Is implantable cardioverter defibrillator surgery in patients with an implanted left ventricular assist device safe under uninterrupted oral anticoagulation?

BACKGROUND: Implantable cardioverter-defibrillator (ICD) surgery in patients with implanted left ventricular assist devices (LVAD) is associated with an increased risk of bleeding complications because of the need to ensure that these patients are adequately anticoagulated. Our study aimed to evaluate the safety of our new strategy of uninterrupted oral anticoagulation compared to heparin-bridging during the surgical interval. METHODS: Between January 2009 and January 2020, 116 patients with LVAD underwent ICD surgery. Since January 2015, 60 patients were operated under continued sufficient oral anticoagulation with a vitamin k antagonist (VKA group). Fifty-six patients underwent a heparin-bridging regimen (heparin group). Demographics, perioperative data, complications, and mortality were analyzed. RESULTS: Bleeding complications attributable to the surgical intervention occurred more often (19.6% vs. 10.0%, p = 0.142) and at a higher rate of re-exploratory surgery (14.3% vs. 5.0%, p = 0.088) in the heparin group without reaching statistical significance. Moreover, the heparin group patients' postoperative total length of stay was 10 days longer (17.8 ± 23.8 days vs. 8.3 ± 9.5 days, p = 0.007). There were no procedure-related deaths, no thromboembolic events, and no LVAD-related thrombosis. CONCLUSION: Our strategy of uninterrupted oral anticoagulation is safe and results in a reduction by more than half the number of days in hospital without an increase in adverse events.

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

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

Predictors of Mortality in Primary Surgical Repair of Postinfarction Ventricular Septal Defects: The Leipzig Experience.

BACKGROUND: A postinfarction ventricular septal defect (pVSD) as a complication of acute myocardial infarction (AMI) is associated with high mortality. This retrospective, single-center study aimed to identify predictors of early and long-term outcomes in patients undergoing primary surgical repair of pVSD managed by various surgical techniques. METHODS: We reviewed data from 77 consecutive patients who underwent primary surgical repair after pVSD in our institution. Prospectively collected demographic and perioperative data were analyzed retrospectively. Predictors of 30-day mortality and long-term outcome were assessed. RESULTS: pVSD was anterior in 45 patients (58.4%) and posterior in 32 (41.6%). Buttressed mattress suture (n = 9, 11.7%), simple single septal patch (n = 34, 44.2%), simple double septal patch (n = 2, 2.6%), sandwich double patch (n = 1, 1.3%), and the infarct exclusion technique (n = 31, 40.3%) were performed for surgical closure. Fifty-three patients (68.8%) had preoperative cardiogenic shock. The 30-day mortality was 42.8% (33 patients). Independent risk factors of 30-day mortality were duration between AMI and surgery <7 days (odds ratio [OR] 5.229, P = .011), preoperative absence of diuretics (OR 6.913, P = .005), and preoperative cardiogenic shock (OR 3.558, P = .011). Cumulative survival rates at 1, 5, and 10 years were 57.1%, 57.1%, and 31.2%, respectively. CONCLUSION: In pVSD, the 30-day mortality remains high, and preoperative cardiogenic shock significantly influenced mortality in our study. None of the surgical techniques or materials used in our investigation influenced the outcome.

Performance of pacemaker leads in alternative lead positions after tricuspid valve replacement.

