Metabolomics implicate eicosanoids in severe functional mitral regurgitation.

AIMS: Secondary, or functional, mitral regurgitation (FMR) was recently recognized as a separate clinical entity, complicating heart failure with reduced ejection fraction (HFrEF) and entailing particularly poor outcome. Currently, there is a lack of targeted therapies for FMR due to the fact that pathomechanisms leading to FMR progression are incompletely understood. In this study, we sought to perform metabolomic profiling of HFrEF patients with severe FMR, comparing results to patients with no or mild FMR. METHODS AND RESULTS: Targeted plasma metabolomics and untargeted eicosanoid analyses were performed in samples drawn from HFrEF patients (n = 80) on optimal guideline-directed medical therapy. Specifically, 17 eicosanoids and 188 metabolites were analysed. Forty-seven patients (58.8%) had severe FMR, and 33 patients (41.2%) had no or non-severe FMR. Comparison of eicosanoid levels between groups, accounting for age, body mass index, and sex, revealed significant up-regulation of six eicosanoids (11,12-EET, 13(R)-HODE, 12(S)-HETE, 8,9-DiHETrE, metPGJ2, and 20-HDoHE) in severe FMR patients. Metabolites did not differ significantly. In patients with severe FMR, but not in those without severe FMR, levels of 8,9-DiHETrE above a cut-off specified by receiver-operating characteristic analysis independently predicted all-cause mortality after a median follow-up of 43 [interquartile range 38, 48] months [hazard ratio 12.488 (95% confidence interval 3.835-40.666), P < 0.0001]. CONCLUSIONS: We report the up-regulation of various eicosanoids in patients with severe FMR, with 8,9-DiHETrE appearing to predict mortality. Our observations may serve as a nucleus for further investigations into the causes and consequences of metabolic derangements in this important valvular abnormality.

Fate of patients weaned from post-cardiotomy extracorporeal life support.

OBJECTIVES: Although post-cardiotomy extracorporeal life support (PC-ECLS) is a potentially life-saving resource for patients with cardiopulmonary failure after cardiac surgery, adverse outcomes have been reported even in successfully weaned patients. The goal of this study was to assess outcome in patients weaned from PC-ECLS. METHODS: Of 573 consecutive patients who received PC-ECLS at a single centre between 2000 and 2019, 478 patients were included in a retrospective analysis. Successful weaning was defined as survival >24 h after extracorporeal life support (ECLS) explantation. Mortality of patients on ECLS, as well as in-hospital mortality of weaned patients, was assessed. A binary logistic regression model with backward elimination was used to identify predictors for in-hospital mortality after successful ECLS explantation. RESULTS: Of 478 included patients, 120 patients (25.1%) died on ECLS or within 24 h after ECLS explantation. A total of 358 patients were successfully separated from ECLS and survived for >24 h (n = 352 weaned, n = 3 transitioned to durable left ventricular assist device and n = 3 transitioned to a heart transplant). A total of 35.5% of patients who were successfully weaned from ECLS did not survive until hospital discharge. In-hospital deaths of the whole cohort were 51.7% (247/478 patients). For patients who survived to discharge (231/478 patients, 48.3%), survival was 87% after 1 year and 68.9% after 5 years. CONCLUSIONS: In-hospital mortality of patients requiring PC-ECLS is high even in case of successful weaning. Longer ECLS duration, older age, female gender and low preoperative glomerular filtration rate were risk factors for in-hospital mortality after ECLS weaning. Survival of patients discharged after PC-ECLS was encouraging.

Prediction of Neurological Recovery After Cardiac Arrest Using Neurofilament Light Chain is Improved by a Proteomics-Based Multimarker Panel.

BACKGROUND: Continuous advances in resuscitation care have increased survival, but the rate of favorable neurological outcome remains low. We have shown the usefulness of proteomics in identifying novel biomarkers to predict neurological outcome. Neurofilament light chain (NfL), a marker of axonal damage, has since emerged as a promising single marker. The aim of this study was to assess the predictive value of NfL in comparison with and in addition to our established model. METHODS: NfL was measured in plasma samples drawn at 48 h after cardiac arrest using single-molecule assays. Neurological function was recorded on the cerebral performance category (CPC) scale at discharge from the intensive care unit and after 6 months. The ability to predict a dichotomized outcome (CPC 1-2 vs. 3-5) was assessed with receiver operating characteristic (ROC) curves. RESULTS: Seventy patients were included in this analysis, of whom 21 (30%) showed a favorable outcome (CPC 1-2), compared with 49 (70%) with an unfavorable outcome (CPC 3-5) at discharge. NfL increased from CPC 1 to 5 (16.5 pg/ml to 641 pg/ml, p < 0.001). The addition of NfL to the existing model improved it significantly (Wald test, p < 0.001), and the combination of NfL with a multimarker model showed high areas under the ROC curve (89.7% [95% confidence interval 81.7-97.7] at discharge and 93.7% [88.2-99.2] at 6 months) that were significantly greater than each model alone. CONCLUSIONS: The combination of NfL with other plasma and clinical markers is superior to that of either model alone and achieves high areas under the ROC curve in this relatively small sample.

