ECMO aggravates platelet GPV shedding and δ-granule deficiency in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation and thrombus formation to exposed matrix proteins via their surface receptors such as glycoprotein (GP)VI or GPIb/V/IX. Recent research has elucidated a regulatory role of the GPV subunit. The cleaved soluble (s)GPV ectodomain was identified to spatio-temporally control fibrin formation through complex formation with thrombin. OBJECTIVES: We aimed to decipher the impact of ECMO on platelet phenotype and function, including the role of GPV and plasmatic sGPV. PATIENTS/METHODS: We recruited 36 patients with ARDS in the wake of coronavirus disease 2019 (COVID-19) pneumonia and performed a longitudinal comparison of platelet phenotype and function in non-ECMO (n=23) versus ECMO (n=13) compared to healthy controls. Patients were assessed at up to three time points (t1=day 1-3; t2=day 4-6; t3=day 7-14 after cannulation/study inclusion). RESULTS: Agonist-induced platelet activation was assessed by flow cytometry and revealed decreased GPIIb/IIIa activation and α-granule release in all ARDS patients. During ECMO treatment, agonist-induced δ-granule release continuously decreased, which was independently confirmed by electron microscopy and associated with a prolonged in vitro bleeding time. GPV expression on the platelet surface markedly decreased in ECMO compared to non-ECMO patients. Plasma sGPV levels were increased in ECMO patients and associated with poor outcome. CONCLUSIONS: Our data demonstrate an ECMO-intrinsic platelet δ-granule deficiency and hemostatic dysfunction beyond the underlying ARDS.

Multiorgan recovery in a cadaver body using mild hypothermic ECMO treatment in a murine model.

BACKGROUND: Transplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4-6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an "out-of-hospital" sudden unexpected death with subsequent "in-hospital" cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin-streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V-A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia-reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem. RESULTS: BGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from < 6.5 to 7.3 ± 0.05, pCO2 was lowered from > 130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6%, - 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p < 0.05). A substantial decrease in hyperlactatemia (from > 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice. CONCLUSIONS: Thus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma.

The completeness of the left atrial appendage amputation during routine cardiac surgery.

BACKGROUND: Left atrial appendage (LAA) is the origin of most heart thrombi which can lead to stroke or other cerebrovascular event in patients with non-valvular atrial fibrillation (AF). This study aimed to prove safety and low complication rate of surgical LAA amputation using cut and sew technique with control of its effectiveness. METHODS: 303 patients who have undergone selective LAA amputation were enrolled in the study in a period from 10/17 to 08/20. The LAA amputation was performed concomitant to routine cardiac surgery on cardiopulmonary bypass with cardiac arrest with or without previous history of AF. The operative and clinical data were evaluated. Extent of LAA amputation was examined intraoperatively by transoesophageal echocardiography (TEE). Six months in follow up, the patients were controlled regarding clinical status and episodes of strokes. RESULTS: Average age of study population was 69.9 ± 19.2 and 81.9% of patients were male. In only three patients was residual stump after LAA amputation larger than 1 cm with average stump size 0.28 ± 0.34 cm. 3 patients (1%) developed postoperative bleeding. Postoperatively 77 (25.4%) patients developed postoperative AF (POAF), of which 29 (9.6%) still had AF at discharge. On 6 months follow up only 5 patients had NYHA class III and 1 NYHA class IV. Seven patients reported with leg oedema and no patient experienced any cerebrovascular event in early postoperative follow up. CONCLUSION: LAA amputation can be performed safely and completely leaving minimal to no LAA residual stump.

