Combined pulsed field ablation with ultra-low temperature cryoablation: A preclinical experience.

BACKGROUND: Combining pulsed field ablation (PFA) with ultra-low temperature cryoablation (ULTC) represents a novel energy source which may create more transmural cardiac lesions. We sought to assess the feasibility of lesions created by combined cryoablation and pulsed field ablation (PFCA) versus PFA alone. METHODS: Ablations were performed using a custom PFA generator, ULTC console, and an ablation catheter with insertable stylets. PFA was delivered in a biphasic, bipolar train. PFCA precooled the tissue for 30 s followed by a concurrent PFA train. Benchtop testing using Schlieren imaging and microbubble volume assessment were used to compare PFA and PFCA. PFA and PFCA lesions using pre-optimized and optimized ablation protocols were studied in 6 swine. Pre and post-ECGs were recorded for each ablation and a gross necropsy was performed at 14 days. RESULTS: Consistent with benchtop comparisons of heat and microbubble generation, PFA deliveries in the animals were accompanied by muscle contractions and significant microbubbles (Grade 2-3) visible on intracardiac echo while neither occurred during PFCA at higher voltage levels. Both PFA and PFCA acutely eliminated or highly attenuated (>80%) local atrial electrograms. Histology of PFA and PFCA lesions indicated depth up to 6-7 mm and nearly all lesions were transmural. Optimized PFCA produced wider cavotricuspid isthmus lesions with evidence of tissue selectivity. CONCLUSION: A novel technology combining PFA and ULTC into one energy source demonstrated in-vivo feasibility for PFCA ablation. PFCA had a more favorable thermal profile and did not produce muscle contraction or microbubbles while extending lesion depth beyond cryoablation.

Staged hybrid totally thoracoscopic maze and catheter ablation for atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a growing health problem and is associated with increased risk of stroke. The Cox-Maze surgical procedure has offered the highest success rate, but utilization of this technique is low due to procedure invasiveness and complexity. Advances in catheter ablation and minimally invasive surgical techniques offer new options for AF treatment. METHODS: In this review, we describe current trends and outcomes of minimally invasive treatment of persistent and long-standing persistent AF. RESULTS: Treatment of persistent and long-standing persistent AF can be successfully treated using a team approach combining cardiac surgery and electrophysiology procedures. With this approach, the 1-year freedom from AF off antiarrhythmic drugs was 85%. DISCUSSION: There are a variety of techniques and approaches used around the world as technology evolves to help develop new treatment strategies for AF. Our report will focus on a hybrid treatment approach using surgical and electrophysiology approaches providing enhanced treatment options by replicating Cox-Maze IV lesions using skills from each specialty. Closure of the left atrial appendage as part of these procedures enhances protection from late stroke. A team approach provides a cohesive evaluation, treatment, and monitoring plan for patients. Development of successful, less invasive treatment options will help address the growing population of patients with AF.

A history of collaboration between electrophysiologists and arrhythmia surgeons.

INTRODUCTION: The notion that medically-refractory arrhythmias might one day be amenable to interventional therapy slowly began to appear in the early 1960's. At that time, there were no "interventional electrophysiologists" or "arrhythmia surgeons" and there was little appreciation of the relationship between anatomy and electrophysiology outside the heart's specialized conduction system. METHODS: In this review, we describe the evolution of collaboration between electrophysiologists and surgeons. RESULTS: Although accessory atrio-ventricular (AV) connections were first identified in 1893 and the Wolff-Parkinson-White (WPW) syndrome was described 37 years later (1930), it was another 37 years (1967) before those anatomic AV connections were proven to be responsible for the clinical syndrome. The success of the subsequent surgical procedures for the WPW syndrome, AV node reentry tachycardia, automatic atrial tachycardias, ischemic and non-ischemic ventricular tachycardias and atrial fibrillation over the next two decades depended on a close, sometimes daily, collaboration between electrophysiologists and surgeons. In the past two decades, that tight collaboration was largely abandoned until the recent introduction of "hybrid procedures" for the treatment of atrial fibrillation. CONCLUSIONS: A retrospective assessment of the 50 years of interventional therapy for arrhythmias clearly demonstrates the clinical benefits of a close collaboration between electrophysiologists and arrhythmia surgeons, regardless of which one is actually performing the intervention.