BACKGROUND: Bradycardic arrhythmias requiring pacemaker (PM) implantation are still common in patients in need of tricuspid valve replacement (TVR). Leaving an existing PM lead in an extravalvular position may represent a helpful alternative in special situations like the implantation of a mechanical TV. This study aimed to examine the short- to mid-term outcome of paravalvular leads concerning lead survival and prosthesis dysfunction in patients after TVR. METHODS: A retrospective case-control study of patients with TVR and ventricular pacing was conducted. Patients from the database of the Leipzig Heart Center were included. Data of the paravalvular lead group (PVG) and coronary sinus lead group (CSG) were compared to a control group with conventional transvalvular leads (TVG). RESULTS: Eighty patients with TVR and cardiac PM (TVG [n = 13], PVG [n = 40], and CSG [n = 27]) were included. The mean follow-up was 2.8 years. The rate of lead revisions (TVG 15.4%, PVG 2.5%, and CSG 7.5%) was lower in PVG but without significance (P = .286). The CSG demonstrated significantly higher pacing thresholds (1.4 V/0.8 ms) than TVG (0.5 V/0.4 ms), P = .004. However, the deterioration of threshold amplitudes during follow-up was similar in CSG (7.4%) and PVG (7.5%) compared with controls (7.7%). Function of TV prosthesis regarding development of stenosis or regurgitation showed a similarity between the groups (regurgitation PVG P = .692, CSG P = 1; stenosis PVG P = .586, CSG P = 0.69). CONCLUSION: Paravalvular positioning of PM leads seems to represent a reasonable alternative to the conventional transvalvular lead positioning concerning the lead and Tricuspid Valve prosthesis's function and durability in selected patients.

Human Pluripotent Stem Cell-Derived Kidney Model for Nephrotoxicity Studies.

Current in vitro models for identifying nephrotoxins are poorly predictive. We differentiated human pluripotent stem cells (hPSCs) into three-dimensional, multicellular structures containing proximal tubule cells (PTCs) and podocytes and evaluated them as a platform for predicting nephrotoxicity. The PTCs showed megalin-dependent, cubilin-mediated endocytosis of fluorescently labeled dextran and active gamma-glutamyl transpeptidase enzymes. Transporters from both the ATP-binding cassette (ABC) and the solute carrier (SLC) families were present at physiological levels in the differentiated cells, but important renal transporters such as organic anion transporter 1 (OAT1), OAT3, and organic cation transporter 2 (OCT2) were present only at lower levels. Radioactive uptake studies confirmed the functional activity of organic cation transporter, novel, type 2 (OCTN2), organic anion transporter polypeptide 4C1 (OATP4C1), and OCTs/multidrug and toxin extrusion proteins (MATEs). When treated with 10 pharmacologic agents as a test of the platform, the known nephrotoxic compounds were distinguished from the more benign compounds by an increase in tubular (PTC, kidney injury molecule 1 (KIM-1), and heme oxygenase 1 (HO-1)) and glomerular (nephrin [NPHS1]/Wilms tumor protein [WT1]) markers associated with nephrotoxicity, and we were able to distinguish the type of nephrotoxin by examining the relative levels of these markers. Given the functions demonstrated and with improved expression of key renal transporters, this hPSC-derived in vitro kidney model shows promise as a platform for detection of mechanistically different nephrotoxins.

Cardiac Surgery in Patients with Parkinson's Disease: A Retrospective Analysis of a High-Risk Cohort.

BACKGROUND: Little is known about the perioperative course of patients with Parkinson's disease (PD) undergoing cardiac surgery. The objective of this study was to identify the influence of PD on the perioperative course and to improve treatment. METHODS: Perioperative data were analyzed retrospectively from 130 patients undergoing cardiac surgery between September 2001 and April 2013 who had PD and were compared using 1:1 matched-pair analysis with 130 controls not affected by PD. RESULTS: The 30-day all-cause mortality (4.6 vs. 9.2%; p = 0.21; odds ratio [OR] = 0.45; 95% confidence interval [CI]: 0.16, 1.31) and the overall all-cause mortality (27.7 vs. 28.5%; hazard ratio [HR] = 0.96 [0.56, 1.66]; p = 1.00) were not significantly different between PD patients and the control group. Emergency surgery (p = 0.04; OR = 3.20; 95% CI: 1.06, 9.66) and postoperative pneumonia (p < 0.001; OR = 11.3; 95% CI: 3.06, 41.6) were associated with 30-day mortality. Independent predictors of all-cause mortality were age at surgery (p = 0.01; OR = 3.58; 95% CI: 1.38, 9.30), NYHA (New York Heart Association) classification stage IV (p = 0.02; OR = 17.3; 95% CI: 1.52, 198), and postoperative pneumonia (p = 0.05; OR = 46.4; 95% CI: 0.97, 2219). We did not observe an association of PD with short- or long-term all-cause mortality after adjustment for associated covariates. CONCLUSIONS: We found that PD is not a significant risk factor for perioperative morbidity and mortality in our cohort. Our study showed that patients with PD had outcomes that were similar to those of non-PD patients.

