Lim et al. [1] provides an extensive review of left ventricular (LV) unloading modalities during venoarterial extracorporeal membrane oxygenation (VA-ECMO). The study outlines the hemodynamic challenges of VA-ECMO, particularly focusing on LV overload and the various unloading techniques available, including Impella, intra-aortic balloon pump (IABP), direct LV venting, percutaneous atrial septostomy (PAS), pulmonary artery drainage (PAD), and transseptal left atrial (LA) cannulation.

This article excels in its detailed use of pressure-volume (PV) curve analysis, effectively elucidating the physiologic interaction between the left ventricle and VA-ECMO. The inclusion of computer-based mathematical simulations of PV loops is particularly commendable. Additionally, the comprehensive comparison of LV unloading modalities and their nuanced mechanisms provides valuable insights, especially in distinguishing preload reduction from afterload management. Table 1 is a highlight, offering a clear summary of these findings.

However, some aspects warrant further discussion. (1) Terminology and classification in Table 1: the authors frequently use the terms “direct” and “indirect” in the manuscript and Table 1. While conceptually useful, these terms may not be intuitive for all readers. The classification criteria for "direct LV unloading" and "direct lung protection" appear to differentiate modalities based on whether they primarily target the left ventricle or left atrium. Modalities actively reducing LV volume or loading (e.g., IABP, Impella, direct LV venting) are marked as "direct LV unloading" and categorized as "yes." Similarly, those decreasing LA volume or loading (e.g., PAS, PAD, transseptal LA cannulation) are marked as "direct lung protection" and categorized as "yes." However, the manuscript also acknowledges that some researchers prefer the term “left heart unloading” over LV unloading, emphasizing the interconnected nature of ventricular and atrial unloading. Given the interdependence of these processes—except in extreme cases such as mitral stenosis—this dichotomy may not fully align with cardiac physiology. For example, both LA and ventricular unloading influence pulmonary capillary wedge pressure, underscoring the overlap between these effects. (2) LV energetics for certain modalities: Table 1 marks LV energetics for direct LV venting and transseptal LA cannulation as "NA (not available)", citing a lack of data from experimental models. While it is true that no direct experimental validation exists, reasonable inferences can be drawn based on analogous mechanisms.

Both direct LV venting and Impella actively drain blood from the LV, exerting comparable effects on LV decompression. Radakovic et al. [2] demonstrated similar unloading characteristics for Impella and surgically inserted LV vents during VA-ECMO. Additionally, a systematic review and meta-analysis by Meuwese et al. [3] reported comparable hemodynamic improvements between direct LV venting and Impella support during VA-ECMO. Similarly, transseptal LA cannulation can be compared to PAS, which has been shown to reduce pulmonary capillary wedge pressure and provide unloading effects comparable to more invasive strategies such as transapical LV venting [4]. Recent studies by Donker et al. [5] have further supported the efficacy of transseptal approaches for left heart decompression. These findings suggest that LV energetics for direct LV venting and transseptal LA cannulation could be reasonably inferred to align with Impella and PAS, respectively. Updating Table 1 to reflect these assumptions may provide a more comprehensive perspective.

To ensure clarity, we define key terms related to LV unloading strategies as follows. Preload reduction refers to interventions that primarily decrease blood volume or pressure returning to the left heart, thereby reducing end-diastolic volume and wall tension. Afterload reduction involves interventions that lower impedance to LV ejection, typically by decreasing arterial resistance or augmenting forward flow. LV unloading encompasses strategies that reduce LV work through preload reduction, afterload reduction, or direct removal of blood from the ventricle. The degree of unloading is indicated in Table 1 using (+) symbols, where a greater number of symbols corresponds to a stronger unloading effect based on available literature. Similarly, lung protection refers to strategies that mitigate pulmonary congestion by reducing LA pressure, with efficacy also rated using (+) symbols according to existing evidence.

The newly suggested Table 1 presents a comparative analysis of various unloading modalities based on available evidence and reasonable inferences where direct data are limited. The quantitative ratings using (+) symbols represent relative efficacy based on published clinical and experimental data, with more symbols indicating stronger effects. We acknowledge that these ratings remain somewhat subjective and should be interpreted within appropriate clinical contexts. The table aims to provide a framework for clinical decision-making while recognizing that individual patient factors may influence outcomes.

While the hemodynamic effects of various LV unloading techniques have been extensively studied, systematic analyses of energetic efficiency measures (such as PVA and MVO₂) across different modalities remain limited. Future research should focus on direct comparisons of energetic indices between unloading strategies, particularly for direct LV venting and transseptal LA cannulation, where current data are extrapolated from similar approaches. Additionally, long-term outcomes and the impact of different unloading strategies on myocardial recovery require further investigation to optimize clinical decision-making in this complex patient population.

In conclusion, while limitations exist in categorizing unloading modalities, this proposed revision aims to foster discussion on developing a more objective and physiologically aligned classification system. By better reflecting the integrated hemodynamics of the heart, these changes can enhance understanding and improve clinical application.