Coronary Artery Bypass Grafting in High-Risk Patients: On-Pump Beating-Heart CABG

Abstract

The tailored surgical approach in high-risk patients undergoing coronary artery bypass graft (CABG) still remains debated. Each classic operative technique has strengths and limitations: on-pump CABG entails the use of cardiopulmonary bypass and cardioplegic arrest, while off-pump “beating heart” CABG is technically challenging and might pose problems in case of preoperative hemodynamic impairment or recent myocardial infarction. The hybrid approach of on-pump beating-heart CABG (OPBHC) has been proposed over the years as an acceptable trade-off in cases of severe complications caused by cardioplegic arrest or manipulation of the heart. This chapter intends to summarize the available literature about OPBHC, considering both original contributions and secondary research papers, trying to define operative indications and future perspectives. OPBHC, preventing hemodynamic deterioration while sustaining adequate end-organ perfusion, has been gradually recognized as an effective technique for performing surgical revascularization in high-risk patients, such as those presenting with acute coronary syndrome, cardiogenic shock, or severe left ventricular dysfunction. In selected cases, OPBHC reduces in-hospital mortality and decreases the risk of perioperative complications such as myocardial ischemia or stroke and should be considered a valid alternative to conventional off-pump and on-pump CABG techniques. OPBHC should be in the armamentarium of the next-generation cardiac surgeon.

1. Introduction

Coronary artery disease is a common pathological condition that is increasingly undermining people's health. This disease can be treated with different targeted strategies, such as medical therapy, percutaneous revascularization (PCI), or coronary bypass surgery. These treatments are often complementary, and they should not be seen as mere alternatives. However, patients with symptoms refractory to medical therapy, left main or triple vessels disease, or complex coronary anatomy not suitable for PCI (or failed PCI) require an inevitable surgery.

Regarding coronary bypass surgeries, there are several methods and techniques have dramatically evolved since the late 1970s. Coronary artery bypass grafting (CABG) is commonly performed for patients with stenosis exceeding a 70% reduction in vessel diameter, delivering blood to the distal coronary artery beyond a stenosis.

There are two different surgical techniques of CABG that are commonly used: on-pump “conventional” CABG and off-pump “beating heart” CABG. The use of cardiopulmonary bypass (CPB) and cardioplegia are the main characteristics that distinguish these two types of surgery. There are several pros and cons to using these two surgical techniques, which should be evaluated carefully before assessing which method is more effective and suitable in different cases.

The cardiopulmonary bypass carries several risks, and in 1% of cases, it leads to cerebral damage due to intracerebral bleeding, embolization of microbubbles, arterial debris, or inadequate cerebral perfusion. Moreover, it brings the activation of several systematic inflammatory mechanisms, with cytokine release and complement activation. Coagulopathy and hemolysis could also occur. All these processes can be the main factors for post-bypass patients in developing pulmonary and renal dysfunctions.

In the on-pump surgery, as mentioned previously, the use of cardioplegic arrest is the main characteristic of this technique. Cardioplegia is a solution made of electrolytic, especially high doses of potassium, which causes heart arrest in diastole. Cardioplegia is typically delivered at a temperature of 4–6°C and via a crystalloid solution or one derived from the patient’s own blood. Coronary arteries are perfused by the cardioplegia via the aortic root or directly via the coronary artery ostia, or retrogradely via a catheter placed in the coronary sinus. Cardioplegia, combined with hypothermia, guarantees a safe period of cardiac arrest in which the surgeon will perform the graft.

Contrarily, during an off-pump surgery, the coronary bypass is performed without the use of any cardioplegia, hence on a beating heart. This alternative surgery is commonly used in specific cases, such as in the presence of a markedly calcified ascending aorta. However, this type of surgery does not avoid cardiac risks, in particular when hemodynamic instability arises from the surgical manipulation and immediate conversion to the on-pump conventional CABG is needed.

Considering the risks of both techniques, a new hybrid approach has been studied and tested to overcome the limitations of each technique trying to gather benefits from both, and the dichotomy between “on-pump” versus “off-pump” CABG has been made more complex by the introduction of the beating heart on-pump CABG (OPBHC). OPBHC technique was introduced in the mid-1990s, and it combined the main characteristics of the previous two methods, providing hemodynamic stability with the CPB without aortic cross-clamp and cardioplegic cardiac arrest, preserving native coronary blood flow.

