Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.

AIMS: Atrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies is hampered by the absence of scalable experimental human models that reflect AF-associated electrical remodelling. Therefore, we aimed to assess if AF-associated remodelling of cellular electrophysiology can be simulated in human atrial-like cardiomyocytes derived from induced pluripotent stem cells in the presence of retinoic acid (iPSC-aCM), and atrial-engineered human myocardium (aEHM) under short term (24 h) and chronic (7 days) tachypacing (TP). METHODS AND RESULTS: First, 24-h electrical pacing at 3 Hz was used to investigate whether AF-associated remodelling in iPSC-aCM and aEHM would ensue. Compared to controls (24 h, 1 Hz pacing) TP-stimulated iPSC-aCM presented classical hallmarks of AF-associated remodelling: (i) decreased L-type Ca2+ current (ICa,L) and (ii) impaired activation of acetylcholine-activated inward-rectifier K+ current (IK,ACh). This resulted in action potential shortening and an absent response to the M-receptor agonist carbachol in both iPSC-aCM and aEHM subjected to TP. Accordingly, mRNA expression of the channel-subunit Kir3.4 was reduced. Selective IK,ACh blockade with tertiapin reduced basal inward-rectifier K+ current only in iPSC-aCM subjected to TP, thereby unmasking an agonist-independent constitutively active IK,ACh. To allow for long-term TP, we developed iPSC-aCM and aEHM expressing the light-gated ion-channel f-Chrimson. The same hallmarks of AF-associated remodelling were observed after optical-TP. In addition, continuous TP (7 days) led to (i) increased amplitude of inward-rectifier K+ current (IK1), (ii) hyperpolarization of the resting membrane potential, (iii) increased action potential-amplitude and upstroke velocity as well as (iv) reversibly impaired contractile function in aEHM. CONCLUSIONS: Classical hallmarks of AF-associated remodelling were mimicked through TP of iPSC-aCM and aEHM. The use of the ultrafast f-Chrimson depolarizing ion channel allowed us to model the time-dependence of AF-associated remodelling in vitro for the first time. The observation of electrical remodelling with associated reversible contractile dysfunction offers a novel platform for human-centric discovery of antiarrhythmic therapies.

Prehabilitation in older patients prior to elective cardiac procedures (PRECOVERY): study protocol of a multicenter randomized controlled trial.

BACKGROUND: Previous studies have demonstrated the efficacy of rehabilitation after a cardiovascular procedure. Especially older and multimorbid patients benefit from rehabilitation after a cardiac procedure. Prehabilitation prior to cardiac procedures may also have positive effects on patients' pre- and postoperative outcomes. Results of a current meta-analysis show that prehabilitation prior to cardiac procedures can improve perioperative outcomes and alleviate adverse effects. Germany currently lacks a structured cardiac prehabilitation program for older patients, which is coordinated across healthcare sectors. METHODS: In a randomized, controlled, two-arm parallel group, assessor-blinded multicenter intervention trial (PRECOVERY), we will randomize 422 patients aged 75 years or older scheduled for an elective cardiac procedure (e.g., coronary artery bypass graft surgery or transcatheter aortic valve replacement). In PRECOVERY, patients randomized to the intervention group participate in a 2-week multimodal prehabilitation intervention conducted in selected cardiac-specific rehabilitation facilities. The multimodal prehabilitation includes seven modules: exercise therapy, occupational therapy, cognitive training, psychosocial intervention, disease-specific education, education with relatives, and nutritional intervention. Participants in the control group receive standard medical care. The co-primary outcomes are quality of life (QoL) and mortality after 12 months. QoL will be measured by the EuroQol 5-dimensional questionnaire (EQ-5D-5L). A health economic evaluation using health insurance data will measure cost-effectiveness. A mixed-methods process evaluation will accompany the randomized, controlled trial to evaluate dose, reach, fidelity and adaptions of the intervention. DISCUSSION: In this study, we investigate whether a tailored prehabilitation program can improve long-term survival, QoL and functional capacity. Additionally, we will analyze whether the intervention is cost-effective. This is the largest cardiac prehabilitation trial targeting the wide implementation of a new form of care for geriatric cardiac patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http://www.drks.de ; DRKS00030526). Registered on 30 January 2023.