Atrial fibrillation and atrial cardiomyopathies.

Atrial fibrillation (AF) is the most common arrhythmia among adults. While there have been incredible advances in the management of AF and its clinical sequelae, investigation of atrial cardiomyopathies (ACMs) is becoming increasingly more prominent. ACM refers to the electromechanical changes-appreciated subclinically and/or clinically-that underlie atrial dysfunction and create an environment ripe for the development of clinically apparent AF. There are several subtypes of ACM, distinguished by histologic features. Recent progress in cardiovascular imaging, including echocardiography with speckle-tracking (e.g., strain analysis), cardiovascular magnetic resonance imaging (CMR), and atrial 4-D flow CMR, has enabled increased recognition of ACM. Identification of ACM and its features carry clinical implications, including elevating a patient's risk for development of AF, as well as associations with outcomes related to catheter-based and surgical AF ablation. In this review, we explore the definition and classifications of ACM, its complex relationship with clinical AF, imaging modalities, and clinical implications. We propose next steps for a more unified approach to ACM recognition that can direct further research into this complex field.

Unique technical challenges in patients undergoing TAVR for failed aortic homografts.

OBJECTIVE: Surgical reoperation for aortic homograft structural valve degeneration (SVD) is a high-risk procedure. Transcatheter aortic valve replacement (TAVR) for homograft-SVD is an alternative to reoperation, but descriptions of implantation techniques are limited. This study compares outcome in patients undergoing into two groups by the type of previously implanted aortic valve prosthesis: TAVR for failed aortic homografts (TAVR-H) or for stented aortic bioprostheses (TAVR-BP). METHODS: From 2015 to 2017, TAVR was performed in 41 patients with SVD. Thirty-three patients in the TAVR-BP group (six for SVD of valved conduits), and eight patients in the TAVR-H group. The Valve Academic Research Consortium criteria were used for outcome reporting purposes. RESULTS: The patients with TAVR-BP had predominant prosthetic stenosis (94%, p = .002), whereas TAVR-H individuals presented mostly with regurgitation (88%, p = <.001). Patients with TAVR-H received: Sapien-3 (6), Sapien-XT (1), and CoreValve (1) devices. Low, 40% ventricular fixation in relation to homograft annulus was attempted to anchor the prosthesis on the homograft suture-line. One patient with TAVR-BP experienced intraoperative distal prosthesis migration and Type-B aortic dissection, and two patients in the TAVR-H group had late postoperative proximal device migration. In both groups, there was zero 30-day mortality, stroke, or pacemaker implantation. CONCLUSIONS: TAVR for failing aortic homografts may be a feasible and safe alternative to high-risk surgical reintervention. Precise, 40%-ventricular device positioning appears crucial for prevention of late paravalvular leak/late prosthesis migration and minimizing the risk of repeat surgical intervention.

Cardiac anatomy pertinent to the catheter and surgical treatment of atrial fibrillation.

In the 1980s when surgery was first introduced for the treatment of atrial fibrillation (AF), one would often hear comments like "Every little old grandmother has AF. Why on earth would you operate on someone like that?".

Epicardial left atrial appendage AtriClip occlusion reduces the incidence of stroke in patients with atrial fibrillation undergoing cardiac surgery.

Aims: Left atrial appendage (LAA) occlusion has emerged as an interesting alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). We report the safety, efficacy, and durability of concomitant device-enabled epicardial LAA occlusion during open-heart surgery. In addition to long-term follow-up, we evaluate the impact on stroke risk in this selected population. Methods and results: A total of 291 AtriClip devices were deployed epicardially in patients (mean CHA2DS2-VASc-Score: 3.1 ± 1.5) undergoing open-heart surgery (including isolated coronary artery bypass grafting, valve, or combined procedures) comprising of forty patients from a first-in-man device trial (NCT00567515) and 251 patients from a consecutive institutional registry thereafter. In all patients (n = 291), the LAA was successfully excluded and overall mean follow-up (FU) was 36 ± 23months (range: 1-97 months). No device-related complications were detected throughout the FU period. Long-term imaging work-up (computed tomography) in selected patients ≥5years post-implant (range: 5.1-8.1 years) displayed complete LAA occlusion with no signs of residual reperfusion or significant LAA stumps. Subgroup analysis of patients with discontinued OAC during FU (n = 166) revealed a relative risk reduction of 87.5% with an observed ischaemic stroke-rate of 0.5/100 patient-years compared with what would have been expected in a group of patients with similar CHA2DS2-VASc scores (expected rate of 4.0/100 patient-years). No strokes occurred in the subgroup with OAC. Conclusion: The long-term results from our first-in-man prospective human trial plus our institutional registry of epicardial LAA occlusion with the AtriClip in patients with AF undergoing cardiac surgery demonstrate the safety and durability of the procedure. In addition, our data are suggestive for the potential efficacy of LAA occlusion in reducing the incidence of stroke. If validated in future large randomized trials, routine LAA occlusion in patients undergoing cardiac surgery (with contraindications to treatment with oral anticoagulants) may represent a reasonable adjunct procedure to reduce the risk of future stroke. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00567515.

