The Role of Matrix Metalloproteinases in Thoracic Aortic Disease: Are They Indicators for the Pathogenesis of Dissections?

The pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients who had coronary heart disease served as "healthy controls". All patients underwent the necessary surgical procedure according to the diagnosed aortic disease in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1 and MMP9 and TIMP1 and TIMP2 as well. Vascularization was monitored by a CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found the smallest changes in the intima area at all. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In the case of arteriosclerotic changes, intima had a capillarization, but not in the media. An opposite pattern was found in the dissected aortas. There are differences in the vascularization between the aneurysm and dissection and the different layers, respectively. A different remodeling process of the ECM in comparison to the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, disturbed nutrition, and dysfunctional vasa vasorum remodeling must be assumed as causes of dissection.

The ratio of cytochrome c oxidase subunit 4 isoform 4I1 and 4I2 mRNA is changed in permanent atrial fibrillation.

AIMS: The conditions of hypoxia are suggested to induce permanent atrial fibrillation (AF). The regulation of COX4I2 and COX4I1 depends on oxygen availability in tissues. A role of COX4I2 in the myocardium of AF patients is supposed for pathogenesis of AF and subsequent alterations in the electron transfer chain (ETC) under hypoxia. METHODS AND RESULTS: In vitro, influence of hypoxia on HeLa 53 cells was studied and elevated parts of COX 4I2 were confirmed. Myocardial biopsies were taken ex vivo from the patients' Right Atria with SR (n = 31) and AF (n = 11), respectively. RT- PCR for mRNA expresson, mitochondrial respiration by polarography and the protein content of cytochrome c oxidase (CytOx) subunit 4I1 and CytOx subunit 4I2 by ELISA were studied. Clinical data were correlated to the findings of gene expressions in parallel. Patients with permanent AF had a change in isoform 4I2/4I1 expression along with a decrease of isoform COX 4I1 expression. The 4I2/4I1 ratio of mRNA expression was increased from 0.630 to 1.058 in comparison. However, the protein content of CytOx subunit 4 was much lower in the AF group, whereas the respiration/units enzyme activity in both groups remained the same. CONCLUSIONS: This study describes a possible molecular correlate for the development of AF. Due to the known functional significance of COX 4I2, mitochondrial dysfunction can be assumed as a part of the pathogenesis of AF.

Combined Minimally Invasive Mitral Valve Surgery and Percutaneous Coronary Intervention: A Hybrid Concept for Patients with Mitral Valve and Coronary Pathologies.

We evaluated the feasibility of hybrid percutaneous coronary intervention (PCI) and minimally invasive mitral valve surgery (MIMVS) in patients with concomitant coronary and mitral disease. Of 534 patients who underwent MIMVS at our institution between 2012 and 2018, those with combined mitral and single vessel coronary pathologies who underwent MIMVS and PCI were included. Patients were excluded if they had endocarditis or required emergency procedures. Preprocedural, procedural, and postprocedural data were retrospectively analyzed. In total, 10 patients (median age, 75 years; 7 males) with a median ejection fraction (EF) of 60% were included. Nine patients underwent PCI before and one after MIMVS. The success rate was 100% in both procedures. There were no postoperative myocardial infarctions or strokes. Two patients developed delirium and one required re-thoracotomy for bleeding. The median stay in intensive care and the hospital was 3 and 8 days, respectively. The 30-day survival rate was 100%. A hybrid PCI and MIMVS approach is feasible in patients with mitral valve and single vessel coronary disease. In combined pathologies, the revascularization strategy should be evaluated independent from the mitral valve pathology in the presence of MIMVS expertise. Extension of this recommendation to multivessel disease should be evaluated in future studies.

Interventional Treatment of Recurrent Ventricular Septal Defect Planed by 3D-Printed Reconstruction of the Heart.

We report a complex case of a 53-year-old male patient with recurrent ischemic ventricular septal defect that had been occluded by a surgical patch. Treatment was accomplished utilizing a 3-dimensional-printed model for preprocedural planning. In the future, printing of 3-dimensional models could offer new therapeutic strategies on an individual level. (Level of Difficulty: Intermediate.).

Preoperative optimization of cardiac valve patients' expectations: Study protocol of the randomized controlled ValvEx-trial.