Development and validation of explainable machine learning models for risk of mortality in transcatheter aortic valve implantation: TAVI risk machine scores.

Aims: Identification of high-risk patients and individualized decision support based on objective criteria for rapid discharge after transcatheter aortic valve implantation (TAVI) are key requirements in the context of contemporary TAVI treatment. This study aimed to predict 30-day mortality following TAVI based on machine learning (ML) using data from the German Aortic Valve Registry. Methods and results: Mortality risk was determined using a random forest ML model that was condensed in the newly developed TAVI Risk Machine (TRIM) scores, designed to represent clinically meaningful risk modelling before (TRIMpre) and in particular after (TRIMpost) TAVI. Algorithm was trained and cross-validated on data of 22 283 patients (729 died within 30 days post-TAVI) and generalisation was examined on data of 5864 patients (146 died). TRIMpost demonstrated significantly better performance than traditional scores [C-statistics value, 0.79; 95% confidence interval (CI)] [0.74; 0.83] compared to Society of Thoracic Surgeons (STS) with C-statistics value 0.69; 95%-CI [0.65; 0.74]). An abridged (aTRIMpost) score comprising 25 features (calculated using a web interface) exhibited significantly higher performance than traditional scores (C-statistics value, 0.74; 95%-CI [0.70; 0.78]). Validation on external data of 6693 patients (205 died within 30 days post-TAVI) of the Swiss TAVI Registry confirmed significantly better performance for the TRIMpost (C-statistics value 0.75, 95%-CI [0.72; 0.79]) compared to STS (C-statistics value 0.67, CI [0.63; 0.70]). Conclusion: TRIM scores demonstrate good performance for risk estimation before and after TAVI. Together with clinical judgement, they may support standardised and objective decision-making before and after TAVI.

An Alternative Mechanism of Subcellular Iron Uptake Deficiency in Cardiomyocytes.

BACKGROUND: Systemic defects in intestinal iron absorption, circulation, and retention cause iron deficiency in 50% of patients with heart failure. Defective subcellular iron uptake mechanisms that are independent of systemic absorption are incompletely understood. The main intracellular route for iron uptake in cardiomyocytes is clathrin-mediated endocytosis. METHODS: We investigated subcellular iron uptake mechanisms in patient-derived and CRISPR/Cas-edited induced pluripotent stem cell-derived cardiomyocytes as well as patient-derived heart tissue. We used an integrated platform of DIA-MA (mass spectrometry data-independent acquisition)-based proteomics and signaling pathway interrogation. We employed a genetic induced pluripotent stem cell model of 2 inherited mutations (TnT [troponin T]-R141W and TPM1 [tropomyosin 1]-L185F) that lead to dilated cardiomyopathy (DCM), a frequent cause of heart failure, to study the underlying molecular dysfunctions of DCM mutations. RESULTS: We identified a druggable molecular pathomechanism of impaired subcellular iron deficiency that is independent of systemic iron metabolism. Clathrin-mediated endocytosis defects as well as impaired endosome distribution and cargo transfer were identified as a basis for subcellular iron deficiency in DCM-induced pluripotent stem cell-derived cardiomyocytes. The clathrin-mediated endocytosis defects were also confirmed in the hearts of patients with DCM with end-stage heart failure. Correction of the TPM1-L185F mutation in DCM patient-derived induced pluripotent stem cells, treatment with a peptide, Rho activator II, or iron supplementation rescued the molecular disease pathway and recovered contractility. Phenocopying the effects of the TPM1-L185F mutation into WT induced pluripotent stem cell-derived cardiomyocytes could be ameliorated by iron supplementation. CONCLUSIONS: Our findings suggest that impaired endocytosis and cargo transport resulting in subcellular iron deficiency could be a relevant pathomechanism for patients with DCM carrying inherited mutations. Insight into this molecular mechanism may contribute to the development of treatment strategies and risk management in heart failure.

Turbulence in surgical suction heads as detected by MRI.

