The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure.

Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions.

Long-term results after mitral valve surgery using minimally invasive versus sternotomy approach: a propensity matched comparison of a large single-center series.

BACKGROUND: Mitral valve (MV) surgery has traditionally been performed by conventional sternotomy (CS), but more recently minimally invasive surgery (MIS) has become another treatment option. The aim of this study is to compare short- and long-term results of MV surgery after CS and MIS. METHODS: This study was a retrospective propensity-matched analysis of MV operations between January 2005 and December 2015. RESULTS: Among 1357 patients, 496 underwent CS and 861 MIS. Matching resulted in 422 patients per group. The procedure time was longer with MIS than CS (192 vs. 185 min; p = 0.002) as was cardiopulmonary bypass time (133 vs. 101 min; p < 0.001) and X-clamp time (80 vs. 71 min; p < 0.001). 'Short-term' successful valve repair was higher with MIS (96.0% vs. 76.0%, p < 0.001). Length of hospital stay was shorter in MIS than CS patients (10 vs. 11 days; p = 0.001). There was no difference in the overall 30-day mortality rate. Cardiovascular death was lower after MIS (1.2%) compared with CS (3.8%; OR 0.30; 95%CI 0.11-0.84). The difference did not remain significant after adjustment for procedural differences (aOR 0.40; 95%CI 0.13-1.25). Pacemaker was required less often after MIS (3.3%) than CS (11.2%; aOR 0.31; 95%CI 0.16-0.61), and acute renal failure was less common (2.1% vs. 11.9%; aOR 0.22; 95%CI 0.10-0.48). There were no significant differences with respect to rates of stroke, myocardial infarction or repeat MV surgery. The 7-year survival rate was significantly better after MIS (88.5%) than CS (74.8%; aHR 0.44, 95%CI 0.31-0.64). CONCLUSION: This study demonstrates that good results for MV surgery can be obtained with MIS, achieving a high MV repair rate, low peri-procedural morbidity and mortality, and improved long-term survival.

Myocardial Accumulations of Reg3A, Reg3γ and Oncostatin M Are Associated with the Formation of Granulomata in Patients with Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a poorly understood disease and is characterized by the focal accumulation of immune cells, thus leading to the formation of granulomata (GL). To identify the developmental principles of fatal GL, fluorescence microscopy and Western blot analysis of CS and control patients is presented here. CS is visualized macroscopically by positron emission tomography (PET)/ computed tomography (CT). A battery of antibodies is used to determine structural, cell cycle and inflammatory markers. GL consist of CD68+, CD163+ and CD206+ macrophages surrounded by T-cells within fibrotic areas. Cell cycle markers such as phospho-histone H3, phospho-Aurora and Ki67 were moderately present; however, the phosphorylated ERM (ezrin, radixin and moesin) and Erk1/2 proteins, strong expression of the myosin motor protein and the macrophage transcription factor PU.1 indicate highly active GL. Mild apoptosis is consistent with PI3 kinase and Akt activation. Massive amounts of the IL-1R antagonist reflect a mild activation of stress and inflammatory pathways in GL. High levels of oncostatin M and the Reg3A and Reg3γ chemokines are in accordance with macrophage accumulation in areas of remodeling cardiomyocytes. We conclude that the formation of GL occurs mainly through chemoattraction and less by proliferation of macrophages. Furthermore, activation of the oncostatin/Reg3 axis might help at first to wall-off substances but might initiate the chronic development of heart failure.

Macrophages represent the major pool of IL-7Rα expressing cells in patients with myocarditis.