Evaluation of risk factors for a fulminant Clostridium difficile infection after cardiac surgery: a single-center, retrospective cohort study.

BACKGROUND: Clostridium difficile (CD) is the most common pathogen causing nosocomial diarrhea. The clinical presentation ranges from mild diarrhea to severe complications, including pseudomembranous colitis, toxic megacolon, sepsis, and multi-organ failure. When the disease takes a fulminant course, death ensues rapidly in severe and complex cases. Preventive screening or current prophylactic therapies are not useful. Therefore, this study was conducted to detect risk factors for a fulminant CD infection (CDI) in patients undergoing cardiac surgery. METHODS: Between April 1999 and April 2011, a total of 41,466 patients underwent cardiac surgery at our institution. A review of our hospital database revealed 1256 patients (3.0%) with post-operative diarrheal disease who tested positive for CD; these patients comprised the cohort of this observational study. A fulminant CDI occurred in 153 of these patients (12.2%), which was diagnosed on the basis of gastrointestinal complications, e.g. pseudomembranous colitis, and/or the need for post-cardiac surgery laparotomy. Demographic, peri-operative, and survival data were analyzed, and predictors of a fulminant CDI were assessed by binary logistic regression analysis. RESULTS: The 30-day mortality was 6.1% (n = 77) for the entire cohort, with significantly higher mortality among patients with a fulminant CDI (21.6% vs. 4.0%, p <  0.001). Overall mortality (27.7%, n = 348) was also higher for patients with a fulminant course of the disease (63.4% vs. 22.8%, p <  0.001), and a laparotomy was required in 36.6% (n = 56) of the fulminant cases. Independent predictors of a fulminant CDI were: diabetes mellitus type 2 (OR 1.74, CI 1.15-2.63, p = 0.008), pre-operative ventilation (OR 3.52, CI 1.32-9.35, p = 0.012), utilization of more than 8 units of red blood cell concentrates (OR 1.95, CI 1.01-3.76, p = 0.046) or of more than 5 fresh-frozen plasma units (OR 3.38, CI 2.06-5.54, p <  0.001), and a cross-clamp time > 130 min (OR 1.93, CI 1.12-3.33, p = 0.017). CONCLUSIONS: We identified several independent risk factors for the development of a fulminant CDI after cardiac surgery. Close monitoring of high-risk patients is important in order to establish an early onset of therapy and thus to prevent a CDI from developing a fulminant course after cardiac surgery.

Inhibition of Hepatobiliary Transport Activity by the Antibacterial Agent Fusidic Acid: Insights into Factors Contributing to Conjugated Hyperbilirubinemia/Cholestasis.

