In the 1990s, interest in performing coronary artery bypass grafting (CABG) on a beating heart, avoiding cardiopulmonary bypass, experienced a resurgence, leading to renewed focus on off-pump surgery [1, 2]. Off-pump coronary artery bypass grafting (OPCABG) has been widely utilized in patients with heart failure (HF) due to its association with reduced perioperative complications and improved long-term outcomes compared to on-pump procedures [3, 4]. The left ventricular ejection fraction (LVEF) is an indicator to evaluate HF, which associates with the outcomes in cardiac surgery [5]. Patients with low LVEF face a high risk of perioperative complications, adversely affecting both immediate and long-term survival. This risk is particularly pronounced in those with ventricular contractility impairment following cardiopulmonary bypass and cardioplegia, regardless of other comorbidities [6, 7]. In OPCABG, reduced LVEF, often associated with ischemic cardiomyopathy, is linked to an increased risk of long-term complications [8, 9, 10]. Further investigation is needed to elucidate the relationship between LVEF and perioperative outcomes in OPCABG, offering greater insight into its prognostic significance.

LVEF refers to the percentage of blood volume in the left ventricle at the end of diastole that is pumped out with each contraction, which can be expressed mathematically as $LVEF(\%)=\frac{\text{Stroke volume}}{\text{End-diastolic volume}}$. End-diastolic volume is influenced by several factors, including a patient’s weight, body mass index (BMI), and body surface area (BSA), the latter being a parameter calculated based on height and weight [11]. BSA is positively correlated with blood pressure and serves as a fairly accurate indicator of total body water. It is commonly used to normalize cardiac output to cardiac index and to estimate the glomerular filtration rate (GFR) [12, 13, 14, 15]. In this context, we propose normalizing the end-diastolic volume by BSA to reduce its bias on LVEF. The resulting BSA-adjusted LVEF (bLVEF) is calculated as the stroke volume divided by the normalized end-diastolic volume ($bLVEF(\%)=\frac{\text{Stroke volume}}{\text{End-diastolic volume}\left(\frac{1}{\mathrm{BSA}}\right)}$). This study aims to investigate the roles of LVEF, BSA, and bLVEF in a special clinical setting and to evaluate whether their interactions following OPCABG can improve patient-centered care.

Consequently, we aimed to explore the distinct effects of LVEF, BSA, and bLVEF on early clinical outcomes for OPCABG patients using data from five leading Chinese cardiovascular centers. The objectives were to investigate (1) the impact of LVEF on perioperative outcomes, (2) the correlation between BSA and LVEF, and (3) the association of bLVEF with perioperative complications and mortality rates among.

In this multi-center cohort investigation, we found that (1) low LVEF is a significant predictor of postoperative survival and adverse events; (2) BSA exhibited a slight negative correlation with LVEF; (3) bLVEF emerged as the most consistent predictor of mortality compared to BSA and LVEF; and (4) a bLVEF cutoff of 85 effectively identified patients at high risk of mortality.

Cardiac surgery improves survival in patients with advanced left ventricular dysfunction compared to medical management [20]. However, low preoperative LVEF is a known risk factor for the adverse outcomes following CABG [21]. Since Benetti et al. [2] successfully performed OPCABG with the emphasis on myocardial protection and the surgeon’s increasing proficiency in bypass grafting, OPCABG has become a well-developed and safe procedure [22]. Recent years have seen increased interest in its use for severe coronary artery disease, with several studies highlighting its efficacy in patients with low LVEF [23]. Shennib et al. [24] reported favorable outcomes and low mortality rates in patients with impaired ventricular function undergoing off-pump surgical revascularization. Arom et al. [22] discovered that performing multivessel coronary artery bypass using the OPCAB technique is both suitable and feasible for patients with left ventricular function at or below 30%. In addition, Ueki et al. [10] reported that OPCABG is linked to significantly lower rates of early mortality and morbidity in patients with an ejection fraction of less than 30%. Despite these findings, comparative studies on OPCABG across different EF categories remain limited. In our cohort, 7093 (89.48%) patients had normal LVEF, 639 (8.06%) had HFmrEF, and 195 (2.46%) had HFrEF, consistent with previously reported population distributions [25]. Patients with HFrEF or HFmrEF exhibited higher rates of diabetes, hypertension, impaired kidney function, and prior myocardial infarctions, along with elevated LVEDd and LAD, worse NYHA Functional Classification scores, and greater statin use (p for trend 0.01). These findings highlight the poorer preoperative baseline condition of patients with low LVEF compared to those with normal LVEF.

CAD with reduced EF presents a significant challenge to OPCABG. Proper exposure of the anastomosis site during OPCABG necessitates cardiac manipulation, which can compress the left ventricular outflow tract and lead to hypotension. In patients with low LVEF, the limited cardiac reserve makes them highly susceptible to abrupt drops in blood pressure. Additionally, patients with left main trunk and three-vessel disease are at increased risk of malignant arrhythmias during cardiac manipulation [4, 26, 27]. Therefore, it is necessary to implement appropriate emergency measures and coordinate with anesthesiologists before repositioning the heart. The use of IABP helps to improve the success rate of OPCABG surgery [28]. Suzuki et al. [29] indicated that preoperative IABP therapy in high-risk coronary patients effectively prevents hemodynamic instability and yields surgical outcomes similar to those seen in moderate to low-risk patients. In our study, HFrEF and HFmrEF were identified as strong negative prognostic factors for mortality, suggesting that a decrease in the odds of mortality compared to the reference group (LVEF $\ge$50%). Similarly, adverse event rates rose by 63% with each LVEF category reduction. Surgeons must carefully assess intraoperative conditions to determine whether to proceed with OPCABG. If cardiac function deteriorates significantly during the procedure, transitioning to on-pump coronary artery bypass grafting should be considered to mitigate further risks.

