
==== Front
Int J Cardiol Heart Vasc
Int J Cardiol Heart Vasc
International Journal of Cardiology. Heart & Vasculature
2352-9067
Elsevier

S2352-9067(24)00172-6
10.1016/j.ijcha.2024.101506
101506
Review
Different strategies in left ventricle unloading during venoarterial extracorporeal membrane oxygenation: A network meta-analysis
Zhang Han 1
Wang Tianlong 1
Wang Jing
Liu Gang
Yan Shujie
Teng Yuan
Wang Jian
Ji Bingyang jibingyang@fuwai.com
⁎
Department of Cardiopulmonary Bypass, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, China
⁎ Corresponding author at: Department of Cardiopulmonary Bypass, National Center for Cardiovascular Disease and Fuwai Hospital, No. 167 Beilishi Road, Xicheng District, 10010 Beijing, China. jibingyang@fuwai.com
1 These authors contributed equally.

04 9 2024
10 2024
04 9 2024
54 1015068 7 2024
22 8 2024
31 8 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
Highlights

• Any LV unloading strategy during VA-ECMO was associated with improved survival as compared to no unloading.

• Different LV unloading strategies may tend to increase the risk of complications.

• IABP performed better in reducing ICU and hospital length of stay and the risk of complications compared with other unloading strategies.

Background

Left ventricular (LV) overload is a frequent complication during VA-ECMO associated with poor outcomes. Many strategies of LV unloading have been documented but lack of evidence shows which is better. We conducted a network meta-analysis to compare different LV unloading strategies.

Methods

We searched databases for all published studies on LV unloading strategies during VA-ECMO. The pre-defined primary outcome was all-cause mortality.

Results

45 observational studies (34235 patients) were included. The Surface Under the Cumulative Ranking values (SUCRA) demonstrated that compared to no unloading strategy (15.4 %), IABP (73.8 %), pLVAD (60.8 %), atrial septostomy (51.2 %), catheter venting (48.8 %) were all associated with decreased all-cause mortality, in which IABP and pLVAD existed statistical significance. For secondary outcomes, no unloading group had the shortest VA-ECMO duration, ICU and hospital length of stay, and the lower risk of complications compared with unloading strategies. IABP was associated with reducing VA-ECMO duration, ICU and hospital length of stay, and the risk of complications (except for hemolysis as the second best) compared with other unloading strategies.

Conclusions

LV unloading strategies during VA-ECMO were associated with improved survival compared to no unloading, but the tendency to increase the risk of various complications deserves more consideration.

Keywords

Atrial septostomy
Intra-aortic balloon pump
Left ventricular unloading
Percutaneous left ventricular assist device
Venoarterial extracorporeal membrane oxygenation
Abbreviations

CI Confidence intervals

IABP Intra-aortic balloon pump

LA Left atrium

LV Left ventricular

NMA Network meta-analysis

NOS Newcastle-Ottawa Scale

OR Odds ratio

pLVAD Percutaneous left ventricular assist device

pRVAD Percutaneous right ventricular assist device

RRT Renal replacement therapy

SMD Standardized mean difference

SUCRA the Surface Under the Cumulative Ranking values

VA-ECMO Venoarterial extracorporeal membrane oxygenation
==== Body
pmc1 Introduction

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is the primary mechanical circulatory support for the initial management in cardiogenic shock or cardiac arrest over the past decades [1]. With the development of ECMO, increasing attention is given to the potential impact of VA-ECMO, including left ventricular (LV) dilation. Peripheral cannulation during VA-ECMO causes retrograde blood flow to the ascending aorta and resistance of LV ejection, thus increasing afterload on the heart and raising myocardial oxygen demand in the already failing ventricle, further leading to reduced stroke volume, LV distention, and complications such as myocardial ischemia, arrhythmias, pulmonary edema, and LV thrombus formation, all of which may impair myocardial recovery and worsen prognosis [2], [3], [4]. Therefore, LV unloading was the key point in the VA-ECMO management.

Various LV unloading strategies have been employed, including pharmacological approach, intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD, mainly as Impella pump), surgically LV cannulation, and percutaneous atrial septostomy [5], [6], [7]. Recent clinical studies and meta-analyses have shown that LV decompression during VA-ECMO is associated with a reduced risk of mortality [3], [8], [9], [10]. However, each strategy is associated with its risks. Several studies have revealed the association between mechanical circulatory support devices and significant adverse events including bleeding or thrombosis [11], [12], [13]. There is no consensus or recommendation on the optimal choice of LV unloading strategies during VA-ECMO. High-quality randomized controlled studies about this question are lacking and the results of observational studies remain controversial. Hence, we conducted a network meta-analysis (NMA) to evaluate the clinical outcomes of different LV unloading strategies during VA-ECMO, thus investigating the efficacy and safety of each LV unloading strategy.

2 Materials and methods

This NMA was performed in accordance with the PRISMA extension statement for NMA [14]. The PRISMA 2020 checklist [15] of this study is included in Supplemental Material 1. The protocol was registered with the PROSPERO (International Prospective Register of Systematic Reviews, CRD42024517760).

2.1 Search strategy

A systematic search was performed independently using MEDLINE, EMBASE, Scopus and Cochrane Library. All English articles published before 1 MARCH 2024 were selected. The search terms included: “VA-ECMO”, “venoarterial extracorporeal membrane oxygenation”, “ECPR”, “left ventricle”, “LV”, “LA”, “unloading”, “decompression”, “venting”, “IABP”, “Impella”, “pLVAD”, “atrial septostomy”, “catheter”, “cannula”, “vasodilators”. The search strategy was shown in Supplemental Material 2. Additionally, snowball searches for reference lists of published systematic reviews and meta-analyses were reviewed. Three authors independently screened study titles and abstracts for potential eligibility, assessed their validity, and reviewed full texts included in the analysis. Disagreement between authors was assessed and resolved through a process of discussion or a senior reviewer, who will be consulted.

2.2 Eligibility criteria

2.2.1 Patients

Adult patients receiving VA-ECMO treatment for any reason.

2.2.2 Comparator

VA-ECMO without LV unloading strategies.

2.2.3 Intervention

VA-ECMO with LV unloading strategies. Each LV unloading strategy is considered as a separate intervention, and patients receive only one type of unloading strategies during VA-ECMO support. We defined the types of LV unloading strategies according to the published articles, as follows: (1) intra-aortic balloon pump (IABP); (2) percutaneous left ventricular assist device (pLVAD); (3) atrial septostomy; (4) catheter venting including pulmonary artery cannula, left atrial cannula, surgical left ventricular cannula [16], [17].

2.2.4 Outcomes

Primary outcomes: all-cause mortality.

Secondary outcomes: in-hospital complications after VA-ECMO initiation, VA-ECMO duration, ICU length of stay, hospital length of stay.

2.2.5 Study selection

All published clinical studies investigating the effects of VA-ECMO with and without LV unloading strategy support or with at least two different LV unloading strategies were evaluated for inclusion in this meta-analysis.

2.3 Data extraction

Two reviewers independently extracted and recorded all data with a standardized form including the following general information.