Benefits of Intra-Aortic Balloon Pump Support in Patients with Postcardiotomy Shock Requiring Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: The benefit of the combined use of an intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO) for postcardiotomy shock remains unclear. We aimed to analyse the potential benefits and safety of combining these two devices. METHODS: We enrolled 200 patients treated with either VA-ECMO only or in combination with IABP (ECMO-I group) between January 2012 and January 2021. To adjust the patients' backgrounds, we used propensity score matching for additional analyses, resulting in 57 pairs. The primary endpoint was 30-day survival. Secondary endpoints included successful weaning and complication rates. We also analysed hemodynamic parameters in both groups. RESULTS: After propensity score matching, 30-day survival was better in the ECMO-I group (log-rank p = 0.004). The ECMO-I and ECMO-only groups differed regarding the secondary endpoints, including successful weaning (50.9% and 26.3%, respectively; p = 0.012) and the need for continuous renal replacement therapy (28.1% and 50.9%, p = 0.021). Complication rates were not statistically different between the two groups. CONCLUSION: Compared to VA-ECMO alone, the combined use of VA-ECMO and IABP is beneficial regarding 30-day survival in selected patients with postcardiotomy shock; successful ECMO weaning and freedom from renal replacement therapy is more common in patients supported with VA-ECMO plus IABP.

Wearable cardioverter defibrillator multicentre experience in a large cardiac surgery cohort at transient risk of sudden cardiac death.

OBJECTIVES: The wearable cardioverter defibrillator (WCD) is an established, safe, effective solution, protecting patients at risk of sudden cardiac death. We specifically investigated WCD use in cardiac surgery patients since data for this patient group are rare. METHODS: Retrospective data analysis in 10 German cardiac surgery centres was performed. Cardiac surgery patients with left ventricular ejection fraction (LVEF) ≤35% or after implantable cardioverter defibrillator (ICD) explantation who received WCD between 2010 and 2020 were assessed using LifeVest Network data. RESULTS: A total of 1168 patients with a median age of 66 years [interquartile range (IQR) 57-73] were enrolled; 87% were male. Clinical indications included coronary artery bypass grafting (43%), valve surgery (16%), combined coronary artery bypass graft/valve surgery (15%), ICD explantation (24%) and miscellaneous (2%). The median wear time of WCD was 23.4 h/day (IQR 21.7-23.8). A total of 106 patients (9.1%) exhibited ventricular tachycardia. A total of 93.2% of episodes occurred within the first 3 months. Eighteen patients (1.5%) received 26 adequate shocks. The inadequate shock rate was low (8 patients, 0.7%). LVEF improved from a median of 28% (IQR 22-32%) before WCD prescription to 35% (IQR 28-42%) during follow-up. Excluding ICD explant patients, 37% of patients received an ICD. CONCLUSIONS: The risk of sudden cardiac death is substantial within the first 3 months after cardiac surgery. Patients were protected effectively by WCD. Due to significant LVEF improvement, the majority did not require ICD implantation after WCD use. Compliance was high despite sternotomy. This multicentre experience confirms existing data regarding effectiveness, safety and compliance. Therefore, WCD should be considered in cardiac surgery patients with severely reduced LVEF.

Decellularized Pulmonary Xenograft Matrix PplusN versus Cryopreserved Homograft for RVOT Reconstruction during Ross Procedure in Adults.

BACKGROUND: Decellularized pulmonary homografts are being increasingly adopted for right ventricular outflow tract reconstruction in adult patients undergoing the Ross procedure. Few reports presented Matrix PplusN xenograft (Matrix) in a negative light. The objective of this study was to compare our midterm outcomes of Matrix xenograft versus standard cryopreserved pulmonary homograft (CPHG). METHODS: Eighteen patients received Matrix xenograft between January 2012 and June 2016, whereas 66 patients received CPHG. Using nonparametric statistical tests and survival analysis, we compared midterm echocardiographic and clinical outcomes between the groups. RESULTS: Except for significant age difference (the Matrix group was significantly older with 57 ± 8 years than the CPHG group, 48 ± 9 years, p = 0.02), the groups were similar in all other baseline characteristics. There were no significant differences in cardiopulmonary bypass times (208.3 ± 32.1 vs. 202.8 ± 34.8) or in cross-clamp times (174 ± 33.9 vs. 184.4 ± 31.1) for Matrix and CPHG, respectively. The Matrix group had significantly inferior freedom from reintervention than the CPHG group with 77.8 versus 98.5% (p = 0.02). Freedom from pulmonary valve regurgitation ≥ 2 was not significantly different between the groups with 82.4 versus 90.5% for Matrix versus CPHG, respectively. After median follow-up of 4.9 years, Matrix xenograft developed significantly higher peak pressure gradients compared with CPHG (20.4 ± 15.5 vs. 12.2 ± 9.0 mm Hg; p = 0.04). CONCLUSION: After 5 years of clinical and echocardiographic follow-up, the decellularized Matrix xenograft had inferior freedom from reintervention compared with the standard CPHG. Closer follow-up is necessary to avoid progression of valve failure into right ventricular deterioration.