BACKGROUND: Blood loss is common during surgical procedures, especially in open cardiac surgery. Allogenic blood transfusion is associated with increased morbidity and mortality. Blood conservation programs in cardiac surgery recommend re-transfusion of shed blood directly or after processing, as this decreases transfusion rates of allogenic blood. But aspiration of blood from the wound area is often associated with increased hemolysis, due to flow induced forces, mainly through development of turbulence. METHODS: We evaluated magnetic resonance imaging (MRI) as a qualitative tool for detection of turbulence. MRI is sensitive to flow; this study uses velocity-compensated T1-weighted 3D MRI for turbulence detection in four geometrically different cardiotomy suction heads under comparable flow conditions (0-1250 mL/min). RESULTS: Our standard control suction head Model A showed pronounced signs of turbulence at all flow rates measured, while turbulence was only detectable in our modified Models 1-3 at higher flow rates (Models 1 and 3) or not at all (Model 2). CONCLUSIONS: The comparison of flow performance of surgical suction heads with different geometries via acceleration-sensitized 3D MRI revealed significant differences in turbulence development between our standard control Model A and the modified alternatives (Models 1-3). As flow conditions during measurement have been comparable, the specific geometry of the respective suction heads must have been the main factor responsible. The underlying mechanisms and causative factors can only be speculated about, but as other investigations have shown, hemolytic activity is positively associated with degree of turbulence. The turbulence data measured in this study correlate with data from other investigations about hemolysis induced by surgical suction heads. The experimental MRI technique used showed added value for further elucidating the underlying physical phenomena causing blood damage due to non-physiological flow.

Molecular and cellular evidence for the impact of a hypertrophic cardiomyopathy-associated RAF1 variant on the structure and function of contractile machinery in bioartificial cardiac tissues.

Noonan syndrome (NS), the most common among RASopathies, is caused by germline variants in genes encoding components of the RAS-MAPK pathway. Distinct variants, including the recurrent Ser257Leu substitution in RAF1, are associated with severe hypertrophic cardiomyopathy (HCM). Here, we investigated the elusive mechanistic link between NS-associated RAF1S257L and HCM using three-dimensional cardiac bodies and bioartificial cardiac tissues generated from patient-derived induced pluripotent stem cells (iPSCs) harboring the pathogenic RAF1 c.770 C > T missense change. We characterize the molecular, structural, and functional consequences of aberrant RAF1-associated signaling on the cardiac models. Ultrastructural assessment of the sarcomere revealed a shortening of the I-bands along the Z disc area in both iPSC-derived RAF1S257L cardiomyocytes and myocardial tissue biopsies. The aforementioned changes correlated with the isoform shift of titin from a longer (N2BA) to a shorter isoform (N2B) that also affected the active force generation and contractile tensions. The genotype-phenotype correlation was confirmed using cardiomyocyte progeny of an isogenic gene-corrected RAF1S257L-iPSC line and was mainly reversed by MEK inhibition. Collectively, our findings uncovered a direct link between a RASopathy gene variant and the abnormal sarcomere structure resulting in a cardiac dysfunction that remarkably recapitulates the human disease.

Bacterial Spectrum and Infective Foci in Patients Operated for Infective Endocarditis: Time to Rethink Strategies?

OBJECTIVE: The rising incidence of infective endocarditis (IE) accompanied by the de-escalation of antibiotic prophylaxis and the complexity of surgical treatment makes IE a daunting foe. We reviewed all patients who underwent cardiac surgery for IE at our institution with a focus on causative organisms and infective foci. METHODS: A review of 3,952 consecutive patients who underwent cardiac surgery at our institution between January 2013 and December 2017 revealed 160 patients (4%) who were operated for IE. RESULTS: The predominantly affected valves were the aortic (30%) and mitral valve (26.9%) as well as a combination of both (8.8%). A total of 28.8% of patients suffered from prosthetic valve endocarditis (PVE). The most frequently identified causative organisms were Staphylococcus (45.7%), Streptococcus (27.5%), and Enterococcus species (16.7%), which was predominantly associated with PVE (p = 0.050). In 13.1% of patients, a causative organism has not been detected. The most frequent infective foci were dental (15%), soft-tissue infections (15%), spondylodiscitis (10%), and infected intravascular implants (8.8%). Relevant predisposing factors were immunosuppression (9.4%) and intravenous drug abuse (4.4%). Septic cerebral infarctions were diagnosed in 28.8% of patients. Postoperative mortality was 22.5%. CONCLUSIONS: As the bacterial spectrum and the infective foci are still the "old acquaintances," and with regard to the increasing incidence of IE, current risk-benefit evaluations concerning antibiotic prophylaxis may need to be revisited.

