Minimally invasive extracorporeal circulation versus conventional cardiopulmonary bypass in patients undergoing cardiac surgery (MiECS): Rationale and design of a multicentre randomised trial.

INTRODUCTION: The ultimate answer to the question whether minimal invasive extracorporeal circulation (MiECC) represents the optimal perfusion technique in contemporary clinical practice remains elusive. The present study is a real-world study that focuses on specific perfusion-related clinical outcomes after cardiac surgery that could potentially be favourably affected by MiECC and thereby influence the future clinical practice. METHODS: The MiECS study is an international, multi-centre, two-arm randomized controlled trial. Patients undergoing elective or urgent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or combined procedure (CABG + AVR) using extracorporeal circulation will be randomized to MiECC or contemporary conventional cardiopulmonary bypass (cCPB). Use of optimized conventional circuits as controls is acceptable. The study design includes a range of features to prevent bias and is registered at clinicaltrials.gov (NCT05487612). RESULTS: The primary outcome is a composite of postoperative serious adverse events that could be related to perfusion technique occurring up to 30 days postoperatively. Secondary outcomes include use of blood products, ICU and hospital length of stay (30 days) as well as health-related quality of life (30 and 90 days). CONCLUSIONS: The MiECS trial has been designed to overcome perceived limitation of previous trials of MiECC. Results of the proposed study could affect current perfusion practice towards advancement of patient care.

Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS).

INTRODUCTION: The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest. METHODS: This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis. RESULTS: The trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250). CONCLUSIONS: MiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain.

Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery on minimal invasive extracorporeal circulation; A prospective randomized study.

INTRODUCTION: Individualized heparin and protamine management is increasingly used as a strategy to reduce coagulation activation and bleeding complications. While it is associated with increased heparin requirements during Cardiopulmonary Bypass (CPB), the impact on protamine administration remains controversial. We aim to investigate the effect of heparin level-guided monitoring on protamine dosing during cardiac surgery where low-anticoagulation protocols are implemented. METHODS: This is a prospective, randomized, controlled trial. A total of 132 patients undergoing elective full-spectrum cardiac surgery with Minimal Invasive Extracorporeal Circulation (MiECC) were recruited. All patients were managed by the same anaesthetic, surgical and perfusion team. Patients were randomly allocated in two groups; the individualized heparin-protamine titration (IHPT) group and the conventional heparinization and reversal group by using ACT (cACT) with a 0.75:1, protamine: heparin ratio. Titration was accomplished with the Hepcon HMS Plus (Medtronic, Minneapolis, MN) system. The primary outcome of the study was the total protamine dose used. Secondary outcomes comprised of the total heparin dose, the percentage of patients achieving target ACT, 24-h transfusion requirements, postoperative bleeding, duration of mechanical ventilation, major morbidity and length of hospital stay. Patients in each group were divided in two subgroups according to the target ACT; those operated for coronary artery bypass grafting (CABG) using a target ACT >300 s and the rest (non-CABG) patients operated with a target ACT >400 s, respectively. RESULTS: Protamine requirements were significantly reduced when IHPT was implemented; CABG (118 ± 24 mg vs 163 ± 61 mg; p < 0.001) and non-CABG cases (151 ± 46 mg vs 197 ± 45 mg; p < 0.001). Moreover, heparin requirements were significantly higher in the non-CABG subgroup managed with IHPT (34,539 ± 7658 IU vs 29,893 ± 9037 IU; p = 0.02). In overall, no significant differences were detected with respect to postoperative bleeding, transfusion of RBC or other blood products. CONCLUSIONS: Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery with MiECC implementing reduced anticoagulation strategy. TRIAL REGISTRATION: clinicaltrials.gov; NCT04215588.

2021 MiECTiS focused update on the 2016 position paper for the use of minimal invasive extracorporeal circulation in cardiac surgery.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

The left-sided aortic arch variants: prevalence meta-analysis of imaging studies.