Functional versus morphological assessment of vascular age in patients with coronary heart disease.

Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VAPWVao in 68% of patients; for VAAIao in 52% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VAtotal-cIMT accelerated vascular aging in 75% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.

Impact of pre-existing comorbidities on outcomes of patients undergoing surgical aortic valve replacement - rationale and design of the international IMPACT registry.

BACKGROUND: Degenerative aortic valve disease accounts for 10-20% of all cardiac surgical procedures. The impact of pre-existing comorbidities on the outcome of patients undergoing surgical aortic valve replacement (SAVR) needs further research. METHODS: The IMPACT registry is a non-interventional, prospective, open-label, multicenter, international registry with a follow-up of 5 years to assess the impact of pre-existing comorbidities of patients undergoing SAVR with the INSPIRIS RESILIA aortic valve on outcomes. IMPACT will be conducted across 25 sites in Austria, Germany, The Netherlands and Switzerland and intends to enroll approximately 500 patients. Patients will be included if they are at least 18 years of age and are scheduled to undergo SAVR with the INSPIRIS RESILIA Aortic Valve with or without concomitant ascending aortic root replacement and/or coronary bypass surgery. The primary objective is to determine all-cause mortality at 1, 3, and 5 years post SAVR. Secondary objectives include cardiac-related and valve-related mortality and structural valve deterioration including hemodynamics and durability, valve performance and further clinical outcomes in the overall study population and in specific patient subgroups characterized by the presence of chronic kidney disease, hypertension, metabolic syndrome and/or chronic inflammation. DISCUSSION: IMPACT is a prospective, multicenter European registry, which will provide much-needed data on the impact of pre-existing comorbidities on patient outcomes and prosthetic valve performance, and in particular the performance of the INSPIRIS RESILIA, in a real-world setting. The findings of this study may help to support and expand appropriate patient selection for treatment with bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04053088 .

Physicians' lifestyle advice on primary and secondary cardiovascular disease prevention in Germany: A comparison between the STAAB cohort study and the German subset of EUROASPIRE IV.

BACKGROUND: We assessed prevalence and determinants in appropriate physician-led lifestyle advice (PLA) in a population-based sample of individuals without cardiovascular disease (CVD) compared with a sample of CVD patients. METHODS: PLA was assessed via questionnaire in a subsample of the population-based Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort free of CVD (primary prevention sample) and the German subset of the fourth EUROASPIRE survey (EUROASPIRE-IV) comprising CVD patients (secondary prevention sample). PLA was fulfilled if the participant reported having ever been told by a physician to: stop smoking (current/former smokers), reduce weight (overweight/obese participants), increase physical activity (physically inactive participants) or keep to a healthy diet (all participants). Factors associated with receiving at least 50% of the PLA were identified using logistic regression. RESULTS: Information on PLA was available in 665 STAAB participants (55 ± 11; 55% females) and in 536 EUROASPIRE-IV patients (67 ± 9; 18% females). Except for smoking, appropriate PLA was more frequently given in the secondary compared with the primary prevention sample. Determinants associated with appropriate PLA in primary prevention were: diabetes mellitus (odds ratio (OR) 4.54; 95% confidence interval (CI) 1.88-10.95), hyperlipidaemia (OR 3.12; 95% CI 2.06-4.73) and hypertension (OR 1.74; 95% CI 1.15-2.62); in secondary prevention: age (OR per year 0.96; 95% CI 0.93-0.98) and diabetes mellitus (OR 2.33; 95% CI 1.20-4.54). CONCLUSIONS: In primary prevention, PLA was mainly determined by the presence of vascular risk factors, whereas in secondary prevention the level of PLA was higher in general, but the association between CVD risk factors and PLA was less pronounced.