Access site complications of postcardiotomy extracorporeal life support.

OBJECTIVE: To assess the influence of primary arterial access in patients receiving peripheral postcardiotomy extracorporeal life support on associated complications and outcome. METHODS: Of 573 consecutive patients requiring PC-ECLS between 2000 and 2019 at a single center, 436 were included in a retrospective analysis and grouped according to primary arterial extracorporeal life support access site. Survival and rate of access-site-related complications with special emphasis on fatal/disabling stroke were compared. RESULTS: The axillary artery was cannulated in 250 patients (57.3%), whereas the femoral artery was used as primary arterial access in 186 patients (42.6%). There was no significant difference in 30-day (axillary: 62%; femoral: 64.7%; P = .561) and 1-year survival (axillary: 42.5%; femoral: 44.8%; P = .657). Cerebral computed tomography-confirmed stroke with a modified ranking scale ≥4 was significantly more frequent in the axillary group (axillary: n = 28, 11.2%; femoral: n = 4, 2.2%; P = .0003). Stroke localization was right hemispheric (n = 20; 62.5%); left hemispheric (n = 5; 15.6%), bilateral (n = 5; 15.6%), or infratentorial (n = 2; 6.25%). Although no difference in major cannulation site bleeding was observed, cannulation site change for bleeding was more frequent in the axillary group (axillary: n = 13; 5.2%; femoral: n = 2; 1.1%; P = .03). Clinically apparent limb ischemia was significantly more frequent in the femoral group (axillary: n = 12, 4.8%; femoral: n = 31, 16.7%; P < .0001). CONCLUSIONS: Although survival did not differ, surgeons should be aware of access-site-specific complications when choosing peripheral PC-ECLS access. Although lower rates of limb ischemia and the advantage of antegrade flow seem beneficial for axillary cannulation, the high incidence of right hemispheric strokes in axillary artery cannulation should be considered.

Patient Selection and Clinical Indication for Chronic Total Occlusion Revascularization-A Workflow Focusing on Non-Invasive Cardiac Imaging.

Percutaneous coronary intervention of chronic total occlusion (CTO PCI) is a challenging procedure with high complication rates and, as not yet fully understood long-term clinical benefits. Ischemic symptom relief in patients with high ischemic burden is to date the only established clinical indication to undergo CTO PCI, supported by randomized controlled trials. In this context, current guidelines suggest attempting CTO PCI only in non-invasively assessed viable CTO correspondent myocardial territories, with large ischemic areas. Hence, besides a comprehensive coronary angiography lesion evaluation, the information derived from non-invasive cardiac imaging techniques is crucial to selecting candidates who may benefit from the revascularization of the occluded vessel. Currently, there are no clear recommendations for a non-invasive myocardial evaluation or choice of imaging modality pre-CTO PCI. Therefore, selecting among available options is left to the physician's discretion. As CTO PCI is strongly recommended to be carried out explicitly in experienced centers, full access to non-invasive imaging for risk-benefit assessment as well as a systematic institutional evaluation process has to be encouraged. In this framework, we opted to review the current myocardial imaging tools and their use for indicating a CTO PCI. Furthermore, based on our experience, we propose a cost-effective systematic approach for myocardial assessment to help guide clinical decision-making for patients presenting with chronic total occlusions.

Catalase Predicts In-Hospital Mortality after Out-of-Hospital Cardiac Arrest.

