Enhanced Cardiac CaMKII Oxidation and CaMKII-Dependent SR Ca Leak in Patients with Sleep-Disordered Breathing.

BACKGROUND: Sleep-disordered breathing (SDB) is associated with increased oxidant generation. Oxidized Ca/calmodulin kinase II (CaMKII) can contribute to atrial arrhythmias by the stimulation of sarcoplasmic reticulum Ca release events, i.e., Ca sparks. METHODS: We prospectively enrolled 39 patients undergoing cardiac surgery to screen for SDB and collected right atrial appendage biopsies. RESULTS: SDB was diagnosed in 14 patients (36%). SDB patients had significantly increased levels of oxidized and activated CaMKII (assessed by Western blotting/specific pulldown). Moreover, SDB patients showed a significant increase in Ca spark frequency (CaSpF measured by confocal microscopy) compared with control subjects. CaSpF was 3.58 ± 0.75 (SDB) vs. 2.49 ± 0.84 (no SDB) 1/100 µm-1s-1 (p < 0.05). In linear multivariable regression models, SDB severity was independently associated with increased CaSpF (B [95%CI]: 0.05 [0.03; 0.07], p < 0.001) after adjusting for important comorbidities. Interestingly, 30 min exposure to the CaMKII inhibitor autocamtide-2 related autoinhibitory peptide normalized the increased CaSpF and eliminated the association between SDB and CaSpF (B [95%CI]: 0.01 [-0.1; 0.03], p = 0.387). CONCLUSIONS: Patients with SDB have increased CaMKII oxidation/activation and increased CaMKII-dependent CaSpF in the atrial myocardium, independent of major clinical confounders, which may be a novel target for treatment of atrial arrhythmias in SDB.

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: A retrospective analysis.

OBJECTIVES: Surgery for acute type A aortic dissection is associated with several perioperative complications, such as acute respiratory dysfunction (ARD). The aim of this study was to investigate perioperative risk factors involved in the development of ARD and whether antibiotic treatment has an impact. METHODS: 243 patients underwent surgery for acute type A aortic dissection between 2008 and 2017. The patients were retrospectively divided into the ARD and NON-ARD group. ARD was defined as PaO2/FiO2 ≤ 200 mmHg (PF ratio) within 48 hours after surgery. All patients received either narrow- or broad-spectrum antibiotics. RESULTS: After the exclusion of 42 patients, 201 patients were analyzed. The PF ratio of the ARD group was significantly lower than of the NON-ARD group within the first 7 days. ARD patients (n = 111) were significantly older (p = .031) and had a higher body mass index (BMI) (p = .017). ARD patients required longer postoperative ventilation (2493 vs. 4695 [min], p = .006) and spent more days in the intensive care unit (7.0 vs. 8.9 [days], p = .043) compared to NON-ARD. The mortality was significantly lower for ARD than for NON-ARD patients (p = .030). The incidence of pneumonia was independent of the antibiotic treatment regime (p = .391). Renal and neurological complication rate was higher in patients treated with broad-spectrum antibiotic. CONCLUSION: ARD is the main complication (55%) that occurs approximately 24 hours after surgery for acute type A aortic dissection. The preoperative risk factors for ARD were higher age and increased BMI. Patients on broad-spectrum antibiotics did not show an improved postoperative outcome compared to patients with narrow-spectrum antibiotics.

Brain Death Induction in Mice Using Intra-Arterial Blood Pressure Monitoring and Ventilation via Tracheostomy.

While both living donation and donation after circulatory death provide alternative opportunities for organ transplantation, donation after donor brain death (BD) still represents the major source for solid transplants. Unfortunately, the irreversible loss of brain function is known to induce multiple pathophysiological changes, including hemodynamic as well as hormonal modifications, finally leading to a systemic inflammatory response. Models that allow a systematic investigation of these effects in vivo are scarce. We present a murine model of BD induction, which could aid investigations into the devastating effects of BD on allograft quality. After implementing intra-arterial blood pressure measurement via the common carotid artery and reliable ventilation via a tracheostomy, BD is induced by steadily increasing intracranial pressure using a balloon catheter. Four hours after BD induction, organs may be harvested for analysis or for further transplantation procedures. Our strategy enables the comprehensive analysis of donor BD in a murine model, therefore allowing an in-depth understanding of BD-related effects in solid organ transplantation and potentially paving the way to optimized organ preconditioning.

