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Background: Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) support., Methods: We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. Patients were allocated to the PP group if PP was performed during VV ECMO treatment or the supine positioning group. VV ECMO weaning success and hospital survival were analysed before and after propensity score matching., Results: A total of 158 patients could be analysed, and 38 patients (24.1%) received PP. There were no significant differences in VV ECMO weaning rate (47.4% vs. 46.7%, p = 0.94) and hospital survival (36.8% vs. 36.7%, p = 0.98) between the prone and supine groups, respectively. The analysis of 38 propensity score matched pairs also showed no difference in hospital survival (36.8% vs. 36.8%, p = 1.0) or VV ECMO weaning rate (47.4% vs. 44.7%, p = 0.82). Hospital survival was superior in the subgroup of patients treated with early PP (cutoff < 17 h via Youden's Index) as compared to late or no PP (81.8% vs. 33.3%, p = 0.02)., Conclusion: In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. However, early initiation of prone positioning was linked to a significant reduction of hospital mortality.

Objective: Aim of this study was to investigate predictors of survival in unstable patients with high SYNTAX-1-score., Background: In significant unprotected left main coronary artery (ULMCA) stenosis, treatment options include percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). While CABG is recommended for stable patients with ULMCA stenosis and a SYNTAX-1-score > 32, PCI may be preferable in unstable or high operative risk patients., Methods: Retrospective single-center all-comers registry study., Results: A total of 142 patients underwent ULMCA-PCI (~72.9 years, 23.2% females, 54.2% survival in 2-year follow-up), 84 of whom had a SYNTAX-1 > 32 (37.4 ± 12.8). Patients in the high-SYNTAX-1-group (score > 32) were more often in an acute condition compared to low-SYNTAX-2-group (score ≤ 32) including acute myocardial infarction (76.2% vs. 57.4%, p = .024), cardiogenic shock (48.2% vs. 14.8%, p = .001), or need for mechanical support (36.1% vs. 11.1%, p = .001). Survival was predicted by the acute condition including cardiogenic shock (OR 0.06 and 0.05) and myocardial infarction (OR 0.03 and 0.34) in both groups. Performance of the SYNTAX-1-score was limited in our patient collective in both groups (c-index 0.65 vs. 0.63) while SYNTAX-2-PCI-score performed better (c-index 0.67 vs. 0.67). EuroScore II had the best discriminative ability (c-index 0.87 vs. 0.78)., Conclusions: The majority of patients undergoing ULMCA-PCI presented in acute conditions with high SYNTAX-1-score, and is therefore underrepresented in clinical trials. Prognosis was best predicted by the acute condition and the EuroScore II. These data suggest that therapy in unstable patients should be guided by clinical condition over the anatomical SYNTAX-1-score., (© 2019 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)

Background: Transcatheter aortic valve replacement (TAVR) is routinely used in patients with severe aortic stenosis at increased operative risk. Due to potential technical difficulties, TAVR is not recommended for pure aortic regurgitation (AR). Smaller studies reported its use in AR, but data from big registries are lacking. The present study analyzes the nationwide use of surgical aortic valve replacement (SAVR) and TAVR in patients with AR from 2008 until 2015., Methods: We identified 138,237 cases of aortic valve replacement in Germany based on ICD and OPS codes., Results: Of 13.2% SAVR-cases and 1.3% of TAVR cases were performed in AR. AR patients undergoing SAVR were younger with lower logistic EuroSCORE (stenosis: 6.1 ± 5.6; AR: 4.5 ± 4.9). Nevertheless, stroke rates, bleedings, prolonged mechanical ventilation, and in-hospital mortality were higher (mortality: stenosis 2.6%, AR: 4.7%). In the TAVR group, patients with AR were at higher operative risk (logistic EuroSCORE: transfemoral (TF)-TAVR: stenosis: 14.3 ± 10.4; AR: 17.3 ± 13.3. Transapical (TA)-TAVR: stenosis: 16.1 ± 11.4; AR: 15.7 ± 12.2). Stroke rates were lower, but bleedings and prolonged ventilation occurred more frequently after TF-TAVR in AR compared to stenosis. The mortality varied markedly (TF-TAVR: 15.2% in 2011; 2.8% in 2015; TA-TAVR: 17.7% in 2012 and 0% in 2014)., Conclusion: TAVR is off-label used in AR in clinical practice. TAVR seems to be a safe option for AR with regard to in-hospital outcomes. However, further research evaluating long-term outcomes is required to establish the feasibility of TAVR in pure AR., (© 2019 Wiley Periodicals, Inc.)

Background: Inflammation drives atherosclerosis and its complications. Anti-inflammatory therapy with interleukin 1 beta (IL-1β) antibody reduces cardiovascular events in patients with elevated high-sensitive C-reactive protein (hsCRP). This study aims to identify the share of patients with coronary heart disease (CHD) and residual inflammation who may benefit from anti-inflammatory therapy., Methods: hsCRP and low-density lipoprotein (LDL) levels were determined in 2741 all-comers admitted to the cardiological ward of our tertiary referral hospital between June 2016 and June 2018. Patients without CHD, with acute coronary syndrome, chronic or recurrent systemic infection, use of immunosuppressant or anti-inflammatory agents, chronic inflammatory diseases, chemotherapy, terminal organ failure, traumatic injury and pregnancy were excluded., Results: 856 patients with stable CHD were included. 42.7% of those had elevated hsCRP ≥ 2 mg/l. Within the group of patients with LDL-cholesterol < 70 mg/dl, 30.9% shared increased hsCRP indicating residual inflammation. After multivariate adjusted backward selection elevated Lipoprotein (a) (OR 1.61, p = 0.048), elevated proBNP (OR 2.57, p < 0.0001), smoking (OR 1.70, p = 0.022), and obesity (OR 2.28, p = 0.007) were associated with elevated hsCRP. In contrast, the use of ezetimibe was associated with normal hsCRP (OR 0.51, p = 0.014). In the subgroup of patients with on-target LDL-cholesterol < 70 mg/dl, backward selection identified elevated proBNP (OR 3.49, p = 0.007) as independent predictor of elevated hsCRP in patients with LDL-cholesterol < 70 mg/dl., Conclusion: One-third of all-comers patients with CHD showed increased levels of hsCRP despite a LDL-cholesterol < 70 mg/dl potentially qualifying for an anti-inflammatory therapy. Elevated proBNP is an independent risk factor for hsCRP elevation.

Aims: Patients with postoperative delirium (POD) after transcatheter aortic valve replacement (TAVR) are ventilated and hospitalized longer and suffer increased in-hospital mortality. This study hypothesized that a minimalistic approach with conscious sedation during transfemoral aortic valve replacement (TF-AVR) protects against delirium, time of mechanical ventilation, and increased length of stay in intensive care unit (ICU) compared to intubation anaesthesia., Methods and Results: 308 patients which underwent TF-AVR in our centre between 01/2013 and 08/2017 were retrospectively evaluated regarding postoperative delirium, time of mechanical ventilation, and days in ICU. TF-AVR was performed with intubation anaesthesia in 245 patients and with conscious sedation in 63. The operative risk estimated by the logEUROScore was similar in both groups (intubation: 13.28 +/-9.06%, conscious sedation: 12.24 +/-6.77%, p = 0.395). In the conscious sedation group procedure duration was shorter (0.61 +/-0.91h vs. 1.75 +/-0.96h, p<0.001). The risk for intraprocedural complications was not influenced by the anaesthesia method (OR conscious sedation instead of intubation 1.66, p = 0.117), but days on ICU (-2.21 days, p<0.0001) and minutes of mechanical ventilation (-531.2 min, p < 0.0001) were reduced. Furthermore, the risk of POD was decreased when TF-AVR was performed under conscious sedation (6.35% vs. 18.18%, OR 0.29, p = 0.021)., Conclusions: Time of mechanical ventilation, risk of POD, and days on ICU were substantially reduced in patients who underwent TF-AVR under conscious sedation. Our data suggest that TF-AVR with conscious sedation is safe with a beneficial postoperative course in clinical practice, and should be considered the favoured approach., Competing Interests: The authors have declared that no competing interests exist.