The generation of harmful reactive oxygen species (ROS), including hydrogen peroxide, in out-of-hospital cardiac arrest (OHCA) survivors causes systemic ischemia/reperfusion injury that may lead to multiple organ dysfunction and mortality. We hypothesized that the antioxidant enzyme catalase may attenuate these pathophysiological processes after cardiac arrest. Therefore, we aimed to analyze the predictive value of catalase levels for mortality in OHCA survivors. In a prospective, single-center study, catalase levels were determined in OHCA survivors 48 h after the return of spontaneous circulation. Thirty-day mortality was defined as the study end point. A total of 96 OHCA survivors were enrolled, of whom 26% (n = 25) died within the first 30 days after OHCA. The median plasma intensity levels (log2) of catalase were 8.25 (IQR 7.64-8.81). Plasma levels of catalase were found to be associated with mortality, with an adjusted HR of 2.13 (95% CI 1.07-4.23, p = 0.032). A Kaplan-Meier analysis showed a significant increase in 30-day mortality in patients with high catalase plasma levels compared to patients with low catalase levels (p = 0.012). High plasma levels of catalase are a strong and independent predictor for 30-day mortality in OHCA survivors. This indicates that ROS-dependent tissue damage is playing a crucial role in fatal outcomes of post-cardiac syndrome patients.

Impact of Venoarterial Extracorporeal Membrane Oxygenation on Alkaline Phosphatase Metabolism after Cardiac Surgery.

(1) Alkaline phosphatase (AP) is consumed during cardiopulmonary bypass (CPB). A high AP depletion leads to an impaired outcome after cardiac surgery. However, data is scarce on the postoperative course of AP under venoarterial ECMO (VA-ECMO) support. (2) A total of 239 patients with VA-ECMO support between 2000 and 2019 at the Department of Cardiac Surgery (Vienna General Hospital, Austria) were included in this retrospective analysis. Blood samples were collected at several timepoints (baseline, postoperative day (POD) 1-7, POD 14 and 30). Patients were categorized according to the relative AP drop (<60% vs. ≥60%) and ECMO duration (<5 days vs. ≥5 days). (3) Overall, 44.4% reached the baseline AP values within 5 days-this was only the case for 28.6% with a higher AP drop (compared to 62.7% with a lower drop; p = 0.000). A greater AP drop was associated with a significantly higher need for renal replacement therapy (40.9% vs. 61.9%; p = 0.002) and an impaired 1-year survival (51.4% vs. 66.0%; p = 0.031). (4) CPB exceeds the negative impact of VA-ECMO; still, ECMO seems to delay alkaline phosphatase recovery. A greater initial AP drop bears the risk of higher morbidity and mortality.

Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with monocyte subsets in patients with stable coronary artery disease.

BACKGROUND: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. OBJECTIVE: The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. METHODS: We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). RESULTS: Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R = -0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9

Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction.

Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to increased NET burden in STEMI and influences long-term outcomes. We enrolled 711 STEMI patients undergoing primary percutaneous coronary intervention (pPCI), and 1422 controls. Genotyping was performed for DNase 1 Q222R SNP. DNase activity, double-stranded (ds)DNA and citrullinated histone H3 were determined in culprit site and peripheral plasma during pPCI. The association of the Q222R variant on cardiovascular and all-cause mortality was assessed by multivariable Cox regression adjusted for cardiovascular risk factors. Homozygous Q222R DNase 1 variant was present in 64 (9.0%) STEMI patients, at the same frequency as in controls. Patients homozygous for Q222R displayed less DNase activity and increased circulating DNA burden. In overall patients, median survival was 60 months. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. dsDNA/DNase ratio independently predicted cardiovascular and all-cause mortality. These findings highlight that the Q222R DNase 1 SNP is associated with increased NET burden and decreased compensatory DNase activity, and may serve as an independent risk factor for poor outcome after STEMI.

Gastric regurgitation predicts neurological outcome in out-of-hospital cardiac arrest survivors.

Hypoxic-ischemic brain injury can affect and disturb the autonomous nervous system (ANS), which regulates various visceral systems including the gastro-intestinal and emetic system. The present study aimed to analyze the predictive value of gastric regurgitation (GReg) for neurological outcome in out-of-hospital cardiac arrest (OHCA) survivors. In this prospective, single-center study, 79 OHCA survivors treated at a university-affiliated tertiary care centre were included and GReg was measured at the first day after successful cardiopulmonary resuscitation. Neurological outcome was assessed by the Cerebral Performance Categories score at discharge. Seventy-six percent of the study population had a poor neurological outcome. GReg was found to be associated with poor neurological outcome with an adjusted OR of 5.37 (95% CI 1.41-20.46; p = 0.01). The area under the ROC curve for GReg was 0.69 (95% CI, 0.56-0.81) for poor neurological outcome. GReg on the first day after OHCA is an early, strong and independent predictor for poor neurological outcome in comatose OHCA survivors. These results are particularly compelling because measurement of GReg is inexpensive and routinely performed in critical care units.

