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.

Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation.

BACKGROUND: Alterations in the buffering of intracellular Ca2+, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that although studies report atrial myofibrillar degradation in patients with persistent atrial fibrillation (persAF), the intracellular Ca2+ buffering profile in persAF remains obscure. Therefore, we aim to investigate the intracellular buffering of calcium and its potential arrhythmogenic role in persAF. METHODS: Simultaneous transmembrane fluxes (patch-clamp) and intracellular Ca2+ signaling (fluo-3-acetoxymethyl ester) were recorded in myocytes from right atrial biopsies of sinus rhythm (control) and patients with persAF, alongside human atrial subtype induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). Protein levels were quantified by immunoblotting of human atrial tissue and induced pluripotent stem cell-derived cardiac myocytes. Mouse whole heart and atrial electrophysiology was measured on a Langendorff system. RESULTS: Cytosolic Ca2+ buffering was decreased in atrial myocytes of patients with persAF because of a depleted amount of Ca2+ buffers. In agreement, protein levels of selected Ca2+ binding myofilament proteins, including cTnC (cardiac troponin C), a major cytosolic Ca2+ buffer, were significantly lower in patients with persAF. Small interfering RNA (siRNA)-mediated knockdown of cTnC in induced pluripotent stem cell-derived cardiac myocytes (si-cTnC) phenocopied the reduced cytosolic Ca2+ buffering observed in persAF. Si-cTnC induced pluripotent stem cell-derived cardiac myocytes exhibited a higher predisposition to spontaneous Ca2+ release events and developed action potential alternans at low stimulation frequencies. Last, indirect reduction of cytosolic Ca2+ buffering using blebbistatin in an ex vivo mouse whole heart model increased vulnerability to tachypacing-induced atrial arrhythmia, validating the direct mechanistic link between impaired cytosolic Ca2+ buffering and atrial arrhythmogenesis. CONCLUSIONS: Our findings suggest that loss of myofilament proteins, particularly reduced cTnC protein levels, causes diminished cytosolic Ca2+ buffering in persAF, thereby potentiating the occurrence of spontaneous Ca2+ release events and AF susceptibility. Strategies targeting intracellular buffering may represent a promising therapeutic lead in AF management.

Influence of minimal invasive extracorporeal circuits on dialysis dependent patients undergoing cardiac surgery.

INTRODUCTION: Cardiac surgery in patients on chronic renal dialysis is associated with significant morbidity and mortality. Minimally invasive extracorporeal circuits (MiECC) have shown a positive impact on patient outcome in different high-risk populations. This retrospective study compares the outcome of these high-risk patients undergoing heart surgery either with a MiECC or a conventional extracorporeal circulation (CECC). METHODS: This is a single-center experience including 131 consecutive dialysis dependent patients undergoing cardiac surgery between January 2006 and December 2016. A propensity score matching was employed leaving 30 matched cases in each group. RESULTS: After propensity score matching the 30-day mortality was significantly lower in the MiECC group (n = 3 (10%) vs n = 10 (33%) in the CECC group, p = .028). Further, intraoperative transfused units of packed red blood cells were lower in the MiECC group (1.4 ± 1.8 units vs 2.8 ± 1.7, p < .001). CONCLUSIONS: There are evident advantages to using MiECC in dialysis dependent patients, especially regarding mortality. These findings necessitate additional research in MiECC usage in high-risk populations.

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.

A 20-year experience with cryopreserved allografts as the valve replacement of choice in aortic root reconstruction for destructive endocarditis with abscess formation.

OBJECTIVES: The aim of this retrospective study was to assess the early- and long-term outcomes following the use of cryopreserved allografts in aortic valve endocarditis with peri-annular abscess formation. METHODS: From 2001 to 2021, 110 consecutive patients with active infective endocarditis and peri-annular abscess, underwent a cryopreserved allograft root replacement. In 100 patients (91%), the operation was performed <48 h after admission due to refractory heart failure and or septic shock. In 95 patients (86.4%), a redo operation was performed due to a prosthetic valve endocarditis. Preoperatively, 12 patients were dialysis-dependent and 30 patients suffered from a recent stroke. RESULTS: The 30-day mortality was 18% (20 patients). Freedom from reintervention was 98.3% (standard deviation: 1.7) at 1 year and 83.3% (standard deviation: 8.5) at 10 years. Four patients required a redo operation. Three patients did develop re-endocarditis. Freedom from re-endocarditis was 95% after 17 years of follow-up. Preoperative dialysis dependency (odds ratio: 22.75, 95% confidence interval: 4.79-108.14, P < 0.001), ejection fraction under 30% (odds ratio: 17.91, 95% confidence interval: 3.27-98.01, P < 0.001) and stroke within 14 days prior to operation (odds ratio: 5.21, 95% confidence interval: 1.28-21.2, P = 0.021) were incremental factors associated with the 30-day mortality. CONCLUSIONS: In aortic root endocarditis with abscesses formation, cryopreserved allografts exhibit excellent clinical performance with a low rate of reinfection and reintervention, which make its use as valve replacement a very desirable option. Dialysis dependency, ejection fraction under 30% and recent stroke have the highest impact on the 30-day mortality.