Study characteristics: year of publication, title, authors, contact address, country.

Methods: study design and statistical analysis methods.

Patient characteristics: overall numbers of patients, number of patients in each intervention, sex, age, BMI, surgery types and preoperative comorbidities.

VA-ECMO and unloading characteristics: VA-ECMO duration, the cannulation site, type of unloading.

Primary and secondary outcomes: Considering that studies presented in-hospital mortality, 2-week mortality, 30-day mortality and 90-day mortality. All-cause mortality included all of the above. In-hospital complications after VA-ECMO initiation included limb ischemia, bleeding, cerebrovascular accident, infection, hemolysis and renal replacement therapy (RRT).

Percentages were extracted for categorical variables. Means with standard deviations or medians with interquartile ranges were extracted for continuous outcomes. Under the assumption of a normal distribution, we transformed the interquartile range into standard deviations according to the Cochrane Handbook for Systematic Reviews of Interventions (Part 2, Chapter 7.7.3.5). If the standard deviation was zero, the lowest standard deviation of another group within the study was used in the meta-analysis.

2.4 Risk of bias

Quality assessment of observational studies included in this report was done with the Newcastle-Ottawa Scale (NOS) tool by three authors independently [18]. Additionally, funnel plots were produced to assess reporting bias.

2.5 Network meta-analysis

A NMA can provide reliable evidence for the comparison of direct and indirect multiple interventions. A design-by-treatment interaction model designed by processing was adopted for network element analysis. The results were reported as standardized mean difference (SMD) or odds ratio (OR) with 95 % confidence intervals (CI). The Surface Under the Cumulative Ranking values (SUCRA) were calculated to hierarchically rank each unloading strategy based on the probability of being the best for a given outcome, and unloading strategies were ranked from best to worst based on progressively lower SUCRA [19].

2.5.1 Transitivity analysis

As an extension of clinical and methodological homogeneity to comparisons across groups of studies, transitivity refers to the validity of indirect comparisons of a treatment network. To meet the transitivity assumption, we evaluated the included studies by comparing the characteristics of the population, intervention, and study design.

2.5.2 Heterogeneity analysis

The homogeneity of direct evidence was assessed using I2.

2.5.3 Consistency analysis

We checked the evidence of consistency between direct and indirect analyses using node splitting analysis [20]. If p < 0.05, inconsistency was considered to exist between direct and indirect analyses.

2.5.4 Sensitivity analysis

Sensitivity analysis was conducted by excluding studies with less than 20 patients per arm.

2.6 Statistics

Data processing was conducted using Review Manager (version 5.3). NMA was performed using the package “netmeta” in R (version 4.2.2).

2.7 Certainty assessment

The quality of each NMA estimate was rated based on the four-step approach suggested by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group [21]. We rated the certainty of the directed and indirect evidence as high, moderate, low, or very low, based on study limitations, publication bias, inconsistency, indirectness, and imprecision. The final quality of the NMA effect estimates was based on a combination of direct and indirect evidence quality ratings.

3 Results

3.1 Search results

A cumulative of 4576 potentially relevant records were obtained: 4565 from the database and 11 from snowball searches. A total of 1080 were excluded after duplicate removal and 3386 were excluded during screening based on title and abstract and 110 studies met the criteria for full-text review. The final meta-analysis included 34,235 patients across 45 observational studies (Fig. 1) [1], [3], [8], [9], [10], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61]. The patients were divided into 5 treatment groups according to LV unloading strategies: IABP (n = 7166), pLVAD (n = 4078), atrial septostomy (n = 130), catheter venting (n = 83), and VA-ECMO without unloading strategies (n = 22645). For the comparison between IABP and no unloading, 22 studies were found; for the comparison between pLVAD and no unloading, 12 studies were included; for the comparison between atrial septostomy and no unloading, 3 studies were found; for the comparison between catheter venting and no unloading, 1 study was found; for the comparison between IABP and pLVAD, 10 studies were found; for the comparison between pLVAD and catheter venting, 2 studies were found; for the comparison between IABP and atrial septostomy, 1 study was included. A summary of the included studies is shown in Supplemental Material 3.Fig. 1 Article retrieval flow chat.

3.2 Preliminary analysis

The pooled mortality of the included studies was 58 % (95 % CI: 55 %, 62 %). The pooled mortality was the highest in no unloading group (63 %; 95 % CI: 56 %, 70 %) and the lowest in IABP group (53 %; 95 % CI: 47 %, 60 %). All LV unloading strategies existed lower pooled mortality compared to no unloading group (Supplemental Material 4).

3.3 Network meta-analysis

3.3.1 All-cause mortality

All studies reported the results of mortality (Supplemental Material 5). All results for the mortality are shown in Table 1. The direct and NMA results both revealed a decreasing trend for mortality in all unloading groups when compared to no unloading group. In the direct results, statistical significance was observed for comparison of IABP vs. no unloading (OR, 0.78; 95 % CI: 0.66, 0.93). In the NMA results, statistical significance was found for comparisons of IABP vs. no unloading (OR, 0.77; 95 % CI: 0.66, 0.90) and pLVAD vs. no unloading (OR, 0.81; 95 % CI: 0.66, 0.99). When all interventions were ranked according to SUCRA (Fig. 2), IABP showed the highest probability of being the best treatment in reducing mortality (73.8 %), followed by pLVAD (60.8 %), atrial septostomy (51.2 %), catheter venting (48.8 %), no unloading (15.4 %).Table 1 Network and direct comparison results for mortality.

IABP	0.90 (0.70, 1.16)	0.92 (0.23, 3.66)	−	0.78 (0.66, 0.93)	
0.95 (0.77,1.17)	pLVAD	−	0.64 (0.30, 1.37)	0.92 (0.73, 1.17)	
0.91 (0.53,1.55)	0.95 (0.55,1.66)	Atrial septostomy	−	0.85 (0.48, 1.50)	
0.89 (0.45,1.76)	0.94 (0.49,1.81)	0.99 (0.42,2.30)	Catheter venting	0.27 (0.07, 1.02)	
0.77 (0.66,0.90)	0.81 (0.66,0.99)	0.85 (0.50,1.43)	0.86 (0.44,1.68)	No unloading	
Note: Comparisons between left ventricle unloading strategies in VA-ECMO should be read from left to right, and the results are all comparisons between treatments defined on the top left and treatments defined on the bottom right. The table is divided into lower left and upper right sections with left ventricle unloading strategies as the dividing line. The lower left part represents the network comparison results, and the upper right part represents the direct comparison results. For comparison results, when odd ratio (OR) < 1, treatment on the left tended to positive effect, when OR > 1, treatment on the lower right tended to positive effect. Significant results are in bold and underline, and “-” means that the results are not available. IABP, intra-aortic balloon pump; pLVAD, percutaneous left ventricular assist device.

Fig. 2 The ranking plot based on the Surface Under the Cumulative Ranking (SUCRA) values of different strategies of left ventricular unloading during VA-ECMO support for all outcomes. Note: For one outcome, the closer the SUCRA value of one unloading strategy is to 100%, the higher the likelihood that this strategy is in the top rank of the positive effect. RRT, renal replacement therapy; IABP, intra-aortic balloon pump; pLVAD, percutaneous left ventricular assist device; VA-ECMO, venoarterial extracorporeal membrane oxygenation; SUCRA, Surface Under the Cumulative Ranking values.