Central Versus Peripheral Arterial Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation in Post-Cardiotomy Patients.

Different arterial cannulation strategies are feasible for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in postcardiotomy shock. We aimed to analyze potential benefits and safety of different arterial cannulation strategies. We identified 158 patients with postcardiotomy cardiogenic shock requiring VA-ECMO between 01/10 and 01/19. Eighty-eight patients were cannulated via axillary or femoral artery (group P), and 70 centrally via the ascending aorta directly or through an 8 mm vascular graft anastomosed to the ascending aorta (group C). Demographics and operative parameters were similar. Change of cannulation site for Harlequin's syndrome or hyperperfusion of an extremity occurred in 13 patients in group P but never in group C (p = 0.001). Surgical revision of cannulation site was also encountered more often in group P than C. The need for left ventricular (LV) unloading was similar between groups, whereas surgical venting was more often implemented in group C (11.4% vs. 2.3, p = 0.023). Stroke rates, renal failure, and peripheral ischemia were similar. Weaning rate from ECMO (52.9% vs. 52.3%, p = NS) was similar. The 30 day mortality was higher in group P (60% vs. 76.1%, p = 0.029). Central cannulation for VA-ECMO provides antegrade flow without Harlequin's syndrome, changes of arterial cannula site, and better 30 day survival. Complication rates regarding need for reexploration and transfusion requirements were similar.

First clinical experience with the novel cold storage SherpaPak™ system for donor heart transportation.

BACKGROUND: The current gold standard for donor heart preservation is a three-bag-technique and storage in a cooler filled with slush ice. This technique can cause freezing injury with protein denaturation. We report our early experience with a single-use disposable device (SherpaPak™, Paragonix Technologies, MA, USA) specifically designed for sterile permanent temperature-controlled transportation of donor hearts. METHODS: In this case control study with 2:1 matching we identified 21 patients after heart transplantation depending on type of organ transport (standard three-bag-technique vs. SherpaPak™). The outcome after donor heart storage in the SherpaPak™ was compared with donor heart transportation with the standard technique. RESULTS: Since July 2018 seven patients (5 males; mean age 50.3±13.2years) underwent heart transplantation with the SherpaPak™ system. Cold ischemic time was longer in the SherpaPak™ group (207.7±23.3 vs. 181.6±21.9, P=0.027). SherpaPak™ kept the organ temperature at 5.1±0.8 °C, with an average outside temperature of 21.4±3.6 °C. Among all 21 transplanted patients four developed fatal early graft failure (28.6% vs. 21.4%, P=0.432). Over the first hours we noticed no difference in hemodynamic parameters, CK-MB levels or vasoactive-inotropic score. During first follow-up we noticed slightly better right heart function in the SherpaPak™ group (TAPSE 17.83±2.71 vs. 14.52±2.61 mm, P=0.020). We identified no positive blood cultures in the SherpaPak™ group within the first 30 days after heart transplantation. CONCLUSIONS: The SherpaPak™ provides a constant temperature during transportation with permanent monitoring, never dropping below 4 °C. Organs transported with this novel device showed a normal perioperative function.

Atrial contractility and fibrotic biomarkers are associated with atrial fibrillation after elective coronary artery bypass grafting.