Awake Implementation of Extracorporeal Life Support in Refractory Cardiogenic Shock.

Background and objectives: Extracorporeal life support (ECLS) is a widely accepted and effective strategy for use in patients presenting with refractory cardiogenic shock. Implantation in awake and non-intubated patients allows for optimized evaluation of further therapy options while avoiding potential side effects associated with the need for sedation and intubation. The aim of the study was the assessment of safety and feasibility of awake ECLS implementation and of outcomes in patients treated with this concept. Materials and Methods: We retrospectively reviewed the concept of awake ECLS implantation in 16 consecutive patients (mean age 58 ± 8 years; male: 88%; ischemic cardiomyopathy: 50%) from 02/2017 to 01/2021. Study endpoints were survival to weaning or bridging to durable support or organ replacement and development of end-organ function and hemodynamic parameters on ECLS. Results: Fourteen patients (88%) were able to be successfully transitioned to definite therapy options. ECLS support stabilized end-organ function, led to a decrease in mean lactate levels (5.3 ± 3.7 mmol/L at baseline to 1.9 ± 1.3 mmol/L 12 h after ECLS start; p = 0.01) and improved hemodynamics (median central venous pressure 20 ± 5 mmHg vs. 10 ± 2 mmHg, p = 0.001) over a median duration of two days (1-8 days IQR). Two patients (13%) died on ECLS support due to multi-organ dysfunction syndrome. Survival to discharge of initially successfully bridged or weaned patients was 64%. Conclusions: Awake ECLS implantation is feasible and safe with the key advantage of omitting or delaying general anesthesia and intubation, with their associated risks in cardiogenic-shock patients, facilitating further decision making.

Veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with cardiogenic shock: rationale and design of the randomised, multicentre, open-label EURO SHOCK trial.

AIMS: Cardiogenic shock (CGS) occurs in 6-10% of patients with acute coronary syndromes (ACS). Mortality has fallen over time from 80% to approximately 50% consequent on acute revascularisation but has plateaued since the 1990s. Once established, patients with CGS develop adverse compensatory mechanisms that contribute to the downward spiral towards death, which becomes difficult to reverse. We aimed to test in a robust, prospective, randomised controlled trial whether early support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides clinical benefit by improving mortality and morbidity. METHODS AND RESULTS: The EURO SHOCK trial will test the benefit or otherwise of mechanical cardiac support using VA-ECMO, initiated early after acute percutaneous coronary intervention (PCI) for CGS. The trial sets out to randomise 428 patients with CGS complicating ACS, following primary PCI (P-PCI), to either very early ECMO plus standard pharmacotherapy, or standard pharmacotherapy alone. It will be conducted in 39 European centres. The primary endpoint is 30-day all-cause mortality with key secondary endpoints: 1) 12-month all-cause mortality or admission for heart failure, 2) 12-month all-cause mortality, 3) 12-month admission for heart failure. Cost-effectiveness analysis (including quality of life measures) will be embedded. Mechanistic and hypothesis-generating substudies will be undertaken. CONCLUSIONS: The EURO SHOCK trial will determine whether early initiation of VA-ECMO in patients presenting with ACS-CGS persisting after PCI improves mortality and morbidity.

Interdependence of VA-ECMO output, pulmonary congestion and outcome after cardiac surgery.

BACKGROUND: Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is a life-saving method for patients with low-output failure after cardiac surgery. However, VA-ECMO therapy may increase left ventricular afterload due to retrograde blood flow in the aorta, which may lead to progression of pulmonary congestion. We examined the predictive value of pulmonary congestion in patients that need VA-ECMO support after cardiovascular surgery. METHODS: We enrolled a total of 266 adult patients undergoing VA-ECMO support following cardiovascular surgery at a university-affiliated tertiary care centre into our single-center registry. Pulmonary edema was assessed on bedside chest X rays at day 0, 3, 5 after VA-ECMO implantation. RESULTS: Median age was 65 (57-72) years, 69% of patients were male and 30-day survival was 63%. At ICU-admission 20% of patients had mild, 54% had moderate and 26% showed severe pulmonary congestion. Pulmonary congestion at day 0 was not associated with outcome (adjusted HR 1.31; 95%-CI 0.89-1.93;P = 0.18), whereas pulmonary congestion at day 3 (adj. HR 2.81; 95%-CI 1.76-4.46;P<0.001) and day 5 (adj. HR 3.01;95%-CI 1.84-4.93;P<0.001) was significantly associated with survival. Linear regression revealed that out of left ventricular function, cardiac output, central venous saturation, maximum dobutamine and norepinephrine dose as well as fluid balance solely ECMO rotation was associated with the evolution of pulmonary congestion (P = 0.007). CONCLUSIONS: Pulmonary edema three and five days after ECMO implantation are associated with poor survival. Interestingly, a high VA-ECMO output was the most important determinant of worsening pulmonary congestion within the first five days.

