ABSTRACT
Rupture or dissection of thoracic aortic aneurysms is still the leading cause of death for patients diagnosed with Marfan syndrome. Inflammation and matrix digestion regulated by matrix metalloproteases (MMPs) play a major role in the pathological remodeling of the aortic media. Regnase-1 is an endoribonuclease shown to cleave the mRNA of proinflammatory cytokines, such as interleukin-6. Considering the major anti-inflammatory effects of regnase-1, here, we aimed to determine whether adeno-associated virus (AAV)-mediated vascular overexpression of the protein could provide protection from the development and progression of aortic aneurysms in Marfan syndrome. The overexpression of regnase-1 resulted in a marked decrease in inflammatory parameters and elastin degradation in aortic smooth muscle cells in vitro. Intravenous injection of a vascular-targeted AAV vector resulted in the efficient transduction of the aortic wall and overexpression of regnase-1 in a murine model of Marfan syndrome, associated with lower circulating levels of proinflammatory cytokines and decreased MMP expression and activity. Regnase-1 overexpression strongly improved elastin architecture in the media and reduced aortic diameter at distinct locations. Therefore, AAV-mediated regnase-1 overexpression may represent a novel gene therapy approach for inhibiting aortic aneurysms in Marfan syndrome.
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Introduction: Unilateral pulmonary edema (UPE) is a potential complication after mitral valve surgery (MVS), and its cause is not yet fully understood. Definitions are inconsistent, and previous studies have reported wide variance in the incidence of UPE. This research aims at the evaluation of the Radiographic Assessment of Lung Edema (RALE) score concerning assessment of UPE after MVS in order to provide an accurate and consistent definition of this pathology. Methods and Results: Postoperative chest X-ray images of 676 patients after MVS (minimally invasive MVS, n = 434; conventional MVS, n = 242) were retrospectively analyzed concerning presence of UPE. UPE was diagnosed only after exclusion of other pathologies up until the eighth postoperative day. RALE values were calculated for each patient. ROC analysis was performed to assess diagnostic performance. UPE was diagnosed in 18 patients (2.8%). UPE occurred significantly more often in the MI-MVS group (p = 0.045; MI-MVS n = 15; C-MVS n = 3). Postoperative RALE values for the right hemithorax (Q1 + Q2) > 12 and the right-to-left RALE difference ((Q1 + Q2) - (Q3 + Q4)) > 13 provide a sensitivity of up to 100% and 94.4% and a specificity of up to 88.4% and 94.2% for UPE detection. Conclusion: The RALE score is a practical tool for assessment of chest X-ray images after MVS with regard to UPE and provides a clear definition of UPE. In addition, it enables objective comparability when assessing of the postoperative course. The given score thresholds provide a sensitivity and specificity of up to 94%. Further, UPE after MVS seems to be a rather rare pathology with an incidence of 2.6%.
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BACKGROUND: Acute type A aortic dissection (AAAD) has high mortality. Improvements in surgical technique have lowered mortality but postoperative functional status and decreased quality of life due to debilitating deficits remain of concern. Our study aims to identify preoperative conditions predictive of undesirable outcome to help guide perioperative management. METHODS: We performed retrospective analysis of 394 cases of AAAD who underwent repair in our institution between 2001 and 2018. A combined endpoint of parameters was defined as (1) 30-day versus hospital mortality, (2) new neurological deficit, (3) new acute renal insufficiency requiring postoperative renal replacement, and (4) prolonged mechanical ventilation with need for tracheostomy. RESULTS: Total survival/ follow-up time averaged 3.2 years with follow-up completeness of 94%. Endpoint was reached by 52.8%. Those had higher EuroSCORE II (7.5 versus 5.5), higher incidence of coronary artery disease (CAD) (9.2% versus 3.2%), neurological deficit (ND) upon presentation (26.4% versus 11.8%), cardiopulmonary resuscitation (CPR) (14.4% versus 1.6%) and intubation (RF) before surgery (16.9% versus 4.8%). 7-day mortality was 21.6% versus 0%. Hospital mortality 30.8% versus 0%. CONCLUSIONS: This 15-year follow up shows, that unfavorable postoperative clinical outcome is related to ND, CAD, CPR and RF on arrival.