Literature search was performed through PubMed, Web of Science, Scopus, and Cochrane database from their inception up to July 2023 using the following search keywords in various combinations: “myocardial infarction”, “myocardial revascularization”, “on-pump beating-heart”, “coronary artery bypass graft”/“CABG”, “cardiogenic shock”, “left ventricular dysfunction”. We also reviewed references of prior randomized trials, prospective/retrospective cohort studies, systematic reviews, meta-analyses, and references from selected articles. All papers describing postoperative outcomes after on-pump beating-heart CABG were included, as this was considered the “intervention”. The “comparators” were on-pump CABG or off-pump CABG when compared to OPBHC. Outcomes included early mortality, postoperative complications, and time-to-event outcomes. Editorials, opinion articles, and repeat publications of the same data set were excluded from the quantitative synthesis.

2. Off-pump CABG vs. on-pump CABG vs. “on-pump beating heart CABG” (OPBHC)

Despite the flourishing literature after its introduction, OPBHC still remains considered a non-valuable option by many surgeons in the real-world scenario, who are afraid of its complications. However, the literature produced a considerable amount of evidence to draw objective conclusions.

A recent study by Jiang et al. [1] studied the main pros and cons of using off-pump CABG vs. the use of OPBHC by analyzing the rate of early mortality and long-term survival of patients. The study enrolled a total of 5615 patients, of which less than one-third underwent OPBHC, and the remaining were treated with off-pump CABG. The main conclusion was that no significant statistical differences have been found, in terms of early mortality and long-term survival rates, among the patients treated with these two techniques. The use of CPB, in both conventional on-pump and OPBHC, can lead to some complications, such as renal failure, strokes, arrhythmia, coagulopathy, platelet dysfunction, and increased drainage or blood loss, increasing postoperative morbidity and mortality. Hence, for some patients, the off-pump CABG might be a suitable surgery. However, patients with hemodynamic instability cannot tolerate prolonged heart manipulation, requiring CPB support. In these cases, the study suggested that the OPBHC can play a crucial role, providing more effective hemodynamic support than off-pump CABG but with a shorter CPB time than conventional on-pump CABG.

Another study by Wang et al. [2] analyzed the benefits of the OPBHC technique vs. the conventional on-pump CABG in high-risk patients. The main conclusions were that OPBHC surgery had lower mortality and similar long-term survival rates than conventional on-pump CABG. Moreover, the study suggests that the OPBHC technique leads to a lower risk of renal failure, thanks to the avoidance of both systemic hypothermia and hypoperfusion of end-organ and the shorter CPB time. This is explained by the fact that in conventional on-pump CABG, the prolonged use of CPB leads to acute kidney injuries. All of this is confirmed by the evidence that a higher number of patients undergone conventional on-pump CABG require hemodialysis than the patients undergone OPBHC surgeries.

Other studies [3, 4] highlighted that OPBHC surgery could lead to a significant acute kidney injury due to higher right atrial pressure, higher distended heart, less venous return from the kidney, and less glomerular filtration function than off and on-pump CABG. The study suggests that the use of left ventricular venting in the conventional on-pump decompresses the heart, lowering the venue's return from kidney. Instead, the off-pump surgery guarantees renal protection thanks to pulsatile flow and normal kidney perfusion pressure. Summarizing data from the literature, factors that might be associated with potential benefits for the OPBHC approach are shown in Table 1. As no randomized evidence is available, recommendations about OPBHC remain based on expert opinions.

Preoperative factors

Acute coronary syndrome; Cardiogenic shock Early graft failure Emergency surgery Redo surgery; Left ventricular dysfunction

Intraoperative factors

Difficult-to-approach coronary targets using off-pump technique; High risk of complications using off-pump technique; Intramyocardial vessels Unstable hemodynamics Poor-quality coronary targets; Diffused calcification; Small diameter

Table 1.

Factors associated with potential benefit from OPBHC approach.

Considering procedural details, heart positioning during OPBHC can be tailored to vessel exposition without compromising hemodynamics, as perfusion is guaranteed by cardiopulmonary bypass. In general, central cannulation is performed (arterial cannula in ascending aorta and venous cannula in right atrium). The graft sequence is similar to off-pump CABG, with the left anterior descending artery being revascularized first (in general with the left internal thoracic artery), followed by obtuse marginal vessels and a posterior descending artery or right circumflex artery. Composite grafts (i.e., Y-graft) can be performed before or after distal anastomosis, depending on the surgeon’s preference. A heart can be moved freely during OPBHC, and stabilization can be achieved with pericardial stitches and epicardial stabilizer to improve exposure. In our clinical practice, the use of an intracoronary shunt to minimize heart ischemia is mandatory, with no other arterial occlude device (e.g., loop above and below the anastomosis site).