Myocarditis is characterized by infiltration and activation of cytokine as well as chemokine receptors frequently producing heart failure. Causes are often infections triggering inflammatory and immune responses but these initial lines of defense might be finally disastrous. To identify mediators we screened various receptors by confocal microscopy and identified cardiac interleukin-7 (IL-7) receptor-α (IL-7Rα) expressing cells in patients with myocarditis. IL-7Rα+ cells were analyzed by markers for leukocytes (CD45), B cells (CD19), T cells (CD3, CD4, CD8) and macrophages (CD68, CD163, CD206). Immune cells were hardly detected in controls. In patients with myocarditis main inflammatory populations consisted of macrophages and T cells. B cells were hardly present. 90% of CD68+ macrophages but less than 20% of CD3+ T cells were IL-7Rα+. This was surprising since T and B lymphocytes are generally regarded as the major IL-7Rα+ cells. Since IL-7 acts as a chemokine, the expression of its receptor might orchestrate cardiac macrophage infiltration. In contrast, consumption of IL-7 by IL-7Rα+ cardiac macrophages might potentially prevent a certain overshooting immune reaction and sepsis by reducing proliferation and survival of lymphocytes. Our data suggest a participation of IL-7Rα+ macrophages in the development of myocarditis and heart failure.

Mitral valve repair for posterior leaflet prolapse: Long-term comparison of loop implantation vs resection.

BACKGROUND: Resection (triangular or quadrangular) is considered the gold standard for the treatment of posterior leaflet prolapse and loop implantation a more recent alternative. We aimed to compare the long-term outcomes of triangular or quadrangular resection vs loop implantation. METHODS: Single-centre, retrospective analysis of mitral valve (MV) surgeries conducted from January 2005 to December 2015. Propensity score matching was based on seven key baseline variables. RESULTS: Data from 721 patients were analyzed; 358 patients received loop implantation and 363 patients underwent resection. Patients had a mean age of 62 years, 33.0% were female and 50.6% had hypertension. Propensity score matching resulted in a matched group of 263 patients who received loop implantation or underwent resection, respectively. Postoperatively, the patients' mitral insufficiency was reduced from grade III/IV to either zero or trace (45.8%) or I (49.8%) and New York Heart Association class reduced from 66.9% in class III/IV preoperatively to 8.3% with no significant differences between groups. Fewer patients receiving loops had procedure-related complications. Fewer patients in the loop implantation group required permanent pacemaker implantation at 30 days (8.4% vs 2.3%; P = .002). The 10-year survival for patients in the resection (88.0%) and loop implantation (89.3%) groups had a hazard ratio of 1.224 (95% confidence interval, 0.633-2.367). CONCLUSION: Our study showed that both loop implantation and resection were associated with comparable long-term survival in patients with posterior leaflet prolapse. Loop implantation is associated with a significantly higher rate of a successful repair, a significantly lower rate of MV replacement after repair failure, fewer procedure-related complications and better 30-day at comparable long-term outcomes.

The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes.

Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK.

Interactions between rheumatoid arthritis synovial fibroblast migration and endothelial cells.

Leukocytes travel within the circulation and enter connective tissues by interactions with endothelium of postcapillary venules mediated by cell adhesion molecules, summarized as the leukocyte adhesion cascade. In the severe combined immunodeficient (SCID) mouse model, rheumatoid arthritis (RA) synovial fibroblasts (SF) migrated to distant cartilage through the vasculature. Therefore, RASF adhesion toward endothelial cells (EC) and E- and P-selectins were analyzed. Cell-to-cell binding assays between SF and EC were performed. Interactions of SF with tumor necrosis factor α (TNFα)-activated EC or selectins were analyzed in flow adhesion assays. Immunohistochemistry for E-selectin ligand CD15s was performed. CD15s induction in RASF by human serum or media was evaluated. Wild-type and E-/-/ P-/- Selectin-SCID mice were used for inverse-wrap surgery. After laser-mediated microdissection, real-time PCR for E-/P-selectin/vascular cell adhesion molecule 1 was performed. Adhesion between SF/EC under static conditions was highest in Roswell Park Memorial Institute-cultured RASF to TNFαα-activated human umbilical vein endothelial cells (2.25-fold) and RASF adhesion was higher toward venous than arterial EC (Dulbecco's modified eagle medium P = 0.0419, RPMI P = 0.0119). In flow chamber assays, RASF adhesion to E-selectin was higher than to P-selectin (e.g. 0.9 dyn cm-2 P = 0.0001). Osteoarthritis synovial fibroblasts showed lower rolling/adhesion properties (e.g. 0.5 dyn cm-2 , P = 0.0010). RASF adhesion to TNFαα-activated EC was increased (e.g. 0.9 dyn cm-2 , P = 0.0061). CD15s induction in RASF was strongest in RA serum. Vimentin/CD15s double-positive cells were detectable. In E-/P-selectin-deficient mice, contralateral invasion was reduced (P = 0.023). E- and P-selectin, and vascular cell adhesion molecule 1 expression in EC of implants was confirmed. Our data indicate that the milieu within vessels induces CD15s which enables RASF to interact with E-selectin/EC under flow. Therefore, RASF may migrate to distant sites and leave the vasculature similarly to leukocytes.

Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties.

Extracellular RNA (exRNA) has been characterized as a molecular alarm signal upon cellular stress or tissue injury and to exert biological functions as a proinflammatory, prothrombotic, and vessel permeability-regulating factor. In this study, we investigated the contribution of exRNA and its antagonist RNase1 in a chronic inflammatory joint disease, rheumatoid arthritis (RA). Upon immunohistochemical inspection of RA, osteoarthritis (OA), and psoriatic arthritis synovium, exRNA was detectable only in the RA synovial lining layer, whereas extracellular DNA was detectable in various areas of synovial tissue. In vitro, exRNA (150-5000 nt) was released by RA synovial fibroblasts (RASF) under hypoxic conditions but not under normoxia or TNF-α treatment. RNase activity was increased in synovial fluid from RA and OA patients compared with psoriatic arthritis patients, whereas RNase activity of RASF and OASF cultures was not altered by hypoxia. Reduction of exRNA by RNase1 treatment decreased adhesion of RASF to cartilage, but it had no influence on their cell proliferation or adhesion to endothelial cells. In vivo, treatment with RNase1 reduced RASF invasion into coimplanted cartilage in the SCID mouse model of RA. We also analyzed the expression of neuropilins in synovial tissue and SF, as they may interact with vascular endothelial growth factor signaling and exRNA. The data support the concepts that the exRNA/RNase1 system participates in RA pathophysiology and that RASF are influenced by exRNA in a prodestructive manner.

The MEK1 inhibitors UO126 and PD98059 block PDGF-AB induced phosphorylation of threonine 292 in porcine smooth muscle cells.

PDGF-AB and FGF-2 (GFs) induce smooth muscle cell (SMC) proliferation which is indispensible for arteriogenesis. While there is common agreement that GFs stimulate SMC proliferation through phosphorylation (P-) of MEK1/2 at Ser218/222, we previously demonstrated that the MEK inhibitors PD98059 and UO126 did not inhibit P-Ser218/222 as originally proposed but caused strong hyperphosphorylation. Here, we demonstrate that GFs increased phosphorylation of MEK1 at Thr292 while UO126 and PD98059 blocked this phosphorylation. This was again surprising since phosphorylation of Thr292 is regarded as a negative feedback loop. Our findings suggest that inhibition of Thr292 phosphorylation in combination with hyperphosphorylation of Ser218/222 serves as an "off" switch of SMC proliferation and potentially of arteriogenesis.

Twelve-month follow-up effects of cognitive training after heart valve surgery on cognitive functions and health-related quality of life: a randomised clinical trial.