Introduction: Complete recovery after surgery depends on psychological factors such as preoperative information, expectations, and surgery-associated anxiety. Prior studies have shown that even a short preoperative psychological intervention aiming at optimized expectations (EXPECT) can improve postoperative outcomes in coronary artery bypass patients. However, this intervention may benefit only a small subgroup of heart surgery patients since implementing preoperative psychological interventions into the daily clinical routine is difficult due to the additional time and appointments. It is unclear whether the EXPECT intervention can be shortened and whether heart valve patients would also benefit from interventions that optimize patients' expectations. The multicenter ValvEx trial aims (i) to adapt an effective preoperative psychological intervention (EXPECT) to make it brief enough to be easily integrated into the preoperative routine of heart valve patients and (ii) to examine if the adapted preoperative psychological intervention improves the subjectively perceived illness-related disability (PDI) up to 3 months after surgery. Materials and analysis: In two German university hospitals, N = 88 heart valve patients who undergo heart surgery are randomized into two groups [standard of care (SOC) vs. standard of care plus interventional expectation manipulation (SOC and EXPECT)] after baseline assessment. Patients in the EXPECT group additionally to standard of care participate in the preoperative psychological intervention (30-40 min), focusing on optimizing expectations and have two booster-telephone calls (4 and 8 weeks after the surgery, approx. 15 min). Both groups have assessments again on the evening before the surgery, 4 to 6 days, and 3 months after the surgery. Discussion: The trial demonstrates excellent feasibility in the clinical routine and a high interest by the patients. Ethics and dissemination: The Ethics Committees of the Department of Medicine of the Philipps University of Marburg and the Department of Medicine of the University of Giessen approved the study protocol. Study results will be published in peer-reviewed journals and presented at congresses. Clinical trial registration: ClinicalTrials.gov, identifier NCT04502121.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

Influence of cardioplegic solution on incidence of delirium after CABG surgery: Use of Calafiore blood cardioplegia versus HTK - Bretschneider - solution in a single-center retrospective analysis from 2017 to 2021.

BACKGROUND: Purpose of the present study is an evaluation of postoperative incidence for delirium after coronary artery bypass surgery (CABG). Study addressed whether application of Histidine-Tryptophan-Ketoglutarate (HTK) solution (Bretschneider) or blood cardioplegia (Calafiore) is associated with increased of postoperative delirium cases. MATERIALS AND METHODS: In a retrospective, single center evaluation a total number of 273 patients were enrolled in the study from January 2017 to October 2021. There were 124 patients assigned to the Calafiore group blood cardioplegic solution (BCC) and 149 patients were included in the Bretschneider group (HTK). The primary endpoint was the postoperative delirium rate in its frequency of occurrence. Definition of the dilirium status was performed using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) score during the first three postoperative days. Secondary endpoints were the time intervals of intensive care duration of stay, mechanical ventilation, total extracorporeal circulation, ischemia and reperfusion. Serum levels of the electrolytes Sodium, Potassium, ionized Calcium, and Chloride were monitored. RESULTS: Although no significant difference in delirium status between the groups were noticed, on third postoperative day, delirium rate dependent on cardioplegia solution used (HTK 12.0%; BCC 3.0%; p = .024) and duration of intensive care stay differed (HTK 4.5 vs. BCC 3.0 days; p = .001). Although Ischemic time (HTK 73.0 vs. BCC 83.0 min; p < .001) and reperfusion time (HTK 35.0 vs. Calafiore 24.0 min; p < .001) were extended in the BCC group less cases of delirium were diagnosed. Serum sodium levels after HTK cardioplegic infusion were decreased (HTK 129.68 vs. BCC 138.96 mmol/l; p < .001). The significant difference persists up to the hundredth extracorporeal circulation circuit min (p = .005). CONCLUSION: The present data suggest an impact of the cardioplegic solution used upon postoperative delirium rates. Optimization of cardiac arrest protocols is needed. Present data encourage further prospective studies regarding the impact of cardioplegic solutions on electrolyte imbalance for postoperative delirium rates in CABG surgery.

Prediction of stroke reconvalescence after coronary bypass surgery indicated by CT scan parameters.

