Sex-specific troponin and creatine kinase thresholds after coronary bypass surgery.

BACKGROUND: The impact of sex-differences on the release of cardiac biomarkers after coronary artery bypass grafting (CABG) remains unknown. The aim of our study was to (a) investigate the impact of sex-differences in cardiac biomarker release after CABG and (b) determine sex-specific thresholds for high-sensitivity troponin (hs-cTn) and creatine kinase-MB (CK-MB) associated with 30-day major adverse cardiovascular event (MACE) and mortality. METHODS: A consecutive cohort of 3687 patients (female: n= 643 (17.4%); male: 3044 (82.6%) undergoing CABG from 2008-2021 in two tertiary university centers with serial postoperative cTn and CK-MB measurement was analyzed. The composite primary outcome was MACE at 30 days. Secondary endpoints were 30-day mortality and five-year mortality and MACE. Sex-specific thresholds for cTn and CK-MB were determined. RESULTS: Lower levels of cTn were found in women after CABG (69.18 vs. 77.57 xURL; p<0.001). Optimal threshold value for cTn was calculated at 94.36 times the URL for female and 206.07 times the URL for male patients to predict 30-day MACE. Female patients missed by a general threshold had increased risk for MACE or death within 30 days (cTn: MACE: OR 3.78 CI: 1.03-13.08; p=0.035; death: OR 4.98; CI: 1.20.-20.61; p=0.027; CK-MB: MACE: OR 10.04; CI: 2.07-48.75; p<0.001; death: OR 13.59; CI: 2.66-69.47; p=0.002). CONCLUSIONS: We provide evidence for sex-specific differences in the outcome and biomarker release after CABG. Sex-specific cut-offs are necessary for the diagnosis of perioperative myocardial injury to improve outcomes of women after CABG.

Cardiac shockwave therapy in addition to coronary bypass surgery improves myocardial function in ischaemic heart failure: the CAST-HF trial.

BACKGROUND AND AIMS: In chronic ischaemic heart failure, revascularisation strategies control symptoms but are less effective in improving left ventricular ejection fraction (LVEF). The aim of this trial is to investigate the safety of cardiac shockwave therapy (SWT) as a novel treatment option and its efficacy in increasing cardiac function by inducing angiogenesis and regeneration in hibernating myocardium. METHODS: In this single-blind, parallel-group, sham-controlled trial (cardiac shockwave therapy for ischemic heart failure, CAST-HF; NCT03859466) patients with LVEF ≤40% requiring surgical revascularisation were enrolled. Patients were randomly assigned to undergo direct cardiac SWT or sham treatment in addition to coronary bypass surgery. The primary efficacy endpoint was the improvement in LVEF measured by cardiac magnetic resonance imaging from baseline to 360 days. RESULTS: Overall, 63 patients were randomized, out of which 30 patients of the SWT group and 28 patients of the Sham group attained 1-year follow-up of the primary endpoint. Greater improvement in LVEF was observed in the SWT group (Δ from baseline to 360 days: SWT 11.3%, SD 8.8; Sham 6.3%, SD 7.4, P = .0146). Secondary endpoints included the 6-minute walking test, where patients randomized in the SWT group showed a greater Δ from baseline to 360 days (127.5 m, SD 110.6) than patients in the Sham group (43.6 m, SD 172.1) (P = .028) and Minnesota Living with Heart Failure Questionnaire score on day 360, which was 11.0 points (SD 19.1) for the SWT group and 17.3 points (SD 15.1) for the Sham group (P = .15). Two patients in the treatment group died for non-device-related reasons. CONCLUSIONS: In conclusion, the CAST-HF trial indicates that direct cardiac SWT, in addition to coronary bypass surgery improves LVEF and physical capacity in patients with ischaemic heart failure.

Five-year outcomes of different techniques for minimally invasive mitral valve repair in Barlow's disease.