Preoperative Delirium Risk Screening in Patients Undergoing a Cardiac Surgery: Results from the Prospective Observational FINDERI Study.

OBJECTIVE: Postoperative delirium (POD) is a common complication of cardiac surgery that is associated with higher morbidity, longer hospital stay, cognitive decline, and mortality. Preoperative assessments may help to identify patients´ POD risk. However, a standardized screening assessment for POD risk has not been established. DESIGN: Prospective observational FINd DElirium RIsk factors (FINDERI) study. PARTICIPANTS: Patients aged ≥50 years undergoing cardiac surgery. MEASUREMENTS: The primary aim was to analyze the predictive value of the Delirium Risk Screening Questionnaire (DRSQ) prior to cardiac surgery. Secondary aims are to investigate cognitive, frailty, and geriatric assessments, and to use data-driven machine learning (ML) in predicting POD. Predictive properties were assessed using receiver operating characteristics analysis and multivariate approaches (regularized LASSO regression and decision trees). RESULTS: We analyzed a data set of 504 patients (68.3 ± 8.2 years, 21.4% women) who underwent cardiac surgery. The incidence of POD was 21%. The preoperatively administered DRSQ showed an area under the curve (AUC) of 0.68 (95% CI 0.62, 0.73), and the predictive OR was 1.25 (95% CI 1.15, 1.35, p <0.001). Using a ML approach, a three-rule decision tree prediction model including DRSQ (score>7), Trail Making Test B (time>118), and Montreal Cognitive Assessment (score ≤ 22) was identified. The AUC of the three-rule decision tree on the training set was 0.69 (95% CI 0.63, 0.75) and 0.62 (95% CI 0.51, 0.73) on the validation set. CONCLUSION: Both the DRSQ and the three-rule decision tree might be helpful in predicting POD risk before cardiac surgery.

Direct proteomic and high-resolution microscopy biopsy analysis identifies distinct ventricular fates in severe aortic stenosis.

The incidence of aortic valve stenosis (AS), the most common reason for aortic valve replacement (AVR), increases with population ageing. While untreated AS is associated with high mortality, different hemodynamic subtypes range from normal left-ventricular function to severe heart failure. However, the molecular nature underlying four different AS subclasses, suggesting vastly different myocardial fates, is unknown. Here, we used direct proteomic analysis of small left-ventricular biopsies to identify unique protein expression profiles and subtype-specific AS mechanisms. Left-ventricular endomyocardial biopsies were harvested from patients during transcatheter AVR, and inclusion criteria were based on echocardiographic diagnosis of severe AS and guideline-defined AS-subtype classification: 1) normal ejection fraction (EF)/high-gradient; 2) low EF/high-gradient; 3) low EF/low-gradient; and 4) paradoxical low-flow/low-gradient AS. Samples from non-failing donor hearts served as control. We analyzed 25 individual left-ventricular biopsies by data-independent acquisition mass spectrometry (DIA-MS), and 26 biopsies by histomorphology and cardiomyocytes by STimulated Emission Depletion (STED) superresolution microscopy. Notably, DIA-MS reliably detected 2273 proteins throughout each individual left-ventricular biopsy, of which 160 proteins showed significant abundance changes between AS-subtype and non-failing samples including the cardiac ryanodine receptor (RyR2). Hierarchical clustering segregated unique proteotypes that identified three hemodynamic AS-subtypes. Additionally, distinct proteotypes were linked with AS-subtype specific differences in cardiomyocyte hypertrophy. Furthermore, superresolution microscopy of immunolabeled biopsy sections showed subcellular RyR2-cluster fragmentation and disruption of the functionally important association with transverse tubules, which occurred specifically in patients with systolic dysfunction and may hence contribute to depressed left-ventricular function in AS.