Strokes associated with left ventricular assist devices.

Ventricular assist devices (VADs) have improved dramatically over the past several decades but stroke remains a problem. There are multiple etiologies of both ischemic and hemorrhagic strokes associated with VADs. While this problem is yet to be solved, there are continuing efforts at improving the design of VADs to decrease the incidence of stroke and to improve long-term survival in patients requiring mechanical circulatory assistance. The purpose is to review the incidence and underlying causes of stroke in VAD patients.

ATP synthase: the right size base model for nanomotors in nanomedicine.

Nanomedicine results from nanotechnology where molecular scale minute precise nanomotors can be used to treat disease conditions. Many such biological nanomotors are found and operate in living systems which could be used for therapeutic purposes. The question is how to build nanomachines that are compatible with living systems and can safely operate inside the body? Here we propose that it is of paramount importance to have a workable base model for the development of nanomotors in nanomedicine usage. The base model must placate not only the basic requirements of size, number, and speed but also must have the provisions of molecular modulations. Universal occurrence and catalytic site molecular modulation capabilities are of vital importance for being a perfect base model. In this review we will provide a detailed discussion on ATP synthase as one of the most suitable base models in the development of nanomotors. We will also describe how the capabilities of molecular modulation can improve catalytic and motor function of the enzyme to generate a catalytically improved and controllable ATP synthase which in turn will help in building a superior nanomotor. For comparison, several other biological nanomotors will be described as well as their applications for nanotechnology.

Surgical Coronary Revascularization in Patients With Underlying Atrial Fibrillation: State-of-the-Art Review.

The number of individuals referred for coronary artery bypass grafting (CABG) with preoperative atrial fibrillation (AF) is reported to be 8% to 20%. Atrial fibrillation is a known marker of high-risk patients as it was repeatedly found to negatively influence survival. Therefore, when performing surgical revascularization, consideration should be given to the concomitant treatment of the arrhythmia, the clinical consequences of the arrhythmia itself, and the selection of adequate surgical techniques. This state-of-the-art review aimed to provide a comprehensive analysis of the current understanding of, advancements in, and optimal strategies for CABG in patients with underlying AF. The following topics are considered: stroke prevention, prophylaxis and occurrence of postoperative AF, the role of surgical ablation and left atrial appendage occlusion, and an on-pump vs off-pump strategy. Multiple acute complications can occur in patients with preexisting AF undergoing CABG, each of which can have a significant effect on patient outcomes. Long-term results in these patients and the future perspectives of this scientific area were also addressed. Preoperative arrhythmia should always be considered for surgical ablation because such an approach improves prognosis without increasing perioperative risk. While planning a revascularization strategy, it should be noted that although off-pump coronary artery bypass provides better short-term outcomes, conventional on-pump approach may be beneficial at long-term follow-up. By collecting the current evidence, addressing knowledge gaps, and offering practical recommendations, this state-of-the-art review serves as a valuable resource for clinicians involved in the management of patients with AF undergoing CABG, ultimately contributing to improved outcomes and enhanced patient care.

Additional bypass graft or concomitant surgical ablation? Insights from the HEIST registry.