3.4 Secondary outcomes

3.4.1 VA-ECMO duration

A total of 26 studies included relevant data on the VA-ECMO duration. Supplemental Material 5 shows the qualified network diagram of the VA-ECMO duration for 5 groups, namely, IABP, pLVAD, atrial septostomy, catheter venting, and no unloading. All results for the VA-ECMO duration are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparisons of IABP vs. no unloading (SMD, 0.19; 95 % CI: 0.01, 0.36), pLVAD vs. no unloading (SMD, 0.51; 95 % CI: 0.29, 0.74), and atrial septostomy vs. no unloading (SMD, 1.10; 95 % CI: 0.76, 1.45). In the NMA results, statistical significance was observed for comparisons of IABP vs. no unloading (SMD, 0.28; 95 % CI: 0.13, 0.43), pLVAD vs. no unloading (SMD, 0.41; 95 % CI: 0.22, 0.59), IABP vs. atrial septostomy (SMD, −0.68; 95 % CI: −1.02, −0.34), and pLVAD vs. atrial septostomy (SMD, −0.55; 95 % CI: −0.91, −0.20). When all interventions were ranked according to SUCRA (Fig. 2), no unloading (98.7 %) was associated with the lowest length of VA-ECMO duration, followed by IABP (66.9 %), pLVAD (45.1 %), catheter venting (34.9 %), and atrial septostomy (4.5 %) was associated with the highest VA-ECMO duration.

3.4.2 ICU length of stay

A total of 10 studies included relevant data on the ICU length of stay. Supplemental Material 5 shows the qualified network diagram of the ICU length of stay for 4 groups, namely, IABP, pLVAD, atrial septostomy, and no unloading. All results for the ICU length of stay are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparisons of pLVAD vs. no unloading (SMD, 1.75; 95 % CI: 0.49, 3.02). In the NMA results, statistical significance was observed for comparisons of pLVAD vs. no unloading (SMD, 1.23; 95 % CI: 0.17, 2.30). When all interventions were ranked according to SUCRA (Fig. 2), no unloading (95.4 %) was associated with the lowest ICU length of stay, followed by IABP (52.7 %), atrial septostomy (38.6 %), and pLVAD (13.3 %) was associated with the highest ICU length of stay.

3.4.3 Hospital length of stay

A total of 15 studies included relevant data on the hospital length of stay. Supplemental Material 5 shows the qualified network diagram of the hospital length of stay for 5 groups, namely, IABP, pLVAD, atrial septostomy, catheter venting, and no unloading. All results for the hospital length of stay are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparisons of pLVAD vs. no unloading (SMD, 0.52; 95 % CI: 0.05, 1.00), and atrial septostomy vs. no unloading (SMD, 0.59; 95 % CI: 0.10, 1.07). In the NMA results, statistical significance was observed for comparisons of pLVAD vs. no unloading (SMD, 0.48; 95 % CI: 0.09, 0.87), and atrial septostomy vs. no unloading (SMD, 0.52; 95 % CI: 0.08, 0.96). When all interventions were ranked according to SUCRA (Fig. 2), no unloading (95.4 %) was associated with the lowest hospital length of stay, followed by IABP (52.4 %), catheter venting (37.1 %), and pLVAD (34.9 %), and atrial septostomy (30.7 %) was associated with the highest hospital length of stay.

3.4.4 Limb ischemia

A total of 20 studies included relevant data on the limb ischemia. Supplemental Material 5 shows the qualified network diagram of the limb ischemia for 5 groups, namely, IABP, pLVAD, atrial septostomy, catheter venting, and no unloading. All results for the limb ischemia are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparisons of IABP vs. no unloading (OR, 1.24; 95 % CI: 1.03, 1.49), and pLVAD vs. no unloading (OR, 1.38; 95 % CI: 1.06, 1.78). In the NMA results, statistical significance was observed for comparisons of IABP vs. no unloading (OR, 1.22; 95 % CI: 1.02, 1.47), and pLVAD vs. no unloading (OR, 1.41, 95 % CI, 1.09, 1.81). When all interventions were ranked according to SUCRA (Fig. 2), no unloading (84.7 %) was associated with the lowest risk of limb ischemia, followed by IABP (53.5 %), atrial septostomy (52.6 %), and pLVAD (31.9 %), and catheter venting (27.4 %) was associated with the highest risk of limb ischemia.

3.4.5 Bleeding

A total of 27 studies included relevant data on the bleeding. Supplemental Material 5 shows the qualified network diagram of the bleeding for 5 groups, namely, IABP, pLVAD, atrial septostomy, catheter venting, and no unloading. All results for the bleeding are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparisons of IABP vs. pLVAD (OR, 0.50; 95 % CI: 0.33, 0.76), and pLVAD vs. no unloading (OR, 1.90; 95 % CI: 1.35, 2.66). In the NMA results, statistical significance was observed for comparisons of IABP vs. pLVAD (OR, 0.54; 95 % CI: 0.38, 0.77), and pLVAD vs. no unloading (OR, 2.08; 95 % CI: 1.52, 2.86). When all interventions were ranked according to SUCRA (Fig. 2), no unloading (80.2 %) was associated with the lowest risk of bleeding, followed by atrial septostomy (66.7 %), IABP (64.3 %), and pLVAD (20 %), and catheter venting (18.9 %) was associated with the highest risk of bleeding.

3.4.6 Cerebrovascular accident

A total of 24 studies included relevant data on the cerebrovascular accident. Supplemental Material 5 shows the qualified network diagram of the cerebrovascular accident for 5 groups, namely, IABP, pLVAD, atrial septostomy, catheter venting, and no unloading. All results for the cerebrovascular accident are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparison pLVAD vs. catheter venting (OR, 0.26; 95 % CI: 0.09, 0.69). In the NMA results, statistical significance was observed for comparisons of IABP vs. catheter venting (OR, 0.22; 95 % CI: 0.08, 0.62), and pLVAD vs. catheter venting (OR, 0.26; 95 % CI: 0.09, 0.69). When all interventions were ranked according to SUCRA (Fig. 2), IABP (80.6 %) was associated with the lowest risk of cerebrovascular accident, followed by no unloading (77.4 %), pLVAD (49.8 %), and atrial septostomy (30.7 %), and catheter venting (11.5 %) was associated with the highest risk of cerebrovascular accident.

3.4.7 Infection

A total of 12 studies included relevant data on the infection. Supplemental Material 5 shows the qualified network diagram of the infection for 4 groups, namely, IABP, pLVAD, catheter venting, and no unloading. All results for the infection are shown in Supplementary Material 6. In the direct results, statistical significance was observed for the comparison of pLVAD vs. no unloading (OR, 1.54; 95 % CI: 1.05, 2.25). In the NMA results, statistical significance was observed for comparison of pLVAD vs. no unloading (OR, 1.54; 95 % CI: 1.06, 2.23). When all interventions were ranked according to SUCRA (Fig. 2), no unloading (82.3 %) was associated with the lowest risk of infection, followed by catheter venting (56.1 %), and IABP (45 %), and pLVAD (16.7 %) was associated with the highest risk of infection.