Predictors of postoperative atrial fibrillation persisting beyond hospital discharge after coronary artery bypass grafting.

OBJECTIVE: Minimal invasive extracorporeal circuits (MiECC) have been associated with a significant reduction in the incidence of postoperative atrial fibrillation (AF). Nevertheless, AF remains one of the most common complications following elective primary coronary artery bypass grafting (CABG). The aim of this study was to identify the predictors of AF persisting beyond the hospital stay in elective primary CABG patients. METHODS: We conducted a retrospective analysis for the predictors of AF that persisted beyond discharge between all patients who received an elective isolated CABG in our institution between 2009 and 2014. Patients with a positive history for intermittent or persistent AF were excluded from the analysis. Almost all patients were discharged to a rehabilitation facility where they stayed for 3 to 4 weeks postoperatively. At rehab approximately 91% of them received Holter monitoring at least once prior to their discharge. RESULTS: A total of 770 patients were included in the analysis of which 763 patients survived the in-hospital stay. The incidence of AF at hospital discharge was 4.2% (32/763) while that on Holter monitor at Rehab was 1.5% (10/685). Age and the type of extracorporeal circuit (ECC) utilized were the only significant predictors for both AF at discharge (p < 0.01 both) and on Holter monitor in rehab (p < 0.01 and 0.02, respectively). This was also confirmed on multivariate analysis. CONCLUSION: Our findings show that the benefits of MiECC regarding the incidence of postoperative AF persist beyond hospital discharge. They may thus positively influence the outcomes of patients beyond the early postoperative period.

Altered atrial cytosolic calcium handling contributes to the development of postoperative atrial fibrillation.

AIMS: Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation-contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF. METHODS AND RESULTS: Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (APs, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaTs) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved sodium-calcium exchanger function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modelling indicated that reduced SERCA activity promotes occurrence of CaT and AP alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25-8 Hz). CONCLUSIONS: Biochemical, functional, and modelling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF.

Is aortic valve replacement with a minimally invasive extracorporeal circuit a contemporary option for octogenarians?

OBJECTIVES: Minimally invasive extracorporeal circuits have been introduced to cardiac surgery in an attempt to reduce the negative effects of cardiopulmonary bypass on patient outcome. On the other hand, transcatheter aortic valve replacement (TAVR) provides an excellent option to replace the aortic valve without the need for cardiopulmonary bypass. Several studies have compared TAVR to surgical aortic valve replacement (SAVR) but none have utilized a minimally invasive extracorporeal circuit. METHODS: We retrospectively analysed the results of both procedures among octogenarians operated in our department from 2003 to 2016. Excluded were patients with an active endocarditis, a history of previous cardiac surgery, as well as those who had a minimally invasive surgical approach. This yielded 81 and 142 octogenarians in the SAVR and TAVR groups, respectively. To compensate for a lack of randomization, we performed a propensity score analysis, which yielded 68 patient pairs for the final analysis. RESULTS: The 30-day postoperative mortality was lower in the SAVR group (1.5% vs 5.9%) but not statistically significant (P = 0.4). In contrast, the incidence of postoperative atrial fibrillation was lower in the TAVR group (13% vs 29%) but also non-significant (P = 0.2). Finally, the incidence of paravalvular leakage was in favour of the SAVR group (2.9% vs 52%; P = 0.001) while the transfusion requirement was significantly lower in the TAVR group (29% vs 72%; P < 0.001). CONCLUSIONS: SAVR utilizing a minimally invasive extracorporeal circuit improves the quality of patient care and can offer an alternative to TAVR in octogenarians.

Aortic valve replacement with or without myocardial revascularization in octogenarians. Can minimally invasive extracorporeal circuits improve the outcome?

