Mechanical Support in Myocardial Infarction Complicated by Cardiogenic Shock: What Have We Learned from Trials?
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsI have the privilege of reviewing "Mechanical Support in Myocardial Infarction Complicated by Cardiogenic Shock: What Have We Learned from Trials?"
This paper elaborately explains the fact that cardiogenic shock (CS) is a highly lethal complication affecting 5%–10% of acute myocardial infarctions (AMI), carrying a 30-day mortality rate of 40%–50%. While early revascularization remains the cornerstone of therapy, the routine use of temporary mechanical circulatory support (tMCS) devices to stabilize patients remains controversial. This review analyzes evidence from major randomized controlled trials (RCTs) and real-world registries, concluding that patient selection, timing, and protocol-driven care are more critical than the choice of device itself.
Overall, the authors discuss 3 Key Devices, mechanisms, and clinical Trial evidence for them in this paper. Authors' Recommendations for Clinical Practice
- Avoid One-Size-Fits-All Approaches: Device implementation must shift from routine use to individualized tailoring based on the hemodynamic stage (SCAI framework), metabolic markers (lactate), and neurological status.
- Multidisciplinary Shock Teams: Utilizing structured, protocol-driven "shock teams" (interventional cardiologists, heart failure specialists, intensivists, and cardiac surgeons) has been shown to improve 30-day and in-hospital survival rates.
- Institutional Volume Matters: Outcomes are significantly better at specialized, high-volume centers (performing 25 mechanical support cases per year), where procedural expertise minimizes the high complication risks associated with these large-bore devices.
Comments
- The author forgot to delete the content from the template in the introduction section: “The introduction should briefly place the study in a broad context and highlight why it is important. It should define the purpose of the work and its significance. The current state of the research field should be carefully reviewed and key publications cited. Please highlight controversial and diverging hypotheses when necessary. Finally, briefly mention the main aim of the work and highlight the principal conclusions. As far as possible, please keep the introduction comprehensible to scientists outside your particular field of research. References should be numbered in order of appearance and indicated by a numeral or numerals in square brackets—e.g., [1] or [2,3], or [4–6]. See the end of the document for further details on references.”
Similarly, “Figure 2. This is a figure. Schemes follow another format. If there are multiple panels, they should be listed as: (a) Description of what is contained in the first panel; (b) Description of what is contained in the second panel. Figures should be placed in the main text near to the first time they are cited.”
Here, proofreading would help avoid this.
- Table 5 is redundant with Table 1’s last row. The 2021/22 chest pain/revascularization guideline is complemented/replaced by the 2025 ACS guideline, so no need to keep the 2022 column
Author Response
We sincerely thank the Editor and the Reviewers for their thorough and constructive assessment of our manuscript. The comments were valuable and have helped us improve the work. We have addressed all points, and the corresponding revisions are marked as tracked changes in the revised file. A point-by-point response follows, with each comment reproduced in italics and our reply beneath it.
Comment 1 — Residual template text.
The manuscript still contains leftover MDPI template/instructional text that should be removed before publication.
Response.
We have removed all residual template text. This includes the MDPI instructional paragraph at the end of the Introduction and the template placeholder that appeared as a second caption for Figure 2. We confirmed that Figure 2 retains a single, correct caption and screened the whole manuscript for any further boilerplate.
Comment 2 — Table 5 redundant with Table 1.
Table 5 is redundant with the information already provided in the last row of Table 1 and should be deleted.
Response.
We agree. Table 5 has been removed in its entirety (title, table body and abbreviations note). The device-specific guideline recommendations it summarized are already captured in the corresponding row of Table 1, where the Class IIa designation for the microaxial flow pump is reported. The single in-text reference to Table 5 has been redirected to Table 1. This change also resolves the inconsistency noted by Reviewer 2 (Comment 2 below), since the recommendation now appears in a single, internally consistent location.
Reviewer 2 Report
Comments and Suggestions for AuthorsMajor Revisions
1. Template text in manuscript body: The Introduction (lines 66–74) contains verbatim MDPI boilerplate instructional text that was not removed prior to submission. An identical issue affects page 13 (lines 369–372), where a template placeholder appears as a second caption for Figure 2, duplicating the correct caption at lines 342–350. Both passages must be deleted and the figure caption verified for uniqueness and correct placement.
2. Internal inconsistency regarding ACC/AHA 2025 recommendation for Impella: Section 3.3 states that "American guidance remained at Class IIb," while the same section, Table 1, and Table 5 all consistently report a Class IIa upgrade in the 2025 ACC/AHA document. This contradiction must be resolved. If the authors intend to reference an interim or earlier version of the guidance, the appropriate source must be specified.