Aims: Women with long QT syndrome 2 (LQT2) have a particularly high postpartal risk for lethal arrhythmias. We aimed at investigating whether oxytocin and prolactin contribute to this risk by affecting repolarization., Methods and Results: In female transgenic LQT2 rabbits (HERG-G628S, loss of IKr), hormone effects on QT/action potential duration (APD) were assessed (0.2-200 ng/L). Hormone effects (200 ng/L) on ion currents and cellular APD were determined in transfected cells and LQT2 cardiomyocytes. Hormone effects on ion channels were assessed with qPCR and western blot. Experimental data were incorporated into in silico models to determine the pro-arrhythmic potential. Oxytocin prolonged QTc and steepened QT/RR-slope in vivo and prolonged ex vivo APD75 in LQT2 hearts. Prolactin prolonged APD75 at high concentrations. As underlying mechanisms, we identified an oxytocin- and prolactin-induced acute reduction of IKs-tail and IKs-steady (-25.5%, oxytocin; -13.3%, prolactin, P < 0.05) in CHO-cells and LQT2-cardiomyocytes. IKr currents were not altered. This oxytocin-/prolactin-induced IKs reduction caused APD90 prolongation (+11.9%/+13%, P < 0.05) in the context of reduced/absent IKr in LQT2 cardiomyocytes. Hormones had no effect on IK1 and ICa,L in cardiomyocytes. Protein and mRNA levels of CACNA1C/Cav1.2 and RyR2 were enhanced by oxytocin and prolactin. Incorporating these hormone effects into computational models resulted in reduced repolarization reserve and increased propensity to pro-arrhythmic permanent depolarization, lack of capture and early afterdepolarizations formation., Conclusions: Postpartum hormones oxytocin and prolactin prolong QT/APD in LQT2 by reducing IKs and by increasing Cav1.2 and RyR2 expression/transcription, thereby contributing to the increased postpartal arrhythmic risk in LQT2., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

X-ray fluoroscopy is the gold standard for coronary diagnostics and intervention. Magnetic resonance imaging is a radiation-free alternative to x-ray with excellent soft tissue contrast in arbitrary slice orientation. Here, we assessed real-time MRI-guided coronary interventions from femoral access using newly designed MRI technologies. Six Goettingen minipigs were used to investigate coronary intervention using real-time MRI. Catheters were custom-designed and equipped with an active receive tip-coil to improve visibility and navigation capabilities. Using modified standard clinical 5 F catheters, intubation of the left coronary ostium was successful in all animals. For the purpose of MR-guided coronary interventions, a custom-designed 8 F catheter was used. In spite of the large catheter size, and therefore limited steerability, intubation of the left coronary ostium was successful in 3 of 6 animals within seconds. Thereafter, real-time guided implantation of a non-metallic vascular scaffold into coronary arteries was possible. This study demonstrates that real-time MRI-guided coronary catheterization and intervention via femoral access is possible without the use of any contrast agents or radiation, including placement of non-metallic vascular scaffolds into coronary arteries. Further development, especially in catheter and guidewire technology, will be required to drive forward routine MR-guided coronary interventions as an alternative to x-ray fluoroscopy.

Aortic stenosis (AS) is the most common valvular heart disease, with a dismal prognosis when untreated. Recommended therapy is surgical (SAVR) or transcatheter (TAVR) aortic valve replacement. Based on a retrospective cohort of isolated SAVR and TAVR procedures performed in Germany in 2015 (N = 17,826), we examine the impact of treatment selection on in-hospital mortality and total in-hospital costs for a variety of at-risk populations. Since patients were not randomized to the two treatment options, the two endpoints in-hospital mortality and reimbursement are analyzed using logistic and linear regression models with 20 predefined patient characteristics as potential confounders. Incremental cost-effectiveness ratios were calculated as a ratio of the risk-adjusted reimbursement and mortality differences with 95% confidence intervals obtained by Fieller's theorem. Our study shows that TF-TAVR is more costly that SAVR and that cost differences between the procedures vary little between patient groups. Results regarding in-hospital mortality are mixed. SAVR is the predominant procedure among younger patients. For patients older than 85 years or at intermediate and higher pre-operative risk TF-TAVR seems to be the treatment of choice. Incremental cost-effectiveness ratios (ICER) are most favorable for patients older than 85 years (ICER €154,839, 95% CI €89,163-€302,862), followed by patients at higher pre-operative risk (ICER €413,745, 95% CI €258,027-€952,273). A hypothetical shift from SAVR towards TF-TAVR among patients at intermediate pre-operative risk is associated with a less favorable ICER (€1,486,118, 95% CI €764,732-€23,692,323), as the risk-adjusted mortality benefit is relatively small (- 0.97% point), while the additional reimbursement is still eminent (+€14,464). From a German healthcare system payer's perspective, the additional costs per life saved due to TAVR are most favorable for patients older than 85 and/or at higher pre-operative risk.

Background Transfemoral transcatheter aortic valve replacement (TF-TAVR) is recommended for patients suffering from aortic valve stenosis at increased operative risk. Beyond that, patients with different comorbidities could benefit from TF-TAVR. The present study compares real-world in-hospital outcomes of surgical aortic valve replacement and TF-TAVR. Methods and Results For all 33 789 isolated TF-TAVR and surgical aortic valve replacement procedures performed in Germany in 2014 and 2015, comorbidities and in-hospital outcomes were identified by International Classification of Diseases (ICD)- and OPS (Operation and procedure key)-codes. Patients undergoing TF-TAVR were older and at increased estimated risk. Outcomes were risk-adjusted to allow comparison. TF-TAVR was associated with a lower risk for acute kidney injuries (odds ratio [OR] 0.62, P<0.001), for bleeding (OR 0.17, P<0.001), and for prolonged mechanical ventilation (>48 hours, OR 0.21, P<0.001). Risk for stroke was similar (OR 1.07, P=0.558). As expected, the risk for pacemaker implantations was higher after TF-TAVR (OR 4.61, P<0.001). In all patients, none of the treatment strategies had a clear advantage on the risk for in-hospital mortality (OR 0.83, P=0.068). However, in patients aged >80 years and at high operative risk undergoing TF-TAVR in-hospital mortality was lower (TF-TAVR versus surgical aortic valve replacement 80-84, OR 0.55; P=0.002; ≥85 years, OR 0.42, P=0.006; EuroSCORE (European System for Cardiac Operative Risk Evaluation) >9: OR 0.62, P=0.001). TF-TAVR was superior in patients with renal failure and in NYHA (New York Heart Association)-Class III/IV. Other risk groups were not found to be factors favoring a treatment strategy. Conclusions The present study indicates a superiority of TF-TAVR in clinical practice for patients at increased operative risk, aged >80 years, in NYHA-Class III/IV, and with renal failure.