A New Evaluation Q-Factor to Be Calculated for Suction Geometries as a Basis for Smooth Suction in the Operating Field to Ensure the Highest Possible Blood Integrity for Retransfusion Systems.

Blood hemolysis caused by mechanical impact is a serious problem in medicine. In addition to the heart-lung machine (artificial surfaces, flow irritating connection points) which contributes to hemolysis, blood suction and surgical suction devices are influencing factors. Goal of our research is to develop best flow optimizing suction geometry that represents the best compromise between all influencing effects. Based on data that negative pressure and turbulence have a negative impact on blood components, 27 surgical suction tips have been examined for acoustic stress and negative pressure behavior. Furthermore, a dimensionless factor Q was introduced to assess the overall performance of the suction tips investigated.

Identification of risk factors for delirium, cognitive decline, and dementia after cardiac surgery (FINDERI-find delirium risk factors): a study protocol of a prospective observational study.

BACKGROUND: Postoperative delirium is a common complication of cardiac surgery associated with higher morbidity, longer hospital stay, risk of cognitive decline, dementia, and mortality. Geriatric patients, patients undergoing cardiac surgery, and intensive care patients are at a high risk of developing postoperative delirium. Gold standard assessments or biomarkers to predict risk factors for delirium, cognitive decline, and dementia in patients undergoing cardiac surgery are not yet available. METHODS: The FINDERI trial (FINd DElirium RIsk factors) is a prospective, single-center, observational study. In total, 500 patients aged ≥ 50 years undergoing cardiac surgery at the Department of Cardiovascular and Thoracic Surgery of the University of Göttingen Medical Center will be recruited. Our primary aim is to validate a delirium risk assessment in context of cardiac surgery. Our secondary aims are to identify specific preoperative and perioperative factors associated with delirium, cognitive decline, and accelerated dementia after cardiac surgery, and to identify blood-based biomarkers that predict the incidence of postoperative delirium, cognitive decline, or dementia in patients undergoing cardiac surgery. DISCUSSION: This prospective, observational study might help to identify patients at high risk for delirium prior to cardiac surgery, and to identify important biological mechanisms by which cardiac surgery is associated with delirium. The predictive value of a delirium screening questionnaire in cardiac surgery might be revealed. Finally, the identification of specific blood biomarkers might help to predict delirium, cognitive decline, and dementia in patients undergoing cardiac surgery. TRIAL REGISTRATION: Ethics approval for this study was obtained from the IRB of the University of Göttingen Medical Center. The investigators registered this study in the German Clinical Trials Register (DRKS; https://www.drks.de ) (DRKS00025095) on April 19th, 2021.

Transmural myocardial repair with engineered heart muscle in a rat model of heterotopic heart transplantation - A proof-of-concept study.

Engineered heart muscle (EHM) can be implanted epicardially to remuscularize the failing heart. In case of a severely scarred ventricle, excision of scar followed by transmural heart wall replacement may be a more desirable application. Accordingly, we tested the hypothesis that allograft (rat) and xenograft (human) EHM can also be administered as transmural heart wall replacement in a heterotopic, volume-loaded heart transplantation model. We first established a novel rat model model to test surgical transmural left heart wall repair. Subsequently and in continuation of our previous allograft studies, we tested outcome after implantation of contractile engineered heart muscle (EHM) and non-contractile engineered connective tissue (ECT) as well as engineered mesenchymal tissue (EMT) allografts as transmural heart wall replacement. Finally, proof-of-concept for the application of human EHM was obtained in an athymic nude rat model. Only in case of EHM implantation, remuscularization of the surgically created transmural defect was observed with palpable graft vascularization. Taken together, feasibility of transmural heart repair using bioengineered myocardial grafts could be demonstrated in a novel rat model of heterotopic heart transplantation.

Feasibility and preliminary efficacy of perioperative interventions in patients undergoing coronary artery bypass grafting: the randomized controlled I-COPE trial.