Echocardiography is extensively utilized for diagnosing and managing cardiac conditions, particularly in the preoperative assessment of patients undergoing cardiac surgery [30, 31]. However, cardiac surgeons often rely on unstandardized absolute values when interpreting echocardiographic parameters, despite the influence of body mass factors on heart structure [32]. Assessing echocardiographic indicators solely based on absolute values does not enable precise diagnosis of cardiac conditions [33]. BSA, a metric for characterizing body size, is frequently employed to normalize mass and volume and to index physiological parameters related to cardiovascular disease [34, 35]. A study has indicated that left ventricle (LV) diameter provides a basic and simplified evaluation of a three-dimensional structure, failing to account for the more intricate variations in ventricular shape or size [36]. To address this, the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommended indexing echocardiographic parameters, such as right and left ventricular sizes, to BSA [35]. Moreover, the Simpson’s biplane method, which uses orthogonal long-axis views, allows for a more accurate calculation of LV volume that can be indexed to BSA for improved precision [37]. LVEF is a parameter obtained from echocardiography that measures the amount of blood ejected from the heart’s left ventricle—the primary pumping chamber—with each contraction [38]. Furthermore, LVEF is acknowledged as an independent risk factor for CABG. A lower ejection fraction correlates with increased perioperative mortality and reduced five-year survival rates [39, 40]. While the conventional definition of the normal range for EF is derived from the general population, encompassing groups with varying clinical characteristics and prognoses. Thuijs DJFM et al. [25] found a U-shaped association between LVEF and all-cause mortality three years after CABG. In our study, we identified a J-shaped curve in LVEF when predicting perioperative mortality in patients undergoing OPCABG. This observation is of considerable clinical significance, as it suggests a potential for misinterpretation among cardiac clinicians. Specifically, clinicians may incorrectly assume that patients with an LVEF at the relatively “good” level have adequate cardiac function, thus deeming them to be at a low risk for perioperative complications. However, this oversimplification can obscure the true risks associated with the procedure. Given the complexity of heart failure and the multitude of factors influencing perioperative outcomes, it is imperative to consider all relevant risk factors beyond just LVEF when making surgical decisions for patients undergoing OPCABG. Relying solely on LVEF could lead to incomplete assessments of a patient’s functional status, potentially compromising patient safety. To mitigate this risk of bias, we advocate for the normalization of LVEF to BSA, a practice that enhances the reliability of prognostic assessments. By doing so, we established a critical numerical threshold of 85 as a ‘divider’ that serves to refine the prediction of perioperative mortality. This threshold represents a key parameter in stratifying patient risk, enabling more accurate and personalized surgical decision-making. It is worth noting that the observed patterns are hypothesis-generating and require validation in cohorts with harmonized analytical frameworks. Ultimately, our findings underscore the importance of incorporating LVEF normalization into clinical practice, ensuring that all relevant factors are weighed appropriately to optimize patient outcomes in OPCABG. This approach can significantly improve the predictive accuracy regarding mortality and enhance the overall management of patients undergoing coronary revascularization.

There are limitations in our study. Firstly, the retrospective cohort design relies on historical patient data, which restricts the availability of comprehensive preoperative activity tolerance information. Additionally, the extended follow-up period resulted in a considerable loss to follow-up. Secondly, common post-surgery complications such as severe heart failure and atrial fibrillation were not included due to challenges in accurately documenting them during follow-up assessments. Thirdly, the study did not discuss gender differences, which will be further explored in future research. Lastly, body surface area is calculated using a formula based on weight and height, which does not reflect the true surface area of an individual. Furthermore, factors like age, gender, and race may confound the BSA measurement, highlighting the need for future research to investigate the correlating variables associated with BSA.

bLVEF serves as a key predictor of mortality in OPCABG, effectively eliminating BSA-related bias and demonstrating a strong capacity to predict mortality.

CABG, coronary artery bypass grafting; OPCABG, off-pump coronary artery bypass grafting; HF, heart failure; LVEF, left ventricular ejection fraction; BMI, body mass index; BSA, body surface area; GFR, glomerular filtration rate; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; LVEDd, left ventricular end-diastolic diameter; LAD, left atrial dimension; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; ICU, intensive care unit; MSA, multiple system atrophy; AKI, acute kidney injury; MI, myocardial infarction; AUC, area under the curve.

All data reported in this paper will be shared by the lead contact upon request.

HBZ and YQL conceived and designed the study; ZPW, ZHZ, YHL, MYW, HBW, DX, YC gathered the data; CYL, ZPW, ZHZ performed statistical analyses; ZPW, ZHZ wrote the first draft of the manuscript; NL, JKL made critical revision of the manuscript for key intellectual component. All authors contributed to the conception and editorial changes in the manuscript. All authors provided approval of the final version of the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study was carried out in accordance with the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Fuwai Hospital (Approval No: 2017-943), and all of the participants provided signed informed consent.

This work is supported by the Beijing Science and Technology Commission of China (grant number: D171100002917001 and D171100002917003) and the Beijing Anzhen Hospital High Level Research Funding (grant number: 2024AZC1003).

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/RCM26681.