Conjugated hyperbilirubinemia accompanied by cholestasis is a frequent side effect during chronic treatment with the antimicrobial agent fusidic acid. Previous studies from our laboratory, addressing mechanisms of musculoskeletal toxicity arising from coadministration of fusidic acid with statins, demonstrated the ability of fusidic acid to potently inhibit human organic anion transporting polypeptides OATP1B1 (IC50 = 1.6 µM) and OATP1B3 (IC50 = 2.5 µM), which are responsible for the uptake-limited clearance of statins as well as bilirubin glucuronide conjugates. In the present work, inhibitory effects of fusidic acid were characterized against additional human hepatobiliary transporters [Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and multidrug resistance-associated proteins MRP2 and MRP3] as well as uridine glucuronosyl transferase (UGT1A1), which mediate the disposition of bile acids and bilirubin (and its conjugated metabolites). Fusidic acid demonstrated concentration-dependent inhibition of human NTCP- and BSEP-mediated taurocholic acid transport with IC50 values of 44 and 3.8 µM, respectively. Inhibition of BSEP activity by fusidic acid was also consistent with the potent disruption of cellular biliary flux (AC50 = 11 µM) in the hepatocyte imaging assay technology assay, with minimal impact on other toxicity end points (e.g., cytotoxicity, mitochondrial membrane potential, reactive oxygen species generation, glutathione depletion, etc.). Fusidic acid also inhibited UGT1A1-catalyzed ß-estradiol glucuronidation activity in human liver microsomes with an IC50 value of 16 µM. Fusidic acid did not demonstrate any significant inhibition of ATP-dependent LTC4 transport (IC50's > 300 µM) in human MRP2 or MRP3 vesicles. R values, which reflect maximal in vivo inhibition, were estimated from a static mathematical model by taking into consideration the IC50 values generated in the various in vitro assays and clinically efficacious unbound fusidic acid concentrations. The magnitudes of in vivo interaction (R values) resulting from the inhibition of OATP1B1, UGT1A1, NTCP, and BSEP transport were ∼1.9-2.6, 1.1-1.2, 1.0-1.1, and 1.4-1.7, respectively, which are indicative of some degree of inherent toxicity risk, particularly via inhibition of OATP and BSEP. Collectively, these observations indicate that inhibition of human BSEP by fusidic acid could affect bile acid homeostasis, resulting in cholestatic hepatotoxicity in the clinic. Lack of direct inhibitory effects on MRP2 transport by fusidic acid suggests that conjugated hyperbilirubinemia does not arise via interference in MRP2-mediated biliary disposition of bilirubin glucuronides. Instead, it is possible that elevation in the level of bilirubin conjugates in blood is mediated through inhibition of hepatic OATPs, which are responsible for their reuptake and/or downregulation of MRP2 transporter as a consequence of cholestatic injury.

Extracorporeal membrane oxygenation: experience in acute graft failure after heart transplantation.

INTRODUCTION: Acute graft failure is the leading cause of early mortality after heart transplantation (HTx). Extracorporeal membrane oxygenation (ECMO) is an efficient therapeutic option to treat various pathologies, unburden the left and right ventricle, and allow for functional recovery of the transplanted heart. We reviewed our ECMO experience and outcomes in HTx patients. METHODS: Retrospectively, we analyzed all patients who received an orthotopic HTx (n = 298) in our department over a 15-yr period (1997 through 2011) to assess the incidence of post-HTx ECMO implantation, perioperative complications, early and one-yr mortality as well as causes of death. RESULTS: ECMO therapy was utilized to treat graft failure in 28 patients (10.6%) with a mean duration of ECMO support of 4.2 d (six h to 9.4 d). Multivariate analysis revealed as independent predictors for mortality low cardiac output (p = 0.028; odds ratio (OR) = 11.3) and stroke (p = 0.008; OR = 19.7). Cumulative survival rates were 46.4 ± 9.4% within 30 d and 25.0 ± 8.2% at one yr. Causes of death were multiorgan failure (n = 9), sepsis (n = 9), lung failure (n = 2), and intracerebral bleeding (n = 2). ECMO was implanted due to primary graft failure (PGF, n = 16), sepsis (n = 4), and right heart failure (n = 6). CONCLUSION: Temporary ECMO support for postoperative output failure is an acceptable option as a last resort for otherwise doomed patients with fatal graft failure after HTx. The small fraction of patients surviving appear to have a decent long-term prognosis.

Predictors of permanent pacemaker implantation after Medtronic CoreValve bioprosthesis implantation.