Aims: Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling., Methods and Results: Transgenic rabbits were generated by oocyte-microinjection of β-myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs. Short-QT syndrome 1 and wild type (WT) littermates were subjected to in vivo ECG, electrophysiological studies, magnetic resonance imaging, and ex vivo action potential (AP) measurements. Electrical remodelling was assessed using patch clamp, real-time PCR, and western blot. We generated three SQT1 founders. QT interval was shorter and QT/RR slope was shallower in SQT1 than in WT (QT, 147.8 ± 2 ms vs. 166.4 ± 3, P < 0.0001). Atrial and ventricular refractoriness and AP duration were shortened in SQT1 (vAPD90, 118.6 ± 5 ms vs. 154.4 ± 2, P < 0.0001). Ventricular tachycardia/fibrillation (VT/VF) inducibility was increased in SQT1. Systolic function was unaltered but diastolic relaxation was enhanced in SQT1. IKr-steady was increased with impaired inactivation in SQT1, while IKr-tail was reduced. Quinidine prolonged/normalized QT and action potential duration (APD) in SQT1 rabbits by reducing IKr. Diverse electrical remodelling was observed: in SQT1, IK1 was decreased-partially reversing the phenotype-while a small increase in IKs may partly contribute to an accentuation of the phenotype., Conclusion: Short-QT syndrome 1 rabbits mimic the human disease phenotype on all levels with shortened QT/APD and increased VT/VF-inducibility and show similar beneficial responses to quinidine, indicating their value for elucidation of arrhythmogenic mechanisms and identification of novel anti-arrhythmic strategies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Prolonged repolarization is the hallmark of long QT syndrome (LQTS), which is associated with subclinical mechanical dysfunction. We aimed at elucidating mechanical cardiac function in LQTS type 1 (loss of I Ks ) and its modification upon further prolongation of the action potential (AP) by I Kr -blockade (E-4031)., Methods: Transgenic LQT1 and wild type (WT) rabbits (n = 12/10) were subjected to tissue phase mapping MRI, ECG, and epicardial AP recording. Protein and mRNA levels of ion channels and Ca 2+ handling proteins (n = 4/4) were determined. In silico single cell AP and tension modeling was performed., Results: At baseline, QT intervals were longer in LQT1 compared to WT rabbits, but baseline systolic and diastolic myocardial peak velocities were similar in LQT1 and WT. E-4031 prolonged QT more pronouncedly in LQT1. Additionally, E-4031 increased systolic and decreased diastolic peak velocities more markedly in LQT1 - unmasking systolic and diastolic LQT1-specific mechanical alterations. E-4031-induced alterations of diastolic peak velocities correlated with the extent of QT prolongation., Conclusion: While baseline mechanical function is normal in LQT1 despite a distinct QT prolongation, further prolongation of repolarization by I Kr -blocker E-4031 unmasks mechanical differences between LQT1 and WT with enhanced systolic and impaired diastolic function only in LQT1. These data indicate an importance of the extent of QT prolongation and the contribution of different impaired ion currents for conveying mechanical dysfunction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Treatment of aortic valve stenosis has been changing since the introduction of transcatheter aortic valve replacement (TAVR). The present study investigates the treatment of aortic valve stenosis in a real-world population 2014 and 2015 in Germany., Methods: Patient characteristics and in-hospital outcomes of all 38 414 isolated surgical aortic valve replacements (SAVR) or TAVR were analyzed., Results: Since 2014 more TAVR than SAVR were performed in Germany. Overall interventions on the aortic valve increases: from 10 858 in 2009 to 19 929 in 2015. In 2015 patients > 75 were mainly treated with transfemoral (TF) TAVR. SAVR was performed in 474 patients over 80 years (for comparison: TF-TAVR: 7519; transapical (TA) TAVR: 1192). Patients treated with TAVR were older, more often female, and had more co-morbidities. Consequently, they were at higher operative risk. Overall in-hospital mortality was 2 % after SAVR, 3 % after TF-TAVR, and 6 % after TA-TAVR. Stroke rates were similar. Relevant bleeding events occurred after SAVR and TA-TAVR in 9 % and 8 % respectively and 3 % after TF-TAVR. 66 % of patients after TF-TAVR and 40 % after SAVR were discharged home., Discussion: TF-TAVR has become the most often performed therapy for patients > 75. Despite a higher operative risk, patients can be treated safely with TF-TAVR., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: POD is associated with a worse postoperative course in patients after cardiac surgery, but its incidence and effects after TAVR are not well-understood. The aim of the present study was to analyze incidence, risk factors, and in-hospital outcomes of postoperative delirium (POD) after transfemoral (TF-AVR) and transapical (TA-AVR) transcatheter aortic valve replacement (TAVR) in a nationwide cohort., Methods and Results: Administrative data on all patients undergoing isolated TAVR in Germany in 2014 were analyzed. 9038 TF-AVR and 2522 TA-AVR procedures were performed. POD incidence was 7% after TF-AVR and 12% after TA-AVR. Atrial fibrillation (TF: OR 1.35, p < 0.001; TA: OR 1.53, p = 0.001) and NYHA III/IV (TF: OR 1.23, p = 0.017, TA: OR 1.51, p = 0.001) were independent risk factors for POD. Dementia was a risk factor only in TF-AVR (OR 3.04, p < 0.001). Female sex was protective (TF: OR 0.56, p < 0.001, TA: OR 0.51, p < 0.001). We found the occurrence of POD to be associated with more postoperative complications such as stroke and bleeding. Consequently, patients with POD were ventilated and hospitalized longer and suffered an increased risk of in-hospital mortality (unadjusted OR TF: 1.83, p = 0.001, TA: 1.82, p = 0.01). After adjusting for postoperative events and comorbidities, POD's effect on in-hospital mortality disappeared. In contrast, stroke and bleeding remained independent predictors for mortality irrespective of POD., Conclusions: Patients with POD after TAVR are at increased risk for in-hospital mortality. However, after adjusting for postoperative events and comorbidities, stroke and bleeding, but not POD, are independent mortality predictors.