BACKGROUND: Stroke in the postoperative time course after heart surgery remains a serious risk. Cranial computer tomography (CCT) is the first line option to detect severe intracranial damage. However, only few data are available to predict neurological outcome. Using visual rating scales (VRSs), this study addresses reliability and effectivity to indicate neurological status and likelyhood of improvement. METHODS: In a single-center retrospective evaluation, 3719 patients underwent coronary bypass surgery. Because of a delayed recovery phase and neurologic deficits after cardiac surgery 109 patients had a cranial CT scan in the early postoperative period. The incidence of clinically relevant findings within the imaging was rated by an experienced neuroradiologist using two VRS, that is, the age-related white matter changes (ARWMCs) and the Mendes-Ribeiro visual rating scale (MRVRS). Both are computer-assisted measurement schemes to detect stroke-related intracranial damage. Follow-up was investigated with regard to clinical outcome and patient-related risk profiles. RESULTS: Of 109 patients with postoperative cranial CT scans due to prolonged recovery phases or proven neurological damage 44.5% had one cerebral defect in CCT imaging scans only. The others showed multiple defects. During hospital stay, 92.3% experienced neurological improvement exposing reduced ARWMC, while 7.1% had no improvement and correlating high scores. Of both scales, the ARWMC-VRS demonstrated superior accuracy and discrimination. The preoperative ejection fraction (EF), arteriosclerotic degeneration of carotid arteries, and reduced glomerular filtration rate were found to have a high correlation (r = 0.0005) with the latter group. In-hospital mortality of this cohort was 8.18%. CONCLUSION: Both the ARWMC and MRVRS were found to be appropriate. They reliably discriminate the groups of stroke patients after coronary artery bypass grafting (CABG)  in the analysis of CCT images. When applied at the onset of neurological symptoms both scales are able to predict neurological reconvalescence upon hospital dismission. The ARWMC scale appeared superior as it demonstrated better accuracy and discrimination. The use of both VRS in patients with suspected stroke after CABG surgery can give insightful information toward a progression of neurological dysfunction or postoperative improvement.

Cytochrome c Oxidase Inhibition by ATP Decreases Mitochondrial ROS Production.

This study addresses the eventual consequence of cytochrome c oxidase (CytOx) inhibition by ATP at high ATP/ADP ratio in isolated rat heart mitochondria. Earlier, it has been demonstrated that the mechanism of allosteric ATP inhibition of CytOx is one of the key regulations of mitochondrial functions. It is relevant that aiming to maintain a high ATP/ADP ratio for the measurement of CytOx activity effectuating the enzymatic inhibition as well as mitochondrial respiration, optimal concentration of mitochondria is critically important. Likewise, only at this concentration, were the differences in ΔΨm and ROS concentrations measured under various conditions significant. Moreover, when CytOx activity was inhibited in the presence of ATP, mitochondrial respiration and ΔΨm both remained static, while the ROS production was markedly decreased. Consubstantial results were found when the electron transport chain was inhibited by antimycin A, letting only CytOx remain functional to support the energy production. This seems to corroborate that the decrease in mitochondrial ROS production is solely the effect of ATP binding to CytOx which results in static respiration as well as membrane potential.

Role of matrix metalloproteinases in mitral valve regurgitation: Association between the of MMP-1, MMP-9, TIMP-1, and TIMP-2 expression, degree of mitral valve insufficiency, and pathologic etiology.

BACKGROUND: The pathogenesis of mitral valve insufficiency is not yet fully understood. Several studies stressed the role of matrix metalloproteinases (MMPs) in the emergence of valvular pathologies. The primary objective of the present study is to analyze the role of selected MMPs and their inhibitors in mitral valve insufficiency. PATIENTS AND METHODS: Eighty patients (33 female/47 male, mean age 67 years) underwent cardiopulmonary bypass surgery for mitral valve reconstruction between 2007 and 2015. All patients suffered from mitral insufficiency (MI) Stages iii and iv. When tissue resection was acquired specimens were taken immediately frozen and used for histological examination. Expression of MMP-1, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 was examined immunohistochemically and distribution was analyzed in regard to preoperative clinical, echocardiographic, and histopathological findings. RESULTS: A clear correlation between the MMP expression and the MI degree of severity could be shown. The expression of MMPs proved to be high in relation to mild insufficiencies and relatively weak in the case of severe ones. Additionally, the etiology of the MI was considered in the analysis and a significant difference in the expression of MMPs between the mitral valves with endocarditis and the ones featuring a degenerative disease could be shown. Within the group of valves with degenerative diseases, no significant difference could be established between the subgroups (myxoid and sclerosed valves). CONCLUSION: The increased expression of MMPs and their inhibitors in mild insufficiencies could prove that the molecular changes in the valve precede the macroscopical and thus the echocardiographically diagnosable changes. Hence, new options for early diagnosis and therapy of MIs should be examined in further studies, respectively. Herein, the correlation of the MMP blood levels with MMP tissue expression should be addressed for surgical therapeutical decisions.