AIMS: High-grade conduction disturbances requiring permanent pacemaker (PPM) implantation occur in up to 40% of patients following transcatheter aortic valve implantation (TAVI). The aim of this study was to identify pre-operative risk factors for PPM implantation after TAVI with the Medtronic CoreValve prosthesis (CVP). METHODS AND RESULTS: We retrospectively analysed 109 patients following transfemoral CVP implantation performed between 2008 and 2009 at the Leipzig Heart Center. Patients who had indwelling PPM at the time of TAVI (n = 21) were excluded, leaving 88 patients for analysis. Mean age was 80.3 ± 6.6 years and logistic EuroScore predicted risk of mortality was 23.3 ± 12.1%. A total of 32 patients (36%) underwent PPM implantation post-TAVI during the same hospital admission. A total of 27/88 (31%) had evidence of pre-operative abnormal conduction, including first degree AV block and left bundle brunch block. Statistically significant risk factors for the need for post-operative PPM were patient age >75 years [P = 0.02, odds ratio (OR) 4.6], pre-operative heart rate <65 beats per minute (b.p.m.; P = 0.04, OR 2.9), CVP oversizing >4 mm (P = 0.03, OR 2.8), CVP prosthesis >26 mm (OR 2.2), atrial fibrillation (P = 0.001, OR 5.2), and ventricular rate <65 b.p.m. at the first post-operative day (P = 0.137, OR 6.0). CONCLUSION: PPM implantation occurs frequently after transfemoral TAVI with the CVP. Older age, chronic atrial fibrillation, pre-operative bradycardia, and larger or significantly oversized prostheses were independent risk factors for PPM implantation following TAVI with the CVP.

Clinical and Microbiological Analysis of Deep Sternal Wound Infections in Fifty-Two Consecutive Patients.

Background: Mediastinitis after cardiac surgery can lead to devastating consequences such as deep sternal wound infections (DSWI). Staphylococcus epidermidis and other coagulase-negative staphylococci belong to the physiological skin flora and therefore generally are not considered pathogenic agents. Thus, local resistance patterns of these bacterial species often recovered from wound specimens generally are ignored while choosing antibiotics for peri-operative prophylaxis in cardiac surgery as well as in the selection of empiric antibiotic therapy of DSWI. Methods: During the period May 2012-May 2013, 52 patients suffering from DSWI were treated at our institution. For every patient, deep tissue samples were obtained during surgical debridement procedures and submitted to microbiologic analysis. The frequency of and the time to occurrence of a DSWI was recorded, and baseline data, previous operative interventions, complications, and the technique used for soft tissue reconstruction, as well as the microbiologic results and individual risk factors, were documented. Results: There were 32 male patients (62%) and 20 female. The patients' age at the time of revision was a mean of 67 ± 11.5 years (range 35-83 years). There was bacterial growth in 31 cases (60%), the predominant species being S. epidermidis (20 patients; 65%). Extended antibiotic therapy was indispensable to controlling the infection. Conclusion: The local resistance patterns of antibiotics should have a greater influence on the standardized prophylaxis or empirical therapy of DSWI and need to be discussed specifically for this high-risk population. Because of its multi-resistance spectrum, S. epidermidis must be classified as a potential pathogen. In the cases reported here, extended antibiotic therapy was necessary to support wound healing and thus good patient outcomes.

Prevalence of permanent pacemaker implantation after conventional aortic valve replacement-a propensity-matched analysis in patients with a bicuspid or tricuspid aortic valve: a benchmark for transcatheter aortic valve replacement.

OBJECTIVES: Elective treatment of aortic valve disease by transcatheter aortic valve replacement (TAVR) is becoming increasingly popular, even in patients with low risk and intermediate risk. Even patients with a bicuspid aortic valve (BAV) are increasingly considered eligible for TAVR. Permanent pacemaker implantation (PMI) is a known-frequently understated-complication of TAVR affecting 9-15% of TAVR patients with a potentially significant impact on longevity and quality of life. BAV patients are affected by the highest PMI rates, although they are frequently younger compared to their tricuspid peers. The aim of the study is to report benchmark data-from a high-volume centre (with a competitive TAVR programme) on PMI after isolated surgical aortic valve replacement (SAVR) in patients with BAV and tricuspid aortic valve (TAV). METHODS: We performed a retrospective single-centre analysis on 4154 patients receiving isolated SAVRs (w/o concomitant procedures), between 2000 and 2019, of whom 1108 had BAV (27%). PMI rate and early- and long-term outcomes were analysed. For better comparability of these demographically unequal cohorts, 1:1 nearest neighbour matching was performed. RESULTS: At the time of SAVR, BAV patients were on average 10 years younger than their TAV peers (59.7 ± 12 vs 69.3 ± 9; P < 0.001) and had less comorbidities; all relevant characteristics were equally balanced after statistical matching. Overall PMI rate was significantly higher in BAV patients (5.4% vs 3.8%; P = 0.03). BAV required PMI exclusively (100%) and TAV required predominately (96%) for persistent postoperative high-degree atrioventricular block. After matching, the PMI rate was similar (5.1% vs 4.4%, P = 0.5). In-hospital mortality in the matched cohort was 1% in both groups. Long-term survival was more favourable in BAV patients (94% vs 90% in TAV at 5 years; 89% vs 82% in TAV at 9 years; P = 0.013). CONCLUSIONS: With SAVR, the overall incidence of PMI among BAV patients seems significantly higher; however, after propensity matching, no difference in PMI rates between BAV and TAV is evident. The PMI rate was remarkably lower among BAV patients after SAVR compared to the reported incidence after TAVR.