3.4.8 Renal replacement therapy implementation

A total of 27 studies included relevant data on the renal replacement therapy (RRT) implementation. Supplemental Material 5 shows the qualified network diagram of the RRT implementation for 3 groups, namely, IABP, pLVAD, and no unloading. All results for the RRT implementation are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparisons of IABP vs. pLVAD (OR, 0.66; 95 % CI: 0.59, 0.74), and pLVAD vs. no unloading (OR, 1.51; 95 % CI: 1.38, 1.64). In the NMA results, statistical significance was observed for comparisons of IABP vs. pLVAD (OR, 0.66; 95 % CI: 0.59, 0.73), pLVAD vs. no unloading (OR, 1.51; 95 % CI: 1.39, 1.65). When all interventions were ranked according to SUCRA (Fig. 2), IABP (78 %) was associated with the lowest risk of RRT implementation, followed by no unloading (72 %), and pLVAD (0 %) was associated with the highest risk of RRT implementation.

3.4.9 Hemolysis

A total of 10 studies included relevant data on the hemolysis. Supplemental Material 5 shows the qualified network diagram of the hemolysis for 4 groups, namely, IABP, pLVAD, catheter venting, and no unloading. All results for the hemolysis are shown in Supplementary Material 6. In the direct results, statistical significance was observed for comparison of pLVAD vs. no unloading (OR, 2.36; 95 % CI: 1.06, 5.23). In the NMA results, statistical significance was observed for the comparison of pLVAD vs. no unloading (OR, 2.36; 95 % CI: 1.06, 5.23). When all interventions were ranked according to SUCRA (Fig. 2), Catheter venting (77.9 %) was associated with the lowest risk of hemolysis, followed by IABP (59.9 %), no unloading (56.4 %), and pLVAD (5.7 %) was associated with the highest risk of hemolysis.

3.5 Publication bias

Funnel plots for NMA analysis are provided in Supplementary Material 7. No evidence of publication bias was found according to funnel plot asymmetry and the Egger’s regression test values were over 0.05 for all outcomes, except for infection (p = 0.005).

3.6 Quality assessment

Quality assessment was conducted for the outcome of the all-cause mortality (Supplementary Material 8). The quality of observational studies was determined according to the NOS tool and quality scores all varied from 7 to 9, except for 2 studies with a quality score of 6 [24], [46].

3.7 Transitivity, heterogeneity, consistency and sensitivity analysis

We analyzed the distribution of baseline variables in the included studies between different unloading strategies to assess transitivity. The difference between baseline variables was small in most comparison groups (Supplemental Material 9). Gender difference was found in the comparisons for IABP vs. no unloading; pLVAD vs. no unloading. Supplemental Material 10 shows the results of the heterogeneity analysis and consistency analysis. The sensitivity analysis was conducted by excluding studies with less than 20 patients (Supplemental Material 11). No changes in SURCA ratings for all outcomes were found in sensitivity analysis results, except for ICU and hospital length of stay.

3.8 Certainty of evidence assessment

Contribution plot revealed that direct evidence accounted for most of the sources of NMA analysis results in this study (Supplemental Material 12). Due to all of the included studies were observational designs; consequently, the level of evidence for all results in this study was of low quality (Supplemental Material 13).

4 Discussion

To the best of our knowledge, this study displayed the largest and most comprehensive meta-analysis comparing different LV unloading strategies during VA-ECMO support, including 45 studies containing data on 34,235 patients. The results demonstrated that all unloading treatments existed a decreased trend in the risk of all-cause mortality when compared to no unloading strategy, in which IABP and pLVAD showed statistical significance. However, it should be noticed that all LV unloading strategies were associated with the increasing trend of the risk for various complications.

In our study, survival was inferior in no unloading group. Although VA-ECMO is an effective therapy for blood oxygenation and circulatory support in patients with cardiogenic shock, 36 % of them have significant LV distension due to retrograde aortic blood flow [4]. LV pressure overload is associated with increased myocardial oxygen consumption and mitochondrial dysfunction [62]. These negative effects contribute to the persistently high mortality rate of VA-ECMO patients without unloading. LV unloading treatments improve the mechanical performance of the heart and reduce cardiac work which may explain the better survival rate. In several previous meta-analysis studies, LV unloading was found to be associated with decreased mortality during VA-ECMO [62], [63], [64], [65], which was similar to and further enhanced the credibility of our results. In addition, the VA-ECMO duration, ICU length of stay, and hospital length of stay were found shorter and the complication rate was lower for no unloading group in this study. One reason may be that the higher early mortality in the no unloading group, thus results in a shorter total in-hospital duration and many complications are failed to exhibit and be recorded.

Although there is reasonable evidence that an effective LV unloading strategy during VA-ECMO can prolong the survival time and improve the survival rate, it comes at the expense of an increased risk of various complications. In our study, each LV unloading strategy showed a trend toward increased risk of multiple complications. Among them, IABP and pLVAD showed statistically significant increases in the risk several of complications compared with no unloading strategy (IABP for limb ischemia, and pLVAD for limb ischemia, bleeding, infection, hemolysis and RRT implementation). Considering a large amount of clinical evidence has confirmed that the application of mechanical circulatory supporting devices (IABP, Impella, and ECMO) is related to the disorder of the kidney and the hematological and coagulation systems, the results obtained in our study are explainable [8], [66]. However, it should be noticed that our findings highlighted the more adverse outcomes associated with LV unloading using pLVAD than IABP. Not only the pLVAD group caused more types of complications with statistically significant increased risk than IABP when both were compared with no unloading group, but the comparison results between IABP and pLVAD showed that IABP performed better in reducing bleeding and RRT implementation with statistical significance. The larger bore arterial access required for pLVAD placement (typically via the femoral artery) and a tendency toward higher intensity of anticoagulation may potentially increase risk of hematological and coagulation complications [67]. In addition, due to the shear forces generated by the rotary mechanism acting on red blood cells of all pump systems, hemolysis and acute renal failure frequently occur as a complication of pLVAD system [64], [68]. More research is required to comprehend why pLVAD leads to more hematological and coagulation complications and find ways to reduce these complications. However, pLVAD and IABP were not inferior in all complication risks. In this study, there was no significant difference between IABP and no unloading strategy in infection, bleeding, and hemolysis and RRT application, thus further demonstrating the safety of IABP. Additionally, both IABP and pLVAD displayed no significant difference in the risk of cerebrovascular accident compared with no unloading group. It is interesting that when compared with surgical catheter venting, IABP and impella have obvious advantages in reducing the risk of cerebrovascular accident. In previous research, the use of IABP and Impella has been shown to improve cerebral blood flow and pulsatility indices, which may indicate that LV unloading strategy with mechanical circulatory supporting devices could be less harmful to cerebrovascular function [69], [70]. Due to the small number of related studies included, there was poor interpretability of the evidence obtained in this study on atrial septostomy and surgical catheter venting strategies. Surgical catheter venting is conducted by percutaneous inserting catheters into the LV cavity, left atrium, or pulmonary artery and connected to the inflow cannula of the VA-ECMO circuit [50], [71], [72]. However, the size of the catheters limits the maximum flow due to a higher risk of hemolysis, so this approach is not commonly used [17]. Considering the medical cost and technical issues, some LV unloading strategies with mechanical circulatory supporting devices cannot be routinely implemented in some countries, therefore, surgical catheter venting may be a good choice for its simplicity and economize [73]. Atrial septostomy is also another straightforward, feasible method for LV unloading. Although our study results revealed that atrial septostomy is slightly inferior to pLVAD and IABP in reducing all-cause mortality, it had higher SURCA values in reducing complications including limb ischemia and bleeding compared to pLVAD. Various techniques such as vent placement, static balloon dilation, and stent implantation could achieve left heart decompression by the transcatheter creation of an atrial septal defect [74]. This unloading method is minimally invasive in contrast to the central venting procedure, avoiding the need for surgery under general anesthesia [48]. However, the current evidence about the safety and effectiveness of atrial septostomy is limited and controversial. The study by Delmas and colleagues reported that the mid-term persistence of interatrial shunting following percutaneous atrial septostomy could potentially increase the risk of ischemic cerebrovascular accident and right heart dilation [49]. Therefore, further research is needed to investigate the advantages of atrial septostomy as a left ventricular decompression method.