Risk factors for postoperative delirium after cardiac surgical procedures with cardioplegic arrest.

OBJECTIVES: The pathophysiology of delirium after cardiac surgery is complex. The present study aims to determine perioperative risk factors and construct a scoring system for postoperative delirium based on the type of surgery. METHODS: Three hundred patients undergoing coronary artery bypass grafting (CABG; n = 150) or valve and/or aortic surgery ± CABG (n = 150) were retrospectively evaluated. RESULTS: The incidence of delirium (32%) was similar in subgroups (28.7% and 33.33%, P = 0.384). Delirium patients were older [71.3 (standard deviation: 8.5) vs 66.6 (standard deviation: 9.5), P < 0.001; 70.0 (standard deviation: 9.6) vs 62.5 (standard deviation: 12.6), P < 0.001] and required more packed red blood cell units [2.1 (standard deviation: 2.1) vs 4.2 (standard deviation: 4.0), P < 0.001; 2.4 (standard deviation: 3.3) vs 5.4 (standard deviation: 5.9), P < 0.001] and fresh frozen plasma units [6.1 (standard deviation: 2.9) vs. 8.0 (standard deviation: 4.2), P < 0.001; 6.3 (standard deviation: 3.4) vs 10.8 (standard deviation: 7.2), P < 0.001] in CABG and valve/aortic subgroups, respectively. Delirium was associated with longer operation time [298.3 (standard deviation: 98.4) vs 250.6 (standard deviation: 67.8) min, P < 0.001], cardiopulmonary bypass (CPB) time [171.5 (standard deviation: 54.9) vs 140.98 (standard deviation: 45.8) min, P < 0.001] and cardiac arrest time [112 (standard deviation: 35.9) vs 91.9 (standard deviation: 28.6), P < 0.001] only in the valve/aortic group (versus non-delirium). Multivariate regression analysis identified an association between delirium and age [odds ratio: 1.056 (95% confidence interval: 1.002-1.113), P = 0.041], CPB time [odds ratio: 1.1014 (95% confidence interval: 1.004-1.025), P = 0.007], fresh frozen plasma transfusion [odds ratio: 1.127 (95% confidence interval: 1.006-1.262), P = 0.039] and atrial fibrillation [odds ratio: 4.801 (95% confidence interval: 1.844-12.502), P < 0.001] after valve/aortic surgery (area under the curve 0.835, P < 0.001) and between delirium and age [odds ratio: 1.089 (95% confidence interval: 1.023-1.160), P = 0.007] and ventilation time [odds ratio: 1.068 (95% confidence interval: 1.026-1.113), P = 0.001] after isolated CABG (area under the curve 0.798, P < 0.001). The cross-validation of the results by k-fold logistic regression revealed for the entire patient cohort an overall average accuracy of the prediction model of 0.764, with a false-positive rate of 0.052 and a false-negative rate of 0.18. CONCLUSIONS: Age, CPB time, ventilation, transfusion and atrial fibrillation are differently associated with delirium depending on the operative characteristics. Optimization of intraoperative parameters and use of risk calculators may enable early institution of pharmacotherapy and improve overall outcome after cardiac surgery.