OBJECTIVES: Barlow's disease is a specific sub-form of mitral valve (MV) disease, characterized by diffuse excessive tissue and multi segment prolapse. The anterolateral mini-thoracotomy represents the standard access for MV regurgitation in many centres. It still remains unclear which surgical technique provides the best results. Therefore, the aim of this study was to compare operative safety and mid-term outcomes after (i) isolated annuloplasty, (ii) use of additional artificial chordae or (iii) leaflet resection in patients suffering from Barlow's disease undergoing minimally invasive MV repair. METHODS: A consecutive series of patients suffering from Barlow's disease undergoing minimally invasive MV surgery between 2001 and 2020 were analysed (n = 246). Patients were grouped and analysed according to the used surgical technique. The primary outcome was a modified Mitral Valve Academic Research Consortium combined end-point of mortality, reoperation due to repair failure or reoccurrence of severe mitral regurgitation within 5 years. The secondary outcome included operative success and safety up to 30 days. RESULTS: No significant difference was found between the 3 surgical techniques with regard to operative safety (P = 0.774). The primary outcome did not differ between groups (P = 0.244). Operative success was achieved in 93.5% and was lowest in the isolated annuloplasty group (77.1%). Conversion to MV replacement was increased in patients undergoing isolated annuloplasty (P < 0.001). CONCLUSIONS: Isolated annuloplasty, use of additional artificial chordae and leaflet resection represent feasible techniques in Barlow patients undergoing minimally invasive MV surgery with comparable 5-year results. In view of the increased conversion rate in the annuloplasty group, the pathology should not be oversimplified.

HerzMobil Tirol PreOp - A Multidisciplinary Telemonitoring Project for Heart Failure Patients Prior to Cardiac Surgery.

BACKGROUND: Patients with heart failure are at risk of perioperative complications with elective cardiac surgery. OBJECTIVES: Conception of a multidisciplinary telemedicine-assisted optimisation project for high-risk patients prior to elective cardiac surgery. METHODS: Multidisciplinary concept design. RESULTS: A pilot-project for 30 patients was developed. CONCLUSION: Design of the first preoperative telemonitoring-assisted optimisation project for high-risk patients undergoing cardiac surgery.

Complexity of coronary artery disease and the release of cardiac biomarkers after CABG.

Objective: In patients with complex coronary artery disease (CAD) undergoing cardiac surgery, myocardial protection might be impaired due to microvascular obstruction, resulting in myocardial injury and subsequent biomarker release. Therefore, this study investigated the correlation between the complexity of CAD, reflected by the SYNTAX Score, and the release of cardiac biomarkers after CABG. Methods: In a consecutive series of 919 patients undergoing isolated CABG SYNTAX scores I and II were calculated to assess the complexity of CAD. Levels of high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) were routinely measured once before and serially after surgery. Patients were divided into tertiles according to their SYNTAX Scores I and II. Spearman correlations and regression models were performed to measure the degree of association between the release of hs-cTnT and CK-MB and the SYNTAX Scores. Results: Patients with a higher SYNTAX Score I had more comorbidities reflected in a higher EuroSCORE II. Preoperatively, higher levels of cardiac biomarkers were found in patients with higher SYNTAX Score II. No correlation was observed between hs-cTnT, CK-MB and SYNTAX Score I or II. Regression models did not show any association between cardiac biomarkers and the complexity of CAD. Conclusion: The complexity of CAD is not associated with the release of cardiac biomarkers after CABG. Factors influencing postoperative biomarker release need to be elucidated in future trials to include postoperative biomarker release into risk stratification models predicting outcome after cardiac surgery.

Postoperative cardiac biomarker release is not associated with myocardial mass in computer tomography scans.

OBJECTIVES: Myocardial hypertrophy results in increased levels of cardiac biomarkers in healthy individuals and in patients suffering from acute myocardial infarction. The influence of cardiac mass on postoperative cardiac biomarkers release remains unclear. This study investigated the correlation between myocardial mass and the release of high-sensitivity cardiac Troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) after isolated aortic valve replacement (AVR) or bypass surgery. METHODS: Myocardial mass of a consecutive retrospective series of patients was measured automatically using preoperative computer tomography scans (636 patients, AVR = 251; bypass surgery = 385). Levels of cardiac biomarkers were measured before and serially after surgery. Spearman and Pearson correlation and a multivariate regression model was performed to measure the degree of association between myocardial mass and the release of hs-cTnT and CK-MB. RESULTS: Patients were divided into 3 tertiles according to their myocardial mass index. Higher biomarker levels were measured preoperatively in the upper tertile of patients undergoing AVR (P = 0.004) or bypass surgery (P < 0.001). Patients with different heart sizes showed no differences in postoperative biomarker release neither after AVR nor bypass surgery. No statistical significant correlation was observed between myocardial mass index and postoperative release of hs-cTnT or CK-MB in any subgroup (ρ maximum 0.106). CONCLUSIONS: Postoperative biomarker release is not correlated with myocardial mass. Patient factors leading to increased postoperative biomarker levels need to be elucidated in future studies.

Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.

BACKGROUND: Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment. METHODS: We examined CD45-/CD31-/CD34+ preadipocytes and CD68+ macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14+ monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR. RESULTS: CD45-/CD31-/CD34+ preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68+ macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs. CONCLUSION: Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.

Association of High-Sensitivity Cardiac Troponin T With 30-Day and 5-Year Mortality After Cardiac Surgery.

BACKGROUND: The relevance of perioperative myocardial injury (PMI) after cardiac surgery for 30-day mortality and long-term survival remains to be determined. OBJECTIVES: This study assessed the association of PMI after cardiac surgery, reflected by postoperative troponin release, with 30-day mortality and long-term survival after: 1) coronary artery bypass grafting (CABG); 2) isolated aortic valve replacement (AVR) surgery; and 3) all other cardiac surgeries. METHODS: A consecutive cohort of 8,292 patients undergoing cardiac surgery with serial perioperative high-sensitivity cardiac troponin T (hs-cTnT) measurements was retrospectively analyzed. The relationship between postoperative hs-cTnT release and 30-day mortality or 5-year mortality was analyzed after adjustment with EuroSCORE II using a Cox proportional hazards model. hs-cTnT thresholds for 30-day and 5-year mortality were determined for isolated CABG (32.3%), AVR (14%), and other cardiac surgery (53.8%). RESULTS: High postoperative hs-cTnT levels were associated with higher 30-day mortality but not 5-year mortality. In CABG, median peak concentration of postoperative hs-cTnT was 1,044 ng/L, in AVR it was 502 ng/L, and in other cardiac surgery it was 1,110 ng/L. hs-cTnT thresholds defining mortality-associated PMI were as follows: for CABG, 2,385 ng/L (170× the upper reference limit of normal in a seemingly healthy population [URL]); for AVR, 568 ng/L (41× URL); and for other cardiac procedures, 1,873 ng/L (134× URL). hs-cTnT levels above the cutoffs resulted in an HR for 30-day mortality for CABG of 12.56 (P < 0.001), for AVR of 4.44 (P = 0.004), and for other cardiac surgery of 3.97 (P < 0.001). CONCLUSIONS: PMI reflected by perioperative hs-cTnT release is associated with the expected 30-day mortality but not 5-year mortality. Postoperative hs-cTnT cutoffs to identify survival-relevant PMI are higher than suggested in current definitions.

Data processing pipeline for cardiogenic shock prediction using machine learning.

Introduction: Recent advances in machine learning provide new possibilities to process and analyse observational patient data to predict patient outcomes. In this paper, we introduce a data processing pipeline for cardiogenic shock (CS) prediction from the MIMIC III database of intensive cardiac care unit patients with acute coronary syndrome. The ability to identify high-risk patients could possibly allow taking pre-emptive measures and thus prevent the development of CS. Methods: We mainly focus on techniques for the imputation of missing data by generating a pipeline for imputation and comparing the performance of various multivariate imputation algorithms, including k-nearest neighbours, two singular value decomposition (SVD)-based methods, and Multiple Imputation by Chained Equations. After imputation, we select the final subjects and variables from the imputed dataset and showcase the performance of the gradient-boosted framework that uses a tree-based classifier for cardiogenic shock prediction. Results: We achieved good classification performance thanks to data cleaning and imputation (cross-validated mean area under the curve 0.805) without hyperparameter optimization. Conclusion: We believe our pre-processing pipeline would prove helpful also for other classification and regression experiments.

Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification.