[Recommendations for Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Patients]. / Empfehlungen für ECMO bei COVID-19-Patienten: Consensus Paper zur Extrakorporalen Membranoxygenierung der Medizinischen Universität Wien.

The pandemic from the SARS-CoV­2 Virus is currently challenging health care systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe work environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develops respiratory or circulatory failure that is refractory to conventional therapies, it is of utmost importance to clearly define criteria for the use of ECMOs in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

Recommendations for extracorporeal membrane oxygenation (ECMO) in COVID-19 patients : Consensus paper of the Medical University of Vienna.

The pandemic from the SARS-CoV­2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

An Extended Duration of the Pre-Operative Hospitalization is Associated with an Increased Risk of Healthcare-Associated Infections after Cardiac Surgery.

Nosocomial infections are a common complication in clinical practice with major impact on surgical success and patient outcome. The probability of nosocomial infections is rapidly increasing during hospitalization. Therefore, we investigated the impact of a prolonged pre-operative hospital stay on the development of post-operative infection. Within this prospective observational study, 200 patients scheduled for elective cardiac surgery were enrolled. Patients were followed during hospital admission and screened for the development of nosocomial infection. Logistic regression analysis was used to assess the impact of a prolonged pre-operative hospital stay on the development of infection. A total of 195 patients were suitable for the final analysis. We found a strong and direct association of the duration of pre-operative hospital stay and the number of patients developing infection (+23.5%; p = 0.006). Additionally, the length of patients' pre-operative hospital stay was independently associated with the development of post-operative nosocomial infection, with an adjusted OR per day of 1.38 (95%CI: 1.02-1.86; p = 0.036). A prolonged pre-operative hospital stay was significantly associated with the development of nosocomial infection after cardiac surgery. Those findings need to be considered in future clinical patient management in order to prevent unnecessary antibiotic use and potential harm to patients.

Left Main Coronary Artery Disease and Outcomes after Percutaneous Coronary Intervention for Chronic Total Occlusions.

BACKGROUND: Concomitant left main coronary artery (LMCA) disease in patients with chronic total occlusions (CTO) commonly results in referral for coronary artery bypass grafting, although the impact of LMCA in CTO patients remains largely unknown. Nevertheless, patient selection for percutaneous coronary intervention of CTOs (CTO-PCI) or alternative revascularization strategies should be based on precise evaluation of the coronary anatomy to anticipate those patients that most likely benefit from a procedure and not on strict adherence to perpetual clinical practice. Therefore, the aim of this study was to assess the impact of LMCA disease on long-term outcomes in patients undergoing percutaneous coronary intervention for CTO. METHODS: We enrolled 3860 consecutive patients undergoing PCI for at least one CTO lesion and investigated the predictive value of concomitant LMCA disease. All-cause mortality was defined as the primary study endpoint. RESULTS: We observed that LMCA disease is significantly associated with mortality. In the Cox regression analysis, we observed a crude hazard ratio (HR) 1.59 (95% confidence interval (CI) 1.23-2.04, p < 0.001) for patients with LMCA disease as compared to patients without. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. CONCLUSION: LMCA disease is associated with excess mortality in CTO patients. Specifically, anatomical features such as CTO of the circumflex artery represent a high risk patient population.

Impact of treatment strategies on long-term outcome of CTO patients.