Background: Differences in baseline characteristics and anatomy between female and male patients with aortic valve stenosis may influence outcomes after surgical and transcatheter aortic valve replacement (TAVR). We evaluated the effect of sex on in-hospital outcomes after transfemoral (TF-TAVR), transapical (TA-TAVR), or surgical (SAVR) aortic valve replacement in a nationwide cohort., Methods: Baseline characteristics and outcomes from all isolated TAVR or SAVR procedures performed between 2011 and 2014 in German hospitals were analyzed (N = 64,794). Primary outcome was in-hospital mortality. Unadjusted and adjusted comparisons between women and men were performed within each treatment group., Results: Females were generally older and had a higher EuroSCORE. Thus, they were preferentially treated with TF-TAVR, whereas the share of TF-TAVR and SAVR was similar in males. Females suffered more relevant bleeding after TF-TAVR and SAVR (TF-TAVR: adjusted odds ratio [aOR] = 1.16, P = 0.018; TA-TAVR: aOR = 0.98, P = 0.799; SAVR: aOR = 1.12, P = 0.005). However, prolonged postoperative ventilation was less frequently necessary in females (aOR TF-TAVR: 0.69, P < 0.001; TA-TAVR: 0.69, P < 0.001; SAVR: 0.76, P < 0.001) and stroke risk was lower (TA-TAVR: aOR = 0.60, P = 0.001; TF-TAVR: aOR = 0.74, P = 0.001; SAVR: aOR = 0.61, P < 0.001). In-hospital mortality was slightly decreased in females undergoing TF-TAVR after adjustment (aOR = 0.87, P = 0.047), and equal in TA-TAVR (aOR = 0.96, P = 0.640) or SAVR (aOR = 1.02, P = 0.807)., Conclusions: This nation-wide analysis of sex-specific outcomes after aortic-valve replacement procedures showed that women are higher-risk for bleeding, but lower-risk for stroke, mechanical ventilation, and TF-TAVR mortality. Understanding these differences and their basis may help improve outcomes., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: We examine the volume-outcome relationship in isolated transcatheter aortic valve implantations (TAVI). Our interest was whether the volume-outcome relationship for TAVI exists on the centre level, whether it occurs equally for different outcomes and how it develops over time., Design: Secondary data analysis of electronic health records. The comprehensive German Federal Bureau of Statistics Diagnosis Related Groups database was queried for data on all isolated TAVI procedures performed in Germany between 2008 and 2014. Logistic and linear regression analyses were carried out. Risk adjustment was applied using a predefined set of patient characteristics to account for differences in the risk factor composition of the patient populations between centres and over time. Centres performing TAVI were stratified into groups performing <50, 50-99 and ≥100 procedures per year., Setting: Germany 2008-2014., Participants: All patients undergoing isolated TAVI in the observation period., Interventions: None., Primary and Secondary Outcome Measures: In-hospital mortality, bleeding, stroke, probability of ventilation >48 hours, length of hospital stay and reimbursement., Results: Between 2008 and 2014, a total of 43 996 TAVI procedures were performed in 113 different centres in Germany with a total of 2532 cases of in-hospital mortality. Risk-adjusted in-hospital mortality decreases over the years and is lower the higher the annual procedure volume at the centre is. The magnitude of the latter effect declines over the observation period. Our results indicate a ceiling effect in the volume-outcome relationship: the volume-outcome relationship is eminent in circumstances of relatively unfavourable outcomes. Alongside improving outcomes, however, the volume-outcome relationship decreases. Also, a volume-outcome relationship seems to be absent in circumstances of constantly low event rates., Conclusions: The hypothesised volume-outcome relationship for TAVI exists but diminishes and may disappear over time. This should be taken into account when considering mandatory minimum thresholds., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Propose: Targeted temperature management improves outcomes in comatose patients after cardiac arrest. Short lasting sedatives might enable rapid awakening after targeted temperature management and therefore early prognostication and extubation. Aim of the present study was to compare sedation with volatile isoflurane to intravenous propofol., Materials and Methods: All patients after cardiopulmonary resuscitation undergoing targeted temperature management treated between 01/2014 and 02/2017 at a single tertiary referral hospital were screened. Exclusion criteria included extracorporeal support or a survival below 48 h., Results: Data on 214 patients (median age 66.1 years, 62.6% shockable rhythm, survival 69.6%) are reported, 178 patients on propofol and sufentanil and 36 patients on isoflurane and sufentanil. Median time to first spontaneous breathing (9.3 h vs. 9.5 h, p = .373), median duration on mechanical ventilation in extubated patients (99.4 h vs. 105.7 h, p = .692) and median ICU stay (11.1d vs. 9.8d, p = .320) were similar in patients on propofol or isoflurane, respectively. Findings were confirmed by propensity score matching. Opioid dose was significantly lower in the isoflurane group (p < .001) while norepinephrine dose was significantly higher (p = .004)., Conclusion: Isoflurane sedation is feasible on during targeted temperature management. Time to spontaneous breathing, mechanical ventilation duration or ICU stay was not reduced by isoflurane., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The impact of various post-procedural complications after transcatheter aortic valve implantation (TAVI) on resource use and their consequences in the German reimbursement system has still not been properly quantified., Methods: In a retrospective observational study, we use data from the German DRG statistic on patient characteristics and in-hospital outcomes of all isolated TAVI procedures in 2013 (N = 9147). The impact of post-procedural complications on reimbursement, length of stay and mechanical ventilation was analyzed using both unadjusted and risk-adjusted linear and logistic regression analyses., Results: A total of 235 (2.57%) strokes, 583 (6.37%) bleeding events, 474 (5.18%) cases of acute kidney injury and 1428 (15.61%) pacemaker implantations were documented. The predicted reimbursement of an uncomplicated TAVI procedure was €33,272, and bleeding events were associated with highest additional reimbursement (€12,839, p < 0.001), extra length of stay (14.58 days, p < 0.001), and increased likelihood of mechanical ventilation for more than 48 h (OR 17.91, p < 0.001). A more moderate complication-related impact on resource use and reimbursement was found for acute kidney injury (additional reimbursement: €5963, p < 0.001; extra length of stay: 7.92 days, p < 0.001; ventilation >48 h: OR 6.93, p < 0.001) as well as for stroke (additional reimbursement: €4125, p < 0.001; extra length of stay: 4.68 days, p < 0.001; ventilation >48 h: OR 5.73, p < 0.001). Pacemaker implantations, in contrast, were associated with comparably small increases in reimbursement (€662, p = 0.006) and length of stay (3.54 days, p = 0.006) and no impaired likelihood of mechanical ventilation more than 48 h (OR 1.22, p = 0.156). Interestingly, these complication-related consequences remain mostly unchanged after baseline risk-adjustment., Conclusions: Post procedural complications such as bleeding events, acute kidney injuries and strokes are associated with increased resource use and substantial amounts of additional reimbursement in Germany, which has important implications for decision making outside of the usual clinical sphere.

Background: Evaluation of recurrent angina after percutaneous coronary interventions is challenging. Since bioresorbable vascular scaffolds (BVS) cause no artefacts in magnetic resonance imaging (MRI) due to their polylactate-based backbone, evaluation of vascular patency by MRI might allow for non-invasive assessment and triage of patients with suspected BVS failure., Methods: Patients with polylactate-based ABSORB-BVS in proximal coronary segments were examined with 3 Tesla MRI directly (baseline) and one year after implantation. For assessment of coronary patency, a high-resolution 3D spoiled gradient echo pulse sequence with fat-saturation, T2-preparation (TE: 40 ms), respiratory and end-diastolic cardiac gating, and a spatial resolution of (1.08 mm)3 was positioned parallel to the course of the vessel for bright blood imaging. In addition, a 3D navigator-gated T2-weighted variable flip angle turbo spin echo (TSE) sequence with dual-inversion recovery black-blood preparation and elliptical k-space coverage was applied with a voxel size of (1.14 mm)3. For quantitative evaluation lumen diameters of the scaffolded areas were measured in reformatted bright and black blood MR angiography data., Results: 11 patients with implantation of 16 BVS in the proximal coronary segments were included, of which none suffered from major adverse cardiac events during the one year follow up. Vascular patency in all segments implanted with BVS could be reliably assessed by MRI at baseline and after one year, whereas segments with metal stents could not be evaluated due to artefacts. Luminal diameter within the BVS remained constant during the one year period. One patient with atypical angina after BVS implantation was noninvasively evaluated showing a patent vessel, also confirmed by coronary angiography., Conclusions: Coronary MRI allows contrast-agent free and non-invasive assessment of vascular patency after ABSORB-BVS implantation. This approach might be supportive in the triage and improvement of diagnostic workflows in patients with postinterventional angina and scaffold implantation., Trial Registration: German Register of Clinical Studies DRKS00007456.