The 'Weekend Effect' in adult patients who receive extracorporeal cardiopulmonary resuscitation after in- and out-of-hospital cardiac arrest.

AIM: This study investigates the potentially adverse association between extracorporeal cardiopulmonary resuscitation (ECPR) after cardiac arrest on weekends versus weekdays. METHODS: Single-centre, retrospective, stratified (weekday versus weekend) analysis of 318 patients who underwent in-hospital ECPR after out-of-hospital and in-hospital cardiac arrest (OHCA/IHCA) between 01/2008 and 12/2018. Weekend was defined as the period between Friday 17:00 and Monday 06:59. RESULTS: Seventy-three patients (23%) received ECPR during the weekend and 245 arrests (77%) occurred during the weekday. Whereas survival to discharge did not differ between both groups, long-term survival was significantly lower in the weekend group (p = 0.002). In the multivariate analysis, independent risk factors associated with hospital mortality were no flow time (OR 1.014; 95% CI 1.004-1.023) and serum lactate prior ECPR (OR 1.011; 95% CI 1.006-1.012), whereas each unit serum haemoglobin above average had a protective effect on in-hospital mortality (OR 0.87; 95% CI 0.79-0.96). New onset kidney failure requiring renal replacement therapy occurred more often in the weekend group (30.1% versus 18.4%; p = 0.04). One third of patients experienced complications regardless ECPR was initiated at weekdays or weekends. CONCLUSION: Extracorporeal cardiopulmonary resuscitation at weekends adversely seems to impact long-term survival regardless timing (dayshift/nightshift). Duration of CPR and serum lactate prior ECPR were demonstrated as independent risk factors for in-hospital mortality. As ECPR at weekends could not be shown to be an independent outcome predictor a thorough analysis of clinical events subsequent to this intervention is warranted to understand long-term consequences of ECPR initiation after cardiac arrest.

Impact of coronary angiography early after CABG for suspected postoperative myocardial ischemia.

BACKGROUND: The incidence of perioperative myocardial infarction is reported to 2-8%. The aim of the study (retrospectively registered) was to evaluate whether control coronary angiography after surgery is useful in case of suspected postoperative myocardial ischemia. METHODS: All patients who demonstrated signs of myocardial ischemia post CABG and underwent coronary angiography from 6/2008 to 06/2015 were retrospectively analyzed. Myocardial ischemia post CABG was defined as an increase of CK/CK-MB, occasionally associated with arrhythmias or low output syndrome. RESULTS: Overall, 108 patients (age 66 ± 9 years) demonstrated signs of myocardial ischemia post CABG and underwent coronary angiography corresponding to an incidence of 2.2%. Of them, 70 patients (65%) demonstrated graft pathologies. A therapeutic consequence was drawn in 62 Patients (57%), which consisted of redo surgery in 10 patients (9%) and PCI with stent placement in 52 patients (48%). Of the remaining 46 patients, 29 patients showed intact bypass grafts (27%), whereas 17 patients had minor pathologies (16%). Demographic data including the extent of the coronary artery disease, urgency of operation, comorbidities, EuroScore, surgical technique, postoperative lab tests and transfusion requirements were comparable among the groups. Redo surgery patients had prior PCI in 33% of patients, which was much higher than in the other groups. Patients with reintervention had a 30d-mortality rate of 13%, conservatively treated patients only 2.2%. Mortality was highest after redo surgery with 25%. CONCLUSIONS: Postoperative coronary angiography is a useful tool with a significant therapeutic value. Pathological findings mandate further revascularization therapy in roughly half of the patients. PCI is a safe choice in the majority of patients, redo surgery is much less indicated.

Sleep-disordered breathing is associated with disturbed cardiac repolarization in patients with a coronary artery bypass graft surgery.