OBJECTIVE: The positive impact of minimally invasive extracorporeal circuits (MiECC) on patient outcome is expected to be most evident in patients with limited physiologic reserves. Nevertheless, most studies have limited their use to low-risk patients undergoing myocardial revascularization. As such, there is little evidence to their benefit outside this patient population. We, therefore, set out to explore their potential benefit in octogenarians undergoing aortic valve replacement (AVR) with or without concomitant myocardial revascularization. METHODS: Based on the type of the utilized ECC, we performed a retrospective propensity score-matched comparison among all octogenarians (n = 218) who received a primary AVR with or without concomitant coronary artery bypass grafting in our institution between 2003 and 2010. RESULTS: A MiECC was utilized in 32% of the patients. The propensity score matching yielded 52 matched pairs. The 30-day postoperative mortality (2% vs. 10%; p=0.2), the incidence of low cardiac output (0% vs. 6%; p=0.2) and the Intensive Care Unit (ICU) stay (2.5 ± 2.6 vs. 3.8 ± 4.7 days; p=0.06) were all in favour of the MiECC group, but failed to reach statistical significance while the 90-day postoperative mortality did (2% vs. 16%; p=0.02). CONCLUSION: MiECCs have a positive influence on the outcome of octogenarians undergoing AVR with or without concomitant coronary artery bypass grafting. Their use should, therefore, be extended beyond isolated coronary artery bypass graft (CABG) surgery.

Impact of minimally invasive extracorporeal circuits on octogenarians undergoing coronary artery bypass grafting. Have we been looking in the wrong direction?

OBJECTIVES: Minimally invasive extracorporeal circuits (MiECCs) aim at the preservation of physiologic reserves, the impact of which is expected to be most evident in patients in whom these are depleted. In this context, octogenarians present a subpopulation of specific interest. METHODS: Based on the type of the utilized ECC, we performed a retrospective comparison between all octogenarians (n = 324) who received a primary coronary artery bypass in our institution from 2003 until 2010. RESULTS: An MiECC was used in 52% of patients. Preoperative variables showed that the MiECC patients were older (83 ± 2 vs 82 ± 2 years; P = 0.001), had higher incidence of renal dysfunction (8% vs 3%; P = 0.04), moderately reduced left ventricular function (43 vs 33%; P = 0.07) and lower incidence of unstable angina (20% vs 28%; P = 0.06). To overcome these differences, a propensity score matching was performed and yielded 126 matched pairs of patients. The overall transfusion of packed red blood cells (2.3 ± 2.3 vs 3.4 ± 3.2 units per patint; P = <0.001), the rate of low cardiac output (0% vs 6%; P = 0.01) and the 30-day postoperative mortality (2.4% vs 9.5%; P = 0.02) were all in favour of the MiECC group in the matched patient population. CONCLUSIONS: The MiECC concept has shown its benefits regarding both morbidity and mortality in this high-risk patient population. We believe that this beneficial effect finds its reason in a better preservation of physiologic reserves that are essential for a positive outcome in this patient group.

Modular minimal invasive extracorporeal circuits: another step toward universal applicability?

INTRODUCTION: Safety concerns have been one of the main reasons opposing a wider acceptance of minimal invasive extracorporeal circuits (MiECC). Following an extensive experience and a multitude of modifications, we have set out to employ a modular MiECC as a universal extracorporeal circuit. METHODS: A total of 129 cardiac surgical procedures were performed by a single surgeon in 2013. Excluding procedures done under circulatory arrest or with the potential need of such, the MiECC was utilized in almost 90% of surgeries. Of sixty-two (simple procedures) patients who underwent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or CABG + AVR, 82% were non-elective, 10% had a left ventricular ejection fraction (EF) <30% and most had an impaired renal function. Thirty-eight patients had more complex surgeries (complex procedures), 37% of which were urgent, 15% had an EF <30% and the majority had renal dysfunction. RESULTS: The 30-day mortality was 5% in simple procedures and 2.5% in complex procedures. The incidence of postoperative atrial fibrillation was 13% and 16%, respectively. Optimum outcome was defined as a freedom from all complications and blood transfusions and was achieved in 52% and 42%, respectively. CONCLUSIONS: This report shows that modular MiECC can be employed with a high safety margin in cardiac surgery. Furthermore, it emphasizes the impact that minimal invasive philosophy could have in improving patient care.

Syphilitic Aortitis Presenting with Coronary Ostial Stenosis and Aortic Regurgitation.