ABSTRACT
BACKGROUND: Chronic kidney disease as well as acute kidney injury are associated with adverse outcomes after transcatheter aortic valve replacement (TAVR). However, little is known about the prognostic implications of an improvement in renal function after TAVR. METHODS: Renal improvement (RI) was defined as a decrease in postprocedural creatinine in µmol/l of ≥1% compared to its preprocedural baseline value. A propensity score representing the likelihood of RI was calculated to define patient groups which were comparable regarding potential confounders (age, sex, BMI, NYHA classification, STS score, log. EuroSCORE, history of atrial fibrillation/atrial flutter, pulmonary disease, previous stroke, CRP, creatinine, hsTNT and NT-proBNP). The cohort was stratified into 5 quintiles according to this propensity score and the survival time after TAVR was compared within each subgroup. RESULTS: Patients in quintile 5 (n = 93) had the highest likelihood for RI. They were characterized by higher creatinine, lower eGFR, higher NYHA class, higher NT-proBNP, being mostly female and having shorter overall survival time. Within quintile 5, patients without RI had significantly shorter survival compared to patients with RI (p = 0.002, HR = 0.32, 95% CI = [0.15-0.69]). There was no survival time difference between patients with and without RI in the whole cohort (p = 0.12) and in quintiles 1 to 4 (all p > 0.16). Analyses of specific subgroups showed that among patients with NYHA class IV, those with RI also had a significant survival time benefit (p < 0.001, HR = 0.15; 95%-CI = [0.05-0.44]) compared to patients without RI. CONCLUSIONS: We here describe a propensity score-derived specific subgroup of patients in which RI after TAVR correlated with a significant survival benefit.
Subject(s)
Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/surgery , Cardio-Renal Syndrome/physiopathology , Kidney/physiopathology , Transcatheter Aortic Valve Replacement , Aged , Aged, 80 and over , Aortic Valve Stenosis/mortality , Cardio-Renal Syndrome/mortality , Cohort Studies , Female , Humans , Male , Propensity Score , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: The purpose of this study was to investigate whether age has an effect on short and long-term outcome in patients who undergo simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy. METHODS: From 2005 to 2017, 186 consecutive elective patients underwent CABG and synchronous endarterectomy at our institution. Patients were retrospectively classified according to age into 2 groups: patients above 70 years (elderly group: n = 97, 76.1 ± 3.9 years) and patients below 70 years (younger group: n = 89, 63.2 ± 4.8 years). RESULTS: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, 4.4% vs. 2.5%; p < 0.001) and Society of Thoracic Surgeons (STS) score (0.7% vs. 1.6%; p < 0.001) were significantly higher in the elderly group. Otherwise, there was no difference between the two groups concerning important preoperative risk factors or the intraoperative data. Postoperatively, the incidence of temporary dialysis was significantly higher in the elderly group (14.4% vs. 3.4%; p = 0.009). The rate of tracheotomy (16.5% vs. 2.2%; p = 0.001), of re-intubation (7.9% vs. 18.6%; p = 0.033) and drainage loss (600 ml vs. 800 ml; p = 0.035) was significantly higher in this elderly group. Neurological complications and 30-day mortality were comparable. Long-term survival was satisfactory for both groups. Nevertheless, 5-year survival rates (63% vs. 85%) were significantly lower in the elderly group (p = 0.003). Logistic regression analysis identified chronic obstructive pulmonary disease (COPD) and arrhythmia as significant risk factors for 30-day-mortality, but not age. CONCLUSIONS: CABG in combination with synchronous endarterectomy can also be performed with satisfactory results in elderly patients.
Subject(s)
Coronary Artery Bypass/mortality , Endarterectomy, Carotid/mortality , Age Factors , Aged , Arrhythmias, Cardiac/etiology , Female , Germany , Humans , Male , Middle Aged , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Survival Rate , Treatment OutcomeABSTRACT
OBJECTIVES: Meta-analyses from observational and randomized studies have demonstrated benefits of off-pump surgery for hard and surrogate endpoints. In some of them, increased re-revascularization was noted in the off-pump groups, which could impact their long-term survival. Therefore, we analyzed the course of all patients undergoing isolated coronary surgery regarding the major cardiac and cerebrovascular event (MACCE) criteria. METHODS: A prospective register was taken from a high-volume off-pump center recording all anaortic off-pump (ANA), clampless off-pump (PAS-Port) and conventional (CONV) coronary artery bypass operations between July 2009 and June 2015. Propensity Score Matching was performed based on 28 preoperative risk variables. RESULTS: We identified 935 triplets (N = 2805). Compared with CONV, in-hospital mortality of both the ANA group (OR for ANA [95% CI] 0.25 [0.06; 0.83], P = 0.021), and the PAS-Port group was lower (OR for PAS-Port [95% CI] 0.50 [0.17; 1.32], P = 0.17). In the mid-term follow-up there were no significant differences between the groups regarding mortality (HR for ANA [95%-CI] 0.83 [0.55-1.26], P = 0.38; HR for PAS-Port [95%-CI] 1.06 [0.70-1.59], P = 0.79), incidence of stroke (HR for ANA 0.81 [0.43-1.53], P = 0.52; HR for PAS-Port 0.78 [0.41-1.50], P = 0.46), myocardial infarction (HR for ANA 0.53 [0.22-1.31], P = 0.17; HR for PAS-Port 0.78 [0.37-1.66], P = 0.52) or re-revascularization rate (HR for ANA 0.99 [0.67-1.44], P = 0.94; HR for PAS-Port 0.95 [0.65-1.38], P = 0.77). CONCLUSIONS: Both off-pump clampless techniques were associated with lower in-hospital mortality compared with conventional CABG. The mid-term course showed no difference with regard to the MACCE criteria between anaortic off-pump, clampless off-pump using PAS-Port and conventional CABG.