OBJECTIVES: Postoperative cognitive decline (POCD) or decreased health-related quality of life (HQL) have been reported after cardiac surgery. A previous investigation showed beneficial effects of postoperative cognitive training on POCD and HQL 3 months after heart surgery. Here, we present the 12-month follow-up results. METHODS: This bicentric, 1:1 randomised and treatment-as-usual controlled trial included elderly patients scheduled for elective heart valve surgery. The training consisted of paper-and-pencil-based exercises practising multiple cognitive functions for 36 min/day 6 days/week over a period of 3 weeks. Neuropsychological tests and questionnaires assessing HQL (36-Item Short Form Health Survey (SF-36)) and cognitive failures in daily living (Cognitive Failures Questionnaire) were performed presurgery and 12 months after training. RESULTS: Twelve months post training, the training group (n=30) showed improvements in HQL compared with the control group (n=28), especially in role limitations due to physical health (U=-2.447, p=0.015, η2=0.109), role limitations due to emotional problems (U=-2.245, p=0.025, η2=0.092), pain (U=-1.979, p=0.049, η2=0.068), average of all SF-36 factors (U=-3.237, p<0.001, η2=0.181), health change from the past year to the present time (U=-2.091, p=0.037, η2=0.075), physical component summary (U=-2.803, p=0.005, η2=0.138), and mental component summary (U=-2.350, p=0.018, η2=0.095). Furthermore, the training group (n=19) showed an improvement compared with the control group (n=27) in visual recognition memory (U=-2.137, p=0.034, η2=0.099). POCD frequency was 22% (n=6) in the control group and 11% (n=2) in the training group (χ²(1) =1.06, p=0.440; OR=2.43, 95% CI 0.43 to 13.61). CONCLUSION: In conclusion, postoperative cognitive training shows enhancing effects on HQL in cardiac surgery patients after 12 months.

Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: a randomized controlled trial.

AIMS: The purpose of the study was to investigate whether intra-operative filter devices protect the brain during coronary artery bypass grafting (CABG) and to determine the impact of solid and gaseous micro-emboli on neuropsychological functioning. METHODS AND RESULTS: Patients undergoing CABG received either an intra-aortic filter (Embol-X) (n = 43), designed to reduce solid micro-emboli, a dynamic bubble trap (DBT) (n = 50), designed to reduce gaseous micro-emboli, or no additional device (control group) (n = 50). Cognitive functioning was assessed before and 3 months after CABG. Micro-emboli signals (MES) were detected during surgery using transcranial Doppler (TCD) sonography. Cerebral magnetic resonance imaging (MRI) was carried out before and after surgery. Primary endpoint was the cognitive outcome of the filter groups compared with the controls. Analysis of covariance was performed using the post-operative cognitive test scores as continuous variables in covariance of the corresponding pre-operative scores. Secondary endpoints were the MES rates and the number of acute ischaemic lesions after CABG. Compared with the controls, cognitive functioning of the DBT group was better in executive functioning (t = 2.525, P = 0.0065) and verbal short-term memory (t = 2.420, P = 0.009). The Embol-X group did not perform better in any test. The total number of MES was lower in the DBT group (median 99, P = 0.0019), but not in the Embol-X group (median 162.5, P > 0.05), both compared with controls (median 164.5). After surgery, 17 patients displayed small ischaemic brain lesions on MRI with equal distribution between the groups. CONCLUSION: Gaseous micro-embolization contributes to neuropsychological decline, which is measurable 3 months post-operatively. No filter device could protect the brain during CABG completely. However, the use of the DBT tends to improve the cognitive outcome after CABG. Gas filters are recommendable for neuroprotection during cardiac surgery.

Transvenous Endomyocardial Biopsy: A Comparison of 2 Approaches.

BACKGROUND: Endomyocardial biopsy (EMB) is a well-established procedure for the diagnosis of specific myocardial diseases and represents the gold standard in monitoring allografts after heart transplantation. In our study, we compared 2 different approaches for harvesting EMB in order to optimize patient safety and efficacy of the procedure. METHODS: As a standard approach for harvesting EMB, a venous introducer sheath was inserted percutaneously via the internal jugular vein using the Seldinger technique. Thereafter, a bioptome was repeatedly introduced throughout this sheath into the right ventricle (RV), each time passing the tricuspid valve (TV). Alternatively, a coronary sinus catheter was inserted via an introducer sheath placed in the subclavian vein and only once was introduced into RV cavity. Hence, just a unique passage of TV was required. Thereafter, a bioptome was introduced via this catheter and precisely guided to the targeted biopsy site. RESULTS: A standard approach was used with 34 patients, and a modified technique was used with 37 patients. Patient characteristics were comparable in both cohorts, and analyses of peri-procedural parameters identified only marginal differences between the groups. Interestingly, the number of harvested tissue samples per procedure was higher in the modified approach compared to the standard approach. No complications occurred. CONCLUSION: The modified approach for EMB is a safe procedure. The facilitated bioptome-guidance and enhanced protection of TV may prevent periprocedural complications.