3. OPBHC: indications and results

OPBHC might be an alternative method useful in high-risk conditions, such as cardiogenic shock, reduced LVEF, or redo-CABG. Several observational studies and meta-analyses have been carried out between 2000 and 2022, but specific and official guidelines for OPBHC are still missing from international societies. In fact, this technique is still underused across the world, but in trained centers with more advanced testing phases, the results are promising and positive.

A study by Zhu et al. [5, 6] has demonstrated that the level of success of this technique is highly correlated to the level of knowledge and experience in using it. The study reviewed the ANZSCTS (Australian and New Zealand Society of Cardiac and Thoracic Surgery) database, in which only 1.3% of patients across Australia with emergent CABG within 7 days after acute myocardial injury underwent OPBHC surgery. By contrast, the same study revealed that in Japan, the same technique was performed in 24% of the cases, highlighting more powerful results than those in Australia on OPBHC. Hence, the choice of which method is more suitable primarily depends on surgical expertise, the patient’s hemodynamical status, and comorbidities.

3.1 OPBHC in specific setting: acute myocardial infarction and cardiogenic shock

Acute myocardial infarction (MI) is an emergent situation treated with percutaneous procedures (PCI). In case of unfavorable coronary anatomy for percutaneous approach or failure/complications of percutaneous interventions or myocardial ischemia refractory to medical therapy, urgent CABG should be performed. Yet, a conventional on-pump CABG might deteriorate cardiac function as the use of cardioplegia delivered into an infarcted myocardium could lead to a high risk of ischemia–reperfusion syndrome. On the other hand, off-pump CABG might not be a safe technique because of hemodynamic instability that requires a higher dose of inotropes and vasopressors, which could lead to end-organ damage. Heart manipulation or compression needed for bypass grafting might cause refractory hypotension or arrhythmias, leading to an emergent intraoperative conversion to on-pump CABG as a life-saving procedure. In this case, an emergent conversion to an on-pump CABG could lead to up to a sevenfold increased risk of mortality and a 40% crude mortality rate [7].

In this context, the OPBHC could be a suitable solution (Table 2). The CPB reduces ventricular volume loading, allowing heart mobilization without significant consequences on coronary flow or myocardial stability. In addition, this approach might guarantee grafting of the lateral and inferior wall of the heart, performing a higher rate of complete revascularization than in off-pump CABG procedures. Cardiogenic shock after acute MI occurs in 10–20% of cases, and it is the leading cause of in-hospital mortality. Despite PCI being the targeted therapy in cardiogenic shock after acute MI, GUSTO-1, and SCHOCK trials [7, 14] reveal that CABG had comparable mortality rates to PCI in patients with complex coronary artery disease anatomy and high-risk profile. In addition, CABG guarantees a higher rate of complete revascularization (87% in CABG vs. 23% in PCI) [7, 14]. In an urgent situation, OPBHC avoids cardioplegic arrest and aortic cross-clamping, provides end-organ perfusion, thanks to CPB, and reduces the injection of inotrope drugs. The Rastan et al. [12] study showed that hospital mortality between conventional on-pump CABG and OPBHC was similar (p = 0.8). The study included patients with stable hemodynamics at admission, performing in 48.4% conventional on-pump CABG and in 51.6% OPBHC. Moreover, the study observed that when an OPBHC was performed, despite the use of an emergent conversion to CPB, the in-hospital mortality of patients with cardiogenic shock at admission was reduced (p = 0.48). The Rastan et al. [12] study also highlighted that in OPBHC surgeries, the use of postoperative intra-aortic balloon pump (IABP) and inotrope drugs after CABG is reduced. In addition, the study showed that the shorter duration of CBP during OPBHC, increasing myocardial perfusion and reducing myocardial stunning, leads to a reduction in myocardial infarction after surgery.