At present, some emerging LV unloading strategies during VA-ECMO deserve careful evaluation of their effectiveness and safety. Percutaneous right ventricular assist device (pRVAD), utilizing a ProTek Duo (TandemLife) MCS device to drain the pulmonary artery (PA), decreases venous return to the LV resulting in physiologic and effective LV unloading [75]. Another novel unloading approach is TandemHeart trans-septal cannula via percutaneous trans-septal left atrium (LA) drainage [76]. No clinical studies compare the outcomes of these two unloading strategies with no unloading strategy and other unloading strategies, and only a few case reports have confirmed their effectiveness. More researches are needed to focus on the effects of these technologies in the future.

5 Limitations

This study has several limitations. First, we had to only include available observational studies due to the lack of randomized clinical trials, leading to low quality of the evidence. The retrospective observational design of all included studies restricted the evaluation of variations in baseline characteristics, proper indications, timing of unloading, underlying etiology, and potential selection bias on the observed outcomes. However, the number of studies we have included was currently the largest among the previous meta-analyses about left ventricular unloading. Second, the timing for mortality was not uniform in the forty-five studies, thirteen studies referred to 30-day mortality, thirty studies reported in-hospital mortality, one study reported 2-week mortality and one study reported 90-day mortality. Third, the majority of the included studies had a limited sample size, which raised the probability of overstating effect sizes for the outcomes. Fourth, there existed a moderate to high level of heterogeneity for certain outcomes among the included studies. However, we used random effects model with inverse variance weighting to reduce this limitation. Fifth, other cardiovascular outcomes were not accessed, because few studies specifically reported on cardiovascular complications and the occurrence of cardiovascular complications during ECMO support was likely to be greatly influenced by primary cardiac diseases.

6 Conclusions

In patients treated with VA-ECMO, the implementation of any unloading strategy was associated with lower mortality compared with no unloading. However, the tendency of LV unloading strategy in increasing the risk of various complications deserves serious consideration. pLVAD and IABP have the better effect in reducing mortality, and there is no significant difference between them. Given the considerable risk of bias and low-quality evidence caused by the observational design of the included studies, further prospective randomized data is urgently required to identify the optimal LV venting strategy.

7 Ethics approval and consent to participate

Not applicable.

8 Consent for publication

All the authors consent to the publication of the manuscript and support material.

9 Availability of data and materials

All the data associated with this manuscript were included in the main text and supplementary materials.

Funding

None.

CRediT authorship contribution statement

Han Zhang: Writing – original draft, Methodology, Data curation, Conceptualization. Tianlong Wang: Writing – original draft, Methodology, Formal analysis, Conceptualization. Jing Wang: Methodology, Data curation. Gang Liu: Visualization, Data curation. Shujie Yan: Writing – original draft, Data curation. Yuan Teng: Visualization, Formal analysis. Jian Wang: Visualization, Formal analysis. Bingyang Ji: Writing – review & editing, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A Supplementary data

The following are the Supplementary data to this article:Supplementary Data 1

Acknowledgements

None.

Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.ijcha.2024.101506.
==== Refs
References