Aims: We aimed to analyse the impact of pulmonary hypertension (PH) on the in-hospital outcome of either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR)., Methods and Results: Data from all 107,057 patients undergoing isolated SAVR or TAVR in Germany between 2007 and 2014 were provided by the German Federal Bureau of Statistics. About 18% of patients with aortic valve stenosis suffered from PH. Patients with PH had more comorbidities with consequently increased EuroSCORE (TAVR without PH: 12.3%; with PH: 24%). The presence of PH led to an increase of in-hospital strokes, bleedings, acute kidney injuries, and pacemaker implantations in both treatment groups (TAVR and SAVR), but the PH-associated increase of complications and mortality was less pronounced among patients receiving TAVR (mortality after TAVR without PH: 5.4%; with PH: 7.2%). After baseline risk adjustment, the TAVR procedure was associated with a reduced risk of in-hospital stroke (OR 0.81, p=0.011), bleeding (OR 0.22, p<0.001), and mortality (OR 0.70, p=0.005) among PH patients, and in comparison to surgical treatment., Conclusions: PH is a risk factor for worse outcome of SAVR and TAVR. This fact is less pronounced among TAVR patients. Our data suggest a shift towards the transcatheter approach in patients suffering from PH.

Background: This study presents data on post-discharge costs of care among patients treated with transcatheter or surgical aortic valve replacement over a two year period., Methods: Based on a prospective clinical trial, post-discharge utilization of health services and status of assistance were collected for 151 elderly patients via 2250 monthly telephone interviews, valued using standardized unit costs and analysed using two-part regression models., Results: At month 1 post-discharge, total costs of care are substantially elevated (monthly mean: €3506.7) and then remain relatively stable over the following 23 months (monthly mean: €622.3). As expected, the majority of these costs are related to in-hospital care (~98% in month 1 post-discharge and ~72% in months 2-24). Patients that died during follow-up were associated with substantially higher cost estimates of in-hospital care than those surviving the two-year study period, while patients' age and other patient characteristics were of minor relevance. Estimated costs of outpatient care are lower at month 1 than during the rest of the study period, and not affected by the event of death during follow-up. The estimated costs of nursing care are, in contrast, much higher in year 2 than in year 1 and differ substantially by gender and type of procedure as well as by patients' age. Overall, these monthly cost estimates add up to €10,352 for the first and €7467.6 for the second year post-discharge., Conclusions: Substantial cost increases at month 1 post-discharge and in case of death during follow-up are the main findings of the study, which should be taken into account in future economic evaluations on the topic. Application of standardized unit costs in combination with monthly patient interviews allows for a far more precise estimate of the variability in post-discharge health service utilization in this group of patients than the ones given in previous studies., Trial Registration: German Clinical Trial Register Nr. DRKS00000797 .

Background: Transcatheter aortic valve implantation (TAVI) is a rapidly evolving technique for therapy of aortic stenosis. Previous studies report learning curves with respect to in-hospital mortality and clinical complications. We aim to determine whether observed improvements of in-hospital outcomes after TAVI are the result of improvements in procedures or due to a change in the patient population, and whether improvements differ between the transfemoral (TF) and the transapical (TA) approach., Methods: Data was analyzed using risk-adjusted regression analyses in order to track the development of clinical outcomes of all isolated TAVI procedures performed in Germany from 2008 to 2013 (N=32.436) in all German hospitals performing TAVI. Measurements include in-hospital mortality, stroke, bleeding, and mechanical ventilation., Results: Unadjusted mortality rates decrease over time for both TA-TAVI and TF-TAVI. Reductions in mortality were smaller for TA-TAVI than for TF-TAVI. These trends could also be observed for risk-adjusted (standardized) mortality rates, indicating that time trends and differences between TA-TAVI (around 7% in 2013) and TF-TAVI (around 4% in 2013) cannot be explained by changes in the risk factor composition of the patient populations. Bleeding complications decreased for both access routes. Both unadjusted and standardized bleeding rates were substantially higher for TA-TAVI. In addition, TA-TAVI procedures were associated with an increased likelihood of requiring >48h of mechanical ventilation., Conclusions: Observed improvements in TAVI-related in-hospital mortality are not due to a change in patient population. The results indicate the superiority of a TF-first approach., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

The purpose of the study to assess the comparability of immediate changes in plaque/media volume (PV) on three modalities of intravascular ultrasound (IVUS) after implantation of either bioresorbable vascular scaffold (BVS) or everolimus-eluting metallic stent (EES) in Absorb II Study. The two devices have different device volume and ultrasound backscattering that may interfere with the "plaque/media" assessed by three modalities on IVUS: grayscale, backscattering of radiofrequency and brightness function. In a multicenter randomized controlled trial, 501 patients with stable or unstable angina underwent documentary IVUS pre- and post- implantation. The change in plaque/media volume (PV) was categorized into three groups according to the relative PV change in device segment: PV "increased" >+5% (PVI), PV unchanged ±5% (PVU), and PV decreased <-5% (PVD). The change in PV was re-evaluated three times: after subtraction of theoretical device volume, after analysis of echogenicity based on brightness function. In 449 patients, 483 lesions were analyzed pre- and post-implantation. "PVI" was more frequently observed in BVS (53.8%) than EES group (39.4%), p = 0.006. After subtraction of the theoretical device volume, the frequency of "PVI" decreased in both BVS (36.2%) and EES (32.1%) groups and became comparable (p = 0.581). In addition, the percentage of "PVI" was further reduced in both device groups after correction for either radiofrequency backscattering (BVS 34.4% vs. EES 22.6%) or echogenicity (BVS 25.2% vs. EES 9.7%). PV change in device segment was differently affected by BVS and EES devices implantation due to their differences in device volume and ultrasound backscattering. It implies that the lumen volume was also artifactually affected by the type of device implanted. Comparative IVUS assessment of lumen and plaque/media volume changes following implantation of BVS and EES requires specific methodological adjustment.

Objectives: The aim of this study was to assess how the introduction of transcatheter aortic valve replacement (TAVR) has changed clinical practice and outcome in patients who have previously undergone coronary artery bypass grafting (CABG)., Background: A significant proportion of patients admitted for aortic valve replacement have previously undergone CABG and are therefore at increased operative risk in case of redo surgery., Methods: In-hospital outcome data were analyzed from patients with or without previous CABG undergoing isolated surgical aortic valve replacement or TAVR in Germany from 2007 to 2013., Results: In total, 32,581 TAVR and 55,992 surgical aortic valve replacement procedures were performed in patients with (n = 6,221) or without (n = 82,352) previous CABG. TAVR increased markedly in patients with previous CABG, from 18 procedures in 2007 to 1,191 in 2013, while surgical aortic valve replacement decreased in these patients from 471 to 179 procedures. In 2013, TAVR was the preferred therapy in almost 90% of patients with previous CABG. In-hospital mortality was increased in patients with previous CABG compared with those without (7.6% vs. 6.3% for TAVR and 7.2% vs. 2.6% for surgical aortic valve replacement). Bleeding and stroke rates were also increased with redo surgical aortic valve replacement procedures (with vs. without previous CABG: stroke, 3.2% vs. 1.8%; relevant bleeding, 29.6% vs. 13.4%; acute kidney injury, 4.2% vs. 2.9%), whereas this was not the case with TAVR (stroke, 2.1% vs. 2.6%; relevant bleeding, 7.3% vs. 8.3%; acute kidney injury, 6.3% vs. 5.4% respectively). A similar influence was seen in resource utilization (discharge destination home: TAVR after CABG, 51%; surgical aortic valve replacement after CABG, 31%)., Conclusions: Since its introduction in 2007, TAVR has been increasingly used in Germany in patients with previous CABG, and in-hospital outcome data support the trend away from redo surgery., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Quality of life (QoL) measurements reported in observational studies are often biased, since patients who failed to improve are more likely to be unable to respond due to death or impairment. In order to observe the development of QoL in patients close to death, we analyzed a set of monthly QoL measurements for a cohort of elderly patients treated for aortic valve stenosis (AS) with special consideration of the effect of distance to death., Methods: QoL in 169 elderly patients (age ≥ 75 years), treated either with transcatheter aortic valve replacement (TAVR; n = 92), surgical aortic-valve replacement (n = 70), or drug-based therapy (n = 7), was evaluated using the standardized EQ-5D questionnaire. Over a two-year period, patients were consulted using monthly telephone interviews or outpatient visits, leading to a total of 2463 time points at which QoL values, New York Heart Association (NYHA) Functional Classification and their status of assistance were assessed. Furthermore, post-procedural clinical events and complications were monitored. Linear and ordered logistic regression analyses with random intercept were carried out, taking into account overall trends and distance to death., Results: QoL measures decreased slightly over time, were temporarily impaired at month 1 after the initial episode of hospitalization and decreased substantially at the end of life with a measurable effect starting at the sixth from last follow-up (month) before death. Many clinical complications (bleeding complications, stroke, acute kidney injury) showed an impairment of QoL measurements, but the inclusion of lagged variables demonstrated medium term (three months) QoL impairments for access site bleeding only. All other complications are associated with event-related impairments that decreased dramatically at the second and third follow-up interviews (month) after event., Conclusions: Distance to death shows clear effects on QoL and should be taken into account when analyzing QoL measures in the elderly patients treated for aortic valve stenosis., Trial Registration: German Clinical Trial Register Nr. DRKS00000797.