3. Duplicate references: Three reference pairs cite the same primary sources:
- References 13 and 44 (Møller et al., JACC 2025)
- References 21 and 43 (Udesen et al., JAMA Cardiol 2025)
- References 29 and 45 (Ostadal et al., Circulation 2023)
The bibliography must be deduplicated and all in-text citations corrected accordingly.
4. Incorrect citation for ECMELLA bleeding data: The major bleeding rates associated with the ECMELLA strategy (BARC 3–5: 64.3% vs. 24.5%) are attributed to Reference 33 (Zweck et al., Circulation 2024), which addresses renal outcomes in the DanGer Shock trial. The correct source for ECMELLA-related bleeding data must be identified and cited.
5. Discrepancy in ECLS-SHOCK mortality figures: The 30-day mortality reported in the text (48.3% vs. 49.5%) differs from the values in Table 2 (47.8% vs. 49.0%). Both must be reconciled against the primary publication (Thiele et al., NEJM 2023).
6. EUROSHOCK trial cited in Table 3 without text discussion or bibliography entry: The EUROSHOCK trial appears in the "Other RCTs" column of Table 3 but is absent from both the manuscript body and the reference list. It must either be removed from the table or appropriately introduced in the text with a corresponding citation.
Minor Revisions
7. NNT and NNH: endpoint specification required. The NNT of ~8 and NNH of ~6 derived from DanGer Shock are reported without specifying the underlying endpoints. Authors should clarify that the NNT refers to 180-day all-cause mortality and define precisely which complication composite or individual event drives the NNH estimate.
8. Literature search methodology: Although a narrative format is appropriate for this review type, a brief description of the search strategy (databases, date range, key search terms) would be informative and is generally encouraged by the journal. Authors may consider adding this as a short methodological note.
9. eCPR as a distinct indication: Extracorporeal CPR represents an evolving and mechanistically distinct indication for VA-ECMO, supported by dedicated trial data (INCEPTION, ARREST). Its current treatment — subsumed within the broader "refractory shock" category — understates its clinical specificity. A brief dedicated paragraph would strengthen the completeness of the VA-ECMO section.
Author Response
We sincerely thank the Editor and the Reviewers for their thorough and constructive assessment of our manuscript. The comments were valuable and have helped us improve the work. We have addressed all points, and the corresponding revisions are marked as tracked changes in the revised file. A point-by-point response follows, with each comment reproduced in italics and our reply beneath it.
Major Revisions
Comment 1 — Template text in manuscript body.
The Introduction contains verbatim MDPI boilerplate instructional text. An identical issue affects the placeholder that appears as a second caption for Figure 2, duplicating the correct caption. Both passages must be deleted and the figure caption verified for uniqueness and correct placement.
Response.
We have removed both passages. The MDPI instructional paragraph at the end of the Introduction (“The introduction should briefly place the study … See the end of the document for further details on references.”) has been deleted. The template placeholder caption following the Conclusions (“This is a figure. Schemes follow another format …”) has also been deleted. We verified that Figure 2 now has a single, correct caption (“Figure 2. Proposed decision-making algorithm for mechanical circulatory support in AMI-related cardiogenic shock …”), and we screened the remainder of the document to confirm no further residual template text is present.
Comment 2 — Internal inconsistency regarding the ACC/AHA 2025 recommendation for Impella.
Section 3.3 states that “American guidance remained at Class IIb,” while the same section, Table 1, and Table 5 all report a Class IIa upgrade in the 2025 ACC/AHA document. This contradiction must be resolved.
Response.
We confirmed against the primary source (Rao SV, O’Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes) that the microaxial flow pump (Impella CP) was upgraded from Class 2b to Class 2a (Level of Evidence B) for STEMI with severe or refractory cardiogenic shock. The contradictory sentence was therefore an internal error and has been deleted. We replaced it with a corrected statement that aligns Section 3.3 with Table 1: “This Class IIa (rather than Class I) designation reflects the balance between the survival benefit demonstrated in DanGer Shock and the substantial device-related complication burden.” In addition, following Reviewer 1’s comment that Table 5 was redundant with Table 1, Table 5 has been removed; the Class IIa designation is now reported consistently in Section 3.3 and Table 1, eliminating the inconsistency.
Comment 3 — Duplicate references.
Three reference pairs cite the same primary sources: 13 and 44 (Møller et al.), 21 and 43 (Udesen et al.), 29 and 45 (Ostadal et al.). The bibliography must be deduplicated and all in-text citations corrected accordingly.
Response.