1 Chen K. Hou J. Tang H. Hu S. Concurrent initiation of intra-aortic balloon pumping with extracorporeal membrane oxygenation reduced in-hospital mortality in postcardiotomy cardiogenic shock Ann. Intensive Care 2019 9 10.1186/s13613-019-0496-9 30659380
2 Cevasco M. Takayama H. Ando M. Garan A.R. Naka Y. Takeda K. Left ventricular distension and venting strategies for patients on venoarterial extracorporeal membrane oxygenation J. Thorac. Dis. 11 2019 1676 1683 10.21037/jtd.2019.03.29 31179113
3 Grandin E.W. Nunez J.I. Willar B. Kennedy K. Rycus P. Tonna J.E. Mechanical left ventricular unloading in patients undergoing venoarterial extracorporeal membrane oxygenation J. Am. Coll. Cardiol. 79 2022 1239 1250 10.1016/j.jacc.2022.01.032 35361346
4 Truby L.K. Takeda K. Mauro C. Yuzefpolskaya M. Garan A.R. Kirtane A.J. Incidence and implications of left ventricular distention during venoarterial extracorporeal membrane oxygenation support ASAIO Journal (American Society for Artificial Internal Organs: 1992) 63 2017 257 265 10.1097/mat.0000000000000553 28422817
5 Alkhouli M. Narins C.R. Lehoux J. Knight P.A. Waits B. Ling F.S. Percutaneous decompression of the left ventricle in cardiogenic shock patients on venoarterial extracorporeal membrane oxygenation J. Card. Surg. 31 2016 177 182 10.1111/jocs.12696 26809382
6 Meani P. Gelsomino S. Natour E. Johnson D.M. Rocca H.B. Pappalardo F. Modalities and effects of left ventricle unloading on extracorporeal life support: a review of the current literature Eur. J. Heart Fail. 19 Suppl 2 2017 84 91 10.1002/ejhf.850 28470925
7 Baldetti L. Gramegna M. Beneduce A. Melillo F. Moroni F. Calvo F. Strategies of left ventricular unloading during VA-ECMO support: a network meta-analysis Int. J. Cardiol. 312 2020 16 21 10.1016/j.ijcard.2020.02.004 32057479
8 Schrage B. Becher P.M. Bernhardt A. Bezerra H. Blankenberg S. Brunner S. Left ventricular unloading is associated with lower mortality in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation: results from an international Multicenter Cohort Study. Circulation. 142 2020 2095 2106 10.1161/circulationaha.120.048792 33032450
9 Kida H. Sotomi Y. Hikoso S. Nakatani D. Mizuno H. Suna S. Prognostic significance of intra-aortic balloon pumping support in patients with acute myocardial infarction and veno-arterial extracorporeal membrane oxygenation therapy J. Cardiol. 79 2022 179 185 10.1016/j.jjcc.2021.10.011 34750027
10 Yeo I. Axman R. Lu D.Y. Feldman D.N. Cheung J.W. Minutello R.M. Impella versus intra-aortic balloon pump in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation: an observational study J. Am. Heart Assoc. 13 2024 e032607 38240236
11 Thiele H. Jobs A. Ouweneel D.M. Henriques J.P.S. Seyfarth M. Desch S. Percutaneous short-term active mechanical support devices in cardiogenic shock: a systematic review and collaborative meta-analysis of randomized trials Eur. Heart J. 38 2017 3523 3531 10.1093/eurheartj/ehx363 29020341
12 Javaid A.I. Michalek J.E. Gruslova A.B. Hoskins S.A. Ahsan C.H. Feldman M.D. Mechanical circulatory support versus vasopressors alone in patients with acute myocardial infarction and cardiogenic shock undergoing percutaneous coronary intervention Catheter. Cardiovasc. Interv. 103 2024 30 41 10.1002/ccd.30913 37997292
13 Dhruva S.S. Ross J.S. Mortazavi B.J. Hurley N.C. Krumholz H.M. Curtis J.P. Association of use of an intravascular microaxial left ventricular assist device vs intra-aortic balloon pump with in-hospital mortality and major bleeding among patients with acute myocardial infarction complicated by cardiogenic shock JAMA 323 2020 734 745 10.1001/jama.2020.0254 32040163
14 Hutton B. Catalá-López F. Moher D. The PRISMA statement extension for systematic reviews incorporating network meta-analysis: PRISMA-NMA Med. Clin. (Barc) 147 2016 262 266 10.1016/j.medcli.2016.02.025 27040178
15 Page M.J. McKenzie J.E. Bossuyt P.M. Boutron I. Hoffmann T.C. Mulrow C.D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews BMJ (Clinical research ed.) 372 2021 n71 10.1136/bmj.n71
16 Zhang P. Wei S. Zhai K. Huang J. Cheng X. Tao Z. Efficacy of left ventricular unloading strategies during venoarterial extracorporeal membrane oxygenation in patients with cardiogenic shock: a protocol for a systematic review and Bayesian network meta-analysis BMJ Open 11 2021 e047046
17 Ezad S.M. Ryan M. Donker D.W. Pappalardo F. Barrett N. Camporota L. Unloading the left ventricle in venoarterial ECMO. In whom, when, and how? Circulation 147 2023 1237 1250 10.1161/circulationaha.122.062371 37068133
18 G. Wells, B. Shea, D. O'Connell, J. Peterson, V. Welch, M. Losos, et al., The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
19 Salanti G. Ades A.E. Ioannidis J.P. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial J. Clin. Epidemiol. 64 2011 163 171 10.1016/j.jclinepi.2010.03.016 20688472
20 Dias S. Welton N.J. Caldwell D.M. Ades A.E. Checking consistency in mixed treatment comparison meta-analysis Stat. Med. 29 2010 932 944 10.1002/sim.3767 20213715
21 Puhan M.A. Schünemann H.J. Murad M.H. Li T. Brignardello-Petersen R. Singh J.A. A GRADE working group approach for rating the quality of treatment effect estimates from network meta-analysis BMJ (Clinical research ed.) 349 2014 g5630 10.1136/bmj.g5630
22 Doll N. Kiaii B. Borger M. Bucerius J. Krämer K. Schmitt D.V. Five-year results of 219 consecutive patients treated with extracorporeal membrane oxygenation for refractory postoperative cardiogenic shock Ann. Thorac. Surg. 77 2004 151 157 10.1016/s0003-4975(03)01329-8 discussion 7 14726052
23 Sakamoto S. Taniguchi N. Nakajima S. Takahashi A. Extracorporeal life support for cardiogenic shock or cardiac arrest due to acute coronary syndrome Ann. Thorac. Surg. 94 2012 1 7 10.1016/j.athoracsur.2012.01.032 22429669
24 Wang J.G. Han J. Jia Y.X. Zeng W. Hou X.T. Meng X. Outcome of veno-arterial extracorporeal membrane oxygenation for patients undergoing valvular surgery PLoS One 2013 8 10.1371/journal.pone.0063924
25 Aoyama N. Imai H. Kurosawa T. Fukuda N. Moriguchi M. Nishinari M. Therapeutic strategy using extracorporeal life support, including appropriate indication, management, limitation and timing of switch to ventricular assist device in patients with acute myocardial infarction J. Artif. Organs 17 2014 33 41 10.1007/s10047-013-0735-z 24162152
26 Park T.K. Yang J.H. Choi S.H. Song Y.B. Hahn J.Y. Choi J.H. Clinical impact of intra-aortic balloon pump during extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock BMC Anesthesiol. 14 2014 27 10.1186/1471-2253-14-27 24725532
27 Ro S.K. Kim J.B. Jung S.H. Choo S.J. Chung C.H. Lee J.W. Extracorporeal life support for cardiogenic shock: influence of concomitant intra-aortic balloon counterpulsation Eur. J. Cardio-thoracic Surg.: Off. J. Eur. Assoc. Cardio-thoracic Surgery 46 2014 186 192 10.1093/ejcts/ezu005 discussion 92