OBJECTIVES: Patients undergoing coronary artery bypass graft (CABG) surgery are exposed to multiple treatment-related stressors, which can impact coping and health-related quality of life (HRQoL). The objective of this trial was to analyse the feasibility and preliminary efficacy of a multi-component intervention that combines psychological support and reduction of hospital-specific stressors on HRQoL, length of hospital and intensive care unit stay, self-efficacy, and plasma interleukin (IL)-6 and -8 levels in CABG patients. METHODS: This three-arm, randomized controlled, single-centre pilot trial assessed the Intervention for CABG to Optimize Patient Experience in 88 patients undergoing elective CABG. Standard medical care (SMC, n = 29) was compared with 2 intervention groups: (i) psychological interventions to optimize treatment expectations (IA group, n = 30) and (ii) multi-component intervention (IB group, n = 29) with psychological interventions plus an additional treatment package (light therapy, noise reduction, music, and if desired, 360° images delivered via virtual reality). RESULTS: The implementation of psychological interventions in routine medical treatment was feasible (91.5% of participants completed all intervention sessions). Both interventions were associated with significantly shorter hospital stay compared to SMC (IA/IB 9.8/9.3 days vs SMC 12.5 days). Self-efficacy expectations at post-surgery were significantly higher compared to SMC both in the IA group (P = 0.011) and marginally in the IB group (P = 0.051). However, there were no treatment effects of the interventions on HRQoL and plasma levels of IL-6 or IL-8 after CABG. CONCLUSIONS: A perioperative multi-component intervention may lead to shorter hospital stay and higher self-efficacy after CABG. Further studies are needed to determine its impact on HRQoL and inflammation. CLINICAL TRIAL REGISTRATION NUMBER: Ethical approval (# 21/2/18) for the study was obtained from the Research Ethics Committee of the University of Göttingen Medical Center, and the trial was registered in the German Clinical Trials Register (DRKS00015309, https://www.drks.de/drks_web/setLocale_EN.do).

Heart transplantation in the era of COVID-19 pandemic: delirium, post-transplant depression, and visitor restrictions; the role of liaison and inpatient psychosomatic treatment-a case report.

BACKGROUND: Heart transplant recipients show a high risk of developing major depression with an increased risk of post-transplant morbidity and mortality. Heart transplant specialists and patients face unprecedented challenges during the COVID-19 pandemic, which have enormous clinical implications such as the increased risk of COVID-19 as well as visitor restrictions with social isolation during the post-transplant inpatient treatment. CASE SUMMARY: We present a case of a 64-year-old woman with end-stage heart failure caused by non-compaction cardiomyopathy who received an orthotopic heart transplant (OHT) without any intra-operative complications. Post-operatively, she showed acute psychotic symptoms in the intensive care unit (ICU) with improvement after switching intravenous tacrolimus treatment to an oral intake. Furthermore, the patient developed severe depressive symptoms with malnutrition and had a prolonged hospitalization. Standard medical care was complemented by intensive psychocardiological treatment to overcome the crisis. CONCLUSION: High complexity of the post-transplant management after OHT underlines the importance of multidisciplinary teamwork, involving heart transplant specialists and allied mental health professionals. This collaboration led to an excellent long-term result. Facing the COVID-19 pandemic, the hospital visitor policies may be scrutinized, carefully looking at the role of social isolation, post-operative experience in the ICU, and medical complications after OHT.

The effect of perioperative hemadsorption in patients operated for acute infective endocarditis-A randomized controlled study.

Patients operated for infective endocarditis (IE) are at high risk of developing an excessive systemic hyperinflammatory state, resulting in systemic inflammatory response syndrome and septic shock. Hemoadsorption (HA) by cytokine adsorbers has been successfully applied to remove inflammatory mediators. This randomized controlled trial investigates the effect of perioperative HA therapy on inflammatory parameters and hemodynamic status in patients operated for IE. A total of 20 patients were randomly assigned to either HA therapy or the control group. HA therapy was initiated intraoperatively and continued for 24 hours postoperatively. Cytokine levels (IL-6, IL-1b, TNF-α), leukocytes, C-reactive protein (CRP), and Procalcitonin (PCT) as well as catecholamine support, and volume requirement were compared between both groups. Operative procedures included aortic (n = 7), mitral (n = 6), and multiple valve surgery (n = 7). All patients survived to discharge. No significant differences concerning median cytokine levels (IL-6 and TNF-α) were observed between both groups. CRP and PCT baseline levels were significantly higher in the HA group (59.5 vs. 26.3 mg/dL, P = .029 and 0.17 vs. 0.05 µg/L, P = .015) equalizing after surgery. Patients in the HA group required significantly higher doses of vasopressors (0.093 vs. 0.025 µg/kg/min norepinephrine, P = .029) at 12 hours postoperatively as well as significantly more overall volume replacement (7217 vs. 4185 mL at 12 hours, P = .015; 12 021 vs. 4850 mL at 48 hours, P = .015). HA therapy did neither result in a reduction of inflammatory parameters nor result in an improvement of hemodynamic parameters in patients operated for IE. For a more targeted use of HA therapy, appropriate selection criteria are required.