BACKGROUND: Surgical ablation for atrial fibrillation at the time of isolated coronary artery bypass grafting is reluctantly attempted. Meanwhile, complete revascularization is not always possible in these patients. We attempted to counterbalance the long-term benefits of surgical ablation against the risks of incomplete revascularization. METHODS: Atrial fibrillation patients undergoing isolated coronary artery bypass grafting for multivessel disease between 2012 to 2022 and included in the HEart surgery In atrial fibrillation and Supraventricular Tachycardia registry were divided into complete revascularization, complete revascularization with additional grafts, and incomplete revascularization cohorts; these were further split into surgical ablation and non-surgical ablation subgroups. RESULTS: A total of 8,405 patients (78% men; age 69.3 ± 7.9) were included; of those, 5,918 (70.4%) had complete revascularization, and 556 (6.6%) had surgical ablation performed. Number of anastomoses was 2.7 ± 1.2. The median follow-up was 5.1 [interquartile range 2.1-8.8] years. In patients in whom complete revascularization was achieved, surgical ablation was associated with long-term survival benefit: hazard ratio 0.69; 95% confidence intervals (0.50-0.94); P = .020 compared with grafting additional lesions. Similarly, in patients in whom complete revascularization was not achieved, surgical ablation was associated with a long-term survival benefit of 0.68 (0.49-0.94); P = .019. When comparing surgical ablation on top of incomplete revascularization against complete revascularization without additional grafts or surgical ablation, there was no difference between the 2: 0.84 (0.61-1.17); P = .307, which was also consistent in the propensity score-matched analysis: 0.75 (0.39-1.43); P = .379. CONCLUSION: To achieve complete revascularization is of utmost importance. However, when facing incomplete revascularization at the time of coronary artery bypass grafting in a patient with underlying atrial fibrillation, concomitant surgical ablation on top of incomplete revascularization is associated with similar long-term survival as complete revascularization without surgical ablation.

Shikonin Causes Non-apoptotic Cell Death in B16F10 Melanoma.

BACKGROUND: Melanoma treatment is highly resistant to current chemotherapeutic agents. Due to its resistance towards apoptotic cell death, non-apoptotic cell death pathways are sought after. OBJECTIVE: We investigated a Chinese herbal medicine, shikonin, and its effect on B16F10 melanoma cells in vitro. METHODS: Cell growth of B16F10 melanoma cells treated with shikonin was analyzed using an MTT assay. Shikonin was combined with necrostatin, an inhibitor of necroptosis; caspase inhibitor; 3-methyladenine, an inhibitor of autophagy; or N-acetyl cysteine, an inhibitor of reactive oxygen species. Flow cytometry was used to assess types of cell death resulting from treatment with shikonin. Cell proliferation was also analyzed utilizing a BrdU labeling assay. Monodansylcadaverine staining was performed on live cells to gauge levels of autophagy. Western blot analysis was conducted to identify specific protein markers of necroptosis including CHOP, RIP1, and pRIP1. MitoTracker staining was utilized to identify differences in mitochondrial density in cells treated with shikonin. RESULTS: Analysis of MTT assays revealed a large decrease in cellular growth with increasing shikonin concentrations. The MTT assays with necrostatin, 3-methyladenine, and N-acetyl cysteine involvement, suggested that necroptosis, autophagy, and reactive oxygen species are a part of shikonin's mechanism of action. Cellular proliferation with shikonin treatment was also decreased. Western blotting confirmed that shikonin-treated melanoma cells increase levels of stress-related proteins, e.g., CHOP, RIP, pRIP. CONCLUSION: Our findings suggest that mainly necroptosis is induced by the shikonin treatment of B16F10 melanoma cells. Induction of ROS production and autophagy are also involved.

Concomitant ablation of atrial fibrillation: New pacemakers and early rhythm recovery.