BACKGROUND: Calcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling. METHODS: Human valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan (Bgn), Tlr3, and IFN-α/ß receptor alpha chain (Ifnar1)-deficient mice and a specific zebrafish model were used to study the implication of the biglycan (BGN)-TLR3-IFN axis in both CAVD and bone formation in vivo. Two large-scale cohorts (GERA [Genetic Epidemiology Research on Adult Health and Aging], n=55 192 with 3469 aortic stenosis cases; UK Biobank, n=257 231 with 2213 aortic stenosis cases) were examined for genetic variation at genes implicated in BGN-TLR3-IFN signaling associating with CAVD in humans. RESULTS: Here, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that Bgn-/-, Tlr3-/-, and Ifnar1-/- mice are protected against CAVD and display impaired bone formation. Meta-analysis of 2 large-scale cohorts with >300 000 individuals reveals that genetic variation at loci relevant to the XYLT1-BGN-TLR3-interferon-α/ß receptor alpha chain (IFNAR) 1 pathway is associated with CAVD in humans. CONCLUSIONS: This study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.

Cardiac troponin release following coronary artery bypass grafting: mechanisms and clinical implications.

The use of biomarkers is undisputed in the diagnosis of primary myocardial infarction (MI), but their value for identifying MI is less well studied in the postoperative phase following coronary artery bypass grafting (CABG). To identify patients with periprocedural MI (PMI), several conflicting definitions of PMI have been proposed, relying either on cardiac troponin (cTn) or the MB isoenzyme of creatine kinase, with or without supporting evidence of ischaemia. However, CABG inherently induces the release of cardiac biomarkers, as reflected by significant cTn concentrations in patients with uncomplicated postoperative courses. Still, the underlying (patho)physiological release mechanisms of cTn are incompletely understood, complicating adequate interpretation of postoperative increases in cTn concentrations. Therefore, the aim of the current review is to present these potential underlying mechanisms of cTn release in general, and following CABG in particular (Graphical Abstract). Based on these mechanisms, dissimilarities in the release of cTnI and cTnT are discussed, with potentially important implications for clinical practice. Consequently, currently proposed cTn biomarker cut-offs by the prevailing definitions of PMI might warrant re-assessment, with differentiation in cut-offs for the separate available assays and surgical strategies. To resolve these issues, future prospective studies are warranted to determine the prognostic influence of biomarker release in general and PMI in particular.

Safety and efficacy of direct cardiac shockwave therapy in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (the CAST-HF trial): study protocol for a randomized controlled trial-an update.

BACKGROUND: Coronary artery disease (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in the progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodelling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function. METHODS: In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min walk test distance, improvement of symptoms and assessment of quality of life. DISCUSSION: This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT03859466. Registered on 1 March 2019.

Different calcification patterns of tricuspid and bicuspid aortic valves and their clinical impact.

OBJECTIVES: Mechanical strain plays a major role in the development of aortic calcification. We hypothesized that (i) valvular calcifications are most pronounced at the localizations subjected to the highest mechanical strain and (ii) calcification patterns are different in patients with bicuspid and tricuspid aortic valves. METHODS: Multislice computed tomography scans of 101 patients with severe aortic stenosis were analysed using a 3-dimensional post-processing software to quantify calcification of tricuspid aortic valves (n = 51) and bicuspid aortic valves (n = 50) after matching. RESULTS: Bicuspid aortic valves exhibited higher calcification volumes and increased calcification of the non-coronary cusp with significantly higher calcification of the free leaflet edge. The non-coronary cusp showed the highest calcium load compared to the other leaflets. Patients with annular calcification above the median had an impaired survival compared to patients with low annular calcification, whereas patients with calcification of the free leaflet edge above the median did not (P = 0.53). CONCLUSIONS: Calcification patterns are different in patients with aortic stenosis with bicuspid and tricuspid aortic valves. Patients with high annular calcification might have an impaired prognosis.

Correlation between structural heart disease and cardiac SARS-CoV-2 manifestations.