Background: Propionic acidemia (PROP) is a rare metabolic disorder caused by deficiency of propionyl-CoA carboxylase. PROP patients demonstrate QT prolongations associated with ventricular tachycardia and syncopes. Mechanisms responsible for this acquired long QT syndrome (acqLQTS) are unknown., Objective: The aim of the study was to investigate acute and chronic effects of metabolites accumulating in PROP patients on major repolarizing potassium currents (IKs and IKr) and their channel subunits., Methods: Voltage clamp studies were performed in CHO-KCNQ1/KCNE1 or HEK-KCNH2 cells to determine effects of propionic acid (PA; 1-10 mM), propionylcarnitine (PC; 25 µM-10 mM), methylcitrate (MC; 25 µM-10 mM), 0.2 M phosphate buffer (PB), or patient serum on IKs and IKr currents. Metabolite effects on action potentials were recorded in current clamp mode in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Protein expression of α- and β-subunits of IKs (KCNQ1/KCNE1) and IKr (KCNH2) was evaluated with Western blots., Results: Acute application of PA, PC, MC, and patient serum had no direct effect on net IKr densities (and KCNH2 expression), although it changed IKr gating kinetics. In contrast, PA, PC, MC, and patient serum all reduced IKs-tail (-67% ± 4.2%, -27% ± 6.7%, -16% ± 6.3%, -42.8% ± 5.15; P < .001) and IKs-end pulse currents. PA significantly prolonged action potential duration (APD) in hiPSC-CM and QT interval in wild-type but not in LQT1 rabbits lacking IKs. Moreover, PC and MC (1 mM) decreased KCNQ1 protein expression (relative density: 0.58 ± 0.08 and 0.16 ± 0.05; P < .01). Chronic exposure to 10 mM PA, in contrast, increased KCNQ1 5.4-fold (P < .001) owing to decreased protein degradation., Conclusion: Acute reduction of IKs by PROP metabolites may be responsible for APD prolongation and acqLQTS observed in PROP patients., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: While severe tricuspid regurgitation contributes significantly to morbidity and a poor prognosis in heart failure patients, isolated surgical repair of the tricuspid valve is associated with a high mortality, especially in patients with prior surgery. Percutaneous tricuspid valve repair could contribute to the solution of this dilemma. A recently published report demonstrated the feasibility of tricuspid edge-to-edge repair with the MitraClip® system (Abbott Vascular, Santa Clara, CA, USA) using a transjugular route. In a highly symptomatic patient with severe functional tricuspid regurgitation unsuitable for surgery, we aimed to reduce tricuspid regurgitation using a modified deployment technique for the MitraClip system using a femoral access., Methods and Results: A 78-year-old male patient with dilated cardiomyopathy was admitted for his fifth episode of acutely decompensated, predominantly right-sided, heart failure in ten months. Echocardiography showed a moderately to severely reduced left ventricular function and severe functional tricuspid regurgitation. Two clips were deployed in the anterior-septal and posterior-septal commissure of the tricuspid valve, resulting in a significant reduction of the effective regurgitant orifice area. The midterm clinical state of the patient improved., Conclusions: In our patient with severe functional tricuspid regurgitation and suitable anatomy, transfemoral percutaneous tricuspid valve repair was technically feasible and safe by using a modified deployment technique of a widely used repair system developed for the mitral valve. The procedure can be performed without technical modification of the device via a transfemoral route and under echocardiographic guidance. However, particular anatomic and technical aspects can compromise an initial procedural success and demand specific considerations in the future.

Background: Aortic annulus rupture is a rare, but potentially fatal complication of transcatheter aortic valve replacement (TAVR), especially when it occurs by balloon-expandable devices. In order to improve the predictability of procedures and avoid ruptures we investigated whether or not the aortic root volume measures is a useful indicator of risk, and if it could be useful for the prosthesis size selection., Methods and Results: From a retrospective series of 172 TAVR patients, seven experienced contained aortic annulus ruptures. The receiver operating curves were used to illustrate sensitivity and specificity of the different aortic annulus size and aortic root volume measures. The annulus area oversizing of ≥20% resulted in a sensitivity of 100%, specificity of 55.76%, and positive predictive value (PPV) of 8.75%. In patients receiving 26 mm prostheses, the aortic root volume (ARV <13600 mm(3)) provided a better specificity and PPV (79.63 and 18.52%, respectively). A two-step testing procedure considering the area derived average annulus diameter (Darea <23 mm) as a first separating parameter and then the ARV (<13,600 mm(3)) as a further indicator showed the most promising results with the PPV of 31.25%. Regardless of the procedure steps no false negative results were predicted., Conclusions: Our data show that the ARV provides a better predictive value for correct prosthesis sizing than established annulus measurements, especially in 'borderline' annuli. We suggest a two-step testing procedure for prostheses size selection, considering Darea and ARV to minimize the risk of annulus rupture. Prospective studies and examination of larger datasets are warranted to confirm these findings., (© 2015 Wiley Periodicals, Inc.)

Background: Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards., Methods: We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013., Results: In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic-valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [±SD] age, 81.0±6.1 years vs. 70.2±10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic-valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined., Conclusions: The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.).

Aims: Little is known about how "Heart Team" treatment decisions among patients suitable for either surgical aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI) are made under routine conditions., Methods and Results: The "Heart Team" decision-making process was analysed with respect to124 patients of a non-randomised prospective clinical trial that included patients aged ≥75 years: 41 patients underwent AVR and 83 underwent TAVI. By use of the non-parametric classification and regression tree (CART) methodology, 21 baseline parameters were tested to reconstruct the decision process retrospectively. Next, multivariate logistic and Cox regression models were fitted to evaluate the decision and outcome relevance (two-year survival) of the parameters as identified in the CART procedure. For patients with a baseline EuroSCORE I ≥13.48%, no further cut-off points were identified and the majority of these patients underwent TAVI. Among patients with a baseline EuroSCORE I <13.48%, age and left ventricular ejection fraction (LVEF) were identified as further relevant decision parameters. The decision relevance of EuroSCORE I (p=0.003), age (p=0.024) and LVEF (p=0.047) were confirmed by multivariate analysis; however, outcome relevance can be confirmed for EuroSCORE I (p=0.015) only, while treatment decision (TAVI or AVR) was not a significant predictor of mortality (p=0.655)., Conclusions: Despite or even because of the systematic risk selection according to EuroSCORE I values, we observed two-year survival rates of about 75% regardless of whether the patient received TAVI or AVR, suggesting that the decisions made by the "Heart Team" were appropriate.