PURPOSE: To estimate the prevalence of the left-sided aortic arch (LSAA) variants, and the effect of possible moderators on variants' detection. METHODS: A systematic online literature search was conducted. The pooled prevalence with 95% confidence intervals was estimated for the typical and atypical branching patterns to compare the overall proportions of different variants. Meta-regression analyses were performed to investigate the effect of the subjects' gender and geographical region, and the multidetector computed tomography (MDCT) scanner's technology on the estimated prevalence. RESULTS: In total, 18,075 cases from 23 imaging studies were included and 33 different LSAA variants were detected. The estimated heterogeneity was statistically significant. Based on the estimated prevalence, approximately 77% of the population is expected to have the typical branching anatomy with sequence brachiocephalic trunk-left common carotid artery-left subclavian artery, and 23% variant branching patterns. Approximately 71%, 23%, 2%, and 0.1% of the atypical populations are expected to have two, four, three, and five emerging branches, respectively. The meta-regression analyses showed that the number of detector rows of the MDCT scanner, and the subjects' geographical region are statistically significant moderators of the estimated prevalence. CONCLUSION: The current findings indicate that the prevalence of the LSAA variant branching anatomy is significantly affected by the subjects' geographical region and the MDCT scanner's technological improvement, with the advanced scanners to facilitate the detection of the aortic arch variants. However, due to the heterogeneity among studies, further research is required.

Modular minimally invasive extracorporeal circulation ensures perfusion safety and technical feasibility in cardiac surgery; a systematic review of the literature.

INTRODUCTION: Despite extensive evidence that shows clinical of superiority of MiECC, worldwide penetration remains low due to concerns regarding air handling and volume management in the context of a closed system. The purpose of this study is to thoroughly investigate perfusion safety and technical feasibility of performing all cardiac surgical procedures with modular (hybrid) MiECC, as experienced from the perfusionist's perspective. METHODS: We retrospectively reviewed perfusion charts of consecutive adult patients undergoing all types of elective, urgent, and emergency cardiac surgery under modular MiECC. The primary outcome measure was perfusion safety and technical feasibility, as evidenced in the need for conversion from a closed to an open circuit. A systematic review of the literature was conducted aiming to ultimately clarify whether there are any safety issues regarding MiECC technology. RESULTS: We challenged modular MiECC use in a series of 403 consecutive patients of whom a significant proportion (111/403; 28%) underwent complex surgery including reoperations (4%), emergency repair of acute type A aortic dissection and composite aortic surgery (1.7%). Technical success rate was 100%. Conversion to an open circuit was required in 18/396 patients (4.5%), excluding procedures performed under circulatory arrest. Open configuration accounted for 40% ± 21% of total procedural perfusion time and was related to significant hemodilution and increase in peak lactate levels. Systematic review revealed that safety of the procedure challenged originated from a single report, while no clinical adverse event related to MiECC was identified. CONCLUSIONS: Use of modular MiECC secures safety and ensures technical feasibility in all cardiac surgical procedures. It represents a type III active closed system, while its stand-by component is reserved for a small (<5%) proportion of procedures and for a partial procedural time. Thus, it eliminates any safety concern regarding air handling and volume management, while it overcomes any unexpected intraoperative scenario.

Minimal invasive extracorporeal circulation preserves coagulation integrity.