BACKGROUND: The prognosis of COVID-19 patients with cardiac involvement is unfavorable and it remains unknown which patients are at risk. The virus enters cells via its receptor angiotensin-converting enzyme 2 (ACE2). Myocardial ACE2 expression is increased in structural heart disease (SHD). We, therefore, aimed to analyze correlations between structural heart disease and cardiac SARS-CoV-2 manifestation. METHODS: The clinical course of COVID-19 in patients with structural heart disease was assessed in a prospective cohort of 152 patients. The primary endpoints consisted of hospitalization and survival. Cardiac tissue of 23 autopsy cases with lethal COVID-19 course was obtained and analyzed for (a) the presence of SHD, (b) myocardial presence of SARS-CoV-2 via RT,-PCR, and (c) levels of ACE2 expression using immunofluorescence staining. RESULTS: Structural heart disease is found in 67 patients, of whom 56 (83.60%) are hospitalized. The myocardium is positive for SARS-CoV-2 in 15 patients (65%) in 23 autopsy cases of lethal COVID-19. Moreover, most hearts with evidence of myocardial SARS-CoV-2 have structural heart disease [11 (91,67%) vs. 1 (8,33%), p = 0.029]. Myocardial presence of SARS-CoV-2 is correlated with a significant downregulation of ACE2 compared to negative control hearts (6.545 ± 1.1818 A.U. vs. 7.764 ± 2.411 A.U., p = 0.003). The clinical course of patients with cardiac SARS-CoV-2 manifestation is unfavorable, resulting in impaired survival (median, 12 days and 4.5 days, respectively, HR 0.30, 95% CI, 0.13 to 0.73, p = 0.0005) CONCLUSIONS: We provide evidence for a correlation between SHD, altered ACE2 receptor expression, and cardiac SARS-CoV-2 manifestation. Consequently, structural heart disease may be considered a distinct risk factor for a severe clinical course after infection with SARS-CoV-2. REGISTRATION NUMBER LOCAL IRB: Ethics Committee of Northwestern and Central Switzerland ID 2020-00629; Ethics Committee of the Medical University Innsbruck EK Nr: 1103/2020. GOV NUMBER: NCT04416100.

SARS-CoV-2, the virus that causes COVID-19, binds to ACE2 receptors to gain entry into cells. The ACE2 receptor is a cell surface protein found in many tissues, including the heart. Studies suggest that people with heart disease are likely to have higher levels of ACE2 receptors, which may explain why they are more susceptible to severe illness from COVID-19. In this study, we identified heart disease as a risk factor for hospitalization in 152 patients who tested positive for SARS-CoV-2. The presence of SARS-CoV-2 in the heart was associated with altered levels of ACE2 receptors and with a shortened survival time in patients. These findings provide evidence for a potential link between heart disease, ACE2 receptor levels, and SARS-CoV-2 infection of the heart, and may help doctors to understand the clinical course of patients with heart disease who contract COVID-19.

Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First-In-Human Results of Shock Wave Therapy Prove Safety and Feasibility.

Background Spinal cord ischemia (SCI) remains a devastating complication after aortic dissection or repair. A primary hypoxic damage is followed by a secondary damage resulting in further cellular loss via apoptosis. Affected patients have a poor prognosis and limited therapeutic options. Shock wave therapy (SWT) improves functional outcome, neuronal degeneration and survival in murine spinal cord injury. In this first-in-human study we treated 5 patients with spinal cord ischemia with SWT aiming to prove safety and feasibility. Methods and Results Human neurons were subjected to ischemic injury with subsequent SWT. Reactive oxygen species and cellular apoptosis were quantified using flow cytometry. Signaling of the antioxidative transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) and immune receptor Toll-like receptor 3 (TLR3) were analyzed. To assess whether SWT act via a conserved mechanism, transgenic tlr3-/- zebrafish created via CRISPR/Cas9 were subjected to spinal cord injury. To translate our findings into a clinical setting, 5 patients with SCI underwent SWT. Baseline analysis and follow-up (6 months) included assessment of American Spinal Cord Injury Association (ASIA) impairment scale, evaluation of Spinal Cord Independence Measure score and World Health Organization Quality of Life questionnaire. SWT reduced the number of reactive oxygen species positive cells and apoptosis upon ischemia via induction of the antioxidative factor nuclear factor erythroid 2-related factor 2. Inhibition or deletion of tlr3 impaired axonal growth after spinal cord lesion in zebrafish, whereas tlr3 stimulation enhanced spinal regeneration. In a first-in-human study, we treated 5 patients with SCI using SWT (mean age, 65.3 years). Four patients presented with acute aortic dissection (80%), 2 of them exhibited preoperative neurological symptoms (40%). Impairment was ASIA A in 1 patient (20%), ASIA B in 3 patients (60%), and ASIA D in 1 patient (20%) at baseline. At follow-up, 2 patients were graded as ASIA A (40%) and 3 patients as ASIA B (60%). Spinal cord independence measure score showed significant improvement. Examination of World Health Organization Quality of Life questionnaires revealed increased scores at follow-up. Conclusions SWT reduces oxidative damage upon SCI via immune receptor TLR3. The first-in-human application proved safety and feasibility in patients with SCI. SWT could therefore become a powerful regenerative treatment option for this devastating injury.