BACKGROUND: The development of malignant ventricular arrhythmias due to abnormal cardiac repolarization is a major complication after coronary artery bypass graft surgery (CABG). Sleep-disordered breathing (SDB) is linked to prolonged cardiac repolarization in non-surgical patients. This study evaluates cardiac repolarization in patients with and without SDB who underwent CABG. METHODS: 100 patients who had received CABG (84% men, age 68 ± 10 years, body-mass-index [BMI] 28.7 ± 4.2 kg/m2) were retrospectively evaluated. Polygraphy was recorded the night before CABG. SDB was defined as an apnea-hypopnea index (AHI) of ≥15/h and differentiated into central (CSA) and obstructive (OSA) sleep apnea. Cardiac repolarization was assessed by means of T-peak-to-end (TpTe) and QTc-intervals and TpTe/QT-ratios derived from 12-lead electrocardiography (ECG). RESULTS: 37% of patients had SDB, 14% CSA and 23% OSA. Before CABG, patients with CSA and OSA had longer TpTe intervals than those without SDB (TpTe: CSA 100 ± 26 vs. OSA 97 ± 19 vs. no SDB 85 ± 14 ms, p = 0.013). QTc intervals and TpTe/QT ratios differed between the two groups (QTc: 444 ± 54 vs. 462 ± 36 vs. 421 ± 32 ms, p < 0.001; TpTe/QT ratio: 0.24 ± 0.04 vs. 0.23 ± 0.05 vs. 0.21 ± 0.03, p = 0.045). SDB was associated with abnormal cardiac repolarization independent of known risk factors for cardiac arrhythmias, such as age, sex, BMI, N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), and heart failure (TpTe: B-coefficient [95%CI]: 16.0, [7.6-24.3], p < 0.001; QTc: 27.2 [9.3-45.1], p = 0.003; TpTe/QT ratio: 2.9 [1.2-4.6], p < 0.001). CONCLUSION: Independent of known risk factors for cardiac arrhythmias, SDB was significantly associated with abnormal cardiac repolarization before CABG. Data suggest that SDB may contribute to an increased risk of ventricular arrhythmias after CABG.

Pericardiectomy for Constrictive Pericarditis: An Institution's 21 Years Experience.

BACKGROUND: The aim of this retrospective study was to evaluate our experience with the surgical pericardiectomy procedure for patients suffering from isolated severe constrictive pericarditis. METHODS: From 1995 to 2016, 39 patients underwent isolated pericardiectomy for constrictive pericarditis. Fifteen patients were excluded because of concomitant surgery. There were 31 male (79.5%) patients and 8 female (20.5%) patients, 28 to 76 years old (mean, 56.6 ± 13.6 years). The underlying etiologies were idiopathic pericarditis (74.5%), infection (10%), rheumatic disorders (8%), status post cardiac surgery (2.5%), tuberculosis (2.5%), and status post mediastinal irradiation (2.5%). RESULTS: Pericardiectomy was performed through midline sternotomy in all cases. Sixteen patients (41%) underwent pericardiectomy electively employing cardiopulmonary bypass with the heart beating, and 23 patients (59%) had surgery without extracorporeal circulation (ECC). The overall 30-day mortality rate was 50% if cardiopulmonary bypass was used (13.8% since 2007). If surgery was performed without a heart-lung machine, mortality was 0%. On-pump patients had a significantly longer intensive care unit (ICU) stay (12 ± 9 vs. 4 ± 4 days, p = 0.013). Likewise, the duration of mechanical ventilation was much longer (171 ± 246 vs. 21 ± 40 hours, p = 0.04). The hospital stay was comparable with 28 ± 10 and 24 ± 18 days (p = 0.21). CONCLUSION: The present study demonstrates that pericardiectomy, without the use of cardiopulmonary bypass as treatment for constrictive pericarditis, is a safe procedure with an excellent outcome in critically ill patients.

Patients under Psychiatric Medication Undergoing Cardiac Surgery Have a Higher Risk for Adverse Events.