Author	Year	Design	Control group	Patients	Risk scores	Short term mortality	Other short-term outcomes	Long term mortality	Other long-term outcomes
Zhu et al. [5]	2019	PS	On-pump CABG	77 vs. 154	EuroSCORE 1 log: 12.3 vs. 14.9, p = 0.98	Similar (11.7% vs. 10.4%, p = 0.85)	Similar MACCEs (22.1% vs. 24.7%, p = 0.84); increased rate of incomplete revascularization (19.5% vs. 9.7%, p = 0.03); slightly reduced left internal mammary artery use (75.3% vs. 84.4%, p = 0.08)	Similar (64.8% [39.4–82.4%] vs. 63.6% [50.5%–74.3%], p = 0.89) (12 years)	NA
Tsai et al. [8]	2012	RS	Off-pump CABG; on-pump CABG	48 OPBHC; 56 off-pump 82 on-pump	EuroSCORE 1 log: OPBHC 11.4%, off-pump 8.4%, on-pump 9.9% (p = 0.01)	Reduced; 4.2% OPBHC vs. 5.4% off-pump vs. 8.5% on-pump (p = 0.57)	Hospital days; 13.1 OPBHC vs. 12.6 off-pump vs. 16.5 on-pump (p = 0.001)	2-, 4-, 6- and 8-year survival rates(%): 70.1, 66.7, 65.1, 65.1 on-pump; 91.1, 81.4, 76.5, 73.8 off-pump; 93.7, 87.0, 87.0, 87.0 OPBHC (p = 0.023)	Similar freedom from cardiac events
Munos et al. [9]	2011	RS	Off-pump CABG; mini-CEC; on-pump CABG	51 OPBHC; 57 off-pump 51 mini-CEC; 55 on-pump	EuroSCORE 1 log >20% in 61% of patients OPBHC, 67% off-pump, 59% mini-CEC, 57% on-pump (p = 0.01)	Similar (OPBHC (2%) compared with the other groups (4.9%), p = 0.36)	Average length of ICU stay 2.53 days vs. 2.16 OPBHC, (p = 0.02); increased complete revascularization (95% vs. 89% for off-pump CABG)	NA	NA
Miyahara et al. [10]	2008	RS	On-pump CABG	38 vs. 23	EuroSCORE 1 log: 9.9 ± 1.6 vs. 9.0 ± 1.6, p = 0.04; preoperative IABP 78.9% vs. 43.5%, p = 0.005	Reduced (2.6% vs. 21.7%, p = 0.046)	Similar graft patency (98.5% vs. 95.7%, p = 0.090); reduced number of distal anastomoses (2.0 ± 0.7 vs. 2.9 ± 0.9, p = 0.001); similar IABP use (0% vs. 3%, p = 0.220); shorter CPB time (126 ± 36 vs. 185 ± 49 min, p = 0.001)	NA	NA
Ferrari et al. [11]	2008	RS	None	25	EuroSCORE 1 log>8 in most patients	8%	Hospital stay 12.0 ± 6.7 days; complete revascularization 92%; IABP use 11%	95.6% (year)	NA
Rastan et al. [12]	2006	RS	On-pump CABG	157 vs. 374 (stable hemodynamics)	EuroSCORE 1 log: 9.6 vs. 8.0, p = 0.01; EuroSCORE > 20: 24.8% vs. 13.9%, p = 0.004	Similar (5.7% vs. 8.6%, p = 0.08)	Reduced hospital stay (10.4 ± 6.8 vs. 12.6 ± 8.2, p = 0.015); increased incomplete revascularization (17.8% vs. 10.7%, p = 0.032); reduced inotropic support (36.3% vs. 52.1%, p < 0.001); reduced reoperation for bleeding (0.6% vs. 4.8%, p = 0.020)	Similar (84.1% vs. 82.1%, p = 0.791) (4 years)	Similar freedom from adverse events (78.2% vs. 74.5%, p = 0.511); similar repeated revascularization rates (7.9% vs. 5.0%, p = 0.74) (4 years)
Rastan et al. [12]	2006	RS	On-pump CABG	83 vs. 24 (cardiogenic shock)	EuroSCORE 1 log: 25.5 vs. 26.2, p = 0.69	Reduced (19.3% vs. 33.3%, p = 0.048)	Reduced stroke (9.6% vs. 33.3%, p = 0.009); reduced atrial fibrillation (39.8% vs. 62.5%, p = 0.041); reduced inotropic support (65.1% vs. 87.5%, p = 0.049); Similar incomplete revascularization rate (12.0% vs. 20.8%, p = 0.275)	Similar (60.3% vs. 44.5%, p = 0.109) (4 years)	Similar freedom from adverse events; 56.4% vs. 36.1%, p = 0.079 (4 years)
Izumi et al. [13]	2006	RS	On-pump CABG	15 vs. 16	NA	Similar (13.3% vs. 31.3%, p = 0.39)	Reduced renal failure (13.3% vs. 64.3%, p = 0.009); similar number of anastomosis (2.3 vs. 2.5, p = 0.202)	NA	NA

Table 2.

Summary of the evidence for OPBHC in patients with acute myocardial infarction, cardiogenic shock, and chronic kidney disease.

AKI: acute kidney injury; CABG: coronary artery bypass grafting; PS: propensity-score adjusted/matched study; RS: retrospective study; REG: registry; RCT: randomized controlled trial; AMI: acute myocardial infarction; MACE: major adverse cardiovascular events; NA: not applicable; NS: not significant; OPBHC: on-pump beating heart coronary artery bypass grafting. Data are referred as OPBHC group versus control group unless otherwise indicated (see table for details). Adapted from Dominici et al. [7].