The three duplicate pairs have been resolved by retaining the lower-numbered entry and deleting the duplicate (deleted: old 43 = 21; old 44 = 13; old 45 = 29). While performing the deduplication we identified two further exact duplicates that had not been flagged: old reference 46 duplicated reference 24 (Burkhoff et al., Hemodynamics of Mechanical Circulatory Support) and old reference 49 duplicated reference 34 (Dettling et al., hospital volume). For a fully clean bibliography we removed these as well. The remaining unique entries were renumbered (old 47 → 43, Pappalardo; old 48 → 44, Abdelnabi). All affected in-text citations were corrected accordingly: [43,44] → [13,21]; [29,45,46] → [24,29]; [47] → [43]; [48] → [44] (two occurrences); [49] → [34].
Comment 4 — Incorrect citation for ECMELLA bleeding data.
The major bleeding rates for the ECMELLA strategy (BARC 3–5: 64.3% vs. 24.5%) are attributed to Reference 33 (Zweck et al.), which addresses renal outcomes. The correct source must be identified and cited.
Response.
We identified the correct primary source. The BARC type 3–5 bleeding rates (64.3% for combined microaxial flow pump + VA-ECMO vs. 24.5% for the pump alone) derive from the DanGer Shock bleeding sub-study: Sørensen R, Møller JE, Vandenbriele C, et al. Bleeding in Patients With Infarct-Related Cardiogenic Shock: A DanGer Shock Substudy. JACC Cardiovasc Interv. 2026;19(3):302–312. This reference has been added (new reference 45) and is now cited inline at the ECMELLA bleeding statement in Section 4.2. Reference 33 (Zweck et al., renal outcomes) is no longer associated with these bleeding figures.
Comment 5 — Discrepancy in ECLS-SHOCK mortality figures.
The 30-day mortality in the text (48.3% vs. 49.5%) differs from Table 2 (47.8% vs. 49.0%). Both must be reconciled against the primary publication (Thiele et al., NEJM 2023).
Response.
Against the primary publication (Thiele H, et al. N Engl J Med 2023;389:1286–1297), the correct 30-day all-cause mortality is 47.8% vs. 49.0% (100/209 vs. 102/208; RR 0.98; 95% CI 0.80–1.19; P = 0.81). The erroneous values (48.3% vs. 49.5%) appeared in both the Section 4.2 text and Table 1; both have been corrected to 47.8% vs. 49.0%. Table 2 already reported the correct figures and was left unchanged, so all three locations are now consistent with the source.
Comment 6 — EUROSHOCK trial cited in Table 3 without text or bibliography entry.
EUROSHOCK appears in the “Other RCTs” column of Table 3 but is absent from the manuscript body and the reference list. It must either be removed or appropriately introduced with a citation.
Response.
As EUROSHOCK is not discussed in the text, we have removed it from Table 3 to avoid an unsupported reference. The column header now reads “Other RCTs (ECLS-SHOCK, ECMO-CS)”, both of which are discussed and cited in the manuscript.
Minor Revisions
Comment 7 — NNT and NNH: endpoint specification.
The NNT (~8) and NNH (~6) from DanGer Shock are reported without specifying the underlying endpoints. Clarify that the NNT refers to 180-day all-cause mortality and define what drives the NNH estimate.
Response.
We have specified both endpoints in Section 3.2. The NNT of approximately 8 is now stated to refer to the trial’s primary endpoint of 180-day all-cause mortality. The NNH of approximately 6 is now defined as referring to the composite of serious device-related adverse events (severe bleeding, limb ischemia, sepsis and renal replacement therapy).
Comment 8 — Literature search methodology.
A brief description of the search strategy (databases, date range, key terms) would be informative and is encouraged by the journal.
Response.
We thank the Reviewer for this suggestion. As the Reviewer kindly acknowledges, a narrative format is appropriate for this review. The manuscript is an expert, topic-focused synthesis of the principal recent randomized trials and current guidelines rather than a systematic review, and therefore does not lend itself to a PRISMA-style search protocol with predefined eligibility and risk-of-bias assessment.
Comment 9 — eCPR as a distinct indication.
Extracorporeal CPR is a mechanistically distinct indication for VA-ECMO, supported by dedicated trial data (INCEPTION, ARREST). Its current treatment within “refractory shock” understates its specificity. A brief dedicated paragraph would strengthen the VA-ECMO section.
Response.
We have added a dedicated paragraph in the VA-ECMO section that frames eCPR as a separate, time-critical indication distinct from VA-ECMO used to support an established shock state. The paragraph summarizes the supporting evidence: the single-center ARREST trial (Yannopoulos D, et al. Lancet 2020;396:1807–1816), stopped early for a survival benefit, and the multicenter INCEPTION trial (Suverein MM, et al. N Engl J Med 2023;388:299–309), which found no significant difference in survival with favorable neurological outcome. These two trials were added as new references 46 and 47.