Basic principles of cardiothoracic surgery training: a position paper by the European Association for Cardiothoracic Surgery Residents Committee.

OBJECTIVES: Across Europe there are significant variations in the fundamental structure and content of cardiothoracic surgery (CTS) training programmes. Previous efforts have been made to introduce a Unified European Training System, which outlined the fundamentals of the ideal programme and supported a paradigm shift from an apprenticeship to a competency-based model. This article's goal was to define key structural, administrative and executive details of such a programme to lay the foundations for the standardization of cardiothoracic surgical training across Europe. METHODS: The European Association for Cardiothoracic Surgery Residents Committee had previously conducted a residents' training survey across Europe in 2020. Training curricula from the twelve most represented countries across Europe were either searched online or obtained from the countries' national trainee representative and reviewed by the committee. Information was collated and placed into one of the following categories to develop the position paper: (i) selection of eligible candidates, (ii) guidance for an outcome-based syllabus, (iii) documentation and evaluation of training progress, (iv) mandatory rotations and training courses, (v) number of independent or assisted cases and (vi) requirements and quality assurance of teachers. RESULTS: An independent professional body should promote an outcome-based syllabus and take responsibility for the training programme's quality assurance. Trainees should be selected on merit by an open and transparent process. Training should be delivered within a defined period and supervised by an appointed training committee to ensure its implementation. This committee should review the trainees progression regularly, provide feedback and offer trainees the opportunity to experience various training environments and trainers. A common electronic portal be used by trainees to record their agreed objectives and to evidence their completion. Trainees should regularly attend specialty-relevant courses and conferences to promote professional and academic development. The end of training is reached when the formal requirements of the training programme are met and the trainee is able to perform at the level expected of a day-1 independent surgeon. CONCLUSIONS: This article defines the key structural, administrative, and executive principles for CTS training. Programmes are encouraged to review and modify their training curricula, if necessary, to ensure the delivery of high-quality, standardized, outcome-orientated CTS training across Europe.

Cardiac Shockwave Therapy - A Novel Therapy for Ischemic Cardiomyopathy?

Over the past decades, shockwave therapy (SWT) has gained increasing interest as a therapeutic approach for regenerative medicine applications, such as healing of bone fractures and wounds. More recently, pre-clinical studies have elucidated potential mechanisms for the regenerative effects of SWT in myocardial ischemia. The mechanical stimulus of SWT may induce regenerative effects in ischemic tissue via growth factor release, modulation of inflammatory response, and angiogenesis. Activation of the innate immune system and stimulation of purinergic receptors by SWT appears to enhance vascularization and regeneration of injured tissue with functional improvement. Intriguingly, small single center studies suggest that SWT may improve angina, exercise tolerance, and hemodynamics in patients with ischemic heart disease. Thus, SWT may represent a promising technology to induce cardiac protection or repair in patients with ischemic heart disease.

Lockdown surgery: the impact of coronavirus disease 2019 measures on cardiac cases.