Comparison of flexible, open with semi-rigid, closed annuloplasty-rings for mitral valve repair.

BACKGROUND: Mitral regurgitation is a frequent valvular disease, with an increasing prevalence. We analysed the long-term outcomes of mitral valve repair procedures conducted over the last 10 years in our clinic using almost exclusively two different annuloplasty ring types. METHODS: A single-centre, retrospective analysis of mitral valve surgeries conducted between January 2005 and December 2015 for patients undergoing first-line mitral valve repair with either open (Cosgrove) or closed (CE Physio / Physio II) annuloplasty (OA or CA, respectively) rings. RESULTS: In total, 1120 patient documentations were available of which 528 underwent OA and 592 patients CA. The median age of patients was 64.0 years and 41.1% were female. The majority of these patients underwent the procedure because of degenerative valve disease. Rates of successful repair were about 90%, 72 h procedural mortality was 0.6% and the rate of re-intervention was 0.6% within the first 30 days. Functional (mitral regurgitation, left ventricular ejection fraction, left ventricular end-diastolic and systolic diameter and New York Heart Association class) as well as hard outcomes were comparable. 77.7 and 74.4% of patients were alive at the 10-year follow-up in the OA and CA groups, respectively. Upon multivariable adjustment, the hazard ratio was 0.926 (95% CI: 0.642-1.3135; p = 0.681). CONCLUSIONS: The functional outcome and survival rates up to 10 years after mitral valve repair were comparable using open and closed annuloplasty rings. Whether this means these rings are interchangeable or a carefully selection of the best-for-the-patient devices will be subject of future investigations.

Long-term outcomes of concomitant tricuspid valve repair in patients undergoing mitral valve surgery.

BACKGROUND: We aimed to find out how the concomitant performance of tricuspid valve repair (TVR) affects outcomes of patients undergoing mitral valve surgery (MVS). METHODS: Single-centre, retrospective analysis of 1357 patients who underwent MVS between January 2005 and December 2015, including 1165 patients with isolated MVS and 192 patients with MVS plus TVR. We used propensity scores to match patients for baseline characteristics other than valve related parameters and arrived at a matched sample of 182 patients per group. RESULTS: The overall procedure duration was longer in the MVS + TVR (224 min) versus the MVS group (176 min; p < 0.001), as were the duration of mechanical ventilation (13 vs. 11 h; p < 0.001), X-clamp (90.5 vs. 66 min; p < 0.001) and cardiopulmonary bypass time (136 vs. 95.5 min; p < 0.001). Rates of procedural complications were not different between groups with the exception of pacemaker rates which were 16.0% in the MVS + TVR group and 8.8% in the isolated MVS group (p = 0.037). There was no difference in death rates within 30 days, stroke, myocardial infarction or repeat MVS. The long-term survival rate was 60.8% in the MVS + TVR vs. 57.5% in the isolated MVS group (HR 1.048; 95%CI 0.737-1.492; p = 0.794). The rate of grade III/IV tricuspid regurgitation (TR) remained low after MVS + TVR during long-term follow-up while the rate of grade ≥ II TR increased slightly in the isolated MVS group. CONCLUSION: The data show that the concomitant performance of TVR in patients undergoing MVS is a safe and effective procedure with good long-term outcomes. Patients can undergo MVS + TVR with confidence as it improves their prognosis up to the level of patients undergoing isolated MVS.