OBJECTIVE: New permanent pacemaker (PPM) implantation after concomitant atrial fibrillation (AF) ablation has been associated with surgical ablation (SA). We sought to determine factors for PPM use as well as early rhythm recovery. METHODS: From 2004 through 2019, 6135 patients underwent valve surgery and were grouped: No AF (n = 4584), AF no SA (n = 346), and AF with SA (n = 1205) to evaluate predischarge PPM and 3-month rhythm recovery (intrinsic heart rate >40 beats per minute). RESULTS: Overall, 282 (4.6%) patients required a predischarge PPM: atrioventricular node dysfunction in 75.3%, sick sinus syndrome in 19.1%, both (5%), and indeterminate (0.7%). Patients with AF had more PPMs: AF with SA (7.9%) versus AF no SA (6.9%) versus No AF (3.6%) (P < .001). For patients with AF, PPM rates were not significantly higher for ablation patients (7.6% SA vs 6.9% AF no SA; P = .56). There were differences in PPM by SA lesion set (biatrial 12.8%; left atrial only 6.1%; pulmonary vein isolation 3.0%; P < .001). Among patients with AF treated with 3-month PPM follow-up, rhythm recovery was common (35 out of 62 [56.5%]) and did not differ by lesion set. Rhythm recovery was seen in 63 out of 141 (44.7%) in the atrioventricular node dysfunction group versus 24 out of 35 (68.6%) in the sick sinus syndrome group (P = .011). In propensity score-matched groups, late survival was similar (P = .63) for new PPM patients. CONCLUSIONS: Avoiding conduction system trauma and delaying implantation reduces the need for postoperative PPM. Rhythm recovery within 3 months is frequent, especially for patients with sick sinus syndrome. A conservative approach to the implantation of a new PPMs is warranted.

Atrial fibrillation ablation improves late survival after concomitant cardiac surgery.

OBJECTIVE: Preoperative atrial fibrillation (AF) increases risk of stroke, heart failure, and all-cause mortality after cardiac surgery. Despite encouraging results and guideline recommendations, surgical ablation (SA) for AF concomitant with other heart surgery remains low. In the current study we aimed to address the long-term mortality after SA concomitant with cardiac surgery. METHODS: This report pertains to the HEart surgery In atrial fibrillation and Supraventricular Tachycardia (HEIST) registry. We identified 20,765 adult patients (62% male) with preoperative AF who underwent conventional sternotomy heart surgery between 2010 and 2021 in 8 tertiary centers in Poland, Netherlands, and Italy. We used Cox proportional hazards models for computations and propensity score matching to minimize differences in baseline characteristics. RESULTS: Of included patients, 2755 (13.4%) underwent SA for AF. The highest rates of SA were observed for mitral interventions (mitral valve repair or replacement and tricuspid intervention, 25.2%), lowest for isolated coronary artery bypass grafting (6.2%). Patients in the SA group were younger (mean age 64.5 ± 9.0 years vs 68.7 ± 16.0 years; P < .001) and lower risk (mean European System for Cardiac Operative Risk Evaluation [EuroSCORE] II, 4.1 vs 5.7; P < .001). During the 11-year study period, there was a mortality reduction associated with SA (hazard ratio, 0.57; 95% CI, 0.52-0.62; P < .001). After propensity matching, 2750 pairs with similar baseline characteristics were identified. SA was associated with 16% mortality decline (hazard ratio, 0.84; 95% CI, 0.75-0.94; P = .003). CONCLUSIONS: In this multicenter, retrospective, propensity matched study, SA concomitant with other cardiac surgery was associated with improved long-term survival regardless of baseline surgical risk.

One hundred percent utilization of a modified CryoMaze III procedure for atrial fibrillation with mitral surgery.

OBJECTIVES: Concomitant atrial fibrillation often goes untreated because of surgeon concerns regarding lesion set complexity and pump times. We describe a new cryoablation procedure to address this. METHODS: From June 2013 to March 2021, a modified CryoMaze III procedure was used using 3 left atrial ± 3 right atrial cryo-applications creating the key lesions of the Cox Maze III procedure. Since 2018, 3-minute cryo-lesions were used for the left atrial box lesion for total cryoablation times of 8 minutes for the left atrium ± 6 minutes for the right atrium. By using propensity matching, patients undergoing mitral valve surgery with no atrial fibrillation history were compared with CryoMaze III-treated patients. RESULTS: A total of 100% of the 277 patients with atrial fibrillation requiring mitral valve surgery ± other procedures received the modified CryoMaze III procedure. After propensity score matching (n = 161 each group), the modified CryoMaze III group had mean crossclamp and bypass times 10.5 and 13.4 minutes longer than the control group, respectively. There were no significant differences in 30-day mortality, morbidity, pacemaker use, renal dysfunction, or late survival between groups, but there were less postoperative strokes in the CryoMaze III group. Freedom from atrial fibrillation off antiarrhythmics was 77% (mean follow-up of 3.0 ± 2.1 years). At 12 months, freedom from atrial fibrillation off antiarrhythmics was 90% for the 3-minute ablation group. Late survival was similar to age- and sex-matched Centers for Disease Control and Prevention controls. CONCLUSIONS: The modified CryoMaze III technique is efficient, safe, and effective. Education of the surgical community regarding the late benefits of ablation and the simplicity of this new technique should improve adoption of the Class I Guidelines to treat concomitant atrial fibrillation.