3.2 Left ventricular dysfunction

The best CABG strategy in patients with poor left ventricular ejection fraction (LVEF) is still debated. Data [1, 6, 7] showed that on-pump CABG carries additional risk in patients with impaired LVEF, mainly because of cardioplegic arrest and related biventricular dysfunction. The results of Prifti et al. [15] underlined how the use of OPHBC may be a successful alternative to CABG with cardioplegic arrest. However, off-pump surgery may lead to incomplete revascularization and intraoperative hemodynamic deterioration. Xia et al. [16] study showed that patients with impaired LVEF, undergoing OPHBC or off-pump surgeries, have the same in-hospital mortality rate (p = 0.741). Yet, in c3.9% of the cases, an emergent conversion from off-pump to OPHBC was needed due to hemodynamic instability or ventricular fibrillation, therefore increasing the mortality rate (reaching around 40%). A recent study by Wang et al. [2] highlighted that, even if in some patients, an emergent conversion from off-pump to OPBHC was required, no differences were found in in-hospital mortality between the two groups (OPBHC vs. off-pump CABG—p = 0.973).

OPHBC had better short-term outcomes, showing a lower rate of early mortality, lower use of IABP, and lower incidence of stroke than on-pump CABG (Table 3). However, the long-term outcomes have shown a clear preference for OPBHC due to incomplete revascularization. Conventional on-pump CABG had higher rates of complete revascularization than OPBHC. On the other hand, off-pump CABG had a lower rate than OPBHC. An analysis of Darwazah et al. [18] showed that OPBHC was the surgical procedure more common than off-pump CABG in redo CABG (13% vs. 3% p = 0.025). According to a similar degree of coronary disease, OPBHC guaranteed an increasing number of distal grafts (p = 0.002) and complete revascularization. The main difference between the two procedures was the hemodynamic instability during cardiac manipulation that prevented complete revascularization in patients who underwent off-pump surgery.

Author	Year	Design	Control group	Patients	Risk scores	Short term mortality	Other short-term outcomes	Long term mortality	Other long-term outcomes
Wang et al. [2]	2019	RS	Off-pump CABG	44 vs. 68	EuroSCORE 1 log: 7.52 vs. 7.68, p = 0.77	Similar (4.5% vs. 4.4%, p = 0.973)	40% mortality rate for conversion; greater number of grafts (3.74 ± 0.84 vs. 3.36 ± 0.80, p < 0.001)	Similar data not shown, p = 0.674, mean follow up of 38.9 ± 16.7 months	Reduced MACEs; data not shown, p = 0.049, mean follow up of 38.9 ± 16.7 months
Xia et al. [16]	2017	RS	Off-pump CABG	88 vs. 128	EuroSCORE 1 log>6: 50% vs. 47%, p = 0.782; all patients with LVEF <35%; increased left ventricular end-diastolic diameter in OPBHC(66.8 ± 6.0 vs. 64.7 ± 5.9, p = 0.013)	Similar (3.4% vs. 4.7%, p = 0.741)	40% mortality rate for conversion; higher number of grafts (3.7 ± 0.8 vs. 2.8 ± 0.6, p < 0.001); higher pre-discharge LVEF(35.6 ± 2.9 vs. 34.8 ± 3.3, p = 0.034	NA	NA
Erkut et al. [17]	2013	RS	On-pump CABG	65 vs. 66	NA	Reduced (3.1% vs. 21.2%, p = 0.001)	Reduced postoperative infarction (1.5% vs. 16.7%, p = 0.012)	Similar 77% vs. 70%, p > 0.05 (18 months)	NA
Darwazah et al. [18]	2010	RS	off-pump CABG	39 vs. 98	EuroSCORE 1 log: 14.1 vs. 12.2, p = 0.443	Similar (8% vs. 6%, p = 0.712)	Increased complete revascularization rate (72% vs. 46%, p = 0.015); increased number of distal anastomosis (2.2 ± 0.7 vs. 1.7 ± 0.7, p = 0.002)	NA	NA
Pegg et al. [19]	2008	RCT	On-pump CABG	25 vs. 25	EuroSCORE 1 log: 12 ± 10 vs. 8 ± 5, p = 0.079	Similar (4% vs. 0%, p = 0.31)	Similar MACEs; 12% vs. 4%, p = 0.30	NA	NA
Prifti et al. [15]	2000	RS	On-pump CABG	107 vs. 191	NA	Similar (6.5 vs. 10%, p = 0.318)	Reduced perioperative infarction (4.7% vs. 13%, p = 0.034), renal dysfunction(29% vs. 41%, p = 0.05), ultrafiltration(5.6% vs. 15.7%, p = 0.017), bleeding >1000 mL(9% vs. 21.4%, p = 0.012)	Similar mortality rates at 1, 3 and 5 years of follow-up (p = NS)	Similar reoperation rates at follow-up (p = NS)

Table 3.