Dynamic responses of single cardiomyocytes to graded ischemia studied by oxygen clamp in on-chip picochambers.

Single mouse cardiomyocytes were exposed to defined ischemia. We designed chambers on glass chips with a volume of 192 pL (picochambers). After a picochamber was loaded with a single cardiomyocyte, P(O2) in the picochamber was equilibrated with that in the headspace, where it was controlled in the critical range between <0.2 and 10 mm Hg. Because the extracellular fluid volume in a picochamber was restricted, these conditions are close to tissue ischemia. Responses of the sarcolemmal K(ATP)-channel current (I(KATP)), the production of reactive oxygen species (ROS), and the mitochondrial membrane potential (delta psi) of single cardiomyocytes to graded ischemia and, in particular, to rapid changes of the ischemic grade by defined oxygen steps were studied. The results show that I(KATP) is readily activated during ischemia and that the grade of ischemia tightly controls the amplitude of I(KATP). Furthermore, maximal ischemia-induced I(KATP) was similar when it followed either reoxygenation or reperfusion, suggesting that there is no major autocrine modulation of maximal I(KATP) during ischemia. A P(O2) staircase from <0.2 to 10 mm Hg increased the ROS signal, starting already at a P(O2) of approximately 0.3 mm Hg. With a similar P(O2) staircase, delta psi first hyperpolarized and then, above 1 mm Hg, depolarized. The depolarizing response of delta psi at a P(O2) of >1 mm Hg could be blocked by increasing the antioxidant defense with glutathione-monoethyl ester. It is concluded that in an ischemic cardiomyocyte I(KATP) is essentially controlled by Po(2) and that at low P(O2) delta psi is balanced by oxygen-induced hyperpolarization and ROS-induced depolarization.

Characteristics of the new AtriCure cryoFORM® cryoablation probe for the surgical treatment of cardiac arrhythmias.

INTRODUCTION: Atrial fibrillation has a significant impact on patient mortality and morbidity. In particular, stroke is a frequent complication associated with atrial fibrillation. In recent years, various treatment options have been developed that are based on the elimination of atypical electrically active atrial areas. Areas covered: This manuscript presents a new cryoablation probe from AtriCure Inc. In addition to describing the characteristics of the probe, we also discuss atrial fibrillation and its surgical therapy options as well as the basics of cryosurgery. The cryoFORM® cryoablation probe is an ablation system developed for cardiothoracic surgeons that utilizes nitrous oxide (N2O) to create continuous transmural lesions that block propagation of atrial activation. The main features of the probe are an excellent working capacity due to the use of N2O, high flexibility, and, in combination with the cryoICE® Box V6, an active defrost mode for quick detachment. Expert commentary: The cryoFORM® ablation probe is a new device for the treatment of atrial fibrillation using N2O as an energy source. The probe is made from stainless steel and has a corrugated surface, a design that provides a higher flexibility than the cryoICE probe.

Assessment of Bile Salt Export Pump (BSEP) Inhibition in Membrane Vesicles Using Radioactive and LC/MS-Based Detection Methods.