Urinary TIMP-2 and IGFBP-7 protein levels as early predictors of acute kidney injury after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication associated with on-pump cardiac surgery. Early recognition may alter their prognosis. Therefore, the urinary concentrations of TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor-binding protein) as predictors for AKI were studied. METHODS: Repetitive blood and urine samples were collected consecutively from 50 patients. Demographic, intra-, and postoperative data were recorded prospectively. To calculate the production of the TIMP-2 and IGFBP-7 protein concentrations, urinary samples were taken preoperatively, intraoperatively at 30 and 60 min after aortic clamping and at 0, 6, 12, and 24 h after admission to the intensive care unit (ICU). RESULTS: AKI occurred in 14 patients (28%), all of them at Kidney Disease: Improving Global Outcomes stage 1. Predictive value for [TIMP-2] × [IGFBP7] was shown at 0 and 24 h after admission to ICU. At 0 h, the sensitivity was 84.6% and the specificity 55.6% for an ideal calculated cutoff at 0.07. After 24 h, the ideal cutoff amounted to 0.35 with a sensitivity of 53.8% and a specificity of 88.2%. The receiver operating characteristic curves demonstrated areas under the curve of 0.725 and 0.718. The suggested cutoffs of 0.3 and 2.0 could not be confirmed. The serum creatinine was reached to the peak median within 48 h after admission to ICU. CONCLUSION: Postoperative risk assessment for the development of AKI can be established by [ TIMP - 2 ] × [ IGFBP 7 ] . Previously suggested cutoff values could not be confirmed. A correlation with urinary dilution parameters may enable the identification of more universal cutoffs.

Video-assisted minimal access surgery for complicated mitral valve endocarditis, tricuspid valve insufficiency and progressive coronary disease after previous CABG - in the time of COVID-19: a case report.

BACKGROUND: The timing for heart surgery following cerebral embolization after cardiac valve vegetation is vital to postoperative recovery being uneventful, additionally Covid-19 may negatively affect the outcome. Minimally invasive methods and upgraded surgical instruments maximize the benefits of surgery also in complex cardiac revision cases with substantial perioperative risk. CASE PRESENTATION: A 68 y.o. patient, 10 years after previous sternotomy for OPCAB was referred to cardiac surgery on the 10th postoperative day after neurosurgical intervention for intracerebral bleeding with suspected mitral valve endocarditis. Mitral valve vegetation, tricuspid valve insufficiency and coronary stenosis were diagnosed and treated by minimally invasive revision cardiac surgery on the 14th postoperative day after neurosurgery. CONCLUSION: The present clinical case demonstrates for the first time that the minimally invasive approach via right anterior mini-thoracotomy can be safely used for concomitant complex mitral valve reconstruction, tricuspid valve repair and aorto-coronary bypass surgery, even as a revision procedure in the presence of florid endocarditis after recent neurosurgical intervention. The Covid-19 pandemic and prophylactic patient isolation slow down the efficacy of pulmonary weaning and mobilisation and prolong the need for ICU treatment, without adversely affecting long-term outcome.

Allegra Transcatheter Heart Valve inside a Degenerated Sutureless Aortic Bioprosthesis.

Transcatheter aortic valve-in-valve implantation (VIV) is increasingly being used to successfully treat degenerated surgical aortic valve bioprostheses (SAVs). The new self-expanding transcatheter heart valve Allegra, from New Valve Technology with its special implantation mechanism, has proven its safety and feasibility for patients with degenerated SAVs, but it has never been used in the latest-generation sutureless SAV. To the best of our knowledge, this is the first description of the successful VIV of the Allegra prosthesis into a degenerated sutureless SAV, and the procedure yielded an excellent postinterventional hemodynamic results.

Mechanical circulatory support for early surgical repair of postinfarction ventricular septal defect with cardiogenic shock.

Postinfarction ventricular septal defect (pVSD) due to acute myocardial infarction complicated by cardiogenic shock (CS) is associated with high mortality. The aim of this study was to determine the outcome of primary surgical repair of pVSD in patients with CS and examine whether it is influenced by the use of mechanical circulatory support (MCS) devices. Between October 1994 and April 2016, primary surgical repair of pVSD complicated by CS was performed in 53 patients. Thirty-six (68%) were implanted pre-operatively with an intra-aortic balloon pump (IABP), 4 (8%) with extracorporeal life support (ECLS), and 13 (24%) received no MCS device. Prospectively collected demographic and perioperative data were analyzed retrospectively. All-cause, 30-day mortality rates were analyzed and multivariate analysis was performed to differentiate independent risk factors. No pre-operatively implanted MCS device was able to improve 30-day survival, whereas pre-operatively implanted ECLS tended to have a positive effect (P = .106). The post-operative need for a MCS device or escalation of MCS invasiveness (IABP upgrade to ECLS) was associated with a higher 30-day mortality (P = .001) compared with patients without any MCS device or those with pre-operatively implanted MCS devices. An independent risk factor for 30-day mortality was the interval between acute myocardial infarction and surgery <7 days (OR 5.895, CI 1.615-21.515; P = .007). Pre-operative implantation of ECLS for CS tends to improve the outcome of early primary surgical pVSD repair. The need for a post-operative MCS device is associated with a worse 30-day survival after early primary surgical pVSD repair.