Summary of the evidence for OPBHG in patients with left ventricular dysfunction.

AKI: acute kidney injury; CABG: coronary artery bypass grafting; PS: propensity-score adjusted/matched study; RS: retrospective study; REG: registry; RCT: randomized controlled trial; AMI: acute myocardial infarction; MACE: major adverse cardiovascular events; NA: not applicable; NS: not significant; OPBHC: on-pump beating heart coronary artery bypass grafting. Data are referred as OPBHC group versus control group unless otherwise indicated (see table for details). Adapted from Dominici et al. [7].

3.3 OPBHC in unselected population

There are several studies showing that the use of OPBHC as an ordinary revascularization strategy reduces the level of in-hospital mortality (Table 4). This was confirmed by the Mizutani et al. [23] study, which found that the level of in-hospital mortality among low-risk patients was lower in the OPBHC group (p < 0.001), adding that the elimination of cardioplegic arrest might play a crucial role in case of deteriorated hemodynamic.

Author	Year	Design	Control group	Patients	Short term mortality	Other short-term outcomes	Long term mortality	Other long-term outcomes
Phothikun et al. [3]	2023	RS	On-pump CABG and off-pump CABG	2028	Similar	Similar rate of cardiac index (p = 0.158)	Similar 10-years survival (80.5% vs. 75.9% vs. 73.7%)	OPBHG: reduced rate in MACE (HR 0.52; p = 0.04) and mortality (HR = 0.33; p = 0.01)
Kim et al. [20]	2018	RS	On-pump CABG	254 vs. 391 (173 vs. 173 propensity score-matched)	Similar (1.2% vs. 0%, p = 0.478)	Similar rate of AKI (5.9% vs. 0.8%, p = 0.001); similar rate of dialysis (4.6% vs. 1.2%, p = 0.109)	Similar (3.0% vs. 2.8%, p = 0.506)	Similar (all MACEs: 4.0% vs. 3.5%, p = 0.382)
Antunes et al. [21]	2015	RS	None	8515	0.7%	Stroke 2.6%, AKI 18.9%, myocardial infarction 2.5%	NA	NA
Narayan et al. [22]	2010	RCT	On-pump CABG	40 vs. 41	Similar (none)	NA	Similar 5-years survival (HR 0.62, 95% CI 0.15–2.59)	NA
Mizutani et al. [23]	2007	RS	On-pump CABG	114 vs. 114	Reduced (2.6% vs. 9.6%, p < 0.001)	Decreased rate of complete revascularization (42.1% vs. 77.2%, p < 0.001)	NA	NA

Table 4.

Summary of the evidence for OPBHG in unselected patients.

AKI: acute kidney injury; CABG: coronary artery bypass grafting; PS: propensity-score adjusted/matched study; RS: retrospective study; REG: registry; RCT: randomized controlled trial; AMI: acute myocardial infarction; MACE: major adverse cardiovascular events; NA: not applicable; NS: not significant; OPBHC: on-pump beating heart coronary artery bypass grafting. Data are referred as OPBHC group versus control group unless otherwise indicated (see table for details). Adapted from Dominici et al. [7].

Furthermore, other studies (like the one of Antunes et al. [21]) have confirmed this thesis, showing that a high level of trained staff, combined with adequate preoperative care, can improve the outcome by lowering the level of mortality. Contrarily, a study by Kim et al. [20] highlighted that the level of mortality and postoperative complications among the OPBHC and on-pump CABG groups were similar.

3.4 OPBHG: results from secondary research and meta-analysis

One of the most common and feared postoperative complications after CABG is stroke, which mainly occurs when calcifications along the aorta embolize in brain vessels. During conventional on-pump CABG, two procedures might lead to postoperative stroke: aortic cannulation and aortic cross-clamping. According to this scenario, off-pump CABG represents the best surgical technique in patients with markedly calcified ascending aorta or in patients with a history of cerebrovascular events. In particular, off-pump CABG, with a no-touch approach, avoids aortic side-clamping, and it guarantees a significant reduction in neurological events. This issue has been carefully investigated in secondary research as it might be one of the most peculiar indications for OPBHC (Table 5).