Subject(s)
Coronary Artery Bypass, Off-Pump/instrumentation , Coronary Artery Bypass/instrumentation , Coronary Artery Disease/surgery , Postoperative Complications/epidemiology , Propensity Score , Registries , Aged , Coronary Artery Disease/mortality , Follow-Up Studies , Germany/epidemiology , Hospital Mortality/trends , Humans , Incidence , Middle Aged , Prospective Studies , Risk Factors , Treatment OutcomeABSTRACT
Atrial fibrillation (AF) may increase the risk of thromboembolic (TE) complications in patients with left ventricular assist devices (LVADs). In a single-center study, we investigated 205 patients with sinus rhythm (SR group) and 117 patients with AF (AF group). Our main read outs were 2 year overall survival (primary end point), perioperative right heart failure (RHF), and 2 year freedom from stroke, pump thrombosis, and gastrointestinal bleeding (secondary end points). Oral anticoagulation was performed with phenprocoumon (international normalized ratio target range: 2.3-2.8) and aspirin (100 mg/day). Propensity score (PS) adjustment was used for statistical analysis. Two year survival was 65.4% (n = 134) in the SR group and 51.3% (n = 60) in the AF group. The PS-adjusted hazard ratio (HR) of 2 year mortality was higher in the AF group than in the SR group (HR = 1.48 [95% confidence interval (CI): 1.02-2.15; p = 0.038]). Right heart failure was a more frequent cause of death in the AF group than in the SR group (p = 0.008). The PS-adjusted odds ratio of perioperative RHF was for the AF group (reference: SR group) 1.32 (95% CI: 0.80-2.18; p = 0.280). The PS-adjusted 2 year HRs of TE and bleeding events were comparable between both groups and were for stroke, pump thrombosis, and gastrointestinal bleeding (reference: SR group) 0.90 (95% CI: 0.53-1.55; p = 0.714), 0.76 (95% CI: 0.14-4.31; p = 0.639), and 1.01 (95% CI: 0.60-1.70; p = 0.978), respectively. Our data indicate that AF increases midterm mortality, but does not influence the risk of stroke, pump thrombosis, and gastrointestinal bleeding. The higher midterm mortality in AF patients is most likely disease-related and should have no influence on LVAD implantation.
Subject(s)
Atrial Fibrillation/complications , Heart-Assist Devices/adverse effects , Adult , Aged , Female , Gastrointestinal Hemorrhage/etiology , Heart Failure/therapy , Humans , Male , Middle Aged , Propensity Score , Stroke/etiologyABSTRACT
BACKGROUND: Coronary artery bypass grafting (CABG) is a well-established procedure for treating diabetic patients with multivessel disease, but extracorporeal circulation and cardioplegia-induced cardiac arrest introduce a severe burden to these patients. The present study investigated if off-pump CABG decreases 30-day mortality and mid-term mortality in diabetic patients in comparison with conventional CABG. METHODS: From February 2009 through October 2011, data from 355 consecutive adult diabetic patients undergoing off-pump CABG and 502 patients undergoing on-pump CABG were prospectively recorded. Data analysis was performed by propensity score (PS)-adjusted logistic regression analysis and PS-adjusted Cox regression analysis. The primary endpoint was 30-day mortality. Secondary endpoints were major complications and mortality on follow-up. RESULTS: Off-pump CABG was associated with a significantly lower 30-day mortality rate (0.3% vs 4.2%; adjusted odds ratio [OR] = 0.09 [95% confidence interval (CI):0.01 to 0.70] p = 0.021) than on-pump CABG. Results coincided with a lower rate of postoperative neurologic complications in patients undergoing off-pump CABG (1.7% vs 5.4%; adjusted OR = 0.31 [95% CI: 0.12 to 0.77] p = 0.012) and a less frequent need for hemofiltration in these patients (3.4% vs 10.4%; adjusted OR = 0.30 [95% CI: 0.14 to 0.64] p = 0.002). The off-pump technique decreased the 6-month mortality rate (2.3% vs 8.8%; adjusted hazard ratio = 0.27 [95% CI: 0.12 to 0.61] p = 0.002) and also the 1-year mortality rate (4.0% vs 10.6%; adjusted hazard ratio = 0.40 [95% CI: 0.22 to 0.75] p = 0.004) significantly. CONCLUSIONS: Our data indicate that in terms of postoperative complications and early and mid-term survival, off-pump CABG is superior to the on-pump technique in diabetic patients.