Pulmonary herniation after minimally invasive cardiac surgery: review and implications from a series of 20 cases.

Minimally invasive cardiac surgery (MICS) via right lateral mini thoracotomy is the gold standard treatment approach for mitral and tricuspid valve disorders. Other selected procedures (e.g. transapical aortic valve implantation, MIDCAB) require a left lateral mini thoracotomy for surgical access. Advantages of MICS over complete sternotomy are well known, but access-related complications post MICS, such as pulmonary herniation, are often underestimated/overlooked. In males, a pulmonary herniation in the proximity of the former thoracotomy is often clinically visible, especially when the intrathoracic pressure rises (e.g. during coughing). In females, clinical symptoms may be hidden by the breast and patients often have unspecific complaints or occasional pain when coughing, making identification of a lung herniation more difficult. Chest computed tomography is the diagnostic tool of choice for pulmonary herniations. Using a series of 20 patients with pulmonary herniation post MICS, we report our findings in diagnosis and treatment of this condition.

Long-term results of endoclamping in patients undergoing minimally invasive mitral valve surgery where external aortic clamping cannot be used - a propensity matched analysis.

BACKGROUND: Minimally invasive mitral valve surgery is standard of care in many centres and it is commonly associated with the need for cardiopulmonary bypass. Conventional external aortic clamping (exoclamping) is not always feasible, so endoaortic clamping (endoclamping) has evolved as a viable alternative. The aim of this study is to compare endoclamping (Intraclude™, Edwards Lifesciences) with exoclamping (Chitwood) during minimally invasive mitral valve procedures. METHODS: This single-centre study included 822 consecutive patients undergoing minimally invasive mitral valve procedures. The endoclamp was used in 64 patients and the exoclamp in 758. Propensity-score (PS) matching was performed resulting in 63 patients per group. Outcome measures included procedural variables, length of intensive care unit (ICU) and hospital stay, major adverse cardiac and cerebrovascular events (MACCE) and repeat surgery. RESULTS: The mean age was similar in the two group (62.2 [endoclamp] vs. 63.5 [exoclamp] years; p = 0.554), as were the cardiopulmonary bypass (145 vs. 156 min; p = 0.707) and the procedure time (203 vs. 211 min; p = 0.648). The X-clamp time was significantly shorter in the endoclamp group (88 vs. 99 min; p = 0.042). Length of ICU stay (25.0 vs. 23.0 h) and length of hospital stay (10.0 vs. 9.0 days) were slightly longer in the endoclamp group, but without statistical significance. There were nominal but no statistically significant differences between the groups in the rates of stroke, vascular complications, myocardial infarction or repeat mitral valve surgery. The conversion rate to open sternotomy approach was 2.4% without difference between groups. The estimated 7-year survival rate was similar for both groups (89.9% [endoclamp]; 84.0% [exoclamp]) with a hazard ratio of 1.291 (95% CI 0.453-3.680). CONCLUSIONS: Endoaortic clamping is an appropriate and reasonably safe alternative to the conventional Chitwood exoclamp for patients in which the exoclamp cannot be used because the ascending aorta cannot be safely mobilised.

Minimally invasive left atrial appendage (LAA) clip insertion after challenging LAA occluder implantation to minimize the risk of stroke.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, requiring lifelong anticoagulation or interventional, transseptal left atrial appendage (LAA) occluder implantation to minimize stroke risk. Incomplete LAA closure post implantation is a frequent observation. Incomplete LAA occlusion after transseptal occluder implantation necessitates anticoagulation in cases of persistent AF to minimze risk of embolism and/or apoplexy. Patients with contraindications to lifelong anticoagulation therapy are challenging to treat and alternative options are needed. We present a case of a patient with persistent AF who underwent frustraneous LAA occluder implantation. The patient's anatomy necessitated surgical closure of the LAA, which was accomplished with an LAA clip 4 weeks after implantation. The patient was discharged in excellent clinical status 5 days after the surgery. No further complications were observed within the following year.