[Deep sternal wound infection after sternotomy - Report of the consensus workshop of the German-Speaking Society for Microsurgery of Peripheral Nerves and Vessels (DAM)]. / Der tiefe sternale Wundinfekt nach Sternotomie.

Deep sternal wound infection (TSWI) is a potentially life-threatening complication that may occur after median sternotomy, contributing to prolonged hospital stay and increased health care costs. Bacterial infection is often characterized by biofilm formation on implant material and/or dead bone. Diagnosis is made upon clinical signs and symptoms of local and systemic infection. Early multidisciplinary decision making is needed for optimal patient care. Repeated surgical wound debridements accompanied by wound conditioning are performed until clean circumstances are achieved. Thereafter, wound closure and defect reconstruction are obtained using a variety of pedicled and microvascular flaps.

Identification of risk factors for renal failure after cardiac surgery by RFILE classification.

OBJECTIVE: Acute kidney injury (AKI) is a major complication after cardiovascular surgery. The unclear etiology of this highly complex event challenges definition, diagnosis and prediction of AKI, and hence hampers adequate patient management. Identification of associated risk factors have the potential to overcome this limitation. METHODS: This retrospective study comprised 3574 patients who underwent cardiac surgery in a hospital in Germany. The patient cohort was interrogated for risk factors for AKI. RESULTS: The analysis identified risk factors for AKI development, such as type of surgery (particularly bypass surgery) (P = 0.02), previous coronary surgeries (P < 0.01), the application of intra-aortic balloon pump in surgery (P < 0.01), and blood loss during surgery (P < 0.01). In addition, old age, duration of surgery as well as ischemia, perfusion and reperfusion times contributed to AKI development (P < 0.01). Further, perioperative hypothermia also appeared as putative risk factor in the analysis (P < 0.01). CONCLUSIONS: This study identified several risk factors for the development of AKI after cardiac surgery. Further validation of these risk factors could allow the implementation of adequate patient management, and the appropriate implementation of risk-adverse interventions in cardiovascular surgery.

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

AIMS: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. METHODS AND RESULTS: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. CONCLUSION: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

Risk assessment of acute kidney injury following cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is a frequent and serious complication of cardiac surgery, associated with a high incidence of morbidity and mortality. Although the RIFLE criteria serve as a prominent tool to identify patients at high risk of AKI, an optimized diagnosis model in clinical practice is desired. METHODS: Based on the SOP-criteria, 365 patients (10%) developed AKI following surgery and were subjected to RRT. In contrast, the incidence of AKI, defined according to the RIFLE criteria, was only 7% (n = 251 patients). Prominent risk factors identified by SOP were patients' sex, valve and combined valve and bypass surgery, deep hypothermia, use of intra-aortic balloon pump (IABP) and previous coronary interventions. Ischemia, reperfusion, blood loss and surgery time also served as significant risk factors for patient evaluated by SOP. RESULTS: Risk assessment by RIFLE differed in as much as most patients with normothermia and those receiving only cardiovascular bypass developed AKI. However, patients' sex and valve surgery did not serve as a risk factor. CONCLUSION: Evaluation of patients by the RIFLE versus SOP criteria yielded different results with more AKI patients detected by SOP. Based on the present data, it is concluded that patients may not prone to AKI when surgery and ischemia time will be kept short, when blood loss is mitigated to a minimum and when surgery is performed under non-hypothermic conditions.