OBJECTIVE: New-onset postoperative atrial fibrillation is common after cardiac surgery. Less has been reported about the relationship among fibrosis, inflammation, calcium-induced left atrial and right atrial contractile forces, and postoperative atrial fibrillation. We sought to identify predictors of postoperative atrial fibrillation. METHODS: From August 2016 to February 2018, we evaluated 229 patients who had preoperative sinus rhythm before elective primary coronary artery bypass grafting. Of 229 patients, 191 maintained sinus rhythm postoperatively, whereas 38 patients developed atrial fibrillation. Preoperative tissue inhibitor of metalloproteinase-1, pentraxin-3, matrix metallopeptidase-9, galectin-3, high-sensitivity C-reactive protein, growth differentiation factor 15, and transforming growth factor-ß were measured. Clinical and echocardiographic findings (tricuspid annular plane systolic excursion for right heart function) and calcium-induced force measurements from left atrial and right atrial-derived skinned myocardial fibers were recorded. RESULTS: Patients with atrial fibrillation were older (P = .001), had enlarged left atrial (P = .0001) and right atrial areas (P = .0001), and had decreased tricuspid annular plane systolic excursion (P = .001). Levels of matrix metallopeptidase-9 and pentraxin-3 were decreased (P < .05), whereas growth differentiation factor 15 was increased (P = .001). We detected lower left atrial force values at calcium-induced force measurements 5.5 (P < .05), 5.4 (P < .01), and 5.3 to 4.52 (P = .0001) and right atrial force values at calcium-induced force measurements 5.0 to 4.52 (P < .05) in patients with postoperative atrial fibrillation. Multivariable analysis showed that advanced age (P = .033), decreased left atrial force value at calcium-induced force measurement of 5.5 (P = .033), enlarged left atrial (P = .013) and right atrial (P = .081) areas, and reduced tricuspid annular plane systolic excursion (P = .010) independently predicted postoperative atrial fibrillation. CONCLUSIONS: Advanced age, decreased left atrial force value at calcium-induced force measurement of 5.5, enlarged left atrial and right atrial areas, and reduced tricuspid annular plane systolic excursion were identified as independent predictors for postoperative atrial fibrillation.

Ischemia time impacts on respiratory chain functions and Ca2+-handling of cardiac subsarcolemmal mitochondria subjected to ischemia reperfusion injury.

BACKGROUND: Mitochondrial impairment can result from myocardial ischemia reperfusion injury (IR). Despite cardioplegic arrest, IR-associated cardiodepression is a major problem in heart surgery. We determined the effect of increasing ischemia time on the respiratory chain (RC) function, the inner membrane polarization and Ca2+ homeostasis of rat cardiac subsarcolemmal mitochondria (SSM). METHODS: Wistar rat hearts were divided into 4 groups of stop-flow induced warm global IR using a pressure-controlled Langendorff system: 0, 15, 30 and 40 min of ischemia with 30 min of reperfusion, respectively. Myocardial contractility was determined from left ventricular pressure records (dP/dt, dPmax) with an intraventricular balloon. Following reperfusion, SSM were isolated and analyzed regarding electron transport chain (ETC) coupling by polarography (Clark-Type electrode), membrane polarization (JC1 fluorescence) and Ca2+-handling in terms of Ca2+-induced swelling and Ca2+-uptake/release (Calcium Green-5 N® fluorescence). RESULTS: LV contractility and systolic pressure during reperfusion were impaired by increasing ischemic times. Ischemia reduced ETC oxygen consumption in IR40/30 compared to IR0/30 at complex I-V (8.1 ± 1.2 vs. 18.2 ± 2.0 nmol/min) and II-IV/V (16.4 ± 2.6/14.8 ± 2.3 vs. 2.3 ± 0.6 nmol/min) in state 3 respiration (p < 0.01). Relative membrane potential revealed a distinct hyperpolarization in IR30/30 and IR40/30 (171.5 ± 17.4% and 170.9 ± 13.5%) compared to IR0/30 (p < 0.01), wearing off swiftly after CCCP-induced uncoupling. Excess mitochondrial permeability transition pore (mPTP)-gated Ca2+-induced swelling was recorded in all groups and was most pronounced in IR40/30. Pyruvate addition for mPTP blocking strongly reduced SSM swelling in IR40/30 (relative AUC, ± pyruvate; IR0/30: 1.00 vs. 0.61, IR15/30: 1.68 vs. 1.00, IR30/30: 1.42 vs. 0.75, IR40/30: 1.97 vs. 0.85; p < 0.01). Ca2+-uptake remained unaffected by previous IR. Though Ca2+-release was delayed for ≥30 min of ischemia (p < 0.01), Ca2+ retention was highest in IR15/30 (RFU; IR0/30: 6.3 ± 3.6, IR 15/30 42.9 ± 5.0, IR30/30 15.9 ± 3.8, IR40/30 11.5 ± 6.6; p ≤ 0.01 for IR15/30 against all other groups). CONCLUSIONS: Ischemia prolongation in IR injury gradually impaired SSM in terms of respiratory chain function and Ca2+-homeostasis. Membrane hyperpolarization appears to be responsible for impaired Ca2+-cycling and ETC function. Ischemia time should be considered an important factor influencing IR experimental data on subsarcolemmal mitochondria. Periods of warm global ischemia should be minimized during cardiac surgery to avoid excessive damage to SSMs.

HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI. PATIENTS AND METHODS: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated. RESULTS: AKI with an incidence of 23.3% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219). CONCLUSION: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.

Myocardial Fibrosis Predicts 10-Year Survival in Patients Undergoing Aortic Valve Replacement.

Background Long-term data on evolution and clinical impact of myocardial fibrosis in valvular heart disease are scarce. Methods and Results In this 10 years' extension of a prospective study in patients undergoing conventional aortic valve replacement because of symptomatic severe aortic valve stenosis, the impact of myocardial replacement fibrosis (MRF) on long-term outcome was assessed. Endomyocardial biopsies were acquired during aortic valve replacement in 58 consecutive patients. MRF was graded using the calculated percentage area of fibrosis and patients categorized as severe (n=21), mild (n=15), and no fibrosis (n=22). Echocardiography including strain imaging, as well as cardiovascular magnetic resonance, to assess late gadolinium enhancement was performed at baseline, 1, and 10 years after aortic valve replacement. Death of any cause occurred in 21 patients (38.9%): 3 (14.3%) in the group without MRF, 6 (42.9%) in the mild MRF group, and 12 (63.2%) in the severe MRF group ( P=0.006), resulting in the lowest cumulative survival for patients with severe MRF (log-rank P=0.003). In the group without MRF, none died of cardiovascular cause. MRF was found to be an independent predictor of survival (hazard ratio, 1.271; 95% CI, 1.032-1.564; P=0.024). Conclusions This 10-year follow-up study underlines the profound impact of replacement fibrosis with regard to cardiac and all-cause mortality in patients undergoing aortic valve replacement for severe aortic valve stenosis. Integrating cardiovascular magnetic resonance and echocardiographic functional imaging beyond ejection fraction quantification could help in clinical decision making to stratify patient prognosis with regard to myocardial longitudinal function and prevalence of replacement fibrosis.

Impact of diabetes mellitus on the contractile properties of the left and right atrial myofilaments.

OBJECTIVES: The incidence of diabetes mellitus in patients with ischaemic cardiomyopathy is increasing. To evaluate the impact of diabetes mellitus on contractility, we examined the calcium-induced force in left and right atrial myofilaments of patients with and without diabetes. METHODS: We included 149 patients (106 without diabetes, 43 with diabetes), scheduled for elective coronary artery bypass grafting from August 2016 to June 2017. The left and right atria were excised and prepared for skinned fibre measurements (pCa-force curve). The unit for the force measurements is Millinewton (mN). Comprehensive demographic data as well as echocardiographic findings of the patients were collected. RESULTS: We observed a significant decrease of left atrial force values in patients with diabetes, averaged over all calcium concentrations (patients with diabetes 0.50 ± 0.19 mN vs 0.68 ± 0.23 mN in patients without diabetes, P = 0.002) as well as in right atrial fibres (patients with diabetes 0.35 ± 0.17 mN vs 0.47 ± 0.21 mN in patients without diabetes, P = 0.005). There was a significant influence of repeated measurements (of the calcium concentrations) on force in left atrial myofilaments (P < 0.001). There was also a significant impact of diabetes on the force values of the different calcium concentrations in left atrial myofilaments (P 0.002). In right atrial myofilaments we also found a significant influence of repeated measurements (of the calcium concentrations) on force (P < 0.001). Additionally the impact of diabetes on the force values was significant (P = 0.005). CONCLUSIONS: We demonstrated that diabetes mellitus has a significantly negative impact on calcium-induced force development in left and right atrial myofilaments.

The COMT-polymorphism is not associated with the incidence of acute kidney injury after cardiac surgery - a prospective cohort study.