INTRODUCTION: Coagulopathy after cardiac surgery is a serious multifactorial complication that results in postoperative bleeding requiring transfusion of red blood cells and procoagulant products. Use of cardiopulmonary bypass represents the major contributing factor affecting coagulation. We sought to prospectively investigate the effect of contemporary minimal invasive extracorporeal circulation (MiECC) on coagulation parameters using point-of-care (POC) rotational thromboelastometry and the relation to postoperative bleeding. METHODS: Patients undergoing elective cardiac surgery on MiECC were prospectively recruited. Anticoagulation strategy was based on individualized heparin management and heparin level-guided protamine titration. Rotational thromboelastometry testing was performed before induction of anesthesia and after aortic cross-clamp release. A strict POC-guided transfusion protocol was implemented. The primary endpoint was the assessment of viscoelastic properties of the coagulating blood at the end of surgery compared to preoperative values and the relation to postoperative bleeding and 24-hour transfusion requirements. RESULTS: Fifty patients were included in the study with a significant proportion having complex surgery. Thirteen patients (26%) required blood transfusion (mean rate: 0.5 ± 1 units per patient), 5/50 (10%) received coagulation factors while no patient received fresh frozen plasma, platelets or fibrinogen. Thromboelastometry analysis showed that the major derangement was CT EXTEM > 100 seconds in 28/50 (56%) and A10 EXTEM < 40 mm in one (2%) patient without clinical significance. Platelet function was preserved throughout surgery. A10-FIBTEM was found predictive of postoperative bleeding at 12 hours. CONCLUSIONS: MiECC preserves clot quality throughout surgery acting in both key determinants of clot strength; fibrinogen and platelets. This is clinically translated into minimal postoperative bleeding and restricted use of blood products and coagulation factors.

From less invasive to minimal invasive extracorporeal circulation.

Development of minimally invasive cardiac surgery (MICS) served the purpose of performing surgery while avoiding the surgical stress triggered by a full median sternotomy. Minimizing surgical trauma is associated with improved cosmesis and enhanced recovery leading to reduced morbidity. However, it has to be primarily appreciated that the extracorporeal circulation (ECC) stands for the basis of nearly all MICS procedures. With some fundamental modification and advancement in perfusion techniques, the use of ECC has become the enabling technology for the development of MICS. Less invasive cardiopulmonary bypass (CPB) techniques are based on remote cannulation and optimization of perfusion techniques with assisted venous drainage and use of centrifugal pump, so as to facilitate the demanding surgical maneuvers, rather than minimizing the invasiveness of the CPB. This is reflected in the increased duration of CPB required for MICS procedures. Minimal invasive Extracorporeal Circulation (MiECC) represents a major breakthrough in perfusion. It integrates all contemporary technological advancements that facilitate best applying cardiovascular physiology to intraoperative perfusion. Consequently, MiECC use translates to improved end-organ protection and clinical outcome, as evidenced in multiple clinical trials and meta-analyses. MICS performed with MiECC provides the basis for developing a multidisciplinary intraoperative strategy towards a "more physiologic" cardiac surgery by combining small surgical trauma with minimum body's physiology derangement. Integration of MiECC can advance MICS from non-full sternotomy for selected patients to a "more physiologic" surgery, which represents the real face of modern cardiac surgery in the transcatheter era.

Minimal invasive extracorporeal circulation preserves platelet function after cardiac surgery: a prospective observational study.

INTRODUCTION: Cardiac surgery on conventional cardiopulmonary bypass induces a combination of thrombocytopenia and platelet dysfunction which is strongly related to postoperative bleeding. Minimal invasive extracorporeal circulation has been shown to preserve coagulation integrity, though effect on platelet function remains unclear. We aimed to prospectively investigate perioperative platelet function in a series of patients undergoing cardiac surgery on minimal invasive extracorporeal circulation using point-of-care testing. METHODS: A total of 57 patients undergoing elective cardiac surgery on minimal invasive extracorporeal circulation were prospectively recruited. Anticoagulation strategy was based on individualized heparin management and heparin level-guided protamine titration performed in all patients with a specialized point-of-care device (Hemostasis Management System - HMS Plus; Medtronic, Minneapolis, MN, USA). Platelet function was evaluated with impedance aggregometry using the ROTEM platelet (TEM International GmbH, Munich, Germany). ADPtest and TRAPtest values were assessed before surgery and after cardiopulmonary bypass. RESULTS: ADPtest value was preserved during surgery on minimal invasive extracorporeal circulation (58.2 ± 20 U vs. 53.6 ± 21 U; p = 0.1), while TRAPtest was found significantly increased (90 ± 27 U vs. 103 ± 38 U; p = 0.03). Postoperative ADPtest and TRAPtest values were inversely related to postoperative bleeding (correlation coefficient: -0.29; p = 0.03 for ADPtest and correlation coefficient: -0.28; p = 0.04 for TRAPtest). The preoperative use of P2Y12 inhibitors was identified as the only independent predictor of a low postoperative ADPtest value (OR = 15.3; p = 0.02). CONCLUSION: Cardiac surgery on minimal invasive extracorporeal circulation is a platelet preservation strategy, which contributes to the beneficial effect of minimal invasive extracorporeal circulation in coagulation integrity.