Study	Year	Studies	Patients	Population	Short term mortality	Other short-term outcomes	Long term outcomes
Hwang et al. [24]	2022	19 (1 RCT)	4320 on-pump CABG vs. 5559 off-pump CABG vs. 1962 OPBHC	9 studies with high-risk patients (AMI)	Lower rate in off-pump CABG vs. OPBHC (OR 0.50; 95% CI 0.20–1.57)	Similar rate of stroke, AKI, and length of intensive care unit in off-pump CABG and OPBHC vs. on-pump CABG; Lower rate of myocardial infarction in off-pump CABG vs. on-pump CABG (OR 0.60; 95% CI 0.38–0.93; p = 0.02); lower risk of reoperation for bleeding in off-pump CABG vs. on-pump CABG (OR 0.54; 95% CI 0.37–0.80; p = 0.002)	NA
Wang et al. [6]	2021	24 (3 RCT)	1847 OPBHC vs. 5015 on-pump-CABG	9 studies with high-risk patients	Higher in on-pump CABG (OR 1.45; 95% CI 1.09–1.93; p = 0.01)	Higher risk of myocardial infarction in on-pump CABG (OR 2.60; 95% CI 1.41 to 4.78; p = 0.002); Higher risk of LOS in on-pump CABG (OR 2.56; 95% CI 1.55–4.23; p < 0.001); higher risk of AKI in on-pump CABG (OR 1.84;95% CI 1.38–2.44; p < 0.01); similar rate of hemodialysis (OR 1.23; 95% CI 0.74 to 2.12; p = 0.41); similar rate of incomplete revascularization (OR 0.65; 95% CI 0.40–1.05; p = 0.08)	Similar mortality (HR 1.08; 95% CI 0.81–1.43)
Jiang et al. [1]	2021	18 (5 RCT)	1548 OPBHC vs. 4067 off-pump CABG	18 studies with pairwise comparison	Similar (OR 1.28; 95% CI:0.91–0.80; p = 0.16)	Higher risk of stroke in OPBHC (OR 1767; 95% CI: 1.08–2.58; p = 0.02); similar heterogeneity of AKI (p = 0.09); lower risk of arrhythmias in off-pump CABG (OR 1.30; 95% CI: 1.06–1.6; p = 0.001); lower risk of incomplete revascularization in OPBHC (OR 0.67; 95% CI:0.49–0.92; p = 0.01); Higher risk of blood loss in OPHBC (CI 42.94–180.18; p = 0.001); Lower rate of distal anastomoses in off-pump CABG (CI 0.29 to 0.61; p < 0.00001)	Similar mortality (HR 0.86, 95% CI: 0.51–1.45; p = 0.57)
Dominici et al. [7]	2020	17 (2 RCT)	2331 OPBHC versus on-pump CABG; 677 OPBHC versus off-pump CABG	17 studies (12 on-pump CABG and 5 off-pump CABG) with pairwise comparison	Reduced (RR 0.59, 95% CI 0.36–0.97)	Reduced postoperative stroke (RR 0.60, 95% CI 0.39–0.91); reduced postoperative intra-aortic balloon pump use (RR 0.56, 95% CI 0.31–1.01); myocardial infarction (RR 0.48, 95% CI 0.22–1.07)	Lower risk of incomplete revascularization in OPBHC vs. off-pump CABG (RR 0.53, 95% CI 0.33–0.87).; Higher risk of incomplete revascularization in OPBHC vs. on-pump CABG (RR 1.71, 95% CI 1.23–2.39)
Ueki et al. [25]	2016	14; (2 RCT)	884 OPBHC; 1156 on-pump conventional CABG	Eight studies with high-risk patients (acute coronary syndrome, reduced LVEF, dialysis, EuroSCORE>9); 67.4% high predicted operative risk	Reduced; (OR 0.55, 95% CI 0.38–0.81, p = 0.008)	Reduced myocardial infarction(OR 0.29, p = 0.001); reduced low cardiac output syndrome (OR 0.33, p < 0.001); reduced renal failure requiring hemodialysis (OR 0.36, p < 0.001); reduced reoperation for bleeding (OR 0.53, p = 0.027); similar number of grafts (WMD −0.12, p = 0.30); similar rates of incomplete revascularization (OR 1.77, p = 0.15); similar incidence of stroke (OR 0.64, p = 0.089)	NA
Chaudhry et al. [26]	2015	13 (2 RCT)	937 OPBHC; 2993 on-pump conventional CABG	83.6% unselected population, a high-risk subgroup was not specifically evaluated	Similar; (OR 0.60, 95% CI 0.32–1.14, p = 0.12)	Reduced postoperative myocardial infarction (OR 0.32, p = 0.03); reduced IABP use (OR 0.51, p = 0.04); reduced CPB time (WMD −13.5, p = 0.03); similar number of grafts (WMD −0.20, p = 0.61); similar incidence of stroke (OR 0.85, p = 0.54); similar risk of renal failure (OR 0.49, p = 0.20); similar length of stay (WMD −2.71, p = 0.08)	Similar mortality; (OR 0.65, 95% CI 0.22–1.88, p = 0.43)

Table 5.