BACKGROUND: The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies suggest that the COMT rs4680 polymorphism is associated with the response to endogenous and exogenous catecholamines. There are, however, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. The aim of the current study is to prospectively investigate the impact of the COMT rs4680 polymorphism on the incidence of AKI in patients undergoing cardiac surgery. METHODS: In this prospective single center cohort study consecutive patients hospitalized for elective cardiac surgery including cardiopulmonary-bypass (CPB) were screened for participation. Demographic clinical data, blood, urine and tissue samples were collected at predefined time points throughout the clinical stay. AKI was defined according to recent recommendations of the Kidney Disease Improving Global Outcome (KDIGO) group. Genetic analysis was performed after patient enrolment was completed. RESULTS: Between April and December 2014, 150 patients were recruited. The COMT genotypes were distributed as follows: Val/Met 48.7%, Met/Met 29.3%, Val/Val 21.3%. No significant differences were found for demography, comorbidities, or operative strategy according to the underlying COMT genotype. AKI occurred in 35 patients (23.5%) of the total cohort, and no differences were evident between the COMT genotypes (20.5% Met/Met, 24.7% Val/Met, 25.0% Val/Val, p = 0.66). There were also no differences in the post-operative period, including ICU or in-hospital stay. CONCLUSIONS: We did not find statistically significant variations in the risk for postoperative AKI, length of ICU or in-hospital stay according to the underlying COMT genotype.

Venovenous extracorporeal membrane oxygenation for the management of contralateral iatrogenic bronchus perforation during lower bilobectomy.

Tracheobronchial rupture by a double-lumen endobronchial tube is a rare but life-threatening complication. We report a case of bronchial rupture during contralateral bilobectomy. Venovenous extracorporeal membrane oxygenation support was instituted via the right femoral vein and the internal jugular vein with the patient in the left lateral decubitus position. Sleeve resection of the ruptured bronchus was performed. The patient was successfully discharged home. Rapid institution of venovenous extracorporeal membrane oxygenation is helpful to manage this intraoperative complication.

Secondary Prevention in Younger vs. Older Coronary Heart Disease Patients-Insights from the German Subset of the EUROASPIRE IV Survey.

PURPOSE: Evidence is limited on implementation of secondary prevention guidelines for coronary heart disease (CHD) in clinical practice and variations between younger and elder patients. We investigated the control of cardiovascular risk factors in German patients with CHD enrolled in the European-wide EUROASPIRE IV survey, stratified by younger (18-69 years) and older (70-79 years) age groups. METHOD: Eligible subjects were identified via the hospitals' patient information system and invited to attend a study visit 6 months to 3 years after hospitalization for CHD (myocardial infarction, ischemia, angioplasty/stent, coronary bypass grafting). Information on lifestyle and medication was collected by interview. RESULTS: Five hundred thirty-six patients were recruited in 2012-2013 (median age 69 years [IQR 62-74 years], 18% female, 44% ≥ 70 years of age, median time between index hospitalization and study visit 1.8 [1.1-2.5] years). Proportion of CHD patients receiving recommended drug therapy was 89% for platelet inhibitors (younger vs. older patients 93 vs. 84%, p < 0.01), 83% for statins (83 vs. 85%, p = 0.9), and 83% for beta-blockers (87 vs. 79%, p = 0.02). Uncontrolled blood pressure was observed in 45% (40 vs. 50%, p = 0.02), LDL cholesterol levels > 2.5 mmol/l in 53% (56 vs. 49%, p = 0.1), and HbA1c levels > 7% in diabetic patients in 39% (45 vs. 32%, p = 0.1). Eighty-five percent were overweight (86 vs. 85%, p = 0.8), 37% were obese (41 vs. 31%, p = 0.01), and 10% reported currently smoking (17 vs. 3%, p < 0.01). CONCLUSION: Although most CHD patients received the drug classes recommended by guidelines, treatment goals were frequently not achieved. Elderly subjects had a less favorable pattern, which may reflect multi-morbidity and weaker identification with treatment targets. National CHD prevention strategies should focus not only on enhancing lifestyle modifications and reaching treatment targets, but also on highlighting the different needs in older individuals.