USA	R, DB, PC	Stable CAD	42	64.3	81	0	4.02	60 min, daily	Sham EECP	7	42	Forearm inflating to 200 mmHg for 5 min
Gloekler 2010	Switzerland	R, DB, PC	Stable CAD	20	63	85	15	5.15	90 min, 5 days/week	Sham EECP	4	30	Forearm inflating to 200 mmHg for 5 min
Chen 2011	China	R, OL	CAD after PCI	165	58	59.4	NR	4.41	60 min, 5 days/week	Conventional therapy	4	20	Forearm inflating to 200 mmHg for 5 min
Martin 2012	USA	R, OL	IGT	18	64.2	NR	NR	3.02	60 min, daily	Usual care	7	49	Forearm inflating to 200 mmHg for 5 min
Xiao 2015	China	R, OL	Ischemic stroke	80	40.5	53.8	NR	4.62	60 min, daily	Conventional therapy	4	28	Forearm inflating to 200 mmHg for 5 min
Chen 2015	China	R, OL	CAD after PCI	30	58.5	66.7	53.3	6.08	60 min, daily	Conventional therapy	5	35	Forearm inflating to 240 mmHg for 5 min
Zheng 2016	China	R, OL	CAD and hypertension	120	68.4	47.5	62.5	6.93	60 min, twice daily	Conventional therapy	3	42	Forearm inflating to 200 mmHg for 5 min
Jiang 2019	China	R, OL	Stable CAD	156	59.3	53.2	NR	3.34	60 min, 6 days/week	Conventional therapy	6	36	Forearm inflating to 200 mmHg for 5 min
Liu 2019	China	R, OL	UA	100	62.1	59	52	6.44	30 min, twice daily	Conventional therapy	4	28	Forearm inflating to 200 mmHg for 5 min
Zhang 2019	China	R, OL	CSFP	50	62.1	52	40	4.25	45 min, twice daily	Usual care	4	42	Forearm inflating to 200 mmHg for 5 min
Tan 2019	China	R, OL	Stable CAD after PCI	89	56.7	52.8	25.8	7.45	90 min, 5 days/week	Conventional therapy	7	52.5	Forearm inflating to 240 mmHg for 5 min
Qiao 2020	China	R, OL	Stable CAD	68	61.3	57.4	NR	4.11	60 min, daily	Conventional therapy	7	49	Forearm inflating to 200 mmHg for 5 min
Liang 2021	China	R, OL	Hypertension	40	35.1	52.5	52.5	7.38	60 min, daily	Usual care	7	49	Forearm inflating to 200 mmHg for 5 min
Zhang 2021	China	R, OL	Stable CAD	102	66.8	52	NR	3.49	60 min, 6 days/week	Conventional therapy	6	36	Forearm inflating to 200 mmHg for 5 min
Wang 2022a	China	R, OL	UA	132	61.5	53.3	29.5	3.53	30 min, daily	Conventional therapy	7	24.5	Forearm inflating to 200 mmHg for 5 min
Zhang 2022	China	R, OL	Stable CAD	200	62.5	62.4	31	6.41	60 min, daily	Conventional therapy	3	21	Forearm inflating to 240 mmHg for 5 min
Wang 2022b	China	R, OL	Stable CAD	60	57	78.3	70	4.48	60 min, daily	Conventional therapy	5	35	Forearm inflating to 200 mmHg for 5 min
Lian 2022	China	R, OL	Stable CAD	125	60	68.8	60.8	7.32	30 min, twice daily	Conventional therapy	7	49	Forearm inflating to 200 mmHg for 5 min

FMD: flow-mediated dilation; EECP: enhanced external counterpulsation; MetS: metabolic syndrome; PCI: percutaneous coronary intervention; IGT: impaired glucose tolerance; CSPF: coronary slow flow phenomenon; UA: unstable angina; R: randomized; DB: double-blind; PC: placebo-controlled; OL: open-label; NR: not reported.

Table 2. Study quality evaluation via the Cochrane risk of bias Tool.