Background: Little is known about preoperative predictors of resource utilization in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. We report results from the prospective, medical-economic "TAVI Calculation of Costs Trial"., Methods: In-hospital resource utilization was evaluated in 110 elderly patients (age ≥ 75 years) treated either with transfemoral (TF) or transapical (TA) transcatheter aortic valve implantation (TAVI, N = 83), or surgical aortic valve replacement (AVR, N = 27). Overall, 22 patient-specific baseline parameters were tested for within-group prediction of resource use., Results: Baseline characteristics differed between groups and reflected the non-randomized, real-world allocation of treatment options. Overall procedural times were shortest for TAVI, intensive care unit (ICU) length of stay (LoS) was lowest for AVR. Length of total hospitalization since procedure (THsP) was lowest for TF-TAVI; 13.4 ± 11.4 days as compared to 15.7 ± 10.5 and 21.2 ± 15.4 days for AVR and TA-TAVI, respectively. For TAVI and AVR, EuroScore I remained the main predictor for prolonged THsP (p <0.01). Within the TAVI group, multivariate regression analyses showed that TA-TAVI was associated with a substantial increase in THsP (55 to 61 %, p <0.01). Additionally, preoperative aortic valve area (AVA) was identified as an independent predictor of prolonged THsP in TAVI patients, irrespective of risk scores (p <0.05)., Conclusions: Our results demonstrate significant heterogeneity in patients baseline characteristics dependent on treatment and corresponding differences in resource utilization. Prolonged ThsP is not only predicted by risk scores but also by baseline AVA, which might be useful in stratifying TAVI patients., Trial Registration: German Clinical Trial Register Nr. DRKS00000797.

Aims: Recently, transcatheter aortic valve replacement (TAVR) has evolved as the standard treatment in patients with inoperable aortic valve stenosis. According to TAVR guidelines, body computed tomography (CT) is recommended for pre-procedural planning. Due to the advanced age of these patients, multiple radiological potentially malignant incidental findings (pmIFs) appear in this cohort. It is unknown how pmIFs influence the decision by the heart team to intervene and the mortality., Methods and Results: We evaluated in a retrospective single-centre observational study 414 participants screened for TAVR with dual-source CT between October 2010 and December 2012. pmIFs are common and appeared in 18.7% of all patients screened for TAVR. The decision to intervene by TAVR or surgical aortic valve replacement (SAVR) was made by an interdisciplinary heart team and the role of pmIF in decision-making and time to treatment with TAVR or SAVR was analysed, retrospectively. The appearance of a pmIF vs. no pmIF did not significantly influence therapeutic decisions [odds ratio (OR) 1.14; P = 0.835] or time to treatment (91 ± 152 vs. 61 ± 109 days, respectively). Several findings, which are highly suspicious for malignancy, were less likely associated with invasive treatment (OR 0.207; P = 0.046). Patient survival was evaluated for at least 2 years until January 2014. Two-year survival of patients after TAVR or SAVR, treated according to the heart team decision, was ∼75% and independent from the presence of a non-severe (P = 0.923) or severe (P = 0.823) pmIF., Conclusion: The study indicates that frequently occurring radiologic pmIF did not influence 2-year survival after a decision to intervene was made by an interdisciplinary heart team., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: This study aims at analyzing complication-induced additional costs of patients undergoing transcatheter aortic valve replacement (TAVR)., Methods: In a prospective observational study, a total of 163 consecutive patients received either transfemoral (TF-, n=97) or transapical (TA-) TAVR (n=66) between February 2009 and December 2012. Clinical endpoints were categorized according to VARC-2 definitions and in-hospital costs were determined from the hospital perspective. Finally, the additional costs of complications were estimated using multiple linear regression models., Results: TF-TAVR patients experienced significantly more minor access site bleeding, major non-access site bleeding, minor vascular complications, stage 2 acute kidney injury (AKI) and permanent pacemaker implantation. Total in-hospital costs did not differ between groups and were on average €40,348 (SD 15,851) per patient. The average incremental cost component of a single complication was €3438 (p<0.01) and the estimated cost of a TF-TAVR without complications was €34,351. The complications associated with the highest additional costs were life-threatening non-access site bleeding (€47,494; p<0.05), stage 3 AKI (€20,468; p<0.01), implantation of a second valve (€16,767; p<0.01) and other severe cardiac dysrhythmia (€10,611 p<0.05). Overall, the presence of complication-related in-hospital mortality increased costs., Conclusions: Bleeding complications, severe kidney failure, and implantation of a second valve were the most important cost drivers in our TAVR patients. Strategies and advances in device design aimed at reducing these complications have the potential to generate significant in-hospital cost reductions for the German Health Care System., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Background. Left main PCI is superior to coronary bypass surgery in selected patients. Registry data, however, suggest significant early adverse event rates associated with unprotected left main PCI. We aimed to evaluate safety of an extracorporeal life support (ECLS) as backup system during PCI. Methods. We report a registry study of 16 high-risk patients presenting with acute coronary syndromes undergoing unprotected left main PCI with an ECLS backup. Results. Seven patients (43.8%) presented with an acute myocardial infarction while 9 patients (56.3%) had unstable angina. Unprotected left main PCI could be successfully performed in all 16 patients. Mortality or thromboembolic event rates were zero within the index hospital stay. General anesthesia was necessary only in 5 patients (31.3%). Access site bleeding requiring transfusion was encountered in 4 patients (25.0%). Three patients (18.8%) developed access site complications requiring surgical intervention. All patients were ECLS-free after 96 hours. Conclusions. Unprotected left main PCI could be safely and effectively performed after ECLS implantation as backup in acute coronary syndromes in our patient collectively. Vascular access site complications however need to be considered when applying ECLS as backup system.

Background: Prolongation of action potential duration (APD), increased spatial APD dispersion, and triangulation are major factors promoting drug-induced ventricular arrhythmia. Preclinical identification of HERG/IKr-blocking drugs and their pro-arrhythmic potential, however, remains a challenge. We hypothesize that transgenic long-QT type 1 (LQT1) rabbits lacking repolarizing IKs current may help to sensitively detect HERG/IKr-blocking properties of drugs., Methods: Hearts of adult female transgenic LQT1 and wild type littermate control (LMC) rabbits were Langendorff-perfused with increasing concentrations of HERG/IKr-blockers E-4031 (0.001-0.1 µM, n=9/7) or erythromycin (1-300 µM, n=9/7) and APD, APD dispersion, and triangulation were analyzed., Results: At baseline, APD was longer in LQT1 than in LMC rabbits in LV apex and RV mid. Erythromycin and E-4031 prolonged APD in LQT1 and LMC rabbits in all positions. However, erythromycin-induced percentaged APD prolongation related to baseline (%APD) was more pronounced in LQT1 at LV base-lateral and RV mid positions (100 µM, LQT1, +40.6 ± 9.7% vs. LMC, +24.1 ± 10.0%, p<0.05) and E-4031-induced %APD prolongation was more pronounced in LQT1 at LV base-lateral (0.01 µM, LQT1, +29.6 ± 10.6% vs. LMC, +19.1 ± 3.8%, p<0.05) and LV base-septal positions. Moreover, erythromycin significantly increased spatial APD dispersion only in LQT1 and increased triangulation only in LQT1 in LV base-septal and RV mid positions. Similarly, E-4031 increased triangulation only in LQT1 in LV apex and base-septal positions., Conclusions: E-4031 and erythromycin prolonged APD and increased triangulation more pronouncedly in LQT1 than in LMC rabbits. Moreover, erythromycin increased APD dispersion only in LQT1, indicating that transgenic LQT1 rabbits could serve as sensitive model to detect HERG/IKr-blocking properties of drugs.