28 Aso S. Matsui H. Fushimi K. Yasunaga H. The effect of intraaortic balloon pumping under venoarterial extracorporeal membrane oxygenation on mortality of cardiogenic patients: an analysis using a nationwide inpatient database Crit. Care Med. 44 2016 1974 1979 10.1097/ccm.0000000000001828 27322361
29 Lin L.Y. Liao C.W. Wang C.H. Chi N.H. Yu H.Y. Chou N.K. Effects of additional intra-aortic balloon counter-pulsation therapy to cardiogenic shock patients supported by extra-corporeal membranous oxygenation Sci. Rep. 6 2016 23838 10.1038/srep23838 27032984
30 Dangers L. Bréchot N. Schmidt M. Lebreton G. Hékimian G. Nieszkowska A. Extracorporeal membrane oxygenation for acute decompensated heart failure Crit. Care Med. 45 2017 1359 1366 10.1097/ccm.0000000000002485 28471885
31 Bréchot N. Demondion P. Santi F. Lebreton G. Pham T. Dalakidis A. Intra-aortic balloon pump protects against hydrostatic pulmonary oedema during peripheral venoarterial-extracorporeal membrane oxygenation Eur. Heart J. Acute Cardiovasc. Care 7 2018 62 69 10.1177/2048872617711169 28574276
32 Overtchouk P. Pascal J. Lebreton G. Hulot J.S. Luyt C.E. Combes A. Outcome after revascularisation of acute myocardial infarction with cardiogenic shock on extracorporeal life support EuroIntervention 13 2018 e2160 e2168 10.4244/eij-d-17-01014 29400656
33 Tepper S. Garcia M.B. Fischer I. Ahmed A. Khan A. Balsara K.R. Clinical outcomes and reduced pulmonary artery pressure with intra-aortic balloon pump during central extracorporeal life support ASAIO Journal (American Society for Artificial Internal Organs: 1992) 65 2019 173 179 10.1097/mat.0000000000000788 29613887
34 Barge-Caballero G. Castel-Lavilla M.A. Almenar-Bonet L. Garrido-Bravo I.P. Delgado J.F. Rangel-Sousa D. Venoarterial extracorporeal membrane oxygenation with or without simultaneous intra-aortic balloon pump support as a direct bridge to heart transplantation: results from a nationwide Spanish registry Interact. Cardiovasc. Thorac. Surg. 29 2019 670 677 10.1093/icvts/ivz155 31257414
35 Djordjevic I. Deppe A.C. Sabashnikov A. Kuhn E. Eghbalzadeh K. Merkle J. Concomitant ECMO and IABP support in postcardiotomy cardiogenic shock patients Heart Lung Circ. 30 2021 1533 1539 10.1016/j.hlc.2021.03.276 33903028
36 Monaco F. Ajello S. Calabrò M.G. Melisurgo G. Landoni G. Arata A. Left ventricular unloading with an IABP in patients undergoing ventricular tachycardia ablation with ECMO support J. Cardiothorac. Vasc. Anesth. 35 2021 2686 2693 10.1053/j.jvca.2020.12.049 33487532
37 Arafat A.A. Almedimigh A.A. Algarni K.D. Ismail H.H. Pragliola C. Adam A.I. Concomitant intra-aortic balloon pump and veno-arterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock Int. J. Artif. Organs 46 2023 384 389 10.1177/03913988231170890 37125784
38 Char S. Fried J. Melehy A. Mehta S. Ning Y. Kurlansky P. Clinical efficacy of direct or indirect left ventricular unloading during venoarterial extracorporeal membrane oxygenation for primary cardiogenic shock J. Thorac. Cardiovasc. Surg. 165 2023 699 707.e5 10.1016/j.jtcvs.2021.06.024 34243933
39 Kang J. Lee K.S. Lee H.S. Lee H. Ahn H. Han J.K. Differential effect of left ventricular unloading according to the aetiology of cardiogenic shock ESC Heart Failure. 11 2024 338 348 10.1002/ehf2.14584 38012086
40 Pappalardo F. Schulte C. Pieri M. Schrage B. Contri R. Soeffker G. Concomitant implantation of Impella(®) on top of veno-arterial extracorporeal membrane oxygenation may improve survival of patients with cardiogenic shock Eur. J. Heart Fail. 19 2017 404 412 10.1002/ejhf.668 27709750
41 Akanni O. Takeda K. Truby L. Kurlansky P. Han J. Sreekanth S. Ecpella: combined use of extracorporeal membrane oxygenation and percutaneous microaxial pump left ventricular assist device J. Heart Lung Transplant. 35 2016 S323
42 Patel S.M. Lipinski J. Al-Kindi S.G. Patel T. Saric P. Li J. Simultaneous venoarterial extracorporeal membrane oxygenation and percutaneous left ventricular decompression therapy with impella is associated with improved outcomes in refractory cardiogenic shock ASAIO J. (American Society for Artificial Internal Organs: 1992) 65 2019 21 28 10.1097/mat.0000000000000767
43 Garan A.R. Takeda K. Salna M. Vandenberge J. Doshi D. Karmpaliotis D. Prospective comparison of a percutaneous ventricular assist device and venoarterial extracorporeal membrane oxygenation for patients with cardiogenic shock following acute myocardial infarction J. Am. Heart Assoc. 8 2019 e012171 31041870
44 Mørk S.R. Stengaard C. Linde L. Møller J.E. Jensen L.O. Schmidt H. Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study Crit. Care 25 2021 174 10.1186/s13054-021-03606-5 34022934
45 Unoki T. Kamentani M. Nakayama T. Tamura Y. Konami Y. Suzuyama H. Impact of extracorporeal CPR with transcatheter heart pump support (ECPELLA) on improvement of short-term survival and neurological outcome in patients with refractory cardiac arrest - a single-site retrospective cohort study Resuscitation plus. 10 2022 100244 10.1016/j.resplu.2022.100244
46 Thevathasan T. Kenny M.A. Krause F.J. Paul J. Wurster T. Boie S.D. Left-ventricular unloading in extracorporeal cardiopulmonary resuscitation due to acute myocardial infarction – a multicenter study Resuscitation 186 2023 10.1016/j.resuscitation.2023.109775
47 Gaisendrees C. Djordjevic I. Sabashnikov A. Adler C. Eghbalzadeh K. Ivanov B. Impact of left ventricular unloading using a peripheral Impella®-pump in eCPR patients Artif. Organs 46 2022 451 459 10.1111/aor.14067 34516014
48 Ok Y.J. Jung S.H. Lee S.W. Ahn J.M. Lim J.Y. Efficacy of left heart decompression during extracorporeal membrane oxygenation: a case-control study J. Thorac. Dis. 11 2019 865 872 10.21037/jtd.2019.01.110 31019775
49 Delmas C. Vallee L. Bouisset F. Porterie J. Biendel C. Lairez O. Use of percutaneous atrioseptotosmy for left heart decompression during veno-arterial extracorporeal membrane oxygenation support: an observational study J. Am. Heart Assoc. 11 2022 10.1161/JAHA.121.024642
50 Schmack B. Seppelt P. Weymann A. Alt C. Farag M. Arif R. Extracorporeal life support with left ventricular decompression-improved survival in severe cardiogenic shock: results from a retrospective study PeerJ 5 2017 e3813 28975053
51 Piechura L.M. Coppolino A. Mody G.N. Rinewalt D.E. Keshk M. Ogawa M. Left ventricle unloading strategies in ECMO: a single-center experience J. Card. Surg. 35 2020 1514 1524 10.1111/jocs.14644 32485030
52 Nakajima T. Tanaka Y. Fischer I. Kotkar K. Damiano R.J. Jr. Moon M.R. Extracorporeal life support for cardiogenic shock with either a percutaneous ventricular assist device or an intra-aortic balloon pump ASAIO Journal (American Society for Artificial Internal Organs: 1992) 67 2021 25 31 10.1097/mat.0000000000001192 33346989