Study	Random sequence generation	Allocation concealment	Blinding in performance	Blinding in outcome detection	Incomplete outcome data	Reporting bias	Other bias
Wang 2006	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Braith 2010	Unclear	Unclear	Low risk	Low risk	Low risk	Low risk	Low risk
Gloekler 2010	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Chen 2011	Unclear	Unclear	High risk	Low risk	Low risk	Low risk	Low risk
Martin 2012	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Xiao 2015	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Chen 2015	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zheng 2016	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Jiang 2019	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Liu 2019	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zhang 2019	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Tan 2019	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Qiao 2020	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Liang 2021	Unclear	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zhang 2021	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Wang 2022a	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Zhang 2022	Low risk	Unclear	High risk	Low risk	Low risk	Low risk	Low risk
Wang 2022b	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk
Lian 2022	Low risk	Unclear	High risk	Unclear	Low risk	Low risk	Low risk

Meta-analysis results

Pooled results showed that compared with usual care or conventional therapy, additional treatment with EECP for 3–7 weeks was associated with a significantly improved FMD (MD: 1.96%, 95% CI: 1.57–2.36, p < 0.001, Figure 2(A)) with moderate heterogeneity (p for Cochrane Q test = 0.004, I² = 52%). Sensitivity analysis by excluding one study at a time showed similar results (MD: 1.88–2.04, p all < 0.05). Subgroup analysis showed consistent results in patients with CAD and in patients with other diseases (p for subgroup difference = 0.21; Figure 2(B)). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p < 0.001; Table 3 and Figure 3), while the other variables such as patient number, age, sex, treatment duration, and accumulating EECP hours did not significantly affect the results (p all > 0.05). Subsequent subgroup analysis according to the baseline FMD suggested that the increment of FMD following EECP was significant larger in patients with baseline FMD ≥ 5% compared to those with baseline FMD < 5% (p for subgroup difference < 0.001; Figure 4). Summarized certainty of evidence using the GRADE system is shown in Table 4. We downgraded evidence by one level for the lack of allocation concealment and the lack of blinding. We judged the evidence to be of moderate certainty.

Figure 2. Forest plots for the meta-analysis of the influence of EECP on brachial artery FMD. (A) Forest plots for the overall meta-analysis; and (B) Forest plots for the subgroup analysis in patients with CAD and other diseases.

Figure 3. Univariate meta-regression analyses for the correlation between FMD at baseline and the improvement of EECP on FMD.

Figure 4. Forest plots for the subgroup analyses of the influence of EECP on brachial artery FMD according to the baseline FMD levels.

Table 3. Univariate meta-regression analysis.

	MD of changes of FMD after treatment (%)
Covariate	Coefficient	95% CI	p
Patient number	0.0039	−0.0045 to 0.0124	0.34
Mean age (years)	−0.0025	−0.0572 to 0.0522	0.92
Men (%)	0.0073	−0.0348 to 0.0494	0.72
Mean FMD at baseline (%)	0.42	0.24 to 0.59	<0.001
Treatment duration (weeks)	0.021	−0.266 to 0.308	0.88
Accumulating hours on EECP	0.026	−0.013 to 0.065	0.18

FMD: flow-mediated dilation; MD: mean difference; CI: confidence interval; EECP: enhanced external counterpulsation.

Table 4. Summarized certainty of evidence using the GRADE system.

Outcome	Quality assessment							Absolute effect MD (95% CI)	Quality
	No. of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations
FMD (%)	19	RCTs	Serious	No serious inconsistency	No serious indirectness	No serious imprecision	None	1.96 (1.57–2.36)	⊕⊕⊕Ο MODERATE

GRADE: Grading of Recommendations, Assessment, Development and Evaluation; FMD: flow-mediated dilation; RCT: randomized controlled trials; MD: mean difference; CI: confidence interval.

Publication bias

The funnel plots for meta-analyses of the influence of EECP on FMD adult patients were symmetrical, suggesting a low risk of publication bias (Figure 5). Egger’s regression test also suggested a low risk of publication bias (p = 0.23).

Figure 5. Funnel plots for the publication bias underlying the meta-analysis of the influence EECP on brachial artery FMD.

Discussion

In this systematic review and meta-analysis, we integrated the evidence from nine controlled clinical studies, and the results showed that, compared to the control group of usual care or conventional treatment only, additional treatment with EECP significantly improved the vascular endothelial function measured by brachial artery FMD. In addition, consistent results were obtained in the sensitivity analysis by excluding one study at a time and in subgroup analysis in patients with CAD and other diseases. Moreover, results of meta-regression and subgroup analyses showed that baseline FMD may significantly influence the effect of EECP on FMD, which fully explained the heterogeneity among the included studies. Specifically, the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% compared to those with baseline FMD < 5%. Taken together, these results suggest that EECP is effective in improving endothelial function in adult patients.

As far as we know, the current study may be the first systematic review and meta-analysis which examined the influence of EECP treatment on vascular endothelial function measured by FMD. A few methodological strengths of the current meta-analysis should be noted before the results are interpreted. First, an extensive literature search was performed in five commonly used English and Chinese electronic databases, which retrieved 19 RCTs based on the objective of the meta-analysis. In addition, consistent results were obtained in sensitivity analysis by excluding one study at a time and in subgroup according to the diagnosis of the patients, which further reflected the stability of the results. Finally, although moderate heterogeneity was observed, results of meta-regression of subgroup analysis suggests that baseline FMD may modify the effect of EECP treatment on vascular function measured by brachial artery FMD. Overall, these findings confirmed that improving endothelial function may be an important mechanism underlying the potential therapeutic efficacy of EECP to various CVDs.