Background: Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias., Objective: To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS., Methods: Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments., Results: In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data., Conclusions: The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder., (© 2013 Heart Rhythm Society. All rights reserved.)

Background: N588K-KCNH2 and V307L-KCNQ1 mutations lead to a gain-of-function of IKr and IKs thus causing short-QT syndromes (SQT1, SQT2). Combined pharmacotherapies using K(+) -channel-blockers and β-blockers are effective in SQTS. Since β-blockers can block IKr and IKs , we aimed at determining carvedilol's and metoprolol's electrophysiological effects on N588K-KCNH2 and V307L-KCNQ1 channels., Methods: Wild-type (WT)-KCNH2, WT-KCNQ1 and mutant N588K-KCNH2 and V307L-KCNQ1 channels were expressed in CHO-K1 or HEK-293T cells and IKs and IKr were recorded at baseline and during β-blocker exposure., Results: Carvedilol (10 μM) reduced IKs tail in WT- and V307L-KCNQ1 by 36.5 ± 5% and 18.6 ± 9% (P < 0.05). IC50 values were 16.3 μM (WT) and 46.1 μM (V307L), indicating a 2.8-fold decrease in carvedilol's IKs -blocking potency in V307L-KCNQ1. Carvedilol's (1 μM) inhibition of the IKr tail was attenuated in N588K-KCNH2 (4.5 ± 3% vs 50.3 ± 4%, WT, P < 0.001) with IC50 values of 2.8 μM (WT) and 25.4 μM (N588K). Carvedilol's IKr end-pulse inhibition, however, was increased in N588K-KCNH2 (10 μM, 60.7 ± 6% vs 36.5 ± 5%, WT, P < 0.01). Metoprolol (100 μM) reduced IKr end-pulse by 0.23 ± 3% (WT) and 74.1 ± 7% (N588K, P < 0.05), IKr tail by 32.9 ± 10% (WT) and 68.8 ± 7% (N588K, P < 0.05), and reduced IKs end-pulse by 18.3 ± 5% (WT) and 57.1 ± 11% (V307L, P < 0.05) and IKs tail by 3.3 ± 1% (WT) and 45.1 ± 13 % (V307L, P < 0.05), indicating an increased sensitivity to metoprolol in SQT mutated channels., Conclusions: N588K-KCNH2 and V307L-KCNQ1 mutations decrease carvedilol's inhibition of the IKs or IKr tail but increase carvedilol's IKr end-pulse inhibition and metoprolol's inhibition of tail and end-pulse currents. These different effects on SQT1 and SQT2 mutated channels should be considered when using β-blocker therapy in SQTS patients., (© 2013 Wiley Periodicals, Inc.)

Background: Despite the known effects of drug-eluting stents (DES), other cofactors attributed to patient characteristics affect their success. Interest focused on designing a study minimizing these factors to answer continuing concerns on the heterogeneity of response to different DESs. The study's aim was to investigate the feasibility and impact of an intra-individual comparison design in patients (pts) with two coronary artery stenosis treated with a Sirolimus- (SES) and a Paclitaxel- (PES) eluting stent., Methods and Results: The study was conducted as a prospective, randomized, multi-center trial in 112 pts who consented to treatment with a SES and a PES. Pts were eligible if they suffered from the presence of two single primary target lesions in two different native coronary arteries. Lesions were randomized to either SES or PES treatment. The primary endpoint was in-stent luminal late loss (LLL), as determined by quantitative angiography at 8 months; clinical follow up was obtained at 1, 8, and 12 months additionally. The LLL (0.13 ± 0.28 mm SES vs. 0.26 ± 0.35 mm PES, p=0.011) showed less neointima in SES. With a predefined cut-off criterion of 0.2mm difference in LLL, 53/87 pts SES and PES were similar effective. 34/87 pts had a divergent result, 26 pts had greater benefit from SES while 8 pts had greater benefit from PES. Overall, MACE (MI, TLR, and death) occurred in 19 (17%) pts. Based on lesion analysis of 108 lesions treated with SES and 110 lesions treated with PES, 5 (4.6%) lesions with SES and 3 (2.7%) lesions with PES required repeated TLR., Conclusion: An intra-individual comparison design to assess differences in efficacy of different DESs is feasible, safe and achieves similar results to inter-individual studies. This study is among the first to show that failure of one DES does not necessarily implicate failure of another DES and vice versa., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The development of "transcatheter aortic valve implantation (TAVI)" is changing the field of cardiovascular medicine rapidly. The basic principle of TAVI is the percutaneous implantation of a bioprosthesis mounted in a metal frame. The prosthesis, which is attached to the tip of the catheter, is positioned in the native aortic valve and expanded. The first successful implantation was made by Alain Cribier in 2002. Several smaller mono- and multicenter studies later confirmed the technical feasibility of this procedure. Its true value as an important, therapeutic alternative to open heart surgery in inoperable and high-risk patients is now confirmed in large multicenter registries and by the prospective, randomized PARTNER trial. Decisive for the future acceptance of the procedure and for a possible expansion of the indication spectrum will be (1) continuous further development of the implantation technique and the prosthesis design, (2) reduction of TAVI-associated complications, (3) confirmation of the initial positive long-term results and (4) confirmation of the promising results in the treatment of surgical prosthesis dysfunctions and of patients with low to intermediate risk.

Although less invasive then SAVR, TAVI is associated with a significant rate of access site and non-access site bleeding. These complications are major determinants of therapy outcome, however, the economic consequences are not well defined. The purpose of this study was to determine the relationship between bleeding, in-hospital resource utilization and costs among patients undergoing transfemoral aortic valve implantation (TF-AVI) at a representative university hospital in Germany. Between February 2010 and December 2011, we prospectively enrolled 60 consecutive patients undergoing TAVI using a 18F transfemoral approach at our institution. The relationship between overt bleeding (OVB), defined according to the definitions provided by the Valve Academic Research Consortium, in-hospital resource utilization and in-hospital costs was investigated. The mean age was 82 (±6) years, 53% were female and the mean EuroScore was 17.2% (±8, 7). Thirty-eight percent (23/60) of the patients had an OVB following TF-AVI procedure. In-hospital mortality was 8.7% in the OVB patients (2/23) and 2.7% among patients without any OVB (1/37; NOVB), which was not statistically significant (p = 0.3). The total length of stay (LOS) of patients with and without bleeding complication were 15.0 ± 6.4 and 10.4 ± 5.1 days, respectively (p < 0.01). Time spent on ICU in the OVB group was twice as long as compared to the NOVB group (120.5 ± 98.5 min vs. 63.6 ± 26.5 min, p < 0.01). Consequently, in-hospital costs were statistically significant higher in OVB patients (40.051 ± 9.293 vs. 33.625 ± 4.368, p < 0.01). Bleeding is associated with increased resource use and in-hospital costs among TF-AVI patients. Our data indicates that strategies reducing bleeding risk may have the potential to generate important in-hospital costs reductions in TF-AVI patients.