Objective The percentage of patients undergoing cardiac surgery under some sort of psychiatric medication (PM) is not negligible. Thus, this study aimed to evaluate a possible impact of preoperative PM on the outcome after cardiac surgery. Methods A matched case-control study was conducted by including all patients who underwent myocardial revascularization and/or surgical valve operation in our institution from December 2008 till February 2011 by chart review and institutional quality assurance database (QS) analysis. Results Out of 1,949 patients included, 184 patients (9%) were identified with PM medication (group A). A control group matched for logistic EuroSCORE II, ejection fraction and age was generated (group C). Patients with PM were in mean significantly longer on the intensive care unit (A: 4.94 days; 95% confidence interval (CI), 3.9-5.9 days vs. C: 3.24 days; CI, 2.84-3.64 days; p = 0.003), had longer mechanical ventilation times (A: 36.70 hours; CI, 19.81-53.59 hours vs. C: 20.14 hours; CI, 14.61-25.68 hours; p = 0.258), and significantly more episodes of respiratory insufficiencies (A: 31 episodes [17%] vs. C: 17 episodes [9%]; p = 0.002). Regression analysis revealed preoperative PM as a significant risk factor for respiratory insufficiency (odds ratio: 1.99, CI: 1.0-3.74; p = 0.04). Chest tube drainage (A: 690 mL, CI: 571-808 mL vs. C: 690 mL; CI: 496-884 mL, p = 0.53) and the total amount of red blood cell transfusion units were similar (A: 1.69 units; CI: 1.21-2.18 units vs. C: 1.50 units; CI: 1.04-1.96 units; p = 0.37). Sternal dehiscence requiring sternal refixation was significantly more frequent in A (12 patients [7%] vs. C: 2 patients [1%]; odds ratio: 6.3, CI: 1.4-28.7; p = 0.01). The 30-day mortality was similar in both groups (A: 6 patients [3%] vs. C: 4 patients [2%]; odds ratio: 1.5; CI: 0.4-5.4; p = 0.5); however, the 100-day mortality was near significantly higher in group A (A: 14 patients (8%) vs. C: 6 patients (3%); odds ratio: 2.4, CI: 0.9-6.5, p = 0.057). Conclusion Patients with preoperative PM developed complications more frequently compared with a matched control group. The underlying multifactorial mechanisms remain unclear. Patients under PM need to be identified and particular care including optimal pre- and postoperative psychiatric assistance is recommended.

Single Institution Experience With Transcatheter Valve-in-Valve Implantation Emphasizing Strategies for Coronary Protection.

BACKGROUND: Transcatheter valve-in-valve (VIV) implantation evolved as a therapeutic alternative, despite an increased risk of coronary obstruction in comparison with a regular transcatheter aortic valve implantation (TAVI). We report a comprehensive single-institution experience emphasizing strategies to reduce the risk of myocardial ischemia. METHODS: Since 2009, 639 patients underwent a TAVI procedure in our institution. All patients are prospectively collected into an institutional registry. In total 31 patients underwent a VIV procedure at our institution (age 77.8 ± 6.3 years; The Society or Thoracic Surgeons predicted risk of mortality 20.9% ± 8.8%; New York Heart Association (NYHA) 3.0 ± 0.6). Degenerated bioprostheses included 24 Mitroflow, 6 Edwards Perimount, and Cryo-Valve O' Brien with label sizes from 21 to 27 mm. The type of failure was mostly regurgitation with or without concomitant stenosis (78%). RESULTS: Patients were provided with 5 Medtronic CoreValves, 15 Edwards SapienXT, 1 Edwards Sapien 3, 7 Medtronic Engager, and 3 Symetis Acurate TA valves. The procedural success rate was 88%. The left main stem was occluded in 1 patient (Sapien XT 26 in a Mitroflow 25 mm) who underwent emergent revascularization. Two patients suffering from a degenerated Mitroflow prosthesis needed a second valve (Sapien XT). Two patients with a degenerated Mitroflow prosthesis treated with a Sapien XT developed postprocedural myocardial ischemia and deceased on postoperative days 1 and 2, accounting to an overall incidence of coronary insufficiency associated to the VIV procedure of 10%. With the introduction of valves allowing commissural alignment (Acurate TA) and leaflet capturing as well (Engager) no further coronary insufficiency occurred. The mean gradient decreased significantly from 39.3 ± 14.0 to 16.1 ± 7.2 mm Hg (p = 0.002). Post-procedural regurgitation was classified as trace in 7 patients (23%) and moderate in 4 patients (13%). The 30-day survival was 77% with a significantly improved NYHA class of 1.79 ± 0.58 (p = 0.001). CONCLUSIONS: Jeopardizing coronary blood flow is likely in stenotic and calcified bioprostheses, particularly in tubelike aortic sinuses. Planning, imaging, and the use of valves allowing commissural alignment as well as leaflet capturing seem to reduce the risk. Further studies are necessary to support this hypothesis.

Left ventricular support adjustment to aortic valve opening with analysis of exercise capacity.