Summary of the evidence for OPBHG: Secondary research and meta-analysis.

OR: odds ratio; WMD: weighted mean difference. NA: not applicable. Data are referred as OPBHC group versus control group. Adapted from Dominici et al. [7].

The most recent metanalysis [1, 6, 7, 24] showed that postoperative stroke rate is similar between patients who underwent off-pump CABG and OPBHC. These data [7] suggest that the only aortic cannulation procedure might not affect cerebral disease after surgery. However, the dynamics of aortic side-clamping for proximal anastomosis are quite different. The OPBHC could lead to a proximal anastomosis in a “softer” aortic lateral clamping due to rapid on-demand hypotension achieved by CPB, while in off-pump CABG, the same procedure leads to a more traumatic side-clamping.

Also, considering short-term outcomes, recent studies are pointing out that a reduced risk of mortality of OPBHC is performed in selected patients (with high preoperative risk) [7, 25], while previous findings in unselected patients might have diluted the benefits [26].

Based on these results, OPBHC was shown to be associated with reduced postoperative mortality and complications (mainly driven by reduced stroke and reduced myocardial infarction) than conventional revascularization and might be suggested as a valid alternative in high-risk patients. However, considering the significant differences in inclusion criteria, future work should focus on registries and multicenter RCTs to definitely assess the benefits of OPBHC.

4. Gaps in evidence

Although several studies have been done on the OPBHC, there are still several aspects to be analyzed in order to have a clear overview of the benefits and implications of using it.

One aspect that would need to be further investigated is the optimal level of perfusion pressure during OPBHC. A low level of perfusion pressure might increase the risk of hypoperfusion in the distal and subendocardial territories, as low perfusion pressure might lead to flow competition and insufficient native coronary artery blood flow. Evidence from metanalysis [1, 6, 7, 24] suggests that a mean pressure between 70 and 80 mmHg could be an optimal level but due to few observations within the sample, more studies should be performed on this topic.

Another risk for patients undergoing an OPBHC is manipulation-induced aortic insufficiency. In fact, the hemodynamic stability of the patient could be affected by an excessive acute aortic regurgitation when the blood flow comes from the aortic cannula. Further investigations on this risk are needed to better assess the OPBHC technique.

In emergency situations, surgeons usually prefer to use vein grafts rather than arterial conduits as this procedure is faster and less complex. However, the use of vein grafts could affect the long-term outcomes of CABG. Hence, more studies should evaluate if long-term outcomes are affected by the type of graft conduits used (vein or arterial) in the OPBHC setting, as several published researches have been conducted for conventional on-pump CABG.

Another aspect to be further investigated is the level of surgeons’ experience, as this might weigh on the overall valuation of the OPBHC technique. For example, emergency conversion to CPB is usually followed by a higher risk of mortality. The use of OPBHC could reduce this risk if it is combined with a well-trained surgeon and anesthesiologic team.

Finally, further investigations should evaluate the risk associated with the use of OPBHC or PCI for the revascularization of left ventricular. In fact, OPBHC surgeries are associated with a high level of risk for patients but with good graft patency over time. On the other hand, PCI techniques require more advanced and difficult procedures to guarantee complete revascularization without avoiding subsequent myocardial injuries.

5. Conclusion

In conclusion, for high-risk patients, such as those with acute coronary syndrome, cardiogenic shock or with left ventricular dysfunction, the OPBHC seems to be a valid alternative to the off-pump and on-pump CABG techniques, reducing early mortality and decreasing the risk of postoperative complications such as myocardial ischemia or stroke. In particular, the OPBHC could provide an acceptable trade-off in cases of severe complications caused by cardioplegic arrest or manipulation of the heart. Although this technique is still in a rising phase, there are several studies and secondary research supporting its benefits, and we advocate its introduction in future guidelines for revascularization. However, more analyses are needed to develop a common consensus to overcome the blind spots (such as its long-term clinical impacts) that are preventing its adoption as a recognized technique worldwide.

Conflict of interest

The authors declare no conflict of interest.

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