A multidisciplinary perioperative strategy for attaining "more physiologic" cardiac surgery.

BACKGROUND: Cardiac surgery is, by definition, a "non-physiologic" intervention associated with systemic adverse effects. Despite advances in surgical technique, cardiopulmonary bypass (CPB) technology as well as anaesthesia management and patient care, there is still significant morbidity and subsequent mortality. AIM: We consider that the contemporary demand for further improving patient outcome mandates the upgrade from optimal perfusion during the procedure as the gold standard to the concept of a "more physiologic" cardiac surgery. Our policy is a multidisciplinary perioperative strategy based on goal-directed perfusion throughout surgery incorporating in-line monitoring. This translates to "prevent rather than correct" malperfusion through real-time adjustment rather than correction of derangement detected late by incremental evaluation. METHOD: The strategy is based on continuous monitoring of cardiac index, SvO2, DO2i, DO2i/VCO2i and rSO2. Data acquisition is followed by action when needed; this includes stepwise: transfusion, increase of cardiac output and initiation of inotropic/vasoactive support. Moreover, implementation of minimally invasive extracorporeal circulation (MiECC) is considered as a fundamental component of physiologic perfusion when on-CPB, providing improved circulatory support and end-organ protection. CONCLUSION: We consider that, with this strategy which establishes optimal perfusion perioperatively, we attain the goal of a "more physiologic" cardiac surgery.

Quantification of Operational Learning in Minimal Invasive Extracorporeal Circulation.

Minimal invasive extracorporeal circulation (MiECC) has initiated important new efforts within science and technology towards a more physiologic perfusion. In this study, we aim to investigate the learning curve of our center regarding MiECC. We studied a series of 150 consecutive patients who underwent elective coronary artery bypass grafting by the same surgical team during the initial phase of MiECC application. Patients were randomly assigned into two groups. Group A (n = 75) included patients operated on MiECC, while group B (n = 75) included patients operated with conventional cardiopulmonary bypass (cCPB). The primary end-point of the study was to identify whether there is a learning curve when operating on MiECC. The following parameters were unrelated with increasing experience, even though the results favored MiECC use: reduced CPB duration (102.9 ± 25 vs. 122.2 ± 33 min, P <0.001), peak troponin release (0.07 ± 0.02 vs. 0.1 ± 0.04 ng/mL, P < 0.01), peak creatinine levels (0.97 ± 0.24 vs. 1.2 ± 0.3 mg/dL, P < 0.001), duration of mechanical ventilation (14.1 ± 7.2 vs. 36.9 ± 59.8 h, P < 0.01) and ICU stay (2.1 ± 0.7 vs. 4.4 ± 6.4 days, P < 0.01). However, need for intraoperative blood transfusion showed a trend towards a gradual decrease as experience with MiECC system was accumulating (R2 = 0.094, P = 0.007). Subsequently, operational learning applied to postoperative hematocrit and hemoglobin levels (R2 = 0.098, P = 0.006). We identified that advantages of MiECC technology in terms of reduced hemodilution and improved end-organ protection and clinical outcome are evident from the first patient. Optimal results are obtained with 50 cases; this refers mainly to significant reduction in the need for intraoperative blood transfusion. Teamwork from surgeons, anesthesiologists, and perfusionists is of paramount importance in order to maximize the clinical benefits from this technology.

Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting: a randomized pilot study.

OBJECTIVES: Perioperative low cardiac output syndrome occurs in 3-14% of patients undergoing isolated coronary artery bypass grafting (CABG), leading to significant increase in major morbidity and mortality. Considering the unique pharmacological and pharmacokinetic properties of levosimendan, we conducted a prospective, double-blind, randomized pilot study to evaluate the effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing CABG. METHODS: Thirty-two patients undergoing CABG with low left ventricular ejection fraction (LVEF ≤ 40%) were randomized to receive either a continuous infusion of levosimendan at a dose of 0.1 µg/kg/min for 24 h without a loading dose or a placebo. The primary outcome of the study was the change in the LVEF assessed with transthoracic echocardiography on the seventh postoperative day. Secondary outcomes included the physiological and clinical effects of levosimendan. RESULTS: All patients tolerated preoperative infusion of levosimendan well. The LVEF improved in both groups; this increase was statistically significant in the levosimendan group (from 35.8 ± 5% preoperatively to 42.8 ± 7.8%, P = 0.001) compared with the control group (from 37.5 ± 3.4% preoperatively to 41.2 ± 8.3%, P = 0.1). The cardiac index, SvO2, pulmonary capillary wedge pressure and right ventricular stroke work index showed a similar trend, which was optimized in patients treated with levosimendan. Moreover, an increase in extravascular lung water was noticed in this group during the first 24 h after surgery. CONCLUSIONS: This pilot study shows that prophylactic levosimendan infusion is safe and effective in increasing the LVEF postoperatively in patients with impaired cardiac function undergoing coronary surgery. This finding may be translated to 'optimizing' patients' status before surgery.

Minimally invasive extracorporeal circulation improves quality of life after coronary artery bypass grafting.

OBJECTIVES: The effect on postoperative health-related quality of life (HRQoL) after coronary artery bypass grafting (CABG) surgery with conventional cardiopulmonary bypass (cCPB) and off-pump surgery has been investigated extensively; however, there are no studies focusing on HRQoL after surgery with minimally invasive extracorporeal circulation (MiECC). Therefore, we sought to prospectively investigate the effect of MiECC on postoperative HRQoL when compared with cCPB in patients undergoing CABG over a short-term (3-month) follow-up period. METHODS: Sixty patients scheduled for elective CABG surgery were randomly assigned into two groups: those who had surgery on MiECC system (n = 30) and those who underwent CABG using cCPB (n = 30). Quality-of-life assessment was performed preoperatively (baseline-T0), at first postoperative month (T1) and at 3-month follow-up (T3). The RAND SF-36 scale was used for data collection, which included both sociodemographic and clinical characteristics of patients. The primary outcome of the study was quantitative measurement of postoperative HRQoL at 3-month follow-up. RESULTS: Both groups were balanced in terms of demographic, socio-economic and operative characteristics. At 3-month follow-up, mean SF-36 component and summary scores in each group were higher in absolute values than the respective mean baseline scores, apart from role-physical score in patients operated with cCPB. Patients operated on MiECC showed uniformly significantly higher values in all individual and summary domains, whereas patients operated on cCPB showed significant improvement in 6/8 individual domains. Patients operated on MiECC showed a more pronounced increase in SF-36 individual domain scores from the first to the third postoperative month when compared with cCPB, which was statistically significant regarding physical functioning (P = 0.001), role-physical (P < 0.001), vitality (P = 0.01) and role-emotional (P = 0.004). This resulted in a significant improvement in physical (P = 0.002) and mental (P = 0.01) summary scores. CONCLUSIONS: The current study proves that MiECC significantly improves HRQoL after coronary surgery compared with cCPB. This finding, combined with results from large-scale studies showing superior clinical outcomes from its use, enhances the role of MiECC as a dominant technique in coronary revascularization surgery.