Does Active Chest Tube Clearance After Cardiac Surgery Provide Any Clear Benefits?

BACKGROUND: Retained blood syndrome (RBS) encompasses complications, acute and chronic, related to inflammation created by retained intrathoracic blood after cardiac surgery. Reports suggest that active chest tube clearance devices reduce RBS and may lower the rates of reoperation for bleeding and postoperative atrial fibrillation. METHODS: In a prospective study (April 2015-October 2017), 1367 patients meeting the study inclusion criteria (1113 control subjects with conventional chest tubes and 254 patients with active chest tube clearance devices [the ATC group]) underwent cardiac surgery through primary sternotomy. RESULTS: Groups were similar in their preoperative and intraoperative characteristics. No differences were found in overall RBS occurrence (4.3% in the ATC group vs 5.3% in the control group; P = .527), including the components of reexploration for bleeding (2.0% [5/254] for the ATC group and 2.4% [27/1113] for the control group; P = .664) and pleural effusion requiring intervention (3.1% [8/254] vs 3.6% [40/1113]; P = .729). Postoperative atrial fibrillation (20.8% [52/254] vs 20.2 % [221/1113]; P = .837) and 30-day mortality were also similar (3.5% vs 2.2%; P = .231). Postoperative blood product use was 31.9% (81/254) in the ATC group and 28.7% (319/1113) in the control group (P = .308). Some complications were more common in the ATC group, including septicemia (2.4% [6/254] vs 0.7% [8/1113]; P = .019) and renal failure (3.9% [10/254] vs 1.7% [19/1113]; P = .026). Median postoperative length of stay was shorter in the ATC group (5 days vs 6 days; P = .025). CONCLUSIONS: Active chest tube clearance devices were not associated with improved postoperative outcomes related to RBS at the study institution (Northwestern Medicine, Chicago, IL). Given the additional cost, the nursing effort to maintain the active chest tube clearance devices, and the lack of apparent benefit, this study did not demonstrate the value of using such devices in cardiac surgery.

Preoperative left atrial strain abnormalities are associated with the development of postoperative atrial fibrillation following isolated coronary artery bypass surgery.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG). Currently, there is no reliable way to determine preoperatively which patients will develop POAF following CABG. The aim of this study was to determine whether preoperative left atrial (LA) strain analysis might identify patients destined to develop POAF following CABG. METHODS: From 2016 to 2018, 211 patients who had a preoperative left ventricular ejection fraction >50% and adequate preoperative, predischarge, and follow-up echo images for interpretation underwent isolated CABG surgery. Postoperatively, patients had continuous rhythm monitoring until hospital discharge. Retrospective speckle-tracking analysis of preoperative echocardiograms was performed to calculate preoperative left ventricular global longitudinal strain and LA compliance and contraction strains in 92 matched patients. Multivariate logistic regression and Cox proportional hazards models were used to determine the predictors of POAF after CABG. RESULTS: POAF occurred in 50 patients (24%). They were older, had longer intensive care unit and hospital stays, and a slightly greater 30-day mortality (P = .07). Preoperative LA volume index was larger in the patients with POAF but still "normal" as defined by current guidelines. However, preoperative LA compliance and contraction strains were significantly lower in patients who developed POAF after CABG. CONCLUSIONS: Decreased preoperative LA strain measurements, especially LA-fractional area change, LA-emptying fraction, and LA-reservoir strain, taken jointly, are more specific and sensitive than other preoperative parameters in identifying patients who will develop POAF following CABG. The ability to identify patients preoperatively who are destined to develop POAF following CABG provides a basis for limiting POAF prophylactic therapy to only those patients undergoing CABG who are most likely to benefit from it rather than to all patients undergoing CABG.