BACKGROUND: The percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) remains debated. Therefore the aim of this large-scale observational multi-center registry was to compare the long-term outcome of CTO patients undergoing different therapeutic approaches comparing successful CTO revascularization either by PCI or coronary artery bypass graft (CABG), failed CTO-PCI and optimal medical therapy (OMT) alone. METHODS AND RESULTS: A total of 6630 CTO patients were enrolled from two high-volume centers to compare different treatment strategies. All procedures were performed by high-volume CTO operators in tertiary university hospital. Successful CTO-PCI was performed in 3906 patients, failed CTO-PCI in 1479 patients, 412 patients underwent CABG surgery and 833 patients were treated with OMT. During the 5-year follow-up period, 1019 (15%) patients died. Kaplan-Meier analysis unveiled a significantly improved long-term outcome for CTO patients undergoing revascularization either by PCI or by CABG compared to patients with failed CTO-PCI or OMT alone (log-rank P < 0.001). In the multivariate Cox-regression analysis successful CTO-PCI was associated with significantly improved long-term outcome compared to patients under OMT (adj. HR 0.39, 95%CI 0.33-0.45, P < 0.001) or CABG (adj. HR 0.68, 95%CI 0.53-0.86, P = 0.002) independent of clinical confounders encompassing age, BMI, diabetes, kidney function and left ventricular function. CONCLUSIONS: This study showed an improved long-term outcome for CTO revascularization compared to optimal medical therapy, independent from revascularization mode, with the highest survival rate in patients undergoing successful CTO-PCI.

Disinfection of contaminated metal implants with an Er:YAG laser.

Infections related to orthopedic procedures are considered particularly severe when implantation materials are used, because effective treatments for biofilm removal are lacking. In this study, the relatively new approach for infection control by using an erbium:yttrium-aluminum-garnet (Er:YAG) laser was tested. This laser vaporizes all water containing cells in a very effective, precise, and predictable manner and results in only minimal thermal damage. For preliminary testing, 42 steel plates and 42 pins were seeded with mixed cultures. First, the minimally necessary laser energy for biofilm removal was determined. Subsequently, the effectiveness of biofilm removal with the Er:YAG laser and the cleansing of the metal implants with octenidine-soaked gauze was compared. Then, we compared the effectiveness of biofilm removal on 207 steel pins from 41 patients directly after explantation. Sonication and scanning electron microscopy were used for analysis. Laser fluences exceeding 2.8 J/cm2 caused a complete extinction of all living cells by a single-laser impulse. Cleansing with octenidine-soaked gauze and irradiation with the Er:YAG laser are both thoroughly effective when applied to seeded pins. In contrast, when explanted pins with fully developed biofilms were analyzed, we found a significant advantage of the laser procedure. The Er:YAG laser offers a secure, complete, and nontoxic eradication of all kinds of pathogens from metal implants without damaging the implant and without the possible development of resistance. The precise noncontact removal of adjacent tissue is a decisive advantage over conventional disinfectants. Therefore, laser irradiation could become a valuable method in every debridement, antibiotics, and implant retention procedure.

Lipoprotein(a) plasma levels are not associated with survival after acute coronary syndromes: An observational cohort study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is associated with coronary artery disease in population studies, however studies on its predictive value in patients with cardiovascular disease, in particular after acute coronary syndromes (ACS), are conflicting. The aim of this study was to investigate whether Lp(a) is associated with survival after ACS. METHODS AND RESULTS: We analyzed Lp(a) measurement in 1,245 patients who underwent coronary angiography for ACS. The median follow-up for cardiovascular and all-cause mortality was 5.0 (IQR 3.2-8.0) years. 655 (52.6%) presented with ST-segment elevation myocardial infarction (STEMI), 424 (34.1%) with Non-ST-segment elevation myocardial infarction (NSTEMI) and 166 (13.3%) underwent coronary angiography for unstable angina. Cardiovascular mortality was 9.1% and all-cause mortality was 15.7%. Patients were stratified into four groups to their Lp(a) levels. (≤15mg/dL, >15-30mg/dL, >30-60mg/dL, and >60mg/dL). Multivessel disease was significantly more common in patients with Lp(a)>60mg/dL (p<0.05). Increased levels of Lp(a) were not associated with cardiovascular mortality (HR compared with Lp(a) ≤15mg/dL were 1.2, 1.2, and 1.0, respectively; p = 0.69) and not with all-cause mortality (HR compared with Lp(a) ≤15mg/dL were 1.2, 1.2, and 1.2, respectively; p = 0.46). CONCLUSIONS: Lp(a) levels at time of ACS were neither associated with cardiovascular nor with all-cause mortality. Although Lp(a) has been shown to be associated with incidence of coronary artery disease, this study does not support any role of Lp(a) as a risk factor for mortality after ACS. This should be taken into account for development of outcome studies for agents targeting Lp(a) plasma levels.