OBJECTIVES: The need to ration medical equipment and interventions during the coronavirus disease 2019 pandemic translated to an ever-lengthening wait list for surgical care. Retrospective analysis of lockdowns is of high importance to learn from the current situation for future pandemics. This monocentric study assessed the impact of lockdown periods on cardiac surgery cases and outcomes. METHODS: The single-centre cross-sectional descriptive observational study was conducted to investigate the first lockdown period and the following post-lockdown period in comparison to the same periods during the previous 3 years at the Department of Cardiac Surgery at the Medical University of Innsbruck. Data were prospectively collected and retrospectively analysed from the department-specific quality management system. The primary objective was to compare the number of open-heart procedures between the prelockdown and the lockdown period. The secondary objectives were to analyse the characteristics and the outcomes of open-heart procedures. RESULTS: There were no differences in patient demographics. A significant decrease of 29% in weekly surgical procedures was observed during the lockdown period. The surgical case-mix was unaffected: The numbers of aortic valve replacements, coronary artery bypass grafts, mitral valve repair or replacement procedures and others remained stable. The urgency of cases increased significantly, and the general health conditions of patients appeared to be worse. However, outcomes were unchanged. CONCLUSIONS: By implementing a rational patient selection process, the quality of open-heart procedures was maintained even though patients who underwent surgery during lockdown were sicker and more symptomatic.

Impact of aortic root repair or replacement in severe destructive aortic valve endocarditis with paravalvular abscesses on long-term survival.

OBJECTIVES: Surgical treatment of destructive infective endocarditis consists of extensive debridement followed by root repair or replacement. However, it remains unknown whether 1 is superior to the other. We aimed to analyse whether long-term results were better after root repair or replacement in patients with root endocarditis. METHODS: A total of 148 consecutive patients with root endocarditis treated with surgery from 1997 to 2020 at our department were included. Patients were divided into 2 groups: aortic root repair (n = 85) or root replacement using xenografts or homografts (n = 63). RESULTS: Patients receiving aortic root repair showed significantly better long-term survival compared to patients receiving aortic root replacement (log-rank: P = 0.037). There was no difference in terms of freedom from valvular reoperations among both treatment groups (log-rank: P = 0.58). Patients with aortic root repair showed higher freedom from recurrent endocarditis compared to patients with aortic root replacement (log-rank: P = 0.022). Patients with aortic root repair exhibited higher event-free survival (defined as a combination end point of freedom from death, valvular reoperation or recurrent endocarditis) compared to patients receiving aortic root replacement (log-rank: P = 0.022). Age increased the risk of mortality with 1.7% per year. Multi-variable adjusted statistical analysis revealed improved long-term event-free survival after aortic root repair (hazards ratio: 0.57, 95% confidence interval: 0.39-0.95; P = 0.031). CONCLUSIONS: Aortic root repair and replacement are feasible options for the surgical treatment of root endocarditis and are complementary methods, depending on the extent of infection. Patients with less advanced infection have a more favourable prognosis. CLINICAL TRIAL REGISTRATION: UN4232 382/3.1 (retrospective study).

When cardiac surgery comes to its limits: a case report of pericardial mesothelioma invading the myocardium.

BACKGROUND: Primary pericardial mesothelioma (PPM) is a rare form of highly aggressive cancer. Many patients are diagnosed only at an advanced stage. Therefore, the overall survival rate is poor with a median survival of 3 months. In some rare cases, the PPM infiltrates the myocardium causing lethal myocardial dysfunction. CASE SUMMARY: A 66-year-old patient was transferred to our centre with the provisional diagnose of pericarditis of unknown origin. Using extensive cardiac imaging [echocardiography, computed tomography (CT), positron emission tomography-CT, cardiac magnetic resonance imaging, left and right heart catheterization, coronary angiography], PPM was finally diagnosed. After consultation with the oncologists, the heart team decided to resect the tumour first due to impaired haemodynamics and then initiate adjuvant chemotherapy. Intraoperatively, myocardial infiltration of the tumour became apparent, which was not detected preoperatively despite intensive imaging. Complete resection of the PPM was not possible and effective decompression of the ventricle could not be achieved. The patient died on the first postoperative day. DISCUSSION: Surgical therapy is indicated in many forms of cardiac tumours. However, when a tumour invades the myocardium, surgery often comes to its limits. In this case, myocardial invasion of PPM could not be detected despite extensive imaging. We therefore suggest that possible myocardial infiltration by PPM, and thus potential limitations of cardiac surgery, should be considered independently of imaging results when therapeutic options are discussed.