53 Shibasaki I. Masawa T. Abe S. Ogawa H. Takei Y. Tezuka M. Benefit of veno-arterial extracorporeal membrane oxygenation combined with Impella (ECpella) therapy in acute coronary syndrome with cardiogenic shock J. Cardiol. 80 2022 116 124 10.1016/j.jjcc.2022.02.013 35288000
54 Takahashi K. Kubo S. Ikuta A. Osakada K. Takamatsu M. Taguchi Y. Incidence, predictors, and clinical outcomes of mechanical circulatory support-related complications in patients with cardiogenic shock J. Cardiol. 79 2022 163 169 10.1016/j.jjcc.2021.08.011 34511239
55 Au S.Y. Fong K.M. Tsang C.F.S. Chan K.C.A. Wong C.Y. Ng W.Y.G. Veno-arterial extracorporeal membrane oxygenation with concomitant Impella versus concomitant intra-aortic-balloon-pump for cardiogenic shock Perfusion (United Kingdom) 38 2023 51 57 10.1177/02676591211033947
56 Inglis S.S. Rosenbaum A.N. Rizzo S.A. Anderson J.H. Yalamuri S. Spencer P.J. Novel left ventricular unloading strategies in patients on peripheral venoarterial extracorporeal membrane oxygenation support ASAIO Journal (American Society for Artificial Internal Organs : 1992) 2024 10.1097/mat.0000000000002136
57 Nitta M. Nakano S. Kaneko M. Fushimi K. Hibi K. Shimizu S. In-hospital mortality in patients with cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation with concomitant use of impella vs. intra-aortic balloon pump - a retrospective cohort study using a japanese claims-based database Circulation J.: Offi. J. Japanese Circulation Society 2024 10.1253/circj.CJ-23-0758
58 Tepper S. Masood M.F. Baltazar Garcia M. Pisani M. Ewald G.A. Lasala J.M. Left ventricular unloading by impella device versus surgical vent during extracorporeal life support Ann. Thorac. Surg. 104 2017 861 867 10.1016/j.athoracsur.2016.12.049 28347536
59 Radakovic D. Zittermann A. Knezevic A. Razumov A. Opacic D. Wienrautner N. Left ventricular unloading during extracorporeal life support for myocardial infarction with cardiogenic shock: surgical venting versus Impella device Interact. Cardiovasc. Thorac. Surg. 34 2022 137 144 10.1093/icvts/ivab230 34999807
60 Hasde A. Sarıcaoğlu M.C. Dikmen Yaman N. Baran Ç. Özçınar E. Çakıcı M. Comparison of left ventricular unloading strategies on venoarterial extracorporeal life support Interact. Cardiovasc. Thorac. Surg. 32 2021 467 475 10.1093/icvts/ivaa284 33249443
61 Kim A.R. Park H. Lee S.E. Ahn J.M. Park D.W. Lee S.W. Outcomes of left ventricular unloading with a transseptal cannula during extracorporeal membrane oxygenation in adults Artif. Organs 45 2021 390 398 10.1111/aor.13838 33001468
62 Thevathasan T. Füreder L. Fechtner M. Mørk S.R. Schrage B. Westermann D. Left-ventricular unloading with impella during refractory cardiac arrest treated with extracorporeal cardiopulmonary resuscitation: a systematic review and meta-analysis Crit. Care Med. 52 2024 464 474 10.1097/ccm.0000000000006157 38180032
63 Bhatia K. Jain V. Hendrickson M.J. Aggarwal D. Aguilar-Gallardo J.S. Lopez P.D. Meta-analysis comparing venoarterial extracorporeal membrane oxygenation with or without impella in patients with cardiogenic shock Am. J. Cardiol. 181 2022 94 101 10.1016/j.amjcard.2022.06.059 35999070
64 Gandhi K.D. Moras E.C. Niroula S. Lopez P.D. Aggarwal D. Bhatia K. Left ventricular unloading with impella versus IABP in patients with VA-ECMO: a systematic review and meta-analysis Am. J. Cardiol. 208 2023 53 59 10.1016/j.amjcard.2023.09.023 37812867
65 Li Y. Yan S. Gao S. Liu M. Lou S. Liu G. Effect of an intra-aortic balloon pump with venoarterial extracorporeal membrane oxygenation on mortality of patients with cardiogenic shock: a systematic review and meta-analysis† Eur. J. Cardio-Thoracic Surgery: Off. J. Eur. Assoc. Cardio-Thoracic Surgery 55 2019 395 404 10.1093/ejcts/ezy304
66 Sen A. Larson J.S. Kashani K.B. Libricz S.L. Patel B.M. Guru P.K. Mechanical circulatory assist devices: a primer for critical care and emergency physicians Crit. Care 20 2016 153 10.1186/s13054-016-1328-z 27342573
67 Cappannoli L. Galli M. Zito A. Restivo A. Princi G. Laborante R. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) with vs. without left ventricular unloading by Impella: a systematic review and meta-analysis Eur. Heart J. Quality Care Clin. Outcomes 9 2023 358 366 10.1093/ehjqcco/qcac076
68 Badiye A.P. Hernandez G.A. Novoa I. Chaparro S.V. Incidence of hemolysis in patients with cardiogenic shock treated with impella percutaneous left ventricular assist device ASAIO Journal (American Society for Artificial Internal Organs 2016 62 1992 11 14 10.1097/mat.0000000000000290
69 Yang F. Jia Z.S. Xing J.L. Wang Z. Liu Y. Hao X. Effects of intra-aortic balloon pump on cerebral blood flow during peripheral venoarterial extracorporeal membrane oxygenation support J. Transl. Med. 12 2014 106 10.1186/1479-5876-12-106 24766774
70 Melmed K.R. Schlick K.H. Rinsky B. Dumitrascu O.M. Volod O. Nezhad M. Assessing cerebrovascular hemodynamics using transcranial doppler in patients with mechanical circulatory support devices J. Neuroimaging: Off. J. Am. Soc. Neuroimaging 30 2020 297 302 10.1111/jon.12694
71 von Segesser L.K. Kwang K. Tozzi P. Horisberger J. Dembitsky W. A simple way to decompress the left ventricle during venoarterial bypass Thorac. Cardiovasc. Surg. 56 2008 337 341 10.1055/s-2008-1038664 18704855
72 Hong T.H. Byun J.H. Lee H.M. Kim Y.H. Kang G.H. Oh J.H. Initial experience of transaortic catheter venting in patients with venoarterial extracorporeal membrane oxygenation for cardiogenic shock ASAIO Journal (American Society for Artificial Internal Organs: 1992) 62 2016 117 122 10.1097/mat.0000000000000327 26720735
73 Jung J.J. Kang D.H. Moon S.H. Yang J.H. Kim S.H. Kim J.W. Left ventricular decompression by transaortic catheter venting in extracorporeal membrane oxygenation ASAIO Journal (American Society for Artificial Internal Organs: 1992) 67 2021 752 756 10.1097/mat.0000000000001450 34170881
74 Baruteau A.E. Barnetche T. Morin L. Jalal Z. Boscamp N.S. Le Bret E. Percutaneous balloon atrial septostomy on top of venoarterial extracorporeal membrane oxygenation results in safe and effective left heart decompression Eur. Heart J. Acute Cardiovasc. Care 7 2018 70 79 10.1177/2048872616675485 27742755
75 Kumar K. Coonse K. Zakhary B. Cigarroa J.E. Novel method for left ventricular unloading utilizing percutaneous pulmonary artery drainage in cardiorespiratory failure due to COVID-19 infection Catheter. Cardiovasc. Interv. 100 2022 175 178 10.1002/ccd.30212 35446478
76 Jumean M. Pham D.T. Kapur N.K. Percutaneous bi-atrial extracorporeal membrane oxygenation for acute circulatory support in advanced heart failure Catheter. Cardiovasc. Interv. 85 2015 1097 1099 10.1002/ccd.25791 25529821