Bilateral coronary ostial stenosis without additional coronary artery involvement is a rare presentation of syphilitic aortitis, with most cases being identified post-mortem. Herein is presented a case of bilateral coronary ostial stenosis and aortic valve insufficiency caused by syphilitic aortitis without aneurysmal dilatation of the aorta. The patient underwent aortic root replacement and coronary artery bypass grafting. The intraoperative macroscopic findings raised the suspicion of an aortitis that was later confirmed to syphilitic aortitis on histological examination. It is of note that syphilis can be a cause of bilateral ostial stenosis in young adults with no predisposition to atherosclerosis, especially if combined with aortic insufficiency resulting from an isolated leaflet dysfunction.

Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS).

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

Late prosthetic graft infection after frozen elephant trunk presenting by haemoptysis and positive ¹8F-fluorodeoxyglucose-positron emission tomography/computed tomography.

In cardiothoracic surgery, prosthetic graft infection represents a diagnostic and therapeutic challenge. Although clinical assessment, imaging techniques and microbiological investigations are helpful, late graft infection can be difficult to identify using classical diagnostic tools. An aggressive surgical approach involving removal and replacement of all prosthetic materials is technically demanding but remains the best strategy to eradicate infection. Herein, we report a case of a late aortic graft infection, after frozen elephant trunk implantation with atypical presentation, diagnosed with (18)F-fluorodeoxyglucose-positron emission tomography and treated successfully through a radical surgical strategy. This case emphasizes the emerging diagnostic role of positron emission tomography and encourages the adoption of an aggressive surgical approach.

Left ventricular pseudoaneurysm following transfemoral aortic valve implantation.

In spite of being a less-invasive technique, transcatheter aortic valve implantation (TAVI) remains associated with potential serious complications. Left ventricular pseudoaneurysm (LVP) is a known, serious complication of transapical TAVI. However, this complication has not been described after the trans-femoral approach. We describe a case of LVP after transfemoral TAVI, emphasizing the importance of an immediate diagnosis of this potential life-threatening complication.

Effect of minimized perfusion circuit on brain injury markers carnosinase and brain-type fatty binding protein in coronary artery bypass grafting patients.

A minimized perfusion circuit (MPC) has proven to be superior to the conventional circulatory perfusion bypass (CCPB) as it reduces the blood-material interaction and hemodilution. Until now not much is known about impact these different perfusion systems have on the brain. The objective of this study is to determine carnosinase and brain-type fatty binding protein (BFABP) activity as novel specific biomarkers for ischemic brain tissue damage and how their activity differs during and after MPC and CCPB as well as to compare the inflammatory response of both perfusion systems. In a prospective pilot study, 28 patients undergoing coronary artery bypass grafting were randomly divided into an MPC group (n = 14) and a CCPB group (n = 14). Blood samples were taken before, during, and after operation until the fifth postoperative day. The brain biomarker carnosinase was determined by measuring the rate of histidine production from the substrate homocarnosine, whereas BFABP and interleukin-6 were determined by enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) and endothelin-1 were determined by enzyme immunoassay. The mean serum carnosinase activity was significantly higher in MPC (0.57 ± 0.34 nM histidine/mL/min) as compared with the CCPB group (0.36 ± 0.13 nM histidine/mL/min) at the end of operation (P = 0.02). The BFABP did not show any difference between the two groups in the immediate postoperative period until the second postoperative day. From that time point onward, it showed a steep increase in the CCPB group (581.3 ± 157.11 pg/mL) as compared with the concentrations in the MPC group (384.6 ± 39 pg/mL) (P = 0.04). The inflammation markers interleukin-6 and CRP showed a similar pattern in both groups without significant difference. In contrast, the leukocyte count on operation day and endothelin-1 on the first postoperative day were significantly higher in the CCPB group (P = 0.01, P = 0.03, respectively). MPC showed a significant higher and stable serum carnosinase activity during extracorporeal circulation as compared with the CCPB due to less hemodilution and a better preserved oxygen capacity. As a consequence, the antioxidant stress during MPC is limited as compared with CCPB, which means less brain tissue damage reflected by a lower BFABP release. Except endothelin-1 and leukocyte count, the inflammatory response of the MPC and CCPB was equal.

Handling of extensive aneurysm of the aorta with bronchomalacia in a Marfan patient.

Surgical management of extensive aneurysms of the aorta still remains demanding. Herein, we describe the successful treatment of a 59-year-old Marfan patient with extensive aneurysm of the aorta complicated by bronchomalacia.