The bile salt export pump (BSEP, ABCB11) belongs to the ATP-binding-cassette superfamily of transporters and is predominately found in the liver. BSEP is an efflux transporter that plays a critical role in the secretion of bile salts into the bile. Inhibition of BSEP function by drugs can result in the buildup of bile salts in the liver and eventually leads to cholestasis and drug-induced liver injury (DILI). DILI is a major cause of withdrawal of drugs from the pharmaceutical market and accounts for >50% of acute liver failures. Therefore, early detection of BSEP inhibition by drugs can help to mitigate the possibility of BSEP-associated liver injury. This unit describes two assays that investigate the relationship between drug interference with BSEP function and liver injury using membrane vesicles prepared from Hi5 insect cells transfected with human BSEP. Comprehensive protocols for assessing BSEP inhibition in a 384-well format using radiolabeled and liquid chromatography/mass spectrometry (LC/MS)-based detection methods are described. © 2017 by John Wiley & Sons, Inc.

Midterm Durability and Hemodynamic Performance of a Third-Generation Bovine Pericardial Prosthetic Aortic Valve: The Leipzig Experience.

BACKGROUND: The Trifecta valve (St. Jude Medical, St. Paul, MN) is a stented bovine pericardial bioprosthesis for aortic valve replacement (AVR). Implantation experience and midterm follow-up of this valve have not yet been reported from a large single-center cohort. METHODS: We retrospectively analyzed data from 918 patients (73.2 ± 6.5 years; logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE], 13.2 ± 14.3) who underwent AVR. Analyses addressed implantation safety, short- and long-term survival, and hemodynamic valve performance. RESULTS: Concomitant procedures were performed in 54.9% of the patients. Low cardiac output syndrome, postoperative bleeding requiring transfusion or reoperation, and acute renal failure requiring temporary hemodialysis occurred at rates of 4.3%, 7.0%, and 11.7%, respectively. At discharge, 44 patients (4.8%) were identified with moderate prosthesis-patient mismatch (PPM) and none was identified with severe PPM. Mean follow-up was 2.7 ± 1.6 years (maximum, 7.4 years). Survival at 30 days was 88.7% and 92.0% for all patients and patients with isolated AVR, respectively; 5-year overall survival for these groups was 73.4% and 82.2%, respectively. Myocardial infarction (odds ratio [OR], 78; 95% confidence interval [CI], 20.8-294) and inotropic medication (OR, 6.8; 95% CI, 3.2-14.5) were the strongest independent predictors for long-term mortality. Five-year freedom from structural valve deterioration (SVD) was 97.9% ± 1.5%. Left ventricular ejection fraction (LVEF) after implantation was similar to baseline and was stable over time (range, 58.9%-62.3%). The mean gradient improved substantially (39.3 mm Hg at baseline versus 9.4 mm Hg at 6 months). CONCLUSIONS: This large single-center cohort shows the easy and safe implantation, adequate hemodynamic performance, and satisfactory durability of the Trifecta valve at midterm follow-up.

Fistula Formation 6 Years after Removal of Infected Pacemaker Leads.

We describe a case of a male patient who presented with a chronic ulcer below the left clavicle. Six years before the present admission a permanent pacemaker, including leads, was explanted related to endocarditis. The initial working hypothesis suspected an infected sebaceous gland as the cause of ulceration. After two periods of unsuccessful surgical treatment of the gland, further examination identified a small pacemaker lead fragment underneath the articulation between sternum and clavicle as a possible reason.

Prosthetic Pulmonary Valve Stenosis: A Different Way to Solve the Problem.

To avoid a third major cardiovascular surgery in an 84-year-old man, a Melody Transcatheter Pulmonary Valve was implanted in a functionally stenotic bioprosthesis in the pulmonary position. The intervention was free of complications with good results.

Coronary Artery Fistula: Two Rare Cases.

Coronary artery fistula (CAF) is an incidental finding in up to 0.2% of cardiac catheterization studies and is a rare pathologic condition affecting up to 1% of the general population. We report two cases of CAF diagnosed by coronary angiography and managed by surgical ligation, with excellent postoperative outcome. Anatomic location, clinical presentation, investigation, and treatment of CAF are discussed.