BACKGROUND: LVAD speed adjustment according to a functioning aortic valve has hypothetic advantages but could lead to submaximal support. The consequences of an open aortic valve policy on exercise capacity and hemodynamics have not yet been investigated systematically. METHODS: Ambulatory patients under LVAD support (INCOR®, Berlin Heart, mean support time 465 ± 257 days, average flow 4.0 ± 0.3 L/min) adjusted to maintain a near normal aortic valve function underwent maximal cardiopulmonary exercise testing (CPET) and right heart catheterization (RHC) at rest and during constant work rate exercise (20 Watt). RESULTS: Although patients (n = 8, mean age 45 ± 13 years) were in NYHA class 2, maximum work-load and peak oxygen uptake on CPET were markedly reduced with 69 ± 13 Watts (35% predicted) and 12 ± 2 mL/min/kg (38% predicted), respectively. All patients showed a typical cardiac limitation pattern and severe ventilatory inefficiency with a slope of ventilation to carbon dioxide output of 42 ± 12. On RHC, patients showed an exercise-induced increase of mean pulmonary artery pressure (from 16 ± 2.4 to 27 ± 2.8 mmHg, p < 0.001), pulmonary artery wedge pressure (from 9 ± 3.3 to 17 ± 5.3 mmHg, p = 0.01), and cardiac output (from 4.7 ± 0.5 to 6.2 ± 1.0 L/min, p = 0.008) with a corresponding slight increase of pulmonary vascular resistance (from 117 ± 35.4 to 125 ± 35.1 dyn*sec*cm-5, p = 0.58) and a decrease of mixed venous oxygen saturation (from 58 ± 6 to 32 ± 9%, p < 0.001). CONCLUSION: An open aortic valve strategy leads to impaired exercise capacity and hemodynamics, which is not reflected by NYHA-class. Unknown compensatory mechanisms can be suspected. Further studies comparing higher vs. lower support are needed for optimization of LVAD adjustment strategies.

Cardiac decompression on extracorporeal life support: a review and discussion of the literature.

Extracorporeal life support is a worldwide expanding technology for patients in critical cardiogenic shock. The device is usually attached to the femoral vessels using percutaneous techniques. Despite sufficient extracorporeal circulatory support, an unclear number of patients develop high end-diastolic pressures leading to left ventricular distension and pulmonary edema, and ventricular thrombus formation may evolve. This article discusses the strategies to prevent ventricular distension by conservative, interventional, and surgical means, also illustrated by case presentations.

Extracorporeal membrane oxygenation by single-vessel access in adults: advantages and limitations.

Veno-venous extracorporeal membrane oxygenation (vvECMO) conventionally requires the cannulation of two vessels. Here we report our initial experience with the "Wang-Zwische" (WZ) double-lumen cannula. In a group of n = 36 patients single venous cannulation for vvECMO was performed. A retrospective analysis was executed. A comparison of flow characteristics to standard two-vessel cannulation was performed. Mean age of the patient population was 48 ± 15 years (body mass index [BMI] 32 ± 13 kg/m(2)). In n = 32 patients (89%) the cannula was implanted percutaneously under echo or fluoroscopic guidance in less than 30 minutes. Nine patients were partially mobilized on extracorporeal membrane oxygenation (ECMO) support. Oxygenation (partial arterial oxygen tension [PaO(2)]/fraction of inspired oxygen [FiO(2)]) improved significantly in all patients from 66 mm Hg (interquartile range [IQR] 58-87 mm Hg) before ECMO to 117 mm Hg (IQR 95-195 mm Hg, p = 0.001) after 24 hours. In seven patients (19%) nonfatal adverse events occurred, including three dislocations, two partial cannula thrombosis, one ventricular perforation, and one retroperitoneal hemorrhage. The negative pressures for drainage at a flow of 2.5 L/min were significantly lower in a standard (S) two-vessel approach compared with a WZ approach (S: -9 mm Hg; IQR -3 to -24 mm Hg, vs. WZ: -23 mm Hg; IQR -4 to -40 mm Hg; p = 0.04). The WZ cannula offers sufficient gas exchange in addition to certain advantages over standard cannulation, including facilitated cannulation in selected patients and improved mobilization.

Pumpless extracorporeal lung assist: a 10-year institutional experience.

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.