Subject(s)
Coronary Artery Bypass, Off-Pump , Coronary Artery Disease/mortality , Coronary Artery Disease/surgery , Diabetic Angiopathies/mortality , Diabetic Angiopathies/surgery , Aged , Cohort Studies , Coronary Artery Bypass/methods , Female , Humans , Male , Middle Aged , Prospective Studies , Survival RateABSTRACT
BACKGROUND: The efficiency of cardiopulmonary resuscitation (CPR) training is dependent upon different influencing factors, such as the presented concepts, the participants' willingness to learn, and the interval between training sessions. However, the optimal interval for refreshing CPR training is less clear. OBJECTIVE: We evaluated the perceived need of simulator-based CPR training for nurses and correlated it with their clinical experience. METHODS: The 60 invited nurses were trained in simulator-based CPR. Knowledge about adult advanced life support was evaluated using a questionnaire after training, and participants rated their desired individual frequency of simulator-based training as well as the value of the presented training using a six-point Likert scale. The same questions were asked again after 1 year. RESULTS: All participants agreed about the usefulness of this type of simulator-based training. The average number of correct answers about typical facts in adult advanced life support showed an almost bell-shaped distribution, with the highest point at 6-15 years of clinical experience and the lowest points at≤5 and≥21 years. The desired training-frequency need was inversely correlated with clinical experience. CONCLUSIONS: There is a high interest in CPR training among nursing staff. Self-assessment about the training-frequency need was inversely correlated with clinical experience. However, the average number of correct answers on resuscitation questions decreased with clinical experience. Therefore, the training effectiveness seems to be extremely dependent on clinical experience, and therefore, training experienced senior nurses might be more challenging than training novice nurses.
Subject(s)
Cardiopulmonary Resuscitation/education , Clinical Competence , Education, Professional, Retraining , Needs Assessment , Nursing Staff, Hospital/education , Adult , Female , Humans , Male , Manikins , Middle Aged , Surveys and Questionnaires , Young AdultABSTRACT
PURPOSE: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is progressively used in severe cardiogenic shock or in-hospital resuscitation to stabilize patients and to bridge to further therapeutic interventions. However, vascular access for coronary catheterization can be difficult under these conditions. It would thus be desirable to use arterial lines that are already inserted. Here, we describe a novel technique to perform coronary angiography and angioplasty in patients with V-A ECMO. METHODS: The technique is described in five patients in whom V-A ECMO was established because of prolonged cardiopulmonary resuscitation and who underwent coronary catheterization after stabilization. At the arterial cannula of the ECMO, a Y connector was inserted. At its free end, a hemostatic valve was placed, over which the coronary catheters were inserted. RESULTS: In one case, diagnostic coronary angiography revealed no significant coronary stenosis. In four other cases, successful coronary angioplasty with and without stent implantation was performed. CONCLUSION: Cardiac catheterization using a Y-shaped adapter introduced into the arterial ECMO cannula is feasible. In a resuscitation setting, a new puncture of the femoral artery always carries the risk of complications, wherefore this new technology can be regarded as fast alternative.
Subject(s)
Cardiac Catheterization/methods , Coronary Angiography , Critical Care , Extracorporeal Membrane Oxygenation/methods , Adult , Aged , Cardiac Catheterization/instrumentation , Cardiopulmonary Resuscitation , Germany , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Pumpless extracorporeal lung assist (PECLA) was developed to support pulmonary function in patients with severe respiratory insufficiency. METHODS: Since 1996, 159 patients with an age ranging from 7 to 78 years were provided with a PECLA system. Fifteen patients were referred to us by air or ground transport after insertion of the system in a peripheral hospital. RESULTS: Main underlying lung diseases were acute respiratory distress syndrome (70.4%) and pneumonia (28.3%). Pumpless extracorporeal lung assist lasted for 0.1 to 33 days, mean 7.0 +/- 6.2 days; cumulative experience was greater than 1,300 days. Successful weaning and survival to hospital discharge was achieved in 33.1% of patients after a mean PECLA support of 8.5 +/- 6.3 days. During PECLA therapy, 48.7% of patients died, mainly as a result of multiorgan failure after a mean interval of 4.8 +/- 5.1 days. Inability to stabilize pulmonary function was noted in 3% of patients only. After PECLA, 30-day mortality was 13.6%. In a subgroup analysis, best outcome was obtained in patients after trauma. CONCLUSIONS: Pumpless extracorporeal lung assist is a simple and efficient method to support patients with deteriorating gas exchange for prolonged periods to allow the lung protective ventilation and transportation. Best indication for use of PECLA is severe hypercapnia and moderate hypoxia.