Protamine Sulfate Induces Mitochondrial Hyperpolarization and a Subsequent Increase in Reactive Oxygen Species Production.

Protamine sulfate (PS) is widely used in heart surgery as an antidote for heparin, albeit its pharmacological effects are not fully understood and applications are often accompanied by unwanted side effects. Here we show the effect of PS on mitochondrial bioenergetics profile resulting in mitochondrial reactive oxygen species (ROS) production. Polarographic measurements were performed in parallel to membrane potential and ROS measurements by FACS analyzer using tetramethylrhodamine ethyl ester and MitoSOX fluorescent dyes, respectively. PS inhibited intact rat heart mitochondrial respiration (stimulated by ADP) to 76% (P < 0.001) from the baseline of 51.6 ± 6.9 to 12.4 ± 2.3 nmol O2⋅min-1⋅ml-1 The same effect was found when respiration was inhibited by antimycin A (101.0 ± 8.9 vs. 38.0 ± 9.9 nmol O2 ⋅min-1⋅ml-1, P < 0.001) and later stimulated by substrates of cytochrome oxidase (CytOx) i.e., ascorbate and tetramethyl phenylene diamine, suggesting that PS exerted its effect through inhibition of CytOx activity. Furthermore, the inhibition of mitochondrial respiration by PS was concentration dependent and accompanied by hyperpolarization of the mitochondrial membrane potential (Δψ m), i.e., 18% increase at 50 µg/ml and an additional 3.3% increase at 250 µg/ml PS compared with control. This effect was associated with a strong consequent increase in the production of ROS, i.e., 85% and 88.6% compared with control respectively. We propose that this excessive increase in ROS concentrations results in mitochondrial dysfunction and thus might relate to the "protamine reaction," contributing to the development of various cardiovascular adverse effects.

The JUPITER registry: One-year outcomes of transapical aortic valve implantation using a second generation transcatheter heart valve for aortic regurgitation.

OBJECTIVES: We present 1-year outcomes of the post-market registry of a next-generation transcatheter heart valve used for aortic regurgitation (AR). BACKGROUND: Transcatheter aortic valve replacement (TAVR) is routine in high-risk patients with aortic stenosis but is not recommended for AR. The JenaValve™ (JenaValve Technology GmbH, Munich, Germany) overcomes technical challenges in AR patients through a leaflet clipping mechanism. METHODS: The JenaValve EvalUation of Long Term Performance and Safety In PaTients with SEvere Aortic Stenosis oR Aortic Insufficiency (JUPITER) Registry is a European study to evaluate safety and effectiveness of this THV. From 2012-2015, 30 patients with AR were enrolled. RESULTS: Mean age was 74.4 ± 9.3 years. Procedural success was 96.7% (29/30). One patient was converted to open surgery. No annular rupture or coronary ostia obstruction occurred. Mortality at 30 days was 10.0% (3/30). Combined safety endpoint was met in 13.3% (4/30). Paravalvular regurgitation was not present/trivial in 84.6% (22/26) and mild in 15.4% (4/26). Rate of permanent pacemaker implantation was 3.8% (1/26). One-year Kaplan-Meier survival was 79.9%, one-year combined efficacy was 73.1% (19/30). No further strokes were observed during 1 year of follow-up. CONCLUSIONS: The JenaValve overcomes technical challenges of TAVR in AR through a clipping mechanism. We report satisfactory outcomes of a multicenter registry using the JenaValve for predominant AR, as rate of THV embolization, residual AR and permanent pacemaker implantation was low. One-year results using the JenaValve for AR encourage its use for this indication.

Treatment of Coronary Artery Disease: Randomized Trials on Myocardial Revascularization and Complete Arterial Bypass Grafting.