Previous studies have indicated the potential benefits of EECP treatment on symptoms and exercise capacity in patients with CAD [14] and HF [15]. However, the potential influence of EECP on clinical outcomes in patients with CVD remains unknown. It has been suggested in a recent cohort study that improvement in FMD may confer additive effects on risk reduction of the achievement of the optimal goals of traditional risk factors in patients with CAD, which may lead to a further reduced risk of future cardiovascular events [43]. These findings suggest that EECP treatment may potentially improve the cardiovascular prognosis of patients with CVDs. The mechanisms underlying the benefits of EECP on endothelial function remain not fully determined. Preclinical studies have proposed multiple potential mechanisms of EECP, such as stimulating the endothelial production of NO [44], attenuating systematic inflammation of atherosclerosis [45,46] and inhibiting endothelial apoptosis [47]. Besides, one of the included RCTs also suggested that EECP may improve FMD in patients with hypertension via enhancing the function of endothelial progenitor cells [37]. Further studies are required to determine the key molecular mechanisms involved in this process.

Interestingly, the subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% compared to those with baseline FMD < 5%, which fully explained the heterogeneity. The underlying mechanisms were not known. However, since the benefits of EECP on endothelial function may at least partially be mediated by the enhanced NO production in endothelium [48], which is likely to depend on the activity of the endothelial cells. Patients with severe endothelial dysfunction (low baseline FMD) are likely to have poor integrity and activity of endothelium, which therefore may respond poorly to EECP treatment. Studies are warranted to validate these hypotheses. Besides EECP, it has been indicated that some cardiovascular medications that improve the clinical outcomes of patients with CAD or CHF could also improve FMD. For example, an early meta-analysis including 46 trials showed that statins treatment statistically improved endothelial function assessed by peripheral FMD [49]. In addition, benefits on FMD were observed for beta-blockers [50], angiotensin converting enzyme inhibitors [51], and angiotensin receptor blockers [52]. These findings may suggest that improving FMD may be a common mechanism of treatments that improve cardiovascular outcomes. In fact, a previous meta-analysis involving 35 FMD studies showed that an increment of 1% FMD is correlated with a 12% reduced risk of major adverse cardiovascular events (MACEs) in the future [9]. These results, together with the findings of our meta-analysis, suggest that EECP may be effective in improving the prognosis of patients with CAD or CHF via benefits on FMD. Studies are warranted in the future to validate these hypotheses. In addition, it is important to determine if the benefits of EECP on FMD remain similar in patients with CAD or CHF with optimal medical treatments.

This study has several limitations. First, the protocol of the meta-analysis was not pre-registered in public platforms for the registration of systematic reviews, such as PROSPERO, which could introduce potential bias to the review. Second, the quality of the included studies was considered moderate, and most of them were open-label studies. Accordingly, the certainty of evidence in accordance with the GRADE system was graded as moderate, and the results of this meta-analysis should be confirmed in double-blind placebo-controlled RCTs. Third, the optimal protocol of EECP treatment for patients with CVD remains unknown. It remains unknown if the potential differences of frequency and treatment duration of EECP may significantly influence endothelial function as evaluated by FMD, and studies should be performed in the future for further investigation. Moreover, the treatment duration for EECP in the included studies was 3–7 weeks. The long-term influence of EECP treatment on FMD, as well as the long-term safety of the treatment, should be observed. Finally, as mentioned earlier, FMD is only a surrogate index of patients. It remains unknown improvement of FMD following EECP in patients with CAD or CHF is related to an improved clinical outcomes. Therefore, studies should be considered to determine if additional treatment with EECP could improve the clinical outcome of in these patients.

Conclusions

In summary, this systematic review and meta-analysis indicated that EECP treatment for 3–7 weeks could significantly improve endothelial function measured by brachial artery FMD in adults. The efficacy of EECP on FMD is consistent in CAD patients and patients with other diseases. Moreover, the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% compared to those with baseline FMD < 5%. Studies are needed to determine the optimal protocol of EECP for improving FMD, and to evaluate the influence of long-term EECP treatment on clinical outcomes of these patients.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by Center for Diagnosis and Treatment of Difficult cases of Cardiac System, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, and Science and Technology Program of Health Commission of Jiangxi Province (202130013).