Friedrich Wilhelm Mohr from the very beginning of his career as a cardiac surgeon was involved in the refinements of coronary artery bypass grafting (CABG). At the Leipzig Heart Center, his spirit of early adapting to new technologies inspired the entire team and led to a matchless scientific atmosphere to find solutions to improve almost all fields of cardiac surgery, including CABG. In combination with a tremendous number of patients with indications for isolated coronary artery bypass Prof. Mohr as the surgical principle investigator and the Leipzig Heart Center were able to include patients in the Synergy between PCI [percutaneous coronary intervention] with Taxus and Cardiac Surgery (SYNTAX) trial, the first randomized trials comparing CABG and PCIs using the drug-eluting stents. Final SYNTAX results after 5 years gave direction and scientific evidence for contemporary European revascularization guidelines. These guidelines recommend PCI as an alternative first-line treatment option in patients with coronary three-vessel disease and left main stenosis having low coronary complexity based on the angiographic SYNTAX score. However, the study demonstrated the significant superiority of CABG over PCI in all other patients, especially in these with complex three-vessel disease. The specific characteristic of the SYNTAX study is that the distinguished results were confirmed by several post-SYNTAX comparative randomized trials on coronary revascularization including left main disease and clinical registries even when contemporary drug-eluting stent designs were used. When performing CABG the question of the best second graft remains unclear. While several mono-institutional reports and large meta-analyses demonstrated clear superiority in terms of long-term survival when using bilateral mammary versus single mammary revascularization, this benefit could not be confirmed in randomized trials after 5 years.

Temporal Trends in Predictors of Early and Late Mortality After Emergency Coronary Artery Bypass Grafting for Cardiogenic Shock Complicating Acute Myocardial Infarction.

BACKGROUND: Cardiogenic shock after acute myocardial infarction is an indication for emergent coronary artery bypass grafting in patients not amenable to percutaneous coronary intervention. Our study aimed to evaluate and identify risk factors for early and long-term outcomes in such patients. METHODS: A total of 508 patients who underwent coronary artery bypass grafting for cardiogenic shock complicating acute myocardial infarction between January 2000 and June 2014 were divided into 3 time cohorts: 2000 to 2004 (n=204), 2005 to 2009 (n=166), and 2010 to 2014 (n=138). Predictors of in-hospital mortality for each time cohort and long-term mortality for all patients were identified by logistic and Cox regression analyses, respectively. RESULTS: Mean age was 68.3±9.8 years. Of the 508 patients, 78.5% had 3-vessel and 47.1% had left main disease. Left ventricular function <30% was observed in 44.1% of patients, with 30.4%, 37.9%, 52.9%, and 3.1% requiring preoperative resuscitation, ventilation, intra-aortic balloon pump, and extracorporeal membrane oxygenation support, respectively. Overall in-hospital mortality was 33.7%; declined from 42.2% to 30.7% to 24.6%, respectively, for the 3 time cohorts (P=0.02); and was independently predicted by serum lactate >4 mmol/L (odds ratio [OR], 4.78; 95% confidence interval, 2.88-7.95; P<0.0001), ST-segment-elevation myocardial infarction (OR, 2.10; 95% confidence interval, 1.36-3.26; P=0.001), age >75 years (OR, 2.01; 95% confidence interval, 1.06-3.85; P=0.03), and left ventricular ejection fraction <30% (OR, 1.83; 95% confidence interval, 1.15-2.91; P=0.01). Cumulative survival was 42.6±2.0% and 33.4±2.0% at 5 and 10 years, respectively, and correspondingly improved to 64.3±3.0% and 49.8±3.0% in hospital survivors. Serum lactate >4 mmol/L (OR, 2.2; P<0.0001), incremental age (OR, 1.05; P<0.0001), New York Heart Association class IV (OR, 1.33; P=0.02), diabetes mellitus (OR, 1.39; P=0.005), and preoperative inotropic (OR, 2.61; P=0.001) and extracorporeal membrane oxygenation (OR, 1.68; P=0.05) support predicted late mortality. CONCLUSIONS: Emergency coronary artery bypass grafting in patients with acute myocardial infarction complicated by cardiogenic shock is associated with a high in-hospital mortality, which showed a significant decline with time. Hospital survivors have good long-term outcomes, which demonstrate the beneficial effect of surgical revascularization. Preoperative serum lactate >4 mmol/L is a strong predictor of both early and late mortality.